Therapeutic efficacy of a newly synthesized benzimidazole compound BTP-OH against murine schistosomiasis mansoni.

Because of the increasingly emerging praziquantel resistance, there is a crucial need to develop new anti-schistosomal agents. This work was conducted to assess the therapeutic efficacy of a new benzimidazole compound (BTP-OH) in mice experimentally infected with Schistosoma mansoni. A total of 40 Swiss albino female mice were divided into an infected untreated group and three infected treated groups (using praziquantel and BTP-OH). The compound activity was evaluated through parasitological, histopathological and scanning electron microscopy studies. Praziquantel and BTP-OH at both doses significantly reduced male (75%, 42.67% and 61.08%, respectively), female (71.45%, 48.94% and 68.13%, respectively) and total worm burden (75.21%, 42.42% and 62.28%, respectively), as well as tissue egg load in the liver (71.22%, 42.12% and 66.04%, respectively). In oogram, praziquantel significantly increased the percentage of dead eggs (65.89%), while BTP-OH significantly reduced the percentage of immature eggs (30.43% and 19.64%). BTP-OH significantly diminished granuloma count (33.87% and 44.77%) and diameter (39.23% and 49.40%), and caused ultrastructural changes in the tegument of adult schistosomes. This study provides evidence for the schistosomicidal efficacy of BTP-OH. However, future studies are needed to elucidate the full mechanisms of action and effects of BTP-OH on other human schistosomes.

Effect of a newly synthesized quinoline-based compound (PPQ-8) on murine schistosomiasis mansoni.

Schistosomiasis represents a public health problem and praziquantel is the only drug used for treatment of all forms of the disease. Thus, the development of new anti-schistosomal agents is of utmost importance to increase the effectiveness, reduce side effects and delay the emergence of resistance. The present study was conducted to report the therapeutic efficacy of PPQ-8, a new synthetic quinoline-based compound against Schistosoma mansoni. Mice were treated with PPQ-8 at day 49 post infection using two treatment regimens (20 and 40 mg/kg). Significant reductions were recorded in hepatic (62.9% and 83.6%) and intestinal tissue egg load (57.4% and 73.5%), granuloma count (75.4% and 89.1%) and diameter (26.2% and 47.3%), in response to the drug regimens, respectively. In addition, both treatment regimens induced significant decrease in liver (23.3% and 32.8%) and spleen (37.5% and 45.3%) indices. Also, there were significant reductions in mature ova, total worm and female count, which were more prominent with the higher dose. The reduction in the level of nitric oxide in the liver by both therapeutic regimens to 22.5% and 47.2% indicates the anti-oxidant activity of PPQ-8. Bright field microscopic examination of worms recovered from infected and PPQ-8-treated mice showed nearly empty intestinal caeca with no observable changes in the tegument. Our findings hold promise for the development of a novel anti-schistosomal drug using PPQ-8, but further in vitro and in vivo studies are needed to elucidate the possible mechanism/s of action and to study the effect of PPQ-8 on other human schistosomes.

Efficacy of artemisinin-naphthoquine phosphate against Schistosoma haematobium adult flukes: dose-effect relationship and tegumental alterations.

Schistosoma haematobium and Schistosoma mansoni infections have broadly overlapping geographical distributions. Praziquantel is the only treatment for human schistosomiasis, so drug tolerance and/or resistance are major concerns. Artemisinin-naphthoquine phosphate (CO-ArNp), an artemisinin-based combination therapy endorsed by the World Health Organization as a gold standard therapy for malaria, has also been identified as a promising treatment for S. mansoni. In this in vitro study, we tested the effect of 1-40 µg/ml CO-ArNp on S. haematobium worms, and inspected tegumental changes by using scanning electron microscopy (SEM), aiming to determine if this combination therapy has a broad-spectrum antischistosomal activity. Incubation of S. haematobium adults with 20 or 30 µg/ml CO-ArNp caused 100% mortality of worms within 72 or 48 h, respectively. SEM examination showed extensive tegumental alterations such as oedema, constriction, shortening and loss of spines, fissuring, sloughing and perforation, resulting in exposure of the underlying basal lamina, mainly in treated male schistosomes. Besides the well-established potent efficacy, bioavailability, tolerability and safety of the antimalarial artemisinin-naphthoquine phosphate combined therapy, these results may also suggest its possible utilization as a new broad-spectrum antischistosomal agent.

Effect of GnRH antagonist therapy on the expression of MUC-1 and heparin binding growth factor expression in the endometrium of hyperstimulated rats.

PURPOSE: To determine the effect of GnRH-antagonist therapy on the expression of heparin binding-epidermal growth factor (HB-EGF) and MUC-1 glycoprotein in hyperstimulated rat ovaries. METHODS: 30 female Wistar rats were divided into three groups (control, FSH and FSH+cetrorelix). Control rats were given 0.2 ml oil/saline mixture for four days beginning from the day of estrus. In the second group, 30 IU/ml purified hFSH was injected SC for four days beginning from the day of estrus. The rats of the third group were injected 30 IU FSH for four days and 10 IU cetrorelix SC for three or four days. The rats were sacrificed and the staining intensity of HB-EGF and MUC-1 of the epithelial cells and stromal cells of the endometrium of the rats was calculated by H-score. RESULTS: Slight MUC-1 immunoreactivity was seen in the epithelial and decidual cells of the control and FSH groups. In the FSH+cetrorelix group, moderate MUC-1 immunostaining appeared in the epithelial and desidual cells. In rats in the control and FSH+cetrorelix groups, HB-EGF immunoreactivity in the epithelial cells and decidual cells was moderate. Strong immunoreactivity was seen in the FSH group. When the MUC-1 H-score values were compared statistically with the control and other groups, FSH+cetrorelix immunoreactivity in epithelial and decidual cells were significantly different from control and FSH groups. HB-EGF immunoreactivity of the epithelium and decidua was similar in the control and FSH+cetrorelix groups, but epithelial and decidual immunoreactivity of the FSH group was different from the other two groups. CONCLUSION: Our findings suggest that GnRH antagonists exert direct effects on the expression of HB-EGF and MUC-1 expression in the rat endometrium.