2024-03-28T14:13:58Zhttp://uvadoc.uva.es/oai/requestoai:uvadoc.uva.es:10324/59502021-06-23T09:48:17Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Functional measurements of [Ca2+] in the endoplasmic reticulum using a herpes virus to deliver targeted aequorin
Alonso Alonso, María Teresa
Barrero, María José
Carnicero Gila, Estela María
Montero Zoccola, María Teresa
García-Sancho Martín, Francisco Javier
Álvarez Martín, Javier
Calcio - Metabolismo
Producción Científica
Changes in the free calcium concentration of the endoplasmic reticulum ([Ca 2+],,) play a central role
controlling cellular functions like contraction, secretion or neuronal signaling. We recently reported that recombinant
aequorin targeted to the endoplasmic reticulum (ER) [Montero M., Brini M., Marsault R. et al. Monitoring dynamic
changes in free Ca2+ concentration in the endoplasmic reticulum of intact cells. EMBO J 1995; 14: 5467-5475,
Montero M., Barrero M.J., Alvarez J. [Ca2+] microdomains control agonist-induced Ca2+ release in intact cells. FASEB J
1997; 11: 881-8861 can be used to monitor selectively [Ca2+le, in intact HeLa cells. Here we have used a herpes
simplex virus type 1 (HSV-1) based system to deliver targeted aequorin into a number of different cell types including
both postmitotic primary cells (anterior pituitary cells, chromaffin cells and cerebellar neurons) and cell lines (HeLa,
NIH3T3, GH, and PC12 cells). Functional studies showed that the steady state lumenal [Ca*+],, ranged from around
300 pM in granule cells to 800 ).rM in GH,cells. InsP,-coupled receptor stimulation with agonists like histamine (in HeLa,
NIH3T3 and chromaffin cells), UTP and bradykinin (in PC12 cells) or thyrotropin-releasing hormone (TRH, in GH,cells)
produced a very rapid decrease in lumenal [Ca’+],,. Caffeine caused a rapid Ca2+ depletion of the ER in chromaffin cells,
but not in the other cell types. Depolarization by high K+ produced an immediate and reversible increase of [Ca2+lerin all
the excitable cells (anterior pituitary, GH,, chromaffin cells and granule neurons). We conclude that delivery of
recombinant aequorin to the ER using HSV amplicon provides the first direct quantitative and dynamic measurements
of [Ca2+le, in several primary non-dividing cells.
2014-09-15T11:18:03Z
2014-09-15T11:18:03Z
1998
info:eu-repo/semantics/article
Cell Calcium, 1998, vol. 24, n. 2, p. 87-96
0143-4160
http://uvadoc.uva.es/handle/10324/5950
87
2
96
Cell Calcium
24
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Harcourt Brace & Co. Ltd
oai:uvadoc.uva.es:10324/59512021-06-23T09:48:01Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Ca 2+ induced Ca 2+ Release in Chromaffin Cells Seen from inside the ER with Targeted Aequorin
Alonso Alonso, María Teresa
Barrero, María José
Michelena, Pedro
Carnicero Gila, Estela María
Cuchillo Ibáñez, Inmaculada
García, Antonio G.
García-Sancho Martín, Francisco Javier
Montero Zoccola, María Teresa
Álvarez Martín, Javier
Calcio - Metabolismo
Producción Científica
The presence and physiological role of Ca 2+
induced Ca 2+
release (CICR) in nonmuscle excitable
cells has been investigated only indirectly through measurements
of cytosolic [Ca 2+] ([Ca 2+]c
). Using targeted
aequorin, we have directly monitored [Ca 2+] changes
inside the ER ([Ca 2+]
ER
) in bovine adrenal chromaffin
cells. Ca 2+
entry induced by cell depolarization triggered
a transient Ca 2+release from the ER that was
highly dependent on [Ca 2+]
ER
and sensitized by low
concentrations of caffeine. Caffeine-induced Ca 2+
release
was quantal in nature due to modulation by
[Ca 2+]
ER
. Whereas caffeine released essentially all the
Ca 2+
from the ER, inositol 1,4,5-trisphosphate (InsP3)-
producing agonists released only 60Ð80%. Both InsP3
and caffeine emptied completely the ER in digitoninpermeabilized
cells whereas cyclic ADP-ribose had no
effect. Ryanodine induced permanent emptying of the
Ca 2+
stores in a use-dependent manner after activation
by caffeine. Fast confocal [Ca 2+]c
measurements
showed that the wave of [C 2+]c
induced by 100-ms depolarizing
pulses in voltage-clamped cells was delayed
and reduced in intensity in ryanodine-treated cells. Our
results indicate that the ER of chromaffin cells behaves
mostly as a single homogeneous thapsigargin-sensitive
Ca 2+
pool that can release Ca 2+
both via InsP3
receptors
or CICR.
2014-09-15T11:53:11Z
2014-09-15T11:53:11Z
1999
info:eu-repo/semantics/article
Journal of Cell Biology, Enero 1999, vol. 144, n. 2, p. 241-254
0021-9525
http://uvadoc.uva.es/handle/10324/5951
241
2
254
Journal of Cell Biology
144
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
The Rockefeller University Press,
oai:uvadoc.uva.es:10324/59522021-06-23T09:48:02Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
The mitochondrial Na+/Ca2+ exchanger plays a key role in the control of cytosolic Ca2+ oscillations
Hernández San Miguel, Esther
Vay, Laura
Santo Domingo, Jaime
Domínguez Lobatón, María Carmen
Moreno Díaz-Calderón, Alfredo
Montero Zoccola, María Teresa
Álvarez Martín, Javier
Calcio - Metabolismo
Producción Científica
There is increasing evidence that mitochondria play an important role in the control of cytosolic Ca2+ signaling. We show here that the
main mitochondrial Ca2+-exit pathway, the mitochondrial Na+/Ca2+ exchanger, controls the pattern of cytosolic Ca2+ oscillations in nonexcitable
cells. In HeLa cells, the inhibitor of the mitochondrial Na+/Ca2+ exchanger CGP37157 changed the pattern of the oscillations
induced by histamine from a high-frequency irregular one to a lower frequency baseline spike type, surprisingly with little changes in the
average Ca2+ values of a large cell population. In human fibroblasts, CGP37157 increased the frequency of the baseline oscillations in cells
having spontaneous activity and induced the generation of oscillations in cells without spontaneous activity. This effect was dose-dependent,
disappeared when the inhibitor was washed out and was not mimicked by mitochondrial depolarization. CGP37157 increased mitochondrial
[Ca2+] and ATP production in histamine-stimulated HeLa cells, but the effect on ATP production was only transient. CGP37157 also activated
histamine-induced Ca2+ release from the endoplasmic reticulum and increased the size of the cytosolic Ca2+ peak induced by histamine
in HeLa cells. Our results suggest that the mitochondrial Na+/Ca2+ exchanger directly modulates inositol 1,4,5-trisphosphate-induced Ca2+
release and in that way controls cytosolic Ca2+ oscillations.
2014-09-15T12:01:52Z
2014-09-15T12:01:52Z
2006
info:eu-repo/semantics/article
https://doi.org/10.1016/j.ceca.2006.03.009
Cell Calcium, 2006, vol. 40, p. 53-61
0143-4160
http://uvadoc.uva.es/handle/10324/5952
53
61
Cell Calcium
40
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Elsevier Ltd.
oai:uvadoc.uva.es:10324/59562022-01-19T09:20:24Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Calcineurin-independent inhibition of mitochondrial Ca2+ uptake by cyclosporin A
Montero Zoccola, María Teresa
Domínguez Lobatón, María Carmen
Gutierrez-Fernández, S.
Moreno Díaz-Calderón, Alfredo
Álvarez Martín, Javier
Calcio - Metabolismo
Producción Científica
Cyclosporin A (CsA) is a widely used compound because ofits potent immunosupressive
properties, derived mainly from the inhibition of calcineurin, and also because of its ability to block
the mitochondrial permeability transition pore (PTP). This second effect has been involved in the
protection against apoptosis mediated by release ofmitochondrial factors. We show here that CsA (1–
10mM) has an additional effect on Ca2+ homeostasis in mitochondria that cannot be attributed to
inhibition ofPTP.
By measuring specifically mitochondrial [Ca2+] with targeted aequorin, we show that CsA
inhibited Ca2+ entry into mitochondria both in intact and in permeabilized cells, and this effect was
stronger when Ca2+ entry was triggered by low cytosolic [Ca2+], below 5 mM.
Inhibition ofmitochondrial Ca2+ uptake required micromolar concentrations ofCsA and was not
mimicked by other inhibitors of calcineurin such as FK-506 or cypermethrin, nor by a different
inhibitor ofthe PTP, bongkrekic acid.
CsA blocked the increase in mitochondrial Ca2+ uptake rate induced by the mitochondrial Ca2+
uniporter activator SB202190.
5 Our results suggest that CsA inhibits Ca2+ entry through the Ca2+ uniporter by a mechanism
independent ofthe inhibition ofPTP or calcineurin. This effect may contribute to reduce
depolarization and Ca2+ overloading in mitochondria after cell stimulation, and thus cooperate
with the direct inhibition ofPTP to prevent apoptosis.
2015-09-15
2014-09-15T16:33:52Z
2015-09-15T23:40:09Z
2004
info:eu-repo/semantics/article
https://doi.org/10.1038/sj.bjp.0705609
British Journal of Pharmacology, 2004, vol. 141, n. 2, p. 263-268
0007-1188
http://uvadoc.uva.es/handle/10324/5956
263
2
268
British Journal of Pharmacology
141
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Nature Publishing Group
oai:uvadoc.uva.es:10324/59572021-06-23T09:48:03Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Measuring [Ca2+] in the endoplasmic reticulum with aequorin
Álvarez Martín, Javier
Montero Zoccola, María Teresa
Calcio - Metabolismo
Producción Científica
The photoprotein aequorin was the first probe used to measure specifically the [Ca2+] inside the lumen of
the endoplasmic reticulum ([Ca2+]ER) of intact cells and it provides values for the steady-state [Ca2+]ER, around 500 M,
that closely match those obtained now by other procedures. Aequorin-based methods to measure [Ca2+]ER offer several
advantages: (i) targeting of the probe is extremely precise; (ii) the use of low Ca2+-affinity aequorin allows covering a
large dynamic range of [Ca2+], from 10−5 to 10−3 M; (iii) aequorin is nearly insensitive to changes in Mg2+ or pH, has
a high signal-to-noise ratio and calibration of the results in [Ca2+] is made straightforward using a simple algorithm;
and (iv) the equipment required for luminescence measurements in cell populations is simple and low-cost. On the
negative side, this technique has also some disadvantages: (i) the relatively low amount of emitted light makes difficult
performing single-cell imaging studies; (ii) reconstitution of aequorin with coelenterazine requires previous complete
depletion of Ca2+ of the ER for 1–2 h, a maneuver that may result in deleterious effects in some cells; (iii) because
of the high rate of aequorin consumption at steady-state [Ca2+]ER, only relatively brief experiments can be performed;
and (iv) expression of ER-targeted aequorin requires previous transfection or infection to introduce the appropriate DNA
construct, or alternatively the use of stable cell clones. Choosing aequorin or other techniques to measure [Ca2+]ER will
depend of the correct balance between these properties in a particular problem.
2014-09-15T16:41:39Z
2014-09-15T16:41:39Z
2002
info:eu-repo/semantics/article
https://doi.org/10.1016/S0143-4160(02)00186-0
Cell Calcium, 2002, vol. 32, n. 5-6, p. 251-260
0143-4160
http://uvadoc.uva.es/handle/10324/5957
251
5-6
260
Cell Calcium
32
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Elsevier Ltd.
oai:uvadoc.uva.es:10324/59592021-06-23T09:48:04Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Monitoring mitochondrial [Ca2+] dynamics with rhod-2, ratiometric pericam and aequorin
Fonteriz García, Rosalba Inés
Fuente Pérez, Sergio de la
Moreno Díaz-Calderón, Alfredo
Domínguez Lobatón, María Carmen
Montero Zoccola, María Teresa
Álvarez Martín, Javier
Calcio - Metabolismo
Producción Científica
The dynamics of mitochondrial [Ca2+] ([Ca2+]M) plays a key role in a variety of cellular processes. The
most important methods available to monitor [Ca2+]M are fluorescent dyes such as rhod-2 and specifically
targeted proteins such as aequorin and pericam. However, significant discrepancies, both quantitative
and qualitative, exist in the literature between the results obtained with different methods. We have
made here a systematic comparison of the response of several fluorescent dyes, rhod-2 and rhod-FF,
and two Ca2+-sensitive proteins, aequorin and pericam. Our results show that measurements obtained
with aequorin and pericam are consistent in terms of dynamic Ca2+ changes. Instead, fluorescent dyes
failed to follow Ca2+ changes adequately, especially during repetitive stimulation. In particular, measures
obtained with rhod-2 or rhod-FF evidenced the previously reported Ca2+-dependent inhibition of
mitochondrial Ca2+ uptake, but data obtained with aequorin or pericam under the same conditions did
not. The reason for the loss of response of fluorescent dyes is unclear. Loading with these dyes produced
changes in mitochondrial morphology and membrane potential, which were small and reversible at low
concentrations (1–2 M), but produced large and prolonged damage at higher concentrations. In addition,
cells loaded with low concentrations of rhod-2 suffered large changes in mitochondrial morphology
after light excitation. Our results suggest that [Ca2+]M data obtained with these dyes should be taken with
care.
2014-09-15T16:50:12Z
2014-09-15T16:50:12Z
2010
info:eu-repo/semantics/article
https://doi.org/10.1016/j.ceca.2010.07.001
Cell Calcium, 2010, vol. 48, p. 61-69
0143-4160
http://uvadoc.uva.es/handle/10324/5959
61
69
Cell Calcium
48
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Elsevier Ltd.
oai:uvadoc.uva.es:10324/59692024-02-14T09:31:33Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Modulation of mitochondrial Ca2+ uptake by estrogen receptor agonists and antagonists
Domínguez Lobatón, María Carmen
Vay, Laura
Hernández San Miguel, Esther
Santo Domingo, Jaime
Moreno Díaz-Calderón, Alfredo
Montero Zoccola, María Teresa
Álvarez Martín, Javier
Hormonas femeninas - Absorción y adsorción
Calcio - Efectos fisiológicos
Producción Científica
Ca2+ uptake by mitochondria is a key element in the control ofcellular Ca2+ homeostasis and
Ca2+-dependent phenomena. It has been known for many years that this Ca2+ uptake is mediated by
the mitochondrial Ca2+ uniporter, a specific Ca2+ channel ofthe inner mitochondrial membrane. We
have shown previously that this channel is strongly activated by a series ofnatural phytoestrogenic
flavonoids. We show here that several agonists and antagonists of estrogen receptors (ERs) also
modulate the activity ofthe uniporter.
2015-09-16
2014-09-16T07:49:09Z
2015-09-16T23:40:09Z
2005
info:eu-repo/semantics/article
https://doi.org/10.1038/sj.bjp.0706265
British Journal of Pharmacology, 2005, vol. 145, p. 862-871
0007-1188
http://uvadoc.uva.es/handle/10324/5969
862
871
British Journal of Pharmacology
145
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Nature Publishing Group
oai:uvadoc.uva.es:10324/59702021-06-23T09:48:21Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Chromaffin-cell stimulation triggers fast millimolar mitochondrial Ca2+ transients that modulate secretion
Montero Zoccola, María Teresa
Alonso Alonso, María Teresa
Carnicero Gila, Estela María
Cuchillo Ibáñez, Inmaculada
Albillos, Almudena
García, Antonio G.
García-Sancho Martín, Francisco Javier
Álvarez Martín, Javier
Calcio - Efectos fisiológicos
Producción Científica
Activation of calcium-ion (Ca2+) channels on the plasma membrane and on intracellular Ca2+ stores, such as the
endoplasmic reticulum, generates local transient increases in the cytosolic Ca2+ concentration that induce Ca2+ uptake
by neighbouring mitochondria. Here, by using mitochondrially targeted aequorin proteins with different Ca2+ affinities,
we show that half of the chromaffin-cell mitochondria exhibit surprisingly rapid millimolar Ca2+ transients upon
stimulation of cells with acetylcholine, caffeine or high concentrations of potassium ions. Our results show a tight
functional coupling of voltage-dependent Ca2+ channels on the plasma membrane, ryanodine receptors on the
endoplasmic reticulum, and mitochondria. Cell stimulation generates localized Ca2+ transients, with Ca2+ concentrations
above 20–40 mM, at these functional units. Protonophores abolish mitochondrial Ca2+ uptake and increase stimulated
secretion of catecholamines by three- to fivefold. These results indicate that mitochondria modulate secretion by
controlling the availability of Ca2+ for exocytosis.
2015-03-16
2014-09-16T08:08:18Z
2015-03-16T00:40:07Z
2000
info:eu-repo/semantics/article
Nature Cell Biology, Febrero 2000, vol. 2, p. 57-61
1465-7392
http://uvadoc.uva.es/handle/10324/5970
57
61
Nature Cell Biology
2
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Macmillan Magazines Ltd.
oai:uvadoc.uva.es:10324/59732021-06-23T09:48:22Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Calcium dynamics in catecholamine-containing secretory vesicles
Moreno Díaz-Calderón, Alfredo
Domínguez Lobatón, María Carmen
Santo Domingo, Jaime
Vay, Laura
Hernández San Miguel, Esther
Rizzuto, Rosario
Montero Zoccola, María Teresa
Álvarez Martín, Javier
Calcio en el organismo
Producción Científica
We have used an aequorin chimera targeted to the membrane of the secretory granules to monitor the free [Ca2+] inside them in neurosecretory
PC12 cells. More than 95% of the probe was located in a compartment with an homogeneous [Ca2+] around 40 M. Cell stimulation with
either ATP, caffeine or high-K+ depolarization increased cytosolic [Ca2+] and decreased secretory granule [Ca2+] ([Ca2+]SG). Inositol-(1,4,5)-
trisphosphate, cyclic ADP ribose and nicotinic acid adenine dinucleotide phosphate were all ineffective to release Ca2+ from the granules.
Changes in cytosolic [Na+] (0–140 mM) or [Ca2+] (0–10 M) did not modify either ([Ca2+]SG). Instead, [Ca2+]SG was highly sensitive to
changes in the pH gradient between the cytosol and the granules. Both carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP) and
nigericin, as well as cytosolic acidification, reversibly decreased [Ca2+]SG, while cytosolic alcalinization reversibly increased [Ca2+]SG. These
results are consistent with the operation of a H+/Ca2+ antiporter in the vesicular membrane. This antiporter could also mediate the effects
of ATP, caffeine and high-K+ on [Ca2+]SG, because all of them induced a transient cytosolic acidification. The FCCP-induced decrease in
[Ca2+]SG was reversible in 10–15 min even in the absence of cytosolic Ca2+ or ATP, suggesting that most of the calcium content of the vesicles
is bound to a slowly exchanging Ca2+ buffer. This large store buffers [Ca2+]SG changes in the long-term but allows highly dynamic free [Ca2+]SG
changes to occur in seconds or minutes.
2014-09-16T08:47:12Z
2014-09-16T08:47:12Z
2005
info:eu-repo/semantics/article
https://doi.org/10.1016/j.ceca.2005.02.002
Cell Calcium, 2005, vol. 37, p. 555-564
0143-4160
http://uvadoc.uva.es/handle/10324/5973
555
564
Cell Calcium
37
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Elsevier Ltd.
oai:uvadoc.uva.es:10324/59742021-06-23T09:48:05Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
A confocal study on the visualization of chromaffin cell secretory vesicles with fluorescent targeted probes and acidic dyes
Moreno Díaz-Calderón, Alfredo
Santo Domingo, Jaime
Fonteriz García, Rosalba Inés
Domínguez Lobatón, María Carmen
Montero Zoccola, María Teresa
Álvarez Martín, Javier
Calcio en el organismo
Producción Científica
Secretory vesicles have low pH and have been classically identified as those labelled by a series of acidic
fluorescent dyes such as acridine orange or neutral red, which accumulate into the vesicles according to
the pH gradient. More recently, several fusion proteins containing enhanced green fluorescent protein
(EGFP) and targeted to the secretory vesicles have been engineered. Both targeted fluorescent proteins
and acidic dyes have been used, separately or combined, to monitor the dynamics of secretory vesicle
movements and their fusion with the plasma membrane. We have now investigated in detail the degree
of colocalization of both types of probes using several fusion proteins targeted to the vesicles (synaptobrevin2-
EGFP, Cromogranin A-EGFP and neuropeptide Y-EGFP) and several acidic dyes (acridine orange,
neutral red and lysotracker red) in chromaffin cells, PC12 cells and GH3 cells. We find that all the acidic
dyes labelled the same population of vesicles. However, that population was largely different from the
one labelled by the targeted proteins, with very little colocalization among them, in all the cell types
studied. Our data show that the vesicles containing the proteins more characteristic of the secretory vesicles
are not labelled by the acidic dyes, and vice versa. Peptide glycyl-L-phenylalanine 2-naphthylamide
(GPN) produced a rapid and selective disruption of the vesicles labelled by acidic dyes, suggesting that
they could be mainly lysosomes. Therefore, these labelling techniques distinguish two clearly different
sets of acidic vesicles in neuroendocrine cells. This finding should be taken into account whenever vesicle
dynamics is studied using these techniques.
2014-09-16T08:55:31Z
2014-09-16T08:55:31Z
2010
info:eu-repo/semantics/article
https://doi.org/10.1016/j.jsb.2010.06.015
Journal of Structural Biology, 2010, vol. 172, p. 261-269
1047-8477
http://uvadoc.uva.es/handle/10324/5974
261
269
Journal of Structural Biology
172
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Elsevier Inc.
oai:uvadoc.uva.es:10324/59772021-06-23T09:48:07Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Calcium dynamics in bovine adrenal medulla chromaffin cell secretory granules
Santo Domingo, Jaime
Vay, Laura
Camacho, Marcial
Hernández San Miguel, Esther
Fonteriz García, Rosalba Inés
Domínguez Lobatón, María Carmen
Montero Zoccola, María Teresa
Moreno Díaz-Calderón, Alfredo
Álvarez Martín, Javier
Médula espinal - Calcio
Producción Científica
The secretory granules constitute one of the less well-known compartments in terms of Ca2+ dynamics. They contain large amounts
of total Ca2+, but the free intragranular [Ca2+] ([Ca2+]SG), the mechanisms for Ca2+ uptake and release from the granules and their
physiological significance regarding exocytosis are still matters of debate. We used in the present work an aequorin chimera targeted
to the granules to investigate [Ca2+]SG homeostasis in bovine adrenal chromaffin cells. We found that most of the intracellular
aequorin chimera is present in a compartment with 50–100 lm Ca2+. Ca2+ accumulation into this compartment takes place mainly
through an ATP-dependent mechanism, namely, a thapsigargin-sensitive Ca2+-ATPase. In addition, fast Ca2+ release was observed
in permeabilized cells after addition of inositol 1,4,5-trisphosphate (InsP3) or caffeine, suggesting the presence of InsP3 and
ryanodine receptors in the vesicular membrane. Stimulation of intact cells with the InsP3-producing agonist histamine or with caffeine
also induced Ca2+ release from the vesicles, whereas acetylcholine or high-[K+] depolarization induced biphasic changes in vesicular
[Ca2+], suggesting heterogeneous responses of different vesicle populations, some of them releasing and some taking up Ca2+
during stimulation. In conclusion, our data show that chromaffin cell secretory granules have the machinery required for rapid uptake
and release of Ca2+, and this strongly supports the hypothesis that granular Ca2+ may contribute to its own secretion.
2015-09-16
2014-09-16T09:52:10Z
2015-09-16T23:40:10Z
2008
info:eu-repo/semantics/article
https://doi.org/10.1111/j.1460-9568.2008.06440.x
European Journal of Neuroscience, 2008, vol. 28, p. 1265-1274
0953-816X
http://uvadoc.uva.es/handle/10324/5977
1265
1274
European Journal of Neuroscience
28
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Federation of European Neuroscience Societies and Blackwell Publishing Ltd
oai:uvadoc.uva.es:10324/59802021-06-23T09:48:08Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Ca2+ Dynamics in the Secretory Vesicles of Neurosecretory PC12 and INS1 Cells
Santo Domingo, Jaime
Fonteriz García, Rosalba Inés
Domínguez Lobatón, María Carmen
Montero Zoccola, María Teresa
Moreno Díaz-Calderón, Alfredo
Álvarez Martín, Javier
Calcio - Metabolismo
Producción Científica
We have investigated the dynamics of the free
[Ca2+] inside the secretory granules of neurosecretory PC12
and INS1 cells using a low-Ca2+-affinity aequorin chimera
fused to synaptobrevin-2. The steady-state secretory granule
[Ca2+] ([Ca2+]SG] was around 20–40 lM in both cell types,
about half the values previously found in chromaffin cells.
Inhibition of SERCA-type Ca2+ pumps with thapsigargin
largely blocked Ca2+ uptake by the granules in
Ca2+-depleted permeabilized cells, and the same effect was
obtained when the perfusion medium lacked ATP. Consistently,
the SERCA-type Ca2+ pump inhibitor benzohydroquinone
induced a rapid release of Ca2+ from the granules
both in intact and permeabilized cells, suggesting that the
continuous activity of SERCA-type Ca2+ pumps is essential
to maintain the steady-state [Ca2+]SG. Both inositol 1,4,
5-trisphosphate (InsP3) and caffeine produced a rapid Ca2+
release from the granules, suggesting the presence of InsP3
and ryanodine receptors in the granules. The response to
high-K+ depolarization was different in both cell types, a
decrease in [Ca2+]SG in PC12 cells and an increase in
[Ca2+]SG in INS1 cells. The difference may rely on the
heterogeneous response of different vesicle populations in
each cell type. Finally, increasing the glucose concentration
triggered a decrease in [Ca2+]SG in INS1 cells. In conclusion,
our data show that the secretory granules of PC12 and INS1
cells take up Ca2+ through SERCA-type Ca2+ pumps and
can release it through InsP3 and ryanodine receptors, supporting
the hypothesis that secretory granule Ca2+ may be
released during cell stimulation and contribute to secretion.
2014-09-16T10:11:25Z
2014-09-16T10:11:25Z
2010
info:eu-repo/semantics/article
https://doi.org/10.1007/s10571-010-9572-2
Cellular and Molecular Neurobiology, 2010, vol. 30, p. 1267-1274
0272-4340
http://uvadoc.uva.es/handle/10324/5980
1267
1274
Cellular and Molecular Neurobiology
30
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Springer Verlag
oai:uvadoc.uva.es:10324/59842021-06-23T09:48:23Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Modulation of Ca2+ release and Ca2+ oscillations in HeLa cells and fibroblasts by mitochondrial Ca2+ uniporter stimulation
Vay, Laura
Hernández San Miguel, Esther
Santo Domingo, Jaime
Domínguez Lobatón, María Carmen
Moreno Díaz-Calderón, Alfredo
Montero Zoccola, María Teresa
Álvarez Martín, Javier
Calcio en el organismo
Producción Científica
The recent availability of activators of the mitochondrial Ca2+ uniporter allows direct
testing of the influence of mitochondrial Ca2+ uptake on the overall Ca2+ homeostasis
of the cell. We show here that activation of mitochondrial Ca2+ uptake by 4,4 ,4 -(4-
propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT) or kaempferol stimulates histamine-induced
Ca2+ release from the endoplasmic reticulum (ER) and that this effect is enhanced if the
mitochondrial Na+–Ca2+ exchanger is simultaneously inhibited with CGP37157. This suggests
that both Ca2+ uptake and release from mitochondria control the ability of local Ca2+ microdomains
to produce feedback inhibition of inositol 1,4,5-trisphosphate receptors (InsP3Rs). In
addition, the abilityof mitochondria tocontrolCa2+ release fromtheERallowsthemtomodulate
cytosolic Ca2+ oscillations. In histamine stimulatedHeLa cells and human fibroblasts, both PPT
and kaempferol initially stimulated and later inhibited oscillations, although kaempferol usually
induced a more prolonged period of stimulation. Both compounds were also able to induce the
generation of Ca2+ oscillations in previously silent fibroblasts. Our data suggest that cytosolic
Ca2+ oscillations are exquisitely sensitive to the rates of mitochondrial Ca2+ uptake and release,
which precisely control the size of the local Ca2+ microdomains around InsP3Rs and thus the
ability to produce feedback activation or inhibition of Ca2+ release.
2014-09-16T10:59:24Z
2014-09-16T10:59:24Z
2007
info:eu-repo/semantics/article
https://doi.org/10.1113/jphysiol.2006.126391
Journal of Physiology, 2007, vol. 580, n. 1, p. 39-49
0022-3751
http://uvadoc.uva.es/handle/10324/5984
39
1
49
Journal of Physiology
580
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Wiley
oai:uvadoc.uva.es:10324/59852021-06-23T09:48:09Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Mitochondrial free [Ca2+] levels and the permeability transition
Vay, Laura
Hernández San Miguel, Esther
Domínguez Lobatón, María Carmen
Moreno Díaz-Calderón, Alfredo
Montero Zoccola, María Teresa
Álvarez Martín, Javier
Calcio - Metabolismo
Producción Científica
Mitochondrial Ca2+ activates many processes, from mitochondrial metabolism to opening of the permeability
transition pore (PTP) and apoptosis. However, there is considerable controversy regarding the
free mitochondrial [Ca2+] ([Ca2+]M) levels that can be attained during cell activation or even in mitochondrial
preparations. Studies using fluorescent dyes (rhod-2 or similar), have reported that phosphate
precipitation precludes [Ca2+]M from increasing above 2–3 M. Instead, using low-Ca2+-affinity aequorin
probes, we have measured [Ca2+]M values more than two orders of magnitude higher. We confirm here
these values by making a direct in situ calibration of mitochondrial aequorin, and we show that a prolonged
increase in [Ca2+]M to levels of 0.5–1mM was actually observed at any phosphate concentration
(0–10mM) during continuous perfusion of 3.5–100 MCa2+-buffers. In spite of this high and maintained
(>10 min) [Ca2+]M, mitochondria retained functionality and the [Ca2+]M drop induced by a protonophore
was fully reversible. In addition, this high [Ca2+]M did not induce PTP opening unless additional activators
(phenyl arsine oxide, PAO) were present. PAO induced a rapid, concentration-dependent and irreversible
drop in [Ca2+]M. In conclusion [Ca2+]M levels of 0.5–1mM can be reached and maintained for prolonged
periods (>10 min) in phosphate-containing medium, and massive opening of PTP requires additional pore
activators.
2014-09-16T11:07:28Z
2014-09-16T11:07:28Z
2009
info:eu-repo/semantics/article
https://doi.org/10.1016/j.ceca.2008.10.007
Cell Calcium, 2009, vol. 45, p. 243-250
0143-4160
http://uvadoc.uva.es/handle/10324/5985
243
250
Cell Calcium
45
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Elsevier Ltd.
oai:uvadoc.uva.es:10324/59862021-06-23T09:48:24Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Calcium dynamics in the secretory granules of neuroendocrine cells
Álvarez Martín, Javier
Calcio en el organismo
Producción Científica
Cellular Ca2+signaling results from a complex interplay among a variety of Ca2+ fluxes going across the
plasma membrane and across the membranes of several organelles, together with the buffering effect of
large numbers of Ca2+-binding sites distributed along the cell architecture. Endoplasmic and sarcoplasmic
reticulum, mitochondria and even nucleus have all been involved in cellular Ca2+ signaling, and the
mechanisms for Ca2+ uptake and release from these organelles are well known. In neuroendocrine cells,
the secretory granules also constitute a very important Ca2+-storing organelle, and the possible role of
the stored Ca2+ as a trigger for secretion has attracted considerable attention. However, this possibility is
frequently overlooked, and the main reason for that is that there is still considerable uncertainty on the
main questions related with granular Ca2+ dynamics, e.g., the free granular [Ca2+], the physical state of
the stored Ca2+ or the mechanisms for Ca2+ accumulation and release from the granules. This review will
give a critical overview of the present state of knowledge and the main conflicting points on secretory
granule Ca2+ homeostasis in neuroendocrine cells.
2014-09-16T11:13:58Z
2014-09-16T11:13:58Z
2012
info:eu-repo/semantics/article
https://doi.org/10.1016/j.ceca.2011.12.002
Cell Calcium, 2012, vol. 51, p. 331-337
0143-4160
http://uvadoc.uva.es/handle/10324/5986
331
337
Cell Calcium
51
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Elsevier Ltd.
oai:uvadoc.uva.es:10324/59932021-06-23T09:48:10Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Dynamics of mitochondrial [Ca2+] measured with the low-Ca2+-affinity dye rhod-5N
Fuente Pérez, Sergio de la
Fonteriz García, Rosalba Inés
Montero Zoccola, María Teresa
Álvarez Martín, Javier
Mitocondria
Producción Científica
Available methods to measure mitochondrial [Ca2+] ([Ca2+]M) include both targeted proteins and fluorescent
dyes. Targeted proteins usually report much higher [Ca2+]M values than fluorescent dyes, up to two
orders of magnitude. However, we show here that the low-Ca2+-affinity dye rhod-5N provides [Ca2+]M
values similar to those reported by targeted aequorin, suggesting that the discrepancies are mainly due
to the higher Ca2+-affinity of the fluorescent dyes used. We find rhod-5N has an apparent in situ intramitochondrial
Kd around 0.5 mM. Addition of Ca2+ buffers containing between 4.5 and 10 M [Ca2+] to
permeabilized cells loaded with rhod-5N induced increases in calibrated [Ca2+]M up to the 100 M–1 mM
range, which were dependent on mitochondrial membrane potential. Ca2+ release from mitochondria was
largely dependent on [Na+]. We have then used rhod-5N loaded cells to investigate the [Ca2+]M response
to agonist stimulation at the single-cell and subcellular level.The [Ca2+]M peaks induced by histamine
varied by nearly 10-fold among different cells, with a mean about 25 M. In the presence of the Ca2+
uniporter stimulator kaempferol, the [Ca2+]M peaks induced by histamine were also highly variable, and
the mean [Ca2+]M peak was 3-fold higher. Simultaneous measurement of cytosolic and mitochondrial
[Ca2+] peaks showed little correlation among the heights of the peaks in both compartments. Studying
the [Ca2+]M peaks at the subcellular level, we found significant heterogeneities among regions in the
same cell. In particular, the [Ca2+]M increase in mitochondrial regions close to the nucleus was more than
double that of mitochondrial regions far from the nucleus.
2014-09-16T15:45:48Z
2014-09-16T15:45:48Z
2012
info:eu-repo/semantics/article
https://doi.org/10.1016/j.ceca.2011.10.007
Cell Calcium, 2012, vol. 51, p. 65-71
0143-4160
http://uvadoc.uva.es/handle/10324/5993
65
71
Cell Calcium
51
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Elsevier Ltd.
oai:uvadoc.uva.es:10324/59942021-06-23T09:48:12Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Ca2+ homeostasis in the endoplasmic reticulum measured with a new low-Ca2+-affinity targeted aequorin
Fuente Pérez, Sergio de la
Fonteriz García, Rosalba Inés
Montero Zoccola, María Teresa
Álvarez Martín, Javier
Calcio en el organismo
Producción Científica
We use here a new very low-Ca2+-affinity targeted aequorin to measure the [Ca2+] in the endoplasmic
reticulum ([Ca2+]ER). The new aequorin chimera has the right Ca2+-affinity to make long-lasting measurements
of [Ca2+]ER in the millimolar range. Moreover, previous Ca2+-depletion of the ER is no longer
required. The steady-state [Ca2+]ER obtained is 1–2 mM, higher than previously reported. In addition,
we find evidence that there is significant heterogeneity in [Ca2+]ER among different regions of the ER.
About half of the ER had a [Ca2+]ER of 1 mM or below, and the rest had [Ca2+]ER values above 1 mM and
in some parts even above 2 mM. About 5% of the ER was also found to have high [Ca2+]ER levels but to be
thapsigargin-insensitive and inositol trisphosphate insensitive. The rate of refilling with Ca2+ of the ER
was almost linearly dependent on the extracellular [Ca2+] between 0.1 and 3 mM, and was only partially
affected by mitochondrial membrane depolarization. Instead, it was significantly reduced by loading cells
with chelators, and the fast chelator BAPTA was much more effective than the slow chelator EGTA. This
suggests that local [Ca2+] microdomains connecting the store operated Ca2+ channels with the ER Ca2+
pumps may be important during refilling.
2014-09-16T15:52:43Z
2014-09-16T15:52:43Z
2013
info:eu-repo/semantics/article
https://doi.org/10.1016/j.ceca.2013.04.001
Cell Calcium, 2013, vol. 54, p. 37-45
0143-4160
http://uvadoc.uva.es/handle/10324/5994
37
45
Cell Calcium
54
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Elsevier Ltd.
oai:uvadoc.uva.es:10324/59952021-06-23T09:48:14Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Calcium signalling mediated through a7 and non-a7 nAChR stimulation is differentially regulated in bovine chromaffin cells to induce catecholamine release
Barrio, Laura del
Egea, Javier
León, Rafael
Romero, Alejandro
Ruiz, Ana
Montero Zoccola, María Teresa
Álvarez Martín, Javier
López, Manuela G.
Calcio
Producción Científica
Ca2+ signalling and exocytosis mediated by nicotinic receptor (nAChR) subtypes, especially the a7 nAChR, in bovine
chromaffin cells are still matters of debate.We have used chromaffin cell cultures loaded with Fluo-4 or transfected with aequorins directed to the cytosol or
mitochondria, several nAChR agonists (nicotine, 5-iodo-A-85380, PNU282987 and choline), and the a7 nAChR allosteric
modulator PNU120596. Minimal [Ca2+]c transients, induced by low concentrations of selective a7 nAChR agonists and nicotine, were markedly
increased by the a7 nAChR allosteric modulator PNU120596. These potentiated responses were completely blocked by the
a7 nAChR antagonist a-bungarotoxin (a7-modulated-response). Conversely, high concentrations of the a7 nAChR agonists,
nicotine or 5-iodo-A-85380 induced larger [Ca2+]c transients, that were blocked by mecamylamine but were unaffected by
a-bungarotoxin (non-a7 response). [Ca2+]c increases mediated by a7 nAChR were related to Ca2+ entry through non-L-type
Ca2+ channels, whereas non-a7 nAChR-mediated signals were related to L-type Ca2+ channels; Ca2+-induced Ca2+-release
contributed to both responses. Mitochondrial involvement in the control of [Ca2+]c transients, mediated by either receptor,
was minimal. Catecholamine release coupled to a7 nAChRs was more efficient in terms of catecholamine released/[Ca2+]c.
2015-09-16
2014-09-16T16:37:02Z
2015-09-16T23:40:10Z
2011
info:eu-repo/semantics/article
https://doi.org/10.1111/j.1476-5381.2010.01034.x
British Journal of Pharmacology, 2011, vol. 162, p. 94-110
0007-1188
http://uvadoc.uva.es/handle/10324/5995
94
110
British Journal of Pharmacology
162
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Wiley
oai:uvadoc.uva.es:10324/59962021-06-23T09:48:15Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Modulation of secretion by the endoplasmic reticulum in mouse chromaffin cells
Rigual Bonastre, Ricardo Jaime
Montero Zoccola, María Teresa
Rico Martín, Alberto José
Prieto Lloret, Jesús
Alonso Alonso, María Teresa
Álvarez Martín, Javier
Retículo endoplasmático
Células neuronales
Producción Científica
The endoplasmic reticulum (ER) has been suggested to modulate secretion either behaving as a Ca2+ sink or as a Ca2+ source
in neuronal cells. Working as a Ca2+ sink, through ER-Ca2+ pumping, it may reduce secretion induced by different stimuli.
Instead, working as a Ca2+ source through the Ca2+ induced Ca2+ release (CICR) phenomenon, it may potentiate secretion
triggered by activation of plasma membrane Ca2+ channels. We have previously demonstrated the presence of CICR in bovine
chromaffin cells, but we now find that mouse chromaffin cells almost lack functional caffeine-sensitive ryanodine receptors in the
ER and, consistently, no CICR from the ER could be observed. In addition, inhibition of ER Ca2+ pumping with ciclopiazonic acid
or thapsigargin strongly stimulated high-K+-evoked catecholamine secretion and cytosolic [Ca2+] ([Ca2+]c) transients. Surprisingly,
5 mM caffeine reduced high-K+-induced [Ca2+]c peaks but considerably potentiated secretion induced by high-K+ stimulation.
However, this potentiation was insensitive to ryanodine and additive to that induced by emptying the ER of Ca2+ with
thapsigargin, suggesting that it is unrelated to the activation of ryanodine receptors. We conclude that, in mouse chromaffin cells,
CICR is not functional and the ER strongly inhibits secretion by acting as a damper of the [Ca2+]c signal.
2015-09-16
2014-09-16T16:45:35Z
2015-09-16T23:40:11Z
2002
info:eu-repo/semantics/article
European Journal of Neuroscience, 2002, vol. 16, p. 1-8
0953-816X
http://uvadoc.uva.es/handle/10324/5996
1
8
European Journal of Neuroscience
16
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Wiley
oai:uvadoc.uva.es:10324/62732021-06-23T09:48:36Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Differential expression and localization of transient receptor potential vanilloid 1 in rabbit and human eyes
Martínez García, María del Carmen
Martínez Valcárcel, Tamara
Pañeda Vázquez-Prada, Covadonga
Gallego Muñoz, Patricia
Jimenez, Ana I.
Merayo Lloves, Jesús
Cornea - Enfermedades - Tratamiento
Producción Científica
Summary. Introduction: The superfamily of transient
receptor potential (TRP) cation channels is involved in
nociception. Members of this family, such as the
vanilloid receptor type 1 (TRPV1) channel, are activated
by a wide range of stimuli including heat (>43°C), low
pH (<6.5), hypoxia, and hypertonicity. Here we report
TRPV1 expression in rabbit and human eyes.
Material and methods: We analyzed the expression
of TRPV1 mRNA by quantitative reverse transcription
polymerase chain reaction (qRT-PCR) and protein by
immunohistochemistry in eyes of New Zealand White
rabbits and humans.
Results: In rabbit and human eyes, TRPV1 protein
was present in all layers of the corneal epithelium, but
only in the basal layer of the conjunctiva. It was also in
the ciliary and lens epithelia of both species as well as in
the secretory cells of the rabbit lacrimal gland. The
retinal pigment epithelium was positive for this protein
in both species. TRPV1 was also present in rabbit Müller
cells, where it had a similar pattern of expression to
vimentin intermediate filaments. Analysis by qRT-PCR
showed that TRPV1 mRNA was found in all of the
structures where the protein was present. The highest
level was in the lens and the lowest in the retina.
Conclusion: TRPV1 is expressed in cells that are
particularly active in Ca2+ exchange as well as in cells
with significant water transport activity. Because TRPV1
is a Ca2+ channel, it probably functions in the regulation
of both water and Ca2+ movements in ocular tissues.
2014-09-25T17:05:10Z
2014-09-25T17:05:10Z
2013
info:eu-repo/semantics/article
Histology and Histopatology, 2013, vol. 28, p. 1507-1516
0213-3911
http://uvadoc.uva.es/handle/10324/6273
1507
1516
Histology and Histopatology
28
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Universidad de Murcia
oai:uvadoc.uva.es:10324/62852021-06-23T09:48:37Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Clinical and pathological effects of different acrylic intracorneal ring segments in corneal additive surgery
Pérez Merino, Pablo
Parra Ruiz, Francisco Javier
Ibares Frías, Lucía
Gallego Muñoz, Patricia
Vázquez Lasa, Blanca
Benito Garzón, Lorena
San Román Calvar, José Alberto
Martínez García, María del Carmen
Merayo Lloves, Jesús
Cornea - Cirugía
Producción Científica
The objective of this work was to evaluate the potential use of less stiff materials based on acrylic copolymers
of methyl methacrylate/2-ethylhexyl acrylate (MMA/EHA) as devices to correct, stabilize and
improve the effect of poly(methyl methacrylate) (PMMA) intracorneal ring segments. MMA/EHA and
PMMA intracorneal ring segments were surgically implanted in the corneas of Lohmann Classic hens.
The effects of the intracorneal ring segments were assessed by optical measurements and corneal tolerance
was evaluated through biomicroscopic examination over a 90-day observation period and by conventional
histology. The experimental results demonstrated that the intracorneal ring segments made
of MMA/EHA copolymers provided a significant change in the corneal curvature and an improved
in vivo response compared to those obtained for PMMA rings, which was attributed to the higher flexibility
of the copolymeric materials, indicating that these systems might be considered suitable as an
alternative to those currently used, for application in clinical practice.
2014-09-26T15:38:40Z
2014-09-26T15:38:40Z
2010
info:eu-repo/semantics/article
https://doi.org/10.1016/j.actbio.2010.01.014
Acta Biomaterialia, 2010, vol. 6, p. 2572-2579
1742-7061
http://uvadoc.uva.es/handle/10324/6285
2572
2579
Acta Biomaterialia
6
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Elsevier
oai:uvadoc.uva.es:10324/62862021-06-23T09:48:40Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Femtosecond infrared intrastromal ablation and backscattering-mode adaptive-optics multiphoton microscopy in chicken corneas
Gualda, Emilio J.
Vázquez de Aldana, Javier R.
Martínez García, María del Carmen
Moreno, Pablo
Hernández Toro, Juan
Roso, Luis
Artal, Pablo
Bueno, Juan M.
Cornea - Cirugía
Producción Científica
The performance of femtosecond (fs) laser intrastromal ablation was evaluated with backscattering-mode adaptive-optics multiphoton microscopy in ex vivo chicken corneas. The pulse energy of the fs source used for ablation was set to generate two different ablation patterns within the corneal stroma at a certain depth. Intrastromal patterns were imaged with a custom adaptive-optics multiphoton microscope to determine the accuracy of the procedure and verify the outcomes. This study demonstrates the potential of using fs pulses as surgical and monitoring techniques to systematically investigate intratissue ablation. Further refinement of the experimental system by combining both functions into a single fs laser system would be the basis to establish new techniques capable of monitoring corneal surgery without labeling in real-time. Since the backscattering configuration has also been optimized, future in vivo implementations would also be of interest in clinical environments involving corneal ablation procedures.
2014-09-26T15:51:35Z
2014-09-26T15:51:35Z
2011
info:eu-repo/semantics/article
Biomedical Optics Express, Noviembre 2011, vol. 2, n. 11, p. 1-11
2156-7085
http://uvadoc.uva.es/handle/10324/6286
1
11
11
Biomedical Optics Express
2
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Optical Society of America
oai:uvadoc.uva.es:10324/62872021-06-23T09:48:42Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Oleanolic acid controls allergic and inflammatory responses in experimental allergic conjunctivitis
Córdova, Claudia
Gutiérrez, Beatriz
Martínez García, María del Carmen
Martín, Rubén
Gallego Muñoz, Patricia
Hernández Garrido, Marita
Nieto Salinas, María de la Paz
Conjuntivitis alérgica - Tratamiento
Producción Científica
Pollen is the most common aeroallergen to cause seasonal conjunctivitis. The result of allergen exposure is a strong Th2-
mediated response along with conjunctival mast cell degranulation and eosinophilic infiltration. Oleanolic acid (OA) is
natural a triterpene that displays strong anti-inflammatory and immunomodulatory properties being an active anti-allergic
molecule on hypersensitivity reaction models. However, its effect on inflammatory ocular disorders including conjunctivits,
has not yet been addressed. Hence, using a Ragweed pollen (RWP)-specific allergic conjunctivitis (EAC) mouse model we
study here whether OA could modify responses associated to allergic processes. We found that OA treatment restricted
mast cell degranulation and infiltration of eosinophils in conjunctival tissue and decreased allergen-specific Igs levels in EAC
mice. Th2-type cytokines, secreted phospholipase A2 type-IIA (sPLA2-IIA), and chemokines levels were also significantly
diminished in the conjunctiva and serum of OA-treated EAC mice. Moreover, OA treatment also suppressed RWP-specific Tcell
proliferation. In vitro studies, on relevant cells of the allergic process, revealed that OA reduced the proliferative and
migratory response, as well as the synthesis of proinflammatory mediators on EoL-1 eosinophils and RBL-2H3 mast cells
exposed to allergic and/or crucial inflammatory stimuli such as RWP, sPLA2-IIA or eotaxin. Taken together, these findings
demonstrate the beneficial activity of OA in ocular allergic processes and may provide a new intervention strategy and
potential therapy for allergic diseases.
2014-09-26T16:07:08Z
2014-09-26T16:07:08Z
2014
info:eu-repo/semantics/article
https://doi.org/10.1371/journal.pone.0091282
PLos ONE, 2014, vol. 9, n. 4. p. 1-11
1932-6203
http://uvadoc.uva.es/handle/10324/6287
1
4
11
PLoS ONE
9
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Macau University of Science and Technology
oai:uvadoc.uva.es:10324/62882021-06-23T09:48:44Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Scleral changes induced by atropine in chicks as an experimental model of myopia
Gallego Muñoz, Patricia
Martínez García, María del Carmen
Pérez Merino, Pablo
Ibares Frías, Lucía
Mayo Iscar, Agustín
Merayo Lloves, Jesús
Miopia - Tratamiento
Producción Científica
Purpose: To determine the effects of intravitreal atropine on scleral growth in the
form-deprived chick as an experimental model of myopia.
Methods: Five groups of five chicks were studied from day 0–12 post-hatching.
One group remained untreated (C), and four were form-deprived by monocular
light diffusers to induce myopia. Two groups (RL and A) wore diffusers for
9 days, and the other two groups (D and D + A) wore diffusers throughout the
study. Group D received no further treatment (myopia positive control). Groups
A and D + A received intravitreal injections of atropine for days 9–12. Measurements
of refractive error and axial length were performed on days 0, 9, and 12.
Sclera changes were assessed in cartilaginous and fibrous layers by histological
analysis.
Results: All form-deprived eyes had a myopic refractive error on day 9. All atropine-
treated groups were hyperopic on day 12. The effect of atropine was most
evident in Group D + A in which diffusers were maintained throughout treatment
and changes in refractive error were statistically significant. The observed
changes in axial length were in line with the changes in refractive error. The scleral
fibrous layer thickness increased, and the sceral cartilaginous layer underwent a
slight thinning compared to Group D, the myopia positive control.
Conclusions: If the signals that induce growth remain during atropine treatment,
morphological changes in sclera are produced: the scleral fibrous layer thickened,
and the sceral cartilaginous layer thinned. These changes resulted in refractive
error recovery, and the ocular growth was stopped. The data suggested the atropine
was acting throughout the scleral fibrous layer.
2015-09-26
2014-09-26T16:27:34Z
2015-09-26T23:40:07Z
2012
info:eu-repo/semantics/article
https://doi.org/10.1111/j.1475-1313.2012.00940.x
Ophtalmic and Physiological Optics, 2012, vol. 32, p. 478-484
0275-5408
http://uvadoc.uva.es/handle/10324/6288
478
484
Ophtalmic and Physiological Optics
32
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
The College of Optometrists
oai:uvadoc.uva.es:10324/64712021-06-23T09:48:25Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Wound healing following refractive surgery in hens
Martínez García, María del Carmen
Merayo Lloves, Jesús
Blanco Mezquita, José Tomás
Mar Sardaña, Santiago
Cirugía refractiva
Producción Científica
The wound-healing response is critical to the outcome of refractive surgery and studying wound healing contributes to an understanding of the
pathophysiology of other corneal injuries. Animal models allow research to be conducted with sufficient samples and under controlled parameters.
We studied the hen to determine the healing process from clinical, biophysical, and biological standpoints after photorefractive keratectomy
(PRK). PRK ( 6.0 diopters) was performed in hen eyes. At 3, 6, 12, 24, 48, and 72 h and 5, 7, 15, 30, and 60 days postoperatively, we
studied the clinical follow-up, objective measurements of light transmission (direct transmittance), apoptosis by TUNEL assay, proliferation by
immunocytochemical analysis of 5-bromo-20-deoxyuridine, and expression of alpha smooth muscle actin (SMA) in myofibroblasts in the
corneas. Hen corneas reepithelialize quickly. Haze developed from 5 to 60 days after surgery and was correlated with the appearance and
finalization of the expression of SMA. The direct transmittance of light was low during the first 15 days and improved at 30 and 60 days.
TUNEL-positive cells were observed 3 h after surgery and the numbers decreased thereafter. Epithelial proliferation began at 12 h and was
greater at 48 h, while stromal cell proliferation began at 24 h and was greater at 72 h. The hen cornea is anatomically similar to the human
cornea, and the manner in which it heals is a good model for studying different surgical techniques and pharmacologic assays.
2014-10-08T08:31:32Z
2014-10-08T08:31:32Z
2006
info:eu-repo/semantics/article
Experimental Eye Research, 2006, vol. 83. p.728-735
0014-4835
http://uvadoc.uva.es/handle/10324/6471
728
735
Experimental Eye Research
83
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Elsevier
oai:uvadoc.uva.es:10324/64722021-06-23T09:48:27Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Measurement of correlation between transmission and scattering during wound healing in hen corneas
Martínez García, María del Carmen
Mar Sardaña, Santiago
Blanco Mezquita, José Tomás
Torres, R.M.
Merayo Lloves, Jesús
Cirugía refractiva
Cornea - Enfermedades
Producción Científica
The aim of this work is to provide experimental data for corneal transparency and scattering to help create
a more complete model of corneal transparency. The scattered light in 96 healing hen corneas was measured
for three wavelengths by a scatterometer constructed in the Optics Laboratory (The University of Valladolid,
Spain). With the help of mirrors and beamsplitters, the light from the three lasers is directed toward the cell
containing the sample to be measured. The measured scattered light varies between six orders of magnitude.
Corneal transmissivity, mean cosine of a scattering angle, and angular distribution of scattered light were all
computed. The total transmitted light remained practically constant over a wide range of light values
transmitted in a forward direction (direct transmissivity). The value of the mean cosine of the scattering
direction is very close to the unit (g40:98), even in corneas with high opacities. The behavior of g indicates
that even damaged corneas evidence extremely small scattering, compared to other biological tissues.
The transmission reduction of each cornea is related to an increase in scattered light. In all cases, scattered
light is concentrated at very small angles. This behavior is acceptable in corneas that are healthy or which
evidence small lesions, but remains in corneas that are severely injured.
2014-10-08T08:53:14Z
2014-10-08T08:53:14Z
2009
info:eu-repo/semantics/article
https://doi.org/10.1080/09500340902871389
Journal of Modern Optics, May 2009, vol. 56, n.8. p.1014-1021
0950-0340
http://uvadoc.uva.es/handle/10324/6472
1014
8
1021
Journal of Modern Optics
56
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Taylor & Francis
oai:uvadoc.uva.es:10324/77482021-06-23T09:48:47Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Embryonic Cerebrospinal Fluid Activates Neurogenesis of Neural Precursors within the Subventricular Zone of the Adult Mouse Brain
Carnicero Gila, Estela María
Alonso Revuelta, María Isabel
Carretero Soto, Raquel
Lamus Molina, José Francisco
Moro Balbás, José Antonio
Mano Bonín, Anibal de la
Fernández Gómez, José María Fidel
Gato Casado, Ángel Luis
Neurorregeneración
Embriología
Producción Científica
Introduction: There is a nondeveloped neurogenic potential
in the adult mammalian brain, which could be the basis for
neuroregenerative strategies. Many research efforts have
been made to understand the control mechanisms which
regulate the transition from a neural precursor to a neuron
in the adult brain. Embryonic cerebrospinal fluid (CSF) is a
complex fluid which has been shown to play a key role in
neural precursor behavior during development, working as
a powerful neurogenic inductor. We tested if the neurogenic
properties of embryonic CSF are able to increase the neurogenic
activity of neuronal precursors from the subventricular
zone (SVZ) in the brains of adult mice. Results: Our results
show that mouse embryonic CSF significantly increases
the neurogenic activity in precursor cells from adult brain
SVZ. This intense neurogenic effect was specific for embryonic
CSF and was not induced by adult CSF. Conclusions:
Embryonic CSF is a powerful neurogenesis inductor in homologous
neuronal precursors in the adult brain. This property
of embryonic CSF could be a useful tool in neuroregeneration
strategies.
2014-12-18T12:47:03Z
2014-12-18T12:47:03Z
2013
info:eu-repo/semantics/article
https://doi.org/10.1159/000356983
Cell Tissues Organs, 2013, 198(5) 398-404
1422-6405
http://uvadoc.uva.es/handle/10324/7748
398
198
404
Cells Tissues Organs
5
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Karger
oai:uvadoc.uva.es:10324/77502021-06-23T09:48:48Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Embryonic cerebrospinal fluid in brain development: neural progenitor control
Gato Casado, Ángel Luis
Alonso Revuelta, María Isabel
Martín, Cristina
Carnicero Gila, Estela María
Moro Balbás, José Antonio
Fernández Gómez, José María Fidel
Lamus Molina, José Francisco
Desmond, Mary E.
Nervioso central, Sistema
Producción Científica
Due to the effort of several research teams across the
world, today we have a solid base of knowledge on the
liquid contained in the brain cavities, its composition, and
biological roles. Although the cerebrospinal fluid (CSF) is
among the most relevant parts of the central nervous system
from the physiological point of view, it seems that it
is not a permanent and stable entity because its composition
and biological properties evolve across life. So, we can
talk about different CSFs during the vertebrate life span.
In this review, we focus on the CSF in an interesting period,
early in vertebrate development before the formation
of the choroid plexus. This specific entity is called “embryonic
CSF.” Based on the structure of the compartment,
CSF composition, origin and circulation, and its interaction
with neuroepithelial precursor cells (the target cells)
we can conclude that embryonic CSF is different from the
CSF in later developmental stages and from the adult CSF.
This article presents arguments that support the singularity
of the embryonic CSF, mainly focusing on its influence
on neural precursor behavior during development and in
adult life.
2014-12-18T13:01:57Z
2014-12-18T13:01:57Z
2014
info:eu-repo/semantics/article
https://doi.org/10.3325/cmj.2014.55.299
Croat Medical J. Agosto 2014, 55(4) 299-305
0353-9504
http://uvadoc.uva.es/handle/10324/7750
299
55
305
Croat Med J.
4
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Karger
oai:uvadoc.uva.es:10324/85772021-06-23T09:48:50Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Susceptibility to Amoxicillin-Clavulanate-Induced Liver Injury Is Influenced by Multiple HLA Class I and II Alleles
Lucena, M. Isabel
Molokhia, Mariam
Shen, Yufeng
Urban, Thomas J.
Aithad, Guruprasad P.
Andrade, Raúl J
Day, Christopher P.
Ruiz Cabello, Francisco
Donaldson, Peter T.
Stephens, Camilla
Pirmohamed, Munir
Romero Gómez, Manuel
Navarro, José María
Fontana, Roberto J.
Miller, Michael
Groome, Max
Bondon-Guitton, Emmanuelle
Conforti, Anita
Stricker, Bruno H.C.
Carvajal García-Pando, Alfonso
Ibánez, Luisa
Yue, Qun-Ying
Eichelbaum, Michel
Floratos, Aris
Pe’er, Itsik
Daly, Mark J.
Goldstein, David B.
Dillon, John F.
Nelson, Matthew R.
Watkins, Paul B.
Daly, Ann K.
Amoxicilina - Efectos secundarios
Producción Científica
Background & Aims
Drug-induced liver injury (DILI), especially from antimicrobial agents, is an important cause of serious liver disease. Amoxicillin-clavulanate (AC) is a leading cause of idiosyncratic DILI, but little is understood about genetic susceptibility to this adverse reaction.
Methods
We performed a genome-wide association study using 822,927 single-nucleotide polymorphism (SNP) markers from 201 White European and US cases of AC-DILI and 532 population controls, matched for genetic background.
Results
AC-DILI was associated with many loci in the major histocompatibility complex. The strongest effect was with a human leukocyte antigen (HLA) class II SNP (rs9274407, P=4.8×10−14), which correlated with rs3135388, a tag SNP of HLA-DRB1*1501-DQB1*0602 that was previously associated with AC-DILI. Conditioned on rs3135388, rs9274407 is still significant (P=1.1×10−4). An independent association was observed in the class I region (rs2523822, P=1.8×10−10), related to HLA-A*0201. The most significant class I and II SNPs showed statistical interaction (P=0.0015). High-resolution HLA genotyping (177 cases and 219 controls) confirmed associations of HLA-A*0201 (P=2×10−6) and HLA-DQB1*0602 (P=5×10−10), and their interaction (P=0.005). Additional, population-dependent effects were observed in HLA alleles with nominal significance. In an analysis of auto-immunerelated genes, rs2476601 in the gene PTPN22 was associated (P=1.3×10−4).
Conclusions
Class I and II HLA genotypes affect susceptibility to AC-DILI, indicating the importance of the adaptive immune response in pathogenesis. The HLA genotypes identified will be useful in studies of the pathogenesis of AC-DILI, but have limited utility as predictive or diagnostic biomarkers because of the low positive-predictive values.
2015-03-02T13:04:12Z
2015-03-02T13:04:12Z
2011
info:eu-repo/semantics/article
https://doi.org/10.1053/j.gastro.2011.04.001
Gastroenterology. 2011 Jul; 141(1): 338–347
0016-5085
http://uvadoc.uva.es/handle/10324/8577
338
1
347
Gastroenterology
141
spa
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
WB Saunders
oai:uvadoc.uva.es:10324/85962021-09-23T07:53:22Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Benzodiazepine use and risk of dementia: prospective population based study
Billiot ide Gage, Sophie
Bégaud, Bernard
Bazin, Fabienne
Verdoux, Hélène
Dartigues, Jean-François
Pérès, Karine
Kurth, Tobias
Pariente, Antoine
Carvajal García-Pando, Alfonso
Benzodiazepinas
Producción Científica
Objective To evaluate the association between use of benzodiazepines
and incident dementia.
Design Prospective, population based study.
Setting PAQUID study, France.
Participants 1063 men and women (mean age 78.2 years) who were
free of dementia and did not start taking benzodiazepines until at least
the third year of follow-up.
Main outcome measures Incident dementia, confirmed by a neurologist.
Results During a 15 year follow-up, 253 incident cases of dementia
were confirmed. New use of benzodiazepines was associated with an
increased risk of dementia (multivariable adjusted hazard ratio 1.60,
95% confidence interval 1.08 to 2.38). Sensitivity analysis considering
the existence of depressive symptoms showed a similar association
(hazard ratio 1.62, 1.08 to 2.43). A secondary analysis pooled cohorts
of participants who started benzodiazepines during follow-up and
evaluated the association with incident dementia. The pooled hazard
ratio across the five cohorts of new benzodiazepine users was 1.46 (1.10
to 1.94). Results of a complementary nested case-control study showed
that ever use of benzodiazepines was associated with an approximately
50% increase in the risk of dementia (adjusted odds ratio 1.55, 1.24 to
1.95) compared with never users. The results were similar in past users
(odds ratio 1.56, 1.23 to 1.98) and recent users (1.48, 0.83 to 2.63) but
reached significance only for past users.
Conclusions In this prospective population based study, new use of
benzodiazepines was associated with increased risk of dementia. The
result was robust in pooled analyses across cohorts of new users of
benzodiazepines throughout the study and in a complementary
case-control study. Considering the extent to which benzodiazepines
are prescribed and the number of potential adverse effects of this drugclass in the general population, indiscriminate widespread use should
be cautioned against.
2015-03-03T12:43:33Z
2015-03-03T12:43:33Z
2012
info:eu-repo/semantics/article
https://doi.org/10.1136/bmj.e6231
BMJ 2012;345:e6231
0959-8138
http://uvadoc.uva.es/handle/10324/8596
BMJ
345
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
BMJ Publishing Group
oai:uvadoc.uva.es:10324/86012021-06-23T09:48:45Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Hip fracture rates and bisphosphonate consumption in Spain. An ecologic study
Martín Arias, Luis Hermenegildo
Treceño Lobato, Carlos
García Ortega, María Pilar
Rodríguez Paredes, Juan
Escudero, Antonio
Sáinz Gil, María
Salado Valdivieso, María Inés
Velasco González, Verónica
Carvajal García-Pando, Alfonso
Osteoporosis - Tratamiento farmacológico
Producción Científica
Introduction Bisphosphonates are used worldwide to treat
osteoporosis and, thus, to prevent fractures. Though they
have been proven in clinical trials to avoid some fractures,
their effectiveness in reducing hip fractures is unclear. The
aim of the present study was to explore the relationship
between bisphosphonate use and hip fracture trends in
Spain.
Methods For this purpose, an ecologic study spanning 2002
to 2008 was conducted in Spain. Consumption data were
obtained from the Spanish Ministry of Health and Social
Policy. The number of hip fractures was obtained from
hospital discharges; annual hip fracture rates were determined
and standardized using the Spanish 2002 population
census. A linear regression was performed between fracture
rate and use of bisphosphonates; R2 and Pearson correlation
coefficient were calculated.
Results From 2002 to 2008, dispensed prescriptions of
bisphosphonates in Spain increased from 3.28 to 17.66
DDD/1,000 inhabitants per day. In the same period, the
crude hip fracture rate increased from 2.85 to 3.02 cases
per 1,000 inhabitants older than 50 years; however, when
age standardized rates were estimated, the rate declined
from 2.85 to 2.79. Analyzed by sex, the standardized rate
for men slightly increased from 1.45 to 1.48, while for
women the rate significantly dropped from 4.00 to 3.91.Conclusion A small effect of bisphosphonates on hip fracture
rates can not be ruled out; however, other factors might
partially explain this decline. Assuming this medication was
the only cause for hip fracture rate reduction, the elevated
medication cost to avoid a single hip fracture makes it
necessary to explore less expensive interventions
2015-03-04T08:56:22Z
2015-03-04T08:56:22Z
2013
info:eu-repo/semantics/article
https://doi.org/10.1007/s00228-012-1337-z
European journal of clinical pharmacology, 2013, vol. 69, no 3, p. 559-564.
0031-6970
http://uvadoc.uva.es/handle/10324/8601
559
3
564
European journal of clinical pharmacology
69
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Springer Verlag
oai:uvadoc.uva.es:10324/86032021-06-23T09:48:46Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Evolución del consumo de fármacos antipsicóticos en Castilla y León (1990-2001)
García del Pozo, Javier
Isusi Lomas, Laura
Carvajal García-Pando, Alfonso
Martín Rodríguez, Igor
Sáinz Gil, María
García del Pozo, Victorina
Velasco Martín, Alfonso
Psicofarmacología
Producción Científica
Fundamento: A lo largo de la última década se han introducido
nuevos fármacos y nuevos abordajes terapéuticos que permiten suponer
cambios en la utilización de antipsicóticos en nuestro medio. El
objetivo del presente estudio fue caracterizar el patrón de utilización
de antipsicóticos en Castilla y León para el periodo 1990-2001 así
como conocer la influencia que la introducción de los nuevos antipsicóticos
ha podido tener en el patrón de consumo de estos fármacos.
Métodos: Los datos de consumo de medicamentos se obtuvieron
de la base de datos ECOM (Especialidades Consumo de Medicamentos)
del Ministerio de Sanidad y Consumo. Esta base contiene información
sobre el consumo de medicamentos dispensados con cargo al
Sistema Nacional de Salud en farmacias comunitarias en todo el territorio
nacional. Con el fin de estimar el consumo fuera del Sistema
Nacional de Salud, se han utilizado datos de la empresa IMS (International
Marketing Services) referidos a los años 2000 y 2001. Los datos
se expresaron en Dosis Diarias Definidas por 1.000 habitantes y día.
Resultados: El uso de antipsicóticos creció un 146 % desde
1990 al 2001. A lo largo del periodo estudiado, haloperidol ha sido el
antipsicótico más utilizado en España y en Castilla y León. Los
antipsicóticos atípicos representaron un 49% del consumo total en el
año 2001 y un 90% de los costes; se observa una fuerte tendencia
hacia un aumento de su consumo en detrimento de los antipsicóticos
típicos. Se ha estimado que un 14% de los antipsicóticos utilizados
en Castilla y León lo fue fuera del Sistema Nacional de Salud. Existen
notables diferencias entre las distintas provincias.
Conclusiones: El consumo de antipsicóticos en Castilla y León
creció un 146% durante los 12 años estudiados. En este incremento,
la oferta de nuevos antipsicóticos atípicos y las medidas legales relacionadas
con la desinstitucionalización de los enfermos mentales
han podido jugar un papel importante. La introducción en el mercado
de los nuevos antipsicóticos ha modificado el patrón de uso de los
mismos y ha ocasionado un incremento en los costes directos. El
consumo sin cargo al Sistema Nacional de Salud
2015-03-04T09:26:22Z
2015-03-04T09:26:22Z
2003
info:eu-repo/semantics/article
https://doi.org/10.1590/S1135-57272003000600006
Revista Española de Salud Pública 2003; 77(6): 725-733
1135-5727
http://uvadoc.uva.es/handle/10324/8603
725
6
733
Revista Española de Salud Pública
77
spa
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Ministerio de Sanidad y Consumo
oai:uvadoc.uva.es:10324/86092021-06-23T09:48:53Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Utilización de ansiolíticos e hipnóticos en España (1995-2002)
García del Pozo, Javier
Abajo Iglesias, Francisco J. de
Carvajal García-Pando, Alfonso
Montero Corominas, Dolores
Madurga Sanz, Mariano
García del Pozo, Victorina
Psicofármacología
Producción Científica
Fundamento: Estudios recientes han señalado un aumento en el
consumo de ansiolíticos e hipnóticos, así como su uso inadecuado,
en países occidentales. El objetivo de este trabajo es conocer su
patrón de utilización en España entre los años 1995 y 2002.
Métodos: Los datos de consumo de medicamentos se obtuvieron
de la base de datos ECOM (Especialidades Consumo de Medicamentos)
del Ministerio de Sanidad y Consumo, que contiene información
sobre el consumo de medicamentos dispensados con cargo al
Sistema Nacional de Salud en farmacias comunitarias. Los datos se
expresaron en Dosis Diarias Definidas por 1.000 habitantes y día.
Resultados: La utilización de ansiolíticos e hipnóticos creció
desde 39,71 Dosis Diarias Definidas por 1.000 habitantes y día en
1995 a 62,02 en 2002. A lo largo del periodo estudiado las benzodiazepinas
de vida media intermedia (8-24 horas) fueron los medicamentos
más utilizados, en especial lorazepam, alprazolam y lormetazepam.
El principio activo que más disminuyó su consumo fue el flunitrazepam.
Conclusiones: Aunque el consumo de ansiolíticos e hipnóticos
en España experimentó un notable incremento en los últimos años, el
patrón de consumo no presentó modificaciones sustanciales.
2015-03-04T13:00:59Z
2015-03-04T13:00:59Z
2004
info:eu-repo/semantics/article
Revista española de salud pública, Vol. 78, Nº. 3, 2004 , págs. 379-387
ISSN-e 1135-5727
http://uvadoc.uva.es/handle/10324/8609
379
3
387
Revista española de salud pública
78
spa
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Ministerio de Sanidad y Consumo
oai:uvadoc.uva.es:10324/90422021-06-23T09:49:00Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Validation of an experimental animal model for corneal additive surgery
Ibares Frías, Lucía
Gallego Muñoz, Patricia
Cantalapiedra Rodríguez, Roberto
Cruz Valsero, Maria Cruz
Mar Sardaña, Santiago
Merayo Lloves, Jesús
Martínez García, María del Carmen
Cirugía oftalmológica
Producción Científica
Purpose: To assess the hen cornea as a model for training and future wound healing studies after implantation
of intrastromal corneal ring segments (ICRS) by clinical and optical outcomes.
Setting: University of Valladolid, Valladolid, Spain.
Design: Experimental study.
Methods: One 90°, 150-μm thick polymethyl methacrylate Ferrara ICRS segment was manually implanted at
70-80% depth of 192 Gallus domesticus corneas. Clinical follow-up for 6 months included monitoring corneal
thickness, epithelial wound closure, edema, haze, and the location and severity of deposits. The refractive state was
also measured. After each animal was euthanized, corneas were processed for direct transmittance and histological
analysis.
Results: Complications were present in 16% of the eyes. Epithelial wound closure was completed at 3 ± 2 days.
A slight corneal edema in the channel site was present for the first 15 days. All corneas had deposits by 4 months
located along the inner, outer curvatures and under the segments. Corneal haze was present only at the incision
site. ICRS induced hyperopic changes in the refractive state without changes in direct transmitance of central
cornea. New cells and extracellular matrix were present around the segment where deposits were seen on clinical
follow-up.
Conclusions: With hen as an animal model, ICRS were implanted in a precise and reproducible way after a
learning curve. Similar to humans, the follow-up period during the first 6 months after implantation showed fast
wound closure, deposits, and haze at the incision site. ICRS in hens also reduced the refractive power withoutaffecting the central cornea.
2015-03-06T09:16:39Z
2015-03-06T09:16:39Z
2014
info:eu-repo/semantics/article
https://doi.org/10.4172/2155-9570.1000360
J Clin Exp Ophthalmol, 2014, vol. 5, no 360
2155-9570
http://uvadoc.uva.es/handle/10324/9042
360
J Clin Experimental Ophthalmology
5
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
OMICS Publishing Group
oai:uvadoc.uva.es:10324/90432021-06-23T09:49:01Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Availability of medicines in the European Union: results from the EURO-Medicines project.
Folino-Gallo, P.
Walley, T.
Frolich, J.C.
Carvajal García-Pando, Alfonso
Edwards, I.R.
Medicamentos - Disponibilidad - Comunidad Económica Europea
Producción Científica
There is at present no comprehensive directory of medicines available in European countries. Such a directory would be valuable to policy analysts, clinicians, regulatory agencies, pharmaceutical companies and consumer groups. The aim of this project was to compile such a directory of all medicines marketed in each of the European Union member countries.
METHODS:
Lists of medicines for each country, compiled from several national sources, classified by Anatomical-Chemical-Therapeutic (ATC) code. Census date was late 1998.
RESULTS:
A comprehensive directory was created using data from 14 of the 15 European Union countries. Numbers of trade names and of active ingredients varied widely, from Germany with 18,554 and 1,973, respectively, to Denmark with 1,915 and 1,016, respectively. In individual therapeutic areas, there were variations in the numbers of active ingredients available: the least variation between countries was in antineoplastic medicines (ATC code L, maximum number available in any country 101, minimum 60) and wider variation in alimentary (ATC code A, maximum 256. minimum 103) or cardiovascular (ATC code C, maximum 269, minimum 112). Only 7% of all the active ingredients were available in all the countries studied. The Scandinavian countries had the greatest proportion of active ingredients (60%) available in all other countries. Each country had a number of active ingredients available only in that country Italy had the largest number of these.
CONCLUSIONS:
The directory illustrates the wide variations in the availability of medicines across the European Union. The range of drugs available in each country represents differences in regulatory and market policies, as well as cultural and historic differences. This directory lends itself to many further analyses.
2015-03-06T09:45:35Z
2015-03-06T09:45:35Z
2001
info:eu-repo/semantics/article
https://doi.org/10.1007/s002280100345
Eur J Clin Pharmacol. 2001 Sep;57(6-7):441-6.
0031-6970
http://uvadoc.uva.es/handle/10324/9043
441
6-7
446
Eur J Clin Pharmacol
57
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Springer Verlag
oai:uvadoc.uva.es:10324/90482021-06-23T09:49:03Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
No differences between men and women in adverse drug reactions related to psychotropic drugs: a survey from France, Italy and Spain
D'Incau, Paola
Lapeyre-Mestre, Maryse
Carvajal García-Pando, Alfonso
Donati, Monia
Salado Valdivieso, María Inés
Rodríguez, Lauriane
Sáinz Gil, María
Escudero, Antonio
Conforti, Anita
Psicofármacos
Producción Científica
A large number of studies have suggested that being a woman represents a potential risk factor for the development of adverse drug reactions (ADRs). The aim of this study is to further explore the differences between men and women with regard to reported ADRs, particularly those associated with psychotropic drugs. We used spontaneous reports of suspected ADRs collected by Midi-Pyrénées (France), Veneto (Italy) and Castilla y León (Spain) Regional Pharmacovigilance Centres (January 2007-December 2009). All the reports including a psychotropic medication were selected in a first step; age distribution, seriousness and type of ADRs were compared between men and women. Reports of nonpsychotropic drugs were similarly identified and treated. The absolute number of reports and the proportion, considering population, were higher in women than in men. This was observed for all reports, but was particularly higher for psychotropic drugs (592 vs. 375; P < 0.001) than for nonpsychotropics drugs (5193 vs. 4035; P < 0.001). Antidepressants were the most reported (women, 303; men, 141; P < 0.001); the reporting rates (number of reports divided by exposed patients in the same period, estimated through sales data) for these drugs, however, were not significantly different between women (0.87 cases per 10 000 treated persons per year) and men (0.81 cases per 10 000 treated persons per year). Although there was a higher number of reports of ADRs in women, ADR reporting rates might be similar as highlighted by the case of antidepressants. Antidepressant ADRs in fact were similarly reported in men and in women. Gender differences are sometimes subtle and difficult to explore. International networks, as the one established for this study, do contribute to better analyse problems associated with medications.
Junta de Castilla y León. Consejería de Sanidad. Dirección General de Salud Pública e Investigación, Desarrollo e Innovación.
2015-03-06T13:36:36Z
2015-03-06T13:36:36Z
2014
info:eu-repo/semantics/article
https://doi.org/10.1111/fcp.12032
Fundam Clin Pharmacol. 2014 Jun;28(3):342-8
http://uvadoc.uva.es/handle/10324/9048
342
3
348
Fundam Clin Pharmacol
28
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
0767-3981
oai:uvadoc.uva.es:10324/90492021-06-23T09:49:04Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Gastroprotection during the administration of non-steroidal anti-inflammatory drugs. A drug-utilization study
Carvajal García-Pando, Alfonso
Martín Arias, Luis Hermenegildo
Vega Cubillo, Eva
García Sánchez, José Antonio
Martín Rodríguez, Igor
García Ortega, María Pilar
García del Pozo, Javier
Gastroprotectores
Producción Científica
There has been an increase of anti-ulcer drug consumption in Spain. A high proportion of this consumption may be due to the use of those drugs as gastroprotective agents when co-prescribed with non-steroidal anti-inflammatory drugs (NSAIDs). The aim of this study was to learn how these treatments are being used: the prevalence of use, the type of drug and the main features of patients. A sample of patients going to pharmacies with a NSAID prescription, with or without a gastroprotective agent, was obtained. A survey questionnaire was distributed to learn clinical and demographic data of the patients. Of the 942 patients interviewed, 41.6% were co-treated with a gastroprotective agent in addition to the NSAID. Most of these patients received proton-pump inhibitors and, to a lesser extent, histamine-2-receptor antagonists, antacids and prostaglandin analogues. The use of gastroprotective agents increased with age, treatment duration and illness chronicity; specialists prescribed a higher proportion of those co-treatments than did general practitioners. There was a high prescription rate of gastroprotective agents; in general, these were used according to recommendations. However, the type of gastroprotective agents being used does not seem to be justified by the current guidelines: histamine-2-receptor antagonists and antacid drugs have not proved their efficacy in this indication. The fact that one in four treatments with gastroprotective drugs was issued to patients without associated risk factors identifies a possible problem where an intervention could be appropriate.
2015-03-09T09:27:54Z
2015-03-09T09:27:54Z
2004
info:eu-repo/semantics/article
https://doi.org/10.1007/s00228-004-0782-8
Eur J Clin Pharmacol. 2004 Aug;60(6):439-44
0031-6970
http://uvadoc.uva.es/handle/10324/9049
439
6
444
European Journal of Clinical Pharmacology
60
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Springer-Verlag
oai:uvadoc.uva.es:10324/90542021-06-23T09:49:05Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Heart rhythm risturbances associated with rupatadine: a case series from the Spanish and Portuguese Pharmacovigilance Systems
Carvajal García-Pando, Alfonso
Macías, Diego
Salado Valdivieso, María Inés
Sáinz Gil, María
Ortega, Sara
Campo, C.
García del Pozo, Javier
Martín Arias, Luis Hermenegildo
Velasco Martín, Alfonso
Gonçalves, R.
Pombal, R.
Carmona, R.
Insuficiencia cardiaca
Rupatadina
Producción Científica
We searched the Spanish and Portuguese pharmacovigilance databases for spontaneous case reports of heart rhythm disturbances associated with rupatadine and other new H1 antihistamines. Five cases were found involving patients treated with rupatadine (13.9% of all reports relating to this drug). In all five cases, the reaction started after exposure and resolved when the drug was discontinued. In two cases, rupatadine was the only medication being taken by the patient, and no other condition that could explain the heart rhythm disturbances was diagnosed. The reporting odds ratio was 3.2 (95% confidence interval, 1.0-10.5). The reporting rate was 2 cases per 100,000 patients treated per year (95% confidence interval, 0.4-6.0). These results suggest a causal relationship between rupatadine and heart rhythm disturbances
Junta de Castilla y León. Consejería de Sanidad. Dirección General de Salud Pública e Investigación, Desarrollo e Innovación.
2015-03-09T12:41:09Z
2015-03-09T12:41:09Z
2009
info:eu-repo/semantics/article
https://doi.org/10.1038/clpt.2008.269
Clinical Pharmacology and Therapeutics. 2009 May;85(5):481-4
0009-9236
http://uvadoc.uva.es/handle/10324/9054
481
5
484
Clinical Pharmacology and Therapeutics
85
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
American Society for Clinical Pharmacology and Therapeutics
oai:uvadoc.uva.es:10324/90562021-06-23T09:49:07Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
HMG CoA Reductase Inhibitors and Impotence Two Case Series from the Spanish and French Drug Monitoring Systems
Carvajal García-Pando, Alfonso
Macías, Diego
Sáinz Gil, María
Ortega, Sara
Martín Arias, Luis Hermenegildo
Velasco Martín, Alfonso
Bagheri, Haleh
Lapeyre-Mestre, Maryse
Montastruc, Jean Louis
Medicamentos - Efectos secundarios
Impotencia sexual
Producción Científica
Objective: HMG CoA Reductase inhibitors, more commonly called statins, are
used in the pharmacological management of hyperlipidaemia. At present, the use
of these drugs is increasing worldwide. They have been linked to certain adverse
drug reactions, including impotence. The aim of the present study is to explore the
basis of the association between statin use and impotence using data from
spontaneous reports.
Method: We analysed the cases of impotence associated with statins that were
collected by the Spanish and French pharmacovigilance systems. We used cases
of impotence as a numerator and consumption data as a denominator to estimate
the cumulative reported incidence of impotence.
Results: Thirty-eight cases of impotence associated with statins have been
identified in the database of the Spanish pharmacovigilance system; overall, there
was a temporal sequence of events in all cases and the adverse reaction disappeared
after drug withdrawal in 93% of the cases. Sixteen patients had also been
treated with other drugs. In France, 37 cases were collected. In 85% of these cases
recovery from the adverse reaction was observed after drug withdrawal; there was
a positive rechallenge in five cases, and 15 patients were receiving other drugs at
the same time. No significant differences among reported incidences with different
statins were found.
Conclusion: Considering the widespread use of this drug class and the under-reporting
of this particular reaction it could affect a large number of patients. The
reaction seems to be reversible in most of the cases after drug withdrawal. Doctors
should be aware of this potential adverse reaction when prescribing statins to their
patients.
2015-03-10T08:35:37Z
2015-03-10T08:35:37Z
2006
info:eu-repo/semantics/article
https://doi.org/10.2165/00002018-200629020-00004
Drug Safety, 2006; 29 (2): 143-149
0114-5916
http://uvadoc.uva.es/handle/10324/9056
143
2
149
Drug Safety
29
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Springer Verlag
oai:uvadoc.uva.es:10324/90602021-06-23T09:49:08Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
EUDRAGENE: European collaboration to establish a case–control DNA collection for studying the genetic basis of adverse drug reactions
Molokhia, Mariam
McKeigue, Paul
Medicamentos - Efectos adversos
Producción Científica
Type B adverse drug reactions (ADRs) are often serious, limit the usefulness of drugs that are otherwise effective, and increase the risks of drug development as they often lead to postmarketing withdrawal. There is evidence that susceptibility to at least some Type B ADRs is under strong genetic influence. Identifying genes in which variation influences susceptibility has obvious practical value for genetic testing and might also make it easier to screen molecules likely to cause ADRs at an early stage of the drug development process. Research in this area is hampered by the lack of a resource in which to study genetic determinants of susceptibility to Type B ADRs. As serious Type B ADRs are rare, case-control designs are the most frequently-used approach. The EUDRAGENE collaboration seeks to develop a resource using an international collaboration. This will provide a basis for adverse drug susceptibility genome association-wide studies using tag single nucleotide polymorphisms, or a direct approach using putative functional polymorphisms.
2015-03-10T12:17:45Z
2015-03-10T12:17:45Z
2006
info:eu-repo/semantics/article
https://doi.org/10.2217/14622416.7.4.633
Pharmacogenomics. 2006 Jun;7(4):633-8.
1462-2416
http://uvadoc.uva.es/handle/10324/9060
633
4
638
Pharmacogenomics
7
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Future Medicine
oai:uvadoc.uva.es:10324/94652021-10-18T12:41:48Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
NADþ protects against EAE by regulating CD4þ T-cell differentiation
Tullius, Stefan G.
Rodriguez-Cetina Biefer, Héctor
Li, Suyan
Trachtenberg, Alexander J.
Edtinger, Karoline
Quante, Markus
Krenzien, Felix
Uehara, Hirofumi
Yang, Xiaoyong
Kissick, Haydn T.
Kuo, Winston P.
Ghiran, Ionita
Fuente García, Miguel Ángel de la
Arredouani, Mohamed S.
Camacho, Virginia
Tigges, John C.
Toxavidis, Vasilis
El Fatimy, Rachid
Smith, Brian D.
Vasudevan, Anju
Elkhal, Abdallah
Inmunología
Medicamentos - Investigación
Producción Científica
CD4(+) T cells are involved in the development of autoimmunity, including multiple sclerosis (MS). Here we show that nicotinamide adenine dinucleotide (NAD(+)) blocks experimental autoimmune encephalomyelitis (EAE), a mouse model of MS, by inducing immune homeostasis through CD4(+)IFNγ(+)IL-10(+) T cells and reverses disease progression by restoring tissue integrity via remyelination and neuroregeneration. We show that NAD(+) regulates CD4(+) T-cell differentiation through tryptophan hydroxylase-1 (Tph1), independently of well-established transcription factors. In the presence of NAD(+), the frequency of T-bet(-/-) CD4(+)IFNγ(+) T cells was twofold higher than wild-type CD4(+) T cells cultured in conventional T helper 1 polarizing conditions. Our findings unravel a new pathway orchestrating CD4(+) T-cell differentiation and demonstrate that NAD(+) may serve as a powerful therapeutic agent for the treatment of autoimmune and other diseases.
2015-03-18T11:48:27Z
2015-03-18T11:48:27Z
2014
info:eu-repo/semantics/article
https://doi.org/10.1038/ncomms6101.
Nature Communications, 2014, 5, Article number: 5101
2041-1723
http://uvadoc.uva.es/handle/10324/9465
Nature Communications
5
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Nature Publish Group
oai:uvadoc.uva.es:10324/98102021-06-23T09:49:13Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Reduced thymic output, cell cycle abnormalities, and increased apoptosis of T lymphocytes in patients with cartilage-hair hypoplasia
Fuente García, Miguel Ángel de la
Recher, Mike
Rider, Nicholas L.
Strauss, Kevin A.
Morton, D. Holmes
Adair, Margaret
Bonilla, Francisco A.
Ochs, Hans D.
Gelfand, Erwin W.
Pessach, Itai M.
Walter, Jolan E.
King, Alejandra
Giliani, Silvia
Pai, Sung-Yun
Notarangelo, Luigi D.
Sistema inmunitario - Enfermedades
Producción Científica
Background: Cartilage-hair hypoplasia (CHH) is characterized by metaphyseal dysplasia, bone marrow failure, increased risk of malignancies, and a variable degree of immunodeficiency. CHH is caused by mutations in the RNA component of the mitochondrial RNA processing (RMRP) endoribonuclease gene, which is involved in ribosomal assembly, telomere function, and cell cycle control. Objectives: We aimed to define thymic output and characterize immune function in a cohort of patients with molecularly defined CHH with and without associated clinical immunodeficiency. Methods: We studied the distribution of B and T lymphocytes (including recent thymic emigrants), in vitro lymphocyte proliferation, cell cycle, and apoptosis in 18 patients with CHH compared with controls. Results: Patients with CHH have a markedly reduced number of recent thymic emigrants, and their peripheral T cells show defects in cell cycle control and display increased apoptosis, resulting in poor proliferation on activation. Conclusion: These data confirm that RMRP mutations result in significant defects of cell-mediated immunity and provide a link between the cellular phenotype and the immunodeficiency in CHH
2015-03-19T12:13:47Z
2015-03-19T12:13:47Z
2011
info:eu-repo/semantics/article
https://doi.org/10.1016/j.jaci.2011.03.042
Journal of Allergy Clinical and Immunology 128(1): 139–146.
0091-6749
http://uvadoc.uva.es/handle/10324/9810
139
1
146
Journal of Allergy Clinical and Immunology
128
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Elsevier
oai:uvadoc.uva.es:10324/98172021-06-23T09:49:15Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Fas-activated serine/threonine phosphoprotein promotes immune-mediated pulmonary inflammation
Simarro Grande, María
Giannattasio, Giorgio
Benarafa, Charaf
Subramanian, Kulandayan K.
Ishizawar, Rumey
Balestrieri, Barbara
Andersson, Emma M.
Luo, Hongbo R.
Orduña Domingo, Antonio
Boyce, Joshua
Fuente García, Miguel Ángel de la
Sistema inmunitario-Enfermedades
Producción Científica
We generated Fas-activated serine threonine phosphoprotein (FAST)-deficient mice (FAST−/−) to study the in vivo role of FAST in immune system function. In a model of house dust mite-induced allergic pulmonary inflammation, wild type mice develop a mixed cellular infiltrate composed of eosinophils, lymphocytes, and neutrophils. FAST−/− mice develop airway inflammation that is distinguished by the near absence of neutrophils. Similarly, LPS-induced alveolar neutrophil recruitment is markedly reduced in FAST−/− mice compared with wild type controls. This is accompanied by reduced concentrations of cytokines (TNF-α and IL-6 and -23) and chemoattractants (MIP-2 and keratinocyte chemoattractant) in bronchoalveolar lavage fluids. Because FAST−/− neutrophils exhibit normal chemotaxis and survival, impaired neutrophil recruitment is likely to be due to reduced production of chemoattractants within the pulmonary parenchyma. Studies using bone marrow chimeras implicate lung resident hematopoietic cells (e.g., pulmonary dendritic cells and/or alveolar macrophages) in this process. In conclusion, our results introduce FAST as a proinflammatory factor that modulates the function of lung resident hematopoietic cells to promote neutrophil recruitment and pulmonary inflammation.
2015-03-20T08:26:56Z
2015-03-20T08:26:56Z
2010
info:eu-repo/semantics/article
https://doi.org/10.4049/jimmunol.1000104
J Immunol. 2010; 184(9): 5325–5332.
0022-1767
http://uvadoc.uva.es/handle/10324/9817
5325
9
5332
Journal of Immunology
184
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
American Association of Immunologists
oai:uvadoc.uva.es:10324/98242021-06-23T09:49:16Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
WASP confers selective advantage for specific hematopoietic cell populations and serves a unique role in marginal zone B-cell homeostasis and function.
Westerberg, Lisa S.
Wermeling, Fredrik
Ochs, Hans D.
Karlsson, Mikael C. I.
Snapper, Scott B.
Notarangelo, Luigi D.
Fuente García, Miguel Ángel de la
Células hematopoyéticas
Producción Científica
Development of hematopoietic cells depends on a dynamic actin cytoskeleton. Here we demonstrate that expression of the cytoskeletal regulator WASP, mutated in the Wiskott-Aldrich syndrome, provides selective advantage for the development of naturally occurring regulatory T cells, natural killer T cells, CD4(+) and CD8(+) T lymphocytes, marginal zone (MZ) B cells, MZ macrophages, and platelets. To define the relative contribution of MZ B cells and MZ macrophages for MZ development, we generated wild-type and WASP-deficient bone marrow chimeric mice, with full restoration of the MZ. However, even in the presence of MZ macrophages, only 10% of MZ B cells were of WASP-deficient origin. We show that WASP-deficient MZ B cells hyperproliferate in vivo and fail to respond to sphingosine-1-phosphate, a crucial chemoattractant for MZ B-cell positioning. Abnormalities of the MZ compartment in WASP(-/-) mice lead to aberrant uptake of Staphylococcus aureus and to a reduced immune response to TNP-Ficoll. Moreover, WASP-deficient mice have increased levels of "natural" IgM antibodies. Our findings reveal that WASP regulates both development and function of hematopoietic cells. We demonstrate that WASP deficiency leads to an aberrant MZ that may affect responses to blood-borne pathogens and peripheral B-cell tolerance.
2015-03-23T08:37:40Z
2015-03-23T08:37:40Z
2008
info:eu-repo/semantics/article
https://doi.org/10.1182/blood-2008-02-140715
Blood. 2008 Nov 15;112(10):4139-47
0006-4971
http://uvadoc.uva.es/handle/10324/9824
4139
10
4147
Blood
112
spa
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
American Society of Hematology
oai:uvadoc.uva.es:10324/98252021-06-23T09:49:19Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Transcellular diapedesis is initiated by invasive podosomes
Carman, Christopher V.
Sage, Peter T.
Sciuto, Tracey E.
Geha, Raif S.
Ochs, Hans D.
Dvorak, Harold F.
Dvorak, Ann M.
Springer, Timothy A.
Fuente García, Miguel Ángel de la
Pie - Enfermedades
Producción Científica
Diapedesis is critical for immune system function and inflammatory responses. This occurs by migration of blood leukocytes either directly through individual microvascular endothelial cells (the “transcellular” route) or between them (the “paracellular” route). Mechanisms for transcellular pore formation in endothelium remain unknown. Here we demonstrate that lymphocytes used podosomes and extended “invasive podosomes” to palpate the surface of, and ultimately form transcellular pores through, the endothelium. In lymphocytes, these structures were dependent on Src kinase and the actin regulatory protein WASP; inhibition of podosome formation selectively blocked the transcellular route of diapedesis. In endothelium, membrane fusion events dependent on the SNARE-containing membrane fusion complex and intracellular calcium were required for efficient transcellular pore formation in response to podosomes. These findings provide insights into basic mechanisms for leukocyte trafficking and the functions of podosomes.
2015-03-23T09:07:48Z
2015-03-23T09:07:48Z
2007
info:eu-repo/semantics/article
https://doi.org/10.1016/j.immuni.2007.04.015
Immunity. 2007 Jun; 26(6): 784–797
1074-7613
http://uvadoc.uva.es/handle/10324/9825
784
6
797
Immunity
26
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Elsevier
oai:uvadoc.uva.es:10324/98262021-06-23T09:49:21Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
WIP is a chaperone for Wiskott–Aldrich syndrome protein (WASP)
Fuente García, Miguel Ángel de la
Sasahara, Yoji
Calamito, Marco
Antón, Inés María
Elkhal, Abdallah
Gallego, María Dolores
Suresh, Koduro
Siminovitch, Katherine
Ochs, Hans D.
Anderson, Kenneth C.
Rosen, Fred S.
Geha, Raif S.
Ramesh, Narayanaswamy
Wiskott Aldrich, Síndrome protéico
Producción Científica
Wiskott–Aldrich syndrome protein (WASP) is in a complex with
WASP-interacting protein (WIP). WASP levels, but not mRNA levels,
were severely diminished in T cells from WIP / mice and were
increased by introduction of WIP in these cells. The WASP binding
domain of WIP was shown to protect WASP from degradation by
calpain in vitro. Treatment with the proteasome inhibitors MG132
and bortezomib increased WASP levels in T cells from WIP / mice
and in T and B lymphocytes from two WAS patients with missense
mutations (R86H and T45M) that disrupt WIP binding. The calpain
inhibitor calpeptin increased WASP levels in activated T and B cells
from the WASP patients, but not in primary T cells from the patients
or from WIP / mice. Despite its ability to increase WASP levels
proteasome inhibition did not correct the impaired IL-2 gene
expression and low F-actin content in T cells from the R86H WAS
patient. These results demonstrate that WIP stabilizes WASP and
suggest that it may also be important for its function
2015-03-23T12:36:37Z
2015-03-23T12:36:37Z
2007
info:eu-repo/semantics/article
https://doi.org/10.1073/pnas.0610275104
Proceedings of the National Academy of Sciences U S A. 2007 Jan 16;104(3):926-31
0027-8424
http://uvadoc.uva.es/handle/10324/9826
926
3
931
Proceedings of the National Academy of Sciences
104
eng
https://www.pnas.org/content/104/3/926
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
National Academy of Sciences
oai:uvadoc.uva.es:10324/98282021-06-23T09:49:23Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
3BP2 Deficiency impairs the response of B cells, but not T cells, to antigen receptor ligation
Fuente García, Miguel Ángel de la
Kumar, Lalit
Lu, Bao
Geha, Raif S.
Biología celular
Producción Científica
The adapter protein 3BP2 is expressed in lymphocytes; binds to Syk/ZAP-70, Vav, and phospholipase C-γ (PLC-γ); and is thought to be important for interleukin-2 gene transcription in T cells. To define the role of 3BP2 in lymphocyte development and function, we generated 3BP2-deficient mice. T-cell development, proliferation, cytokine secretion, and signaling in response to T-cell receptor (TCR) ligation were all normal in 3BP2−/− mice. 3BP2−/− mice had increased accumulation of pre-B cells in the bone marrow and a block in the progression of transitional B cells in the spleen from the T1 to the T2 stage, but normal numbers of mature B cells. B-cell proliferation, cell cycle progression, PLC-γ2 phosphorylation, calcium mobilization, NF-ATp dephosphorylation, and Erk and Jnk activation in response to B-cell receptor (BCR) ligation were all impaired. These results suggest that 3BP2 is important for BCR, but not for TCR signaling.
2015-03-24T10:24:59Z
2015-03-24T10:24:59Z
2006
info:eu-repo/semantics/article
https://doi.org/10.1128/MCB.00087-06
Molecular and Cellular Biology, 2006, vol. 26, n. 14. p. 5214–5225
0270-7306
http://uvadoc.uva.es/handle/10324/9828
5214
14
5225
Molecular and Cellular Biology
26
eng
https://mcb.asm.org/content/26/14/5214.long
Attribution-NonCommercial-NoDerivatives 3.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
American Society for Microbiology
oai:uvadoc.uva.es:10324/98382021-06-23T09:49:25Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
WIP and WASP play complementary roles in T cell homing and chemotaxis to SDF-1a
Gallego, María Dolores
Fuente García, Miguel Ángel de la
Antón, Inés María
Snapper, Scott B.
Fuhlbrigge, Robert
Geha, Raif S.
Biología celular
Producción Científica
Homing of lymphocytes to tissues is a biologically important multistep process that involves selectindependent
rolling, integrin-dependent adhesion and chemokine-directed chemotaxis. The actin
cytoskeleton plays a central role in lymphocyte adhesion and motility. Wiskott–Aldrich syndrome
protein (WASP), the product of the gene mutated in Wiskott–Aldrich syndrome, and its partner,
the Wiskott–Aldrich syndrome protein-interacting protein (WIP), play important roles in actin
re-organization in T lymphocytes. We used mice with disruption of the WASP and WIP genes to
examine the role of WASP and WIP in T cell homing. T cell homing to spleen and lymph nodes in vivo
was deficient in WASP / and WIP / mice and severely impaired in WASP / WIP / double knockout
(DKO) mice. Deficiency of WASP, WIP or both did not interfere with selectin-dependent rolling or
integrin-dependent adhesion of T cells in vitro. Chemotaxis to stromal cell-derived factor-1a (SDF-1a)
in vitro was mildly reduced in T cells from WASP / mice. In contrast, it was significantly impaired in
T cells from WIP / mice and severely reduced in T cells from DKO mice. Cellular F-actin increase
following SDF-1a stimulation was normal in WASP / and WIP / T cells, but severely reduced in
T cells from DKO mice. Actin re-organization and polarization in response to SDF-1a was abnormal in
T cells from all knockout mice. Early biochemical events following SDF-1a stimulation that are
important for chemotaxis and that included phosphorylation of Lck, cofilin, PAK1 and extracellular
regulated kinase (Erk) and GTP loading of Rac-1 were examined in T cells from DKO mice and found to
be normal. These results suggest that WASP and WIP are not essential for T lymphocyte rolling and
adhesion, but play important and partially redundant roles in T cell chemotaxis in vitro and homing
in vivo and function downstream of small GTPases.
2015-03-25T09:03:01Z
2015-03-25T09:03:01Z
2005
info:eu-repo/semantics/article
https://doi.org/10.1093/intimm/dxh310
International Immunology, 2005, vol. 18, n. 2, p. 221-232
0953-8178
http://uvadoc.uva.es/handle/10324/9838
221
2
232
International Immunology
18
eng
https://academic.oup.com/intimm/article/18/2/221/664515
Attribution-NonCommercial-ShareAlike 3.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-sa/3.0/
application/pdf
Oxford University Press
oai:uvadoc.uva.es:10324/98432022-06-28T11:46:06Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Defective nuclear translocation of nuclear factor of activated T cells and extracellular signal-regulated kinase underlies deficient IL-2 gene expression in Wiskott-Aldrich syndrome
Cianferoni, Antonella
Massaad, Michel
Feske, Stefan
Fuente García, Miguel Ángel de la
Gallego, María Dolores
Ramesh, Narayanaswamy
Geha, Raif S.
Wiskott Aldrich, Síndrome
Biología celular
Producción Científica
Background: Proliferation and IL-2 production in response to
T-cell receptor ligation are impaired in patients with Wiskott-
Aldrich syndrome (WAS). The transcription factors nuclear
factor-kB (NF-kB), nuclear factor of activated T cells (NF-AT),
and activating protein-1 (AP-1) play a critical role in IL-2 gene
expression.
Objective: To investigate the mechanisms of impaired IL-2
production after T-cell receptor ligation in T cells deficient in
WAS protein (WASP).
Methods: T cells from WASP2/2 mice were stimulated with
anti-CD3 and anti-CD28. Nuclear NF-kB, NF-AT, and AP-1
DNA-binding activity was examined by electroshift mobility
assay. NF-ATp dephosphorylation and nuclear localization
were examined by Western blot and indirect immunofluorescence.
Phosphorylation of the mitogen-activated protein
kinases Erk and Jnk, and of their nuclear substrates Elk-1 and
c-Jun, was examined by Western blot. Expression of mRNA for
IL-2 and the NF-kB–dependent gene A20 and of the AP-1
components c-fos and c-Jun was examined by quantitative
RT-PCR.
Results: Nuclear translocation and activity of NF-kB were
normal in T cells from WASP2/2 mice. In contrast, NF-ATp
dephosphorylation and nuclear localization, nuclear AP-1
binding activity, and expression of c-fos, but not c-Jun, were all
impaired. Phosphorylation of Jnk, c-Jun, and Erk were normal.
However, nuclear translocation of phosphorylated
Erk and phosphorylation of its nuclear substrate Elk1,
which activates the c-fos promoter, were impaired.
Conclusion: These results suggest that WASP is essential for
NF-ATp activation, and for nuclear translocation of p-Erk,
Elk1 phosphorylation, and c-fos gene expression in T cells.
These defects underlie defective IL-2 expression and T-cell
proliferation in WAS.
2015-03-25T13:23:50Z
2015-03-25T13:23:50Z
2005
info:eu-repo/semantics/article
https://doi.org/10.1016/j.jaci.2005.09.006
Journal of Allergy and Clinical Immunology, 2005 ;116(6):1364-71.
0091-6749
http://uvadoc.uva.es/handle/10324/9843
1364
6
1371
Journal of Allergy and Clinical Immunology
116
eng
Attribution-NonCommercial-ShareAlike 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-sa/4.0/
application/pdf
Elsevier
oai:uvadoc.uva.es:10324/101172021-06-23T09:49:27Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
CD229 (Ly9) lymphocyte cell surface receptor Interacts homophilically through Its N-Terminal domain and relocalizes to the immunological synapse
Romero, Xavier
Zapater, Nuria
Calvo, María
Kalko, Susana G.
Fuente García, Miguel Ángel de la
Tovar, Victoria
Ockeloen, Charlotte
Pizcueta, Pilar
Engel, Pablo
Inmunología
Producción Científica
CD229 is a member of the CD150 family of the Ig superfamily expressed on T and B cells. Receptors of this family regulate
cytokine production and cytotoxicity of lymphocytes and NK cells. The cytoplasmic tail of CD229 binds to SAP, a protein that is
defective in X-linked lymphoproliferative syndrome. To identify the CD229 ligand, we generated a soluble Ig fusion protein
containing the two N-terminal extracellular domains of human CD229 (CD229-Ig). CD229-Ig bound to CD229-transfected cells,
whereas no binding was detected on cells expressing other CD150 family receptors, showing that CD229 binds homophilically.
Both human and mouse CD229 interacted with itself. Domain deletion mutants showed that the N-terminal Ig-domain mediates
homophilic adhesion. CD229-CD229 binding was severely compromised when the charged amino acids E27 and E29 on the
predicted B-C loop and R89 on the F-G loop of the N-terminal domain were mutated to alanine. In contrast, one mutation, R44A,
enhanced the homophilic interaction. Confocal microscopy image analysis revealed relocalization of CD229 to the contact area of
T and B cells during Ag-dependent immune synapse formation. Thus, CD229 is its own ligand and participates in the immunological
synapse.
2015-03-26T09:14:22Z
2015-03-26T09:14:22Z
2005
info:eu-repo/semantics/article
https://doi.org/10.4049/jimmunol.174.11.7033
The Journal of Immunology, 2005, vol. 174, n. 11. p. 7033–7042.
0022-1767
http://uvadoc.uva.es/handle/10324/10117
7033
11
7042
The Journal of Immunology
174
eng
https://www.jimmunol.org/content/174/11/7033
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
American Association of Immunologists
oai:uvadoc.uva.es:10324/101252021-06-23T09:49:29Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
WIP regulates signaling via the high affinity receptor for immunoglobulin E in mast cells
Kettner, Alexander
Kumar, Lalit
Antón, Inés María
Sasahara, Yoji
Pivniouk, Vadim
Falet, Hervé
Hartwig, John H.
Geha, Raif S.
Fuente García, Miguel Ángel de la
Síndrome de Wiskott-Aldrich
Producción Científica
Wiskott-Aldrich syndrome protein-interacting protein (WIP) stabilizes actin filaments and is important for immunoreceptor-mediated signal transduction leading to actin cytoskeleton rearrangement in T and B cells. Here we report a role for WIP in signaling pathways downstream of the high affinity receptor for immunoglobulin (Ig)E (FcepsilonRI) in mast cells. WIP-deficient bone marrow-derived mast cells (BMMCs) were impaired in their capacity to degranulate and secrete interleukin 6 after FcepsilonRI ligation. Calcium mobilization, phosphorylation of Syk, phospholipase C-g2, and c-Jun NH2-terminal kinase were markedly decreased in WIP-deficient BMMCs. WIP was found to associate with Syk after FcepsilonRI ligation and to inhibit Syk degradation as evidenced by markedly diminished Syk levels in WIP-deficient BMMCs. WIP-deficient BMMCs exhibited no apparent defect in their subcortical actin network and were normal in their ability to form protrusions when exposed to an IgE-coated surface. However, the kinetics of actin changes and the cell shape changes that follow FcepsilonRI signaling were altered in WIP-deficient BMMCs. These results suggest that WIP regulates FcepsilonRI-mediated mast cell activation by regulating Syk levels and actin cytoskeleton rearrangement.
2015-03-26T12:57:47Z
2015-03-26T12:57:47Z
2004
info:eu-repo/semantics/article
https://doi.org/10.1084/jem.2003065
Journal of Experimental Medicine, 2004, vol. 199, n. 3. p. 357-368
0022-1007
http://uvadoc.uva.es/handle/10324/10125
357
3
368
Journal of Experimental Medicine
199
eng
https://rupress.org/jem/article/199/3/357/40031/WIP-Regulates-Signaling-via-the-High-Affinity
Attribution-NonCommercial-NoDerivatives 3.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/3.0/
application/pdf
Rockefeller University Press
oai:uvadoc.uva.es:10324/101362021-06-23T09:49:30Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Mechanism of recruitment of WASP to the immunological synapse and of its activation following TCR ligation
Sasahara, Yoji
Rachid, Rima
Byrne, Michael J.
Abraham, Robert T.
Ramesh, Narayanaswamy
Geha, Raif S.
Fuente García, Miguel Ángel de la
Biología molecular
Producción Científica
F-actin polymerization following engagement of the T cell receptor (TCR) is dependent on WASP and is critical for T cell activation. The link between TCR and WASP is not fully understood. In resting cells, WASP exists in a complex with WIP, which inhibits its activation by Cdc42. We show that the adaptor protein CrkL binds directly to WIP. Further, TCR ligation results in the formation of a ZAP-70-CrkL-WIP-WASP complex, which is recruited to lipid rafts and the immunological synapse. TCR engagement also causes PKCtheta-dependent phosphorylation of WIP, causing the disengagement of WASP from the WIP-WASP complex, thereby releasing it from WIP inhibition. These results suggest that the ZAP-70-CrkL-WIP pathway and PKCtheta link TCR to WASP activation.
2015-03-27T09:03:44Z
2015-03-27T09:03:44Z
2002
info:eu-repo/semantics/article
https://doi.org/10.1016/s1097-2765(02)00728-1
Molecular Cell, 2002, vol. 10, n. 6. p. 1269-1281
1097-2765
http://uvadoc.uva.es/handle/10324/10136
1269
6
1281
Molecular Cel
10
eng
https://www.sciencedirect.com/science/article/pii/S1097276502007281?via%3Dihub
Attribution-NonCommercial-ShareAlike 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-sa/4.0/
application/pdf
Elsevier
oai:uvadoc.uva.es:10324/101442021-06-23T09:49:31Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
WIP deficiency reveals a differential role for WIP and the actin cytoskeleton in T and B cell activation
Antón, Inés María
Fuente García, Miguel Ángel de la
Sims, Tasha N.
Freeman, Sheryl
Ramesh, Narayanaswamy
Hartwig, John H.
Dustin, Michael L.
Geha, Raif S.
Biología celular
Producción Científica
WIP stabilizes actin filaments and is important for filopodium formation. To define the role of WIP in immunity, we generated WIP-deficient mice. WIP(minus sign/minus sign) mice have normal lymphocyte development, but their T cells fail to proliferate, secrete IL-2, increase their F-actin content, polarize and extend protrusions following T cell receptor ligation, and are deficient in conjugate formation with superantigen-presenting B cells and anti-CD3 bilayers. In contrast, WIP-deficient B lymphocytes have enhanced proliferation and CD69 expression following B cell receptor ligation and mount normal antibody responses to T-independent antigens. Both WIP-deficient T and B cells show a profound defect in their subcortical actin filament networks. These results suggest that WIP is important for immunologic synapse formation and T cell activation.
2015-03-27T11:57:50Z
2015-03-27T11:57:50Z
2002
info:eu-repo/semantics/article
https://doi.org/10.1016/S1074-7613(02)00268-6
Immunity, 2002, 16(2):193-204
1074-7613
http://uvadoc.uva.es/handle/10324/10144
193
2
204
Immunity
16
eng
Attribution-NonCommercial-ShareAlike 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-sa/4.0/
application/pdf
Elsevier (Cell Press)
oai:uvadoc.uva.es:10324/101522022-06-28T07:30:28Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
CD84 Functions as a homophilic adhesion molecule and enhances IFN- g secretion:adhesion is mediated by Ig-like domain 1
Martín, Margarita
Romero, Xavier
Fuente García, Miguel Ángel de la
Tovar, Victoria
Zapater, Nuria
Esplugues, Enric
Pizcueta, Pilar
Bosch, Jaime
Engel, Pablo
Biología molecular
Producción Científica
CD84 is a member of the CD2 subset of the Ig superfamily of cell surface molecules. Its cytoplasmic tail binds to Src homology 2 domain-containing protein 1A (signaling lymphocytic activation molecule-associated protein), a protein encoded by the X-linked lymphoproliferative disease gene. It is preferentially expressed on B lymphocytes, monocytes, and platelets. We show that it is also expressed on thymocytes and T cells. CD84 was positive on CD4 CD8 thymocytes, and its expression decreased with cell maturation. It is expressed on mature T cells preferentially on CD45RO . To identify the CD84 ligand, we generated a soluble
Ig fusion protein containing the human CD84 extracellular domains (CD84-Ig). Because receptor-ligand interactions occur between several members of this subfamily, we assayed CD84-Ig binding with all members of the CD2 family. CD84-Ig bound to CD84-transfected cells, whereas no binding was detected with cells expressing other CD2 subfamily receptors, showing that CD84 binds to itself. Anti-CD84 mAbs recognizing epitopes wholly within domain 1 of CD84 blocked the binding of the CD84-Ig fusion protein to CD84-transfected cells and platelets. Data from CD84 domain human/mouse chimeras further revealed that only the first extracellular domain of the molecule is involved in the ligand receptor recognition. The CD84-CD84 interaction was independent of its cytoplasmic tail. Finally, concurrent ligation of human CD84 with mAbs or CD84-Ig and CD3 enhanced IFN-secretion in human lymphocytes. Thus, CD84 is its own ligand and acts as a costimulatory molecule.
2015-04-08T11:33:45Z
2015-04-08T11:33:45Z
2001
info:eu-repo/semantics/article
https://doi.org/10.4049/jimmunol.167.7.3668
The Journal of Immunology 2001, 167(7): 3668–3676.
0022-1767
http://uvadoc.uva.es/handle/10324/10152
3668
7
3676
The Journal of Immunology
167
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
American Association of Immunologists
oai:uvadoc.uva.es:10324/101532021-06-23T09:48:29Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Differential role of SLP-76 domains in T cell development and function
Kumar, Lalit
Pivniouk, Vadim
Fuente García, Miguel Ángel de la
Laouini, Dhafer
Geha, Raif S.
Biología molecular
Producción Científica
The adapter SLP-76 is essential for thymocyte development. SLP-76−/− mice were reconstituted with SLP-76 deletion mutant transgenes to examine the role of SLP-76 domains in T cell development and function. The N-terminal domain deletion mutant completely failed to restore thymocyte development. Mice reconstituted with Gads-binding site and SH2 domain deletion mutants had decreased thymic cellularity, impaired transition from double to single positive thymocytes, and decreased numbers of mature T cells in the spleen. Calcium mobilization and extracellular signal-regulated protein kinase activation were decreased in the Gads-binding site mutant but almost normal in the SH2 domain mutant. T cells from both mutants failed to proliferate following T cell antigen receptor ligation. Nevertheless, both mutants mounted partial cutaneous hypersensitivity responses and normal T cell dependent IgG1 antibody responses. These results indicate differential roles for SLP-76 domains in T cell development, proliferation and effector functions.
2015-04-08T12:30:39Z
2015-04-08T12:30:39Z
2002
info:eu-repo/semantics/article
https://doi.org/10.1073 pnas.022619199
Proceedings of the National Academy of Sciences of the United States of America, 2002, vol. 99, n. 2. p. 884-889
1091-6490
http://uvadoc.uva.es/handle/10324/10153
884
2
889
PNAS
99
eng
https://www.pnas.org/content/99/2/884
Attribution-NonCommercial-NoDerivatives 3.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/3.0/
application/pdf
oai:uvadoc.uva.es:10324/103602021-06-23T09:48:54Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Molecular characterization and expression of a novel human leukocyte cell-surface marker homologous to mouse Ly-9
Fuente García, Miguel Ángel de la
Tovar, Victoria
Villamor, Neus
Zapater, Nuria
Pizcueta, Pilar
Campo, Elias
Jaime Bosch, Jaime
Engel, Pablo
Hematología
Producción Científica
.Ly-9 is a mouse cell-surface glycoprotein that is selectively expressed on thymocytes and on mature T and B lymphocytes. Ly-9 belongs to the CD2 subset of the immunoglobulin superfamily, an emerging family of cell signaling receptors. Recently, a partial human Ly-9 complementary DNA (cDNA) sequence has been described. Full-length cDNA clones were isolated that included the initiation codon, the sequence encoding the full signal peptide, and 14 amino acids more in the cytoplasmic domain than in the previously reported clone. The predicted extracellular domain of human Ly-9 contains 4 immunoglobulinlike domains, similar to those in mouse Ly-9. Northern blot analysis revealed that the human Ly-9 messenger RNA (2.6 kb) is expressed predominantly in lymph node, spleen, thymus, and peripheral blood leukocytes. Four monoclonal antibodies (mAbs) were raised against human Ly-9 by immunizing mice with the pre-B-cell line 300.19 stably transfected with human Ly-9 full-length cDNA. These mAbs strongly stained the surfaces of cells transfected with human Ly-9 cDNA but not of untransfected cells. Human Ly-9 expression was restricted to T and B lymphocytes and thymocytes, with the highest levels of expression on CD4(+)CD8(-) and CD4(-)CD8(+) thymocytes. Monocytes, granulocytes, platelets, and red blood cells were uniformly negative for Ly-9. These mAbs immunoprecipitated major polypeptides of 120 kd from the transfected cells and 120 kd and 100 kd from B-cell line Daudi, probably because of the cell-surface-expressed isoforms. These data demonstrate that human Ly-9 is a new marker for the study of normal and malignant leukocytes
2015-04-09T07:45:18Z
2015-04-09T07:45:18Z
2001
info:eu-repo/semantics/article
https://doi.org/10.1182/blood.V97.11.3513
Blood, 2001, 97(11):3513-3520
0006-4971
http://uvadoc.uva.es/handle/10324/10360
3513
11
3520
Blood
97
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
American Society of Hematology
oai:uvadoc.uva.es:10324/103652021-06-23T09:49:32Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
CD148 is a membrane protein tyrosine phosphatase present in all hematopoietic lineages and is involved in signal transduction on lymphocytes
Fuente García, Miguel Ángel de la
Nicolás, Josep Maria
Freed, John H.
Palou, Eduard
Thomas, Andrew P.
Vilella, Ramón
Vives, Jordi
Gayá, Antoni
Células hematopoyéticas
Hematología
Producción Científica
Evidence is presented showing that a protein tyrosine phosphatase different from CD45 is present on the membrane of human hematopoietic cells. The molecule recognized by the monoclonal antibody 143-41, which has been classified as CD148 in the VI International Workshop on Leukocyte Differentiation Antigens, was immunopurified and sequenced. The sequence obtained from N-terminus as well as from two different CNBr-digested peptides showed a close identity with a previously described tyrosine phosphatase named HPTP-eta/DEP-1. CD148 is present on all hematopoietic lineages, being expressed with higher intensity on granulocytes than on monocytes and lymphocytes. Interestingly, whereas it is clearly present on peripheral blood lymphocytes, it is poorly expressed on different lymphoid cell lines of T and B origin. When this protein tyrosine phosphatase was cocrosslinked with CD3, an inhibition of the normally observed calcium mobilization was observed. This inhibition correlates with a decrease in phospholipase C-gamma (PLC-gamma) phosphorylation and is similar to the one observed with CD45. In addition, it is shown that the crosslinking of the CD148 alone is also able to induce an increase in [Ca2+]i. This increase is abolished in the presence of genistein and by cocrosslinking with CD45. These data, together with the induction of tyrosine phosphorylation on several substrates, including PLC-gamma, after CD148 crosslinking, suggest the involvement of a tyrosine kinase-based signaling pathway in this process. In conclusion, the data presented show that CD148 corresponds to a previously described protein tyrosine phosphatase HPTP-eta/DEP-1 and that this molecule is involved in signal transduction in lymphocytes.
2015-04-09T12:14:46Z
2015-04-09T12:14:46Z
1998
info:eu-repo/semantics/article
Blood. 1998; 91(8):2800-2809
0006-4971
http://uvadoc.uva.es/handle/10324/10365
2800
8
2809
Blood
91
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
American Society of Hematology
oai:uvadoc.uva.es:10324/103792021-06-23T09:48:56Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
CD84 leukocyte antigen is a new member of the Ig superfamily
Fuente García, Miguel Ángel de la
Pizcueta, Pilar
Nadal, Marga
Bosch, Jaime
Engel, Pablo
Hematología
Células hematopoyéticas
Producción Científica
cDNA isolated from a human B-cell line Raji library was ana- (CD48 and HumLy9) have been mapped. CD84 monoclonal lyzed and shown to encode the full-length cDNA sequence antibodies (MoAbs) were shown to react with cells transof a novel cell-surface glycoprotein, initially termed HLy9-b. fected with the cloned cDNA. These MoAbs were further
The predicted mature 307-amino acid protein was composed used to show that CD84 is expressed as a single chain cellof two extracellular Ig-like domains, a hydrophobic trans- surface glycoprotein of Mr 64,000 to 82,000, which was
membrane region, and an 83-amino acid cytoplasmic do- highly glycosylated. CD84 had a unique pattern of expresmain.
The extracellular Ig-like domains presented structural sion, being found predominantly on lymphocytes and monoand sequence homology with a group of members of the Ig cytes. Thus, the glycoprotein HLy9-b is recognized by MoAbs superfamily that included CD2, CD48, CD58, and Ly9. North- previously clustered as CD84 and represents a newly identiern blot analysis showed that the expression of HLy9-b was fied member of the Ig superfamily that may play a significant predominantly restricted to hematopoietic tissues. Chromo- role in leukocyte activation.
2015-04-10T11:10:55Z
2015-04-10T11:10:55Z
1997
info:eu-repo/semantics/article
Blood,1997, Vol 90, No 6, pp 2398-2405
0006-4971
http://uvadoc.uva.es/handle/10324/10379
2398
6
2405
Blood
90
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
American Society of Hematology
oai:uvadoc.uva.es:10324/103802021-06-23T09:49:11Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
CD148, a membrane protein tyrosine phosphatase, is able to induce tyrosine phosphorylation on human lymphocytes
Palou, Eduard
Fuente García, Miguel Ángel de la
Nicolás, Josep Maria
Vilardell, Carme
Vives, Jordi
Gayá, Antoni
Células hematopoyéticas
Hematología
Producción Científica
CD148 is a new cluster of differentiation defined in the VI International Workshop on Leucocyte Differentiation Antigens. It has been identified as the hematopoietic form of a formerly described membrane protein tyrosine phosphatase called HPTP eta/ DEP-1. Previous data have demonstrated that this molecule is able to give rise to [Ca2+]i increase. In the present work we show its capability to induce protein tyrosine phosphorylation in human lymphocytes in spite of its intrinsic protein tyrosine phosphatase activity. The induction of kinase activity suggests the involvement of some protein tyrosine kinase based signaling pathway. The activation of this postulated kinase could be carried out through a direct association or via an adapter molecule.
2015-04-10T11:29:46Z
2015-04-10T11:29:46Z
1997
info:eu-repo/semantics/article
https://doi.org/10.1016/S0165-2478(97)00069-2
Immunology Letters, 1997, 57(1-3):101-103
0165-2478
http://uvadoc.uva.es/handle/10324/10380
101
1-3
103
Immunology Letter
57
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Elsevier
oai:uvadoc.uva.es:10324/103842021-06-23T09:49:33Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Desialylation of T lymphocytes overcomes the monocyte dependency of pokeweed mitogen-induced T-cell activation.
Gallart, T.
Barceló, Josep
Alberola-Ila, J.
Lozano, F.
Fuente García, Miguel Ángel de la
Células hematopoyéticas
Hematología
Producción Científica
Activation of T lymphocytes by pokeweed mitogen (PWM) is strictly monocyte (Mo)-dependent and results in T-cell mitogenesis and interleukin-2 (IL-2) secretion, coupled with an inability to utilize IL-2 due to an impaired expression of functional IL-2 receptor (IL-2R). Such IL-2R impairment could arise in PWM-activated T cells themselves or, alternatively, be the result of Mo-derived influences, as it is known that PWM binds Mo strongly and does not or poorly binds lymphocytes, and Mo becomes rapidly destroyed in PWM-stimulated cultures of blood mononuclear cells or T cells plus Mo. The present study investigated these possibilities. The results show for the first time that desialylation of T lymphocytes strongly increases their PWM-binding capacity and, in addition, overcomes the Mo requirement for PWM to induce T-cell mitogenesis and IL-2 secretion. Such secreted IL-2 levels were even higher that those found in cultures of Mo-dependent PWM-activated T lymphocytes but similarly to the latter, PWM-activated desialylated purified T lymphocytes exhibited negligible high-affinity IL-2 binding capacity and an inability to utilize the IL-2 they produced. These effects were not due to desialylation itself, as indicated by data obtained with peanut agglutinin, a lectin that becomes strongly reactive with desialylated T lymphocytes. The data clearly indicate the existence of PWM-related events capable of impairing the expression of functional IL-2R without affecting IL-2 secretion, and indicate that such events are due to mechanisms arising at the level of PWM-activated T cells themselves.
2015-04-10T11:53:20Z
2015-04-10T11:53:20Z
1997
info:eu-repo/semantics/article
https://doi.org/10.1046/j.1365-2567.1997.00129
Immunology, 1997, 90(1):57-65
0019-2805
http://uvadoc.uva.es/handle/10324/10384
57
1
65
Immunology
90
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Wiley
oai:uvadoc.uva.es:10324/103862021-06-23T09:48:57Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
CD50 (Intercellular Adhesion Molecule 3) Stimulation induces calcium mobilization and tyrmine phosphorylation through p59b and p56 in jurkat T cell line
Juan, Manel
Viñas, Odette
Pino Otín, María Rosa
Places, Lourdes
Martínez Cáceres, Eva
Barceló, Juan J.
Miralles, Agustí
Vilella, Ramón
Vives, Jordi
Yagüe, Jordi
Gayá, Antoni
Fuente García, Miguel Ángel de la
Biología celular
Producción Científica
The leukocyte differentiation antigen, CD50, has been recently identified as the intercellular adhesion molecule 3 (ICAM-3), the third counter-receptor of leukocyte function-associated antigen 1 (LFA-1). This molecule seems to be specially involved in the adhesion events of the initial phases of the immune response. To characterize the role of CD50 in leukocyte interactions, the different molecular events induced after cross-linking of CD50 on T cell-derived Jurkat cell line have been analyzed. When cells were incubated with anti-CD50 mAbs and cross-linked with polyclonal goat anti-mouse immunoglobulins, a rise in intracellular calcium concentration ([Ca2+]i) was observed. This increase in [Ca2+]i was mainly due to the uptake of extracellular Ca2+. This Ca2+ flux involved tyrosine phosphorylations and was further increased by CD3 costimulation. These data, together with those obtained by phosphotyrosine (P-Tyr) immunoprecipitation and in vitro kinase assays, suggested the involvement of protein-tyrosine kinases (PTK) in CD50 transduction pathways. By using specific antisera, the presence of p56lck and p59fyn protein tyrosine kinases (PTK) was clearly demonstrated in the CD50 immunoprecipitates. These findings suggest that the interaction of CD50 with its natural ligand (LFA-1) may result in T lymphocyte activation events, in which CD50 could play a very active role after antigen triggering.
2015-04-13T08:17:11Z
2015-04-13T08:17:11Z
1994
info:eu-repo/semantics/article
https://doi.org/10.1084/jem.179.6.1747
Journal of Experimental Medicine, 1994, vol. 179, n. 6. p. 1747-1756
0022-1007
http://uvadoc.uva.es/handle/10324/10386
1747
6
1756
Journal of Experimental Medicine
179
eng
https://rupress.org/jem/article/179/6/1747/24965/CD50-intercellular-adhesion-molecule-3-stimulation
info:eu-repo/semantics/openAccess
application/pdf
Rockefeller University Press
oai:uvadoc.uva.es:10324/152412022-06-27T11:47:31Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Predicting cardiac surgery–associated acute kidney injury: The CRATE score
Jorge Monjas, Pablo
Bustamante Munguira, Juan
Lorenzo López, Mario
Heredia Rodríguez, María
Fierro Lorenzo, María Inmaculada
Gómez Sánchez, Esther
Hernández, Alfonso
Álvarez González, Francisco Javier
Bermejo Martín, Jesús Francisco
Gómez Pesquera, Estefanía
Gómez Herreras, José Ignacio
Tamayo Gómez, Eduardo
Cardiovascular, Aparato - Cirugía - Complicaciones y secuelas
Enfermedad renal
Producción Científica
Purpose: Acute kidney injury (AKI) is a frequent complication after cardiac surgery and is associated with
increased mortality. The aim was to design a nondialytic AKI score in patients with previously normal renal
function undergoing cardiac surgery.
Methods: Data were collected on 909 patients who underwent cardiac surgery with cardiopulmonary bypass between
2012 and 2014. A total of 810 patients fulfilled the inclusion criteria. Patients were classified as having AKI
based on the RIFLE criteria. Postoperative AKI occurred in 137 patients (16.9%). Several parameters were recorded
preoperatively, intraoperatively, and at intensive care unit admission, looking for a univariate andmultivariate associationwith
AKI risk. A second data set of 741 patients, from2 different hospitals,was recorded as a validation cohort.
Results: Four independent risk factors were included in the CRATE score: creatinine (odds ratio [OR], 9.66; 95% confidence
interval [CI], 4.77-19.56; P b .001), EuroSCORE (OR, 1.40; CI, 1.29-1.52; P b .001), lactate (OR, 1.03; CI, 1.01-
1.04; P b .001), and cardiopulmonary bypass time (OR, 1.01; CI, 1.01-1.02; P b .001). The accuracy of the model was
good, with an area under the curve of 0.89 (CI, 0.85-0.92). The CRATE score retained good discrimination in validation
cohort, with an area under the curve of 0.81 (95% CI, 0.78-0.85).
Conclusions: CRATE score is an accurate and easy to calculate risk score that uses affordable andwidely available variables
in the routine care surgical patients.
2016-01-13T08:18:11Z
2016-01-13T08:18:11Z
2015
info:eu-repo/semantics/article
https://doi.org/10.1016/j.jcrc.2015.11.004
Journal of Critical Care, 2016, 31 (1): 130–138
0883-9441
http://uvadoc.uva.es/handle/10324/15241
130
1
138
Journal of Critical Care
31
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Elsevier
oai:uvadoc.uva.es:10324/152432021-06-23T09:49:36Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Drugs, Substance Use Disorder and Driving: Intervention of Health Professionals in the Treatment of Addictions
Álvarez González, Francisco Javier
González Luque, Juan Carlos
Seguí Gómez, María
Automóviles - Conducción en estado de embriaguez
Producción Científica
Without a doubt, driving with the presence
of drugs in the body is a real problem associated
with a higher risk of being involved
in road traffic collisions. Thus, intervention
aimed at preventing drug driving is a top priority (Álvarez
& González-Luque, 2010; DRUID, 2012; Schulze et al.,
2012).
In this article, we use the concept injuries due to road traffic
collisions and not the inadequate term, traffic accidents. Most
injuries resulting from road traffic collisions are preventable
(Álvarez, 2005; Redelmeier & McLellan, 2013), hence the
aim of this article: making professionals aware of the fact
that these injuries are avoidable, particularly professionals
who treat patients for any Substance Use Disorder (SUD),
and that they can and should intervene in the prevention
of injuries due to road traffic collisions. Like the slogan of
the 2004 World Health Day: “Road safety is no accident”
2016-01-13T09:38:23Z
2016-01-13T09:38:23Z
2015
info:eu-repo/semantics/article
Adicciones 2015 15;27(3):161-7
0214-4840
http://uvadoc.uva.es/handle/10324/15243
161
3
167
Adicciones
27
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Socidrogalcohol
oai:uvadoc.uva.es:10324/152482021-06-23T09:49:38Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Alcohol and drug use by Spanish drivers: Comparison of two cross-sectional road-side surveys (2008–9/2013)
Fierro Lorenzo, María Inmaculada
González Luque, Juan Carlos
Seguí Gómez, María
Álvarez González, Francisco Javier
Automóviles - Conducción en estado de embriaguez
Producción Científica
Driving under the influence of substances (DUI) other than
alcohol has been the subject of increasing interest over the past few
decades (Schulze et al., 2012). As with alcohol, research has shown
that drug intake increases the risk of road traffic accidents (Elvik,
2013; Schulze et al., 2012; Verstraete & Legrand, 2014). Intervention
in this area is a priority. A key factor for deterring DUI is to
convince drug-using drivers that the risk of detection is high
(Jones, Donnelly, Swift, & Weatherburn, 2006; Watling, Palk,
Freeman, & Davey, 2010) thus, adequate law enforcement, and the
continuity of roadside testing for drug use among drivers, play an
important role (Shepherd, 2001; Watson & Freeman, 2007).
For the European Project DRUID (Driving under the Influence
of Drugs, Alcohol and Medicines; http://www.druid-project.eu),
roadside surveys were conducted in 13 European countries and
results showed large differences in the prevalence of alcohol and
drug intake by country (Schulze et al., 2012). The highest
prevalence was found in Southern Europe (Italy, Spain and
Portugal). In Spain, avoiding driving after alcohol or drug use
has been recognized as crucial to improving road safety. Five
years after the DRUID project, a new roadside survey was
conducted following a similar methodology in order to study
whether the use of alcohol and drugs among Spanish drivers had
changed.
2016-01-13T13:09:42Z
2016-01-13T13:09:42Z
2015
info:eu-repo/semantics/article
https://doi.org/10.1016/j.drugpo.2015.04.021
International Journal of Drug Policy 26 (2015) n. 8. 794–797
0955-3959
http://uvadoc.uva.es/handle/10324/15248
794
8
797
International Journal of Drug Policy
26
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Elsevier
oai:uvadoc.uva.es:10324/152502021-06-23T09:49:39Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Challenges in care of trauma patient in Spain. The need for implementation of scientific evidence including secondary prevention
Retos asistenciales en la atención al paciente traumatizado en España. La necesidad de implementación de la evidencia científica incluyendo la prevención secundaria
Fernández Mondéjar, Enrique
Álvarez González, Francisco Javier
González Luque, Juan Carlos
Traumatismos
Uso de drogas
Producción Científica
The mortality of trauma patients has improved significantly in recent decades due
to a combination of factors: medical care, educational campaigns and structural changes. Generalization
of both out-of hospital emergence medical services and the hospital care in specific
centers for traumatized has undoubtedly contributed to this decline, but other factors such as
periodic campaigns to prevent workplace and traffic accidents, as well as improvements in the
road network have played a key role.
The challenge now is to contain mortality, for which is essential an analysis of the situation
to detect potential areas of improvement.
The application of diagnostic or therapeutic actions with scientific evidence is associated
with lower mortality, but as in other areas of medicine, the application of scientific evidence
in trauma patients is barely 50%. Moreover, nearly 90% of trauma deaths occur in the crash
site or during the first 72 h of hospitalization, the vast majority as a result of injuries incompatible
with life. In these circumstances it is clear that prevention is the most cost-effective
activity. As medical practitioners, our role in prevention is mainly focused on the secondary
prevention to avoid recidivism, for which it is necessary to identify the possible risk factors
(frequently alcohol, illegal drugs, psychotropic medication, etc.) and implement a brief motivational
intervention. This activity can reduce recidivism by nearly 50%. In Spain, the activity
in this field is negligible; therefore, measures should be implemented for dissemination of
secondary prevention in trauma.
2016-01-13T13:24:17Z
2016-01-13T13:24:17Z
2014
info:eu-repo/semantics/article
https://doi.org/10.1016/j.medin.2014.05.001
Medicina Intensiva. 2014; 8(6):386-90
0210-5691
http://uvadoc.uva.es/handle/10324/15250
386
6
390
Medicina Intensiva
8
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Elsevier Doyma
oai:uvadoc.uva.es:10324/152942021-06-23T09:49:41Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
The Spanish pictogram on medicines and driving: The population's comprehension of and attitudes towards its use on medication packaging.
Fierro Lorenzo, María Inmaculada
Gómez Talegón, Trinidad
Álvarez González, Francisco Javier
Accidentes de tráfico - Prevención
Uso de drogas
Producción Científica
The Spanish pictogram on medicines and driving is legally binding since 2011. We have evaluated
patients’ comprehension, change in driving frequency and the perceived usefulness, information, comprehensibility,
and simplicity of this pictogram on 1385 Spaniards users of the National Health Service
(pharmacies, primary care and hospital centres). Most, 85.7%, correctly related the symbol with the possible
effects of the medicine on driving and the 83.9% of the drivers would reduce the frequency with
which they drive when prescribed a medicine with such pictogram. The pictogram was found, in a 10-
point Likert, useful (8.3
±
1.7), informative (7.7
±
1.9), comprehensible (7.8
±
1.9) and simple (7.8
±
1.9).
The Spanish pictogram on medicines and driving is understood by the great majority of those interviewed;
is well considered by the users of the National Health Service; and offers good prospects for
reinforce the awareness of health care professionals and patients on the effects of medicines on driving.
2016-01-18T09:06:05Z
2016-01-18T09:06:05Z
2013
info:eu-repo/semantics/article
https://doi.org/10.1016/j.aap.2012.08.009
Accident Analysis and Prevention, 2013; 50 : 1056-61.
http://uvadoc.uva.es/handle/10324/15294
1056
1061
Accident Analysis and Prevention
50
eng
Attribution-NonCommercial-ShareAlike 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-sa/4.0/
application/pdf
Elsevier
oai:uvadoc.uva.es:10324/152952021-06-23T09:49:42Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Road rage among drug dependent patients
Benavidez, Daniela C.
Flores, Antonio M.
Álvarez González, Francisco Javier
Accidentes de tráfico - Prevención
Uso de drogas
Producción Científica
The consumption of alcohol, cocaine and cannabis is associated with aggressive behaviour, being a victim
of injuries from various causes, and suffering traffic accidents. On the other hand, there is a significant
association between road rage and traffic accidents, yet this has not been studied in persons suffering a
substance dependence disorder. This study analyses the prevalence of road rage in substance dependent
patients undergoing treatment. 100 patients randomly selected at an outpatient treatment centre were
included in the study. 63% of the patients had experienced road rage in the year prior to the interview,
and 18% were serious perpetrators. There was a higher frequency among drivers and those who were
starting treatment for cocaine and cocaine + heroin. The study shows that road rage is very frequent among
patients with disorders due to substance dependence who are undergoing treatment, in particular the
most severe form (“serious perpetrators”). Special attention should be addressed to the issue of driving
and road rage during the treatment of these patients.
2016-01-18T09:28:09Z
2016-01-18T09:28:09Z
2013
info:eu-repo/semantics/article
https://doi.org/10.1016/j.aap.2012.07.010
Accident Analysis and Prevention, 50 (2013) : 848–853
0001-4575
http://uvadoc.uva.es/handle/10324/15295
848
853
Accident Analysis and Prevention
50
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Elsevier
oai:uvadoc.uva.es:10324/152992021-06-23T09:49:44Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Evolution of neutrophil apoptosis in septic shock survivors and nonsurvivors
Tamayo Gómez, Eduardo
Gómez Sánchez, Esther
Bustamante Munguira, Juan
Gómez Herreras, José Ignacio
Fonteriz García, Rosalba Inés
Bobillo, Felipe
Bermejo Martín, Jesús Francisco
Castrodeza Sanz, José Javier
Heredia Rodríguez, María
Fierro Lorenzo, María Inmaculada
Álvarez González, Francisco Javier
Septicemia - Prevención
Producción Científica
The aims were to analyze the temporal evolution of neutrophil apoptosis, to determine the differences in neutrophil apoptosis among 28-day survivors and nonsurvivors, and to evaluate the use of neutrophil apoptosis as a predictor of mortality in patients with septic shock. [Materials and Methods]: Prospective multicenter observational study carried out between July 2006 and June 2009. The staining solution study included 80 patients with septic shock and 25 healthy volunteers. Neutrophil apoptosis was assessed by fluorescein isothiocyanate (FITC)-conjugated annexin V and aminoactinomycin D staining. [Results]: The percentage of neutrophil apoptosis was significantly decreased at 24 hours, 5 days, and 12 days after the diagnosis of septic shock (14.8% ± 13.4%, 13.4% ± 8.4%, and 15.4% ± 12.8%, respectively; P < .0001) compared with the control group (37.6% ± 12.8%). The difference in apoptosis between 28-day surviving and nonsurviving patients was nonsignificant (P > .05). The mortality rate at 28 days was 53.7%. The crude hazard ratio for mortality in patients with septic shock did not differ according to the percentage of apoptosis (hazard ratio, 1.006; 95% confidence interval, 0.98-1.03; P = .60). [Conclusions]: During the first 12 days of septic shock development, the level of neutrophil apoptosis decreases and does not recover normal values. No differences were observed between surviving and nonsurviving patients.
2016-01-18T13:21:05Z
2016-01-18T13:21:05Z
2012
info:eu-repo/semantics/article
https://doi.org/10.1016/j.jcrc.2011.09.001
Journal of Critical Care, (2012); 27(4): 415.e1- 415.e11
0883-9441
http://uvadoc.uva.es/handle/10324/15299
415.e1
4
415.e11
Journal of Critical Care
27
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Elsevier
oai:uvadoc.uva.es:10324/154142023-07-17T08:16:25Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Toll-Like receptor 2 R753Q polymorphisms are associated with an increased risk of infective endocarditis
Bustamante Munguira, Juan
Tamayo Gómez, Eduardo
Flórez, Santiago
Tellería Orriols, Juan José
Bustamante Munguira, Elena
López Díaz, Javier
San Román Calvar, José Alberto
Álvarez González, Francisco Javier
Endocarditis
Producción Científica
The ability to respond to the ligands of toll-like receptors (TLR) could be affected by single nucleotide
polymorphisms in TLR codifying genes. The influence of the polymorphisms TLR2 (R753Q, R677W), TLR4
(D299G, T399I) and CD14 (C-159T) was consecutively studied in 65 patients with infective endocarditis.
The control group (n=66) consisted of healthy volunteers. All the polymorphisms were genotyped by
means of restriction analysis after their amplification. An association between endocarditis and variants
of TLR2 R753Q (P < .001) was observed, but no association with other polymorphisms was found.
The TLR2 R753Q co-dominant (odds ratio=13.33), recessive (odds ratio=9.12) and dominant
(odds ratio=3.65) genotypes showed a positive association with the infective endocarditis phenotype.
The polymorphism TLR2 R753Q was associated with a greater susceptibility towards the development of
infective endocarditis. Further studies are required to validate these results and identify other genetic
risk factors.
2016-01-19T09:21:12Z
2016-01-19T09:21:12Z
2011
info:eu-repo/semantics/article
https://doi.org/10.1016/j.rec.2011.02.027
Revista Española de Cardiología, 2011;64(11):1056–1059
1885-5857
http://uvadoc.uva.es/handle/10324/15414
1056
11
1059
Revista Española de Cardiología
64
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Elsevier
oai:uvadoc.uva.es:10324/154152021-06-23T09:49:47Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Ventilator-associated pneumonia is an important risk factor for mortality after major cardiac surgery
Tamayo Gómez, Eduardo
Álvarez González, Francisco Javier
Martínez Rafael, Beatriz
Bustamante Munguira, Juan
Bermejo Martín, Jesús Francisco
Fierro Lorenzo, María Inmaculada
Eiros Bouza, José María
Cardiovascular, Aparato - Cirugía - Complicaciones y secuelas
Neumonía
Producción Científica
Ventilator-associated pneumonia (VAP) is the main infectious complication in cardiac surgery patients and is associated with an important increase in morbidity and mortality. The aim of our study was to analyze the impact of VAP on mortality excluding other comorbidities and to study its etiology and the risk factors for its development. MATERIALS AND METHODS: This prospective cohort study included 1610 postoperative cardiac surgery patients' status post cardiopulmonary bypass (CPB) between July 2004 and January 2008. The primary outcome measures were the development of VAP and in-hospital mortality. RESULTS: Ventilator-associated pneumonia was observed in 124 patients (7.7%). Patients with VAP had a longer length of hospitalization (40.7 ± 35.1 vs 16.1 ± 30.1 days, P <.0001) and greater in-hospital mortality (49.2% [61/124] vs 2.0% [30/1486], P =.0001) in comparison with patients without VAP. After performing the Cox multivariant analysis adjustment, VAP was identified as the most important independent mortality risk factor (adjusted hazard ratio [HR], 8.53; 95% confidence interval, 4.21-17.30; P =.0001). Other independent risk factors of in-hospital mortality were chronic renal failure (HR, 2.56), diabetes mellitus (HR, 1.90), CPB time (HR, 1.51), respiratory failure (HR, 2.13), acute renal failure (HR, 2.39), and mediastinal bleeding of at least 1000 mL (HR, 1.81).
2016-01-19T09:41:51Z
2016-01-19T09:41:51Z
2012
info:eu-repo/semantics/article
https://doi.org/10.1016/j.jcrc.2011.03.008
Journal of Critical Care, (2012);27(1):18-25
0883-944
http://uvadoc.uva.es/handle/10324/15415
18
1
25
Journal of Critical Care
27
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Elsevier
oai:uvadoc.uva.es:10324/154162021-06-23T09:49:48Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Agresividad vial en la población general
Fierro Lorenzo, María Inmaculada
Gómez Talegón, Trinidad
Álvarez González, Francisco Javier
pendiente de asignar
Producción Científica
Objetivos: Analizar la prevalencia y los factores sociodemográficos asociados con la agresividad vial en la población.
Métodos: Se han realizado 2.500 entrevistas a la población de Castilla y León de entre 14 y 70 años de edad. Se evaluó la agresividad vial en el año previo a la realización de la encuesta utilizando un test de ocho preguntas.
Resultados: El 31,1% refirió haber vivido alguna situación de agresividad vial en el último año, y el 26,8% en más de una ocasión. El 2,6% fueron agresores viales «graves». Entre los conductores, la probabilidad de experimentar agresividad vial aumenta a medida que aumentan los miles de kilómetros conducidos a la semana (odds ratio [OR]=1,52), es menor cuanto mayor es la edad del entrevistado (OR=0,975) y es mayor en los hombres (OR=1,287), en los que tienen estudios universitarios (OR=1,408) y en los que viven en localidades de más de 10.000 habitantes (OR=1,25).
Conclusiones: Los datos del presente estudio muestran que la agresividad vial afecta a casi un tercio de la población general de Castilla y León, lo que justificaría la adopción de medidas para su prevención y reducción
2016-01-19T10:13:50Z
2016-01-19T10:13:50Z
2010
info:eu-repo/semantics/article
https://doi.org/10.1016/j.gaceta.2010.07.004
Gaceta Sanitaria, 2010;24(5):423–427
0213-9111
http://uvadoc.uva.es/handle/10324/15416
423
5
427
Gaceta Sanitaria
24
spa
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Elsevier España
oai:uvadoc.uva.es:10324/154172021-09-13T09:14:55Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Self-reported drug allergies and the diagnostic work-up in the surgical population
Tamayo Gómez, Eduardo
Álvarez González, Francisco Javier
Castrodeza Sanz, José Javier
Yánez, Javier
Arnáiz, Pilar
Lajo, Carmen
Soria, Susana
Alergia a los medicamentos
Cirugía
Producción Científica
Objective The diagnostic work-up of a drug hypersensitivity reaction is indeed difficult. In
general, medical documentation of allergic reactions in medical reports is usually highly
deficient or non-existent. The aim of this study was to analyse the prevalence of selfreported
drug allergies in the surgical population as well as the criteria used in the diagnosis
of drug hypersensitivity reactions.
Methods A prospective study with the consecutive participation of 1439 patients, following
surgical intervention, attended the Post-Operative Care Unit. Previously, as a routine
process during the pre-anesthesia consultation, all patients were questioned about whether
they had any drug allergies to report and diagnostic work-up.
Results The prevalence of self-reported drug allergies was 8.3% (119/1439): 3.6% considered
themselves allergic to b-lactams and 2.4% to non-steroidal anti-inflammatory
drugs. Approximately one-third of the subjects (40 out of the 119) had not been subjected
to any allergy diagnostic procedure and with 79 (66.4%), the only diagnostic test used by
the Allergy Unit had been the skin prick-test. None of those participating in the study had
tryptase, methylhistamine, specific IgE or intradermal tests carried out to characterize the
diagnosis of the allergic reaction.
Conclusions These results show that self-reported drug allergies are highly prevalent and
as yet little explored. It is an important prevalence which should bring about modifications
to the prescription of certain medicaments. The medical personnel must be made aware of
the need to make an accurate diagnosis of allergies to medicaments.
2016-01-19T12:52:20Z
2016-01-19T12:52:20Z
2010
info:eu-repo/semantics/article
https://doi.org/10.1111/j.1365-2753.2009.01212.x
Journal of Evaluation in Clinical Practice, (2010);16(5):902-4
1356-1294
http://uvadoc.uva.es/handle/10324/15417
902
5
904
Journal of Evaluation in Clinical Practice
16
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Blackwell Publishing
oai:uvadoc.uva.es:10324/154242021-06-23T09:49:51Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Differences in alcohol-related mortality between foreign-born and native-born Spaniards
Fierro Lorenzo, María Inmaculada
Yáñez Ortega, José Luis
Álvarez González, Francisco Javier
Automóviles - Conducción en estado de embriaguez - España
Alcohol - Mortalidad
Producción Científica
Background: Alcohol consumption is associated with high rates of mortality. This study aimed to analyse
mortality attributable to alcohol consumption in foreign-born and native-born Spaniards in 2004 and to
determine whether differences existed between these groups.
Methods: The number of deaths attributable to alcohol consumption was calculated by means of the
alcohol-attributable fractions devised by the Center for Disease Control and Prevention for calculating
mortality rates in the USA. Alcohol-related mortality rates and age-adjusted mortality rates per 100,000
persons (using European standard population) were calculated by gender.
Results: The mortality rates attributable to alcohol per 100,000 inhabitants were lower among foreignborn
Spaniards (7.0) than native-born Spaniards (16.7). Chronic conditions accounted for only 23.6% of
all alcohol-related mortality for foreign-born Spaniards, but 60% for native-born Spaniards. The former
were much more likely to suffer unintentional injuries, particularly road traffic accidents, while the latter
showed high rates of alcohol-related death for digestive diseases, cardiovascular disorders, intentional
injuries and malignant neoplasm.
Conclusion: Alcohol consumption is an important cause of death among the native-born Spanish population.
The observed differences in alcohol-related mortality between native and foreign-born Spaniards
should be considered when developing targeted harm reduction policies
2016-01-20T09:00:22Z
2016-01-20T09:00:22Z
2010
info:eu-repo/semantics/article
https://doi.org/10.1016/j.drugpo.2009.08.006
International Journal of Drug Policy, (2010); 21(3) : 240–243
0955-3959
http://uvadoc.uva.es/handle/10324/15424
240
3
243
International Journal of Drug Policy
21
eng
Attribution-NonCommercial-ShareAlike 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-sa/4.0/
application/pdf
Elsevier
oai:uvadoc.uva.es:10324/154402021-06-23T09:49:52Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Mortalidad prematura y años potenciales de vida perdidos relacionados con el consumo de alcohol en España y en las comunidades autónomas en el año 2004
Fierro Lorenzo, María Inmaculada
Yáñez Ortega, José Luis
Álvarez González, Francisco Javier
Producción Científica
Objetivo: Analizar la mortalidad prematura relacionada con el consumo de alcohol 2004
en España y en las diferentes comunidades autónomas (CC.AA.) españolas.
Diseño: Se partió de los datos de las muertes atribuibles al consumo de alcohol en 2004
para España y las distintas CC.AA.; a partir de éstos se calcularon los años potenciales de
vida perdidos (APVP) hasta los 70 años para cada categoría diagnóstica, sexo y grupos
quinquenales de edad.
Emplazamiento: España: 17 CC.AA., Ceuta y Melilla.
Participantes: Datos de defunciones según causa de muerte, desagregados por sexo y
edad para cada una de las 17 CC.AA., Ceuta y Melilla.
Mediciones principales: Los APVP, el porcentaje sobre el total de APVP y la media de APVP
por muerte atribuible al consumo de alcohol.
Resultados: Durante 2004 se perdieron 118.411 APVP, 4 veces más en varones, y la media
por cada muerte atribuible al consumo de alcohol fue de 22,6 años (34,7 años en Ceuta y
20,2 años en Asturias). Las causas agudas (el 68,0% de los APVP) y en particular los
accidentes no intencionales (el 47,9% de los APVP) son los que más contribuyen a la
mortalidad prematura relacionada con el consumo de alcohol en España y las distintas
CC.AA.
Conclusiones: La estimación de los APVP pone de manifiesto el elevado impacto del
consumo de alcohol en la mortalidad prematura en las CC.AA. españolas. El consumo de
alcohol es una causa evitable de mortalidad y deberían adoptarse medidas de prevención
para reducir la exposición al consumo, así como para detectar y tratar precozmente los
posibles problemas relacionados con el consumo de alcohol.
2016-01-20T11:45:51Z
2016-01-20T11:45:51Z
2010
info:eu-repo/semantics/article
https://doi.org/10.1016/j.aprim.2009.04.017
Atención Primaria, 2010 ; 42(2) : 95-101
0212-6567
http://uvadoc.uva.es/handle/10324/15440
95
2
101
Atención Primaria
42
spa
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Elsevier España
oai:uvadoc.uva.es:10324/156122021-06-23T09:50:01Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Presión venosa central, tiempo de recalentamiento y líquidos totales son factores postoperatorios de morbi-mortalidad en cirugía cardiaca
Rodríguez, Ronael
Tamayo Gómez, Eduardo
Álvarez González, Francisco Javier
Castrodeza Sanz, José Javier
Lajo, Carmen
pendiente de asignar
Producción Científica
OBJETIVOS: Analizar la influencia de factores del postoperatorio
inmediato (primer día), como posibles marcadores
de la evolución postoperatoria en los enfermos
operados de cirugía cardiaca.
PACIENTES Y MÉTODOS: Se diseñó un estudio transversal
en el que se incluyeron consecutivamente pacientes
intervenidos de cirugía cardiaca. Se analizó el efecto de
la presión venosa central, el tiempo de recalentamiento
hasta alcanzar los 35,5ºC de temperatura central y los
líquidos totales administrados en 24 horas, sobre la mortalidad
y las complicaciones cardiacas, pulmonares y
renales.
RESULTADOS: Se incluyeron 236 pacientes. Se observó
que la presión venosa central mayor de 18 mmHg, el
tiempo de recalentamiento mayor de 6 horas y la administración
de líquidos mayores a 5 litros durante las primeras
24 horas, se asoció a un incremento de la mortalidad
y a la aparición de complicaciones cardiovasculares,
pulmonares y renales.
CONCLUSIONES: La presión venosa central, el tiempo
de recalentamiento y los líquidos administrados durante
el primer día son determinantes de la evolución postoperatoria.
2016-01-27T09:26:56Z
2016-01-27T09:26:56Z
2008
info:eu-repo/semantics/article
Revista Española de Anestesiologia Y Reanimación, 2008;55(10):605-9.
0034-9356
http://uvadoc.uva.es/handle/10324/15612
605
10
609
Revista Española de Anestesiología y Reanimación
10
spa
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
oai:uvadoc.uva.es:10324/156192021-06-23T09:50:02Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Comparative study of single-dose and 24-hour multiple-dose antibiotic prophylaxis for cardiac surgery
Tamayo Gómez, Eduardo
Gualis, Javier
Flórez, Santiago
Castrodeza Sanz, José Javier
Eiros Bouza, José María
Álvarez González, Francisco Javier
Cardiovascular, Aparato - Cirugía - Infecciones
Producción Científica
Use of single-dose antibiotic prophylaxis is associated with reduced antibiotic resistance, lower costs,
and fewer problems with drug toxicity and superinfections. We tested the hypothesis that single doses of cefazolin
are as effective as a 24-hour regimen of cefazolin in preventing surgical site infections in adults undergoing cardiac
procedures.
This random, prospective, clinical study included 838 adult patients undergoing elective coronary artery
bypass grafting, valve operations, or both. These patients were randomly given a single dose of cefazolin (2 g)
or a 24-hour treatment (2-g initial dose, followed by 1 g every 8 hours). Investigators blinded to the drug regimen
diagnosed wound infections according to Centers for Disease Control and Prevention criteria. Patient clinical and
demographic characteristics were noted, with follow-up for 12 postoperative months. The primary objective was
to compare the incidence of surgical infections between groups up to 12 months postoperatively.
Results: A total of 419 patients received single-dose cefazolin, and another 419 received the 24-hour treatment.
Surgical site infection occurred in 35 (8.3%) patients receiving single doses and 15 (3.6%) patients administered
the 24-hour treatment (P ¼ .004). We identified no differences between groups for mortality or duration of hospitalization
(preoperative hospitalization, intensive care unit stay, and hospitalization after surgical intervention).
The microorganisms isolated showed a similar distribution in both groups. The germs isolated were gram-positive
cocci in 86% of the surgical site infections.
Single-dose cefazolin used as antibiotic prophylaxis in cardiac surgery is associated with a higher
surgical site infection rate than the 24-hour, multiple-dose cefazolin regimen.
2016-01-27T10:06:39Z
2016-01-27T10:06:39Z
2008
info:eu-repo/semantics/article
https://doi.org/10.1016/j.jtcvs.2008.05.013
The Journal of Thoracic and Cardiovascular Surgery, 2008; 136( 6 ): 1522-1527
0022-5223
http://uvadoc.uva.es/handle/10324/15619
1522
6
1527
The Journal of Thoracic and Cardiovascular Surgery
136
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Elsevier
oai:uvadoc.uva.es:10324/156232021-06-23T09:50:03Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
The inflammatory response to colloids and crystalloids used for pump priming during cardiopulmonary bypass
Tamayo Gómez, Eduardo
Álvarez González, Francisco Javier
Alonso, Oscar
Castrodeza Sanz, José Javier
Bustamante, Rosa
Gómez Herreras, José Ignacio
Flórez, Santiago
Rodríguez, Roberto
Cardiovascular, Aparato - Cirugía
Producción Científica
Background: Systemic inflammatory response frequently
occurs after coronary artery bypass surgery and is strongly
correlated with the risk of postoperative morbidity and
mortality. This study tests the hypothesis that the priming
of the extracorporeal circuit with colloid solutions results
in less inflammation in patients undergoing cardiac surgery
than priming with crystalloid solutions.
Methods: A prospective, randomized studywas designed.
Forty-four patients undergoing elective coronary artery
bypass grafting were randomly allocated to one of two
groups: 22 patients primed with Ringer’s lactate (RL)
solution and 22 patients primed with gelatin-containing
solution during the surgery. Plasma levels of interleukin
(IL)-6, IL-8, tumor necrosis factor (TNF)-a, C-reactive
protein (CRP) and, complement 4 were measured during
the surgical intervention and over the following 48
postoperative hours. Cytokine levels were measured by
enzyme-linked assays from plasma samples obtained at
specific time points pre- and post-operatively.
Results: In both groups the serum levels of the pro-inflammatory
cytokines (IL-6, IL-8, TNF-a), CRP, complement 4, and
leukocytes increased significantly over the baseline, although no
significant differences were observed between the two groups.
The operation time, blood loss, need for inotropic support,
extubation time, and length of intensive care unit stay did not
differ significantly between the two groups.
Conclusion: Priming with gelatin vs. RL produces no
significant differences in the inflammatory response in
patients undergoing coronary artery bypass grafting with
cardiopulmonary bypass.
2016-01-27T12:31:53Z
2016-01-27T12:31:53Z
2008
info:eu-repo/semantics/article
https://doi.org/10.1111/j.1399-6576.2008.01758.x
Acta Anaesthesiologica Scandinavica,2008; 52(9): 1204–1212
0001-5172
http://uvadoc.uva.es/handle/10324/15623
1204
9
1212
Acta Anaesthesiologica Scandinavica
52
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Wiley
oai:uvadoc.uva.es:10324/156242021-06-23T09:50:05Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Mortalidad y mortalidad prematura relacionadas con el consumo de alcohol en España entre 1999 y 2004
Fierro Lorenzo, María Inmaculada
Ochoa, Rufina
Yáñez Ortega, José Luis
Valderrama Zurián, Juan Carlos
Álvarez González, Francisco Javier
Alcohol - Intoxicación
Producción Científica
El propósito del estudio
ha sido analizar la mortalidad y la mortalidad
prematura atribuibles al consumo de alcohol en
España entre 1999 y 2004.
Se han utilizado los datos de
defunciones según causa de muerte, agrupados
por edad y sexo, para 60 procesos. Para cada
proceso se calcularon, por sexos y grupos quinquenales
de edad, el número de muertes atribuibles
al consumo de alcohol, los porcentajes, las
tasas por 100.000 habitantes ajustadas a la población
estándar europea y los años potenciales
de vida perdidos (APVP) hasta los 70 años.
La mortalidad, ajustada a la población
estándar europea, atribuible al consumo de
alcohol fue del 2,1% y descendió entre 1999 y
2004. Los procesos crónicos contribuyeron al
60% de la mortalidad. Las enfermedades del
aparato digestivo, y en particular «Otras cirrosis
», fueron los procesos que más contribuyeron
a la mortalidad. El 9,3% de todos los APVP fue
atribuible al consumo de alcohol. Los procesos
agudos provocaron casi el 70% de estos APVP, y
los accidentes no intencionales fueron la causa
principal.
El consumo de alcohol es una causa
importante de mortalidad
2016-01-27T12:58:14Z
2016-01-27T12:58:14Z
2008
info:eu-repo/semantics/article
https://doi.org/10.1157/13123036
Medicina Clínica, (2008);131(1):10-3
0025-7753
http://uvadoc.uva.es/handle/10324/15624
10
1
13
Medicina Clínica
131
spa
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Elsevier España
oai:uvadoc.uva.es:10324/156262021-09-21T09:28:21Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Efecto de la simvastatina en la concentración de las proteínas de fase aguda después de la cirugía cardíaca
Tamayo Gómez, Eduardo
Alonso, Oscar
Álvarez González, Francisco Javier
Castrodeza Sanz, José Javier
Flórez, Santiago
Di Stefano, Salvatore
Vascular, Sistema - Cirugía
Simvastatina
Producción Científica
Fundamento y objetivo: Existe información contradictoria referente a que los efectos pleiotrópicos de las estatinas mejoran la morbimortalidad de las intervenciones con circulación extracorpórea, ya que reducen las concentraciones plasmáticas de proteínas de fase aguda. Pacientes y método: Se ha realizado un estudio prospectivo y aleatorizado que incluyó a 44 pacientes a los que se efectuó derivación aortocoronaria con circulación extracorpórea. Se dividieron en 2 grupos: A (n = 22), formado por pacientes que tomaron simvastatina, y B (n = 22), que fue el grupo control. Se determinaron las concentraciones plasmáticas de proteínas de fase aguda (interleucina 6, fracción C4 del complemento y proteína C reactiva). Resultados: No se observaron diferencias significativas entre ambos grupos en las concentraciones de proteínas de fase aguda ni en las complicaciones postoperatorias. En ambos grupos, las concentraciones máximas de interleucina 6 se observaron a las 6 h de la cirugía y las de proteína C reactiva a las 48 h. Las concentraciones de C4 descendieron al inicio de la derivación cardiopulmonar y volvieron a la normalidad a las 48 h. Conclusiones: La administración de simvastatina a pacientes intervenidos de revascularización miocárdica con circulación extracorpórea no modifica las concentraciones plasmáticas de proteínas de fase aguda
2016-01-27T13:23:55Z
2016-01-27T13:23:55Z
2008
info:eu-repo/semantics/article
https://doi.org/10.1157/13121102
Medicina Clinica, (2008); 130(20):773-775
0025-7753
http://uvadoc.uva.es/handle/10324/15626
773
20
775
Medicina Clínica
130
spa
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Elsevier España
oai:uvadoc.uva.es:10324/156372021-06-23T09:50:08Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Older drivers, medical condition, medical impairment and crash risk
Álvarez González, Francisco Javier
Fierro Lorenzo, María Inmaculada
Personas de edad - Conducción - Riesgos
Producción Científica
New evidence has appeared to support the fact that the over-involvement of older drivers in traffic accidents disappears when the low mileage
bias is taken into account. As a group, older drivers are as safe as or safer than other age groups, and only low mileage older drivers have a high
crash rate. Furthermore, the role of the medical condition of older drivers in traffic accidents, as well as the fitness to drive evaluation, are objects of
controversy.We examined all this with a cohort of 4316 drivers attending Medical Driving Test Centres for a mandatory fitness to drive evaluation.
Our data shows that older drivers (≥75) have a lower crash rate. Medical conditions that impair fitness to drive, as a tendency, increased with
advanced age and with lower mileage group. The multivariate analysis of variance showed that there is an effect (p < 0.0001) of age-range and
mileage on the annual crash rate per million kilometres driven, while a medical restriction (“fit to drive with restriction”) has no effect (p > 0.05).
Our data suggests that health status is not associated with increased crash risk for the low mileage group, although further studies are needed.
2016-01-28T08:14:24Z
2016-01-28T08:14:24Z
2008
info:eu-repo/semantics/article
https://doi.org/10.1016/j.aap.2007.04.001
Accid. Anal. Prev. 2008; 40(1): 55-60
0001-4575
http://uvadoc.uva.es/handle/10324/15637
55
1
60
Accident Analysis and Prevention
40
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Elsevier
oai:uvadoc.uva.es:10324/156382021-06-23T09:50:09Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Assessment of Fitness to Drive and Cardiovascular Diseases at the Spanish Medical Traffic Centres
Álvarez González, Francisco Javier
Fierro Lorenzo, María Inmaculada
Vicondoa, África
Ozcoidi, Marta
Gómez Talegón, Trinidad
Cardiovascular, Aparato
Automóviles - Conducción
Producción Científica
Background There is an increased risk of automobile accidents in patients with some cardiovascular disorders
and licensing authorities have imposed certain restrictions on such persons. Experience assessing fitness to drive
among drivers with cardiovascular disorders, and the relevance of other associated medical conditions among
drivers assessed as unfit, are reported here.
Methods and Results The study included 5,234 drivers attending 2 Spanish Medical Driver Test Centres to
assess their fitness to drive. Information regarding sociodemographic aspects, driving patterns, medical conditions,
medication use and alcohol consumption patterns was recorded: 11.6% of the drivers had a cardiovascular
disorder that potentially impaired fitness to drive, 82.5% were found fit to drive, 15.9% were fit to drive with
restrictions and 1.6% were unfit. The 10 unfit patients with cardiovascular disorders were primarily considered
unfit because of their associated ophthalmologic and medical comorbidities, but the cardiovascular disorders
were a contributing factor.
Conclusion Most (98.4%) drivers with cardiovascular disorders will be completely fit to drive or fit to drive
with restrictions. There is a need for a personalized evaluation of fitness to drive for each driver/patient, taking
into account such aspects as the associated pathology, the taking of medicinal drugs and alcohol consumption.
2016-01-28T08:51:14Z
2016-01-28T08:51:14Z
2007
info:eu-repo/semantics/article
https://doi.org/10.1253/circj.71.1800
Circulation Journal, (2007); 71 (11) : 1800-1804
1346-9843
http://uvadoc.uva.es/handle/10324/15638
1800
11
1804
Circulation Journal
71
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Japanese Circulation Society
oai:uvadoc.uva.es:10324/156392021-06-23T09:50:10Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Cannabis and driving: results from a general population survey.
Álvarez González, Francisco Javier
Fierro Lorenzo, María Inmaculada
Río, María del Carmen del
Consumo de cannabis
Automóviles - Conducción
Producción Científica
The role of illicit drugs on driving, and particularly of cannabis and driving, is the object of increasing awareness. While there is increasing evidence of their effect on psychomotor performance and increased risk of involvement in traffic accidents, limited information is available concerning factors that can predict the likelihood of driving under the influence of cannabis. The present study aims to determine the past year prevalence of driving under the influence of cannabis, and of being a passenger in a vehicle driven by a person under the influence of cannabis, as well as to examine the correlations with a broad range of potential risk factors. A total of 2500 people, aged between 14 and 70 and living in Castille and Leon (Spain), were surveyed in 2004 with regard to their consumption of alcohol and illicit drugs. Among those who reported cannabis use in the previous year, further assessment was carried out. 15.7% of those surveyed reported cannabis consumption in the previous 12 months, of whom 9.7% reported driving a vehicle under the influence of cannabis during this period, on average eight times. One out of five (19.9%) reported being a passenger in a vehicle driven by a person under the influence of cannabis, on average five times in the previous 12 months. The predictors of driving under the influence of cannabis were the population size of community, the number of drugs consumed, reference to cannabis-related problems and to being a passenger in a vehicle driven by a person under the influence of alcohol. The data show that cannabis consumption and driving is common, and requires more attention from policy makers.
2016-01-28T09:05:39Z
2016-01-28T09:05:39Z
2007
info:eu-repo/semantics/article
https://doi.org/10.1016/j.forsciint.2007.03.024
Forensic Science International, (2007); 170(2-3):111-116
0379-0738
http://uvadoc.uva.es/handle/10324/15639
111
2-3
116
Forensic Science International
170
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Elsevier
oai:uvadoc.uva.es:10324/156402022-03-30T08:14:53Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Prevalence of positive prick test to anaesthetic drugs in the surgical population
Tamayo Gómez, Eduardo
Álvarez González, Francisco Javier
Rodríguez Ceron, Gemma
Gómez Herreras, José Ignacio
Castrodeza Sanz, José Javier
Cardiováscular, Aparato - Cirugía - Riesgos
Producción Científica
Prevalence of patients with positive prick tests to anaesthetics occurred in 4.7% of the surgical population
2016-01-28T10:00:03Z
2016-01-28T10:00:03Z
2006
info:eu-repo/semantics/article
https://doi.org/10.1111/j.1398-9995.2006.01121.x
Allergy, (2006); 61(8):952–953
0105-4538
http://uvadoc.uva.es/handle/10324/15640
952
8
953
Allergy
61
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Wiley
oai:uvadoc.uva.es:10324/156412021-06-23T09:50:12Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Road traffic accidents among alcohol-dependent patients: The effect of treatment
Gómez Talegón, Trinidad
Álvarez González, Francisco Javier
Automóviles - Conducción en estado de embriaguez - España
Producción Científica
It is well known that driving under the influence of alcohol increases the risk of traffic accidents. Alcohol-dependent patients are responsible for two-thirds of motor vehicle crashes involving alcohol. Studies carried out on the general population have shown a relation between alcohol dependence and traffic accidents. The aim of the study is to analyse the effect on traffic accidents of treatment of patients with alcohol-related problems. To do so, the prevalence of traffic problems in a sample of patients with a diagnosed dependence on alcohol was assessed for three periods: during their lifetime, in the year preceding the start of treatment and over the year of treatment. A prospective study was carried out of 176 patients (147 males, 29 females; mean age 42.9 years) diagnosed as alcohol dependent according to the DSM-IV criteria in three alcoholic treatment centres in Castilla y León, Spain. 36.9% of the alcohol-dependent patients had had some kind of traffic problem during their life and 8.5% in the year prior to starting treatment. The most frequent problem was positive breath tests, followed by accidents with damage to the vehicle. Sixty-nine of the 176 patients were still receiving treatment after a year. The prevalence of traffic problems among those patients who followed treatment for 1 year (4.3%) was lower than in the year before treatment (15.9%). The study showed that the treatment is also effective in reducing traffic problems.
2016-01-28T10:38:31Z
2016-01-28T10:38:31Z
2006
info:eu-repo/semantics/article
https://doi.org/10.1016/j.aap.2005.09.006
Accident; Analysis and Prevention, (2006); 38(1):201-207
0001-4575
http://uvadoc.uva.es/handle/10324/15641
201
1
207
Accident Analysis and Prevention
38
spa
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Elsevier
oai:uvadoc.uva.es:10324/156422021-06-23T09:50:13Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Medication and fitness to drive
Río, María del Carmen del
Álvarez González, Francisco Javier
Automóviles - Conducción en estado de embriaguez
Medicamentos - Interacción
Producción Científica
Purpose The aim of this study is to analyze the consumption patterns of medicaments among motor vehicle drivers who
attend ‘Medical Driving Test Centres’ and the relation between habitual consumption of medicaments and fitness to drive.
Methods The study was carried out on 8043 drivers who attended 25 Medical Driving Test Centres.
Results 24.7% of drivers chronically consume medicaments while 6.8% consume medicaments along with alcohol every
day. Of those who chronically consume medicaments with a warning about the medications on driving, 65.8% were considered
‘fit’ to drive, 27.3% ‘fit with restrictions’, 5.1% ‘suspended’ and 0.4% ‘unfit’.
Conclusions The results show how frequent the consumption of medicaments along with alcohol is and that the great
majority of drivers who take medicaments are considered fit to drive.
2016-01-28T10:59:29Z
2016-01-28T10:59:29Z
2003
info:eu-repo/semantics/article
https://doi.org/10.1002/pds.806
Pharmacoepidemiology and Drug Safety, (2003); 12(5):389-394
1053-8569
http://uvadoc.uva.es/handle/10324/15642
389
5
394
Pharmacoepidemiology and Drug Safety
12
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Wiley
oai:uvadoc.uva.es:10324/156612021-09-20T06:34:14Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Alcohol, illicit drugs and medicinal drugs in fatally injured drivers in Spain between 1991and 2000
Río, María del Carmen del
Gómez, Josefina
Sancho, Manuel
Álvarez González, Francisco Javier
Automóviles - Conducción en estado de embriaguez
Producción Científica
The aim of this study was to assess the presence of alcohol, illicit drugs and medicinal drugs among Spanish drivers involved
in fatal road accidents between 1991 and 2000. Samples were obtained for 5745 drivers killed in road accidents from January
1991 to December 2000. Of the samples, 91.7% represented males and 8.3% females; 40.7% were under 30 years of age, 31.9%
were under 31–50 years of age, 19.5% were over 51 years of age, and for 7.9% the age was unknown. Between 1991 and 2000,
some type of psychoactive substance was detected among 50.1% of those drivers killed in road accidents, this being mainly
alcohol (43.8%) and, less frequently, illicit drugs (8.8%) and medicinal drugs (4.7%). In all the cases, in which alcohol was
detected, combined use with other substances accounted for only 12.5%, whilst in the case of illicit and medicinal drugs, figures
representing combined use with other substances were 75.6% for the former and 65.8% for the latter. For one in every three cases
(32.0%), a blood alcohol level over 0.8 g/l was recorded; cocaine (5.2%), opiates (3.2%) and cannabis (2.2%) were the three
illicit drugs most frequently detected. Among medicinal drugs, were benzodiazepines (3.4%), anti-depressant drugs (0.6%) and
analgesics (0.4%). The results show the frequent presence of psychoactive substances, particularly alcohol, among Spanish
motor vehicle users involved in fatal road accidents. It should be pointed out that illicit and medicinal drugs in combination with
other substances were a common feature.
2016-02-01T08:10:51Z
2016-02-01T08:10:51Z
2002
info:eu-repo/semantics/article
https://doi.org/10.1016/S0379-0738(02)00116-0
Forensic Science International, (2002); 127(1-2): 63–70
0379-0738
http://uvadoc.uva.es/handle/10324/15661
63
1-2
70
Forensic Science International
127
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Elsevier
oai:uvadoc.uva.es:10324/156642021-06-23T09:50:15Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Do Spanish patients drink alcohol while undergoing treatment with benzodiazepines?
Río, María del Carmen del
Prada Puentes, Carlos
Álvarez González, Francisco Javier
Medicamentos - Interacción
Producción Científica
In this study, we analyzed patterns of combined benzodiazepines and alcohol use among the Spanish general population over the age of
16 years. The study was based on information from the 1997 Spanish National Household Health Survey. A total of 6,396 persons over 16 years
of age, a representative sample of noninstitutionalized Spaniards, were surveyed. One percent of the population are consumers of
benzodiazepines and daily drinkers of alcohol; fundamentally, these consumers are men, of whom 15.4% drink alcohol at a high level
( > 50 units/week). Findings show the frequency of concurrent use of benzodiazepines and alcohol by the Spanish population
2016-02-01T08:33:56Z
2016-02-01T08:33:56Z
2002
info:eu-repo/semantics/article
https://doi.org/10.1016/S0741-8329(01)00195-1
Alcohol, (2002); 26(1): 31–34
0741-8329
http://uvadoc.uva.es/handle/10324/15664
31
1
34
Alcohol
26
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Elsevier
oai:uvadoc.uva.es:10324/156682021-06-23T09:50:16Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Alcohol-related problems and fitness to drive
Río, María del Carmen del
González Luque, Juan Carlos
Álvarez González, Francisco Javier
Automóviles - Conducción en estado de embriaguez
Producción Científica
This paper analyses the alcohol consumption patterns in Spanish drivers, the incidence of alcohol-related problems and attempts to ascertain whether, in the end, drivers with alcohol-related problems are considered fit or unfit to drive. In accordance with Spanish and European Union legislation, driving licences cannot be issued or renewed to people suffering from alcohol-related problems. A medical, psychological and eyesight evaluation was performed to test the driving fitness of 8043 drivers attending 25 Medical Driving Test Centres on a national scale. Among other things, information was collected on the patterns of alcohol consumption, the AUDIT and CAGE tests, the incidence of alcohol-related problems (DSM-IV criteria for abuse, dependence and alcohol-induced disorder), as well as an evaluation of their fitness to drive. In all, 60.3% of drivers drink alcohol on a regular basis; 7.3% of drivers scored ≥8 points in the AUDIT test, and 2% met criteria for DSM-IV alcohol abuse, dependence or induced disorder. Drivers with alcohol-related problems have been involved in traffic accidents (23.2%) and have infringed driving regulations (18.7%) more frequently (P < 0.0001) than those without alcohol-related problems. Of those with alcohol-related problems, 72.2% were considered fit to drive. The study reveals that alcohol consumption is common among drivers, that a significant number of drivers have alcohol-related problems, and that three in four of the latter were considered fit to drive
2016-02-01T09:15:18Z
2016-02-01T09:15:18Z
2001
info:eu-repo/semantics/article
https://doi.org/10.1093/alcalc/36.3.256
Alcohol Alcohol. 2001;36(3):256-61
0735-0414
http://uvadoc.uva.es/handle/10324/15668
256
3
261
Alcohol Alcohol
36
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Oxford University Press
oai:uvadoc.uva.es:10324/156692021-06-23T09:50:17Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Presence of illegal drugs in drivers involved in fatal road traffic accidents in Spain
Río, María del Carmen del
Álvarez González, Francisco Javier
Drogas - Conducción - Riesgos
Producción Científica
This study investigated the presence of illegal drugs in the blood of 285 fatally injured drivers in Spain. Illegal drugs were
detected in 10.2% of all samples. Illicit drugs alone were detected in 2.5% and together with other substances in 7.7%. Cocaine
was the most common drug detected. The mean number (9S.D.) of substances detected was 2.691.2: consisting of 46 illegal
drugs, 14 alcohol cases and 16 medicines. Three concentration levels of the different substances have been established: low,
medium and high-toxic. In 68.9% of the samples in which an illegal drug was detected, a substance was also found at the
high-toxic level. The results show that illegal drugs are commonly detected in road accident victims.
2016-02-01T09:31:23Z
2016-02-01T09:31:23Z
2000
info:eu-repo/semantics/article
https://doi.org/10.1016/S0376-8716(99)00042-3
Drug and Alcohol Dependence, (2000);57(3) 177–182
0376-8716
http://uvadoc.uva.es/handle/10324/15669
177
3
182
Drug and Alcohol Dependence
57
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Elsevier
oai:uvadoc.uva.es:10324/156712021-06-23T09:50:18Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Allergy to anaesthetizing agents in Spain
Tamayo Gómez, Eduardo
Carmona Pérez, María Luz
Gómez Herreras, José Ignacio
Álvarez González, Francisco Javier
Anestesia - Alergia
Producción Científica
We have investigated the incidence of requests for allergy testing in 5005 patients attending an anaesthetic assessment clinic. Diagnosis of allergy to anaesthetic drugs was established using cutaneous tests. Allergy tests were requested in 151 (3.0%) patients, proving positive in 43 (0.86%). No allergic reactions were observed during subsequent anaesthesia.
2016-02-01T10:08:54Z
2016-02-01T10:08:54Z
1999
info:eu-repo/semantics/article
https://doi.org/10.1093/bja/83.2.336
British Journal of Anaesthesia,(1999); 83 (2) : 336–7
0007-0912
http://uvadoc.uva.es/handle/10324/15671
336
2
337
British Journal of Anaesthesia
83
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Elsevier
oai:uvadoc.uva.es:10324/156722021-06-23T09:50:19Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Alcohol use among fatally injured drivers in Spain
Río, María del Carmen del
Álvarez González, Francisco Javier
Automóviles - Conducción en estado de embriaguez - España
Producción Científica
Blood from 285 fatally injured drivers in Northern Spain was collected and tested for the presence of alcohol and drugs. Alcohol was detected in 50.5% of all fatalities. Alcohol alone was detected in 44.2% of all samples and in the remaining 6.3% another substance was found together with alcohol. Blood alcohol concentration was classified in different levels. It has been observed that in 35.4% of the cases the blood alcohol level was≥0.8 g/l, the legal limit in Spain for car drivers. Alcohol together with other substances was encountered in 18 cases, with medication in 22.2% (4 out of 18), alcohol with illegal drugs in 66.6% of the cases (12 out of 18), and alcohol with medicines and illegal drugs in 11.1% (2 out of 18). Cocaine was the most commonly detected drug. The study shows how widespread the incidence of a high level of alcohol concentration among drivers involved in fatal accidents in Spain.
2016-02-01T10:22:57Z
2016-02-01T10:22:57Z
1999
info:eu-repo/semantics/article
https://doi.org/10.1016/S0379-0738(99)00101-2
Forensic Science International, (1999); 104 (2-3): 117–125
0379-0738
http://uvadoc.uva.es/handle/10324/15672
117
2-3
125
Forensic Science International
104
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Elsevier
oai:uvadoc.uva.es:10324/162182021-06-23T09:49:58Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Medication use by the driving population
Río, María del Carmen del
Álvarez González, Francisco Javier
Automóviles - Conducción - Riesgos
Medicamentos
Producción Científica
This study investigated patterns of medicine use among Spanish drivers. The study was conducted in the
fall of 1993 on 1500 drivers aged over 16, all of whom completed accordingly and then returned the
questionnaires. Among those surveyed, 45.1% had used drugs at least once in the previous year, while
17.3% of drivers surveyed were using medicines chronically. Chronic users, the majority of whom were
female and belonging to the older age group, were using an average of two drugs. Central nervous
system drugs (21.7%), respiratory system drugs (19.2%), cardiovascular system drugs (14.9%) and
alimentary tract drugs (14.3%) were the most frequent groups of medication used, Of those surveyed
76.5% who took drugs regularly had never been warned by health professionals about the effects of the
medication use on driving skills. The study shows both how often drivers use medication as well as the
need to inform patients and drivers about the effect of medication on driving performance.
2016-02-23T12:57:56Z
2016-02-23T12:57:56Z
1996
info:eu-repo/semantics/article
https://doi.org/10.1002/(SICI)1099-1557(199607)5:4<255::AID-PDS226>3.0.CO;2-5
Pharmacoepidemiology and Drug Safety, (1996); 5 (4): 255–261
1053-8569
http://uvadoc.uva.es/handle/10324/16218
255
4
261
Pharmacoepidemiology and Drug Safety
5
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Wiley
oai:uvadoc.uva.es:10324/162112021-06-23T09:49:57Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
The use of medication by the Spanish population
Río, María del Carmen del
Prada Puentes, Carlos
Álvarez González, Francisco Javier
Medicamentos
Toxicomanía
Producción Científica
The aim of the study was to assess patterns of the use of medicines by the general population older than
0 years. The study was based on the information contained in the computerized database from the 1993
Spanish Household Health Survey. A representative sample of the population older than 0 was identi-
®ed, and a survey of 26,334 persons was carried out. Of the population 45.3% had taken some medicine
in the last 2 weeks prior to the carrying out of the survey. The proportion was greater for women
(50.6%) than for men (39.6%). With increasing age, the frequency and amount of medication use
increased. A little over 20% of the medicines used were not prescribed by a doctor (self-medication).
Data show the frequency of the use of medicines by the Spanish population. # 1997 by John
Wiley & Sons, Ltd.
2016-02-23T09:35:43Z
2016-02-23T09:35:43Z
1997
info:eu-repo/semantics/article
https://doi.org/10.1002/(SICI)1099-1557(199701)6:1<41::AID-PDS250>3.0.CO;2-6
Pharmacoepidemiology and Drug Safety, (1997); 6(1): 41–48
1053-8569
http://uvadoc.uva.es/handle/10324/16211
41
1
48
Pharmacoepidemiology and Drug Safety
6
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Wiley
oai:uvadoc.uva.es:10324/162422021-06-23T09:49:53Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
The use of medication and alcohol among the Spanish population
Río, María del Carmen del
Prada Puentes, Carlos
Álvarez González, Francisco Javier
Medicamentos - Interacción
Alcohol en el organismo
Producción Científica
The 1993 Spanish National Health Survey data were used to estimate how
frequently both medication and alcohol were used among 21084 people over 16
years of age. A total of 47.1% of the population, especially women and an
increasingly older section, had taken some kind of medication during the previous
fortnight. A total of 9.8% of the population took medication and alcohol together.
This was more frequently observed among men than among women, and
especially so among the older age groups. These data reveal that concomitant
alcohol and medication use is frequent among the Spanish population, and
suggest a need to devote much more attention to this potential problem.
2016-02-24T08:59:24Z
2016-02-24T08:59:24Z
1996
info:eu-repo/semantics/article
https://doi.org/10.1111/j.1365-2125.1996.tb00193.x
Br J Clin Pharmacol. 1996;41(3):253-5.
0306-525
http://uvadoc.uva.es/handle/10324/16242
253
3
255
British Journal of Clinical Pharmacology
41
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Wiley
oai:uvadoc.uva.es:10324/163362021-06-23T09:49:54Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Patterns of smoking in Spain. Results from a regional general population survey
Río, María del Carmen del
Álvarez González, Francisco Javier
Tabaquismo - España
Producción Científica
Smoking patterns were examined in 2500 individuals, aged 14-70 years living in Castille and Leon (Spain) in the fall of 1992. Of these, 39.6% were regular smokers, 7.2% were occasional smokers, 14.8% were former smokers, and 30.4% were non-smokers. Sex differences were striking: there was a higher prevalence of regular smokers among males than females, males smoked much more, and were more frequently French-type cigarette smokers. A comparison of the present figures with data from an earlier survey carried out in 1989 suggests that smoking is decreasing in Spain.
2016-02-29T12:55:55Z
2016-02-29T12:55:55Z
1994
info:eu-repo/semantics/article
https://doi.org/10.1007/BF01719578
Eur J Epidemiol. (1994);10(5):595-8
0393-2990
http://uvadoc.uva.es/handle/10324/16336
595
5
598
European Journal of Epidemiologi
10
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Springer Verlag
oai:uvadoc.uva.es:10324/163402021-06-23T09:49:56Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Alcohol consumption among University students in Spain
Queipo Burón, Daniel
Álvarez González, Francisco Javier
Velasco Martín, Alfonso
Jóvenes - Consumo de alcohol
Producción Científica
Alcohol consumption in 1984 among 2921 students of nine Faculties in the University of Valladolid (Spain) is reported. Alcoholic drinks were frequently consumed, especially by males and during weekends. Per capita consumption was 9.85 l of absolute alcohol/year for males and 4.971 for females. Beer, wine and gin were the favourite drinks. Alcohol consumption was similar in the different faculties and age groups but was to some extent related to age and place of residence in male students. Students' alcohol consumption was not as high as in the general Spanish population, and seems to have been stable during the last 10 years.
2016-03-01T09:16:18Z
2016-03-01T09:16:18Z
1986
info:eu-repo/semantics/article
https://doi.org/10.1016/0376-8716(86)90113-4
Drug Alcohol Depend.,(1986);18(1):41-9.
0376-8716
http://uvadoc.uva.es/handle/10324/16340
41
1
49
Drug and Alcohol Dependence
18
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Elsevier
oai:uvadoc.uva.es:10324/163412021-06-23T09:49:59Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Predictors of driving after alcohol and drug use among adolescents in Valencia (Spain).
Tomás Dols, Sofía
Álvarez González, Francisco Javier
Llorens Aleixandre, Noelia
Vidal Infer, Antonio
Torrijo Rodrigo, María José
Valderrama Zurián, Juan Carlos
Automóviles - Conducción - Drogas
Automóviles - Conducción en estado de embriaguez
Producción Científica
Background: Driving under the influence of alcohol and drugs has been identified as a risk factor for road
traffic crashes. We have assessed the prevalence and predictor factors for driving after alcohol and drug
use by adolescents.
Methods: A cross-sectional survey involving 11,239 students aged 14–18 years from 252 private and
public schools in the Valencia region of Spain was conducted. The prevalence and predictors of driving
after alcohol use, alcohol and drug use, or drug use during the previous 6 months were measured.
Results: Of the students who reported driving (20%), 45.1% indicated driving after alcohol and drug use.
The consumption of various drugs was higher among students who drove a vehicle compared with those
whodid not. The likelihood of driving after consuming alcohol, or alcohol and drugs, increased in line with
the number of standard drink units per week, reports of any lifetime alcohol- or drug-related problems,
and poor family relationship. In addition, masculine gender and early alcohol use increased the likelihood
of driving after consuming alcohol.
Conclusions: Driving after alcohol and drug use is quite prevalent among adolescents in the Valencia
region of Spain. There is a need for implementation of targeted policies for adolescents. This should focus
on education and information on alcohol/drug use and driving.
2016-03-01T09:35:26Z
2016-03-01T09:35:26Z
2010
info:eu-repo/semantics/article
https://doi.org/10.1016/j.aap.2010.06.013
Accident Analysis & Prevention, 2010, vol. 42, n. 6. p. 2024-2029
0001-4575
http://uvadoc.uva.es/handle/10324/16341
2024
6
2029
Accident Analysis & Prevention
42
eng
Attribution-NonCommercial-NoDerivatives 3.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/3.0/
application/pdf
Elsevier
oai:uvadoc.uva.es:10324/163602021-10-13T15:04:31Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Mortality related to alcohol consumption in Spain: 1981-1990
Prada Puentes, Carlos
Río, María del Carmen del
Yáñez Ortega, José Luis
Álvarez González, Francisco Javier
Alcohol - Consumo
Producción Científica
The aim of this study was to assess the overall contribution of alcohol to Spanish mortality during 1981 to 1990, as well as the impact on the premature death. To this purpose we have used the sources of data furnished by the 'Movimiento Natural de la Población' that provides data of causes of death. Figures of proportional mortality, adjusted mortality and years of potential life lost were calculated, as well as trend analysis. 6.3% (mean in the ten years period) of the mortality was due to alcohol. This mortality was higher among males than females. Adjusted mortality show a light increase during the period. This study shows the importance of alcohol related mortality in our country and the large premature death. The most important category referring to years of potential life lost was unintentional injuries. In this category, motor vehicle accidents were responsible for the majority of premature death
2016-03-02T08:52:30Z
2016-03-02T08:52:30Z
1996
info:eu-repo/semantics/article
https://doi.org/10.1016/S0213-9111(96)71891-5
Gac Sanit.,(1996);10(55):161-8
0213-9111
http://uvadoc.uva.es/handle/10324/16360
161
55
168
Gaceta Sanitaria
10
spa
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Elsevier
oai:uvadoc.uva.es:10324/220852021-06-23T09:50:21Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Tissue reaction after intrastromal corneal ring implantation in an experimental animal model
Ibares Frías, Lucía
Gallego Muñoz, Patricia
Cantalapiedra Rodríguez, Roberto
Cruz Valsero, Maria Cruz
Mar Sardaña, Santiago
Merayo Lloves, Jesús
Martínez García, María del Carmen
Gallinas - Ensayos técnicos
Córnea - Cirugía
Producción Científica
Purpose To evaluate corneal wound healing in the hen animal
model after additive surgery with an intracorneal ring segment
(ICRS).
Methods We implanted one ICRS in each eye of 76 hens. In
control group 1 (n=22 hens), the stromal channel was prepared
but no ICRS was inserted. In control group 2 (n=2
hens), no surgery was performed. Animals were randomly
separated into groups and euthanized after clinical follow-up
of 4 and 12 hours, 1, 2, 3, and 7 days, and 1, 2, 3, 4, and
6 months. Corneas were stained with hematoxylin-eosin. Apoptosis
was measured by terminal uridine nick end-labeling
assays. Cell proliferation and myofibroblast-like differentiation
were assayed by BrdU and α-smooth muscle actin immunofluorescence
microscopy. Stromal matrix changes were
documented by electron microscopy.
Results Epithelial and stromal cell apoptosis around the
ICRS-implanted and control group 1 eyes peaked at
12 hours, but continued for 72 hours. In ICRSimplanted
eyes, epithelial and stromal proliferation was
present at 12 and 24 hours, respectively, and peaked at
7 days and 72 hours, respectively. Some proliferation in
the ICRS-implanted group continued through the 6-
month follow-up, and myofibroblast-like cells differentiated
one to three months after ICRS implantation. The
segments rotated within the stroma as the limbal inferior
angle approached the epithelium.
Conclusions Wound healing after ICRS implantation in hen
corneas was similar to that of other corneal surgical wounds in
stages. However, there were some specific features related to
the small size of the epithelial wound and the device permanently
implanted inside the cornea.
2017-01-12T09:06:22Z
2017-01-12T09:06:22Z
2015
info:eu-repo/semantics/article
https://doi.org/10.1007/s00417-015-2959-5
Graefe's Archive for Clinical and Experimental Ophthalmology, (2015); 253:1071–1083
0721-832X
http://uvadoc.uva.es/handle/10324/22085
1071
1083
Graefe's Archive for Clinical and Experimental Ophthalmology
253
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Springer Verlag
oai:uvadoc.uva.es:10324/220962021-06-23T09:50:22Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
Human corneal fibroblast migration and ECM synthesis during stromal repair: Role played by PDGF-BB, bFGF, and TGFβ1 (HCFs migration and ECM synthesis during stromal repair: GFs effects)
Gallego Muñoz, Patricia
Ibares Frías, Lucía
Garrote Adrados, José Antonio
Valsero Blanco, María Cruz
Cantalapiedra Rodríguez, Roberto
Merayo Lloves, Jesús
Martínez García, María del Carmen
Córnea - Enfermedades
Producción Científica
The development of treatments that modulate corneal wound healing to avoid fibrosis during tissue repair is important for the restoration of corneal transparency after an injury. To date, few studies have studied the influence of growth factors (GFs) on human corneal fibroblast (HCF) expression of extracellular matrix (ECM) proteins such as collagen types I and III, proteoglycans such as perlecan, or proteins implicated in cellular migration such as α5β1-integrin and syndecan-4. Using in vitro HCFs, we developed a mechanical wound model to study the influence of the GFs basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF-BB), and transforming growth factor beta 1 (TGFβ1) on ECM protein production and cellular migration. Our results show that mechanical wounding provokes the autocrine release of bFGF and TGFβ1 at different time points during the wound closure. The HCF response to PDGF-BB was a rapid closure due to fast cellular migration associated with a high focal adhesion replacement and a high expression of collagen and proteoglycans, producing a non-fibrotic healing. bFGF stimulated non-fibrotic ECM production and limited the migration process. Finally, TGFβ1 induced expression of the fibrotic markers collagen type III and α5β1 integrin, and it inhibited cellular migration due to the formation of focal adhesions with a low turnover rate. The novel in vitro HCF mechanical wound model can be used to understand the role played by GFs in human corneal repair. The model can also be used to test the effects of different treatments aimed at improving the healing process.
2017-01-12T13:06:39Z
2017-01-12T13:06:39Z
2016
info:eu-repo/semantics/article
https://doi.org/10.1002/term.2360
J Tissue Eng Regen Med. 2016 Nov 15
1932-6254
http://uvadoc.uva.es/handle/10324/22096
pp
pp
Journal of Tissue Engineering and Regenerative Medicine
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Wiley
oai_dc///col_10324_1209/100