Enhancement of chloroquine activity against resistant parasites by co-administration of cimetidine

In vivo studies on reversal of chloroquine [CQ] resistance by cimetidine [CIM] were carried out in thirty five patients infected with Plasmodium falciparum in Omdurman Hospital for Tropical Diseases and Elhaj Yousif area, Khartoum Sudan. Parasites were considered resistant if still present in peripheral blood circulation, three days after the start of standard dose of CQ treatment. Patients with CQ resistant parasites were admitted to the hospital and given CIM [800 mg in two divided doses], 48 hours after the start of standard dose of chloroquine treatment. They were followed clinically and microscopically, daily for one week and then discharged. Treatment in the dose used was found to reverse CQ resistance in [70%] of the patients studied within three days of CIM treatment. No side effects were reported by any of the patients. Glutamicoxaloacetic transaminase [GOT] content in the treated group was found to be 31.57 I.U/L [ +/- 0.85], protein content 6.5 g/dl [ +/- 0.85] and the uric acid 6.5 mg /dl [ +/- 0.71]. The values of GOT, protein and uric acid in the resistant group were found to be slightly higher than those in by the sensitive one

Antischistosomal efficacy study on praziquantel, its alkaline hydrolysis and the sun-decomposed products

Praziquantel [PZQ] administered in a dose of 40 mg /kg body weight to S. mansoni infected albino mice, was not active enough to cause a significant reduction in the mean worm recovery 16.6%. The reduction caused by the alkaline hydrolysis product, [PZQ-HP] 28.6%, and the sun decomposed product, [PZQ-SDP] 47.6% of PZQ suggested higher antischistosomal activity of these two products compared to PZQ. There were no significant differences in liver and intestine tissue egg count carried on the infected-treated groups, and the infected-untreated group. The granulomas observed in the livers of the experimentally S. mansoni infected-untreated mice were mainly cellular existing within the portal tract and subcapsular parenchyma. Schistosome pigments were observed in the Kuffer cell with thickening of the portal tract. The vascular lesions comprised granulomatous occlusions, periphelebitis, perivascular cuffing of the central vein and sinusoidal dilatation. The hepatic histopathological changes observed in the PZQ, and the PZQ-HP-treated groups were similar. characterized by the scattering of the granulomas in the portal tract and intralobular parenchyma. The vascular lesions in these groups [PZQ and [PZQ-HP]] comprised periphelebitis of some portal radicles, granulomatous occlusions and rarely the perivascular cuffing of the central vein. These results indicated comparable efficacy of the two compounds. The granulomas of the PZQ-SDP treated group were found distributed between the portal radicles and parenchyma in equal manner with central egg and/or shell or necrosis. Schistosome pigments were less intense than in the infected-untreated mice with infrequent leucocytic foci, perivascular cuffing of the central vein and periphlebitis of the portal vein. The number of granulomas in the SP-treated group was less than in the infected-untreated mice with greater size whereas that of PZQ- and PZQ-HP-treated groups were comparable in number and size but significantly different in number [p= 0.01] in comparison with the infected-untreated mice. These variations were interpreted and justified. Despite of the death of half the group treated with PZQ-SDP compound within the first and second week post treatment; there were no signs of hepatotoxic effects as revealed by the histopathological study conducted at our laboratories