Establishment of asymptomatic Leishmania donovani infection in Indian langurs (Presbytis entellus) through intradermal route.

Indian langurs, which were previously reported to be highly susceptible, were infected intradermally using variable numbers of promastigotes along with different doses, 1/2 pair, 5 pairs and 10 pairs respectively of salivary gland lysate (SGL). Although, all the monkeys developed mild infection and remained subclinically infected throughout the observation period, which later resolved, none of them could develop the classical disease. No marked antigen specific antibody or lymphoproliferative response was noticed throughout the experimental period. However, a late IFN-gamma response (by day 90 pi.) was demonstrated in monkeys infected with 2 x 10(6) promastigotes +10 pairs SGL. It seems that a single intradermal dose of promastigotes with or without SGLs had a vaccines like effect. Perhaps, multiple frequent inoculations, as happens in the natural situation, may be necessary for the development of full-blown disease.

Metabolic disposition of methyl [5-[[4-(2-pyridinyl)-1-piperazinyl] carbonyl]-1-H-benzimidazol-2-yl] carbamate in hamsters: a study to understand chemoprophylactic action against experimental Ancylostomiasis.

Methyl [5-[[4-(2-pyridinyl-1-piperazinyl] carbonyl]-1H- benzimidazol-2-yl] carbamate (CDRI Compound 81-470) exhibits a long prophylactic action against experimental ancylostomiasis, when given parenterally but not orally. To find out an explanation for such a behaviour, metabolic disposition studies were performed in hamsters using [3H] compound 81-470. Following intramuscular administration, the compound was found to form a depot at the site of injection and to remain there in substantial amount for more than 7 weeks. The compound was fairly distributed in all the organs studied and the presence of radioactivity could be easily detected up to 7 weeks of observation period. The compound was very slowly eliminated from the body and only 38% of the radioactivity could be recovered in the urine and faeces during 14 days. The oral dose, to the contrary, was poorly absorbed and more than 62.8% was excreted in the faeces within 48 hr. Consequently, this dose yielded lesser area under plasma curve. More than 95% of the oral dose was eliminated within a week and hardly and radioactivity could be detected in the tissues after day 14. In accord with this pattern, in blood also the im dose was detected up to 7 weeks while the orally given compound reached undetectable level within 6 days only. The lower clearance and prolonged stay in the body of the im dose compared to quick elimination of the oral dose may be responsible for the long chemoprophylactic action of compound 81-470 when given through im route.

Evaluation of enzyme-linked immunosorbent assay in the diagnosis of kala-azar in Malda district (West Bengal).

An immunological test based on indirect (plate) ELISA has been successfully standardized and modified using promastigote soluble antigen. The test carried out on 813 subjects from a kala-azar endemic area (including parasitologically confirmed patients, subjects presenting with clinical symptoms of visceral leishmaniasis and endemic controls) and a non-endemic area (with diseases other than kala-azar and apparently normal subjects) was found to detect, specifically, antileishmanial antibodies. The plate ELISA has been simplified to a more sensitive dot-ELISA where the results are read within 2-3 h. The antigen requirement is 250 ng per test. No cross-reactivity with sera from patients of malaria, tuberculosis, leprosy, amoebiasis and filariasis was observed. The follow up monitoring of antibodies in successfully treated kala-azar patients showed a decline of antibodies. A drop of blood taken on filter paper is sufficient to conduct the test. Dot ELISA therefore is a simple, inexpensive and stable test in serodiagnosis of visceral leishmaniasis.

Efficacy of methyl 5(6)-(alpha-hydroxyphenylmethyl) benzimidazole-2-carbamate, a metabolite of mebendazole, against developing forms of experimental helminth parasites.

Methyl 5(6)-(alpha-hydroxyphenylmethyl) benzimidazole-2- carbamate, a metabolite of mebendazole, was evaluated against metamorphic forms of Ancylostoma ceylanicum in hamsters, Nippostrongylus brasiliensis in rats and cysticercoids of Hymenolepis nana in grain beetles. The test compound offered better action than mebendazole except against H. nana cysticercoids where the activity of the compound and mebendazole was comparable, but was inferior to the standard cestodicidal drug, praziquantel. The results suggest that the action was better by ip route compared to per os route of drug administration.

Effects of methyl [5 [[4-(2-pyridinyl)-1-piperazinyl]carbonyl]-1H-benzimidazol-2-yl] carbamate on energy metabolism of Ancylostoma ceylanicum and Nippostrongylus brasiliensis.

Effects of methyl [5[[4-(2-pyridinyl)-1-piperazinyl] carbonyl] 1H-benzimidazol-2-yl] carbamate (CDRI Comp. 81-470) and mebendazole on the energy metabolism of A. ceylanicum and N. brasiliensis were compared. At 10 and 50 microM concentration both compounds inhibited glucose uptake and its conversion into metabolic endproducts. The shift towards the increased production of lactic acid appeared to be the result of inhibition of PEP carboxykinase and increase in LDH activity. The compounds also caused significant inhibition of ATP production in mitochondria.