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Biomedical subjects

C Bories

Publications and source records attributed to C Bories.

At least 19 recordsLinked to original sources
PubMed2000

In vivo antileishmanial action of Ir-(COD)-pentamidine tetraphenylborate on Leishmania donovani and Leishmania major mouse models.

Ir-(COD)-pentamidine tetraphenylborate which has previously been studied on promastigote forms of Leishmania, was investigated for its antileishmanial properties compared with pentamidine used as reference compound. In vitro, the iridium complex had the same IC50 value on intracellular forms of Leishmania as pentamidine (15 microM). In vivo, the compound could not be injected intravenously due to the DMSO excipient so that the treatments were performed intraperitoneally or subcutaneously. On the L. donovani LV9/Balb/C mouse model, the iridium complex was not toxic after intraperitoneal treatment at 232 mg/kg/day x 5 or 147 mumoles/kg/day x 5, whereas all the mice died within five days when treated at the same dose with pentamidine isethionate. However, only 23% of parasite suppression was observed with the iridium complex. On a L. major MON 74/Balb/C mouse model, susceptible to intravenously administered pentamidine at 6.7 mumoles/kg/day x 5 (54% of parasite suppression), the iridium complex exhibited 32% of parasite suppression after a treatment at 76 mumoles/kg/day x 5 administered subcutaneously. This slight activity is of interest since pentamidine isethionate is not active under these conditions. Transmission electron microscopy of amastigotes from infected and treated mice show aggregation of ribosomal material, distension of the nuclear membrane and kDNA depolymerization. The mechanism of action therefore involves several targets: membranes, ribosomes and kDNA. According to our results, the Iridium complex is a suitable candidate to be encapsulated in drug carriers such as liposomes or nanoparticles.

Animals↗
PubMed2000

Squamocin and benzyl benzoate, acaricidal components of Uvaria pauci-ovulata bark extracts.

Annonaceae have been commonly described in traditional medicine as remedies against head lice and for their insecticidal properties. Acaricidal effects of Uvaria pauci-ovulata bark extracts were investigated on Dermatophagoides pteronyssinus, the European house dust mite, and compared with those of benzyl benzoate used as standard acaricidal compound. A dichloromethane extract was the most effective with an EC50 = 0.028 g/m2 after a 24 h period as compared with benzyl benzoate (EC50 = 0.06 g/m2). Bioassay-guided fractionation of this extract led to the isolation of benzyl benzoate and squamocin; this latter compound also had acaricidal properties (EC50 = 0.6 g/m2). Moreover, squamocin was shown to potentiate the activity of benzyl benzoate using the fractional effective concentration (FEC) method.

Animals↗
PubMed2000

In vitro reversion of amphotericin B resistance in Leishmania donovani by poloxamer 188.

A micellar formulation of amphotericin B (AmB) solubilized with poloxamer 188 was evaluated against an AmB Leishmania donovani-resistant line. A concave isobologram showed a synergistic effect of this association against promastigotes. This result was confirmed with amastigotes since the 50% effective concentration of the new formulation was 100 times less than that of the control AmB formulation.

Amphotericin B↗
PubMed1999

Antiprotozoal activity of aporphine alkaloids isolated from Unonopsis buchtienii (Annonaceae).

On a preliminary screening, substantial leishmanicidal activity was observed for the petroleum ether and alkaloidal extracts of the stem bark of Unonopsis buchtienii, the alkaloids and sterols isolated from these were studied. Of the alkaloids, liriodenine exhibited the highest activity against Leishmania major and L donovani (IC100 = 3.12 micrograms/mL). On the other hand, O-methylmoschatoline and the petroleum ether extract without alkaloids showed an interesting in vitro activity against Trypanosoma brucei with an IC100 of 6.25 micrograms/mL. The highest cytotoxic activities were found with the petroleum ether extracts without alkaloids and with all alkaloids isolated (IC50 < 9 micrograms/mL for Vero cell line).

Alkaloids↗
PubMed1999

A new photometric assay with bromocresol purple for testing in vitro antitrichomonal activity in aerobic environment.

A new colorimetric assay relying on the acidic metabolism of Trichomonas vaginalis was developed for in vitro screening of various compounds against axenically grown trichomonads. Parasites from continuous culture were exposed to series of drug dilutions in a microtiter plate. After an incubation period of 48 h at 37 degrees C, the pH indicator of the medium had changed its colour in non-inhibited cultures due to the production of lactate and acetate. Inhibited cultures showed no colour changes. The use of bromocresol purple, a pH indicator, was suitable for several reasons: it is not toxic at the concentration used in the assay; the absorbance of bromocresol purple at 405 nm showed a linear correlation with both the pH of the medium and the viability of the trichomonads observed microscopically; plates could easily be read by eye or using an enzyme-linked immunosorbant assay (ELISA) reader. By comparison of the decreases in absorbance in test cultures with those in control cultures, IC50 values could be determined. Thus, IC50 of metronidazole was calculated at 25.5 +/- 2.3 mumol/l (n = 5) with the bromocresol purple assay and about 25 mumol/l after microscope observation. Minimal lethal concentrations (MLCs) could be read by eye. This test is now routinely used for anti-trichomonas evaluation of various chemical compounds and natural products.

Aerobiosis↗
PubMed1998

Synthesis and biological evaluation of ureido and thioureido derivatives of 2-amino-2-deoxy-D-glucose and related aminoalcohols as N-acetyl-beta-D-hexosaminidase inhibitors.

Ureido and thioureido derivatives of 2-acetamido-2-deoxy-beta-D-glucose, 1-amino-1-deoxy-D-glucitol and 2-(2-aminoethoxy)ethanol were prepared as N-acetyl-beta-D-hexosaminidase (NAHase) inhibitors and were evaluated on Trichomonas vaginalis NAHase. Although none showed complete inhibition of the enzyme at 100 microM, 1-amino-1-deoxy-D-glucitol derivatives acted as competitive inhibitors of the NAHase of T. vaginalis.

Animals↗
PubMed1998

Chitinolytic activities in Trichomonas vaginalis.

Chitinolytic activities were identified in the Protozoa Trichomonas vaginalis. Overall chitinase activity assessed using chitine-azure as substrate was 10.93 +/- 1.21 nmoles/min/mg prot. End nonreducing chitobiosidase (exochitinase) and chitotriosidase (endochitinase) activities were shown using p-nitrophenyl-substrates and had specific activities of 4.55 +/- 0.53 and 0.47 +/- 0.06 nmol/min/mg prot, Kmapp. = 1.32 mM and 5 microM and pH optimum = 7.0 and 6.1 respectively. beta-N-acetylhexosaminidase (NAHase) activity was also detected with a specific activity of 5.40 +/- 0.65 nmol/min/mg prot., Kmapp = 0.656 mM and pH optimum at 7.0. No release of these enzymes into the culture medium was found. The possible role of chitinases in T. vaginalis remains to be investigated.

Animals↗
PubMed1998

Lack of a nitric-oxide response during the course of Leishmania infantum infection in the golden hamster (Mesocricetus auratus), with or without treatment with liposomal amphotericin B.

Liver and spleen volumes and serum concentrations of nitrate (the end-product of NO in vivo), albumin, gamma-globulin, protein, creatine and urea were measured during the course of progressive infections with Leishmania infantum MON-1 (MHOM/PR/93/CRE29) in 10 Syrian golden hamsters. Each hamster was infected by intraperitoneal injection with 4 x 10(7) promastigotes. Five of the infected animals were treated, with 6 mg liposomal amphotericin B (L-AmB)/kg given by intracardiac injection, on day 107 post-infection (p.i.). Compared with those in the uninfected hamsters used as controls, the liver volumes in the infected animals became significantly enlarged by day 40 p.i. (38% larger than the controls; P < 0.001) whereas significant enlargement of the spleen was first detected on day 72. Each infected animal had detectable serum levels of antileishmanial antibodies on day 72. There were significant elevations in gamma-globulin concentration as early as day 40 (P < 0.05) but significant falls in albumin concentrations were only detected from day 107 (P < 0.001). Nitrate, creatinine and urea concentrations remained unchanged during the course of infection, even after L-AmB treatment. Serum nitrate levels were not enhanced by L. infantum infection nor by the L-AmB treatment which induced a 98.2% decrease in parasite burden. The lack of NO production in visceral leishmaniasis, with or without L-AmB treatment, points to the unresponsiveness of inducible nitric oxide synthase in this rodent model.

Amphotericin B↗
PubMed1998

[Portal hypertension and neutrocytic ascites in POEMS syndrome].

We report a case of portal hypertension and neutrocytic ascites in a 52 year old man with POEMS syndrome. POEMS syndrome is an association of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammapathy and skin changes. Portal hypertension is rare in POEMS syndrome and this is the first time that culture negative neutrocytic ascites has been described with this syndrome.

Ascites↗
PubMed1998

Epoxyethane-/ethynesulfonamides with antifilarial activities. Degradation kinetics and inhibitory effect on filarial malate dehydrogenase and lactate dehydrogenase.

Some epoxyethane-/ethynesulfonamides had shown strong filaricidal activity with inconstant reproducibility as a result of a lack of stability in aqueous solution. The degradation in hydroxylic and aprotic solutions of two epoxyethanesulfonamides and one ethynesulfonamide was investigated using TLC, HPLC, GC and mass spectrometry. For both epoxydes, the degradation rate followed first-order kinetics and was more rapid in hydroxylic than in aprotic solutions. The degradation increased with the temperature whereas it was not modified with and without light exposure. Four kinds of degradation products were found: the first one involved the oxidation of the epoxyde bond, the second the breaking of the N-S bond, the third a desulfonation product and the fourth was not identified. In contrast, the stability of ethynesulfonamide was better than those of epoxyethanesulfonamide. These results suggest that epoxyethanesulfonamides should be kept at +4 degrees C before being injected to animals during the study of biological activity. Since epoxyde compounds are known to have inhibitory effects on parasite energy metabolism enzymes, the compunds were evaluated on two major filarial enzymes: lactate dehydrogenase (LDH) and cytoplasmic malate dehydrogenase (MDH). Both epoxyethanesulfonamides showed only a slight inhibitory effect on filarial LDH and MDH confirming the evidence that the main mode of action of these compounds remains to discover. Moreover, ethynesulfonamide and the degradation products of both epoxyethane-sulfonamides had no effect on LDH and MDH.

Animals↗
PubMed1997

Ultrastructural changes in parasites induced by nanoparticle-bound pentamidine in a Leishmania major/mouse model.

Drug targeting enhances drug efficacy. This principle was tested in the treatment of an experimental visceral leishmaniasis. Using transmission electron microscopy (TEM) we localized pentamidine-loaded polymethocrylate nanoparticles in the liver of mice infected with Leishmania major and compared the ultrastructural changes in the parasites of these mice when they were treated with bound versus free pentamidine. Between days 13 and 17 after infection, loaded nanoparticles treated group were injected i.v. with 3 doses of 0.17 mg/kg bound pentamidine loaded on 2 x 10(11) nanospheres; control groups received 2 x 10(11) unloaded nanospheres. Drug reference control groups received five doses of 200 mg/kg pentavalent antimony (Glucantime) or three doses of free pentamidine (0.17 mg/kg or 2.28 mg/kg). Mice treated with bound pentamidine displayed a 77% reduction in their parasite burden versus the untreated controls. Nanoparticles were located by TEM inside parasitized Küpffer cells, in the phagolysosomes without entering the Leishmania. The low dose of 0.17 mg/kg bound pentamidine damaged the Leishmania to the same extent as 2.28 mg/kg of free pentamidine (the usual dose in human chemotherapy). In the parasites inside the Küpffer cells, TEM showed a swollen mitochondrian with loss of cristae, destruction or fragmentation of the kinetoplast, loss of ribosomes and destruction of parasite structures except for the subpellicular microtubules. This study therefore shows that a dose of bound pentamidine 13 times smaller than the usual dose of free pentamidine has a similar effect on the parasite.

Animals↗
PubMed1996

Synthesis of catecholamide spiroarsoranes and their in vitro anthelmintic properties against Molinema dessetae and Nippostrongylus brasiliensis infective larvae.

Catecholamide spiroarsoranes were synthesized and evaluated for anthelmintic properties on two in vitro models, infective larvae of the filaria Molinema dessetae and infective larvae of an intestinal nematode. Nippostrongylus brasiliensis. On the N dessetae model, the most active compound after 24 h incubation time had an EC50 of 0.1 mumol/l. Eleven compounds had EC50 's in a range from 2 to 200 mumol/l. After 7 days incubation time, the two most active compounds had EC50 's of 0.03 and 0.07 mumol/l, respectively. On the N brasiliensis model, only three compounds were slightly active after 4 days incubation time. The ligands used for the spiroarsoranes synthesis were also evaluated for anthelmintic activity in order to know the contribution of these structures in the spiroarsoranes activity. Spiroarsoranes as prodrugs of arsonic acids were very active on the filaria, nematode having predominantly transcuticular uptake of nutrients while the activity on the intestinal nematode having both the types, transcuticular and intestinal uptake was low. The high sensitivity of filarial infective larvae is probably in relation to their location in the mosquito whereas N. brasiliensis infective larvae are telluric and should be more unsensitive to survive in a variable environment.

Animals↗