Magister Scientiae - MSc (Medical BioSciences)
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Item CIMT and cardiovascular risk in five-year-old children in a low socioeconomic population exposed to alcohol and nicotine during pregnancy: a case-control study(University of the Western Cape, 2020) Hartel, Tammy Charlene; De Smidt, JuléyCardiovascular diseases (CVD) are among the top 10 causes of death in all ages in South Africa. The prevalence of maternal smoking and alcohol consumption during pregnancy is alarmingly high in South Africa. In utero exposure to nicotine and alcohol may cause CVD later in life. There is a global need for early detection of CVD especially those vulnerable during early childhood, to prevent the development of CVD risk factors in adulthood. The aim of this study was to compare CVD risk in five-year-old children from a low socio-economic population with in utero dual exposure to nicotine and alcohol and in utero nicotine exposure by measuring carotid intima-media thickness (cIMT), anthropometric measurements and clinical measurements including blood pressure. A case-control study was conducted on 468 children at five years old through interviews to collect data on demographic characteristics and health statistics. The cIMT was measured using B-mode ultrasonography. Anthropometric measurements were taken such as skinfold thickness, waist circumference, height and weight to calculate Body Mass Index (BMI). Blood pressure measurements such as systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and heart rate (HR) were taken. The data was analysed using SPSS version 26. Descriptive and inferential statistics (Spearman’s correlations, non-parametric partial correlations), Kruskal-Wallis H, Chi-square tests and logistic regression were used for statistical analysis. Results showed a significantly higher right cIMT (RcIMT) (0.36 ± 0.05 mm; P < 0.01) in children with in utero exposure to nicotine and alcohol during pregnancy and a higher RcIMT in males (0.37 ± 0.06 mm; P < 0.01) with in utero dual exposure to nicotine and alcohol when compared to females. A significant association was found between in utero dual exposure to nicotine and alcohol and a high RcIMT, specifically in females at five years old after the adjustment for confounders (B= -1.618, P = 0.002). Consequently, females in the dual exposed group were 7.6 times more likely to exhibit higher RcIMT with a relative risk of 2.6 times greater to children with no exposure. Females also had significantly higher SBP (U= 3829.50, p <0.01), DBP (U= 3527.50, p <0.05), MAP (U= 3561.00, p <0.05) and HR (U= 3887.50, p <0.01) in the dual exposed group. Cardiovascular risk factors were modestly prevalent at five years old in children with in utero teratogen exposures. However, increased adiposity indices were not observed in this population at five years old and were not associated with teratogen exposures. This may indicate that dual exposure to nicotine and alcohol has a significant effect on the intima-media thickness of the carotid arteries in children, but not necessarily on central and peripheral adiposity at five years old. Therefore, CVD risk factors need to be identified early in children in low socioeconomic regions with in utero exposure to nicotine and alcohol to prevent CVD later in life.Item In vitro modulatory effects of fermented rooibos extract (Aspalathus linearis) against ethanol-induced effects on the mouse blood-brain barrier(University of the Western Cape, 2014) Mentor, Shireen; Fisher, D; Cummings, F.; Gamieldien, K.Alcohol abuse is a growing crisis within South Africa, with severe health and socio-economic implications. Alcohol compromises the function of the blood-brain barrier (BBB), and thus its ability to regulate the homeostatic environment of the CNS is interrupted. In this study, an in vitro model of the BBB was utilized to study the effects of selected concentrations of alcohol (25mM-200mM) and the ameliorating effects of fermented rooibos (Aspalathus linearis) (0.003125%-1%), in an attempt to reverse the harmful oxidative effects of alcohol. The literature clearly states that alcohol (ethanol) compromises the BBB by reactive oxygen species (ROS) production and, therefore, rooibos, a shrub high in antioxidants and widely utilized nationally, was added to alcohol-exposed mouse brain endothelial (bEnd5) cells with the view to reverse the alcohol-induced effects on the BBB model. Alcohol-treated (25mM-400mM) bEnd5 monolayers expressed no toxicity, however, cell numbers were significantly suppressed (P<0.0274). To validate this finding, the activity of the mitochondria was investigated in order to understand if the cell’s metabolism was related to the decrease in cell division. Results showed that for both acute and chronic exposure there was a decrease in mitochondrial activity (MA) for a period of 24-48 hours, thereafter, the MA of the bEnd5 cells returned to normality. However, in experiments which chronically (600mM and 800mM) exposed cells to alcohol over a period of 96 hours, MA was suppressed and did not return to normal. Fermented rooibos caused a biphasic response to cellular proliferation at 24-72 hours, where the lower concentrations (0.0625-0.125 %) caused an increase in cellular proliferation and the higher concentrations (0.5-1%) resulted in a relative decrease in cellular proliferation. The long-term effect, after acute exposure, however, resulted in cell suppression at 96 hours (P<0.0073). With respect to the MA, bEnd5 cells exposed to fermented rooibos showed that lower concentrations (0.003125-0.0125%) were suppressed at 24 hours and was elevated at 48 hours and96 hours for all concentrations. The exception being the highest concentration (0.1%), which showed a depression in MA (P<0.05). Treating cells with both alcohol and rooibos, resulted in exacerbated suppressing of the MA. The physiological function of the BBB model was investigated by monitoring the permeability using transendothelial electrical resistance (TEER) studies and the in vitro model used in this study was endorsed for the first time using high resolution scanning electron microscopy. TEER indicated incidental changes in the permeability, only at 24 hours, for both acute and chronic exposure to alcohol and rooibos. A novel finding, within this study, was the increase in electrical resistance across the formation of the cell monolayer, after treatment with alcohol. The data lead to the hypothesis for the effect of ROS on resistivity and provides a rationale to explain the effects of combinatory treatments that were expected to ameliorate the negative effect of alcohol, however, this study showed synergistically negative effects on the bEnd5 cells. In summary the main findings in this study were: (a) alcohol was not toxic on bEnd5cells, (b) alcohol increased the permeability across monolayers of bEnd5 cells and(c) rooibos did not significantly reverse the ROS-induced effects of alcohol, but exacerbated the effects. Rooibos treatment caused the following: (i) biphasic effect on cellular proliferation, (ii) an increase in MA, and (iii) a cyclic effect in TEER studies.