Effect of omega-3 fatty acids administered as monotherapy or combined with artemether on experimental Schistosoma mansoni infection.

Schistosomiasis is on the top list of endemic diseases in sub-Saharan Africa. Praziquantel is the drug of choice for treatment of human schistosomiasis. Yet, the sole dependence on the drug raises concerns about the potential for increased drug resistance, which would subsequently result in searching for alternative preventive chemotherapy options, ideally among natural compounds. Therefore, we conducted this work to assess the effect of omega-3 polyunsaturated fatty acids [(ω-3) PUFAs] monotherapy or combined therapy with artemether (ART) against Schistosoma mansoni infection in a mouse model. A total of 42 mice were divided into 4 groups and infected with 50 ± 5 S. mansoni cercariae for 10 weeks. Mice were treated orally with either (ω-3) PUFAs as 273 mg/ kg, 4 times/ week throughout the experiment, ART as a single dose of 400 mg/ kg, 3 weeks post-infection, or combined ART + (ω-3) PUFAs using the same respective treatment regimen, while infected untreated mice were served as controls. The study explored that combined administration of (ω-3) PUFAs and ART has the best schistosomicidal efficacy as it significantly reduced liver and spleen indices, worm count, egg burdens, and granulomas count as well as diameter. Besides, the combined regimen was associated with a significant decrease in both hepatic nitric oxide and serum interleukin-4 level. The results highlighted the possibility of using (ω-3) PUFA combined with ART as a novel anti-schistosomal combination therapy. However, further researches should be conducted to clarify the possible synergistic mechanism/s between the two natural compounds.

Effectiveness of vinpocetine and isosorbide-5-mononitrate on experimental schistosomiasis mansoni: Biochemical and immunohistochemical study.

Schistosomiasis is one of the most important tropical and subtropical devastating diseases, where praziquantel is the sole drug of choice. Praziquantel effectively kills the adult worms, however, drug resistance has been repeatedly reported. Moreover, there is currently no efficient anti-fibrotic therapy available for chronic schistosomiasis. So, novel drugs which exert anti-fibrotic efficacy are urgently needed. This research is complementary to our previous work that evaluated the anti-schistosomal effects of the anti-inflammatory vinpocetine, as well as the vasodilator and the anti-oxidant isosorbide-5-mononitrate. In the present study, we assessed the therapeutic efficacies of drugs in Swiss albino female mice experimentally infected with an Egyptian strain of Schistosoma mansoni, using some biochemical and immunohistochemical parameters. Our results revealed that both vinpocetine and isosorbide-5-mononitrate monotherapy significantly decreased hepatic nuclear factor-kappaB, 10 weeks post infection. The best effects were seen in mice administered praziquantel combined with isosorbide-5-mononitrate, as detected by reduction in hydroxyproline and collagen contents of the liver, and significant increase in the hepatic nitric oxide content. The data provides insight into the potential effects of the assessed drugs with isosorbide-5-mononitrate being more superior to vinpocetine, hence it can be used as novel adjuvant to praziquantel to alleviate schistosomal hepatic fibrosis. However, molecular mechanism/s and clinical trials are worthy to be scrutinized.

A comparative study on the anti-schistosomal and hepatoprotective effects of vinpocetine and isosorbide-5-mononitrate on Schistosoma mansoni-infected mice.

Schistosomiasis is a remarkable public health problem in developing countries. Presently, praziquantel is the optional drug for all human schistosomiasis. Owing to the increased praziquantel resistance, there is an urgent need to develop new alternatives. This study aims at determining the anti-schistosomal and/or the hepatoprotective effects of the anti-inflammatory drug; vinpocetine, and the vasodilator and the nitric oxide donor; isosorbide-5-mononitrate, in comparison to praziquantel. In the present research, the therapeutic efficacies of these drugs were assessed in Swiss albino female mice (CD-I strain) experimentally infected with an Egyptian strain of Schistosoma mansoni, using some general, parasitological, and histopathological parameters. In this work, praziquantel significantly reduced worm burden and hepatic egg load, increased the percentage of dead eggs in the small intestine and decreased granuloma count, but did not reduce granuloma diameter. While, either vinpocetine or isosorbide-5-mononitrate monotherapy did not induce significant reduction in the worm count, hepatic egg load or shift in the oogram pattern, but significantly reduced granuloma count and diameter. Moreover, isosorbide-5-mononitrate significantly reduced hepatic inflammation and necrosis. The best results were obtained in the mice groups treated with isosorbide-5-mononitrate combined with praziquantel or vinpocetine. Our results point to vinpocetine and isosorbide-5-mononitrate as a convenient and promising adjuvant to praziquantel for ameliorating schistosomal liver pathology. Further studies are recommended to reveal the actual pathways responsible for the different activities of vinpocetine and isosorbide-5-mononitrate.

[Clinical aspects, diagnosis and therapy of nesidioblastosis]. / Klinik, Diagnostik und Therapie der Nesidioblastose.

Hyperinsulinemia due to an excessive secretion of insulin independent on normal regulation is the most frequent cause of persistent neonatal hypoglycemia. We report on clinical course, diagnostic procedures and treatment of nesidioblastosis in three patients. Main symptoms observed in newborn period were hypoglycemia, respiratory embarrassment, cyanosis and convulsions. Primary treatment was started by continuous infusion of glucose, administration of diazoxide and prednisolone or glucagon. Most important investigations were performed simultaneously. In all three children subtotal resection of pancreas was necessary, because there was no constant blood glucose level. Histological specimens confirmed diagnosis. In two of three patients pancreatectomy followed. One suffers from diabetes mellitus, the other one fed normally, has stable blood glucose level possibly due to existence of extrapancreatic insulin producing cells.

Quantitative rating of manic states. Correlation between clinical assessment and Biegel's Objective Rating Scale.

We have investigated Biegel's manic-state rating scale and found the interrater reliability high when the scale was administered both by nurses and psychiatrists. In our study of validation, we tested each item of the scale for calibration, ascending monotonicity and dispersion parallel to a global clinical assessment of the manic state. Six of the scale items were then found valid and those items differed from the valid items in studies of Biegel by including increased social contact. Like Biegel, we found a positive correlation between items concerned with depressed mood, indicating a fluctuation in the mood of manic patients during 8 hours of observation.

Quantitative rating of depressive states.

A step-by-step analysis of Beck's and Hamilton's rating scales showed that both scales failed to differentiate adequately between moderate and severe depression measured by a global clinical assessment. Each item of the scales was tested for calibration, ascending monotonicity, and dispersion parallel to the clinical assessment. Twelve items of Beck's scale and six items of Hamilton's scale were found valid with respect to these criteria. Those items should be taken into account in future research for baseline ratings and for change ratings of depressive states quantitatively.