Search

As a part of ongoing study about the role that different technical factors may play in influencing the sensibility of HIV isolation procedures, the authors have evaluated the effects of PHA stimulation of infected cells on HIV replication in cell cultures. Data presented demonstrate that the use of PHA in cell cultures for HIV isolation causes a slower viral replication and, in some cases, inhibits HIV growth.

The effect of L-cysteine on the depletion of serotonin and 5-hydroxyindoleacetic acid concentrations caused by p-chloroamphetamine and d-fenfluramine was studied in various brain regions one week after drug injection. p-Chloroamphetamine (2.5 and 5 mg/kg i.p.) and d-fenfluramine (13.4 mg/kg i.p.) significantly reduced serotonin and 5-hydroxyindoleacetic acid levels in the striatum, hippocampus and cortex, particularly in the latter areas. L-cysteine (500 mg/kg i.p.), administered 30 min before and 5 h after p-chloroamphetamine or d-fenfluramine, significantly reduced the effect of either drug on the concentrations of both indoles without causing any effect by itself. In another experiment, the rats were treated as above and were killed at various times after p-chloroamphetamine or d-fenfluramine injection to determine, in parallel, the indole levels in the whole brain and the concentration of p-chloroamphetamine, d-fenfluramine and its metabolite d-norfenfluramine in the plasma and brain. p-Chloroamphetamine and d-fenfluramine markedly lowered both indoles, particularly 16 and 24 h after injection. L-cysteine had no effect on the indole concentrations but significantly reduced the effect of p-chloroamphetamine, d-fenfluramine 16 and 24 h after injection. At these times, the brain concentrations of p-chloroamphetamine, d-fenfluramine and d-norfenfluramine were markedly lower in the L-cysteine-treated than in the control rats. Analysis of the blood concentration of p-chloroamphetamine, d-fenfluramine and d-norfenfluramine showed that the rats treated with L-cysteine eliminated the drugs studied more rapidly than the control animals.(ABSTRACT TRUNCATED AT 250 WORDS)

The anorectic drug D-fenfluramine (D-F) was administered as single i.v. doses of 1.25 and 6.25 mg/kg to lean female Sprague-Dawley and lean and obese female Zucker rats. Blood samples were collected serially and analysed by electron capture gas-liquid chromatography for D-F and its main metabolite, D-norfenfluramine (D-NF). At the lowest dose the disappearance of D-F followed an apparent first-order process with mean elimination half-life (T1/2) of approximately 2 h in female Sprague-Dawley and 4 h in lean and obese Zucker rats. Mean absolute steady-state volume of distribution (Vss) was the same in the lean female of both strains but total clearance (Cl) was significantly lower in the Zucker rats. Therefore elimination T1/2 of D-F was longer in female Zucker than Sprague-Dawley animals. Obese rats presented lower relative Cl and Vss but no change in absolute Cl and Vss and elimination T1/2 of the drug. Intra- and inter-strain differences were observed in hepatic microsomal protein and P-450 content. As in the case of D-F the elimination T1/2 of D-NF was also longer in Zucker than Sprague-Dawley rats. No differences were observed between lean and obese rats but in all cases the elimination T1/2 of the metabolite was much longer than that of its parent drug. After larger doses (6.25 mg/kg) the kinetics of the drug were not linear. The apparent Cl declined changing the metabolite-to-parent drug ratios in all types of rats, but more evidently in Zucker than Sprague-Dawley rats and in obese than lean animals. Inter- and intra-strain differences in D-F and D-NF kinetics should be considered in neurochemical studies of the drug and extrapolation of data across animal species requires consideration of dose dependence in the rat.