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Biomedical subjects

P Gayral

Publications and source records attributed to P Gayral.

At least 73 records · Page 4Linked to original sources

[Antiparasitic activity of Cis-Pt (II) pentamidine in experimental trypanosomiasis of sheep caused by Trypanosoma brucei brucei].

The failure of trypanocidal therapeutics have made it a duty to use other classes of molecules which show a comparable trypanocidal efficacy with well-known medicines. In this study, the authors have evaluated the trypanocidal activity of a Cis-Platinum (II) salt, DNA-intercalating medicine used in antineoplastic therapeutics, associated with pentamidine: Cis-Pt (II) pentamidine. After primary screenings on a murine model of T. brucei brucei, Cis-Pt (II) pentamidine was evaluated on an experimental sheep trypanosomiasis model, standardized by the Institute of Neurological Epidemiology and Tropical Neurology of Limoges (France). Cis-Pt (II) pentamidine was able to cure infected mice, without relapse, after a single subcutaneous injection of 12.5 mg.kg-1 body weight. In sheep trypanosomiasis, the same treatment was used successfully during the first stage of infection. Neurological stage susceptibility and pharmacokinetics in sheep will be evaluated in a further study.

Amidines↗

[Dihydro-5,6-imidazo[2,1-b]thiazoles, dihydro-2,3-imidazo[2,1-b]benzothiazoles, analogs of levamisole].

New compounds containing 5,6-dihydro imidazo[2,1-b]thiazole, 2,3,5,6-tetrahydro imidazo[2,1-b]thiazole and 2,3-dihydro imidazo[2,1-b]benzothiazole rings, substituted by heterocycles analogue to chromones, were synthesized and screened against three nematodes, in vitro. The results indicate moderate anthelmintic properties, compared to levamisole; nevertheless, some products exhibit a significant degree of activity.

Animals↗

[A new model for the study of filarial physiopathology: Molinema dessetae in its definitive natural host, Proechimys oris. 1].

The filarial rodent model Molinema dessetae/Proechimys oris, recently adapted in the laboratory allows studies on the host/parasite relationships. Development of filarial worm was described elsewhere, and the model standardized. Biological, parasitological data and antifilarial drug response were determined. Natural models can seldom be used in laboratory; in non natural models many informations on the host-parasite relationships are lost and pathological studies can only be fragmentary and punctual. With inbred Proechimys oris we have the possibility to investigate with a natural filarial model. Three rodent groups have been studied for over a period of one year. The first group comprises eleven parasite free animals; the second one, eight rodents infected once by L3, and the last with eight rodents regularly re-infected during the period of experiment. Several biological parameters were considered: weight, total red and white blood cell counts, haemoglobinemia, mean cell volume, differential leucocyte count, blood urea nitrogen, total serum proteins and electrophoretic pattern, endogenous creatinine clearance, circulating immune complexes. On the whole, more than 19,700 biological data were obtained and several multivariate statistical analysis were necessary for a valid interpretation. The Principal Component Analysis (ACP) shows in each infected rodent distinct trajectories related either with the age of the host or with the filarial infection itself. Three graphic methods were used: individual graphics of each rodent, graphics of each rodent group and, individual and group statistical center of gravity. At the end of the experiments, the rodents were autopsied and a detailed histological study of the whole body was made. Different lesions and stages of inflammatory processes found were analysed and classified as follows: granulomatous nodule with eosinophilic and neutrophilic polymorphs; foreign-body granulomatous nodule; sclerocicatricial nodule; mononucleate cell infiltrate. Secondary pathological alterations, such as irritative lesions and blocage of lymph and blood vessels, were found. A comprehensive study of all our qualitative histological results was performed by a second multivariate analysis: the Correspondence Analysis (AFC). This analysis confirmed the heterogeneity of each Proechimys infected and multi-infected groups. The cross checking between the ACP and AFC allows the separation of two physiopathological filarial groups; the first group (A) is characterized by moderate biological variations and the absence of hepatosplenic lesions.(ABSTRACT TRUNCATED AT 400 WORDS)

Aedes↗

Putative neurotransmitters in three experimental filariasis models.

Some putative neurotransmitters in three experimental filariasis models were investigated by a new relevant chromatographic method, sensitive and specific. No catecholaminergic compounds have been detected, but serotonin was found in Dipetalonema vitae. However, further investigations revealed very high levels of gamma amino butyric acid (GABA) in the macro-filariae. These data allow us to foresee new fields in filariasis therapeutics.

5-Hydroxytryptophan↗

Molluscicides in schistosomiasis control.

Although mollusciciding can be a cost-effective method of controlling schistosomiasis transmission, only one organic molluscicide, niclosamide, is now being produced commercially, and only a few compounds are at present being tested in the laboratory. In future, improved cost-effective use of molluscicides will require more precise knowledge of schistosomiasis transmission patterns in each endemic area and improved application techniques. In snail control studies using controlled-release formulations only the organotins, especially tributyltin oxide (TBTO), have given satisfactory long-term results. However, large-scale field trials of organotin formulations have not been implemented and their use cannot be recommended as their chronic toxicity in mammals has not yet been determined. The development of molluscicides of indigenous plant origin deserves support. Endod, derived from the berries of the climbing plant Phytolacca dodecandra, is the most extensively tested plant molluscicide, but data on its chronic toxicity to non-target organisms are lacking. The mode of action of molluscicides has not been extensively studied, though knowledge of the properties required of molluscicidal molecules has contributed to the discovery and development of niclosamide and nicotinanilide. In general, molluscicides probably cause stress on the water balance system, which in gastropods in thought to be under neurosecretory control.

Drug Resistance↗

[Gas chromatographic determination of diethylcarbamazine (Hetrazan) in serum of laboratory rodents (author's transl)].

After chloroform extraction in an alkaline solution, diethylcarbamazine (DEC) is measured in the presence of dipropylacetamid (internal standard), treated in the same manner, by a gas chromatographic procedure using a nitrogen detector in a 10% BDS column. Results can be easily reproduced for analysis of DEC in sera up to levels of 10 mg/1 and sensibility allows determination of approximately 0.5 mg/l levels on 50-microliter samples of serum. This method is suitable for pharmacokinetic studies.

Animals↗

[Preliminary results of the use of a new rodent filaria, Dipetalonema dessetae (Bain, 1973), in the evaluation of filaricides].

The sensitivity of this filarial worm living in his natural host has been identified with respect to 2 well known filaricidal compounds. With diethylcarbamazine the microfilaremia drops rapidly but not completely and a long term treatment destroys the adults. Suramin is toxic to the adults and to the microfilariae. This experimental model is therefore more sensitive than anything presently available.

Animals↗

Experimental filariasis of Dipetalonema dessetae in Proechimys oris: 3. Effects of parasitism on the pharmacokinetics of diethylcarbamazine.

The pharmacokinetic parameters of diethylcarbamazine were compared in the plasma and peritoneal fluid of 5 non-infected rodents. In the filarial animals, the absorption rate constant and the elimination rate constant were significantly increased. The peak plasma concentration was twofold higher in the infested rodents than the control animals, and this may account for the rapid action of diethylcarbamazine on blood-circulating microfilariae. The area under the curve was unchanged. Total clearance is slightly increased in filarial rodents. These data are explained by an important reduction of renal clearance combined with a moderate increase of extra renal clearance. High levels of diethylcarbamazine in peritoneal fluid, resulting from the excellent diffusion of the drug in filarial animals explains the activity on adult worms. But the parasitism does not affect the mechanism of distribution of the drug between plasma and peritoneal liquid.

Animals↗

[Experimental filariasis in Proechimys oris by Dipetalonema dessetae: 4. Effect of parasitism on protein and tissue binding of diethylcarbamazine].

Several groups of control and filaria-infected Rodents were treated by radio-labelled diethylcarbamazine in order to study the effect of parasitism on the protein binding and tissue distribution of the drug. These studies were performed using equilibrium dialysis, chromatography and autoradiography. The plasmatic protein concentrations were lower in the group of infected Rodents, due to a decrease of albumin. The binding rate depended on the electrophoretic fractions, but remained low and unaffected by parasitism. The radioactivity of DEC and its metabolites appeared very quickly in the tissues, particularly in infected Rodents. This was due to the fact that the already rapid intestinal absorption and diffusion were enhanced by filariasis.

Animals↗

[Experimental filariasis in Proechimys oris by Dipetalonema dessetae. 5. Effect of parasitism on metabolism of diethylcarbamazine].

The metabolism of diethylcarbamazine (DEC) in healthy and filaria-infected Proechimys oris Rodents was investigated. DEC and 14C labelled DEC were orally administrated (100 mg/kg). The drug was quickly and intensively metabolised. About 90% of the dose administered was eliminated in the urine within 24 hours. Monodeethylation was the major pathway. The major urinary metabolites were ethylcarbamazine and its N-oxide. Traces of N methylpiperazine 2,5 dione and their N-oxide were also found. Elimination was faster in filarial than in healthy animals, but metabolites were the same.

Animals↗