ORCID Profile
0000-0002-7879-1776
Current Organisation
North-West University
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Publisher: Oxford University Press (OUP)
Date: 11-2009
DOI: 10.1038/AJH.2009.158
Abstract: Sub-Saharan Africans face an increasing burden of hypertension and related cardiac and cerebrovascular morbidity and mortality, making the identification of factors leading to early vascular abnormalities imperative. We investigated the possible influence of the antioxidant glutathione (GSH) on early subclinical atherosclerosis in 63 hypertensive (aged 45.2 years) and 34 normotensive (aged 38.9 years P < 0.001) nondiabetic African men. We measured ambulatory daytime systolic and diastolic blood pressure (SBP, DBP) as well as daytime mean arterial pressure (MAP), carotid intima-media thickness (CIMT), and calculated the cross-sectional wall area. We determined the reduced form of GSH in whole blood and blood glucose in serum. Blood glucose (110 vs. 92 mg/dl P < 0.001) and CIMT (0.75 vs. 0.61 mm P < 0.001) were higher in hypertensives compared to normotensives. No significant difference existed for GSH. Associations in normotensives suggested the hypotensive effect of GSH after single (SBP: r = -0.35, P < or = 0.05 DBP: r = -0.37, P < or = 0.05 MAP: r = -0.38, P < or = 0.05) and multiple (SBP: B = -0.015, P < 0.05 DBP: B = -0.011, P < 0.05 MAP: B = -0.012, P < 0.05) regression analyses. In hypertensives, CIMT (B = -0.00027, P < 0.01) and cross-sectional wall area (CSWA) (B = -0.0066, P < 0.05) correlated negatively with GSH. These findings were consistent after excluding 10 human immunodeficiency virus (HIV)-positive hypertensive subjects. In hypertensive African men, CIMT is negatively associated with GSH, suggesting a possible contributory role of attenuated GSH levels in the development of subclinical atherosclerosis.
Publisher: Springer Science and Business Media LLC
Date: 27-01-2011
DOI: 10.1038/JHH.2010.134
Abstract: Many mechanisms, including oxidative stress, contribute to hypertension. This study investigated the possible associations between oxidative stress, blood pressure and arterial stiffness in black South Africans. Ambulatory blood pressure measurements were taken for 101 black South African men and 99 women. The stiffness indices included ambulatory arterial stiffness index (AASI) and pulse pressure (PP). Reactive oxygen species (ROS) levels (P<0.0001) were higher in the African women compared with men. ROS levels were also higher in hypertensive compared with normotensive men. The 24 h systolic blood pressure (SBP P<0.01), 24 h diastolic blood pressure (DBP P<0.0001) and pulse wave velocity (PWV P<0.01) were significantly higher in African men compared with women. There were unadjusted positive associations of 24 h SBP (r=0.33 P=0.001), 24 h DBP (r=0.26 P=0.008) and 24 h PP (r=0.29 P=0.003) with ROS in African men only. A positive association between AASI and ROS existed only in hypertensive men (r=0.27 P=0.035), but became nonsignificant (B=0.0014 P=0.14) after adjustments. Adjusted, positive associations of 24 h SBP (B=0.181 P=0.018) and 24 h PP (B=0.086 P=0.050) with ROS were again only evident in African men. ROS is positively associated with SBP and PP in African men, suggesting that increased ROS levels may contribute to hypertension in this population group.
Publisher: Informa UK Limited
Date: 02-09-2014
DOI: 10.3109/10715762.2014.951840
Abstract: Various studies indicate a relationship between increased oxidative stress and hypertension, resulting in increased DNA damage and consequent excretion of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG). The aim of this study was to compare urinary 8-oxodG levels in African and Caucasian men and to investigate the association between ambulatory blood pressure (BP) and pulse pressure (PP) with 8-oxodG in these groups. We included 98 African and 92 Caucasian men in the study and determined their ambulatory BP and PP. Biochemical analyses included, urinary 8-oxodG, reactive oxygen species (ROS) (measured as serum peroxides), ferric reducing antioxidant power (FRAP), total glutathione (GSH), glutathione peroxidase (GPx) and glutathione reductase (GR) activity. The African men had significantly higher systolic (SBP) and diastolic blood pressure (DBP) (both p < 0.001). Assessment of the oxidative stress markers indicated significantly lower 8-oxodG levels (p < 0.001) in the African group. The African men also had significantly higher ROS (p = 0.002) with concomitant lower FRAP (p < 0.001), while their GSH levels (p = 0.013) and GR activity (p < 0.001) were significantly higher. Single and partial regression analyses indicated a negative association between urinary 8-oxodG levels with SBP, DBP and PP only in African men. These associations were confirmed in multiple regression analyses (SBP: R(2) = 0.41 β = -0.25 p = 0.002, DBP: R(2) = 0.30 β = -0.21 p = 0.022, PP: R(2) = 0.30 β = -0.19 p = 0.03). Our results revealed significantly lower urinary 8-oxodG in African men, accompanied by a negative association with BP and PP. We propose that this may indicate a dose-response relationship in which increased oxidative stress may play a central role in the up-regulation of antioxidant defence and DNA repair mechanisms.
Publisher: Springer Science and Business Media LLC
Date: 16-03-2017
Publisher: Elsevier BV
Date: 07-2013
DOI: 10.1016/J.JASH.2013.04.005
Abstract: Reactive oxygen species (ROS) play a fundamental role in angiogenesis, and in turn, angiogenic growth factors also affect ROS. Angiogenesis and ROS are intricately involved in vascular deterioration. Since black populations are known to have elevated oxidative stress and hypertension, we determined whether relationships exist between angiogenic growth factors and serum peroxides in Africans and Caucasians and evaluated the relationships with cardiovascular measurements. We measured vascular endothelial growth factor-A (VEGF), angiopoietin 2 (Ang-2), and serum peroxides in Africans (N = 262) and Caucasians (N = 364) aged 20 to 70 years. Africans displayed higher blood pressure, serum peroxide levels, VEGF, and Ang-2 (all P ≤ .002) than similarly aged Caucasians (P = .44). In multivariable adjusted analyses, Ang-2 was independently associated with serum peroxides in African men (R² = 0.31 β = 0.21 P = .014) and women (R² = 0.09 β = 0.22 P = .025) and VEGF with serum peroxides in African men (R² = 0.12 β = 0.24 P = .014), with no statistically significant associations in Caucasians. Cardiovascular measurements did not associate with serum peroxides or angiogenic factors in any subgroup. Significant independent relationships exist between angiogenic growth factors and serum peroxides only in Africans who also displayed an unfavorable cardiovascular profile when compared with Caucasians. These results suggest that interplay between ROS and angiogenesis occur in African in iduals that may form part of the mechanisms involved in vascular deterioration.
Publisher: Springer Science and Business Media LLC
Date: 18-01-2012
Publisher: Wiley
Date: 25-01-2013
DOI: 10.1007/S10545-012-9579-6
Abstract: Elevated urinary excretion of 3-methylglutaconic acid is considered rare in patients suspected of a metabolic disorder. In 3-methylglutaconyl-CoA hydratase deficiency (mutations in AUH), it derives from leucine degradation. In all other disorders with 3-methylglutaconic aciduria the origin is unknown, yet mitochondrial dysfunction is thought to be the common denominator. We investigate the biochemical, clinical and genetic data of 388 patients referred to our centre under suspicion of a metabolic disorder showing 3-methylglutaconic aciduria in routine metabolic screening. Furthermore, we investigate 591 patients with 50 different, genetically proven, mitochondrial disorders for the presence of 3-methylglutaconic aciduria. Three percent of all urine s les of the patients referred showed 3-methylglutaconic aciduria, often in correlation with disorders not reported earlier in association with 3-methylglutaconic aciduria (e.g. organic acidurias, urea cycle disorders, haematological and neuromuscular disorders). In the patient cohort with genetically proven mitochondrial disorders 11% presented 3-methylglutaconic aciduria. It was more frequently seen in ATPase related disorders, with mitochondrial DNA depletion or deletion, but not in patients with single respiratory chain complex deficiencies. Besides, it was a consistent feature of patients with mutations in TAZ, SERAC1, OPA3, DNAJC19 and TMEM70 accounting for mitochondrial membrane related pathology. 3-methylglutaconic aciduria is found quite frequently in patients suspected of a metabolic disorder, and mitochondrial dysfunction is indeed a common denominator. It is only a discriminative feature of patients with mutations in AUH, TAZ, SERAC1, OPA3, DNAJC19 TMEM70. These conditions should therefore be referred to as inborn errors of metabolism with 3-methylglutaconic aciduria as discriminative feature.
Publisher: Springer Science and Business Media LLC
Date: 23-12-2020
Publisher: Hindawi Limited
Date: 02-07-2012
DOI: 10.1002/HUMU.22118
Publisher: The Endocrine Society
Date: 05-2010
DOI: 10.1210/JC.2009-2329
Abstract: Low serum IGF-I is an independent risk factor for diabetes and cardiovascular disease. These noncommunicable diseases are extremely common in urban black South Africans, but their IGF-I concentration is unknown. We aimed to compare serum IGF-I concentrations of African and Caucasian people, investigate their age-related IGF-I decline, and determine whether IGF-I could account, at least in part, for the high prevalence of noncommunicable diseases in black Africans. This cross-sectional study involved 211 African and 316 Caucasian men and women (aged 20-70 yr). Fasting glucose, insulin, lipids, albumin, creatinine, liver enzymes, cotinine, high-sensitivity C-reactive protein, reactive oxygen species, IGF-I, blood pressure (BP), and pulse wave velocity were determined. IGF-I was lower in Africans (P < 0.001) and in both ethnicities declined significantly by age quartiles (P < 0.001). In African men and women, IGF-I declined significantly from age quartile 1 to 2 (r = -0.65, P < 0.001), not seen in young Caucasian men and women (r = -0.08, P = 0.45 r = -0.10, P = 0.34). This was confirmed after adjustment for BP, insulin resistance, high-sensitivity C-reactive protein, cotinine, gamma-glutamyl transferase, and reactive oxygen species. Only young Africans showed significant negative correlations of IGF-I with BP, pulse wave velocity, and high-density lipoprotein cholesterol. Africans presented lower IGF-I levels than Caucasians due to an accelerated decline in serum IGF-I concentration prior to 40 yr of age. Strong associations of low serum IGF-I with blood pressure and arterial stiffness in young Africans suggest that the loss of cardiometabolic protection by IGF-I could predispose them to earlier disease onset.
Publisher: Elsevier BV
Date: 07-2018
DOI: 10.1016/J.SPEN.2017.03.002
Abstract: This report describes the first case of a child with genetically confirmed Brown-Vialetto-van Laere syndrome in sub-Saharan Africa. This is an extremely rare clinical condition that presents with an auditory neuropathy, bulbar palsy, stridor, muscle weakness, and respiratory compromise that manifests with diaphragmatic and vocal cord paralysis. It is an autosomal recessive condition for which the genetic mutation has only recently been linked to a riboflavin transporter deficiency. We describe an 11-month-old affected male infant. He has required long-term respiratory support and a gastrostomy tube to support feeding. With high-dose riboflavin supplementation, he had limited recovery of motor function. His respiratory chain enzyme studies were abnormal suggestive of mitochondrial (mt) dysfunction. In the setting of limited resources, recognition of this striking clinical phenotype is important to highlight, specifically regarding the genetic implications of the condition and the potentially remedial response to vitamin supplementation.
No related grants have been discovered for Francois van der Westhuizen.