Effects of natural selection and gene conversion on the evolution of human glycophorins coding for MNS blood polymorphisms in malaria-endemic African populations

Malaria has been a very strong selection pressure in recent human evolution, particularly in Africa. Of the one million deaths per year due to malaria, more than 90% are in sub-Saharan Africa, a region with high levels of genetic variation and population substructure. However, there have been few studies of nucleotide variation at genetic loci that are relevant to malaria susceptibility across geographically and genetically diverse ethnic groups in Africa. Invasion of erythrocytes by Plasmodium falciparum parasites is central to the pathology of malaria. Glycophorin A (GYPA) and B (GYPB), which determine MN and Ss blood types, are two major receptors that are expressed on erythrocyte surfaces and interact with parasite ligands. We analyzed nucleotide diversity of the glycophorin gene family in 15 African populations with different levels of malaria exposure. High levels of nucleotide diversity and gene conversion were found at these genes. We observed divergent patterns of genetic variation between these duplicated genes and between different extracellular domains of GYPA. Specifically, we identified fixed adaptive changes at exons 3-4 of GYPA. By contrast, we observed an allele frequency spectrum skewed toward a significant excess of intermediate-frequency alleles at GYPA exon 2 in many populations; the degree of spectrum distortion is correlated with malaria exposure, possibly because of the joint effects of gene conversion and balancing selection. We also identified a haplotype causing three amino acid changes in the extracellular domain of glycophorin B. This haplotype might have evolved adaptively in five populations with high exposure to malaria

Toxicity studies in rats fed nature cure bitters

Graded doses of Nature Cure Bitters (NCB) were administered daily (100, 200 and 400 mg/kg p.o) to rats for 28 days and the effects on body weight, organ weight, clinical signs, gross pathology, haematology, histology and serum biochemical parameters were evaluated. The relative weights of the heart, liver and testes of treated rats were unaffected in contrast to a significant increase in the relative weights of the lungs, kidneys and spleen. The packed cell volume and haemoglobin concentrations were significantly reduced whereas total leucocyte counts and glucose levels were remarkably increased. A significant decrease in alkaline phosphatase occurred in all the groups but alanine aminotransferase and albumin levels were significantly elevated. NCB elicited hypo-cholesterolaemic effects in addition to lowering urea, uric acid, BUN and total protein concentrations. Histological findings did not reveal any treatment-related effects. The calculated therapeutic index was >37.5. These preliminary results suggest that NCB was not likely to produce severe toxicological effects on organ weights, haematological and biochemical indices when given at normal therapeutic doses. Key Words: Nature Cure Bitters, organ weight; pathology, haematology; serum biochemistry. African Journal of Biotechnology Vol.4(1) 2005: 72-7

The Genetic Structure and History of Africans and African Americans.

Africa is the source of all modern humans, but characterization of genetic variation and of relationships among populations across the continent has been enigmatic. We studied 121 African populations, four African American populations, and 60 non-African populations for patterns of variation at 1327 nuclear microsatellite and insertion/deletion markers. We identified 14 ancestral population clusters in Africa that correlate with self-described ethnicity and shared cultural and/or linguistic properties. We observed high levels of mixed ancestry in most populations, reflecting historical migration events across the continent. Our data also provide evidence for shared ancestry among geographically diverse hunter-gatherer populations (Khoesan speakers and Pygmies). The ancestry of African Americans is predominantly from Niger-Kordofanian (approximately 71%), European (approximately 13%), and other African (approximately 8%) populations, although admixture levels varied considerably among individuals. This study helps tease apart the complex evolutionary history of Africans and African Americans, aiding both anthropological and genetic epidemiologic studies

Status of national research bioethics committees in the WHO African region

BACKGROUND: The Regional Committee for Africa of the World Health Organization (WHO) in 2001 expressed concern that some health-related studies undertaken in the Region were not subjected to any form of ethics review. In 2003, the study reported in this paper was conducted to determine which Member country did not have a national research ethics committee (REC) with a view to guiding the WHO Regional Office in developing practical strategies for supporting those countries. METHODS: This is a descriptive study. The questionnaire was prepared and sent by diplomatic pouch to all the 46 Member States in the WHO African Region, through the WHO country representatives, for facilitation and follow up. The data were entered in Excel spreadsheet and subsequently exported to STATA for analysis. A Chi-Squared test (χ(2)) for independence was undertaken to test the relationship between presence/absence of Research Ethics Committee (REC) and selected individual socioeconomic and health variables. RESULTS: The main findings were as follows: the response rate was 61% (28/46); 64% (18/28) confirmed the existence of RECs; 36% (10/28) of the respondent countries did not have a REC (although 80% of them reported that they had in place an ad hoc ethical review mechanism); 85% (22/26) of the countries that responded to this question indicated that ethical approval of research proposals was, in principle, required; and although 59% of the countries that had a REC expected it to meet every month, only 44% of them reported that the REC actually met on a monthly basis. In the Chi-Squared test, only the average population in the group of countries with a REC was statistically different (at 5% level of significance) from that of the group of countries without a REC. CONCLUSION: In the current era of globalized biomedical research, good ethics stewardship demands that every country, irrespective of its level of economic development, should have in place a functional research ethics review system in order to protect the dignity, integrity and safety of its citizens who participate in research

Status of national health research systems in ten countries of the WHO African Region

BACKGROUND: The World Health Organization (WHO) Regional Committee for Africa, in 1998, passed a resolution (AFR/RC48/R4) which urged its Member States in the Region to develop national research policies and strategies and to build national health research capacities, particularly through resource allocation, training of senior officials, strengthening of research institutions and establishment of coordination mechanisms. The purpose of this study was to take stock of some aspects of national resources for health research in the countries of the Region; identify current constraints facing national health research systems; and propose the way forward. METHODS: A questionnaire was prepared and sent by pouch to all the 46 Member States in the WHO African Region through the WHO Country Representatives for facilitation and follow up. The health research focal person in each of the countries Ministry of Health (in consultation with other relevant health research bodies in the country) bore the responsibility for completing the questionnaire. The data were entered and analysed in Excel spreadsheet. RESULTS: The key findings were as follows: the response rate was 21.7% (10/46); three countries had a health research policy; one country reported that it had a law relating to health research; two countries had a strategic health research plan; three countries reported that they had a functional national health research system (NHRS); two countries confirmed the existence of a functional national health research management forum (NHRMF); six countries had a functional ethical review committee (ERC); five countries had a scientific review committee (SRC); five countries reported the existence of health institutions with institutional review committees (IRC); two countries had a health research programme; and three countries had a national health research institute (NHRI) and a faculty of health sciences in the national university that conducted health research. Four out of the ten countries reported that they had a budget line for health research in the Ministry of Health budget document. CONCLUSION: Governments of countries of the African Region, with the support of development partners, private sector and civil society, urgently need to improve the research policy environment by developing health research policies, strategic plans, legislations, programmes and rolling plans with the involvement of all stakeholders, e.g., relevant sectors, research organizations, communities, industry and donors. In a nutshell, development of high-performing national health research systems in the countries of the WHO African Region, though optional, is an imperative. It may be the only way of breaking free from the current vicious cycle of ill-health and poverty

Fetal Hemoglobin Inducers from the Natural World: A Novel Approach for Identification of Drugs for the Treatment of β-Thalassemia and Sickle-Cell Anemia

The objective of this review is to present examples of lead compounds identified from biological material (fungi, plant extracts and agro-industry material) and of possible interest in the field of a pharmacological approach to the therapy of β-thalassemia using molecules able to stimulate production of fetal hemoglobin (HbF) in adults. Concerning the employment of HbF inducers as potential drugs for pharmacological treatment of β-thalassemia, the following conclusions can be reached: (i) this therapeutic approach is reasonable, on the basis of the clinical parameters exhibited by hereditary persistence of fetal hemoglobin patients, (ii) clinical trials (even if still limited) employing HbF inducers were effective in ameliorating the symptoms of β-thalassemia patients, (iii) good correlation of in vivo and in vitro results of HbF synthesis and γ-globin mRNA accumulation indicates that in vitro testing might be predictive of in vivo responses and (iv) combined use of different inducers might be useful to maximize HbF, both in vitro and in vivo. In this review, we present three examples of HbF inducers from the natural world: (i) angelicin and linear psoralens, contained in plant extracts from Angelica arcangelica and Aegle marmelos, (ii) resveratrol, a polyphenol found in grapes and several plant extracts and (iii) rapamycin, isolated from Streptomyces hygroscopicus

Guidelines for evaluation of safety and efficacy of African traditional medicines

Meeting: Methodology Workshop on Medicinal Plants and Traditional Medicine, 5-7 December, 2005, Nairobi, K

Keynote address policies and directions for traditional medicine and medicinal plants: the way forward In the next decade

Keynote address on Policies and directions for traditional medicine and medicinal plants: the way forward in the next decade. Prof. Charles Wambebe, President, International biomedical research institute (IBRI), Abuja, Nigeria. At the 15th meeting of the Inter-African Expert Committee onAfrican Traditional Medicine and Medicinal Plants Arusha,tanzania: 15-17 January 2002 2001-2010: oau decade on African Traditional Medicin

Air Quality Levels and Health Risk Assessment of Particulate Matters in Abuja Municipal Area, Nigeria

This study focuses on assessing the health risk by particulate matter (PM) inhalation within the Abuja municipal area, Nigeria. Particulate matters (PM2.5 and PM10), HCHO and VOCs were collected by A handheld portable smart air quality detector BR-SMART-126. A hybrid single-particle Lagrangian integrated trajectory (HYSPLIT) model for backward trajectory was applied to tract the air flow (transportation) and potential sources. Health risk was estimated by comparing with the air quality index (AQI) stipulated by the World Health Organization (WHO). The result shows that the daily averaged concentrations of PM2.5 varied from 15.30 µg/m3 to 70.20 µg/m3. The top four most-polluted locations (Locations 10, 14, 17 and 18) of the twenty locations were found to be above the acceptable (25 µg/m3) AQI limit stipulated by WHO, which all fell far under the unhealthy AQI value index level. In general, business/commercial locations had the highest PM2.5 level followed by transport/market, offices/mixed use and residential. The results from the backwards trajectories show that the source of local particles for the four most-polluted locations is long-range air transport originating from the Atlantic Ocean. The results of the health-risk assessment implies that for PM2.5, the AQI varied from 73.2 to 280.8 in this assessment. Based on this, the population of workers within the business location are at health risk based on the relatively poor air quality in these areas—especially location 10 and 17. Based on these findings, it is recommended that the regulatory and enforcement agency needs to develop a more robust monitoring mechanism, regulations and enforcement. Furthermore, there is need for a national drive on renewable energy, clean energy for business/commercial district to help reduce fumes from generators and to form cleaner air initiatives in order to ensure a safe environment to live in as well as reduce particulate matters in the city