Magister Scientiae - MSc (Medical BioSciences)

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Analyses of spermatozoa surface proteins using different separation techniques
(University of the Western Cape, 2013) Fortuin, Kay Arlene; Henkel, Ralph; Menkveld, Rudolf
Passage of spermatozoa through the female reproductive tract is essential for the regulation of fertilization, ensuring that healthy sperm reach the oocyte. Previous studies were devoted to morphological selection of sperm cells by the cervical mucus. However, research prove that the loss of integrity of the sperm plasma membrane is associated with infertile men, irrespective of their normal semen parameters. This indicates that the sperm plasma membrane plays an important role in fertilization. Further studies indicated that sperm surface proteins assist penetration through the female reproductive tract and would therefore provide useful insight in understanding other factors associated with male infertility. The aim of this project was to determine if there are any differences between sperm surface proteins of fertile donor samples in relation to infertile patient samples using different separation techniques and different detergents. Three different sperm separation techniques were employed, including wash, swim-up (SU) and Percoll density gradient centrifugation (DGC).Parallel to this, the deoxy-ribose nucleic acid (DNA) fragmentation of these cells were analysed for comparison of the extent of DNA damage induced due to different separation techniques used. This provided evidence that the best separation technique is the DGC as it minimises the amount of DNA fragmentation caused. Four different detergents were used in the process of extracting the membrane proteins from spermatozoa, namely sodium dodecyl sulphate (SDS), saponin,cetyl-trimethyl-ammonium bromide (CTAB), and TWEEN-20. The membrane proteins were then separated on a12% SDS poly-acrylamide gel electrophoresis (PAGE), and analysed by Coomassie blue and silver staining techniques as well as densitometry. Due to the different chemical nature of the detergents that extracted different surface proteins, CTAB (cationic) and SDS (anionic) extracted the most because of its strong solubilising abilities as non-ionic detergents. Common proteins that were extracted in donor samples included; 115, 92.5, 89, 61, 55.5, 51.5, 47, 44.5, 43, 38.5, 34 and 28 kDa proteins. In patients, commonly occurring proteins included; 92.5, 74.5, 70, 60.5, 51.5, 50, 44.5, 43, 36, 29.5, and 25.5 kDa proteins. Marked differences were found between membrane proteins extracted from donor samples in comparison to patient samples. Identification of these proteins was done using the SwissProt database and a literature search. Mostly non-genomic progesterone receptors were identified; others included oestrogen receptor, a phosphotyrosyl protein, P34H, equatorial segment protein, mannose lectin receptor, human guanylylcyclase receptor, epididymal protease inhibitor receptor, PH30 and estradiol binding protein. The function of the membrane surface proteins identified in this study plays a vital role in fertilization. A few of these functions include sperm attachment and binding to the oocyte as well as penetration thereof. Others play a role in signalling events such as capacitation, hyperactivation and acrosome reaction. The absence of these proteins in patient sperm possibly accounts for the functional inability to successfully achieve fertilization suggesting that this provides molecular insight to reasons for infertility amongst men. In addition to this, proteins presented by patient samples that were absent in healthy donors may too account for their infertility status. Estradiol binding protein and PH30 are two proteins presented only in patient samples. Their function plays a role in the inhibition of the acrosome reaction and sperm-egg fusion, respectively. In conclusion, these differences in protein expression between fertile donors and patients may form the molecular basis of infertility amongst men and indicates possibilities for novel proteonomic approaches to improve andrological diagnosis in future.
Antibacterial activity of some South African plant extracts against streptococcus mutans
(University of the Western Cape, 2015) Kelani, Madeha Mohammed; Hiss, Donavon; Mohammed, Ahmed
Good oral health has a major influence on the general quality of life and well-being. Several chronic and systemic diseases have been attributed to poor oral health. With the increasing incidence of oral diseases, the global need for alterative prevention and treatment methods and safe, effective, and economical products has expanded. There are many studies showed that Streptococcus mutans has been implicated as major etiological agent of dental caries. South African has very rich natural flora especially Cape region. Several South African medicinal plants have been used since immemorial time for treatment of different human pathologies including dental problems. The antibacterial activities of plants extracts have been recognized and documented scientifically during the last few decades. In this project we aimed at the screening of 31 South African plants randomly collected from Cape region for their antibacterial activity against Streptococcus mutans initially at two concentrations (500 and 100 µg/ml).MIC’s and MBC’s were determined for the active plant extracts, as well as the qualitative studies of the effect of the active extracts on the biofilm formation. The best or the most active safe plant (Psoralea fruticans) was submitted to chromatographic separation to isolate the bioactive compounds which could be responsible for such activity. Identification of the pure active compounds was carried out using different spectroscopic techniques. Finally the biological evaluation of the isolated pure compounds was measured against S. mutans and also the cytotoxicity studies in-vitro against normal cells lines was carried out.
The antihypertentive effect of aqueous extract O Africana leaves
(University of the Western Cape, 2007) Wang, Xu; Dietrich, Daneel; Johnson, Quinton; Dept. of Medical BioSciences; Faculty of Science
The incidence of cardiovascular diseases, including hypertension, is on the increase worldwide. Medicinal plants played an important role in the treatment of hypertension for centuries. Very few scientific studies have, however, been done to validate the use of these phytotherapies. O africana is on of the many phytotherapies that has been use indigenously for years to treat hypertension. The objectives of this study were to determine the most effective does of O africana aqueous extract which will reduce blood pressure; to determine whether chronic administration of O africana can be used to prevent and treat hypertension; to determine whether O africana exert its effects by modulation of the renin-angiotensin system.
The antioxidant properties of melatonin during chemical hypoxia and reoxygenation injury in rat ventricular myocytes
(University of the Western Cape, 2000) Salie, Ruduwaan; Dietrich, Daneel; Lochner, Amanda
It is well known that ischaemia chemical hypoxia followed by reperfusion is not always accompanied by recovery of myocardial function and often produces further cell damage (Hearse et al., 1973). This phenomenon commonly referred to as the oxygen paradox (Hearse et al., 1973), is usually characterised by extensive tissue damage and the formation of oxygen free radicals / reactive oxygen species (ROS). As the work on free radicals progressed it became apparent that there is a fine balance between cellular systems that produce free radicals and those that sustain their tolerable levels, to maintain normal cell function (Ferrari et al., 1990). The relative importance of free radicals in the production of irreversible cell damage, as well as the mechanisms involved are not fully understood. Using the rat mode of myocardial infarction followed by reperfusion, many investigators employed various antioxidants / free radical scavengers in various combinations at different stages of hypoxia / reoxygenation with the intention of reducing free radical mediated damage (Meerson et al., 1981; Shlafer et al., 1982; Stewart et al., 1983; Hess et a1., 1983; McCord and Fridovich, 1973). There is also an increasing interest in defining new antioxidants of high potency, low toxicity and good solubility properties in aqueous as well as organic phases. Recently it has been shown that melatonin (n-acetyl-5-methoxytryptamine) has the ability to directly scavenge free radicals (Reiter, 1993) It was therefore the aim of this study, to investigate oxidative stress during chemical hypoxia and reoxygenation in isolated rat ventricular myocytes and to study the antioxidant effects sf 6sl4fsnin, employed at different stages of chemical hypoxia and / or reoxygenation. To reveal the phenomenon of oxidative stress using laser scanning confocal microscopy, myocytes were preloaded with tetramethyl rhodamine (TMRM) together with one of the following fluorophores: (i) dihydric loro fluorescein diacetate (DCDHF) or dihydrorhodaminel23 (DHR) to illustrate the formation of HzOz and / or ROS; or (ii) fluo'3, AM (fluo) to show changes in intracellular free calcium. In superfused myocytes, chemical hypoxia was induced for 12.5 min by the addition of 1.5 mM KCN and 20 mM deoxy glucose to the superfusion buffer followed by 0, 1.5 or 15 min reoxygenation. Cells were also exposed to 27 .5 min chemical hypoxia without reoxygetration. Melatonin (50 pM) was added at different time intervals during the experimental protocol. All the myocytes (untreated and melatonin treated), indicated increased DCDHF but not DHR or fluo fluorescence under control oxygenated conditions (norrroxia). This probably implicate nonanal physiological levels of H2O2 and I or ROS and presumably an intact endogenous antioxidant system, since none of the cells suffered any damage. It was also indicated that melatonin had no effect on H2O2 and / or ROS formation and the viability of any of the cells during normoxia. Exposure of myocytes to chemical hypoxia for 12.5 min caused contracture and damage to 70 - 89 % of cells. This was associated with the generation of H2O2 and/ or ROS, an increase in intracellular calcium but maintenance of membrane potential. Early reoxygenation did not exacerbate or improve the changes observed during chemical hypoxia. Melatonin protected myocytes from hypoxic induced damage and increased cell viability from 20 to 80 % (p<0.05). Melatonin treated cells had reduced levels of ROS and intracellular calcium. The protection conferred by melatonin during exposure of cells to 12.5 min chemical hypoxia disappears if chemical hypoxia is prolonged to 27.5 min. After 27 -5 mn chemical hypoxia > 85 Vo of cells showed marked morphological changes and were considered to be irreversibly damaged. Myocytes indicated increased DCDHF; DHR and fluo fluorescence, implicating increased H2O2 and I or ROS formation and increased intracellular calcium respectively, after 12.5 min chemical hypoxia. However, the application of melatonin, effectively scavenged H2O2 and / or ROS and protected cells only for the first 14.5 min of chemical hypoxia, after which all of the cells indicated increased H2O2 and / or ROS formation, increased intracellular calcium and suffered irreversible damage. Presumably, as chemical hypoxia progressed, the accumulation of H2O2, the formation of ROS and degradation of endogenous antioxidant enzymes transpired, which resulted in damage to the majority of cells by the end of this period.
Aspects of the interrelation between hypertension and insulin resistance
(University of the Western Cape, 2009) Osuafor, Godswill Nwabuisi; Dietrich, Daneel; Dept. of Medical BioSciences; Faculty of Science
Conclusion of this study: These data suggest that 6 weeks of high-fat feeding induces hypertension but does not produce obesity, dyslipidemia and insulin resistance. However, this model may be useful in studying vascular reactivity in hypertension in the absence of insulin resistance.
Aspects of the interrelation between hypertension and insulin resistance: a preliminary study
(2009) Nwabuisi, Osuafor Godswill; Dietrich, Daneel
Background: It is well known that some genetic factors and dietary factors, such as excessive salt intake and excessive caloric intake (resulting in obesity) are risk factors for hypertension. Fifty percent of all hypertensive patients are also insulin resistant. Both hypertension and insulin resistance are again risk factors for other cardiovascular diseases such as atherosclerosis and heart failure. The nature of the association between hypertension and insulin resistance has not been clearly elucidated. Spontaneously hypertensive rats are the ideal models to study the aspects of the relationships between hypertension and insulin resistance. Models of high-fat feeding induce obesity,hypertension and insulin resistance and are thus used extensively to study hypertension because these models closely mimic some of the renal and cardiovascular changes found in human hypertensive patients. The present study was initiated to evaluate if insulin resistance will develop within 6 weeks in a model of high-fat diet induced hypertension and if so, to determine whether captopril will affect the presence of insulin resistance.This model should in future be used to study vascular reactivity to phenylephrine (PHE),acetylcholine (ACH) and sodium nitroprusside (SNP) in hypertensive animals in theabsence or presence of insulin resistance and in normotensive insulin resistant animals. Methods: In a series of experiments, rats were divided into four groups that received different treatments: (i) laboratory pellets, (ii) high-fat diet, (iii) high-fat diet plus captopril and (iv) high-fat diet plus vehicle. Body weight was measured weekly for 6 weeks. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured every week during the 6-weeks feeding period by the tail cuff method using a two channel computerized non-invasive system from Kent Scientific Corporation, USA.m Intraperitonealy glucose tolerance tests (IPGTTs) were performed at week 3 and week 6.After 6 weeks, and after an overnight fast, the plasma lipid profile was determined using a portable CardiochekTM blood test system. Fasting plasma insulin was determined using an immunoenzymatic assay for the in vitro quantitative measurement of rat insulin (INS) in serum and plasma. Insulin sensitivity was estimated by the quantitative insulin sensitivity check index (QUICKI) using the fasting plasma insulin and fasting glucose levels. After week 6 on the high-fat diet, thoracic aortae from the control and high-fat fed(HFD) animals were excised and vascular response to PHE, ACH and SNP were assessed in intact and denuded endothelium.Result: High-fat feeding did not cause a significant increase in body weight. High-fat feeding significantly increased systolic blood pressure from 125±2.1 mmHg in control animals to 155±5.9 mmHg in the HFD group (P < 0.05) and 158±5.6 mmHg in the HFDV group (P < 0.05). Diastolic blood pressure was increased from 86±2.8 mmHg in the control group to 117±2.5 mmHg in the HFD group (P < 0.05) and 113±3.4 mmHg in the HFDV group (P < 0.05). Visceral fat was increased from 0.8±0.1g in the control group to 3.1±0.6 g in the HFD group and 3.8±0.6 g in the HFDV group. IPGTTs performed at weeks 3 and 6 respectively did not differ significantly from the control group as evidenced from the AUC’s at weeks 3 and 6 respectively. High-fat feeding had no significant effects on blood cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) values or and fasting plasma insulin levels. The KCl induced contraction in both aortic rings with intact and denuded endothelium did not differ significantly between the control and HFD groups (P= 0.4 and 0.8) respectively. The contraction mediated by KCl in aortic rings with intact and denuded endothelium from the control or HFD groups also did not differ significantly(control: intact vs denuded, P = 0.2; HFD: intact vs denuded, P = 1). Dose responsecurves(1-10 μM) to PHE indicated slightly stronger contractions in the high-fat fed animals at submaximal doses tested. The maximum contraction achieved was however the same (94±19% and 99±2.6% relative to KCl induced contraction, in the control and HFD group respectively, P<0.05). Relaxation responses to ACH and SNP represent preliminary data.Conclusion: These data suggest that 6 weeks of high-fat feeding induces hypertension but does not produce obesity, dyslipidemia and insulin resistance. However, this model may be useful in studying vascular reactivity in hypertension in the absence of insulin resistance.
Aspects of the reproductive physiology of male vervet monkeys maintained in a laboratory environment
(University of the Western Cape, 1995) Seier, Jurgen Victor; van der Host, Gerhard; Menkveld, Roelof
In biomedical research limited use has been made internationally of African non-human primates. As a result, their reproductive physiology has been less well defined, when compared to the more commonly used macaque species. There have also been no extensive developments in the associated field of assisted reproduction for African non-human primates. To contribute to the knowledge of the reproductive physiology of African non-human primates, this study presents semen characteristics from the vervet monkey. The focus is on abnormal sperm morphology which has not been described in detail. AII individuals utilized here either wild caught or colony bred and maintained in an indoor laboratory breeding colony. A detailed description of the frequency and prevalence of specific morphologically abnormal forms of sperm from vervet monkeys and illustrations of the different types of abnormalities is provided for the first time. Most features, such as the prevalence of tail abnormalities, particularly coiled and bent tails, were similar to what has been reported for other OId World cercopithecines. A total of 28 types of morphologically abnormal forms were found including 13 head abnormalities, seven midpiece abnormalities and eight principal- and endpiece abnormalities. Sperm head abnormalities were rare, occurring at a rate of less than 2t in each group. Except for the nipple defect, there was no difference between colony bred and wild caught individuals in the rate at which defective forms occurred. on the other hand not aII types of abnormalities were found in each group. A relationship between morphology and fertility could not be established because some individuals with the highest rate of abnormal morphology were successful breeders. Evaluation of consecutive ejaculates revealed highly variable semen characteristics both within and amongst different individuals. This observation extends to other sperm characteristics such as the concentration, vitality, speed of forward progression (F.P) and motility. The evaluation of reproductive potential based on one or two ejaculates is therefore not possible. The pH of vervet monkey semen was similar to that of humans. out of two indicator papers tested to determine this variable, only one was found to be reliable in terms of reference values obtained with a pH meter. Another aim of the study was to develop a cryopreservation method which yields a satisfactory post-thaw recover of progressively motile sperm. No specialized equipment other than a liquid nitrogen storage container was needed. Semen samples were diluted with a Tes-Tris extender containing 5% glycerol before being cooled to 50 over 3O minutes. This was followed by aspiration of the samples into paillettes and freezing to a plunge temperature of -139oC for 20 minutes in liquid nitrogen vapour. The paillettes were finally stored in liquid nitrogen. Conspicuous features of this method were the addition of glycerol at 32oc, a short glycerol equilibration time, a fast freezing rate, a low plunge temperature and a fast thawing rate.
An assessment of carpobrotrn actnacifurmis and cissampelos capensis as potential antimicrobial agents and their effects on animal metabolism
(University of the Western Cape, 2002) Bowie, Andrea; Johnson, Quinton
An assessm entof Carpobrotus acinaciformib and Cissampelos capensis as potential antimicrobialagentsandtheireffectsonanimalmetabolism
An assessment of Carpobrotus acinaciformis and Cissampelos capensis as potential antimicrobial agents and their effects on animal metabolism
(University of the Western Cape, 2002) Bowie, Andrea; Johnson, Quinton
The definition of a medicinal plant (as formulated by the WHO) is a plant that consists of either one or more plant parts with therapeutic properties that can be used in the development of drugs (sofowora lg82). Various medicinal plants have been used over the years for their healing properties, and it can even be said that this is an ancient practice (Cowan 1999). Plant derived medicines have been part of traditional healthcare in most parts of the world for thousands of years @alombo & Semble 2001- Salie 1998))' Presently, approximately l|%of the world population make use of plants and its extracts (salie 1998; Abelson 1990). Despite this widespread use of medicinal plants, only a fraction has been tested. Many plant derived natural products must be investigated for their pharmacological activity (Mendelson & Balick 1998; Gentry 1993)' Hence it is of utmost importance to study medicinal plants for safety and efficacy @loff 1998)' since there is still an infinite number that must be studied and discovered (Abelson 1990; Sofowora 1982). Hippocratus in the late fifth century B.C.) was a physician who strongly believed in herbal remedies to treat many ailments and recorded the use of approximately 300 to 400 medicinal plants (cowan 1999; Sofowora 1982; Schultes 1978). It is also believed that the Egyptians (1500 B.C) made use of medicinal plants as some records excavated from ancient Egyptian tombs stated (Sofowora 1982). The De Materia Medical medicinal plant catalogue of about 600 medicinal plants, was compiled by the Greek Dioscorides (A. D. 60) and was used by Europeans as a standard reference during medieval times (Cowan Lggg,Sofowora lg82). The works of the physician Galen were used in the middle ages but many of his records were destroyed. In spite of these unfortunate circumstances, present allopathic and homeopathic systems have been derived from the works of Galen (Sofowora 1982)'
The Assessment of Effects of Carbon Quantum Dots on Immune System Biomarkers Using RAW 264.7 Macrophage Cells
(University of the Western Cape, 2020) Fowler, Jodi; Pool, Edmund
Nanotechnology is a rapidly growing field of research. Due to major innovations brought about by developments in nanotech, several consumer products are currently available containing nanomaterials. The increase of nanomaterial production and use is accompanied by the increased potential of human, plant and animal exposure to these nanomaterials. As a relatively new nanomaterial, carbon quantum dots (CQDs) are being extensively used and researched due to its unique properties. Although many studies have assessed the toxic potential of CQDs, and found them to exhibit low toxicity, there is lack of work assessing the effects on the immune system. In the present study, RAW 264.7 murine macrophages were used as model to assess the immunomodulatory potential of CQDs. RAW cells exposed to varying concentrations of CQDs (0-500μg/ml), showed that CQDs caused a reduction at cell viability. In the absence of a mitogen CQDs, induced an inflammatory response by stimulating the release of various cytokines and chemokines such as, TNFα, MIP-1α, MIP-1β, MIP-2, IP-10, G-CSF, GM-CSF, and JE.
Assessment of raw and treated sewage using in vitro assays
(University of the Western Cape, 2014) Booysen, Robin Alvin; Pool, Edmund J.
Water scarcity is becoming an increasingly relevant problem for urban centres, especially in Southern Africa. However, water availability is not the only concern for consumers, because water quality is just as relevant. Many studies have revealed adverse health effects in organisms exposed to polluted waters, and the main source of that water pollution was traced back to sewage treatment works (STWs). Physiological systems that are affected include the endocrine system (as well as the reproductive system) and the immune system. Recently, the Stellenbosch STW started upgrading its facility, but this procedure would also affect the STW‘s operations. Stellenbosch STW uses an activated sludge treatment, but also employs trickling filters (biofilters). After screening and grit removal, wastewater enters trickling filters, and then undergoes activated sludge treatment (aerobic basin). After activated sludge treatment (and settling) some water is chlorinated before entering a maturation pond. The other water goes directly to a larger maturation pond (for a longer period), instead. The final effluent then gets discharged into the Veldwagters River. Since STW operations is an important factor in STW effluent quality, this study aimed to investigate the water quality (at Stellenbosch STW) during the upgrade. Specifically, the bacterial quality, the steroidal quality (testosterone, progesterone, estrone: E1, 17 β- estradiol: E2 and 17 α-ethinyl estradiol: EE2) and the potential immunotoxic quality of waters were assessed. Water samples were collected after the grit removal (influent), after the trickling filters (biofilter effluent), while it was leaving the aerobic basin activated sludge effluent) and as it was leaving the maturation ponds (final effluent). To determine bacterial quality a semi-quantitative ReadyCult® assay was performed on raw water samples (detects total coliforms and Escherichia coli). Bacterial levels were high for all influent samples, water from the biofilter, water from the aerobic digester (activated sludge) and the final effluent (most days). The first collection date, however, showed less than 1cfu/mL of both E. coli and total coliforms for the final effluent. Raw water also underwent solid phase extraction, before the steroid concentrations were determined by enzyme-linked immunosorbent assays (ELISAs). Steroid levels were very high in the influent. Each treatment progressively reduced the steroid concentration. However, progesterone concentration increased during the biofilter treatment. The increase in progesterone was probably due to bacterial de-conjugation of hydrophilic-progesterone-conjugates. Nonetheless effluent steroid levels were significantly lower than the influent. Steroid reduction through the Stellenbosch STW was 96%, 95%, 55%, 78% and 87% for testosterone, progesterone, estrone, estradiol and ethinyl estradiol respectively. Much variability in steroid concentrations was noted between sampling dates. The activated sludge treatment was the best at reducing steroid concentration. Nonetheless, the STW still discharged steroids into the environment. Finally, the humoral immune effects of Stellenbosch STW influent and effluent was determined by using hybridoma cells and assessing affects on antibody production. Antibody levels were then detected by ELISA. No adverse effects to antibody synthesis/secretion were noted as a result of exposure to either influent or effluent.
The association between environmental exposures during childhood and the subsequent development of crohn's disease in the Western Cape
(University of the Western Cape, 2015) Sabe, Victor T.; Basson, Abigail; Dietrich, Daneel
Background: A subtype of inflammatory bowel disease, Crohn’s disease is thought to represent a complex interaction between environmental factors, a defective immune system, the gastrointestinal microbiome and genetic susceptibility. Aim: The focus of this study was to investigate the association between environmental exposures during childhood and the subsequent development of Crohn’s disease, thus the two primary aims were to: 1) conduct a systematic review of the literature evaluating environmental risk factors during childhood, defined by studies either as, age intervals (e.g., 0-5, 6-10 and 11-18 years), or more 'broadly' as 0-18 years; and 2) investigate the association between childhood environmental exposures during three age intervals (0-5, 6-10 and 11-18 years), as well as frequency of childhood infections and the future development of Crohn's disease based on a score analysis, using a subset of previously collected data from a completed doctoral thesis involving a case control study design in study population, in the Western Cape, South Africa. The aim included a primary analysis of the latter dataset for childhood infections. Design: For the first aim of the study, a systematic search was conducted during March 2015 in electronic databases, such as EMBASE, EBSCOhost (Medline), Ovid, Scopus and World Cat, PubMed and Biomed Central, to identify epidemiological studies that examined the association between childhood environmental exposures and the subsequent development of Crohn's disease. Studies evaluating childhood exposure either by age intervals, or more broadly, from birth until 18 years were included. The environmental exposures evaluated in the review were; farm animal contact, place of upbringing, sibship size, household pets, primary water source and hot water availability. Of the 181 identified articles, 16 were included in the final systematic review. The second aim of the study involved a post hoc analysis of a subset of findings from the completed doctoral research by Abigail Basson with regard to the multiple logistic regression analysis evaluating environmental risk factor exposure during three age intervals; 0-5 years, 6-10 years and 11-18 years. In the present research, two different methodological approaches were undertaken. Briefly, exposure variables, of similar nature, were combined into subgroups and assigned weighting scores. The two 'subgroup models' were designated as: Group A and Group B. Based on these premises, a score analysis was performed, and the difference in scores, between case and control groups, was compared. In addition, multiple logistic regression models were conducted on a subset of original data from the aforementioned completed doctoral study to assess the association between the frequency of childhood infections between 0-20 years and risk of Crohn’s disease development. Following this, a score analysis was again performed. Results: Sixteen studies were included in the systematic review. Of the five studies that investigated the association between place of upbringing during the age interval 0-5 years and the subsequent development of Crohn's disease, three found no significant association; however of the three studies evaluating place of upbringing during the age intervals 6-10 and 11-18 years, only one study identified a significant association. Three studies investigated exposure to farm animals during the age interval 0-5 years, of which, two identified a significant association. Of the latter three studies, two investigated farm animal contact during the age intervals 6-10 and 11-18 years, but only one reported a significant association during these age intervals. Notably, this was the study which had failed to identify an association during the 0-5 year age interval. Both studies which broadly evaluated farm animal exposure during 'childhood' reported that not having contact with animals significantly increased the risk of developing Crohn's disease. Of the five studies that investigated exposure to pets during the age interval 0-5 years, only one identified a significant risk association, namely with exposure to cats. Of the three which investigated pet exposure during the age intervals 6-10 years and 11-18 years, one identified a significant association, for both age intervals. Five studies investigated pet exposure during 'childhood'; one found that having a pet significantly increased the risk of developing Crohn's disease, two reported that not having a pet significantly increased risk in developing Crohn's disease, whereas the remaining studies found no significant association. Only one study evaluated primary water source during the three age intervals; during the age interval 0-5 years and 11-18 years, having piped tap or bottled water was significantly associated with CD development. Of the four studies investigating primary water source during ‘childhood’, only one reported a significant association between primary water source and the development of Crohn's disease. The availability of hot water during the age interval 0-5 years was significantly associated with Crohn's disease development in one of the three relevant studies. Two studies investigated hot water availability during 6-10 and 11-18 years, however both failed to identify a significant association. When broadly evaluated, hot water availability during 'childhood' was significantly associated with Crohn's disease risk, in two of the three relevant studies. None of the studies which investigated sibship size and the risk of future Crohn's disease development during defined age intervals reported a significant association. Only two of the seven studies that evaluated sibship size during childhood reported a significant association. Results of the score analysis revealed a significant difference during all three age intervals between the case and control groups with Group A and Group B, with cases having significantly lower exposure scores (approximately 30% and 40% lower, respectively), when compared with that of controls. On multiple logistic regression analysis, subjects who never had tooth decay/cavity (OR = 1.78; 95% CI, 1.05-3.04), periodontitis (OR = 1.95; 95% CI, 1.10, 3.48), diarrhoea (OR = 2.71; 95% CI, 1.62-4.62), gastritis (OR = 2.13; 95% CI, 1.30-3.35), or mouth ulcers (OR = 2.02; 95% CI, 1.12-3.70), at least once per year or more, were at an increased risk for later development of Crohn's disease, when compared to those who were exposed to these infections at least once per year or more. There was a significant difference in exposure scores between the case and control groups (OR = 0.88; 95% CI, 0.82-0.94), thus indicating that cases had 12% less exposure to childhood infections from birth until the age of 20 years, when compared to the controls. Conclusion: The systematic review of the literature provides evidence in support of the hygiene hypothesis, in that delayed exposure to immunostimulatory microbes through the environmental exposures increases the risk for future CD development, in genetically susceptible individuals. In addition, the literature supports that the childhood environment plays an important role in the aetiology of Crohn's disease. However, the lack of consistent findings between studies, particularly those which have broadly defined ‘childhood’ implies that timing of exposure plays a crucial role in this ever evolving paradigm. Results from the score analysis provide insight into the 'compound' effects from multiple environmental exposures in the aetiology of Crohn's disease. While the present research was unable to provide any explanation for the underlying mechanism of disease pathogenesis, overall, the findings have important implications for future IBD-related studies as they demonstrate the importance of accounting for environment as a 'whole' when conducting epidemiological studies, as opposed to focusing on individual environmental factors, as well as that it is imperative to investigate environmental exposures within the context of defined age intervals.
The association of BMI and blood pressure measurements with depressive and quality of life scores in university students
(University of the Western Cape, 2022) Gamieldien, Ammaarah; De Smidt, Juley
Depression is a very common and serious mental illness. Studies have shown that depression has a significant impact on both social and economic aspects of sufferers worldwide as well as in South Africa. Research has shown that university students in South Africa have a higher prevalence than the general South African population. Major Depressive Disorder (MDD) is the most common and incapacitating form of depression. MDD is characterized as at least two weeks of a low mood that is apparentafter most situations. There are several contributing factors to depression as well as comorbidities which may lead to depression. When a patient suffers from depression along with another illness, it is described as the comorbidity of depression.
The association of mercury from dental amalgam with urinary selenium
(University of the Western Cape, 2017) Aljabo, Rukaia Emhemed; Oelofse, Andre; Osman, Yusuf
Background: Dental amalgam has been the traditional material for filling cavities in teeth. Mercury (Hg) is a component of dental amalgam, from where it is continuously released and deposited in different tissues, mostly in the brain and the kidneys. Selenium is an important essential element in the human body. Mercury exposure from dental amalgam fillings associated with reduced the levels of selenium. Aims and objectives: The aims of the current study were to investigate the leaching of mercury from dental amalgam fillings and also to investigate the relationship between the leached mercury from dental amalgam fillings and selenium concentrations in the bloodstream. The objective was to determine the mercury from dental amalgam fillings and urinary selenium levels. Methods: Samples were collected from patients attending Tygerberg Oral Health Centre, Cape Town (South Africa). 107 patients who had 1-12 dental amalgam fillings provided the samples of urine, buccal swabs and did the chewing gum test. The samples were analysed by using inductively coupled plasma-mass spectrometry. The data were analysed by IBM (p<0.05) test with an SPSS computer software package version 24. The study involved analyses of samples of urine (n=107), chewing gum and buccal swabs (n= 102). Results: The median urinary concentrations of mercury and selenium in female and male samples were 0.40 μg/L, 0.60 μg/L Hg and 26.29 μg/L, 29.32 μg/L Se respectively. While the median Hg concentrations in chewing gum test and buccal swabs samples in female and male were 2.04 mg/g, 1.89 mg/g Hg and 0.16 μg/L, 0.09 μg/L respectively. Conclusion: The excretion of urinary selenium concentration was influenced by concentration of mercury in urine and age of participants but not affected by concentrations of mercury in buccal swabs, chewing gum and gender of participants.
A baseline evaluation of the cytotoxicity of gold nanoparticles in different types of mammalian cells for future radiosensitization studies
(University of the Western Cape, 2020) De Bruyn, Shana; de Kock, M.; Vandevoorde, C.
Recently nanoparticles (NPs) have been introduced and used in combination with therapeutic approaches to develop nanotechnology-enabled medicine. These nanostructures allow for the exploitation of the physiochemical properties which may be beneficial in cancer treatment. The use of NPs in nanomedicine has proven successful in modern chemotherapeutics and has demonstrated promising potential in in vivo and in vitro radiosensitization studies. This is a baseline study aimed to determine the cytotoxic effects of AuNPs for potential radiosensitization analysis. The study analysed the effects of different AuNP sizes (30, 50 and 80nm), concentrations (5, 10 and 15 μg/ml) over various time periods in CHOK1 and A549 cells.
A baseline evaluation of the cytotoxicity of gold nanoparticles in different types of mammalian cells for future radiosensitization studies
(University of the Western Cape, 2020) De Bruyn, Shana; De Kock, M
Recently nanoparticles (NPs) have been introduced and used in combination with therapeutic approaches to develop nanotechnology-enabled medicine. These nanostructures allow for the exploitation of the physiochemical properties which may be beneficial in cancer treatment. The use of NPs in nanomedicine has proven successful in modern chemotherapeutics and has demonstrated promising potential in in vivo and in vitro radiosensitization studies. This is a baseline study aimed to determine the cytotoxic effects of AuNPs for potential radiosensitization analysis. The study analysed the effects of different AuNP sizes (30, 50 and 80nm), concentrations (5, 10 and 15 μg/ml) over various time periods in CHOK1 and A549 cells. AuNPs were characterised by DLS and ZP analysis and showed that particles were moderately polydispersed and moderately to highly stable in charge. The effects on viability and metabolic activity of cells were determined using crystal violet and the WST-1 assay.
Brine shrimp lethality test and acetylcholine esterase inhibition studies on selected South African medicinal plants
(University of the Western Cape, 2012) Jooste, Clarese Staley; Mabusela, Thozamile Wilfred; Johnson, Quinton
Research into traditional medicines is often conducted in a multidisciplinary approach as motivated by a desire to understand them in as complete a manner as possible,realizing their chemistry, biology and pharmacology. One biological approach involves monitoring the cytotoxicity of the extracts of subfractions against the nauplii,Artemia salina (brine shrimp). Organic and aqueous extracts of seven South African medicinal plants was investigated for biological activity. Selected plant extracts was also evaluated for AChE inhibitory activity. The objectives of this study was to look for any correlation between known biological activities of the investigated plants and BSLT lethality data and also to look for any correlation between AChEI activity and BSLT lethality data for selected plant extracts. The most active of the plants was the n-hex extract of T.alliacea, followed by the aqueous extract of C.mellei and the MeOH extract of C.quadrifidus; the MeOH and the DCM extracts of A.afra; the DCM extract of P.undulatum and the EtOAc extract of A.annua. The results from this study show a good correlation with antitumor, antimicrobial and anti-trypanocidal activity.The various plants extracts investigated showed good inhibitory activity towards AChE using the TLC bioautography method. The results obtained from this study indicate that this type of activity is not only subject to plants containing alkaloids, but rather a diverse class of compounds may exhibit this kind of activity. The extracts that showed good AChE inhibitory activity also showed good cytotoxicity towards brine shrimp nauplii.
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, Juléy
Cardiovascular 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.
Circadian activity rhythms and early gene expression in the suprachiasmatic nucleus of a diurnal rodent, Rhabdomys pumilio
(UWC, 2001) Thomas, D; Hofmeyer, MD; Bennett, N; Cooper, HM
Although humans are diurnal in behavior, animal models used for the study of circadian rhythms are mainly restricted to nocturnal rodents. This study focused on circadian behavior and gene expression in a diurnal rodent from South Africa, the four-striped field mouse (Rhabdomys pumilio). In contrast to nocturnal rodents which have rod-dominated retinas, the retina of this field mouse contained approximately an equal amount of cones as rods. The cones included short-wavelength (blue-sensitive) and mid-wavelength (green-sensitive) cones. In order to characterize the behavioral pattern of daily activity, locomotor rhythms were studied under different light regimes using an automated data recording system. Under conditions of natural daylight which include dawn and dusk transitions, R. pumilio showed activity restricted to the daytime period. Activity was concentrated around morning and evening hours with a decrease during mid-day.
Cloning and characterization of the human coronavirus NL63 nucleocapsid protein
(University of the Western Cape, 2011) Berry, Michael; Tan, Y.J.; Dept. of Medical BioSciences
The human coronavirus NL63 was discovered in 2004 by a team of researchers in Amsterdam. Since its discovery it has been shown to have worldwide spread and affects mainly children, aged 0-5 years old, the immunocompromised and the elderly. Infection with HCoV-NL63 commonly results in mild upper respiratory tract infections and presents as the common cold, with symptoms including fever, cough, sore throat and rhinorrhoea. Lower respiratory tract findings are less common but may develop into more serious complications including bronchiolitis, pneumonia and croup. The primary function of the HCoV-NL63 nucleocapsid (N) protein is the formation of theprotective ribonucleocapsid core. For this particle to assemble, the N-protein undergoes N-N dimerization and then interacts with viral RNA. Besides the primary structural role of the Nprotein, it is also understood to be involved in viral RNA transcription, translation and replication, including several other physiological functions. The N-protein is also highly antigenic and elicits a strong immune response in infected patients. For this reason the N-protein may serve as a target for the development of diagnostic assays. We have used bioinformatic analysis to analyze the HCoV-NL63 N-protein and compared it to coronavirus N-homologues. This bioinformatic analysis provided the data to generate recombinant clones for expression in a bacterial system. We constructed recombinant clones of the N-protein of SARS-CoV and HCoV-NL63 and synthesized truncated clones corresponding to the N- and C-terminal of the HCoV-NL63 N-protein. These heterologously expressed proteins will serve the basis for several post-expression studies including characterizing the immunogenic epitope of the N-protein as well identifying any antibody crossreactivity between coronavirus species.

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