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- ItemDoes sexual violence alter social behvaiour via a maladaptive HPA-axis?(Stellenbosch : Stellenbosch University, 2023-03) Fortuin, Chelsi Shante; Qulu, Lihle; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences. Medical Physiology.ENGLISH ABSTRACT: Background and Aim: South Africa was identified as the rape capital of the world, recording one of the highest rates of sexual violence worldwide with 72.1 reported cases per 100 000 in the 2019/2020 year. The mental health and well-being of sexual assault survivors exhibit a dysregulated HPA-axis stress response, which may be a primary source of structural and functional alterations leading to PTSD symptoms, but they don’t always co-exist. Chronic stress and psychiatric diseases cause dysregulation of the HPA axis. A cortisol imbalance brought on by the dysregulation of the HPA-axis leads to a decrease in oxytocin secretion, which eliminates oxytocin's potential to attenuate HPA-axis activity. A lack of oxytocin has been linked to broken social and maternal bonds as well as losing relationship attachments as a result of trauma exposure such as sexual violence / rape. Oxytocin dysregulation has been associated in a large variety of dysregulated social behaviour and PTSD diagnosis. Additionally, when bound to cortisol, glucocorticoid receptor sensitivity modifies the stress response's equilibrium point, which in turn regulates the HPA axis's negative feedback loop. As a result, they have been linked to anticipating the effects of stress. Therefore, the aim of this study is to determine whether being subjected to sexual violence alters social behavior via a dysregulated HPA-axis. Methods: Data analysis was completed using PTSD, perceived stress and social support scores to investigate the effects of rape on mental health trajectory. Additionally, enzyme-linked immunosorbent assays were used, to explore the role of oxytocin and cortisol as indicators of PTSD in rape-exposed women. Both cortisol and oxytocin found within plasma samples were analysed over a one-year period at four time points (baseline [± twenty days], three months, six months and twelve months post rape) to assess whether these hormone levels, that are activated by sexual violence, were transient or long lasting, and whether these hormone levels may lead to the formation of PTSD. Mixed effect regression analysis were done to determine if cortisol and oxytocin concentrations predict PTSD outcomes. Results: PTSD symptoms significantly decreased overtime, p = 0.000. Similarly, perceived stress, p = 0.0023, and cortisol concentrations, p = 0.004, significantly decreased overtime. Whereas social support scores, p = 0.5851, and oxytocin concentrations, p = 0.995, had no significant changes. Additionally, cortisol concentrations, p = 0.1660, and social support, p = 0.827, were not able to predict PTSD outcome, however oxytocin concentrations, slope = 9.32, p = 0.002 and perceived stress scores, slope = -5.654, p = 0.033, could predict PTSD. Conclusion: These findings demonstrate a relationship between PTSD symptom severity and HPA-axis maladaptation, via augmented oxytocin responses in victims of rape. We conclude that these findings may have significant clinical ramifications for women who have been subjected to rape. Particularly, offering scientific based PTSD interventions to rape exposed victims may show promise in alleviating symptoms and "normalizing" HPA axis receptivity to stress related stimuli.
- ItemThe impact of SARS-CoV-2 on respiratory function(Stellenbosch : Stellenbosch University, 2023-02) Van Heerden, Jacques; Strijdom, Hans; Koegelenberg, Coenraad; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences. Medical Physiology.ENGLISH ABSTRACT: The iliocapsularis (IC) is a deep skeletal muscle that overlies and attaches to the anteromedial hip joint capsule and is an important anatomical landmark in anterior approaches to hip replacement surgery. Researchers have proposed the IC functions to stabilise the anterior hip joint and limit impingement of the hip capsule, between the femoral head and acetabulum, in hip flexion. However, a conclusive description of the function of the IC is not yet known. This study, therefore, aims to determine the skeletal muscle properties of the IC muscle and to compare these to that of the iliacus (IL) and vastus lateralis (VL). A cross-sectional observational study was conducted on 11 recently deceased unembalmed bodies with a mean age of 83 ± 9 years (range 69 - 95 years). Muscle samples, harvested from the IC, IL, and VL, were analysed for muscle fibre type distribution and fibre cross-sectional area (CSA) using fluorescent immunohistochemistry, while relative mitochondrial density was visualised histochemically using the NADH stain. IC had predominantly type I fibres (63 ± 12%), followed by type IIA (32 ± 13%) and IIX (5 ± 3%) fibres. IL comprised of a similar high distribution of type I fibres (61 ± 8%), compared to type IIA (31 ± 7%) and IIX (8 ± 8%) fibres. Conversely, VL had equal amounts of type I (47 ± 12%) and IIA (40 ± 11%) fibres, with lower proportions of type IIX (13 ± 10%) fibres. No difference in fibre type distributions were found between the IC and IL, whereas VL had less type I fibres compared to the IC and IL. The latter two muscles observed higher relative mitochondrial density (darker fibres) and, therefore, oxidative capacity, compared to the VL with a more equal proportion of light and dark stained fibres. The IC had larger (p < 0.0001) type I fibres (3607 ± 1422 μm2) compared to its type IIA (1849 ± 1306 μm2) and IIX (1379 ± 900 μm2) fibres. Similarly, the IL and VL had larger (p < 0.0001) type I fibres (3320 ± 1182 μm2 and 4235 ± 882 μm2, respectively) compared to type IIA (1790 ± 987 μm2 and 2738 ± 1650 μm2, respectively) and IIX (1428 ± 769 μm2 and 2170 ± 1355 μm2, respectively) fibres. No difference in the CSA of fibre types were found when the IC was compared with the IL and VL. However, the VL reported larger CSA compared to IL for type I and IIA fibres. Mean fibre CSA of the IC and IL were similar in size, while the VL had larger fibres. Fibre type distribution and fibre CSA showed no association with age. Therefore, the predominant oxidative type I fibre distribution of the IC may supports its proposed function to stabilise the hip joint and limit impingement of the hip capsule in hip flexion. Therefore, conclusive knowledge of the function of the IC will allow for more informed decisions regarding patient care and rehabilitation following anterior approaches for hip-replacement surgery.
- ItemThe role of the intestinal immune system in the development and treatment of type 2 diabetes(Stellenbosch : Stellenbosch University, 2022-11) Parker, Kauthar; Riedel, Sylvia; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences. Medical Physiology.ENGLISH ABSTRACT: Background: Type 2 diabetes (T2D) is largely correlated with obesity. Low-grade systemic inflammation and altered immune homeostasis in the gut are implicated in the pathogenesis of T2D. The intestinal mucosal immune response and tissue repair mechanisms are reduced while a state of dysbiosis is induced in T2D. Rooibos has been associated with hypoglycaemic and anti-inflammatory effects. Therefore, rooibos potentially improves the intestinal immune status in a type 2 diabetic state. This study aims to investigate the role of the intestinal immune homeostasis and tissue repair in animal models of early and late stages of T2D development, and to elucidate the effects of rooibos treatment on the intestinal immune status and tissue repair. Method: Male Wistar rats (n=60) were fed either a control, high-fat diet (HFD) or high-sugar diet (HSD) for 10 weeks and thereafter, green rooibos extract (GRT) (60 mg/kg) was supplemented (n=10 per group) for 7 weeks. Jejunum and ileum, and stool were harvested to assess immunoglobulin A (IgA) content by immunohistochemistry staining and ELISA respectively to measure intestinal mucosal immune responses. Diabetic, db/db and non-diabetic, db/+ mice (n=64) were treated with vehicle control, pioglitazone as a positive control (15 mg/kg), GRT low dose (74 mg/kg), or GRT high dose (740 mg/kg) for 16 weeks. Small intestinal tissue were stained to quantify IgA-expressing cells, Foxp3 to measure regulatory T-cells (Tregs), and Ki-67 to measure proliferating cells. Colonic IgA was assessed as well as Cox-2 as a measure of tissue repair using Western blot. IL-10 and TGF-β were assessed in the colon using ELISA for differentiation of Tregs. Alterations of the gut microbiota was assessed from cecum DNA by sequencing hypervariable regions via an Ion-torrent platform. Statistical significance was determined by 2-way ANOVA and Tukey Kramer post-hoc test. Results: HSD increased IgA-expressing cells in the jejunum of rats compared to the HFD- (p=0,00001) and control-fed rats (p=0,02056), while GRT was able to increase IgA-expressing cells in the jejunum compared to the non-treated rats (p=0,01044). No significant changes in IgA expression was observed in the ileum or stool of HSD- or HFD-fed rats.
- ItemThe vascular and endothelial effects of HIV, antiretroviral therapy and rooibos - functional effects and mechanism(Stellenbosch : Stellenbosch University, 2022-12) Molopi, Dintle; Dr Genis, Amanda; Dr Windvogel, Shantal; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences. Medical Physiology.ENGLISH ABSTRACT: Individuals infected with human immunodeficiency virus-1 (HIV-1) are living longer but are at increased risk of cardiovascular disease (CVD). Antiretroviral therapy (ART) has been implicated in the development of CVD in people living with HIV-1, however a gap remains in the mechanisms involved. Rooibos (RB) has been shown to exert potential ameliorative effects against cardiovascular risk factors. Endothelial dysfunction is characterized by reduction of the bioavailability of vasodilators, particularly nitric oxide (NO), and/or an increase in endothelium-derived contracting factors. The aortic-ring model measures optimal contraction/relaxation by measuring isometric-tension (g) as an indication of vasomotor function. Therefore, the aim of this study was to investigate the effects of HIV-1 proteins, ART and rooibos, and a combination thereof on vascular and endothelial function and the possible mechanisms thereof. By evaluating the following objectives: (i) objective 1 to assess vascular reactivity by performing aortic-ring tension studies, utilizing treated thoracic aortas of aged-matched Wistar rats. (ii) Objective 2 To investigate the underlying mechanism involved in endothelial, by assessing the proteins involved in vascular signaling by means of Western blot analysis. Methods Isolated 3-4mm sized aortic rings were incubated for 24 hours with either of the following cocktails: Control (vehicle control), HIV1 (nef, tat & gp160 = 100ng/ml), ART1 (efavirenz = 11.2nM, tenofovir = 1μM and emtricitabine = 2.6µM), ART2 (lopinavir = 20µM and ritonavir = 4µM), RB (2%), HIV1+ART1, HIV1+ART2, HIV1 +RB and HIV1 + ART2 + RB. Thereafter, aortic ring was mounted, and contraction/relaxation reactivity of the vessels were determined in an organ bath perfusion system (AD Instruments, Australia). The remaining tissue of the excised aortas were snap frozen in liquid nitrogen for western blot analysis (n=2-3/group). Results No difference in treatment with HIV1 or ART1 compared to controls were observed. Treatment with ART2 decreased %contraction but had no effect on %relaxation. Treatment with RB decreased %contraction and %relaxation. Co-treatment with HIV1+ART1 decreased %contraction and %relaxation, while HIV1+ART2 decreased %contraction but increased %relaxation. HIV1+ART1 group, HIV1+ART2 group, as well as HIV1+RB group showed decreased %contraction and %relaxation compared to HIV1 only treated aortic rings. HIV1+ART2+RB had no effect on %contraction or %relaxation compared to HIV1. Cleaved-PARP expression was increased in HIV1+ART2 compared to HIV1. Total IκBα expression was increased in HIV1+ART2+RB compared to HIV1 and HIV1+ART2 groups. Conclusion HIV-1 (Nef, Tat and Gp160) had no effect on vasomotor function. While efavirenz, tenofovir and emtricitabine treatment alone had no effect, it had ambiguous effects within this HIV-1 protein environment. Interestingly, lopinavir and ritonavir co-treatment with HIV-1 proteins improved vasomotor function but increased apoptosis. Rooibos caused had an ambiguous effect in aortic reactivity when treated alone, co-treated with HIV1 and had no effect when co-treated with HIV1 and protease inhibitors. However, Rooibos co-treatment with HIV1 and protease inhibitors downregulated the inflammatory NF-κB signaling pathway. Although this study could not pertinently show the harmful effect that HIV-1 proteins and protease inhibitors have on vascular function, the effect of Rooibos in this environment was promising and warrants further investigation into an optimal concentration within this environment.
- ItemIs there a combined dose-response effect of cigarette smoking and alcohol use during pregnancy on birth weight in a diverse western cape community of South Africa?(Stellenbosch : Stellenbosch University, 2022-04) Nolan, Heidi; Geerts, Lut; Odendaal, Hein; Windvogel, Shantal; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences: Medical Physiology.Introduction: Prenatal cigarette exposure (PCE) and prenatal alcohol exposure (PAE) are associated with obstetric complications such as intrauterine growth restriction. This could lead to small for gestational age (SGA) fetuses (who are either constitutionally or pathologically small), potentially resulting in low birth weight (LBW), preterm delivery, perinatal mortality, and infant mortality. Despite public health warnings and awareness campaigns, a high prevalence of PCE (47 %) and PAE (34 – 51 %) is st ill reported in South Africa ( SA), an upper-middle-income country. This may contribute to the high prevalence (14.2 %) of preterm birth and LBW found in SA, making PCE and PAE two of the largest preventable causes of fetal/infant morbidity and mortality. Many studies have assessed the effect of PCE and PAE separately, focusing on adverse pregnancy outcomes. However, the combined dose-response relationship between PCE and PAE on birth weight remains unclear. This study aimed to determine whether there is a combined dose-response effect of cigarette smoking and alcohol during pregnancy on birth weight in a diverse cohort of a well- defined geographical area of low socioeconomic status in the Western Cape community of SA. Method: Data from the Safe Passage Study, a large, prospective, multidisciplinary study who enlisted 11 892 pregnant women of diverse ancestry residing in well-defined residential areas between August 2007 and January 2015 from two clinical sites were used. Exposure data was collected at 30-day intervals preceding the last recorded exposure. PCE was captured by asking about the participant’s smoking habits (i.e. quantity and frequency of smoking a tobacco cigarette on a typical day or chewing tobacco during a typical week) using grouped frequency options (detailed under methodology). PAE was captured using quantity questions such as sharing of drinks, duration for each drinking occasion, type/brand of beverages consumed, number, container size, and iced or frozen. All drinking was converted to number of standard drinks per day. Brink et al. formulated a nine-level alcohol- smoking exposure grouping to examine the prenatal dose-relationship on birth weight. Data from the South African cohort was used for this study. Only patients with singleton pregnancies that resulted in a live birth with birth weight, infant s ex, and gestational age (GA) recorded at birth were included. Birth weight data were converted to birth weight z- scores and centiles according to the reference ranges of the Intergrowth-21st Project and Gardosi. Distributions of z-scores and proportions of SGA (< p10, < p5 and < p3) fetuses were compared across the nine-level alcohol-smoking exposure groups, as well as the collapsed four-level alcohol-smoking exposure groups. Results: The percentage of newborns identified in our study as SGA was significantly higher than expected. Compared against the nine-level alcohol-smoking exposure grouping, the highest percentage was seen in the dual exposure groups (either or both heavy exposure). The same was seen in the smoking and drinking (SD) category when compared against the four-level alcohol-smoking exposure grouping. Conclusion: Alcohol and smoking exposure has a combined dose-response effect on birth weight and the proportion of SGA infants, especially when one or both exposures are high.