The determination of safety of Muhanse M4®, a traditional herbal preparation used to treat HIV/AIDS-related conditions and diseases in Tanzania

Muhanse M4® is a traditional herbal preparation that has been in use in Tanzania for the past 17 years to improve the quality of life among people living with HIV/AIDS. This study was carried out to determine the safety of the extract Muhanse M4® in animal models. The qualitative test to identify alkaloids and saponins compounds was carried out. The toxicity tests in Swiss albino mice and rats were done according to WHO guidelines of 1993. Muhanse M4® was dissolved homogeneously in distilled water and was administered both intraperitonially and orally for 14 days for sub-acute test and 24 hours for acute test. Qualitatively, the extract was found to contain no alkaloids or saponins. In rats intraperitoneal doses that caused 100% lethality were 758.55 mg/kg and 553.7415mg/kg when administered singly and repeated, respectively. Single oral dose up to 3034.200mg/kg did not cause any death in the tested mice or rats. NOEL during intraperitoneal repeated doses for liver in rats was 424.788mg/kg, and NOAEL was 455.130mg/kg. In rats LD10%, LD50% and LD100% were 485.472mg/kg, 526.4337mg/kg and 553.7415mg/kg, respectively. In conclusion, Muhanse M4® extract is considered to be safe in laboratory animals. Keywords: Muhanse M4®, toxicity, medicinal plants, traditional medicine, HIV/AIDS Tanzania Health Research Bulletin Vol. 7(3) 2005: 168-17

In vitro multistage malaria transmission blocking activity of selected Malaria Box compounds

Purpose: Continuous efforts into the discovery and development of new antimalarials are required to face the emerging resistance of the parasite to available treatments. Thus, new effective drugs, ideally able to inhibit the Plasmodium life-cycle stages that cause the disease as well as those responsible for its transmission, are needed. Eight compounds from the Medicines for Malaria Venture (MMV) Malaria Box, potentially interfering with the parasite polyamine biosynthesis were selected and assessed in vitro for activity against malaria transmissible stages, namely mature gametocytes and early sporogonic stages. Methods: Compound activity against asexual blood stages of chloroquine-sensitive 3D7 and chloroquine-resistant W2 strains of Plasmodium falciparum was tested measuring the parasite lactate dehydrogenase activity. The gametocytocidal effect was determined against the P. falciparum 3D7elo1-pfs16-CBG99 strain with a luminescent method. The murine P. berghei CTRP.GFP strain was employed to assess compounds activities against early sporogonic stage development in an in vitro assay simulating mosquito midgut conditions. Results: Among the eight tested molecules, MMV000642, MMV000662 and MMV006429, containing a 1,2,3,4-tetrahydroisoquinoline-4-carboxamide chemical skeleton substituted at N-2, C-3 and C-4, displayed multi-stage activity. Activity against asexual blood stages of both strains was confirmed with values of IC50 (50% inhibitory concentration) in the range of 0.07-0.13 µM. They were also active against mature stage V gametocytes with IC50 values below 5 µM (range: 3.43-4.42 µM). These molecules exhibited moderate effects on early sporogonic stage development, displaying IC50 values between 20 and 40 µM. Conclusion: Given the multi-stage, transmission-blocking profiles of MMV000642, MMV000662, MMV006429, and their chemical characteristics, these compounds can be considered worthy for further optimisation toward a TCP5 or TCP6 target product profile proposed by MMV for transmission-blocking antimalarials

Upper Subrings of a Ring

We describe maximal ideals of rings that are contained in the adjoint groups of their upper subrings.Описано максимальні ідеали кілець, що містяться в приєднаних групах їхніх верхніх кілець

The block-by-block method with Romberg quadrature for the solution of nonlinear volterra integral equations on large intervals

We investigate the numerical solutions of nonlinear Volterra integral equations by the block-by-block method especially useful for the solution of integral equations on large-size intervals. A convergence theorem is proved showing that the method has at least sixth order of convergence. Finally, the performance of the method is illustrated by some numerical examples.Дослiджено чисельний розв’язок нелiнiйних iнтегральних рiвнянь Вольтерра поблочним методом, який є особливо корисним при розв’язуваннi iнтегральних рiвнянь на великих iнтервалах. Доведено теорему про збiжнiсть, яка показує, що цей метод має щонайменше шостий порядок збiжностi. Дiю методу проiлюстровано на кiлькох числових прикладах

A BLOCK BY BLOCK METHOD FOR SOLVING SYSTEM OF VOLTERRA INTEGRAL EQUATIONS WITH CONTINUOUS AND ABEL KERNELS

The aim of the present paper is to introduce a block by block method for solving system of nonlinear Volterra integral equations with continuous kernels and system of Abel integral equations. We prove convergence of the method and show that its convergence order is at least six. To illustrate performance of the method, numerical experiments are presented and they are compared with HPM (Homotopy Perturbation Method) and RBFN (Radial Basis Function Network) method. The given results demonstrate remarkable ability of the proposed method

Forest Resources Assessment

Forest resource assessment is fundamental in decision making to provide essential data and information for forest managers and decision makers to ensure sustainable forest management. This chapter has described objectives and importance of forest resource assessment, forest inventory planning and methods/designs and important descriptive statistics which should be applied when describing forest parameters of interest. Other essential aspects which also guide and compliment forest resource assessment, i.e. survey and mapping; and remote sensing are described. Application of remote sensing and GIS in forestry has also been covered

Nonfimbrial Adhesin Mutants Reveal Divergent Escherichia coli O157:H7 Adherence Mechanisms on Human and Cattle Epithelial Cells

Shiga toxin-producing, enterohemorrhagic Escherichia coli (EHEC) serotype O157:H7 is a major foodborne pathogen causing symptoms ranging from simple intestinal discomfort to bloody diarrhea and life-threatening hemolytic uremic syndrome in humans. Cattle can be asymptomatically colonized by O157:H7 predominantly at the rectoanal junction (RAJ). Colonization of the RAJ is highly associated with the shedding of O157:H7 in bovine feces. Supershedding (SS) is a phenomenon that has been reported in some cattle that shed more than 104 colony-forming units of O57:H7 per gram of feces, 100–1000 times more or greater than normal shedders. The unique bovine RAJ cell adherence model revealed that O157:H7 employs a LEE-independent mechanism of attachment to one of the RAJ cell types, the squamous epithelial (RSE) cells. Nine nonfimbrial adhesins were selected to determine their role in the characteristic hyperadherent phenotype of SS O157 on bovine RSE cells, in comparison with human HEp-2 cells. A number of single nucleotide polymorphisms (SNPs) were found amongst these nonfimbrial adhesins across a number of SS isolates. In human cells, deletion of yfaL reduced the adherence of both EDL933 and SS17. However, deletion of eae resulted in a significant loss of adherence in SS17 whereas deletion of wzzB and iha in EDL933 resulted in the same loss of adherence to HEp-2 cells. On RSE cells, none of these nonfimbrial deletion mutants were able to alter the adherence phenotype of SS17. In EDL933, deletion of cah resulted in mitigated adherence. Surprisingly, four nonfimbrial adhesin gene deletions were actually able to confer the hyperadherent phenotype on RSE cells. Overall, this study reveals that the contribution of nonfimbrial adhesins to the adherence mechanisms and functions of O157:H7 is both strain and host cell type dependent as well as indicates a possible role of these nonfimbrial adhesins in the SS phenotype exhibited on RSE cells