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Biomedical subjects

J Fabre

Publications and source records attributed to J Fabre.

At least 307 records · Page 17Linked to original sources
PubMedDate not supplied

The genetic control of bufuralol metabolism in man.

Bufuralol (Ro 3 - 4787, Angium) is a non selective beta-adrenoceptor blocking drug with some degree of sympathomimetic action and a longer duration of action than propranolol. Plasma concentrations of bufuralol and 1'-hydroxybufuralol, its main blood derivative which shows similar beta-adrenoceptor blocking properties, were determined in healthy volunteers after a 60 mg oral and a 20 mg intravenous dose. Peak plasma concentrations were higher for the parent drug but due to a longer elimination half-life, the metabolite concentrations became higher after a few hours (bufuralol t 1/2 = 2.7 +/- 0.9 h, metabolite t 1/2 = 6.1 +/- 1.5h). The bioavailability of the tablet tested was 46 +/- 15%. The occurrence of side-effects in a subject with abnormal pharmacokinetics of the drug in this study and in a previous study with this drug suggested the possibility of a pharmacogenetic anomaly. Determination of the plasma metabolic ratio in the family of this subject and in a larger population confirmed that aliphatic hydroxylation of bufuralol is under polymorphic control. Phenotyping of our volunteers with debrisoquine showed the present pharmacogenetic anomaly to be the same as the one reported for debrisoquine alicyclic hydroxylation. The occurrence of side-effects in poor metabolizers as seen with bufuralol illustrates the clinical relevance of the hydroxylation polymorphism. In Switzerland the frequency of poor metabolizers is about 9% as previously reported for caucasian British subjects.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

[Portal hypertension and hypervitaminosis A. Apropos of 2 cases and review of the literature].

Portal hypertension consecutive to hypervitaminosis A has seldom been well documented. Two cases are reported here. The first case concerns a 39-year old woman who had taken meladinine (8-methoxypsoralen) for the purpose of tanning. In the second case, a 43-year old woman had absorbed Plethoryl (a combination of tiratricol, cyclovalone and retinol) in order to lose weight. Both patients had histological hepatic lesions, such as hypertrophic Ito cells, perisinusoidal cirrhosis and spontaneous autofluorescence, suggestive of vitamin A overload, associated with a hepatic vein pressure gradient of 10 mmHg or more and high liver concentrations of vitamin A. The responsibility of Plethoryl in case 2 is beyond any doubt, but the mechanism of hypervitaminosis in case 1 is controverted. A review of the literature has provided detailed information on the signs of vitamin A overload, the frequency of which is probably underestimated. Patients with portal hypertension of unknown origin should be investigated for hypervitaminosis A.

Adult↗
PubMedDate not supplied

Differences in kinetic properties of drugs: implications as to the selection of a particular drug for use in patients with renal failure with special emphasis on antibiotics and beta-adrenoceptor blocking agents.

Adjustment of dosage of a renally excreted drug (or active metabolite) for patients with severe renal failure still causes some difficulties. It is therefore helpful to select, within a given therapeutic group of drugs, a compound that is particularly safe and easy to use and, if possible, does not require adjustment of dosage. This is 'the drug of choice for renal patients'. Such a drug would ideally meet the following pharmacokinetic criteria: normal urinary excretion less than 30% of the administered dose, predominant biliary and intestinal removal, disposition essentially unaffected by parameters likely to be modified in renal failure (e.g. changes in serum proteins or fluid compartments: receptor sensitivity, etc), and pharmacokinetics not complicated by the formation of active or toxic metabolites that depend on urinary elimination. Above all, the drug should have a wide therapeutic margin and must be free of nephrotoxicity. Examples of drugs of choice for patients with impaired renal function are given for some important therapeutic groups and special emphasis is placed on antibiotics and beta-adrenoceptor blocking agents.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

[Isolation of Thogoto virus from Amblyomma and Boophilus ticks in Central Africa].

A survey has been carried out in the Cameroons and the Central African Republic about the role of the ticks in the ecology of arboviruses in Central Africa. Attempts for virus isolation were made for 12,678 Amblyomma variegatum, 3,276 Boophilus decoloratus and 1,769 Boophilus annulatus, by inoculation into suckling mice. From 968 pools which were inoculated, 20 yielded isolates which were identified to Thogoto virus. Considering previously published results concerning tick-borne virus isolations in the Central African Republic, it appears now that five arboviruses are present in the ticks in central Africa : Dugbe, Jos and Thogoto (in A. variegatum, B. decoloratus and B. annulatus), Bhanja (in A. variegatum) and Chf. Congo (in Hyalomma nitidum).

Africa, Central↗
PubMedDate not supplied

[Pharmacokinetic perturbations in kidney failure. Anomalies of metabolites and tissue diffusion (author's transl)].

Complex pharmacokinetic perturbations follow kidney failure. Delayed excretion affects not only the original substance but also metabolites, as illustrated by the behaviour of glipizide and glibenclamide. Moreover, abnormal absorption, distribution, and metabolism of these drugs also often occur and are particularily evident for some beta-blocking agents. Analysis of tissue pharmacokinetics shows that aminosides accumulate in the renal cortexand persist there for several months. This phenomenon is markedly enhanced in acute obstructive kidney failure and largely accounts for the nephrotoxicity of these drugs.

Absorption↗
PubMedDate not supplied

Effect of recombinant interferon gamma and interleukin-2 and of a monoclonal antibody against interferon gamma on the rat immune response against heart allografts.

We studied the effect of rat rec-IFN-gamma, human rec-IL-2, and an IgG1 monoclonal antibody (DB1) directed against rat IFN-gamma on allograft survival in the rat in various experimental conditions. The DB1 monoclonal antibody did not prolong heart allograft survival in the (LEW/BN)F1 to LEW combination, even when used at high doses (2 mg/rat x 9 days). Rec-IFN-gamma induced major histocompatibility antigen expression in vivo, but its administration had no effect on the graft survival either of untreated LEW recipients of (LEW x BN)F1 heart allografts or of donor blood-transfused LEW recipients. In addition, rec-IFN-gamma alone had no effect on graft survival in cyclosporine-treated rats. In contrast, rec-IL-2 shortened heart allograft survival both in untreated and in cyclosporine-treated recipients. Rec-IFN-gamma partially reversed the effects of rec-IL-2 in cyclosporine-treated rats. The data suggest that in vivo administration of IFN-gamma in allograft recipients may have a suppressor effect, in addition to the postulated augmenting effect on the immune response by increasing MHC antigen expression.

Animals↗