Increased Sensitivity to the Anticonvulsant Effect of Valproate in Aging BN/BiRij Rats

The aim of the present investigations was to study the influence of increasing age on the pharmacodynamics of valproate in BN/BiRij rats, applying a threshold for electrically induced localized seizure activity as a measure of the anticonvulsant effect. Seven groups of healthy male BN/BiRij rats were used, aged 3, 6, 12, 19, 25, 31, and 37 months. Individual plasma concentration versus anticonvulsant effect relationships were determined during a continuous intravenous infusion of sodium valproate at a rate of 5.5 mg/min/kg. The infusion was terminated when the anticonvulsant effect intensity had reached the maximum attainable level or at a total infusion time of three hours. A nonlinear relationship between valproate concentration and anticonvulsant effect intensity was observed with no maximal effect in the concentration range up to 1200 mg · L^–1. With increasing age a parallel shift in the concentration versus anticonvulsant effect relationships toward lower concentrations occurred. Thus increasing age appears to be associated with an increased sensitivity to the anticonvulsant effect of valproate.Suzanne Hovinga: Deceased January 30, 1991.     

Tetraspanins: molecular organisers of the leukocyte surface

Tetraspanins are a large superfamily of cell surface membrane proteins characterised by their four transmembrane domains. They are expressed in a wide variety of cell types and have functional roles in processes, such as cellular adhesion, motility, activation and tumour invasion. Leukocytes express 相似文献   

Regulating the gene: From genetic consumption to regulatory trust

In this article, we examine the changing terms on which genetics-based technologies in two areas agriculture (Genetically Modified Organism, GMOs) and health (genetic diagnostics) have been regulated. These are used to illustrate and examine the proposition that shifts in the politics of governance and regulation (associated in part with the advent of the negotiation state) have meant that the responsibility for the social management of new technology is increasingly shared between the state and the consumer. However, this redistribution of the social management of risk, we argue, fails to establish a sufficient basis for a legitimate regulatory trust. We suggest that trust will depend on embedding broad social values and a self-critical agenda within the regulatory regime itself.     

Risk behaviours and seroprevalence to HIV, HBV and HCV in patients of the AIDS information and prevention center in Valencia, Spain

OBJECTIVE: The purpose of this study was to describe the sociodemographic and serologic profiles in a first time consultant population at the Information and AIDS Prevention Center of Valencia (Spain). In addition, the HIV infection risk factors were analyzed. METHOD: A cross-sectional study was performed on 1,573 persons who consulted during the year 1995. Sociodemographic and infection risk practices data were recorded and serologic information about HIV, HBV and HCV infection were obtained. Exact binomial method with a 95% interval confidence was used to calculate infection prevalence and the chi square test to make comparisons between qualitative variables. RESULTS: Sex distribution was 66,1% males and 31,9% females; mean age was 29,01 (SD: 9.2) years. Sexual intercourse without condom (25.2%) and parenteral drug abusers (22.6%) were the more frequent risk groups seeking consultation about HIV infection. Global HIV infection prevalence was 12.7% (95% CI= 11,2-14,5%). Among HIV seropositive patients, sexual transmission accounted for 30.8% of cases, of which 69.4% were heterosexual relations. The HIV infection prevalence for different risk groups were the following: parenteral drug abusers 36.8% (95% CI= 31,7-42%), heterosexual intercourse with an HIV-infected partner 24.1% (95% CI= 17,1-32,2%) and homosexual intercourse between men 9,5% (95% CI= 5,8-14,5%). HCV antibody prevalence for parenteral drug abusers was 81.2% (95% CI= 76,7-85,1%). Risk practices with a statistically significant association with HIV infection were: being an injecting drug abuser, as well as having an HIV infected and/or a injecting drug abuser partner. CONCLUSIONS: Drug parenteral abusers are still the target population for prevention programs. Data suggest that prevention and sexual education programs must continue. The main effort should be focused on the young population and on sexual partners of injecting drug abusers and/or HIV seropositive partners.     

Adjuvant immunization of HLA-A2-positive melanoma patients with a modified gp100 peptide induces peptide-specific CD8+ T-cell responses.

PURPOSE: To measure the CD8+ T-cell response to a melanoma peptide vaccine and to compare an every-2-weeks with an every-3-weeks vaccination schedule. PATIENTS AND METHODS: Thirty HLA-A2-positive patients with resected stage I to III melanoma were randomly assigned to receive vaccinations every 2 weeks (13 vaccines) or every 3 weeks (nine vaccines) for 6 months. The synthetic, modified gp100 peptide, g209-2M, and a control peptide, HPV16 E7, were mixed in incomplete Freund's adjuvant and injected subcutaneously. Peripheral blood mononuclear cells obtained before and after vaccination by leukapheresis were analyzed using a fluorescence-based HLA/peptide-tetramer binding assay and cytokine flow cytometry. RESULTS: Vaccination induced an increase in peptide-specific T cells in 28 of 29 patients. The median frequency of CD8+ T cells specific for the g209-2M peptide increased markedly from 0.02% before to 0.34% after vaccination (P <.0001). Eight patients (28%) exhibited peptide-specific CD8+ T-cell frequencies greater than 1%, including two patients with frequencies of 4.96% and 8.86%, respectively. Interferon alfa-2b-treated patients also had significant increases in tetramer-binding cells (P <.0001). No difference was observed between the every-2-weeks and the every-3-weeks vaccination schedules (P =.59). CONCLUSION: Flow cytometric analysis of HLA/peptide-tetramer binding cells was a reliable means of quantifying the CD8+ T-cell response to peptide immunization. This assay may be suitable for use in future trials to optimize different vaccination strategies. Concurrent interferon treatment did not inhibit the development of a peptide-specific immune response and vaccination every 2 weeks, and every 3 weeks produced similar results.     

Hepatitis E Virus: Current Concepts and Future Perspectives

For many years, hepatitis E was considered a disease found only in certain developing countries. In these geographical settings, hepatitis E virus (HEV) causes a self-limiting hepatitis in young adults, except in pregnant females, in whom the mortality is 25 %. Our understanding of HEV has changed radically in the past decade. It is now evident that HEV is a threat to global health. This review article considers the current concepts and future perspectives of HEV and its effects on human health, with particular reference to developed countries.