Vitellogenin induction and reduced fecundity in zebrafish exposed to effluents from the City of Bulawayo, Zimbabwe.

Industrial and municipal effluents regularly pollute water bodies and cause various toxic effects to aquatic life. Because of the diverse nature of industrial processes and domestic products, urban effluents are often tainted with various anthropogenic endocrine disrupting chemicals that may interfere with the reproductive physiology of aquatic fauna. In this study, we tested effluents from the City of Bulawayo for the presence of estrogenic endocrine disrupting chemicals and their effects on fish gonads and fecundity. Effluents were collected from two sewage treatment plants (STPs), which receive largest volume of industrial effluents from the City, and from a textile factory. Male and female zebrafish (Danio rerio) were exposed to effluents and analyzed for vitellogenin induction, gonad alterations, and fertility. Male zebrafish exposed to effluent from Thorngrove STP had significantly higher (p ≤ 0.05) vitellogenin compared to control. Textile effluent caused adverse gonad alterations such as oocyte atresia (females) and increased proportion of spermatogonia (males) which could lead to reduced fertility. Textile effluent (5% v/v) and Thorngrove effluent also caused a decline in fertilization success of breeding groups of zebrafish. The results of this study show the potential effects of effluent pollution and the occurrence of EDCs in developing countries. This underscores the need to effectively prevent pollution of environmental water bodies from industrial and municipal sewage treatment plant effluents. We recommend a follow-up study to monitor the effects of the effluents on feral fish in effluent polluted downstream dams of Bulawayo.

Strengthening research governance for sustainable research: experiences from three Zimbabwean universities.

A robust research system requires a robust governance framework. As part of the Medical Education Partnership Initiative, three Zimbabwean universities partnered with two U.S. universities in a project to strengthen research governance in the Zimbabwean universities. The project aimed at (1) developing research policies, (2) strengthening central research management offices, (3) developing a research administration curriculum, and (4) enhancing awareness about the role and relevance of research administration in other universities and research institutions in Zimbabwe. Through the efforts of the partners, a generic research policy was developed and successfully adapted by the institutions. A curriculum was drafted, and module development experts are helping to finalize the curriculum to meet university requirements for accreditation of training research administrators. The Association of Research Managers of Zimbabwe was established to promote information sharing and professionalize research administration. The consortium approach enabled rapid and smooth development and adoption of research policies in the institutions. It also helped researchers and managers accept research administration as an essential structure and function. The experiences and lessons learned are reported here to benefit other institutions and consortia.

Inhibition of glutathione S-transferases by antimalarial drugs possible implications for circumventing anticancer drug resistance.

A strategy to overcome multidrug resistance in cancer cells involves treatment with a combination of the antineoplastic agent and a chemomodulator that inhibits the activity of the resistance-causing protein. The aim of our study was to investigate the effects of antimalarial drugs on human recombinant glutathione S-transferase (GSTs) activity in the context of searching for effective and clinically acceptable inhibitors of these enzymes. Human recombinant GSTs heterologously expressed in Escherichia coli were used for inhibition studies. GST A1-1 activity was inhibited by artemisinin with an IC(50) of 6 microM, whilst GST M1-1 was inhibited by quinidine and its diastereoisomer quinine with IC(50)s of 12 microM and 17 microM, respectively. GST M3-3 was inhibited by tetracycline only with an IC(50) of 47 microM. GST P1-1 was the most susceptible enzyme to inhibition by antimalarials with IC(50) values of 1, 2, 1, 4, and 13 microM for pyrimethamine, artemisinin, quinidine, quinine and tetracycline, respectively. The IC(50) values obtained for artemisinin, quinine, quinidine and tetracycline are below peak plasma concentrations obtained during therapy of malaria with these drugs. It seems likely, therefore, that GSTs may be inhibited in vivo at doses normally used in clinical practice. Using the substrate ethacrynic acid, a diuretic drug also used as a modulator to overcome drug resistance in tumour cells, GST P1-1 activity was inhibited by tetracycline, quinine, pyrimethamine and quinidine with IC(50) values of 18, 27, 45 and 70 microM, respectively. The ubiquitous expression of GSTs in different malignancies suggests that the addition of nontoxic reversing agents such as antimalarials could enhance the efficacy of a variety of alkylating agents.