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G Peytavin

Publications and source records attributed to G Peytavin.

45 records · Page 3Linked to original sources
PubMed1995

Anesthetics affect the uptake but not the depolarization-evoked release of GABA in rat striatal synaptosomes.

BACKGROUND: Numerous classes of anesthetic agents have been shown to enhance the effects mediated by the postsynaptic gamma-aminobutyric acid A (GABAA) receptor-coupled chloride channel in the mammalian central nervous system. However, presynaptic actions of anesthetics potentially relevant to clinical anesthesia remain to be clarified. Therefore, in this study, the effects of intravenous and volatile anesthetics on both the uptake and the depolarization-evoked release of GABA in the rat striatum were investigated. METHODS: Assay for specific GABA uptake was performed by measuring the radioactivity incorporated in purified striatal synaptosomes incubated with 3H-GABA (20 nM, 5 min, 37 degrees C) and increasing concentrations of anesthetics in either the presence or the absence of nipecotic acid (1 mM, a specific GABA uptake inhibitor). Assay for GABA release consisted of superfusing 3H-GABA preloaded synaptosomes with artificial cerebrospinal fluid (0.5 ml.min-1, 37 degrees C) and measuring the radioactivity obtained from 0.5 ml fractions over 18 min, first in the absence of any treatment (spontaneous release, 8 min), then in the presence of either KCl alone (9 mM, 15 mM) or with various concentrations of anesthetics (5 min), and finally, with no pharmacologic stimulation (5 min). The following anesthetic agents were tested: propofol, etomidate, thiopental, ketamine, halothane, enflurane, isoflurane, and clonidine. RESULTS: More than 95% of 3H-GABA uptake was blocked by a 10(-3)-M concentration of nipecotic acid. Propofol, etomidate, thiopental, and ketamine induced a dose-related, reversible, noncompetitive, inhibition of 3H-GABA uptake: IC50 = 4.6 +/- 0.3 x 10(-5) M, 5.8 +/- 0.3 x 10(-5) M, 2.1 +/- 0.4 x 10(-3) M, and 4.9 +/- 0.5 x 10(-4) M for propofol, etomidate, thiopental, and ketamine, respectively. Volatile agents and clonidine had no significant effect, even when used at concentrations greater than those used clinically. KCl application induced a significant, calcium-dependent, concentration-related, increase from basal 3H-GABA release, +34 +/- 10% (P < 0.01) and +61 +/- 13% (P < 0.001), respectively, for 9 mM and 15 mM KCl. The release of 3H-GABA elicited by KCl was not affected by any of the anesthetic agents tested. CONCLUSIONS: These results indicate that most of the intravenous but not the volatile anesthetics inhibit the specific high-affinity 3H-GABA uptake process in vitro in striatal nerve terminals. However, this action was observed at clinically relevant concentrations only for propofol and etomidate. In contrast, the depolarization-evoked 3H-GABA release was not affected by anesthetics. Together, these data suggest that inhibition of GABA uptake, which results in synaptic GABA accumulation, might contribute to propofol and etomidate anesthesia.

Anesthetics↗
PubMed1995

Nebulizer performance: AFLM study. Association Française de Lutte contre la Mucoviscidose.

This study was conducted by the AFLM order to determine the performance characteristics of 12 commercially available nebulizers (6 ultrasonic and 6 jet) used in the treatment of cystic fibrosis (CF). The nebulizers were connected to a circuit which simulated the ventilation of a CF child and CF adult, and were tested using three drug solutions: tobramycin (T), colistin (C), and amiloride (A). Nebulizer performance was evaluated according to the volume of drug solution delivered in 10 min during the simulated inspiratory phase (VI), drug granulometry (G%), drug concentration modification in the nebulizer reservoir (delta C), and percentage of efficiently aerosolized drug EA%). The ultrasonic devices delivered a significantly higher VI than the jet nebulizers (p < 0.0001) for all three study drug. Ventilation rate did not influence VI. Regarding granulometry, higher percentages of T and A were found to be contained in droplets ranging from 0.5 to 5.0 micron following ultrasonic nebulization. Drug concentration modifications were independent of the nebulizer used but were influenced by drug type; overconcentrations of T and A were observed (delta C = +10.5 +/- 18.6 and +13.4 +/- 8.9%, respectively). On average, the ultrasonic devices achieved a higher EA% than the jet nebulizers (17.3 +/- 6.7 and 9.7 +/- 9.6%, respectively). This study highlights the significant variability in performance of different nebulizer types and empahsizes the importance of accurately testing nebulizers prior to clinical use so that the most efficacious nebulizer/drug combinations may be prescribed.

Administration, Inhalation↗
PubMed1994

In vitro activity of the enantiomers of N-desbutyl derivative of halofantrine.

The in vitro activity of the enantiomers of N-desbutylhalofantrine, the major human metabolite of halofantrine, was compared using the semi-microtest against the multidrug-resistant Plasmodium falciparum FCM 29/Cameroon clone. The mean 50% inhibitory concentration (IC50) values (+/- standard deviation) of the enantiomers were equivalent (2.07 +/- 0.41 and 1.70 +/- 0.33 nmol/L). The enantiomers of the metabolite of halofantrine, as well as those of the parent compound, have the same antimalarial activity. Since (+)-halofantrine and enantiomer-1 of the metabolite attain higher plasma concentrations in man, our study suggests that these enantiomers may be more active in vivo.

Animals↗
PubMed1991

Calcium channel blocking agents protect against acetaminophen-induced cytotoxicity in rat hepatocytes.

The effect on acetaminophen-induced cytotoxicity of three calcium channel blocking agents--diltiazem, verapamil and gallopamil--was studied in primary cultures of rat hepatocytes and compared with the chelating agent EGTA. Using the measurement of cytosolic lactate dehydrogenase (LDH) as an index of cytotoxicity, it was demonstrated that a 1-hr pretreatment with calcium channel blocking agents protected cells against acetaminophen cytotoxicity, but were less effective than EGTA. These data suggest that influx of extracellular Ca2+ into the cells could have a role in the genesis of hepatocyte injury by acetaminophen.

Acetaminophen↗
PubMed1989

Oxalato-platinum or 1-OHP, a third-generation platinum complex: an experimental and clinical appraisal and preliminary comparison with cis-platinum and carboplatinum.

A new platinum complex, oxalatoplatin or l-OHP, which, at the same metal dose in experimental tests is as efficient as cisplatin, and is more so at a lower metal dose than carboplatin; which is as efficient in human tumors of the testis and ovary as these other analogs, and more so in melanoma and breast cancer; which is not nephrotoxic, cardiotoxic or mutagenic, and hardly hematotoxic and neurotoxic, is described and compared with the above-mentioned platinum complexes. Combined with 5Fu, it induces a high number of remissions in colorectal cancer, and has brought about cures in inoperable gastric cancers. Combined with carboplatin, it has resulted in a high proportion of cures in L1210-carrying mice, which no other two-by-two combination of these complexes has achieved.

Animals↗
PubMedDate not supplied

Early virologic failure and rescue therapy of tenofovir, abacavir, and lamivudine for initial treatment of HIV-1 infection: TONUS study.

BACKGROUND: To assess the efficacy and safety of the triple NRTI combination of abacavir (ABC), lamivudine (3TC), and tenofovir (TDF) in a once-daily regimen. METHOD: 38 HIV-naive patients (pts) were treated in a prospective open-arm study over 48 weeks (W48). Virological failure was defined as never achieving plasma HIV-1 RNA < 400 copies/mL or rebound of > or = 0.7 log10. RESULTS: 12/36 (33%) pts had virologic failure at W24 and 10 additional pts had HIV RNA > 50 copies/mL at W12 or W24. There was a significant association between baseline viral load (VL) and virologic failure in 0%, 29%, and 64% pts with baseline VL levels < 4, 4-5, and > 5 log10 copies/mL, respectively (p = .014). 76% of pts developed K65R and M184V/I mutations by W24, and 19% developed M184V/I alone. At W4, 86% of pts had adequate plasma Cmin for the 3 drugs. 14 pts with K65R and M184V/I were given a rescue therapy with a successful outcome (< 50 copies/mL; median follow-up 48 weeks). CONCLUSION: Convergent genetic pathway to resistance, in conjunction with lower antiretroviral potency, may explain the high rate of selection K65R and M184V mutations. These mutations did not appear to have a negative effect on rescue therapy with a variety of regimens.

Adult↗
PubMedDate not supplied

Randomized salvage therapy with saquinavir-ritonavir versus saquinavir-nelfinavir for highly protease inhibitor-experienced HIV-infected patients.

PURPOSE: To compare saquinavir + ritonavir and saquinavir + nelfinavir with nucleoside recycling in patients with multiple failures of highly active antiretroviral therapy (HAART). METHOD: This was a prospective, multicenter, randomized open trial. Inclusion criteria were the following: consent, age > 18, previous protease inhibitor (PI) exposure > 6 months, unchanged HAART > 3 months, and viral load > 3 log. The treatments compared were ritonavir 200 mg bid + saquinavir 600 mg bid (Rito-Saq), and nelfinavir 1,000 mg bid + saquinavir 600 mg bid (Nelf-Saq). Nucleoside analogues were recycled, and nonnucleoside inhibitors were not permitted. Trough levels of the three drugs were measured by high-performance liquid chromatography at the month 3 visit. After the study had been completed, genotyping analysis was done on the first serum at entry. RESULTS: The study was interrupted due to the availability of new anti-HIV drugs. A random sample of 31 (16 Rito-Saq and 15 Nelf-Saq) patients was divided into two groups, which were comparable in terms of demographic data and previous history of HIV infection. Mean CD4 cell count and plasma viral load (pVL) were 316 +/- 169 and 3.89 +/- 0.87 for Rito-Saq and 448 +/- 238 and 3.85 +/- 0.32 for Nelf-Saq. Previous duration of PI exposure was 31 months for both groups. The mean number of protease gene mutations was 3.8 (range, 2-7) and 4.4 (range, 2-9), respectively. On intention-to-treat (ITT) analysis at month 6, pVL stabilization or decrease >/= 0.5 log was observed in 18 patients (58%): 10 for Rito-Saq and 8 for Nelf-Saq. In a multivariate logistic regression analysis, virological success at month 3 was inversely correlated to baseline viral load (R = 0.14; 95% CI 0.03-2.9; p =.01); and at month 6, virological success was inversely associated to the number of mutations in the protease gene (R = 2.2; 95% CI 0.73-6.53; p =.06). CONCLUSION: Nelf-Saq and Rito-Saq combinations can be proposed in case of multiple HAART failures. The fact that the virological response was inversely correlated to baseline viral load makes the case for an early switch after a HAART failure.

Adult↗
PubMedDate not supplied

Evaluation of the Patient Medication Adherence Questionnaire as a tool for self-reported adherence assessment in HIV-infected patients on antiretroviral regimens.

PURPOSE: Adherence to antiretroviral medications is critically important for the success of therapy in patients treated for HIV infection. Patient self-report is a simple method to measure and explore adherence. Even though a variety of surveys have been developed to monitor self-reported adherence, there is no standardized instrument that may be used in routine clinical practice. The usefulness of the Patient Medication Adherence Questionnaire (PMAQ) was evaluated in HIV-infected patients on protease inhibitor (PI)-containing regimens. METHOD: Data from 149 patients were collected. Study participants completed the PMAQ and provided blood samples to measure plasma HIV-1 RNA concentrations and trough plasma levels of PI. Patients were considered adherent if they had a virologic response and/or had an adequate trough plasma level of PI. RESULTS: A close relationship was found between patient reports of adherence during the previous 4 days and objective measures such as HIV RNA level and plasma levels of PI. Motivation with regard to antiretroviral treatment, confidence in personal skills, and an optimistic attitude to life were identified as important determinants of adherence. On the other hand, sociodemographic background, social support, alcohol and illicit drug use, bothersome symptoms, and depression were not associated with a lower medication adherence. CONCLUSION: Patients' psychological and behavioral factors are central in the acceptance and adherence to antiretroviral therapy. To improve the feasibility and the reproducibility of the PMAQ, we propose a revised form of the PMAQ, focusing on the variables identified as strong predictors of adherence.

Adult↗