Pharmacology of DB844, an orally active aza analogue of pafuramidine, in a monkey model of second stage human African trypanosomiasis

Novel drugs to treat human African trypanosomiasis (HAT) are still urgently needed despite the recent addition of nifurtimox-eflornithine combination therapy (NECT) to WHO Model Lists of Essential Medicines against second stage HAT, where parasites have invaded the central nervous system (CNS). The pharmacology of a potential orally available lead compound, N-methoxy-6-{5-[4-(N-methoxyamidino) phenyl]-furan-2-yl}-nicotinamidine (DB844), was evaluated in a vervet monkey model of second stage HAT, following promising results in mice. DB844 was administered orally to vervet monkeys, beginning 28 days post infection (DPI) with Trypanosoma brucei rhodesiense KETRI 2537. DB844 was absorbed and converted to the active metabolite 6-[5-(4-phenylamidinophenyl)-furanyl-2-yl]-nicotinamide (DB820), exhibiting plasma C(max) values of 430 and 190 nM for DB844 and DB820, respectively, after the 14th dose at 6 mg/kg qd. A 100-fold reduction in blood trypanosome counts was observed within 24 h of the third dose and, at the end of treatment evaluation performed four days post the last drug dose, trypanosomes were not detected in the blood or cerebrospinal fluid of any monkey. However, some animals relapsed during the 300 days of post treatment monitoring, resulting in a cure rate of 3/8 (37.5%) and 3/7 (42.9%) for the 5 mg/kg×10 days and the 6 mg/kg×14 days dose regimens respectively. These DB844 efficacy data were an improvement compared with pentamidine and pafuramidine both of which were previously shown to be non-curative in this model of CNS stage HAT. These data show that synthesis of novel diamidines with improved activity against CNS-stage HAT was possible

El Conocimiento Didáctico del Contenido en ciencias: estado de la cuestión

This paper gives a descriptive overview of the literature related to Pedagogical Content Knowledge - PCK - in the sciences. It is expected that this review can contribute to a better understanding of PCK, pointing out what has been investigated about this concept. Specifically, we analyze: a) how PCK is defined, what are its main features and how it has been appropriated by teachers; b) the relationship between PCK, knowledge of the contents to be taught and students learning; c) how PCK was actually used in teachers' training and teachers' evaluation; and, d) the scientific areas in which PCK has been studied. It concludes that PCK is an essential tool for improving the quality of teacher training

Analysis of the Yellow Bean Corridor in Tanzania

The yellow bean value chain in Tanzania was necessary to understand value chain. The objective of the survey was to characterize and explore trade of yellow bean grain and potential seed. The survey collected data and grain samples from 298 grain traders (including wholesalers, exporters, aggregators, and retailers) and 64 potential seed traders (large and retail traders) from 12 regions across four administrative zones in Tanzania. The grain samples collected were for DNA analyses. Results show existence of an established yellow bean corridor across Tanzania and the region at large (Burundi, DRC, Kenya, Rwanda, Uganda, Zambia) and demonstrated a huge market pull in the Eastern and Southern Africa regions. There are also strong perceptions on the organoleptic quality of various yellow bean grains and varieties that are traced to their sources