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Abstract
The present study has aimed to investigate whether low dose Gamma irradiated promastigotes of Leishmania major could influence the subsequent development of clinical disease in cutaneous leishmaniasis murine model. The present study had also headed to define whether inoculation with irradiated promastigotes protect against virulent L. major infection, and consequently to minimize the required dose of the drug pentostam with its known side effects. The BALB/c mice were used as experimental animals. The animals were injected with non-irradiated and irradiated promastigotes, intradermally. At different intervals, animals were sacrificed, sera were collected whereas bodies were rapidly dissected, and suitable parts of skin, liver, and spleen were taken and processed for histopathological investigation. Direct agglutination test (DAT) was used for serological studies. DAT test results showed a difference of titers exists between the end points of the sera collected from mice vaccinated with non-irradiated promastigotes (> 1:25600), and of the sera of mice vaccinated with irradiated promastigotes and sacrificed at 25 & 50 days after infection (1:25600), and those sacrificed at 84 days after infection ( 1:12800). Furthermore, the sera samples had clearly reflected the immunological responses to parasitic infection in a more pronounced manner in case of non-irradiated-promastigote-vaccinated BALB/c mice than in those of irradiated-promastigote-vaccinated BALB/c mice. The examined specimens have brought into vision consequences of pathological alterations comparable to the corresponding normal specimens. In the skin, lesions were developed whereas thickening and compactness of the epidermal layer, damage of the dermis, and widening as well as marked injury of the blood vessels were recorded. The liver of the infected animals showed to suffer from tissue disorganization, and degeneration of liver cells in addition to nuclear deterioration. Severe inflammatory reactions were clearly noticed in those tissues. In the spleen, cell proliferation and abundance of inflammatory cells were conspicuously prevailing in the Leishmania infected BALB/c mice. The severity of such pathological changes was time-dependent. Moreover, pathological consequences were relatively more striking in case of non-irradiated immunized BALB/c mice. For Pentostam activity evaluation, intracellular amastigotes had greater values of IC50 than what have been obtained in non-irradiated amastigotes and lower values of IC50 were obtained in irradiated amastigotes. Indicating that, non-irradiated promastigotes were more susceptible to Pentostam compared to non-irradiated amastigotes. At the same time, both irradiated promastigotes and amastigotes responded generally to lower values of Pentostam. The behavior shown by Acid phosphatase (AP) activity was higher at higher concentrations of Pentostam, in case of non-irradiated promastigotes, compared to lower values of promastigote response in irradiated promastigotes. The in vivo Pentostam evaluation indicated that, the tissue responses of animals were clear, especially for the skin toward cure at the dose level of 18 mg / kg body weight. This dose appeared to have been therapeutically equivalent while being less toxic than the standard dose utilized at 20 mg / kg body weight.