الفهرس 
Schistosoma mansoniOnly 14 pages are availabe for public view
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Abstract
S. mansoni is a blood fluke responsible for the chronic human disease schistosomiasis mansoni, the second endemic disease worldwide, with high-prevalence endemicity in Egypt. Infection occurs by contact with fresh water that contains the cercariae which penetrate intact skin and transform into schistosomula that travel through the blood stream before differentiating into male and female adult worms. The immunopathology of schistosomiasis mansoni is due to delayed hypersensitivity reaction which results in granuloma formation around eggs leading to obstructive intestinal disease, hepatosplenic inflammation and liver fibrosis. PZQ is the mainstay of schistosomiasis treatment. However, PZQ is not effective against the larval stages of schistosomes, it also does not prevent re-infection with the possibility of emergence of drug resistance. CPs play numerous roles in the biology of parasites. Despite the presence of host homologues, the difference in nature between parasite CPs and the host proteins has given chances for its use as a target for chemotherapy. The schistosome digestive tract digests the macromolecules derived from mammalian host blood then absorb the soluble products by several proteases. Thereby, CPIs would compromise S. mansoni development inside the host and lead them to death through starvation. The current work was done to study the effect of phenyl vinyl sulphone (PVS), a CPI, on different stages of S. mansoni in an in vitro study, and on the parasite subjected to PVS at different durations of schistosomiasis mansoni in experimentally-infected mice, in comparison to the conventionally employed drug; praziquantel (PZQ). As regards in vitro study, the S. mansoni schistosomula and adult worms were maintained, separately, in RPMI-1640 medium. Then were subjected to different concentrations of PVS (1 µg/ml, 2 µg/ml, 4 µg/ml, 6µg/ml, 8µg/ml and 10 µg/ml). Positive and negative controls (PZQ at 1 μg/ml and DMSO) were also studied. S. mansoni schistosomula and adults were kept for a 4- and 6- day period, respectively, and monitored every 24 hours. The parameters used for the in vitro study were: A) Dose-response studies by detection of the percent worm mortality for each of S. mansoni schistosmoula and adult worms. B) Growth inhibition studies by detection of hemoglobin degradation for schistosomula and oviposition for adults. As regards the in vivo study, mice experimentally infected with S.mansoni (by subcutaneous injection of 60±10 cercariae) and subjected to either intraperitoneal injection PVS (50mg/kg/mouse/day for 7 days) or oral PZQ (500mg/kg/mouse/day for 2 days) were employed. The study was carried out on Swiss albino mice divided into 8 groups: group I (Infected mice treated 1 wk pi). group II (Infected¬ mice treated 3 wks pi). group III (Infected mice treated 5 wks pi). group IV (Infected mice treated 7 wks pi). Each of the previous groups was equally divided into 2 subgroups (6 mice each); a: infected PVS-treated and b: infected PZQ-treated. group V (Infected non-treated mice). group VI (Non-infected PVS treated mice). group VII (Non-infected PZQ treated mice). group VIII (Non-infected non-treated mice) groups V-VIII were 6 mice each. Mice of all groups were sacrified10 wks pi. The anti-schistosomal effects of PVS was assessed by the following parameters: A) Parasitological parameters where stool samples, small intestine and liver were examined by fecal egg counts, total worm burden, tissue egg load in small intestine and liver and oogram pattern. B) Histopathological parameters by examining hepatic sections for detection of egg-induced granulomatous cellular reaction and measurement of hepatic granulomas number and size. C) Haematological parameter by examining blood samples for the detection of haemoglobin concentration. Results of the in vitro study revealed that PVS was effective against S.mansoni schistosomula and adults in a concentration and time dependent manner. At concentrations of 1µg/ml and 2µg/ml PVS, death of schistosmoula started at day 3 with 30% and 40% worm mortality, respectively. At concentrations of 4µg/ml, 6µg/ml and 8µg/ml PVS death of schistosomula started at day 1 with 20%, 40% and 70% worm mortality, respectively, on day 2 the percent was 50%, 60% and 90%, respectively, while on day 3 the percent was 70%, 80%, 100% . On day 4 all worms were dead by previous concentrations. At a concentration of 10µg/ml PVS, death of schistosomula started at day 1 with 90% worm mortality, reaching 100% by day 2. Death of PZQ treated schistosomula started from day 1 (80%) reaching 100% by day 2. The death of S. mansoni adult worms by all tested concentrations of PVS started from day 4, with the highest mortality rate (67%) using 10 µg/ml PVS. The highest concentration of PVS (10 µg/ml) showed 92% worm mortality by day 5. All worms treated by different concentrations of PVS were dead by day 6 (100%). Death of adult worms by PZQ started by day 2 with 100% worm mortality. The different concentrations of PVS showed a concentration dependent arrest of hemoglobin degradation in schistosomula, determined by lack of black pigmentation of the gut. A decrease in black pigmentation of the gut was detected at a concentration of 4, 6 and 8 µg/ml PVS with complete absence of black gut at 10 µg/ml PVS in comparison to black gut in schistosomula treated with PZQ. As regards in vivo study, PVS decreased the mean fecal egg count in subgroups Ia, IIa, IIIa and IVa with significant decrease in each of subgroup IIIa and IVa compared to group V, and in subgroup IVa compared to each of IIa and IIIa, and a non-significant difference in subgroup a compared to b in groups I, III, and IV. PZQ significantly decreased the mean fecal egg count in each of subgroup IIb, IIIb and IVb in comparison to group V. PVS decreased the total worm burden in subgroups Ia, IIa, IIIa and IVa with non-significant decrease when each was compared to group V, and compared to each other, and when subgroup Ia and IIa compared to Ib and IIb, respectively. PZQ significantly decreased the total worm burden in each of subgroups IIIb and IVb compared to group V, and in IIIb and IVb compared to IIIa and IVa, respectively. PVS significantly decreased the mean egg count / gm intestine and liver in each of subgroups Ia, IIa, IIIa and IVa compared to group V, in subgroup IVa compared to each of subgroup Ia, IIa and IIIa, in subgroup IIIa compared to each of Ia and IIa, and in subgroup Ia compared to IIa. PZQ significantly decreased the mean egg count / gm intestine and liver in each of subgroups Ib, IIb, IIIb and IVb compared to group V. PZQ significantly decreased the mean egg count / gm intestine in each of subgroup Ib and IIb compared to Ia and IIa respectively, whereas PVS significantly decreased the mean egg count / gm intestine in subgroups IIIa and IVa compared to IIIb and IVb, respectively. Moreover, PZQ significantly decreased the mean egg count / gm liver in subgroup b of each of groups I, II, III and IV compared to subgroup a in the same groups, respectively. As regards oogram results, PVS showed non- significant difference in mean number of dead ova in subgroups Ia, IIa, IIIa, and a significant increase in mean number of dead ova in subgroup IVa when each was compared to group V. Moreover, subgroup IVa showed significant increase in mean number of dead ova compared to each of subgroups Ia, IIa and IIIa. PZQ showed significant increase in mean number of dead ova in each of subgroup IIIb and IVb compared to group V, and in IIIb and IVb compared to IIIa and IVa, respectively. Each of PVS and PZQ in groups I and II resulted in a nearly similar histopathological picture as group V showing cloudy swelling in liver cells with cellular granuloma made up of plasma cells, lymphocytes and scattered fibroblasts with bilharzial pigment in Von-Kupffer cells. Meanwhile, in groups III and IV each of PVS and PZQ resulted in fibrocellular granulomas made up of fibroblasts, intervening collagen with a decrease in bilharzial pigment in Von-Kupffer cells, a pattern which is different from that of group V. Each of group VI and VII gave a histological picture as that group VIII. Each of PVS and PZQ resulted in a significant decrease in mean hepatic granuloma size in each of subgroup a and b in groups I, II, III and IV compared to group V, with PVS resulting in smaller granuloma size than PZQ in subgroups IIa, IIIa and IVa. As regards hepatic granuloma number, there was a significant decrease in each of subgroup a and b in groups II, III and IV compared to group V, and in each of subgroup IIIa and IVa compared to each of subgroup Ia and IIa. PVS increased mean hemoglobin concentration in subgroups Ia, IIa, IIIa and IVa, with a significant increase in each of subgroup Ia and IIIa compared to group V. Moreover, there was non-significant difference in mean hemoglobin concentration when comparing subgroup a in groups I, II, III and IV with each other. PZQ significantly increased mean hemoglobin concentration in subgroups Ib, IIb, IIIb and IVb compared to group V. Meanwhile, there was nonsignificant difference in mean hemoglobin concentration when comparing subgroup a to subgroup b in each of group I, II, III and IV. There was non-significant difference in mean hemoglobin concentration when comparing each of group VI and group VII to group VIII, and a significant decrease in mean hemoglobin concentration in group V compared to group VIII.