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Biomedical subjects

C Bories

Publications and source records attributed to C Bories.

At least 55 records · Page 3Linked to original sources
PubMed1995

Development of an injectable formulation of albendazole and in vivo evaluation of its efficacy against Echinococcus multilocularis metacestode.

The loading of poly (D, L-lactide) nanoparticles with ABZ has led us to evaluate the potential of this new colloidal drug delivery system against E. multilocularis, using a murine model of hepatic alveolar echinococcosis. ABZ-loaded nanoparticles had a monodisperse size distribution between 100 and 150 nm. The efficiency of drug loading to nanoparticles was over 97%. In vitro, at an ABZ concentration of 1.0 microgram ml-1, the formulation had no toxicity for peritoneal macrophages harvested from uninfected mice. In vivo, the ABZ-loaded nanoparticles exhibited no signs of toxicity at any of the doses tested. Intravenous injections of 6 mg kg-1 of bound ABZ to infected mice had an equivalent antiparasitic effect on the metacestode growth to that of a treatment with 1500 mg kg-1 of orally administered free ABZ. The parasite hepatic superficial size as well as the peritoneal metastatic burden was significantly reduced by these 2 courses of treatment, as compared to those of untreated mice. Our results should encourage further study in order to explain the absence of dose-dependent efficacy of ABZ-loaded nanoparticles demonstrated in the present study.

Albendazole↗
PubMed1995

[Importance of drug carriers in the treatment of visceral leishmaniasis].

Visceral leishmaniasis is caused by hemoflagellate protozoa which are obligatory parasites of the mononuclear phagocyte system. Leishmaniasis causes high morbidity and mortality worldwide. The treatment of choice remains pentavalent antimonials, but high toxicity and failures have been reported. An alternative to conventional treatment is delivery anti-leishmania agents using colloidal carrier systems. Carriers improve drug activity against intracellular disease involving the mononuclear phagocyte system. The principle of drug delivery by carrier systems has been applied successfully for anticancer drugs. Recently complete remission of polyresistant visceral leishmaniasis was obtained by injection of liposomal amphotericin B. At present, no colloidal drug carrier for antimony derivatives is available, but pentamidine can be linked experimentally to methacrylate polymer nano-particles. Drug-loaded nanoparticles have been shown to be effective against amastigote leishmania both in vitro and in vivo. Another colloidal system of major interest for drug delivery, the liposome has already been loaded with amphotericin B and used for human therapy. The concept of particulate drug carriers opens the way for new chemotherapeutic approaches in the field of parasitology.

Amphotericin B↗
PubMed1995

Nitrate determination in biological fluids by an enzymatic one-step assay with nitrate reductase.

We report a simple, enzymatic, end point method for determining nitrate in serum and urine with use of nitrate reductase from Aspergillus sp. (EC 1.6.6.2). The decrease in absorbance at 340 nm as a result of the oxidation of beta-NADPH is measured. We used FAD as a supplementary electron carrier and added an internal standard to avoid interference from possible inhibitors of the enzymatic reaction. The method was linear from 5 to 200 mumol/L nitrate in serum. Within-run (n = 12) and total (n = 14 days) imprecisions (CV) were 5.1-7.7% and 6.2-9.8%, respectively, at 20-90 mumol/L nitrate in serum. Recoveries of added nitrate were 80-106%. The median (range) concentration in serum of 20 healthy subjects was 16 (0-42) mumol/L.

Adult↗
PubMed1995

In vitro and in vivo antifilarial activity of ethynesulfonamides, epoxyethanesulfonamides and carboxamide analogues.

A series of 2-substituted trans-1,2-epoxyethanesulfonamides (1T), ethynesulfonamides (2), and their carboxamide analogues 3 (cis and trans) and 4 were evaluated for their antifilarial activity, first in vitro against the infective larvae of the filaria Molinema dessetae, then in vivo against the same filaria in Proechimys oris, its natural host. On the whole, compounds 2 displayed a high level of activity in vitro, while 4 showed a wider range and 3 were virtually inactive. The modest activity found within the series 1T was assumed to be due, in part, to the instability of the products under the conditions of the biological tests. Five new compounds within the series 1T, 2 and 4 showed a macrofilaricidal activity in vivo. There is no clear correlation between in vivo and in vitro data. It was observed, however, that within the series 2 and 4 all the compounds active in vivo were among the most potent compounds in vitro. Nevertheless, the in vitro model, although of limited value, could help in selecting compounds for further evaluation within a given series.

Aedes↗
PubMed1994

Action of pentamidine-bound nanoparticles against Leishmania on an in vivo model.

The efficiency of antileishmanial agents may be enhanced by improving their bioavailability with a colloidal drug carrier. We have investigated the action of free pentamidine, compared with pentamidine bound to polymethacrylate nanoparticles, in a rodent model. BALB/c mice were infected, via the tail vein, with 4 x 10(7) L. major (MON 74) promastigotes. Twelve days after infection, seven groups of mice were treated respectively with methylglucamine antimoniate (Glucantime) 5.56 mg/kg i.p. x 5 d., pentamidine bound nanoparticles (100 microM), unloaded polymethacrylate nanoparticles, unloaded nanoparticles associated with free pentamidine (100 microM) 0.1 ml i.v. x 3 d and free pentamidine isethionate (2.28 mg/kg and 0.17 mg/kg i.v. x 3 d.). Twenty-one days post infection, the mice were sacrificed and the Leishmania load in the liver calculated from the number of amastigotes/500 liver cells and total liver weight in treated and untreated mice. Results demonstrated a 77% amastigote reduction in the group treated with targeted pentamidine relative to the control group. The ratio free pentamidine/bound-pentamidine was approx. 12.

Animals↗
PubMed1994

Cytotoxic and antiparasitic activity from Annona senegalensis seeds.

Several extracts of Annona senegalensis (Annonaceae) seeds were tested for antiparasitic activity against Leishmania major, Leishmania donovani, Trypanosoma brucei brucei, and for cytotoxic activity against KB and VERO cell lines. Fractionation of seeds extracts was mainly guided by means of a biocidal assay against Artemia salina nauplii. The biological activities resulted from extract-isolated acetogenins.

Animals↗
PubMed1994

The activity and ultrastructural localization of primaquine-loaded poly (d,l-lactide) nanoparticles in Leishmania donovani infected mice.

The activity of primaquine (PQ) was compared to that of PQ-loaded Poly (D,L-Lactide) (PLA) nanoparticles against Leishmania donovani. The association of PQ with PLA nanoparticles increased the antileishmanial in vitro and in vivo effects of intravenously administered drug while its toxicity was reduced. The effectiveness of PQ-loaded PLA nanoparticles was 3.3 times as high as that of free drug in the suppression of amastigotes in the liver of BALB/c mice. A total dose of 30 mg PQ bound/kg (600 mg PLA/kg) was well tolerated and no sign of acute toxicity was observed. A similar dose of free drug resulted in 15% weight loss. No significant leishmanicidal activity was observed for unloaded PLA nanoparticles. Ultrastructural studies showed the uptake of drug-loaded nanoparticles by Leishmania-infected Kupffer cells. Nanoparticles were identified closed to amastigotes.

Animals↗
PubMed1994

Synthesis and nematocidal activity of arylmercaptovinyltetrahydropyrimidines.

A set of mercaptovinyl tetrahydropyrimidines was synthesized in good yields by lithiation of 1,2-dimethyltetrahydropyrimidine with n-butyl lithium in tetrahydrofurane, followed by condensation with aromatic thioesters. Against three nematode genera, anthelminthic screening shows little activity; 2b and 2d were the most potent against Molinema dessetae.

Animals↗
PubMed1993

Experience with doxorubicin-bound polyisohexylcyanoacrylate nanoparticles on murine alveolar echinococcosis of the liver.

The parasiticidal properties of doxorubicin against the metacestode of Echinococcus multilocularis were investigated after binding of that drug to polyisohexylcyanoacrylate nanoparticles, a colloidal biodegradable drug carrier. A reduction of the hepatic parasite development and a reduced viability of the metacestode were observed in mice injected with 5 mg kg-1 body weight-1, but 7.5 mg kg-1 body weight-1 did not appear more efficient. Free doxorubicin or unbound nanoparticles had no antiparasitic activity.

Animals↗
PubMed1993

[In vitro study of leishmanicidal agents with drug carriers].

Antileishmanial chemotherapy is hampered by the location of parasites within lysosomal vacuoles of the macrophages which restricts the bioavailability of many potential antileishmanial compounds. In this study, the effectiveness of pentamidine targeted to the infected cells by a linkage to a colloidal drug carrier, methacrylate polymer nanoparticles was explored. In the same way, polyisoalkylcyanoacrylate nanospheres which have, in vitro, trypanolytic properties were also tested. The study was performed in an in vitro model using Leishmania major amastigote stages within the U 937 human monohistiocytic cell line. The antileishmanial activities of unloaded or pentamidine-loaded nanoparticles were compared to those of the free drugs. The 50% effective concentration of targeted pentamidine was 0.10 microgram/ml, while it was up to 2.7 micrograms/ml with the free drug after a 24-hour incubation time. The pentamidine-bound nanoparticles proved to be 25 times more active than the free drug. Unloaded polyisoalkylcyanoacrylate nanoparticles destroyed intracellular amastigote stages (50% EC = 15 micrograms/ml) but at a level close to the cytotoxic concentration.

Cell Line↗
PubMed1992

Elution mode of Pneumocystis carinii cysts in gravitational field-flow fractionation.

The simplest field-flow fractionation technique, i.e. gravitational, was used in an attempt to purify a Pneumocystis carinii cyst suspension. This parasite is an opportunistic invader in immunocompromised patients, especially those suffering from AIDS. The cyst stage is spherical and 5 microns in diameter. Unexpected retention times, not systematically related to the size and the density of the parasite, were obtained under various experimental conditions. When silicone-coated walls were used, Pneumocystis carinii cysts were eluted in the void volume, whereas when uncoated walls were used with a sodium dodecyl sulphate-enriched carrier phase, retention was observed. These phenomena are probably related to the high degree of hydrophobicity of these micrometre-sized biological particles; this degree can be easily determined. The use of the gravitational field-flow fractionation technique can be of a great interest for the development of new methods for diagnostic purposes. Particle-wall interactions and their modifications due to the carrier phase or to the wall treatment can be employed in the search for new bronchoalveolar lavage solutions.

Animals↗
PubMed1991

Isolation of microfilariae from blood by gravitational field-flow fractionation.

Over 100 million persons suffer from diseases caused by filariae infestation, and one billion are at risk. A simple isolation method for both analytical and preparative separation is presented. Based on the simplest field-flow fractionation technique, the gravitational one, effective isolation of microfilariae is achieved. Microfilariae are eluted in the void volume of the channel without pollution by red blood cells. The red blood cell elution peak shows a total absence of microfilariae, as demonstrated after fraction collection and microscopic investigation. The elution mode of microfilariae and red blood cells appears to be a steric one, as confirmed by a reinjection experiment. The simplicity, low cost and the relatively short time required for this separation (10 min) indicate that gravitational field-flow fractionation could become a new separation tool for screening of microfilariae. With both live and dead microfilariae, the high recovery (66-80%) allows preparative fractionation for diagnostic purposes or fundamental research.

Animals↗
PubMed1991

Sulindac causes regression of rectal polyps in familial adenomatous polyposis.

In familial adenomatous polyposis, sulindac-induced polyp regression has been reported by several authors. In this study, the goal was to confirm these results by a randomized, placebo-controlled, double-blind crossover study in 10 patients with rectal polyps that had been previously treated by colectomy and ileorectal anastomosis. Patients received sulindac, 300 mg/day, or placebo during two 4-month periods separated by a 1-month wash-out phase. One patient was not compliant and was excluded. With sulindac, the authors observed a complete (6 patients) or almost complete (3 patients) regression of the polyps. With placebo, the authors observed an increase (5 patients), no change (2 patients), and a relative decrease (2 patients) in the number of polyps. The difference between sulindac and placebo was statistically significant (P less than 0.01). In biopsy specimens of polyps and normal rectal mucosa of 6 patients, the authors conducted an immunohistochemical study of the cellular proliferation index using the Ki 67 monoclonal antibody (Ki 67 index), at the beginning and at the end of each treatment period. They were not able to show a sulindac-induced modification of the Ki 67 index. The authors conclude that sulindac is effective in inducing the regression of rectal polyps in familial adenomatous polyposis.

Adenomatous Polyposis Coli↗
PubMed1991

Antiparasitic activity of Annona muricata and Annona cherimolia seeds.

Methanolic extracts of Annona muricata and A. cherimolia (Annonaceae) seeds were tested for antiparasitic activity against E. histolytica, N. brasiliensis, M. dessetae and A. salina. The acetogenins isolated from these extracts are found to be responsible for the important activity on infective larvae of Molinema desetae.

Animals↗
PubMed1990

Synthesis and anthelminthic evaluation of 2-amidino-1,3,4-oxa and 1,3,4-thiadiazoles, structurally related to tetramisole.

N-(1,3,4-thiadiazol-2-yl) 1a-1k and N-(1,3,4-oxadiazol-2-yl-) amidines 2a-2g, N-(1,3-thiazol-2-yl) 3a, 3b and N-(1,3-benzothiazol-2-yl-)amidines 4a, 4b were synthesized and tested as anthelminthics, in vitro, against a free nematode (Rhabditis pseudoelongata), against infecting larvae of an intestinal parasite of rats (Nippostrongylus brasiliensis) and against infecting larvae of a filaria (Molinema dessetae).

Amidines↗
PubMed1989

Macrofilaricidal activity of metabolites of diethylcarbamazine.

The antifilarial compound diethylcarbamazine (N,N-diethyl-4-methyl-2-piperazine, DEC) is known rather for its micro- than macrofilaricidal activity. But in some human filariasis i.e. loaiasis, lymphatic filariasis, the spectrum of DEC activities extends to adult filaria. The potential role of the metabolites of DEC in the action of the parent drug once it had been metabolized in the body of infected animals was investigated. The metabolites were evaluated in a new experimental model on which DEC is active: Molinema dessetae in its natural host, the rodent Proechimys oris. Experimental studies were carried out in vivo and in vitro, on microfilariae, infective larvae and adult filaria. Several other nematodes were also used. The metabolites were DEC itself, N-ethyl-4-methyl-1-piperazine-carboxamide (MEC) and their N-oxides, 4-methyl-piperazine-carboxamide and N,N-diethyl-1-piperazine-carboxamide. In vivo most of the metabolites were found active on microfilariae and both N-oxides active on adults and infective larvae. In vitro, the activity of the metabolites was observed only with high concentrations; the in vitro test could not be used as a screening method for antifilarial chemotherapy with piperazine derivatives. Infective larvae were the most sensitive stage. In the rodent and in man, the antifilarial action of DEC is swift and of short duration. This action is prolonged by the activity of metabolites, especially the N-oxides.

Animals↗