The pharmacology of VA21B7: an atypical 5-HT3 receptor antagonist with anxiolytic-like properties in animal models

VA21B7 (3-[2-(4-piperonylpiperazinyl) indolyl] carboxaldehyde) was synthesized as a potential 5-HT₃ receptor antagonist. Even though VA21B7 showed a higher affinity towards 5-HT₃ receptors as compared to other receptors studied, it was not a potent 5-HT₃ receptor antagonist either in the periphery or in the brain. In a simple animal model of anxiety such as the two-compartment box in mice, a remarkable anxiolytic-like effect was found at doses of 2–500 µg/kg IP and also at low oral doses, in the microgram range. These drug doses did not produce any significant effect on spontaneous motor activity of mice. The anxiolytic profile of VA21B7 was further explored using other models of anxiety in rats such as the elevated plus-maze and punished-drinking. VA21B7 was compared with standard 5-HT₃ receptor antagonists such as ondansetron, tropisetron and granisetron, with the 5-HT_1A agent buspirone and with diazepam. In the plus-maze, VA21B7 showed an anxiolytic-like profile after doses of 0.25–0.5 mg/kg IP or 2–4 mg/kg PO which did not modify the number of total entries into the open and closed arms of the maze. Diazepam, granisetron and tropisetron were also effective in this test but not ondansetron and buspirone. VA21B7 was also able to release suppressed behaviour in the punished-drinking test. The dose-response curve was bell-shaped with a peak at 2–4 mg/kg. At variance with other studies, 5-HT₃ receptor antagonists also increased the number of shocks taken in this test and the dose-response curve was also bell-shaped. VA21B7 was not anticonvulsant like diazepam, its anxiolytic action in the light/dark test was not flumazenil-sensitive and there was no rebound anxiogenic effect on withdrawal from chronic VA21B7 treatment for 15 consecutive days. Moreover, VA21B7 was not amnesic like the benzodiazepines but low doses of 2–4 mg/kg reduced the memory deficits induced in rats by scopolamine. Much higher doses were necessary to decrease spontaneous motor activity in rats. Since VA21B7 appears to be well tolerated in rodents at high doses, we think that it is of potential interest as an anxiolytic in humans.     

Population study of 3 STR loci in the Basque Country (northern Spain)

The tetrameric STRs, HUMTH01, HUMVWA31A and HUMFES/FPS, were studied in a population from the Basque Country (northern Spain) for their frequency distribution and applicability to identity and paternity testing. All systems conformed to Hardy-Weinberg equilibrium; pairwise comparisons demonstrated the allelic independence between loci, and furthermore, all systems seemed to be in agreement with expectations from the Stepwise Mutation Model (SMM) of the mutation-drift theory, which indicates the homogeneity of the population and suggests a replication slippage mechanism as a possible model for generating alleles. A comparison with other population groups appeared to indicate that frequencies are well conserved in Caucasians, but differ from other racial groups. The calculated parameters a priori probability of exclusion (PEX) and index of discrimination (ID), show the informativeness of these loci for the determination of identity and relatedness of individuals.     

The use of the STRs HUMTH01, HUMVWA31/A,HUMF13A1, HUMFES/FPS,HUMLPL in forensic application: Validation studies and population data for Galicia (NW Spain)

The 5 tetranucleotide short tandem repeats, HUMTHOI, HUMVWA31/A, HUMF13A1, HUMFES/FPS and HUMLPL were studied using different electrophoretic methods and PCR amplification conditions in order to optimize the typing conditions. A genetic population study in the population of Galicia was carried out and the allele and genotype frequencies are given. Compliance with the Hardy-Weinberg equilibrium was tested using different statistical parameters, with clear advantages resulting in favor of using the exact test (Guo-Thompson method) instead of conventional chi-square methods. Some statistical parameters of forensic interest (PD, CE, h) were also calculated. There were no mutations found in a total of 73 paternal meioses and 101 maternal meioses. Abnormal electrophoretic mobility was found in the AT-rich STR HUMF13AI under non-denaturing conditions and, therefore, the use of denaturing conditions is absolutely necessary. No "stutter" bands were found, although double peaks in the HUMFES/FPS system were observed in some samples. The advantage of using automated sequencers with fluorescent technology is also reported.     

Blood retinol and β-carotene levels in rural Guatemalan preschool children

Plasma retinol and -carotene levels were measured in 502 preschool Guatemalan children from five rural hamlets. Their ages ranged from 6 to 78 months (mean: 42.9±19.2 months); 45% males and 55% females. The mean retinol value in the whole group was 0.9±0.4 µmol/1 (range: 0.1 to 8.4 µmol/1). There was no significant difference between sexes in retinol mean values nor in the incidence of retinol values less than 0.7 µmol/1 (22% in males, 18% in females). When grouped by age and community, significant low retinol mean values were found in two hamlets in the youngest age group (12 to 23 months) as compared to the other age-groups (p<0.05). In the other two hamlets, there were no significant differences among retinol means by age-group. The highest prevalence of deficient retinol values by age-group was in the 12 to 23 months group (40%), and decreased as age increased. The mean value for -carotene in the whole group was 0.13±0.18 µmol/1 (range: 0.01 to 2.23 µmol/1). There were no significant differences in -carotene means between sexes in the whole group. Stratifying the -carotene data by age-groups and community, values were significantly higher in the 48–59 months and 72–83 months groups, as compared with the other age groups in two of the communities (p<0.05). Significant differences across communities for -carotene were found only in the 12 to 23 months group.     

Effect of ethylene on naringin, narirutin and nootkatone accumulation in grapefruit

This paper studies the effect of different concentrations of ethephon on the levels of the sesquiterpene, nootkatone, and of the flavanones, naringin and narirutin, in grapefruit fruits. The results show that nootkatone synthesis and/or accumulation was stimulated by all the concentrations of ethephon assayed, while the levels of naringin and narirutin in the rind diminished. These results open up new perspectives concerning the possible regulation of the secondary metabolism of the plants.     

Clinical features of hepatic artery thrombosis after pediatric liver transplantation

Thrombosis of the hepatic artery (HAT) is a severe complication of liver transplantation, and most cases need regrafting. The aim of this study was to review our experience with this complication. From January 1986 through January 1992, 76 liver transplants were performed in 59 pediatric patients at the Children's Hospital La Paz, Madrid. The diagnosis of HAT was made in 12 cases (15.7%). The common patterns of clinical presentation were: fulminant liver necrosis (5), bile leak due to necrosis of the bile duct (4), and relapsing bacteremia (3). Clinical symptoms of fulminant liver necrosis started within the first 2 weeks after transplantation, with rapid deterioration and steep rises in SGOT and SGPT levels. All these patients were retransplanted on an urgent basis, but only 1 is alive 4 years later. Four patients developed bile leaks 13 to 60 days after transplantation; SGOT, SGPT, and total bilirubin were only slightly increased. Three children were retransplanted electively and are alive with a mean follow-up of 3 years. One exceptional patient had a Roux-en-Y jejunostomy and is doing well 30 months later with his original graft. The 3 remaining children had episodes of septicemia with hepatic abscess, liver infarction, and pleural effusion. Liver function tests were normal, with bilirubin levels below 2 mg/dl. All patients were retransplanted, but only 1 is alive and well 13 months later. In the present series, we found that early HAT produces fulminant clinical deterioration requiring an urgent regraft. Late HAT presenting with either infection or bile leak allows time for treatment by elective retransplantation. The best survival was obtained in the latter group. Correspondence to: J. Vázquez     

Epidemiology of dengue and hemorrhagic dengue in Santiago, Cuba 1997]

A dengue epidemic that Cuba reported in 1997 registered more than 500,000 cases of dengue fever produced by viral serotype 1. In 1981, there was an epidemic of dengue hemorrhagic fever produced by serotype 2 of the virus. This time 344,203 clinical cases were reported, 10,312 of which were severe cases of hemorrhagic fever that led to 158 fatalities (101 of them among children). The reintroduction of dengue, and specifically of dengue viral serotype 2 (Jamaica genotype), was quickly detected in January 1997 through an active surveillance system with laboratory confirmation of cases in the municipality of Santiago de Cuba, in the province of the same name. The main epidemiological features of this outbreak are reported in this paper. A total of 3,012 cases were reported and serologically confirmed. These included 205 cases classified as dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), 12 of which were case fatalities (all among adults). Secondary infection with dengue virus was one of the most important risk factors for DHF/DSS. Ninety-eight percent of the DHF/DSS cases and 92% of the fatal cases had contracted a secondary infection. It was the first time dengue hemorrhagic fever was documented as a secondary infection 16 to 20 years after initial infection. Belonging to the white racial group was another important risk factor for DHF/DSS, as had been observed during the 1981 epidemic. During the most recent epidemic it was demonstrated that the so called "fever alert" is not useful for early detection of an epidemic. Measures taken by the country's public health officials prevented spread of the epidemic to other municipalities plagued by Aedes aegypti.     

When is research participatory? Reflections on a reproductive health project in Brazil

This article addresses women's participation in an organization development project designed to improve public sector family planning and reproductive health services in Brazil. Although community women collaborated in aspects of the intervention and research, the project nonetheless raises the basic question whether such involvement of community women does or does not correspond to what scientific writers consider to be the essence of participatory research. We review key project features in the context of recent literature and conclude that although the project is committed to the sharing of power and control, it does not fully correspond to the characteristics of participatory research. Moreover, we argue that given the project's central focus on reproductive health outcomes, complete adherence to the process-oriented, pure version of participatory research would have been inappropriate.     

Underreporting of percutaneous exposure accidents in a teaching hospital in Spain

The study's objectives were to determine the frequency of biological-risk accidents involving percutaneous exposure and to identify factors associated with underreporting. Two hundred fifty healthcare professionals from inpatient services at high risk for exposure at the Puerta del Mar University Hospital of Cádiz, Spain, participated in the study. A questionnaire was used to measure personal and work variables, the number of accidents suffered and reported in the last year, and the circumstances motivating the reporting or nonreporting. Two hundred thirty-two persons (92.8%) completed the questionnaire. The accident rate was 12 per 100,000 hours worked. Physicians were the most frequent accident victims (rate 22/100,000 hours). The general surgery and emergency services had higher rates than other services (rates 19.82 and 14.17, respectively). Sixty-six percent of the accidents were not reported to the register. The main predictors of the underreporting were length of professional service greater than 19 years, working in the surgery service, and the perception that the accidents did not involve health risk. The true accident rate was higher than that reflected in the Accident Register. Underreporting was high. The main variables associated with underreporting were length of professional service, work area or department, and perception of risk from the accident.