Population pharmacokinetics of antimalarial naphthoquine in combination with artemisinin in Tanzanian children and adults: dose optimization

The combination antimalarial therapy of artemisinin-naphthoquine (ART-NQ) was developed as a single-dose therapy, aiming to improve adherence relative to the multiday schedules of other artemisinin combination therapies. The pharmacokinetics of ART-NQ has not been well characterized, especially in children. A pharmacokinetic study was conducted in adults and children over 5 years of age (6 to 10, 11 to 17, and >/=18 years of age) with uncomplicated malaria in Tanzania. The median weights for the three age groups were 20, 37.5, and 55 kg, respectively. Twenty-nine patients received single doses of 20 mg/kg of body weight for artemisinin and 8 mg/kg for naphthoquine, and plasma drug concentrations were assessed at 13 time points over 42 days from treatment. We used nonlinear mixed-effects modeling to interpret the data, and allometric scaling was employed to adjust for the effect of body size. The pharmacokinetics of artemisinin was best described by one-compartment model and that of naphthoquine by a two-compartment disposition model. Clearance values for a typical patient (55-kg body weight and 44.3-kg fat-free mass) were estimated as 66.7 L/h (95% confidence interval [CI], 57.3 to 78.5 L/h) for artemisinin and 44.2 L/h (95% CI, 37.9 to 50.6 L/h) for naphthoquine. Nevertheless, we show via simulation that patients weighing >/=70 kg achieve on average a 30% lower day 7 concentration compared to a 48-kg reference patient at the doses tested, suggesting dose increases may be warranted to ensure adequate exposure. (This study has been registered at ClinicalTrials.gov under identifier NCT01930331.)

Mobility, Expansion and Management of a Multi-Species Scuba Diving Fishery in East Africa

Background: Scuba diving fishing, predominantly targeting sea cucumbers, has been documented to occur in an uncontrolled manner in the Western Indian Ocean and in other tropical regions. Although this type of fishing generally indicates a destructive activity, little attention has been directed towards this category of fishery, a major knowledge gap and barrier to management. Methodology and Principal Findings: With the aim to capture geographic scales, fishing processes and social aspects the scuba diving fishery that operate out of Zanzibar was studied using interviews, discussions, participant observations and catch monitoring. The diving fishery was resilient to resource declines and had expanded to new species, new depths and new fishing grounds, sometimes operating approximately 250 km away from Zanzibar at depths down to 50 meters, as a result of depleted easy-access stock. The diving operations were embedded in a regional and global trade network, and its actors operated in a roving manner on multiple spatial levels, taking advantage of unfair patron-client relationships and of the insufficient management in Zanzibar. Conclusions and Significance: This study illustrates that roving dynamics in fisheries, which have been predominantly addressed on a global scale, also take place at a considerably smaller spatial scale. Importantly, while proposed management of the sea cucumber fishery is often generic to a simplified fishery situation, this study illustrates

Physical characteristics and selection criteria of Pare white goats in Kilimanjaro and Manyara districts, Tanzania

Tanzania Journal of Agricultural Sciences (2018) Vol. 17 No. 2, 46-53The study was conducted in semi-arid areas of Kilimanjaro and Manyara districts Tanzania to describe the phenotypic attributes, selection preferences and criteria employed by the Pare White Goats (PWG) keepers. A total of 280 does and 140 bucks were measured for live body weight, linear and other morphometric characters. The general linear model (GLM) procedure (SAS, 2002) was used to analyse metric and scored parameters. The bucks were significantly (P<0.001) heavier (33.2±0.5kg) than does (30.4 ± 0.2kg). The heart girth, body length, wither height and rump height were 72.5±0.2, 64.4±0.2, 64.3±0.2 and 64.3±0.2 for females and 75.0±0.4, 66.1±0.4, 67.2±0.3, 67.0±0.3cm for males. Furthermore, the result showed that PWG are predominantly white, with long legs. The percentage of goats with wattles, beards and horns were 33.1, 38.1 and 84.5% respectively. Most of the goats (81.0%) had their ears held horizontally, while 82.4% had straight face and 76.2% of the goats had straight short hairs. Farmers do prefer the PWG because of their ability to deposit fats and high adaptability to semi- arid areas. Thus, the strain can be exploited through selective breeding for hot tropical environments

Properties and Subcellular Localization of Myocardial Fatty Acyl-coenzyme A Oxidase

The properties and subcellular localization of fatty acyl-CoA oxidase (FAO) were studied in rat heart homogenates. After differential centrifugation, FAO was sedimentable and enriched in a “light-mitochondrial” fraction. FAO had a pH optimum of 8–9. Among straight-chain, saturated fatty acyl-CoAs, the enzyme showed a marked preference for medium chain substrates (C12 \u3e C10 = C8 \u3e C16 = C14 \u3e C6) over a concentration range up to 100 µM. No activity was observed with C4-CoA. The apparent Michaelis constant (Km) for C12-CoA was 5-10 µM. After removal of nuclei by low-speed centrifugation, combined subcellular particle preparations were obtained by high-speed centrifugation and layered on linear density gradients of metrizamide. After density equilibration, FAO showed a symmetric distribution centered at ρ = 1.16–1.18, like that of the enzyme catalase, a marker for microperoxisomes. In contrast, enzyme markers for mitochondria, lysosomes, sarcolemma, and sarcoplasmic reticulum were recovered in low-density regions of the gradient. These results provide a direct demonstration of fatty acyl-CoA oxidase in cardiac tissue and its association with microperoxisomes

Fluorometric Assay for Rat Liver Peroxisomal Fatty Acyl-Coenzyme A Oxidase Activity

These studies report the development of a simple, specific, and highly sensitive fluorometric assay for rat liver peroxisomal fatty acyl-CoA oxidase activity. In this in vitro procedure fatty acyl-CoA-dependent H2O2 production was coupled in a peroxidase-catalyzed reaction to the oxidation of scopoletin (6-methoxy-7-hydroxycoumarin), a highly fluorescent compound, to a nonfluorescent product. Enzyme-catalyzed reaction rates as low as 5 pmol of H2O2 produced per minute could readily be detected. The reaction was studied in liver homogenates from normal rats with respect to absolute activity, time course, protein concentration dependence, substrate concentration dependence, pH optimum, substrate specificity, and cofactor requirements. The properties of the enzyme activity as assessed by the fluorometric assay agree well with those determined by other investigators using other assay methods. After subcellular fractionation of liver homogenates by differential centrifugation, the fatty acyl-CoA oxidase activity distributed like known peroxisomal marker enzymes. These results demonstrate that the fluorometric assay of fatty acyl-CoA oxidase should be useful in studying the distribution, properties, and subcellular localization of the enzyme, particularly in enzyme sources of low activity or in situations when only small amounts of material are available

Fluorometric Assay for Rat Liver Peroxisomal Fatty Acyl-Coenzyme A Oxidase Activity

These studies report the development of a simple, specific, and highly sensitive fluorometric assay for rat liver peroxisomal fatty acyl-CoA oxidase activity. In this in vitro procedure fatty acyl-CoA-dependent H2O2 production was coupled in a peroxidase-catalyzed reaction to the oxidation of scopoletin (6-methoxy-7-hydroxycoumarin), a highly fluorescent compound, to a nonfluorescent product. Enzyme-catalyzed reaction rates as low as 5 pmol of H2O2 produced per minute could readily be detected. The reaction was studied in liver homogenates from normal rats with respect to absolute activity, time course, protein concentration dependence, substrate concentration dependence, pH optimum, substrate specificity, and cofactor requirements. The properties of the enzyme activity as assessed by the fluorometric assay agree well with those determined by other investigators using other assay methods. After subcellular fractionation of liver homogenates by differential centrifugation, the fatty acyl-CoA oxidase activity distributed like known peroxisomal marker enzymes. These results demonstrate that the fluorometric assay of fatty acyl-CoA oxidase should be useful in studying the distribution, properties, and subcellular localization of the enzyme, particularly in enzyme sources of low activity or in situations when only small amounts of material are available

Properties and Subcellular Localization of Myocardial Fatty Acyl-coenzyme A Oxidase

The properties and subcellular localization of fatty acyl-CoA oxidase (FAO) were studied in rat heart homogenates. After differential centrifugation, FAO was sedimentable and enriched in a “light-mitochondrial” fraction. FAO had a pH optimum of 8–9. Among straight-chain, saturated fatty acyl-CoAs, the enzyme showed a marked preference for medium chain substrates (C12 \u3e C10 = C8 \u3e C16 = C14 \u3e C6) over a concentration range up to 100 µM. No activity was observed with C4-CoA. The apparent Michaelis constant (Km) for C12-CoA was 5-10 µM. After removal of nuclei by low-speed centrifugation, combined subcellular particle preparations were obtained by high-speed centrifugation and layered on linear density gradients of metrizamide. After density equilibration, FAO showed a symmetric distribution centered at ρ = 1.16–1.18, like that of the enzyme catalase, a marker for microperoxisomes. In contrast, enzyme markers for mitochondria, lysosomes, sarcolemma, and sarcoplasmic reticulum were recovered in low-density regions of the gradient. These results provide a direct demonstration of fatty acyl-CoA oxidase in cardiac tissue and its association with microperoxisomes

The impact of agricultural research on poverty and income distribution: A case study of selected on-farm research projects at Sokoine University of Agriculture, Morogoro, Tanzania

Tanzania Journal of Agricultural Sciences 2013, Vol. 12(1) : 1-9Improved technologies induce productivity growth that generates pro-poor improvement processes. However, improving welfare and equity is a difficult task. This study investigated whether interventions in agriculture benefit farmers who are more capable to derive sufficient gains than others using data from on-farm research projects in Tanzania.Data were collected during baseline and impact assessment studies using questionnaires. The distributions of income were assessed using coefficients of variation, Gini coefficients and Theil’s Tstatistic. Results show that the projects contributed to increase farm income through enhanced productivity and sales of products and these gains were equitably shared. To encourage adoption and sustainability of these interventions it is important to sensitize Local Government Authorities and Agricultural Sector Lead Ministries on these technologies to allow incorporation of research findings in development plans. Involvement of extension staff in research and demonstrations through farmers’ shows should also be encouraged to increase adoption

The impact of agricultural research on poverty and income distribution: A case study of selected on-farm research projects at Sokoine University of Agriculture, Morogoro, Tanzania

Tanzania Journal of Agricultural Sciences (2013) Accepted August, 2010 Vol. 12 No. 1, 1-9Improved technologies induce productivity growth that generates pro-poor improvement processes. However, improving welfare and equity is a difficult task. This study investigated whether interventions in agriculture benefit farmers who are more capable to derive sufficient gains than others using data from on-farm research projects in Tanzania.Data were collected during baseline and impact assessment studies using questionnaires. The distributions of income were assessed using coefficients of variation, Gini coefficients and Theil’s Tstatistic. Results show that the projects contributed to increase farm income through enhanced productivity and sales of products and these gains were equitably shared. To encourage adoption and sustainability of these interventions it is important to sensitize Local Government Authorities and Agricultural Sector Lead Ministries on these technologies to allow incorporation of research findings in development plans. Involvement of extension staff in research and demonstrations through farmers’ shows should also be encouraged to increase adoption

The capacity of on-farm research in reducing poverty: Experiences from twenty seven projects in Tanzania

Tanzania J.Agric.Sc. (2007) Vol. 8 No.2, 103 -114 Accepted May, 2008Poverty can be categorized into income poverty and non-income poverty. At the smallscale Jarmers level income poverty results Jrom low productivity oj agricultural enterprises. hence low sales oj products. On the other hand. non income poverty encompasses a wide range oj live phenomena, including level oj education, poor survival strategies, poor nutritional status. lack oj clean and saJe drinking water, poor social wellbeing, vulnerability , etc. In 2000/01 about 62% oj households in Tanzania succumbed to income poverty. While the Poverty Reduction Strategy Paper (PRSP) was silent on research as one oj the strategic approaches to reduce poverty in Tanzania, a study was conducted between 2001 and 2004 by Sokoine University oj Agriculture (SUA) in collaboration with the Agricultural Sector Lead Ministries (ASLMs) to evaluate the effectiveness oj onjarm research and development (R&D) approaches in bringing about poverty reduction amongst the smallholder Jarmers in the country. The study was based on 27 projects under Tanzania Agricultural Research Project Phase II (TARPII) managed by SUA (TARPII-SUA) conducted in the Eastern and Southern Highlands Zones oj country. By responding to a questionnaire. smallholder Jarmers evaluated technologies introduced through research. Results have shown that smallholder Jarmers' poverty could be signijkantly reduced by inb'oducing appropriate technologies. Thus. on average, participating Jarmers observed reductions in income poverty by the period oj this study. It is concluded that introduction oj technologies through onJarm research increases technology adoption and reduces income poverty