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Biomedical subjects

A Gual

Publications and source records attributed to A Gual.

At least 19 recordsLinked to original sources

Relation of Apo E and ACE genes to cognitive performance in chronic alcoholic patients.

Apolipoprotein E epsilon4 and ACE genes have been related to several conditions involving cognitive impairment, including Alzheimer's disease, normal ageing and cerebrovascular disease. However, it has not been established whether their genotypes are associated with alcoholism or its cognitive functioning. Genotypic distributions of 140 chronic alcoholic patients were compared with a non-alcoholic sample, and the cognitive performance of a subsample of the alcoholic subjects was assessed with standard neuropsychological tests. No differences in allele or genotype distributions of Apo E or ACE genes were found when comparing controls and alcoholics (Apo E epsilon2/2; patients 1.4%, controls 0% p < 0.06; epsilon2/epsilon3; patients 9.3%, controls 6.6% p < 0.29; epsilon2/epsilon4; patients 0%, controls 1% p < 0.31; epsilon3/epsilon3 patients 71.4%, controls 72% p < 0.89; epsilon3/epsilon4; patients 15.7%, controls 19.2%, p < 0.36; epsilon4/epsilon4; patients 2.1%, controls 1.2% p < 0.44; ACE D/D; patients 35%, controls 28.5% p < 0.14; I/D; patients 47.5%, controls 51.1% p < 0.51; I/I; patients 14.5%, controls 20.4% p < 0.19). In terms of cognitive performance, epsilon4/epsilon3 patients did better on visuoconstructive (p < 0.001) and visual memory (p < 0.04) functions compared with epsilon2/epsilon3 bearers. Furthermore, ACE D/D patients performed better on a test of abstract reasoning (p < 0.03) compared with the ACE I/I homozygous group. The cognitive results suggest that Apo E or ACE genotypes may modify the effects of ethanol on cognitive deterioration in alcoholic patients. However, the data do not support an association between the Apo E epsilon4 allele and reduced cognitive performance in alcoholism.

Adult↗

[The ISCA (Systematic Interview of Alcohol Consumption), a new instrument to detect risky drinking].

BACKGROUND: The World Health Organisation Collaborative Project on Alcohol and Primary Health Care has stressed the need to develop standardised screening tools to enable early identification. The aim of this study was to develop a new systematic tool to register alcohol consumption and to validate its usefulness in order to detect risky drinking in primary health care settings. SUBJECTS AND METHOD: The Systematic Interview of Alcohol Consumption (ISCA) was administered together with the Alcohol Use Disorders Identification Test (AUDIT), which was used as main external criterium, to 255 patients who attended 5 primary health care centers. RESULTS: The correlation between both procedures was highly positive and significant (r = 0.831; p < 0.001). The cut-off scores (> 28 for men and > 17 for women) showed an ISCA sensitivity rank to detect risky drinking of 70-81% for men and 46-100% for women. The ISCA specificity ranks were 82-99% and 97-100%, respectively. CONCLUSIONS: The ISCA seems to be useful to detect risky drinking and it is easy to administer by primary health care professionals. ISCA and AUDIT can be used indistinctly and complementarily.

Adolescent↗

Human myofibroblastic hepatic stellate cells express Ca(2+)-activated K(+) channels that modulate the effects of endothelin-1 and nitric oxide.

BACKGROUND/AIMS: High-conductance Ca(2+)-activated K(+) (BK(Ca)) channels modulate the effects of vasoactive factors in contractile cells. It is unknown whether hepatic stellate cells (HSCs) contain BK(Ca) channels and what their role in the regulation of HSCs contractility is. METHODS: The presence of BK(Ca) channels in HSCs was assessed by the patch-clamp technique. The functional role of BK(Ca) channels was investigated by measuring intracellular calcium concentration ([Ca(2+)](i)) and cell contraction in individual cells after stimulation with endothelin-1 in the presence or absence of specific modulators of BK(Ca) channels. RESULTS: BK(Ca) channels were detected by patch-clamp in most of the activated HSCs studied. Incubation of cells with iberiotoxin, a BK(Ca) channel blocker, increased both the sustained phase of [Ca(2+)](i) elicited by endothelin-1 and the number of cells undergoing contraction, while the use of NS1619, a BK(Ca) channel opener, induced opposite effects. Stimulation of HSCs with S-nitroso-N-acetyl-penicillamine (SNAP), a nitric oxide (NO)-donor, increased the opening of BK(Ca) channels and reduced the effects of endothelin-1. Conversely, iberiotoxin abolished the inhibitory effect of SNAP on endothelin-induced [Ca(2+)](i) increase and cell contraction. CONCLUSIONS: Activated human HSCs contain BK(Ca) channels that modulate the contractile effect of endothelin-1 and mediate the inhibitory action of NO.

Benzimidazoles↗

Auditory sensory memory as indicated by mismatch negativity in chronic alcoholism.

OBJECTIVES: A pre-conscious auditory sensory (echoic) memory of about 10 s duration can be studied with the event-related brain potential mismatch negativity (MMN). Previous work indicates that this memory is preserved in abstinent chronic alcoholics for a duration of up to 2 s. The authors' aim was to determine the integrity of auditory sensory memory as indexed by MMN in chronic alcoholism, when this memory has to be functionally active for a longer period of time. METHODS: The presence of MMN for stimuli that differ in duration was tested at memory probe intervals (MPIs) of 0.4 and 5.0 s in 17 abstinent chronic alcoholic patients and in 17 healthy age-matched control subjects. RESULTS: MMN was similar in alcoholics and controls when the MPI was 0.4 s, whereas MMN could not be observed in the patients when the MPI was increased to 5.0 s. CONCLUSIONS: These results provide evidence of an impairment of auditory sensory memory in abstinent chronic alcoholics, whereas the automatic stimulus-change detector mechanism, involved in MMN generation, is preserved.

Adult↗

SOCIDROGALCOHOL: the Spanish Scientific Society for the Study of Alcohol, Alcoholism and other Drug Dependencies.

Founded in 1969, SOCIDROGALCOHOL is a reference point for professionals interested in drug dependencies, both for Spaniards and for professionals belonging to Spanish-speaking areas. In its 32 years of existence SOCIDROGALCOHOL has spread to all the regions of Spain and most of the Latin-American countries. In the past 5 years SOCIDROGALCOHOL has undergone notable growth, increasing the number of members (from 460 to 816), as well as the number of scientific activities carried out. The National Conferences represent an annual meeting point for the members, where multiple scientific sessions take place, as well as the ordinary general assembly. They are usually held in the spring and last 3 days, with an attendance of around 400 professionals. Within the field of ongoing training, SOCIDROGALCOHOL also carries out other activities: the Autumn School, the Latin-American Virtual Congress of Drug Dependence, distance learning courses, etc. Special mention should be made to the official journal of the Society, Adicciones, founded in 1989. Adicciones is published quarterly in Spanish and its articles are subjected to peer review; 2000 copies of each issue are published. The abstracts can be accessed free on the website of the Society, www.SOCIDROGALCOHOL.org. In this paper the most relevant historical aspects of SOCIDROGALCOHOL will be summarized, along with its current activities and future perspectives.

Alcoholism↗

In vitro and in vivo activation of rat hepatic stellate cells results in de novo expression of L-type voltage-operated calcium channels.

Following chronic liver injury, hepatic stellate cells (HSCs) transdifferentiate into myofibroblast-like cells, which develop contractile properties and contribute to increased resistance to blood flow. We investigated whether this phenotypic activation includes changes in the expression of L-type voltage-operated Ca2+ channels (VOCC), which mediate Ca2+ influx and regulate cell contraction in vascular cell types. Rat HSCs were studied in the quiescent phenotype and after their activation in vitro (cultured on plastic for 14 days) and in vivo (isolated from rats with CCl(4)-induced cirrhosis). Patch-clamp studies showed Ca2+ currents through L-type VOCC in HSCs activated both in vitro and in vivo, whereas no currents were detected in quiescent HSCs. Moreover, binding studies with (3)H-isradipine, a specific L-type VOCC antagonist, showed a large number of binding sites in activated HSCs, while no specific binding was found in quiescent HSCs. Finally, messenger RNA (mRNA) encoding L-type VOCC was not detected in quiescent HSCs as assessed by reverse transcription-polymerase chain reaction (RT-PCR) and Northern blot analysis, whereas it was present in activated HSCs. Stimulation of L-type VOCC with KCl resulted in a marked increase in [Ca2+](i) followed by cell contraction in HSCs activated both in vitro and in vivo, whereas no effects were observed in quiescent HSCs. We conclude that the activation of HSCs is associated with up-regulation of L-type VOCC that mediate Ca2+ influx and cell contraction. These results may be relevant to the pathogenesis of portal hypertension.

Animals↗

Identification of Kir2.1 channel activity in cultured trabecular meshwork cells.

PURPOSE: To study the presence of inwardly rectifying K(+) (Kir) channels in cultured bovine (BTM) and human (HTM) trabecular meshwork cells. METHODS: Cultures of BTM and HTM cells were obtained by an extracellular matrix digestion technique. Whole-cell patch-clamp recordings of BTM cells were performed with the appropriate solutions to detect K(+) currents. Also, Western blot analysis of Kir2.1 protein expression was performed on both cultured BTM and HTM cells. RESULTS: A strong inwardly rectifying current at negative potentials to the equilibrium potential for K(+) (E(K+)) and highly selective for K(+) was detected in 60% of cultured BTM cells. The slope conductance of the inward rectification was more pronounced when the extracellular [K(+)] was increased and was proportional to [K(+)](0.45). The current was blocked by Ba(2+) and Cs(+) in a voltage- and concentration-dependent manner, with K(d) at 0 mV, of 74.7 microM and 45.6 mM, respectively. Current amplitude was reduced by increasing extracellular [Ca(2+)]. The current was insensitive to 10 microM glibenclamide and 10 nM tertiapin. The application of 100 microM 8-Br-cAMP reduced the current by 50%. Kir2.1 channel expression was detected in confluent monolayers of BTM and HTM cells by Western blot analysis. CONCLUSIONS: A population of cultured BTM cells expressed an inwardly rectifying K(+) current that illustrates the biophysical and pharmacologic characteristics of the detected Kir2.1 channel protein. Kir2.1 channels are also thought to be present in HTM cells. Kir2.1 channels could be related to TM physiology, because they are involved in contractile and cell volume regulatory responses, two mechanisms that modify TM permeability.

8-Bromo Cyclic Adenosine Monophosphate↗

Functional analysis of the terminase large subunit, G2P, of Bacillus subtilis bacteriophage SPP1.

The terminase of bacteriophage SPP1, constituted by a large (G2P) and a small (G1P) subunit, is essential for the initiation of DNA packaging. A hexa-histidine G2P (H6-G2P), which is functional in vivo, possesses endonuclease, ATPase, and double-stranded DNA binding activities. H6-G2P introduces a cut with preference at the 5'-RCGG downward arrowCW-3' sequence. Distamycin A, which is a minor groove binder that mimics the architectural structure generated by G1P at pac, enhances the specific cut at both bona fide 5'-CTATTGCGG downward arrowC-3' sequences within pacC of SPP1 and SF6 phages. H6-G2P hydrolyzes rATP or dATP to the corresponding rADP or dADP and P(i). H6-G2P interacts with two discrete G1P domains (I and II). Full-length G1P and G1PDeltaN62 (lacking domain I) stimulate 3.5- and 1.9-fold, respectively, the ATPase activity of H6-G2P. The results presented suggest that a DNA structure, artificially promoted by distamycin A or facilitated by the assembly of G1P at pacL and/or pacR, stimulates H6-G2P cleavage at both target sites within pacC. In the presence of two G1P decamers per H6-G2P monomer, the H6-G2P endonuclease is repressed, and the ATPase activity stimulated. Based on these results, we propose a model that can account for the role of terminase in headful packaging.

Adenosine Triphosphatases↗

[Efficacy of group therapy of alcoholics. Results of a controlled clinical trial].

BACKGROUND: Group therapy is widely used in psychiatry and psychology, specially in the treatment of alcoholism. Nevertheless, scientific evidence of its efficacy is scarce, and professionals tend very often to doubt about its usefulness. METHODS: Clinical trial to test the efficacy of group therapy to improve abstinence and compliance of alcoholics (CIE-10 criteria) randomly assigned to standard treatment plus group therapy (TG+, n = 45) versus standard treatment alone (TG-, n = 43) during 12 months. RESULTS: At 6 months follow up, the percentage of alcohol consumers (26 vs 20%) and dropouts (49 vs 36%), was slightly higher among the TG- group; while Cumulated Abstinence Duration (131 days [SD 57] versus 135 days [SD 64]) tended to be higher in the TG+ group. Differences increase at the one year follow up, reaching a significant level when measuring time to first relapse (233 vs 382 days; p = 0.04). Also, the probability to remain abstinent is clearly lower in the TG- (31 vs 76%). CONCLUSIONS: These results clearly show the efficacy of group therapy. Its effect appears from the 3rd month and increases from 6th to 12th months. Some patients, specially those who will have worse clinical evolution, refuse to attend group sessions. Also, some others who don't accept an abstinence oriented treatment, may interfere in group dynamics. In order to maximize group efficacy, extreme care should be taken in selection of patients, group composition, setting and leadership style.

Adult↗

Selective versus non-selective neural stimulation in the monitoring of muscular relaxation during general anesthesia.

AIM: The depth of muscular relaxation during general anesthesia is monitored through the analysis of the contraction evoked by selective electrical stimulation of a peripheral nerve. The aim of this study was to compare the method of selective stimulation (SS) to a new method based on non-selective electrical stimulation (NSS) delivered over the muscle. METHOD: Electrical stimuli were delivered as train-of-four impulses to the ulnar nerve (SS) and to the ventral aspect of the contralateral forearm (NSS). The muscular responses of the adductor pollicis brevis (SS) and the forearm supinator longus (NSS) were studied at 30-60 s intervals with piezoelectric transducers before and after the administration of atracurium bolus doses of 0.5 mg/kg to patients under general anesthesia. SS and NSS evoked muscular responses were quantitized as percentages of the control response and compared with linear correlation and concordance analysis. RESULTS: Twenty patients were studied. Basal and post-atracurium muscular responses were similar for the SS and the NSS methods. Precision between SS and NSS was >85% and accuracy >92%. Concordance was: basal <15%, relaxation <5%, recovery <10%. CONCLUSION: NSS is equivalent to SS for muscular relaxation monitoring during general anesthesia. This has important implications to simplify muscular relaxation monitor design.

Adult↗

Mismatch negativity and auditory sensory memory in chronic alcoholics.

BACKGROUND & METHODS: Preattentive auditory processing and sensory memory were investigated by means of mismatch negativity (MMN) in a sample of 22 middle-aged abstinent chronic alcoholics and 25 age-matched healthy controls. Stimuli were presented at two inter-stimulus intervals (ISIs, 0.75 sec and 2.0 sec) in separate blocks. RESULTS: No significant differences in amplitude or latency of MMN were found between alcoholic and control subjects in either of the two ISI conditions. However, when age was included as a factor in the analysis, MMN amplitude was attenuated in chronic alcoholics who were older than 40 years of age. CONCLUSIONS: These results indicate that the automatic stimulus-change detector mechanism associated with MMN generation is impaired in chronic alcoholics over the age of 40, suggesting that the neurotoxic effects of chronic consumption of alcohol are more prone to appear after a critical age.

Adult↗

Bradykinin decreases outflow facility in perfused anterior segments and induces shape changes in passaged BTM cells in vitro.

PURPOSE: To investigate the effects of bradykinin (BK) on the outflow facility (C) of human and bovine perfused anterior segments, the [Ca2+]i of cultured bovine trabecular meshwork (BTM) cells, and the area and major axis of BTM cells. METHODS: Cellular studies were performed using first- through third-passage cultures of BTM cells. For [Ca2+]i and shape change assessment, BTM cells were loaded with fura-2 acetoxymethyl ester, and individual fluorescence images were analyzed after the different experimental manipulations. C studies were performed in vitro using human and bovine anterior segments perfused at constant pressure. RESULTS: Bradykinin at 10(-6) M elicited a [Ca2+]i increase of 8 to 10 times the basal levels in 90% of the studied cells. From the responder cells, 60% elicited a 15%+/-1% reduction of the initial cell area, and 37% showed a 13%+/-2% reduction of their major axis. Bradykinin failed to induce any effect in the presence of the BK-B2 receptor antagonist HOE-140. Zero [Ca2+]o the depletion of intracellular stores with thapsigargin, or the presence of the calmodulin antagonist W13, decreased the BK response significantly (P < 0.001; P < 0.001; and P < 0.05). A second application of BK elicited a significantly lower (P < 0.001) response than the previous one. Perfusion with 10(-6) M BK decreased CD, calculated as the area under the curve, by 13%+/-4% (P < 0.05) in human anterior segments and 12%+/-4% (P < 0.05) in bovine anterior segments. The presence of 10(-6) M HOE-140, a BK-B2 receptor antagonist, completely blocked the decrease in C after perfusion with BK. CONCLUSIONS: The C of human and bovine trabecular meshwork (perfused anterior segments) is decreased by BK, acting through BK-B2 receptors. Primary cultured BTM cells respond to BK stimulation by increasing their [Ca2+]i by mobilization of extracellular and intracellular Ca2+. Moreover, these cells are reduced in area and their major axis shortened after the [Ca2+]i peak elicited by BK through BK-B2 receptors. The [Ca2+]i mobilization and shape changes are calmodulin dependent. Taking into account the [Ca2+]i mobilization, the BTM shape changes, the decrease of C, and the temporal sequence of these parameters, a contraction of trabecular meshwork cells related to the functional role of trabecular meshwork is discussed.

Aged↗

Characterization of the small subunit of the terminase enzyme of the Bacillus subtilis bacteriophage SPP1.

The small subunit of bacteriophages SPP1 and SF6 terminase, G1P, share 71% identity clustered in three conserved segments (I, II, and III). Within segment I the helix-turn-helix DNA-binding domain was mapped, whereas segment III was found to be nonessential. For terminase activity, chimeric G1Ps, obtained by domain swapping between gene 1 of SPP1 and the SF6 origin (Chi1 to Chi4), were purified. The chimeric proteins behave in all respects similarly to the G1P of SPP1 or SF6. The major determinant for G1P:G1P interactions was found to lie within segment II. We showed that a G1P derivative (G1P*) lacking the 62 N-terminal residues (segment I), and Chi1 lacking the 45 C-terminal residues (segment III) interact with G1P. The N-terminal domain of G1P is necessary for terminase subunit assembly, because the large subunit of the terminase (G2P) interacts only with G1P and Chi1, but fails to do so with G1P*. These results suggest that segment III and the extended C-terminal part of SPP1 G1P do not play a major role in DNA recognition and that G1P recognizes an extended nucleotide sequence and DNA structure.

Amino Acid Sequence↗

Facility changes mediated by cAMP in the bovine anterior segment in vitro.

The aim of this study was to investigate the influence of substances that increase intracellular cAMP levels on the aqueous humor outflow facility (C) of isolated bovine anterior segments. Anterior segments were perfused in vitro at a constant pressure of 10 mmHg for 270 min with a general protocol as follows: 90 min control perfusion with DMEM, 90 min of experimental perfusion with DMEM containing the test drug(s), and 90 min of postdrug-perfusion with DMEM. C was calculated as the ratio between the rate of medium inflow (microliter/min) and the perfusion pressure (mmHg). Anterior segments can be perfused in vitro for up to 5 hr without significantly modifying their C. The addition of epinephrine, forskolin, dibutyryl-cAMP or isobutylmethylxanthine to the control perfusion medium elicited a significant increase of C. If, during isobutylmethylxanthine perfusion, forskolin or epinephrine was added, C increased significantly. Finally, perfusion with indomethacin prior to addition of epinephrine prevented the increase of C induced by epinephrine. Epinephrine, the adenylate cyclase activator forskolin, the cAMP analog dibutyryl-cAMP, and the phosphodiesterase inhibitor isobutylmethylxanthine all increase aqueous facility. It seems reasonable to suspect that the cAMP system is involved in epinephrine's effects on bovine trabecular meshwork cells. Moreover, the complete inhibition by indomethacin of the outflow facility increase induced by epinephrine suggests that prostaglandins may be involved in the outflow facility mechanisms related to adrenoreceptor stimulation of trabecular meshwork cells.

1-Methyl-3-isobutylxanthine↗

Why has alcohol consumption declined in countries of southern Europe?

Alcohol consumption seems to be decreasing in the traditional wine countries of southern Europe. This paper describes the evolution of alcohol consumption over the last 30 years in France, Greece, Italy, Portugal and Spain. For this purpose, data on alcohol production and per capita alcohol consumption in southern Europe are examined, and their reliability discussed. To analyse alcohol-related mortality, liver cirrhosis death rates are also reviewed. Since 1980 overall alcohol production has increased by 10%, while wine production has decreased by 13%. The consumption of pure alcohol equivalent per capita has continually decreased, from a peak of 14 litres per year in 1974 to 10.4 litres in 1992. The reduction is dramatic for wine (42.3%) and slight for spirits (4.7%), while beer consumption has grown by 36.6%. These data seem to confirm a European trend towards the homogenization of drinking patterns. Marketing factors, public health policies, the evolution of prices and taxation, European Union agricultural policies, a growing awareness of public opinion about the toxicity of alcohol and competition from non-alcoholic drinks are all factors that may partially explain these observed changes.

Alcohol Drinking↗