Ethics committees for biomedical research in some African emerging countries: which establishment for which independence? A comparison with the USA and Canada.

Context: The conduct of medical research led by Northern countries in developing countries raises ethical questions. The assessment of research protocols has to be twofold, with a first reading in the country of origin and a second one in the country where the research takes place. This reading should benefit from an independent local ethical review of protocols.

Automated measurement of carbohydrate-deficient transferrin using the Bio-Rad %CDT by the HPLC test on a Variant HPLC system: evaluation and comparison with other routine procedures.

Aims: In this study, we evaluated the new %CDT by the HPLC method (Bio-Rad, Germany) on a Varianttrade mark HPLC system (Bio-Rad), checked the correlation with well-known methods and calculated the diagnostic value of the test.

Methods: Intra-run and day-to-day precision values were calculated for samples with extreme serum transferrin concentrations, high trisialotransferrin and interfering conditions (haemolysed, lactescent and icteric samples). The method was compared with two routine procedures, the %CDT TIA (Bio-Rad, Hercules, CA, USA) and the Capillarystrade mark CDT (Sebia, France).

Analytical evaluation of a new capillary electrophoresis method for carbohydrate-deficient transferrin measurement.

Background: Carbohydrate-deficient transferrin (CDT), the sum of a- and disialotransferrin, is considered the most efficient routine biological marker of alcohol abuse. In recent years, methods based on capillary zone electrophoresis (CZE) have been developed using specialized monocapillary systems. These are characterized by a high analytical detection level, counterbalanced by a poor productivity.

Rapid determination of valaciclovir and acyclovir in human biological fluids by high-performance liquid chromatography using isocratic elution.

A rapid high-performance liquid chromatographic assay with isocratic elution is developed for the simultaneous quantification of valaciclovir (VACV) prodrug and its active converted compound, acyclovir (ACV), in biological fluids of treated patients. For serum, the samples are deproteinized with perchloric acid in presence of 1-methylguanosine as the internal standard (IS). For urine and dialysis liquid, the samples are diluted with a mobile phase containing the IS, then filtered.

Impact of long-term ethanol consumption on CYP1A2 activity.

Ethanol is a well-known inducer of CYP2E1; whether or not it is an inducer of other cytochromes has not been investigated systematically. The aim of our study was to evaluate the impact of ethanol consumption on the activity of CYP1A2, which has been shown to be influenced by drugs (inhibited or induced). We evaluated CYP1A2 activity by the ratio of the molar urinary concentrations of the three end products of paraxanthine demethylation of caffeine to the molar concentration of a paraxanthine 8-hydroxylation product.

Omeprazole and lansoprazole are not inducers of cytochrome P4501A2 under conventional therapeutic conditions.

Objectives: Claims that substituted benzimidazole molecules induce cytochromes P4501A2 are still controversial. This study was undertaken to evaluate their inducing potency under conventional therapeutic conditions.

Methods: Twelve healthy non-smoking young volunteers were given 20 mg omeprazole or 30 mg lansoprazole daily, in random order, for 2 weeks, separated by a 3 week wash-out period.

Cytochrome P450 2E1 genotype and chlorzoxazone metabolism in healthy and alcoholic Caucasian subjects.

Susceptibility to cancer or ethanol-related liver diseases may be associated with a large variability in cytochrome P450 2E1 activity. This variability may be of genetic origin or reflect environmental factors. To test the role of genetics, the phenotype and genotype of this enzyme were determined in 42 non-alcoholic and 74 alcoholic patients hospitalized for detoxification treatment.

Alcohol consumption and visual contrast sensitivity.

Visual contrast sensitivity (VCS) was measured in 30 alcoholic patients and 52 controls. The results showed a significant reduction in VCS for all the spatial frequencies. The mean reduction for all spatial frequencies was 2.

Decrease in cytochrome P4502E1 as assessed by the rate of chlorzoxazone hydroxylation in alcoholics during the withdrawal phase.

To evaluate cytochrome P4502E1 (CYP2E1) induction in alcoholics, the ratio of the concentrations of 6-hydroxychlorzoxazone (6-OH-CHZ) and chlorzoxazone (CHZ) was measured in blood 2 hr after CHZ ingestion using a HPLC method. This ratio was determined in controls and in alcoholic patients after 1, 2, 3, 4, 5, 8, and 21 days withdrawal. It was found to be 0.

Assessment of cytochrome P4502E1 induction in alcoholic patients by chlorzoxazone pharmacokinetics.

Chlorzoxazone is mainly metabolized to 6-hydroxychloroxazone (6-OHchlorzoxazone) by the ethanol-inducible cytochrome P450 2E1 (CYP2E1). To evaluate the impact of ethanol consumption on the enzyme induction, the pharmacokinetics of chlorozoxazone and 6-OHchlorzoxazone were studied in alcoholic and control subjects. Fifteen alcoholic male inpatients (all smokers, daily intake 333 +/- 191 g of absolute ethanol) and 20 healthy male volunteers (10 smokers and 10 non-smokers, weekly intake < 100 g of absolute ethanol) participated in this study.

Pharmacokinetics and absolute bioavailability of colchicine after i.v. and oral administration in healthy human volunteers and elderly subjects.

The pharmacokinetics of colchicine were studied in six healthy male and four elderly female volunteers after i.v. and oral administration.

High-performance liquid chromatographic determination of chlorzoxazone and 6-hydroxychlorzoxazone in serum: a tool for indirect evaluation of cytochrome P4502E1 activity in humans.

Chronic alcohol consumption is known to induce the enzyme cytochrome P4502E1 (CYP2E1), which is involved in the toxicity and carcinogenicity of a number of solvents and xenobiotics. It was recently suggested that in vivo chlorzoxazone metabolism could be a potential tool as a non-invasive probe for measuring CYP2E1 activity in humans. Therefore, a simple and sensitive method was developed for the determination of chlorzoxazone and its major metabolite 6-hydroxychlorzoxazone in both serum and urine.

Increased metabolism of acetaminophen in chronically alcoholic patients.

The aim of this work was to determine whether the metabolism of acetaminophen increases in chronic alcoholics, and consequently whether the production of its hepatotoxic metabolite is enhanced. For this purpose, the pharmacokinetics of acetaminophen were compared in 12 alcoholic men and 12 healthy controls. After a 12-hr fast, the patients (on the 3rd hospital day) and volunteers were given 1 g of oral acetaminophen at 8.

Comparison of performance of healthy volunteers given prazepam alone or combined with ethanol. Relation to drug plasma concentrations.

The interaction between a single dose of 20 mg of prazepam and 0.5 g/kg body weight ethanol was investigated in 12 healthy male volunteers by nine objective performance tests, eight visual analogue self-rating scales and measurement of prazepam and ethanol plasma concentrations, using a double-blind three-way crossover design. The volunteers were each given three treatments (prazepam+ethanol, placebo+ethanol and prazepam alone), separated by a 2-week interval.

Comparative effects on psychomotor performance of the muscle relaxant afloqualone, alone and with ethanol.

The purpose of this study was to investigate the interaction between 40 mg afloqualone, a new centrally acting muscle relaxant and 0.5 g/kg ethanol using a double-blind three-way cross-over trial in which subjects were each given afloqualone with ethanol, ethanol alone and afloqualone alone. We first compared the effects of 40 mg oral afloqualone and 15 mg diazepam (considered as a reference drug) on the psychomotor and cognitive performance and muscular relaxation of 12 healthy male volunteers.

Enhancement of propoxyphene bioavailability by ethanol. Relation to psychomotor and cognitive function in healthy volunteers.

The interaction between a single oral dose of 130 mg propoxyphene and 0.5 g/kg body weight ethanol was investigated in 12 healthy male volunteers by 9 objective performance tests, 8 visual analogue self-rating scales and the measurement of plasma propoxyphene, norpropoxyphene and ethanol concentrations, using a double-blind threeway crossover design. Volunteers were each given one of three treatments, propoxyphene + ethanol, placebo + ethanol and propoxyphene alone, separated by a two week interval.

Effect of abstinence from alcohol on the depression of glutathione peroxidase activity and selenium and vitamin E levels in chronic alcoholic patients.

Glutathione peroxidase activity and selenium and vitamin E levels were measured in the plasma and erythrocytes of 25 chronic alcoholic patients without liver cirrhosis before and after 14 days of abstinence from alcohol, and compared with the levels in 25 sex- and age-matched healthy controls. Before abstinence, all three levels were shown significantly depressed in the alcoholic patients compared with the controls, in both plasma (80, 71, and 89% of control values) and erythrocytes (68, 70, and 83% of control values). After a 14-day abstinence period with no dietary supplementation, a trend towards normalization was noted in erythrocyte (vitamin E and glutathione peroxidase 74 and 91% of control values respectively), in whole blood selenium (82%) and plasma in vitamin E (74%).

Comparison of the effect of two prazepam formulations on psychomotor and cognitive function in healthy volunteers.

A double-blind crossover design was used to evaluate the effect of two different formulations of prazepam, on motor and cognitive functions and subjective symptoms. Ten healthy male volunteers received 20 mg of prazepam both in tablet and liquid (as drops) formulation, separated by a 1 week interval. All subjects completed a battery of 9 performance tests 2.

Clobazam increases pulsatile luteinizing hormone secretion in normal men.

To investigate the effects of the 1,5-benzodiazepine, clobazam, on LH secretion in normal men, LH pulsatile secretion was defined after oral administration of 40 mg of clobazam or a placebo to 6 healthy male volunteers, according to a randomized cross-over design. LH pulse frequency increased significantly from a mean of 3.8 (range 3-5) pulses/8 h after placebo, to a mean of 5 (range 4-7) pulses/8 h (P less than 0.

High blood lead level in alcoholics: wine vs. beer.

One hundred and sixty one alcoholics (121 men and 40 women) were studied during a social rehabilitation program. All had a daily intake of ethanol higher than 1 g/kg/day. The mean lead blood level was 28 micrograms/100 ml and was as high as 72.

Model-independent pharmacokinetics of colchicine after oral administration to healthy volunteers.

The pharmacokinetics of colchicine were studied after oral administration of three doses (0.5, 1.0 and 1.

Zero-order absorption and linear disposition of oral colchicine in healthy volunteers.

The pharmacokinetics of colchicine has been studied in nine healthy male volunteers after oral doses of 0.5, 1, and 1.5 mg as tablets.

[Presence of benzodiazepines in the serum of patients after accidents. Relation to alcoholism].

In a study of 2.021 injured persons (accidents at home or at work, road accidents), qualitative assays of serum benzodiazepines by the EMIT method were positive in 9.6 per cent of the cases, including 3.

Detection of blood benzodiazepines in injured people. Relationship with alcoholism.

In 2021 accident victims (household, work and road accidents) the qualitative test for benzodiazepines in the serum by the EMIT method was positive in 9.6% of cases, including 3.2% of subjects who also had a blood alcohol level greater than 0.