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 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

A comparative study: long and short term effect of a nutrition sensitive approach to delay the progression of HIV to AIDS among people living with HIV (PLWH) in Nigeria

Background: Malnutrition has a negative impact on optimal immune function, thus increasing susceptibility to morbidity and mortality among HIV positive patients. Evidence indicates that the prevalence of macro and micronutrient deficiencies (particularly magnesium, selenium, zinc, and vitamin C) has a negative impact on optimal immune function, through the progressive depletion of CD4 T-lymphocyte cells, which thereby increases susceptibility to morbidity and mortality among PLWH. Objective: To assess the short and long term effects of a nutrition sensitive intervention to delay the progression of human immune-deficiency virus (HIV) to AIDS among people living with HIV in Abuja, Nigeria. Methods: A randomized control trial was carried out on 400 PLWH (adult, male and female of different religious background) in Nigeria between January and December 2012. Out of these 400 participants, 100 were randomly selected for the pilot study, which took place over six months (January to June, 2012). The participants in the pilot study overlapped to form part of the scale-up participants (n 400) monitored from June to December 2012. The comparative effect of daily 354.92 kcal/d optimized meals consumed for six and twelve months was ascertained through the nutritional status and biochemical indices of the study participants (n=100 pilot interventions), who were and were not taking the intervention meal. The meal consisted of: Glycine max 50g (Soya bean); Pennisetum americanum 20g (Millet); Moringa oleifera 15g (Moringa); Daucus carota spp. sativa 15g (Carrot). Results: At the end of sixth month intervention, mean CD4 cell count (cell/mm3) for Pre-ART and ART Test groups increased by 6.31% and 12.12% respectively. Mean mid upper arm circumference (MUAC) for Pre-ART and ART Test groups increased by 2.72% and 2.52% within the same period (n 400). Comparatively, participants who overlapped from pilot to scale-up intervention (long term use, n 100) were assessed for 12 months. Mean CD4 cell count (cell/mm3) for Pre-ART and ART test groups increased by 2.21% and 12.14%. Mean MUAC for Pre-ART and ART test groups increased by 2.08% and 3.95% respectively. Moreover, student’s t-test analysis suggests a strong association between the intervention meal, MUAC, and CD4 count on long term use of optimized meal in the group of participants being treated with antiretroviral therapy (ART) (P<0.05). Conclusion: Although the achieved results take the form of specific technology, it suggests that a prolong consumption of the intervention meal will be suitable to sustain the gained improvements in the anthropometric and biochemical indices of PLWHIV in Nigeria

Survivability of Salmonella typhimurium L1388 and Salmonella enteritidis L1225 under stressful growth conditions

In an earlier study with Salmonella typhimurium L1388 (ST) and Salmonella enteritidis L1225 (SE) isolated from diseased chickens, we found that SE formed more biofilm than ST on abiotic surfaces in a time-dependent manner. Since the ability of salmonellae to survive extreme environment is related to their virulence, the present study examined the survival of Salmonella typhimurium L1388 and Salmonella nteritidis L1225 under the usual stresses that salmonellae encounter during their life cycle. This is with a view to understanding the strains’ stress tolerance that could be used to explain their virulence. Incubation at 37oC for various time periods was done for: i) stationary phase (SP) cells at pH 2.6; ii) log-phase (LP) cells at pH 4.0; log-phase or stationary phase cells in broth containing iii) hydrogen peroxide, iv) sodium chloride and v) ethanol; vi) stationary phase cells in Hank’s balanced salt solution (single strength) containing 10% human serum; and vii) prolong stationary phase cells. Stationary phase cells were also incubated at 52oC for 15 min. Surviving cells at the various incubation times were counted on trypticase soy agar (TSA) after appropriate dilution in saline and overnight incubation at 37oC. Growth iron-poor medium was determined by growing a single bacterial colony in Medium A with shaking at 37oC or 40oC for 24 h. Statistics was done by one-way analysis-of-variance (ANOVA) at P = 0.05. Differences in the survival of ST and SE were insignificant (p>0.05) in acid pH at both pH 4.0 (p = 0.3783) and pH 2.6 (p = 0.4711); at high salinity for log-phase (p = 0.1416) and stationary phase (p = 0.1816) cells; in ethanol (p = 0.5984), human serum (p = 0.8139), prolonged stationary phase (p = 0.3506); and under heat (p = 0.5766). SE was significantly (p<0.05; p = 0.0031) more tolerant to oxidative-killing by hydrogen peroxide. Culturable growth of the ST and SE in an iron-poor medium A revealed insignificant differences at 37oC (p = 0.8381) but marginally significant at 40oC (p = 0.0508). Thus, with the exception of survival in hydrogen peroxide, SE had similar response pattern with ST to the usual stresses that salmonellae encounter during their life cycle, despite the former’s preferential ability to form biofilm on abiotic surfaces. The relationship between the observed enhanced ability of SE to survive in hydrogen peroxide and virulence need to be investigated in subsequent study

Analysis of the responsed of guinea pig ileum to the root extract of Calliandra protoricensis

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Does Niprisan&#3598; Retard the Evolution of Sickle Cell Retinopathy?

Objective: To investigate the efficacy of Niprisan®, an antisickling agent, in the management of sickle cell retinopathy. Methods: The study was designed as a phase IIb double-blind, placebo-controlled crossover trial. Eighty-eight patients aged between 5 and 36 years (mean 15.3 years) were randomized into 2 treatment groups. One group received Niprisan® at a dose of 12mg/kg per os per day and the other group a placebo in a similarly encapsulated form, for an initial period of six months. After a crossover without interval washout, the treatment was continued for a further six months. Ocular signs, including jaundice and corkscrew/comma sign in the anterior segment, and signs of non-proliferative, pre-proliferative and proliferative retinopathy in the posterior segment, were assessed with a view to identifying deteriorations within these parameters. Results: A within-person analysis provided no evidence that Niprisan® reduced the risk of anterior segment deterioration (odds ratio = 0.91; 95% c.i. 0.35, 2.36; p=1.00). Thirteen individuals contributed to the posterior segment analysis, 3 of whom experienced deterioration whilst receiving Niprisan® (odds ratio = 0.30, 95% c.i. 0.05-1.17; p=0.09; Mcnemar chi2 = 3.17, p=0.05). Conclusion: This study provides evidence that Niprisan® may reduce substantially the risk of posterior segment deterioration. [Nig. J. Ophthalmology Vol.11(1) 2003: 34-41