Hepatitis C virus in Zimbabwe

A research article on the prevalence of the Hepatitis C virus in ZimbabweLiver disease is an important cause of morbidity and mortality in Zimbabwe, accounting for more than six per cent of the deaths in three medical wards of Harare Central Hospital (IT Gangaidzo, 1994, unpublished observations). In western countries, HCV infection is the most common cause of chronic viral hepatitis and ranks a slight second below chronic alcoholism as a cause of cirrhosis, liver failure and hepatom

Engulfment and cell motility 1 (ELMO1) and apolipoprotein A1 (APOA1) as candidate genes for sickle cell nephropathy

Sickle cell disease (SCD) and apolipoprotein L1 (APOL1) G1/G2 variants increase chronic kidney disease (CKD) risk in African Americans by poorly understood mechanisms. We applied bioinformatics to identify new candidate genes associated with SCD-related CKD. An interaction network demonstrated APOA1 connecting haemoglobin subunit β (HBB) and APOL1 with 36 other candidate genes. Gene expression revealed upregulation of engulfment and cell motility 1 (ELMO1) and downregulation of APOA1 in the kidney cortex of SCD versus non-SCD mice. Analysis of candidate genes identified ELMO1 rs10951509 to be associated with albuminuria and APOA1 rs11216132 with haemoglobinuria in patients with SCD. A bioinformatic approach highlights ELMO1 and APOA1 as potentially associated with SCD nephropathy

Rare genetic variants explain missing heritability in smoking

Common genetic variants explain less variation in complex phenotypes than inferred from family-based studies, and there is a debate on the source of this ‘missing heritability’. We investigated the contribution of rare genetic variants to tobacco use with whole-genome sequences from up to 26,257 unrelated individuals of European ancestries and 11,743 individuals of African ancestries. Across four smoking traits, single-nucleotide-polymorphism-based heritability (hSNP2) was estimated from 0.13 to 0.28 (s.e., 0.10–0.13) in European ancestries, with 35–74% of it attributable to rare variants with minor allele frequencies between 0.01% and 1%. These heritability estimates are 1.5–4 times higher than past estimates based on common variants alone and accounted for 60% to 100% of our pedigree-based estimates of narrow-sense heritability (hped2, 0.18–0.34). In the African ancestry samples, hSNP2 was estimated from 0.03 to 0.33 (s.e., 0.09–0.14) across the four smoking traits. These results suggest that rare variants are important contributors to the heritability of smoking

Aminothiol multidentate chelators against Chagas disease

Three compounds of an aminothiol family of iron chelators were examined for activity against trypomastigote (human) and epimastigote (vector) forms of Trypanosoma cruzi: tetraethyl and tetramethyl derivatives of ethane-1,2- bis (N-1-amino-3-ethyl butyl-3-thiol) (BAT-TE and BAT-TM) and N\u27,N\u27,N\u27-tris- (2-methyl-2-mercaptopriopyl)-1.4.7-triazacyclonane (TAT). BAT-TE at 270 μM completely arrested the growth of trypomastigote forms in mouse blood stored at 4°C for 24 h (IC50 67.7 ± 7 μM), while BAT-TM arrested growth at 630 μM (IC50 158 ± 17 μM) and TAT at concentrations \u3e800 μM (IC50 415 ± 55 μM). In T. cruzi-infected mice, BAT-TE and BAT-TM had no antitrypanosomal activity in doses up to 200 mg/kg, whether the route of administration was intraperitoneal or oral, and TAT was not tested due to insufficient quantity. TAT had an IC50 of 52 ± 7 μM against the epimastigote forms while BAT-TM and BAT-TE were inhibitory only at concentrations \u3e250 μM. The trypanocidal activity of BAT derivatives in blood stored at 4°C makes these compounds potential candidates for the purpose of clearing donated blood of trypomastigotes. (C) 2000 Academic Press

Hyperfiltration is Associated with the Development of Microalbuminuria in Patients 1 with Sickle Cell Anemia

Non

Dietary iron overload in southern African rural blacks

A survey conducted in rural southern African black subjects indicated that dietary iron overload remains a major health problem. A full blood count, erythrocyte sedimentation rate, serum concentrations of iron, total iron-binding capacity, ferritin, C-reactive protein (CRP), 1'-glutamyltransferase (GGn and serological screening for hepatitis B and human immunodeficiency virus (HIV) infections were carried out in 370 subjects (214 inpatients and 156 ambulatory Mozambican refugees). The fact that the geometric mean (SD range) serum ferritin concentration was much higher in the male hospital patients than in subjects living in the commpnity [1 581 ug/l (421 - 5944 ug/l) and 448 ug/l (103 - 1945 ug/l) respectively] suggested that dietary iron overload was not the only factor raising the serum ferritin concentration. The major additional factor appeared to be inflammation, since the geometric mean (SO range) serum CRP was significantly higher in male hospital patients [21 mg/l (8 - 53 mg/l)] than in subjects in the community [3 mg/l (1 - 5 mg)]. Alcohol ingestion, as judged by history and by serum GGT concentrations, was also associated with significantly raised serum ferritin concentrations. This finding was ascribed to the fact that traditional brews are not only associated with alcoholinduced hepatic damage but are also a very rich source of highly bio-available iron. The role of iron overload in the genesis of the raised serum ferritin concentrations are confirmed in the diagnostic liver biopsy study. The majority of biopsies showed heavy siderosis, with varying degrees of hepatic damage. No subject tested positive for HIV antibodies, while the hepatitis B infection rate was high (± 70%) in both hospital and community subjects, with a surface antigen carrier rate of roughly 10%

Comparison of Patients from Nigeria and U.S.A. Highlights Modifiable Risk Factors for Sickle Cell Complications

To identify factors that affect manifestations of sickle cell anemia (SCA), we compared patients 11-30 years of age from University of Ibadan, Nigeria (n=214) and University of Illinois at Chicago, U.S.A. (n=209). Paralleling findings in the general populations of the two countries, Chicago patients were more often overweight or obese defined by CDC Guidelines (Age<18: 6% vs. 3%, P=0.02; Age≥18: 25% vs. 3%, P<0.0001) and more often had elevated blood pressure defined by NHLBI Guidelines (Age<18: 16% vs. 3%, P=0.02; Age≥18: 47% vs. 17%, P<0.0001). Ibadan patients less often had received pneumococcal vaccination (Age<18: 0% vs. 88%, P<0.0001; Age≥18: 1% vs. 91%, P<0.0001) or hydroxyurea therapy (Age<18: 7% vs. 44%, P<0.0001; Age≥18: 3% vs. 46%, P<0.0001). Consistent with lower rates of elevated blood pressure and increased body mass index (BMI), stroke history was less frequent in Ibadan patients ≥ 18 years old (2% vs. 24%, P<0.0001). Furthermore, in combined analyses, systolic and diastolic blood pressure directly correlated with BMI, and elevated weight status independently associated with history of stroke (OR 2.7, P=0.019). In conclusion, our findings are consistent with the possibility that higher values for BMI and blood pressure in Chicago SCA patients may contribute to an increased risk of stroke and highlights the need for measures to reduce these risk factors. On the other hand, in Ibadan patients, lower pneumococcal vaccination and hydroxyurea therapy rates highlight the need for more improved vaccination coverage and for studies to define the role of hydroxyurea therapy in Africa