Electronic Theses and Dissertations (PhDs)
Permanent URI for this collectionhttps://hdl.handle.net/10539/37982
Browse
9 results
Search Results
Item Cognitive, Cardiovascular and Muscular Stress Imposed by a Twenty20 Batting Simulation(University of the Witwatersrand, Johannesburg, 2024) Lopes, Tiago; Olivier, BenitaIn the sport of cricket, batting requires prolonged cognitive control accompanied with high muscular and cardiovascular stress. However, the acuity of information processing (cognition) during bouts of physical activity is not fully studied. This investigation is the first to investigate the influence of striking rare in Twenty20 cricket on the physiology of the batter. Phase 1 a retrospective analysis of competitive individual innings in Twenty20 matches between 2006–2019. Per-delivery probabilities of run type and on/o↵-strike demarca- tion were calculated for two innings subsets. Both simulations replicate a 1-hour and 2-minute partnership of 93 deliveries, 51 of which are ‘on-strike’. The low strike rate innings replicates scoring 61 runs, compared to 88 runs in the high strike rate innings. Phase 2, a randomised, repeated measures laboratory design, recruited 14 skilled batters (competitive playing experience > 6 years) to perform both simulations. The physical (heart rate, muscular output, blood lactate accumulation, fluid loss) and cogni- tive (working memory, executive functioning, prefrontal cortex haemodynamics) strain of Twenty20 batting was quantified. High strike rate batting was found to augment responses of heart rate (p < 0.01), and produce slower sprint performance (p < 0.01). However, changes to lower-limb peak power output (p = 0.08), fluid loss (p = 0.71) and accumulation of blood lactate (p = 0.67) were comparable. Working memory response times improved with moderate e↵ects (d = 0.61) in the low strike rate simulation. Compared to large e↵ects following the high strike rate simulation (d = 1.20) where ex- ecutive functioning was moderately more error-prone (r = 0.60). The prefrontal cortex displays substantially less reserve to increase concentrations of oxygenated haemoglobin when confronted with cognitively demanding tasks following either simulation. In Phase 3, a novel device (Pitch Reaction Test - PRT) is developed to ecologically quantify response times of implicit and explicit information processing. The record- ing accuracy of the PRT was assessed using a high-speed camera. Overall, a strong relationship is observed between video footage and PRT responses ( = 0.99 0.97). Neither subject height ( = 0.01, p = 0.54) or true leg length ( = 0.00, p = 0.58) were significant predictors of PRT performance. Future studies should continue to elucidate how batting modulates information processing eciency.Item Effects of dietary supplementation with β-sitosterol on Cobb 500 broiler chicken productivity, health and product quality(University of the Witwatersrand, Johannesburg, 2024) Bopape, Malebogo Audrey; Chivandi, ElitonAntibiotic use as growth promoters in chicken feeds results in antibiotic resistance and environmental pollution. To mitigate these challenges alternatives natural growth promoters are required. Beta-sitosterol is one of several phytosterols with chemical structures similar to that of cholesterol. β-sitosterol has antimicrobial, antioxidant, anti-inflammatory and hypocholesterolaemic activities, thus might replace synthetic antibiotics as a feed supplement in chicken feeds. The current study evaluated β-sitosterol’s potential to replace oxytetracycline in Cobb 500 broiler chicken feeds by determining its effects on growth performance, meat yield and quality and bird health. β-sitosterol replaced oxytetracycline at 0 (control: 50 mg/kg oxytetracycline), 500, 1000 and 1500 mg/kg feed for diet 1 to 4, respectively with doses similar in starter, grower, and finisher diets. Chickens were fed from day 1 to 42 days of age. Body mass and feed intake were measured. Body mass gain, average daily gain and feed conversion ratio were computed. Terminally, broiler chickens were fasted, weighed, humanely slaughtered and dressed. The carcass yield, viscera morphometry and plasma surrogate markers of health were also determined. Meat pH, colour, thawing and cooking loss (TL; CL), water holding capacity (WHC), tenderness and myofibrillar fragmentation length (MFL) and nutrient content were determined. Femora and tibiae mass, length, breaking strength and liver fat content and histology were determined. Dietary β- sitosterol had similar (P > 0.05) effects as oxytetracycline on the chickens’ growth performance and feed intake utilization efficiency, gastrointestinal tract (GIT) and GIT accessory viscera macromorphometry, meat yield, meat colour, pH, TL, CL, WHC, tenderness and MFL. However, breast meat crude protein content of chicken fed diet 4 was higher (P < 0.0001) compared to that of counterparts fed diets 2 and 3. Breast meat fat content of chicken fed diet 2 and diet 4 was higher (P < 0.0001) compared to that of counterparts fed diets 1 and 3. Dietary β-sitosterol had similar (P > 0.05) broiler chickens’ breast meat total saturated fatty acids (TSFAs), monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs), palmitic, oleic and linoleic content as oxytetracycline. Dietary treatments had no effect on chickens’ tibiae masses and breaking strength (P > 0.05) albeit tibiae from chickens fed diet 4 were shorter (P < 0.01) than those of counterparts fed diet 2. Dietary β-sitosterol at 1000 and 1500 mg/kg feed increased (P < 0.05) liver lipid content but had no effect on hepatic microarchitecture. However, at 1500 mg/kg feed it caused micro- and macro hepatic steatosis and lobular inflammation and higher (P < 0.05) non-alcoholic fatty liver disease activity scores (NAS). Compared to control, dietary β- vii sitosterol decreased (P < 0.0001) the chickens’ malondialdehyde (MDA) concentration but increased superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) activities and glutathione S-transferase (GST) and glutathione (GSH) concentration (P < 0.05). Diet 4 increased (P < 0.01) plasma AST and GGT activities compared to diet 1 (control). At 1000 and 1500 mg/kg feed it increased plasma cholesterol concentration compared to control and β-sitosterol at 500 mg/kg feed. β-sitosterol can replace oxytetracycline as growth promoter in Cobb 500 broiler chicken diets without negatively affecting growth performance, meat yield and quality and potentially mitigates oxidative stress by upregulating systemic antioxidant enzymes activities. However, at 1500 mg/kg feed, it can increase the risk of fatty liver disease development and hypercholesterolaemia.Item Myrmecophagous mammals in a changing world: the ecology of aardvarks and temminck’s pangolins in the kalahari(University of the Witwatersrand, Johannesburg, 2024) Phakoago, Makabudi valery; Fuller, A.Little is known about the distribution and ecology of the aardvark (Orycteropus afer) and Temminck’s pangolin (Smutsia temminckii) in southern Africa as they are rarely seen and difficult to study. Both species are myrmecophagous (feed on ants and termites), primarily nocturnal, 2and they tend to be solitary. Climate change, which is resulting in hotter and drier environments in most parts of southern Africa, may affect the aardvark and Temminck’s pangolin through direct impacts on the animals and through impacts on their prey resources. Understanding how climate change may impact these two myrmecophagous mammals requires us to gather further insights on how their environment and food sources are changing, how their diets overlap, how they use the environment and alter their activity to source food and buffer themselves from heat and cold, and how they are distributed across southern Africa. Previous research conducted in the semi-arid Kalahari of southern Africa showed that a decline in ant and termite populations (as indicated by counts in pitfall traps) associated with drought resulted in starvation of aardvarks and pangolins and decreased reproductive output of pangolins. Individuals of both species starved, despite previous work indicating that the diets do not overlap, with aardvark preying predominantly on harvester termites (Hodotermes mossambicus) and pangolins preying predominantly on ants (mainly Crematogaster ants). However, the research on each species was conducted at different times, so the dietary differences may have arisen from various factors that differed between the study periods. As part of a long-term project aimed at assessing the potential impacts of climate change on myrmecophagous mammals in the Kalahari ecosystem, the present study collected faecal samples from aardvark and Temminck’s pangolin at the same time in the Kalahari for one year to compare their diets and assess dietary overlap (Chapter 3). In addition to dietary analysis, the study added to our long-term data (since September 2014) of grass cover and counts of ants and termites in pitfall traps, from September 2019 to August 2022 (Chapter 2). These long-term data revealed substantial fluctuations in grass and insect availability over time, with termite populations apparently less likely to recover after drought years compared to ants (Chapter 2). The study also assessed the abundance xiii and orientation of burrows that are available to the aardvark and Temminck’s pangolin in the duneveld in the Kalahari during winter of 2021 (Chapter 4). Lastly, the study assessed the distribution and ecology of the aardvark and Temminck’s pangolin in southern Africa using freely available images and videos from Facebook and Instagram over 10 years (2010 – 2019) (Chapter 5). During the study, the study site, Tswalu Kalahari Reserve, experienced higher than average rainfall (2020 and 2021), resulting in high grass cover and an increase in the number of ants in pitfall traps, following a very hot and dry period in 2019. In contrast, termite numbers remained low. Despite the apparent low number of termites, as reflected in the pitfall traps, aardvark preferred termites over ants in their diet, and consumed predominantly termites of the genus Trinervitermes (45% of their diet) over the study period. Temminck’s pangolin preferred ants over termites and consumed mainly ants of the genus Crematogaster (42%). Although aardvarks and Temminck’s pangolin had preferences for their specific prey items, it was shown for the first time that there was dietary overlap between the two mammal species, with higher overlap when prey resources were readily available during autumn, and lower dietary overlap when prey resources were scarce during spring. The present study, however, was conducted during an unusually wet period characterized by above-average rainfall, so it is important to determine how competition for dietary items will change in hotter and drier years, when insect populations will likely be lower. Ants and termites rely on grasses for their survival; therefore, one would predict that the abundance of burrows, dug primarily by aardvark, is likely to be related to grass cover. The present study site comprised two distinct areas, differing in grass cover as a result of differences in historical grazing pressure. I therefore investigated the availability and use of burrows in the area with low grass cover and the area with high grass cover, during winter. Burrows serve as a beneficial buffer against climatic conditions for burrowing species, offering heat avoidance during the day and warmth during the night. It was found that burrow numbers were positively associated with grass cover. More burrows also were found on the western side of the dunes than on the eastern side, most likely because the xiv western side receives more direct sunlight in the afternoon, providing a warmer microclimate overnight during the cold winter. Finally, the study explored whether social media could provide supplementary information on the distribution and ecology of the aardvark and Temminck’s pangolin in southern Africa. The data, which were collected through examining photos and videos on Facebook and Instagram, confirmed that the aardvark is found throughout South Africa while Temminck’s pangolin is restricted to the northern regions of South Africa. The images also confirmed recent research that poor body condition is associated with greater diurnal activity for the aardvark, likely a response to high energetic demands of being active on cold nights. Little is known about drinking behaviour by the aardvark and Temminck’s pangolin, with only 7 records previously published for the aardvark. It was found a further 32 records for the aardvark, and 7 for the pangolin, showing that both species do occasionally drink opportunistically. The records also provided information on the predation of both myrmecophagous mammals. Predation was observed at almost all times of the year for both species, with leopard (Panthera pardus) the most common predator for the aardvark, and lion (Panthera leo) the most common predator for Temminck’s pangolin. Even though there were far fewer records of images in other southern African countries, social media appears to be a useful tool for collecting data on the distribution and ecology of the aardvark and Temminck’s pangolin. Understanding the ecology and distribution of the aardvark and Temminck’s pangolin in the Kalahari and other regions in relation to available prey resources and local climate is crucial for improving our conservation efforts of the species through informed management practices.Item Isolated nocturnal hypertension and target organ damage in a population of African descent(University of the Witwatersrand, Johannesburg, 2024) Phukubje, Edgar Matome; Maseko, MuziThe use of ambulatory blood pressure monitoring (ABPM) has revolutionised the approach to hypertension diagnosis and management. The ability to monitor blood pressure over a 24-hour period has enabled researchers to monitor blood pressure profile away from the doctor’s clinic, which has led to the diagnosis of various hypertension phenotypes like masked hypertension, isolated nocturnal hypertension (INH) and isolated daytime hypertension (IDH), and others. Previous studies have shown that night-time blood pressure is more closely related to target organ damage compared to daytime blood pressure. Since more studies indicate that people of African ancestry have elevated night-time blood pressure compared to other population groups, nocturnal blood pressure monitoring in this population group is crucial. However, there are few studies that have investigated the prevalence of INH, and their results are inconclusive. Hence the impact of INH on cardiovascular target organ damage is not well understood in this population group. It has been reported that dietary salt intake (DSI) has more severe cardiovascular outcomes in African populations compared to non-African populations groups because they are said to be salt sensitive. However, there are no studies that have investigated the relationship between 24-hour urinary salt excretion and 24-hour dipping patterns in populations of African ancestry. In addition, the impact of INH on target organ damage has never been compared to that of IDH. Hence, current intervention strategies primarily rely on daytime blood pressure to diagnose and treat hypertension. The relationship between age and blood pressure is well understood, but current studies have mainly focused on daytime blood pressure. The impact of age on nocturnal blood pressure is not well understood in this population group, and it is also unclear whether the age-related changes in nocturnal blood pressure translate to any cardiovascular target organ changes. Therefore, the aim of this study was to determine the relationship between INH and cardiovascular target organ damage in a South African population of African ancestry. A total 1600 participants above 18 years were recruited. These form part of the ongoing South African Hypertension and Diet Study in the Human Nutrition Research Laboratory. Office blood pressure was measured conventionally and through SpaceLabs ambulatory oscillometric monitors for 24-hours. Target organ function was determined through echocardiographic measurements and applanation tonometry using the sphygmocor device. 24-hour urine samples were collected to determine electrolyte excretion rates. Blood was collected when the participants visited the clinic. Only data with complete 24-hour ABPM matched with complete urinary collections were included for data analysis and the final sample was 796 participants. v Findings from the current study showed that 11% of the participants had INH, 13% had 24- hour sustained hypertension and 4% had IDH. The three groups had different dipping patterns. The sustained hypertensive group were non-dippers, IDH group were dippers, and the INH group had two dipping patterns: non-dipping (IND) and reverse dipping (IRD). Urinary electrolyte concentrations were significantly higher in IDH, and lower in INH. The INH group and 24-hour sustained hypertensives were the oldest cohort, while the NT and IDH were youngest. Pulse wave velocity (PWV) was significantly higher in the IND and IRD. The NT and IDH group had the lowest PWV. PWV in the INH was similar but not significantly different to the 24-hour sustained HT group. These findings indicate that the two INH subtypes (IND and IRD) damage large arteries to a similar effect as 24-hour sustained hypertension, while IDH does not cause any damage. The ABPM results were used to show changes in blood pressure with age. Different age group ranges were used, in increments of 10 years. Increased nocturnal blood pressure was associated with being older. Additionally, age-related changes in nocturnal blood pressure were associated with pre-clinical diastolic dysfunction. The current findings further show that blood pressure related cardiovascular target organ damage occurs during night-time in this population group. Urine analysis showed increased excretion in IDH and sodium retention in INH. Aldosterone levels were significantly higher in the INH, compared to 24-hour sustained HT group. Low aldosterone and salt retention increased nocturnal BP in the INH group. This means the current rise in the prevalence of cardiovascular disease in people of African descent despite increased efforts to diagnose and treat hypertension, is driven by INH, which remains undiagnosed because of the over reliance on conventional blood pressure measurementItem Effects of Supplemental Zingerone on Cobb 500 Broiler Chicken (Gallus gallus domesticus) Growth Performance, Health and Meat Quality(University of the Witwatersrand, Johannesburg, 2023-07) Mdoda, Bayanda; Chivandi, Eliton; Lembede, Busisani WisemanCommercial broiler and pullet chicken producers supplement chicken diets with sub-therapeutic doses of antibiotics such as zinc bacitracin that act as growth promoters to enhance production performance, meat and egg quality. Use of these antibiotics as growth promoters, in addition to causing environmental pollution, causes the public health challenge of antibiotic resistance which compromises poultry and consumer, hence the need to search for environmentally friendly and health-friendly alternatives to antibiotics. Phytochemicals, zingerone included, display biological activities similar to those of antibiotics. This study evaluated zingerone`s potential to replace bacitracin (ZnBcn) as a growth-promoting diet supplement in broiler feed specifically determining its effects on growth performance, meat quality and bird health. One hundred and twenty unsexed 1-day-old Cobb 500 broiler chicks (10 chicks per replicate with 3 replicates per diet) were randomly assigned to four dietary treatments where zingerone replaced ZnBcn at: diet 1 – 0 mg kg-1 (control: 500 mg akg-1 of zinc bacitracin); diet 2 – 40 mg kg-1; diet 3 – 80 mg kg-1 and diet 4 – 120 mg kg-1 in the starter, grower and finisher diets. The broiler chicks were fed ad libitum for 6 weeks: starter (week 1-2), grower (week 3-4), and finisher (week 5-6). Initial and weekly body mass, daily feed intake (FI), and terminal body mass (TBM) were measured. Body mass gain (BMG), average daily gain (ADG), and feed conversion ratio (FCR) were computed. On day 42, the chickens were humanely slaughtered, blood collected and carcasses dressed. The gastrointestinal tract (GIT) and accessory GIT viscera organs were weighed and small and large intestine lengths were measured. Empty carcass masses were measured and the dressing percentages were computed. Viscera macromorphometry, long bone indices and carcass traits, the meat’s physical quality [initial and ultimate pH (pHi and pHu), colour, thawing loss (TL), cooking loss (CL), and tenderness] traits, proximate and amino acid content and fatty acid profiles were measured. Plasma malonaldehyde (MDA) concentration, glutathione peroxidase (GSH-Px), glutathione-S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) activities, surrogate markers of liver and kidney function, liver fat content and histology were determined. Across growth phases and overall, dietary zingerone had similar effects (p > 0.05) as ZnBcn on the chicken’s TBM, BMG, ADG, FI, and FCR. It also had similar effects (p > 0.05) as ZnBcn on the chicken’s empty carcass mass, dressing percentage, long bone indices and viscera macromorphometry. Dietary zingerone had similar (p > 0.05) effects as ZnBcn on the broiler chicken meat’s pHi, pHu, CL, TL and tenderness. However, at 40 mg kg-1 of feed (diet 2) it increased the meat’s redness (a*) compared to that of counterparts fed the ZnBcn-fortified control diet. Furthermore, supplemental zingerone had a similar effect to that of ZnBcn on the meat’s crude protein content but it significantly increased the meat’s ash and fat contents (p < 0.01; p < 0.0001). Meat from chickens fed diet 2 (40 mg kg-1 of feed zingerone) had the highest concentration of essential amino acids (p < 0.05) and that from chickens fed diets 3 (80 mg kg-1 of feed zingerone) had the lowest (p > 0.001) total amino acid content. Dietary zingerone had a similar (p > 0.05) effect as ZnBcn on the chicken meat’s total saturated fatty acids, but breast meat from chickens fed diets 3 (80 mg kg-1 of feed zingerone) had significantly increased (p < 0.0001) total monounsaturated fatty acid and oleic acid content. Meat from chicken-fed diet 4 (120 mg kg-1 of feed zingerone) had the highest total polyunsaturated fatty acid and linoleic acid content and a higher PUFA:SFA ratio compared to that from counterparts fed diets 1, 2 and 3. Supplemental zingerone had similar effects (p > 0.05) as ZnBcn on the chickens’ liver masses and fat contents, plasma MDA concentration, GSH-Px, GST, SOD, CAT, alkaline phosphatase, alanine transaminase activities, albumin, total bilirubin, creatinine and urea concentrations. Chickens’ hepatic inflammation and steatosis scores were similar across diets (p > 0.05). At 120 mg kg-1 of feed zingerone, though similar to the control, supplemental zingerone decreased the chickens’ plasma globulin and total protein concentration (p < 0.01; p < 0.05) compared to counterparts supplemented at low and medium dose of zingerone. Zingerone can be used as a growth promoter in place of zinc bacitracin in broiler chicken diets without compromising growth, feed use efficiency, carcass yield, long bone and GIT viscera growth and development, the meat’s pH, CL, TL and tenderness. Furthermore, it can be used without eliciting oxidative stress in the birds and with no risk to kidneys, liver and general health of the birds. Importantly, zingerone, as a dietary supplement, can be used to enhance broiler chicken meat’s redness, positively impacting its acceptability and meat’s total monounsaturated, oleic acid, total polyunsaturated and linoleic acid fatty acid profile; thus improving its nutritional value.Item The potential of zingerone to protect against alcohol-induced liver disease(University of the Witwatersrand, Johannesburg, 2023-05) Asiedu, Bernice; Chivandi, Eliton; Nyakudya, Trevor; Lembede, BusisaniAlcohol can cross the placental blood-barrier and can also be secreted into breast milk. This can affect developing foetuses and/or nursing neonates negatively, thus impacting on metabolic health in early or later life. Zingerone (ZO) has anti-oxidant, anti-diabetic, anti-inflammatory, hypolipidaemic and hepato-protective properties. I hypothesised that neonatal oral administration of ZO could programme for protection against alcohol-induced metabolic derangements in suckling Sprague-Dawley (SD) rat pups mimicking human neonates that indirectly consume alcohol through their mother’s breast milk. The first experiment evaluated ZO’s potential to protect suckling rat pups against alcohol-induced metabolic derangements. Seventy 10-day old SD rat pups (males = 35; females = 35) were randomly assigned to four groups and administered treatments daily from postnatal (PND) 12-21: group 1-nutritive milk (NM), group 2-1 g/kg body mass ethanol (Eth), group 3-40 mg/kg body mass ZO and group 4 - NM+Eth+ZO. Terminal body mass, blood glucose concentration, lipid profile and hepatic antioxidant status were determined. Zingerone and ethanol had no effect on pups’ growth performance, blood glucose, total cholesterol, HDL- and LDL-cholesterol and hepatic thiobarbituric acid (TBARs), superoxide dismutase and catalase concentrations (p > 0.05). Ethanol decreased plasma triglyceride concentration in female rat pups (p = 0.04) but increased hepatic cytochrome P450E21 (CYP2E1) and decreased total glutathione (tGSH) concentration in male rat pups (p < 0.05). Zingerone increased tGSH in male rat pups (p = 0.003). A combination of ZO and ethanol increased (p = 0.047) hepatic CP2E1 concentration in male rat pups compared to control but had no effect (p = 0.717) on tGSH concentration. Neonatal orally administered ethanol induced hepatic oxidative stress which ZO, administered during the suckling period, failed to protect against. In experiment II, 123 SD rat pups (males = 60; females = 63) were administered the same neonatal interventions as in experiment I but from PDN22 they were grown to adolescence (PND45) with ad libitum access to normal rat chow and tap water. From PND 46-100, rats from each of the four neonatal groups were divided into two subgroups: subgroup I had tap water and subgroup II had ethanol solution as drinking fluids, for eight weeks. Body mass, feed, fluid and caloric intake were measured. Blood glucose concentration, plasma alanine transaminase and aspartate transaminase (ALT and AST) activities, adiponectin (ADP), leptin (LEP) and insulin (INS), tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and cytochrome P4502E1 (CYP2E1) concentrations were measured. HOMA-IR was computed. Visceral fat mass, hepatic fat content and histomorphometry were assessed. Hepatic TBARs and mRNA expressions of peroxisome proliferator activator receptor-alpha (PPAR-α), sterol regulatory element binding protein 1c (SREBP1c), nuclear factor kappa beta (NF-Kβ) and TNF-α were measured. Ethanol consumption in adulthood decreased feed and fluid intake but increased calorie intake and plasma CYP2E1 concentration (p < 0.05 vs control). It decreased blood glucose concentration of male rats (p = 0.026). A late single- and a double-alcohol hit had no effect on body and visceral fat mass of the rats (p > 0.05). Neonatal orally administered zingerone and ethanol and consumption of ethanol in adulthood had no effect on body mass, plasma lipid profile, adiponectin, leptin and insulin concentrations, HOMA-IR, AST and ALT activities, IL-6, TNF-α and hepatic TBARS and mRNA expression of NF-KB and TNF-α (p >0.05). A late single hit with ethanol increased hepatic fat content of male rats only (p = 0.014). A double and or late single ethanol hit increased liver fat content in female rats (p < 0.05). Both a late single and double ethanol hit downregulated PPAR-α but upregulated SREBP1c expression in male and female rats (p < 0.05) and it caused the development of large droplet macrosteatosis. A combination of neonatal orally administered ZO and a late single ethanol hit decreased visceral fat mass of female rats (p = 0.045 vs control) but it did not affect the blood glucose concentration of male rats (p > 0.05). Neonatal orally administered ZO with either a late single- or a double-ethanol hit caused hepatic macrosteatosis, but it had no effect on mRNA expression of PPAR-α of the rats (p > 0.05). However, neonatal orally administered ZO in combination with a late single ethanol hit did not affect SREBP1c expression of the rats but a combination of neonatal orally administered ZO with a double ethanol hit increased SREBP1c expression of female rats (p = 0.005). The responses of the rats to interventions showed sexual dimorphism: ethanol consumption in adulthood decreased blood glucose concentration of male rats only and an early single ethanol hit caused microsteatosis only in female rats. Zingerone protected male rats against ethanol-induced hepatic fat accumulation. It attenuated the ethanol-induced upregulation of hepatic SREPB1c expression in males but not in females. Ethanol (late single and/or double hit) downregulated the hepatic PPAR-α expression in the rats which was mitigated by ZO. Neonatal orally administered ZO attenuated the late single- and double-hit ethanol-induced macrosteatosis in the rats. Thus, neonatal orally administered ZO can potentially be used as a prophylactic agent against ethanol-induced hepatic lipid accumulation in males and steatosis in both males and females.Item The association between adult attachment style and pain perception in a South African cohort(University of the Witwatersrand, Johannesburg, 2024) Stamp, Gabriella ElisabethOur response to threats, including pain, is believed to be learnt during our early interpersonal connections and experiences. Interpersonal relationships can be measured through four adult attachment style classifications: Secure, Dismissing, Preoccupied and Fearful, with the latter three being collectively classified as Insecure attachment styles. Preliminary epidemiological evidence suggests that Insecure attachment styles are more prevalent in those with chronic pain, while experimental studies investigating the association between adult attachment and pain are inconclusive. In two separate investigations, the aims of my research were (i) to determine the association between adult attachment style and chronic pain prevalence and burden in a South African population, and (ii) to determine the association between the different adult attachment styles and measures of experimental pain as a way of assessing a potential mechanism for possible differences in pain perception between the attachment styles. In the first study, a nationwide online survey of a general South African population assessed adult attachment style (using The Experience in Close Relationships - Relationship Structures (ECR-RS) Questionnaire), prevalence of chronic pain and psychological factors that are typically associated with pain, including depression, anxiety and pain catastrophising. In participants who reported experiencing chronic pain, the association with attachment style and pain burden (pain sites, severity and interference, using the Brief Pain Inventory) was further investigated. A total of 2371 participants completed the survey, with the cohort being generally young in age (median age 23 years; IQR 20-28), well-educated and primarily female (74%), with predominantly a middle-to-high socioeconomic status. In this cohort, I found a higher-than-expected prevalence of chronic pain (27%); previously reported prevalence data in a South African population found the prevalence to be 18%. All three Insecure attachment styles were associated with increased chronic pain prevalence when compared to the Secure attachment style (Dismissing: 31%, Odds ratio [95%CI] = 1.38 [1.02-1.85], p=0.037; Preoccupied: 42%, Odds ratio [95%CI] = 2.26 [1.62-3.13], p<0.001; Fearful: 49%, Odds ratio [95%CI] = 2.95 [2.03-4.29], p<0.001). In participants with chronic pain, adult attachment style was not directly associated with the overall burden of chronic pain. Rather, my study found that pain catastrophising was the mediating factor between Insecure adult attachment styles and an increased burden of chronic pain. Female volunteers who had completed the survey were invited to participate in the second study, which involved in-person experimental procedures to evaluate the experience of thermal pain and mechanisms of pain analgesia using the Conditioned Pain Modulation (CPM) paradigm. In the 103 young (median age 21 years; IQR 20- 23) and well-educated (all completed at least secondary education) sample, no significant relationship was found between attachment style and heat pain threshold (t(54) = -0.45, p = 0.654), heat pain tolerance (t(47) = -1.16, p = 0.250), and intensity of heat pain (Estimate [95%CI] = -0.11 [-0.34-0.11], p-value = 0.330). Similarly, descending pain inhibition (assessed using CPM) was not associated with adult attachment style (t(59) = -0.97, p = 0.338). In these South African cohorts, adult attachment style directly associated with chronic pain prevalence, with remarkably more than double the chronic pain prevalence in Fearfully, compared to Securely, attached individuals. A possible mechanism underlying the association between insecure attachment style and high chronic pain prevalence may be differences in pain modulatory pathways, which was investigated through the CPM test paradigm in Part 2 of my research. Pain catastrophising mediated the relationships between attachment style and burden of pain, highlighting the role and impact of cognitive factors and the perception of threat on both attachment style and pain. Adult attachment style did not associate with perception of experimental pain, nor did it associate with mechanisms of pain inhibition. The data of the two research components of my thesis highlight the differences between chronic clinical pain and the once-off experience of experimental pain in a controlled and safe environment. The negative data in the experimental study may be explained by three main limitations: (i) The experimental protocol was not threatening enough and was unlikely to consistently activate the adult attachment system; (ii) individuals with high attachment anxiety and attachment avoidance dimension scores did not participate in the experimental study, which means the sample was biased and may not have shown any differences even if the protocol was threatening enough to activate the attachment system; (iii) the experimental pain protocol likely does not capture the threatening nature of chronic pain due to complex interactions of psychosocial factors that accompany chronic pain. These limitations are informative for future experimental pain studies, and I believe that CPM cannot, at this point, be ruled out as a mechanism for the increased chronic pain prevalence in insecurely compared to securely attached individuals. Moreover, pain catastrophising as a potential mechanism underlying the association between adult attachment style and the prevalence of chronic pain may also be a potential avenue for future studies to pursue.Item Determinant of metabolic syndrome and its cardiovascular complications among people of African ancestry(2024) Eluwole, Omotayo AlabaCardiovascular disease is now a leading cause of death globally. However, metabolic syndrome is an extremely critical healthcare issue worldwide due to progressive increase in obesity and its related factors. Obesity is strongly associated with insulin resistance and other components of metabolic syndrome. There is discrepancy in the use of parameters for the diagnostic criteria of metabolic syndrome due to genetic and environmental variability in different ethnicity. Body mass index and waist circumference (WC) are commonly used in the assessment of central obesity and abdominal obesity respectively. Fahed et al observed that waist circumference was employed because measurement was easy, however, waist circumference alone is inconclusive of abdominal adiposity and must be interpreted with body mass index. The two measurements (WC and BMI) have been documented to be strongly related to insulin resistance. (Fahed et al., 2022). However, there is controversial assessment of metabolic syndrome using either waist circumference (WC) or body mass index (BMI) or waist hip ratio (WHR) or combination of two measurements (Kassi et al., 2011; Fahed et al., 2022). Our study assessed the prevalence of metabolic syndrome among apparently healthy 1516 participants from African ancestry using seven established diagnostic criteria (NCEP-ATPIII- National Cholesterol Education Program Adult Treatment Panel III, WHO- World Health Organization, IDF-International Diabetes Federation, AHA/NHLBIAmerican Heart Association/National Heart, Lung and Blood Institute, EGIR - European Group for the study of Insulin Resistance, AACE- American Association of Clinical Endocrinology). The result revealed highest prevalence of metabolic syndrome when modified NCEP-ATPIII [National Cholesterol Education Program Adult Treatment Panel III (ATP III)] was considered. The predictive assessment of blood pressure and arterial stiffness may be useful in achieving early detection and prevention of target organ damage. This study further compared clinic blood pressure, ambulatory blood pressure and central pressure using conventional blood pressure monitor, Spacelabs 90207 (Spacelabs Inc., Redmond, Washington, USA) and applanation tonometry Sphygmocor device respectively. The findings revealed that central blood pressure and ambulatory blood pressure are more predictive of cardiovascular events among people of African ancestry. Our findings are pointers to cardiovascular risk in the study population. Additionally, this study provides new insights to the role of obesity in the perturbation of left ventricular geometry of people of African ancestry with metabolic syndrome; using quantitative and comprehensive evaluation of biochemical and echocardiographic profile. Aldosterone produced locally in adipose tissue, heart, kidney and vasculature increase the expression of cytokines and other fibrotic factors. Thus, role of the local renin angiotensin aldosterone system (RAAS) in the pathophysiology of atherosclerosis and cardio-renal fibrosis was evaluated in animal study. With high prevalence of metabolic syndrome and obesity in Africans, elevated aldosterone from diet may likely predispose African community to diastolic dysfunction; this may be a pointer to increased incidence of heart failure in groups of African ancestry. Hence, this study lends insights into the potential role of TRPM7; a novel non selective cation channel and chanzyme in aldosterone-induced cardiovascular fibrosis. This study concluded that modified NCEP-ATPIII has suitable components for the diagnosis of MS in people of African ancestry. Metabolic syndrome in people of African ancestry is strongly associated with factors such as sex, smoking and alcohol. Consequently, MS and other risk factors such as obesity, aldosterone and insulin resistance may lead to left diastolic dysfunction among individuals with MS. Experimentally, aldosterone-salt induced cardio-renal fibrosis, aggravated by TRPM7 might be the underlying pathogenesis of MS and its cardiovascular complications in Africans; thus suggests TRMP7 inhibitors has potential anti-fibrotic agents.Item The potential of zingerone to protect against ethanol-induced liver disease(2024) Asiedu, BerniceAlcohol can cross the placental blood-barrier and can also be secreted into breast milk. This can affect developing foetuses and/or nursing neonates negatively, thus impacting on metabolic health in early or later life. Zingerone (ZO) has anti-oxidant, anti-diabetic, anti-inflammatory, hypolipidaemic and hepato-protective properties. I hypothesised that neonatal oral administration of ZO could programme for protection against alcohol-induced metabolic derangements in suckling Sprague-Dawley (SD) rat pups mimicking human neonates that indirectly consume alcohol through their mother’s breast milk. The first experiment evaluated ZO’s potential to protect suckling rat pups against alcohol-induced metabolic derangements. Seventy 10-day old SD rat pups (males = 35; females = 35) were randomly assigned to four groups and administered treatments daily from postnatal (PND) 12-21: group 1-nutritive milk (NM), group 2-1 g/kg body mass ethanol (Eth), group 3- 40 mg/kg body mass ZO and group 4 - NM+Eth+ZO. Terminal body mass, blood glucose concentration, lipid profile and hepatic antioxidant status were determined. Zingerone and ethanol had no effect on pups’ growth performance, blood glucose, total cholesterol, HDL- and LDL-cholesterol and hepatic thiobarbituric acid (TBARs), superoxide dismutase and catalase concentrations (p > 0.05). Ethanol decreased plasma triglyceride concentration in female rat pups (p = 0.04) but increased hepatic cytochrome P450E21 (CYP2E1) and decreased total glutathione (tGSH) concentration in male rat pups (p < 0.05). Zingerone increased tGSH in male rat pups (p = 0.003). A combination of ZO and ethanol increased (p = 0.047) hepatic CP2E1 concentration in male rat pups compared to control but had no effect (p = 0.717) on tGSH concentration. Neonatal orally administered ethanol induced hepatic oxidative stress which ZO, administered during the suckling period, failed to protect against In experiment II, 123 SD rat pups (males = 60; females = 63) were administered the same neonatal interventions as in experiment I but from PDN22 they were grown to adolescence (PND45) with ad libitum access to normal rat chow and tap water. From PND 46-100, rats from each of the four neonatal groups were divided into two subgroups: subgroup I had tap water and subgroup II had ethanol solution as drinking fluids, for eight weeks. Body mass, feed, fluid and caloric intake were measured. Blood glucose concentration, plasma alanine transaminase and aspartate transaminase (ALT and AST) activities, adiponectin (ADP), leptin (LEP) and insulin (INS), tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and cytochrome P4502E1 (CYP2E1) concentrations were measured. HOMA-IR was computed. Visceral fat mass, hepatic fat content and histomorphometry were assessed. Hepatic TBARs and mRNA expressions of peroxisome proliferator activator receptor-alpha (PPAR-α), sterol regulatory element binding protein 1c (SREBP1c), nuclear factor kappa beta (NF-Kβ) and TNF-α were measured. Ethanol consumption in adulthood decreased feed and fluid intake but increased calorie intake and plasma CYP2E1 concentration (p < 0.05 vs control). It decreased blood glucose concentration of male rats (p = 0.026). A late single- and a double-alcohol hit had no effect on body and visceral fat mass of the rats (p > 0.05). Neonatal orally administered zingerone and ethanol and consumption of ethanol in adulthood had no effect on body mass, plasma lipid profile, adiponectin, leptin and insulin concentrations, HOMA-IR, AST and ALT activities, IL-6, TNF-α and hepatic TBARS and mRNA expression of NF-KB and TNF-α (p > 0.05). A late single hit with ethanol increased hepatic fat content of male rats only (p = 0.014). A double and or late single ethanol hit increased liver fat content in female rats (p < 0.05). Both a late single and double ethanol hit downregulated PPAR-α but upregulated SREBP1c expression in male and female rats (p < 0.05) and it caused the development of large droplet macrosteatosis. A combination of neonatal orally administered ZO and a late single ethanol hit decreased visceral fat mass of female rats (p = 0.045 vs control) but it did not affect the blood glucose concentration of male rats (p > 0.05). Neonatal orally administered ZO with either a late single- or a double-ethanol hit caused hepatic macrosteatosis, but it had no effect on mRNA expression of PPAR-α of the rats (p > 0.05). However, neonatal orally administered ZO in combination with a late single ethanol hit did not affect SREBP1c expression of the rats but a combination of neonatal orally aministered ZO with a double ethanol hit increased SREBP1c expression of female rats (p = 0.005). The responses of the rats to interventions showed sexual dimorphism: ethanol consumption in adulthood decreased blood glucose concentration of male rats only and an early single ethanol hit caused microsteatosis only in female rats. Zingerone protected male rats against ethanol-induced hepatic fat accumulation. It attenuated the ethanol-induced upregulation of hepatic SREPB1c expression in males but not in females. Ethanol (late single and/or double hit) downregulated the hepatic PPAR-α expression in the rats which was mitigated by ZO. Neonatal orally administered ZO attenuated the late single- and double-hit ethanol-induced macrosteatosis in the rats. Thus, neonatal orally administered ZO can potentially be used as a prophylactic agent against ethanolinduced hepatic lipid accumulation in males and steatosis in both males and females.