Browsing by Author "Charania, Sana"

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    Investigating the effects of first line and second line antiretroviral drugs on HIV exposed endothelial function - A clinical study, supported by a mechanistic in-vitro approach
    (Stellenbosch : Stellenbosch University, 2017-03) Charania, Sana; Strijdom, Hans; Genis, Amanda; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences: Medical Physiology
    ENGLISH ABSTRACT : Background: There is an interaction between HIV, antiretroviral treatment (ART) and endothelial dysfunction; furthermore, HIV-infected individuals (± ART) show an increased incidence of cardiovascular risk factors. However, the evidence stems mainly from studies in developed countries with a paucity of data on these interactions in the South African context. Aims: To investigate the effects of first line and second line ART on HIV exposed vascular endothelial function, in a clinical and in vitro setting. Methods: In the clinical study, participants were recruited in Worcester and allocated to one of four study groups: HIV-negative, HIV-positive ART naïve, HIV-positive first line ART and HIV-positive second line ART. Data were collected via health questionnaires, anthropometric assessments, blood pressure measurements, brachial artery flow mediated dilatation (FMD) and blood chemistry analyses (C-reactive protein (CRP), fasting glucose, HbA1c, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, as well as CD4 count and viral load in HIV-infected individuals). For the in vitro sub-study, a conditioned growth medium was developed containing HIV-related proteins in which aortic endothelial cells (AECs) were incubated. Additionally, AECs were treated with first and second ART drugs. End-points were nitric oxide (NO) production, cell viability and ROS production measured by flow cytometric analysis. Results: There were no inter-group differences with regard to FMD. The median BMI and waist circumference measurements were lower in the HIV-positive groups versus HIV-negative (p < 0.05). Median total cholesterol levels were lower (p < 0.05) in the HIV-positive ART groups versus HIV-negative, and higher in the HIV-positive first line ART group versus the ART naïve group (p< 0.05). Furthermore, mean LDL-cholesterol levels were lower in all HIV-positive groups versus HIV-negative (p< 0.05). Median HBA1C% values were lower in the HIV-positive second line ART versus ART-naïve group (p < 0.05). Regression analyses showed that smoking in first line ART, and CRP and CD4 levels in second line ART were negatively associated with FMD%. In the in vitro sub-study, the HIV-1 gp160 protein was identified in the HIV-conditioned medium. No effects were observed in HIV-conditioned medium treated AECs. In the first and second line ART dose-response investigations, it was found that double first line drug concentration and normal second line drug concentration exerted no harmful effects on AECs. Discussion and Conclusion: Clinical data suggested that the cardiovascular risk profile appeared to be more favourable in HIV-positive groups versus HIV-negative. There were no inter-group differences in terms of endothelial function (FMD). CD4 and CRP, as well as female gender were independent predictors of vascular endothelial function in the HIV-positive second line ART group. Furthermore, smoking was found to be a negative independent predictor of endothelial function in the HIV-positive first line ART group. The in vitro findings showed that the HIV-conditioned medium protocol successfully resulted in the expression of the HIV-1 gp160 protein; however, the conditioned medium failed to induce injury. In the ART dose-response investigations, the double drug concentration for first line ART and normal drug concentration for second line ART, could be considered a safe concentration to use in future investigations.
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    Personal NO2 and volatile organic compounds exposure levels are associated with markers of cardiovascular risk in women in the Cape Town region of South Africa
    (MDPI, 2019) Everson, Frans; De Boever, Patrick; Nawrot, Tim S.; Goswami, Nandu; Mthethwa, Mashudu; Webster, Ingrid; Martens, Dries S.; Mashele, Nyiko; Charania, Sana; Kamau, Festus; Strijdom, Hans
    ENGLISH ABSTRACT: Exposure to ambient NO2 and benzene, toluene ethyl-benzene and m+p- and o-xylenes (BTEX) is associated with adverse cardiovascular effects, but limited information is available on the effects of personal exposure to these compounds in South African populations. This 6-month follow-up study aims to determine 7-day personal ambient NO2 and BTEX exposure levels via compact passive diffusion samplers in female participants from Cape Town, and investigate whether exposure levels are associated with cardiovascular risk markers. Overall, the measured air pollutant exposure levels were lower compared to international standards. NO2 was positively associated with systolic and diastolic blood pressure (SBP and DBP), and inversely associated with the central retinal venular equivalent (CRVE) and mean baseline brachial artery diameter. o-xylene was associated with DBP and benzene was strongly associated with carotid intima media thickness (cIMT). Our findings showed that personal air pollution exposure, even at relatively low levels, was associated with several markers of cardiovascular risk in women residing in the Cape Town region.