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Dandara C.,University of Cape Town | Huzair F.,University of Edinburgh | Borda-Rodriguez A.,Open University Milton Keynes | Chirikure S.,University of Cape Town | And 4 more authors.
OMICS A Journal of Integrative Biology | Year: 2014

Interest in genomics research in African populations is experiencing exponential growth. This enthusiasm stems in part from the recognition that the genomic diversity of African populations is a window of opportunity for innovations in postgenomics medicine, ecology, and evolutionary biology. The recently launched H3Africa initiative, for example, captures the energy and momentum of this interest. This interdisciplinary socio-technical analysis highlights the challenges that have beset previous genomics research activities in Africa, and looking ahead, suggests constructive ways H3Africa and similar large scale science efforts could usefully chart a new era of genomics and life sciences research in Africa that is locally productive and globally competitive. As independent African scholars and social scientists, we propose that any serious global omics science effort, including H3Africa, aiming to build genomics research capacity and capability in Africa, needs to fund the establishment of biobanks and the genomic analyses platforms within Africa. Equally they need to prioritize community engagement and bioinformatics capability and the training of African scientists on these platforms. Historically, the financial, technological, and skills imbalance between Africa and developed countries has created exploitative frameworks of collaboration where African researchers have become merely facilitators of Western funded and conceived research agendas involving offshore expatriation of samples. Not surprisingly, very little funding was allocated to infrastructure and human capital development in the past. Moving forward, capacity building should materialize throughout the entire knowledge co-production trajectory: idea generation (e.g., brainstorming workshops for innovative hypotheses development by African scientists), data generation (e.g., genome sequencing), and high-throughput data analysis and contextualization. Additionally, building skills for political science scholarship that questions the unchecked assumptions of the innovation performers be they funders, scientists, and social scientists, would enable collective innovation that is truly sustainable, ethical, and robust. © 2014, Mary Ann Liebert, Inc.

Ongarora D.S.B.,University of Cape Town | Gut J.,University of California at San Francisco | Rosenthal P.J.,University of California at San Francisco | Masimirembwa C.M.,Harare Institute of Technology | Chibale K.,University of Cape Town
Bioorganic and Medicinal Chemistry Letters | Year: 2012

The synthesis and evaluation of antiplasmodial activity of benzothiazole, benzimidazole, benzoxazole and pyridine analogues of amodiaquine is hereby reported. Benzothiazole and benzoxazole analogues with a protonatable tertiary nitrogen atom possessed excellent activity against the W2 and K1 chloroquine resistant strains of Plasmodium falciparum, with IC50s ranging from 7 to 22 nM. © 2012 Elsevier Ltd. All rights reserved.

Ding J.,Jiangnan University | Cao Y.,Jiangnan University | Mpofu E.,Jiangnan University | Mpofu E.,Harare Institute of Technology | Shi Z.,Jiangnan University
Chemical Engineering Research and Design | Year: 2012

In industrial glutamate fermentation by biotin-auxotroph Corynebacterium glutamicum, biotin content variation in corn slurry greatly affects fermentation performance. To maintain the fermentation stability, a hybrid support vector machine (SVM) and fuzzy reasoning based fault diagnosis and rescue system was developed. The system uses SVM outputs as the inputs of the fuzzy reasoning classifier having a couple of production rules and condition membership functions related with SVM outputs, to categorize multiple faults. The effectiveness of the proposed system was verified in a normal fermentation run and two abnormal runs with different biotin initial-content faults with the aid of using on-line measurable data such as ammonia consumption rate and CO 2 evolution rate. The results indicated that the proposed faults-diagnosis system could cluster multiple fermentation faults quickly, accurately and stably, and faults and their types could be identified at the earliest fermentation stage. Based on the diagnosis results, the proposed system was further applied for real fault-rescue in two fermentations with different biotin initial-content faults. In both cases, by immediately taking relevant rescue measures after identifying the faults and their types, glutamate fermentations with initial faults were restored to normal, and final glutamate concentrations reached a normal level of 75-80g/L at 34h. © 2012 The Institution of Chemical Engineers.

Njuguna N.M.,University of Cape Town | Masimirembwa C.,Harare Institute of Technology | Chibale K.,University of Cape Town
Journal of Natural Products | Year: 2012

Toxicity of natural products arising from their metabolic biotransformation into reactive chemical intermediates is an important reason for high attrition rates in early drug discovery efforts. Screening promising natural products for their likelihood to form such metabolites is therefore an important step in identifying potential liabilities in the drug development process. However, such screening is complicated by the need to have test methods that are sensitive, reliable, accurate, efficient, and cost-effective enough to allow for routine identification and characterization of the reactive metabolites. These metabolites are typically formed in minute quantities, usually through minor metabolic pathways, and, due to their highly reactive and therefore transient chemical nature, pose considerable analytical challenges in attempts to determine their properties. Understanding the formation of reactive metabolites may be used as the basis for synthetic chemical modification of parent natural products aimed at bypassing such harmful bioactivation. This paper highlights the general principles and protocols commonly used to predict and study the formation of reactive metabolites in vitro and how the data obtained from such studies can be used in the development of safer drugs from natural products. © 2012 The American Chemical Society and American Society of Pharmacognosy.

Maimbo M.,RIKEN | Maimbo M.,Harare Institute of Technology | Kiyotani K.,RIKEN | Mushiroda T.,RIKEN | And 3 more authors.
European Journal of Clinical Pharmacology | Year: 2012

Objective: Efavirenz, an antiretroviral medicine, is extensively metabolized by cytochrome P450 2B6 (CYP2B6), UDP-glucuronosyltransferase 2B7 (UGT2B7), and CYP2A6. In this study, we investigated the association of single nucleotide polymorphisms (SNPs) in these genes with plasma efavirenz levels in Zimbabwean human immunodeficiency virus (HIV)-positive patients treated with efavirenz. Methods: The exon regions of the CYP2B6, CYP2A6, and UGT2B7 genes were re-sequenced in 49 HIV-infected Zimbabwean patients treated with a combination therapy including efavirenz. Associations of SNPs in these three genes with efavirenz plasma concentrations 11-16 h after the administration of treatment were evaluated. Results: Eight patients carrying CYP2B6*6/ *18 showed the highest plasma efavirenz levels, with a fourfold higher concentration than patients who carried CYP2B6*1/*1. Patients with CYP2B6*6/*6 also showed higher efavirenz plasma concentrations than those with CYP2B6*1/*1. Among the 17 and 12 SNPs identified in CYP2A6 and UGT2B7, respectively, no SNP showed a significant association with the plasma efavirenz concentration. Conclusion: Although based on only a limited number of subjects, our results suggest that the CYP2B6*6 and CYP2B6*18 alleles should affect hepatic metabolic activity and elevate the systemic circulation level of efavirenz, which may lead to toxicity in Zimbabwean HIV patients. © 2011 Springer-Verlag.

Fashu S.,Harare Institute of Technology | Khan R.,Zhejiang University
Transactions of the Institute of Metal Finishing | Year: 2016

Ternary Zn–Ni–Sn alloy coatings with a range of compositions were potentiostatically electrodeposited on steel substrates from a deep eutectic solvent-based electrolyte. The effect of electrodeposition potential on the morphology, chemical and phase compositions, and corrosion behaviour of the deposits was analysed. The co-deposition mechanism of Zn–Ni–Sn alloys was found to be normal whereby increasing the electrodeposition potential enhanced the ternary alloy Zn content (active element) and greatly suppressed the alloy Sn and Ni content (noble elements). The X-ray diffraction phase analyses showed that Ni in the deposits exists in the form of metal compounds including β-Ni3Sn2 as well as γ-NiZn3. The improved corrosion resistance observed in all ternary alloys was attributed to their compact morphology, phase content and chemical composition. Comparison of corrosion performances shows that ternary Zn–Ni–Sn alloys are superior for sacrificial corrosion protection of steel metallic substrates compared to binary Zn–Sn and Zn–Ni alloys. © 2016 Institute of Materials Finishing.

Chiteka K.,Harare Institute of Technology | Enweremadu C.C.,University of South Africa
Journal of Cleaner Production | Year: 2016

Reliable knowledge of solar radiation is a requirement for informed design and deployment planning of solar energy delivery systems. This study presents the artificial neural network approach for predicting global horizontal irradiation for major locations in Zimbabwe. The prediction of global horizontal irradiation was carried out using geographical data of altitude, latitude and longitude and meteorological data of humidity, pressure, clearness index and average temperature. A neural network with an input layer that has seven inputs was used together with one hidden layer and an output layer with one output. A network with 10 neurons and a tansig transfer function in both the input and output layers was found to be the best predictive model of all of the models evaluated. This network achieved a coefficient of determination of 99.894%, a root mean square error of 0.223 kWh/m2/day, a mean absolute error of 0.17 kWh/m2/day and a mean absolute percentage error of 2.56%. The study shows that the artificial neural network model can also be used to predict global horizontal irradiation the day before and the day after with mean absolute percentage errors of 5.9% and 7.6%, respectively. Statistical analysis of the results indicates that the clearness index, temperature and humidity had significant contributions of 19%, 18% and 17%, respectively, to the general performance of the artificial neural network model. An artificial neural network model developed using the clearness index alone as the input parameter gave a mean absolute percentage error of 5%. It may, therefore, be concluded that the clearness index could be used as the only parameter to predict global horizontal irradiation. © 2016 Elsevier Ltd

Masimirembwa C.,Harare Institute of Technology | Hasler J.A.,Harare Institute of Technology
CPT: Pharmacometrics and Systems Pharmacology | Year: 2013

The modern human appeared in Africa around 200,000 years ago with subsequent later migrations to populate Europe, Asia, and North America.1 As humans adapted to various diets, diseases, climates, and so on, inherited traits emerged that gave rise to distinct population groups with physical and physiological differences, including the response to xenobiotic challenges (Figure 1). This Perspective highlights the interpopulation differences in response to drugs focusing on Africa and implications for global pharmacometric studies. ©2013 ASCPT All rights reserved 2163-8306/12.

Thelingwani R.,Harare Institute of Technology | Masimirembwa C.,Harare Institute of Technology
Current Drug Metabolism | Year: 2014

The safety and efficacy of herbal medicines remain major issues of concern especially in the developing world where the use is high. The World Health Organisation estimates up to 80% of the population in Africa relies on herbal medicines for treatment of many diseases. Minimum safety evaluations need to be done for both the herbal and conventional drugs, in particular when there is a high likelihood of co-administration. This is particularly important in Africa where there is increased access to antiretrovirals in the treatment of HIV/AIDS, which are being used in a population background characterized by rampant use of herbal medicines. Many techniques used in the discovery and evaluation of conventional drugs can be adapted to herbal medicines. Such evaluations will add value to herbal medicines as doctors and patients will be better informed on which drugs and herbal medicines to take or not take together. This can also lead to the adoption of guidelines by regulatory agents such as the European Medicines Agency (EMA), Food and Drug Administration (FDA) and governmental agencies controlling the use of medicines. Of current interest is the evaluation of drug-herb interactions (DHI) involving the absorption, distribution, metabolism and excretion (ADME) of medicines where there is a promising possibility to adopt the current FDA and EMA guidelines on the evaluation of herbal medicines for drug-drug interactions (DDI). In this review we demonstrate progress made so far in DHI and point to possible future developments that will contribute to the safe use of herbal medicines. © 2014 Bentham Science Publishers.

Ericsson T.,Gothenburg University | Masimirembwa C.,Harare Institute of Technology | Abelo A.,Gothenburg University | Ashton M.,Gothenburg University
Drug Metabolism Letters | Year: 2013

Artemisinin-based combination therapy (ACT) is the recommended treatment of uncomplicated P.falciparum malaria by the World Health Organisation (WHO). Some artemisinin compounds and anti-retroviral drugs have been shown to be metabolized by CYP2B6. In the African clinical settings, the likelihood of co-administration of ACTs and antiretroviral drugs is higher than elsewhere, posing the risk of drug-drug interactions (DDIs). This study aimed to investigate whether artemisinin compounds inhibit CYP2B6 activity in vitro using recombinant CYP2B6 (rCYP2B6) and human liver microsomes (HLM). Values for IC50 and Ki were determined by kinetic analyses using non-linear regression. In vitro to in vivo extrapolations of the likelihood of DDIs where done using a static [I]/Ki approach. Artemisinin and artemether were shown to inhibit CYP2B6 in vitro through a partial mixed type of inhibition, while dihydroartemisinin did not inhibit the enzymatic activity. IC50 values for artemisinin were 9.5 and 9.1 μM for rCYP2B6 and HLM, respectively, after 30 min of incubation. Corresponding values for artemether were 7.5 and 5.4 μM. Artemisinin did not show any time-dependency or requirement of NADPH in its mechanism, indicating a reversible mode of inhibition. Based on the [I]/Ki approach using rCYP2B6, the risk of DDIs for artemisinin was indicated to be medium to high, while artemether had a low risk. The findings indicate a potential but moderate risk of DDIs in the co-administration of artemisinin or artemether with efavirenz in the co-treatment of malaria and HIV/AIDS. © 2013 Bentham Science Publishers.

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