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Biomedical subjects

E García

Publications and source records attributed to E García.

At least 163 records · Page 9Linked to original sources

Resistance to atracurium in rats with experimental inflammation: role of protein binding.

The influence of altered protein binding on the neuromuscular effect of atracurium has been studied in rats with experimental inflammation induced by subcutaneous injection of turpentine oil. Doses of atracurium ranging from 0.45 to 1.5 mg.kg-1 were administered to control (n = 30) and to experimental inflammation induced rats (n = 30). Neuromuscular transmission was monitored by recording the twitch tension of the tibialis-anterior muscle elicited by stimulation of the sciatic nerve. Three effect parameters were recorded: (i) intensity of the effect, measured as percentage depression of baseline twitch tension, (ii) duration of drug action (min) and (iii) recovery time (min). The dose-intensity of the effect relationship was modelled using a sigmoid Emax model. The ED50 (effective dose eliciting 50% of the maximum effect) was significantly increased (P < 0.01) in the inflammation group as compared to the control group (0.94 vs. 0.68 mg.kg-1). This change was reflected in a shift of the dose-response curve to the right in the pretreated rats. For equipotent doses ED95 (defined as the effective dose eliciting 95% of maximum effect), no differences were found in recovery time and duration of action between the two groups of rats. Mucoproteins levels (index of alpha 1-acid glycoprotein (AAG) and protein binding were significantly increased in rats with experimental inflammation as compared to control rats. Based on these results, altered serum protein binding of atracurium appears to be responsible, at least in part, for the resistance to atracurium.

Animals↗

Isolation of microsatellites from the spinal muscular atrophy (SMA) candidate region on chromosome 5q and linkage analysis in Spanish SMA families.

A locus responsible for autosomal recessive spinal muscular atrophy (SMA) on chromosome 5q11.2-q13.3 has been mapped to a critical interval delimited by markers D5S435 and D5S557. By a modification of the Vectorette-(GT)n method, we have isolated three polymorphic CA repeats from two YACs of the SMA region. Two of them (D5S1417 and D5S1416) map within the SMA critical region, and the other (D5S1415) is centromeric to D5S435. Linkage analysis in Spanish SMA families with eleven markers showed that in our families the disease is linked to this region and confirmed that the novel markers are tightly linked to the SMA locus. The most likely order of markers was 5cen-(D5S63/D5S1356)-(D5S125/D5S465)- (D5S435/D5S1417/D5S1416/D5S557)-D5S610- D5S112-D5S127-5qter, with odds against alternative orders > 1,000:1. Genetic distances are in agreement with those previously published. However, the recombination fraction between D5S610 and D5S112 is remarkably greater than expected from the physical distance, suggesting a hot spot for recombination in this region. Our results from haplotype and multipoint analyses show that the SMA locus must lie between D5S465 and D5S112, and lend further support to the current location of the SMA locus.

Base Sequence↗

[The anatomical correction of transposition of the great arteries in the neonatal period].

INTRODUCTION AND OBJECTIVES: Anatomic correction of transposition of the great arteries in simple and complex form is theoretically the only procedure which offers the possibility of real cure to the problem. We report there our operative results and mid-term follow-up with this approach. METHODS: From June 1989 to February 1994, anatomical surgical correction was performed in 41 patients in the neonatal period, 31 with simple TGA and 9 patients with transposition associated with ventricular septal defect. We report our preoperative management, anatomic findings and surgical technique. RESULTS: Our initial experience with the arterial repair was associated with a high operative mortality. The actuarial survival rate was 74% at 56 months. Hospital mortality of the last 31 patients was 12.9%. Intermediate-term follow-up was 18 months. No late deaths. One patient underwent reoperation for supravalvular pulmonary stenosis. All survivors are in functional class I. The only significant risk factor of in-hospital mortality was the time of surgery (learning curve). CONCLUSION: The initial experience with arterial repair is associated with a difficult learning curve. Primary repair must be performed during the newborn period in simple and complex transpositions. Mid-term results are very encouraging. Longer follow-up is necessary to secure this technique and to render obsolete all other types of repair.

Aortic Coarctation↗

[Registry of activities of the Hemodynamics and Interventional Cardiology Section in 1994].

Results of the Spanish Registry for Hemodynamic and Interventional Cardiology are presented. As previous years, has been done by the Chapter of Hemodyamics and Interventional Cardiology of the Spanish Society of Cardiology. Seventy seven cardiac catheterization laboratories have collaborated, which represents 100% of those who had any activity in 1994. Sixty nine performed cardiac catheterization in adults, in 90% of the cases performing coronary intervention, and 22 performed both adult and pediatric studies. Eight laboratories exclusively performed pediatric cardiac catheterizations. Fifty five thousand one hundred sixty nine diagnostic procedures were performed, the majority of them being coronariographies (41,887), representing an increase of 10% from 1993. Ten thousand four hundred thirty three angioplasty procedures were performed in 1994. This represents 274 PTCA per million people (an increase of 21% compared to 1993). Eighty seven per cent of these procedures were done with conventional balloon, 1,361 stents were implanted (724 electivily), and 308 directional and 305 rotational atherectomies were performed. The overall results are similar to those of 1993, except for a marked reduction in complications of stents procedures (mainly in those implanted in a rescue situation). PTCA success was 91% with a complication rate of 3.4% and a mortality of 0.69%. The number of mitral valvuloplasties decreased 16% (694 vs 825 in 1993), and the pediatric interventional procedures were 7% less than those of 1993.

Adult↗

Synthesis of 2-piperazinylbenzothiazole and 2-piperazinylbenzoxazole derivatives with 5-HT3 antagonist and 5-HT4 agonist properties.

New 2-piperazinylbenzothiazole and 2-piperazinylbenzoxazole derivatives were prepared and tested as 5-HT3 receptor antagonists. Some of the new compounds antagonized the effect of 5-HT at the longitudinal muscle myenteric plexus (LMMP) preparation of the guinea pig ileum, and two benzothiazole derivatives, compounds 2e and 2f, were more potent than ondansetron in this regard. However, these two compounds were much weaker than the typical 5-HT3 receptor antagonist as displacers of [3H]BRL-43694 binding to rat cerebral cortex homogenates or as antagonists of the bradycardia response to 5-HT in the anaesthetized rat. Like the prokinetic agent cisapride, some of the new compounds enhanced gastric emptying in rats. Compound 2f not only markedly enhanced gastric emptying but was also a potent agonist at the isolated rat oesophageal tunica muscularis mucosae, a preparation sensitive to 5-HT4 receptor stimulation, and enhanced the twitch response in the LMMP preparation. The latter effect was blocked by a high concentration of tropisetron or by previous desensitization with 5-methoxytryptamine. Compound 2f appears to show a promising pharmacological profile as a potential gastrokinetic agent.

Animals↗

Molecular basis of the optochin-sensitive phenotype of pneumococcus: characterization of the genes encoding the F0 complex of the Streptococcus pneumoniae and Streptococcus oralis H(+)-ATPases.

The gene responsible for the optochin-sensitive (OptS) phenotype of Streptococcus pneumoniae has been characterized. Sequence comparisons indicated that the genes involved encoded the subunits of the F0 complex of an H(+)-ATPase. Sequence analysis and transformation experiments showed that the atpC gene is responsible for the optochin-sensitive resistant (OptS/OptR) phenotype. Our results also show that natural as well as laboratory OptR isolates have arisen by point mutations that produce different amino acid changes at positions 48, 49 or 50 of the ATPase c subunit. The nucleotide sequence of the F0 complex of the Streptococcus oralis ATPase has also been determined. In addition, comparison of the sequence of the atpCAB genes of S. pneumoniae R6 (OptS) and M222 (an OptR strain produced by interspecies recombination between pneumococcus and S. oralis), and S. oralis revealed that, in M222, an interchange of atpC and atpA had occurred. We also demonstrate that optochin specifically inhibited the membrane-bound ATPase activity of the S. pneumoniae wild-type (OptS) strains, and found a 100-fold difference between OptS and OptR strains, both in growth inhibition and in membrane ATPase resistance.

Amino Acid Sequence↗

Molecular characterization of cap3A, a gene from the operon required for the synthesis of the capsule of Streptococcus pneumoniae type 3: sequencing of mutations responsible for the unencapsulated phenotype and localization of the capsular cluster on the pneumococcal chromosome.

The complete nucleotide sequence of the cap3A gene of Streptococcus pneumoniae, which is directly responsible for the transformation of some unencapsulated, serotype 3 mutants to the encapsulated phenotype, has been determined. This gene encodes a protein of 394 amino acids with a predicted M(r) of 44,646. Twelve independent cap3A mutations have been mapped by genetic transformation, and three of them have been sequenced. Sequence comparisons revealed that cap3A was very similar (74.4%) to the hasB gene of Streptococcus pyogenes, which encodes a UDP-glucose dehydrogenase (UDP-GlcDH) that catalyzes the conversion of UDP-glucose to UDP-glucuronic acid, the donor substances in the pneumococcal type 3 capsular polysaccharide. Furthermore, a PCR-generated cap3A+ gene restored encapsulation in our cap3A mutants as well as in a mutant previously characterized as deficient in UDP-GlcDH (R. Austrian, H. P. Bernheimer, E.E.B. Smith, and G.T. Mills, J. Exp. Med. 110:585-602, 1959). These results support the conclusion that cap3A codes for UDP-GlcDH. We have also identified a region upstream of cap3A that should contain common genes necessary for the production of capsule of any type. Pulsed-field gel electrophoresis and Southern blotting showed that the capsular genes specific for serotype 3 are located near the genes encoding PBP 2X and PBP 1A in the S. pneumoniae chromosome, whereas copies of the common genes (or part of them) appear to be present in different locations in the genome.

Amino Acid Sequence↗

Struggling and flumazenil effects in the swimming test are related to the level of anxiety in mice.

The possible involvement of anxiety and learning/memory processes in escape-directed (struggling) behavior in a two-trial swimming test was investigated in mice, as well as the differential effects that low doses of flumazenil (a benzodiazepine receptor antagonist) could display depending on the animals' anxiety levels. Mice showing less anxiety in the plus-maze test exhibited less struggling behavior in the first swimming trial than the more anxious animals, suggesting a relationship between anxiety and struggling behavior in the swimming test. Flumazenil (5 mg/kg) given before the first swimming trial displayed differential effects depending upon the animals' anxiety levels. Thus, it increased struggling behavior in the first swimming trial in 'low-anxiety' mice whereas the opposite tendency was observed in 'high-anxiety' animals. Struggling decreased in the second swimming trial in all the animals, giving support to the involvement of learning/memory processes in the two-trial swimming test. That reduction in escape-directed behavior was greater in animals treated with flumazenil before the first swimming session, thus indicating a slight enhancement of retention.

Animals↗

Clastogenicity of triazinoindole derivatives in relation with the physicochemical properties of the substituents.

The clastogenicity of four compounds of the series 3-(4'-substituted-benzylidenamino)5H-1,2,3-triazin [5,4-b]indol-4-one, which showed an important activity as inhibitors of platelet aggregation, has been evaluated. The compounds studied differed in the physicochemical properties of the substituent occupying the 4' position of the benzilidenamino group. The 4' substituents were: -H, -NO2, -OCH3 and -C6H5. They were tested on V-79 cells, both with and without metabolic activation, and structural chromosome aberrations were scored. Compounds with -H, -NO2 and -OCH3 radicals were active both with and without metabolic activation. Compound with -C6H5 radical was clastogenic only at the highest dose tested and with metabolic activation. It appears that the compound with the biggest and most hydrophobic substituent is the least clastogenic of the series. These results are in agreement with some previous ones obtained in bacteria and show a good correlation between the results of the Ames test and the structural chromosome aberrations test.

Bacteria↗

[Results of endoscopic dilatation treatment of benign esophageal stenosis].

The management of benign esophageal stenoses is based on endoscopic dilatation of the tight segment for the remission of dysphagia. Five hundred and twenty sessions of dilatation with Savary-Guilliard bougies have been performed in one hundred and twenty-nine patients with benign esophageal stenoses. Patients with peptic stenoses (n = 59) needed a lesser number of sessions (mean: 2.47) than patients with postsurgical (n = 44; mean: 4.86) or caustic (n = 18; mean: 7.77) stenoses. The treatment failed in 4 patients (3.2%) and severe complications were observed in 3 patients (2.4%). These results support the efficacy and safety of this technique.

Adolescent↗

Evaluation of the mutagenicity of 1-hydrazino-4-(3,5-dimethyl-1-pyrazolyl) pyridazino[4,5-b]indole.

The mutagenic potential of 1-hydrazino-4-(3,5-dimethyl-1-pyrazolyl) pyridazino [4,5-b]indole(A80a, CAS 135561-93-2), a new antihypertensive agent, was investigated in 3 test systems, according to the current EC Guidelines: Ames test with strains TA1535, TA1537, TA98 and TA100, SCE (sister chromatid exchange) test in V79 cells and micronucleus test in Swiss mice. No indications for a mutagenic potential were detected in bacteria and mice; positive results were obtained in eukaryotic cells. The potential for inducing chromosome aberrations in eukaryotic cells will be studied.

Animals↗

[Vaccination coverage in the districts of the city of Castellon and the relationship with sociodemographic factors: an ecologic study].

BACKGROUND: The state of vaccination in 1987 of those born in the city of Castellon and the relation with a group of sociodemographic variables by districts collected from a study based on the census of inhabitants of 1986 was analyzed. METHODS: The state of vaccination of each child was obtained from the Computerized Municipal Registry of Vaccinations with good vaccination being considered when the child had received all the doses corresponding to the age of two years (four doses of oral trivalent poliomyelitis and three doses of diphtheria-tetanus-pertussis and one dose of diphtheria-tetanus and one dose of triple virus) and was considered as badly vaccinated when one of the doses had been missed. Following classification of each child according to the district of residence, the effect of the state of vaccination, the sex of the child and the month of birth as well as the group of variables collected in the district (ecologic base), the relative risks were estimated by logistic regression analysis. RESULTS: Neither the sex of the child nor the month of birth had any relation with the risk of being badly vaccinated. Upon analysis of the effect being born in a determined district had, five presented between two and four times less risk of bad vaccination than that taken by reference (La Vila) and another three presented up to two times more risk. Among the significant predictors of risk of bad vaccination the following were found: crowding, old age, rate of dependence, rate of widowhood, and the proportion of single people, while the percentage of active women and the density of population were protective. In multivariant analysis, only the proportion of single people and the number of active women persisted as significant predictors. CONCLUSIONS: Although great inequality has been reported in vaccination coverage among the districts of the city of Castellon, the general coverage of the city may be considered as satisfactory in the light of the criteria used and from comparisons with other similar studies. The associations found between bad vaccination and some sociodemographic variables by districts (proportion of single people, and active women) together with possible methodologic limitations, do not allow the important inequalities found to be satisfactorily explained.

Child↗

[Anthropometric reference parameters for the aged population].

BACKGROUND: Anthropometry is an effective method used in the evaluation of the state of nutrition. Anthropometric reference values obtained from the general population have frequently been used. The aim of this study was to determine the anthropometric parameters of the elderly in Manresa and demonstrate the different evolution of these values in both sexes between the ages of 65 and 85 or more. METHODS: Following randomization a representative sample of 1,034 healthy elderly subjects living in Manresa was obtained with the following being determined: weight, height, tricipital, subscapular and abdominal fat folds, arm circumference, arm muscle perimeter, weight/height indexes, muscle and fat areas of the arm and percentage of fat. All the measurements were obtained by the same person with the use of a tallimeter scale with a flexible metric tape and a Holtain lipocalibrater. RESULTS: The values are presented in percentiles by subgroups of age and sex. The weight, height and indexes of lean mass were greater in males while those determining fatty mass were greater in females. In females all the values decreased between 65 and 85 or more years of age (p < 0.001), while in males all decreased (p < 0.001) except; tricipital and abdominal skin folds. Upon comparison of these parameters with those obtained in other geographic areas, differences were observed between both. CONCLUSIONS: By the characteristics of the population studied it was considered that the anthropometric parameters obtained are extensible to all the elderly population of Catalonia and may be used as reference values of the same.

Aged↗

Cloning and sequencing of a gene involved in the synthesis of the capsular polysaccharide of Streptococcus pneumoniae type 3.

A 4.5 kb ScaI chromosomal DNA fragment of a clinical isolate of Streptococcus pneumoniae serotype 3 was cloned in Escherichia coli. Combined genetic and molecular analyses have allowed the localization, in a 781 bp EcoRV subfragment, of a gene (cap3-1) directly responsible for the transformation of an unencapsulated, serotype 3 mutant to the capsulated phenotype. Comparison of the deduced amino acid sequence of CAP3-1 with the protein sequences compiled in the data banks revealed that the CAP3-1 polypeptide was highly similar to the amino-terminus of the GDP-mannose dehydrogenase of Pseudomonas aeruginosa, an enzyme that participates in the synthesis of the mucoid polysaccharide of this species. In addition, the 32 N-terminal amino acids of CAP3-1 perfectly matched structures common to NAD(+)-binding domains of many dehydrogenases. Our results indicate that the 4.5 kb ScaI fragment might also contain genes common to 13 different pneumococcal serogroups or serotypes tested. To the best of our knowledge, this is the first time that a gene of the capsular complex of S. pneumoniae has been cloned and sequenced. The findings reported here provide new insights for the study of the molecular biology of the main virulence factor responsible for the pathogenesis of pneumococcal infections and might represent a basic step in the identification of cross-reactive antigens that should allow the preparation of new and improved vaccines.

Amino Acid Sequence↗