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    Respiratory health of aluminium smelter workers in relation to exposure to sulphur dioxide and fluoride.
    (2020) Macaringue Raja, Edite Mara Joana Afonso.; Naidoo, Rajen.
    Introduction Aluminium smelter factory workers are exposed to hazardous chemicals while performing the smelting process. The main process of smelting aluminium occurs in the potroom department, where the chemical reaction called reduction, using alumina, electricity and carbon-based anode, takes place. Sulphur dioxide and fluorides are chemicals that are generated in a gas and particulate form during the process and are known as respiratory irritants and, depending on the level and duration of exposure can cause chronic obstructive pulmonary disease (COPD) and asthma in this population. Declines in lung function are therefore expected to occur in this group of workers in an accelerated manner, as compared to age related declines in the general population. However, within this group of workers, exposures related to tasks vary and are likely to contribute different risks and respiratory effects. Aim The purpose of the study was to investigate the personal and environmental factors influencing the respiratory health among potroom workers in an aluminium smelting factory, over a 10-year period. Methods A longitudinal assessment of annual lung function, respiratory symptoms as well as doctor diagnosed diseases was performed in 265 potroom workers using retrospective data from 2004 to 2014. A quantitative exposure matrix was made based on 46 specific job tasks divided in 5 sections within the potroom department. Cumulative exposure to SO2 and fluorides were calculated and assigned to different exposure groups. Descriptive statistics were performed to assess the respiratory health of reduction workers and analytic mixed modelling was performed to find association between the change in lung function and exposure to SO2 and fluorides, using two exposure metrics (annual estimated exposure and lifetime cumulative exposure) 28 together with one-year lags of these measures. Annual estimates of exposure for sulphur dioxide and fluoride for the specific study period were calculated based on estimations of 8 years exposure data available from the occupational hygiene measurements done by the health and safety department of the company (n=816). These estimations were used to analyse the relationship between the exposure and lung function Results 1 Over the 10-year period, 2226 repetitive observations of lung function and symptoms were performed on the 265 potroom department workers in 5 sections. Of the total numbers of participants, 40% had a full 10-year observation history and 60% had at least 2 years of observation. The study sample had a mean age of 27 years on the first observation and 33.9 years on last observation, 98% of them were men and the majority employed in the lower job categories (operators). The mean exposure level ranged from 0.01 (95%CI: 0.01-0.012) to 0.4 (95%CI0.34-0.46) for SO2 and 0.04 (95%CI 0.03-0.05) to 0.31 (95%CI 0.31-0.32) for fluoride. The prevalence of morbidities on first observation were lower for allergy (4.3%) and asthma (1.08%) compared to the last observation 6.45% and 2.15% respectively. The prevalence of morbidities was generally similar over the duration of the study, nevertheless the annual lagged fluoride exposure was associated with 18.85 % decrease of percentage predicted FVC and 18.98% of percentage predicted FEV1. Cumulative exposure to fluoride was associated with decrease of 0.15% in percentage predicted FEV1 /FVC and cumulative exposure to sulphur dioxide was associated with decrease of 2.94% on FEV1 /FVC. Conclusion and Recommendations In this retrospective study the exposure-related findings were found at exposure levels below the current South African OEL (2ppm for SO2 and 3ppm for fluoride). Considerations to reduce the current OEL should be sought as it shows to have a negative impact at respiratory health of potroom workers.
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    Genotyping of Chlamydia trachomatis detected in South African pregnant women.
    (2022) Ramnarain, Caitlin.; Abbai, Nathlee Samantha.; Mabaso, Nonkululeko.
    Background Chlamydia trachomatis (C. trachomatis) is a common cause of bacterial sexually transmitted infections (STIs). The genetic characterisation of C. trachomatis serovars reveals significant genetic diversity in this organism. Untreated C. trachomatis infection in pregnant women has been linked to miscarriage, low birth weight babies, premature rupture of membranes, postpartum endometritis, and transmission to the new-born babies. Currently, there is limited data and analyses on the serovars of C. trachomatis circulating in South African pregnant women. In this study, the prevalence of C. trachomatis infection was determined, and the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) of the outer membrane protein gene (omp1) was performed in order to identify the different serovars circulating in the population of pregnant women. Methods In this study, 385 vaginal swab samples were analysed for the presence of C. trachomatis. The swabs were collected from human immunodeficiency virus (HIV)-positive pregnant women at the King Edward VIII hospital in Durban, South Africa. Chlamydia trachomatis was detected using commercial primers and probes (TaqMan Assay, assay ID Ba04646249_s1) which targets the gene encoding the translocated actin-recruiting phosphoprotein of C. trachomatis. Genotyping of C. trachomatis positive samples was performed by an omp1 semi-nested polymerase chain reaction (PCR) assay followed by restriction fragment length polymorphism (RFLP) analysis. The omp1 from C. trachomatis was amplified with gene-specific primers in the first round PCR to yield a 1033 base pair (bp) fragment. Following the first round PCR, 1 μL of the first-round PCR product was used for the semi-nested PCR, amplifying a 978 bp fragment. The 978 bp omp1 amplicons were digested with AluI, DdeI and HinfI, and the banding patterns were compared across the three digests for assignment of serovars. Associations between categorical variables was assessed using chi square (𝑥2) tests. All statistical analysis was conducted using RStudio, version 3.6.3. All p-values were considered significant at < 0.05. Results The actin-recruiting phosphoprotein of C. trachomatis was detected in 47/385 swab samples using the TaqMan Assay. The prevalence of C. trachomatis in the study population was 12.2%. All negative no-template controls did not produce any amplification. Factors associated with testing positive for C. trachomatis included, having a low level of education, being unemployed, being unmarried, not cohabitating with sex partner, early age of first sex, high number of lifetime sex partners, partner having other partners, lack of condom use, lacking symptoms of STIs, lacking treatment for STIs and women having a perceived risk of getting STIs. Serovar E (20/43) - 46.5% was the most frequent serovar in our study population, followed by serovar F (9/43) - 20.9%, G (6/43) - 14.0%, D (5/43) - 11.6%, and the least frequent serovar I (2/43) - 4.7% which was detected in two samples. From the five women that carried serovar D, 20.0% (1/5) reported past treatment of STIs. From the 20 women that carried serovar E, 20.0% (4/20) reported having abnormal vaginal discharge. Of the women with serovar E, 20.0% (4/20) reported past treatment of STIs. From the nine women that carried serovar F, 11.1% (1/9) reported having abnormal vaginal discharge and 22.2% (2/9) reported past treatment of STIs. From the six women that carried serovar G, 16.7% (1/6) reported past treatment of STIs. From the two women that carried serovar I, 50.0% (1/2) reported having abnormal vaginal discharge. Conclusion This study detected an overall 12.2% prevalence rate for C. trachomatis in the pregnant women. The identification of factors associated with infection provided evidence on the importance of antenatal clinics to screen women during their routine check-ups for vaginal infections and provide continuous risk reduction counselling to this vulnerable population. Five different serovars were observed in the studied population with serovars E and F being the most prevalent. The observed diversity of serovars reported within specific populations can be challenging for future vaccine design and development for chlamydia. However, many of the South African serovars detected correlated with serovars found in studies conducted throughout the world. This suggests the possibility of conserved C. trachomatis strains from various geographical areas, which may offer some hope for future vaccine development and diagnostic research aimed at the entire C. trachomatis population.
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    Characterization of Candida isolates from South African pregnant and non-pregnant women.
    (2023) Sukali, Gloria.; Abbai, Nathlee Samantha.; Mabaso, Nonkululeko.
    Candida infections are a serious health threat to women. Characterization of Candida isolates has become the gold standard method used in determining antimicrobial susceptibility profiles and resistance mechanisms in vaginal Candida infections. However, there is a lack of data on the antimicrobial susceptibility profiles of South African Candida isolates to amphotericin B. This study investigated antimicrobial resistance profiles and genotypes of Candida isolated from South African pregnant and non-pregnant women. This study was a sub-study of a larger study which involved the diagnosis of vaginitis and vaginosis pathogens in women. For the parent study, n=150 women were recruited from the King Edward VIII hospital in Durban, KwaZulu-Natal, South Africa. The women enrolled in the parent study were; 18 years and older, were willing to provide written informed consent and were willing to provide self-collected vaginal swabs. A total of 72 Candida isolates were obtained by culture. Of the 72 isolates, 31 isolates were obtained from pregnant women and 41 isolates were from non-pregnant women. The isolates were typed using the ABC genotyping method. Susceptibility testing was performed using the broth microdilution assay to measure the minimal inhibitory concentrations (MICs) for clinical isolates to amphotericin B. The Candida albicans ATCC 10231 strain was used as a control strain, and untreated cultures of the respective isolates were used as growth controls. Descriptive characteristics of the study participants according to Candida status were presented as frequencies and percentages. Comparisons by Candida status in the descriptive characteristics were performed using Chi square tests with a 5% significance level. P-values ≤0.05 were considered significant. All analyses were conducted using STATA. The prevalence of Candida in the study population was 48.0% (72/150). All the isolates (100%) were confirmed to be C. albicans as per the germ tube test and quantitative polymerase chain reaction (PCR) using primers and probes specific for C. albicans. All 72 isolates (100%) produced positive PCR results for C. albicans. The majority of the isolates (45/72; 62.5%) yielded a 450bp band which was assigned Genotype A. Of the 72 isolates, 19 isolates (26.4%) yielded a band size of 840bp and was assigned Genotype B. A total of 11.1% (8/72) of the isolates yielded band sizes of 450bp and 840bp which was Genotype C. Of the 72 isolates tested, 79.2% (57/72) of the isolates were resistant to amphotericin B (MIC >1ug/ml) and 20.8% (15/72) of the isolates were susceptible to amphotericin B (MIC ≤ 1 ug/ml). When linking MIC patterns to distribution of genotypes, it was observed that the majority (80%) of the isolates which were assigned genotype A were resistant to amphotericin B. When linking clinical symptoms with the distribution of genotypes, it was observed that the majority (58.8%) of women who reported having current symptoms of abnormal vaginal discharge carried genotype A. Genotype A was most prevalent in women who had been treated for vaginal infections in the past and in women who were HIV positive with prevalence of 64.1% and 60.8%, respectively. genotype A was most prevalent in the non-pregnant women with a prevalence of 63.4%. Genotype A was prevalent (61.3%) amongst the pregnant women and the majority (66.7%) of the HIV negative women had Candida infections which belonged to genotype A. The prevalence of Candida was shown to be high in both pregnant and non-pregnant women in this study. This study also found a high level of resistance to the antifungal amphotericin B. Currently in our local setting, resistance patterns to the commonly used antifungals to treat Candida infections are not being monitored. There is a need for antifungal resistance monitoring in order to reduce the risk of future persistent and untreatable infections.
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    The role of mir-29a, mir-181a, and mir-222 in preeclamptic and gestational hypertensive patients.
    (2017) Khaliq, Olive Pearl.; Mackraj, Irene.
    Backgrounds Hypertensive disorders of pregnancy, a major cause of maternal and neonatal morbidity worldwide are characterized by widespread maternal endothelial dysfunction and metabolic disorders (blood pressure and insulin resistance). Dysregulation in proteins (AKT and PI3K) involved in the insulin signaling pathway lead to insulin resistance, which is a common feature in the second half of most pregnancies complicated by preeclampsia and gestational hypertension. The objective of this study was to quantify microRNAs in serum and placental tissue of women with gestational hypertension (GH) and preeclampsia (PE). Methods This study is a prospective cross-sectional study involving 32 normotensive pregnant women (control), 32 women with preeclampsia (PE) and 28 with gestational hypertension (GH). The patients were recruited from a regional hospital in Durban, KwaZulu-Natal Province, South Africa. Serum and placental microRNA were quantified using RT-qPCR to compare levels of expression in the control, PE, and GH. In addition, a western blot analysis was carried out to investigate the levels of protein expression (AKT and PI3K) in the insulin signaling pathway. Results Serum, miRNA-222 quantitative real-time PCR expression levels were significantly lower in PE compared to normotensives (p=0.0186). miR-29 expression levels were significantly higher in PE (p<0.0001) and GH (p<0.0001) groups compared to normotensives. miR-181a serum expression levels of GH were significantly higher compared to normotensives (p=0.0070). Placental tissue expression showed significantly higher expression levels of miR-181a in PE (p=0.0344) and GH (p=0.0344) groups compared to normal controls. Western blot analysis of proteins showed a lower expression of AKT-serine and threonine in the PE (p=0.0001) compared to the normal control groups and significantly higher expression in the GH (p=0.0001) groups compared to the normal controls. Furthermore, the expression of the phosphatidyl-inositol-3 kinase (PI3K) was statistically lower in PE (p=0.0001) and GH (p=0.0001) compared to the normal controls. Discussion/Conclusion MicroRNAs may be used as potential biomarkers for PE and GH. The results of this study showed a correlation between the expression levels of miRNAs with AKT/PI3K in the insulin signaling pathway, reinforcing the existence of metabolic dysregulation in PE and GH
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    The role of endoplasmic reticulum stress in shedding of syncytiotrophoblast microparticles in pregnant black South African women.
    (2016) Verma, Sonal Raj.; Mackraj, Irene.
    Background and aim: Preeclampsia, accounts for the majority of maternal deaths emanating from hypertension in pregnancy. Although its exact aetiology is unclear, endoplasmic reticulum (ER) stress and trophoblast apoptosis are implicated. The placental microenvironment in preeclampsia is hypoxic and induces the expression of Hypoxia inducible factor-1 alpha (HIF-1 α) and CHOP (C/EBP homologous protein) which are activated due to ER stress. Hypoxia-induced oxidative and endoplasmic reticulum stress initiate a cascade of apoptotic events with the consequential shedding of microparticles which mediate the peripheral maternal syndrome of preeclampsia. The main aim of the study was to immuno-localise the expression of HIF-1 α and CHOP in placental tissues and concomitantly characterise and quantify the syncytiotrophoblast microparticles in the maternal circulation. Materials and Methods: Plasma and placental tissue were obtained from normotensive and pre-eclamptic pregnant women. The expression of HIF-1α and CHOP was analysed using immunohistochemistry. Microvesicles in maternal circulation were isolated and their size distribution was determined using nanoparticle tracking analysis. The relative concentration of syncytiotrophoblast microvesicles (STBMs) from isolated microvesicles was determined using Placental Alkaline Phosphatase ELISA. Results: This study demonstrated an increased immuno-expression of HIF-1 α and CHOPS in preeclampsia compared to the controls (p < 0.05). Additionally, a significant increase in the mean syncytiotrophoblast microparticles concentration was observed in PE, compared to the controls (p < 0.05). Further analysis showed a positive correlation between the immunohistochemical expression of HIF-1 α and CHOP and the STBMs concentration. Conclusion: This study demonstrates increased placental-expression of HIF-1α and CHOP in preeclampsia compared to normotensive pregnancies which directly relate to the increase syncytiotrophoblast microvesicles concentration in maternal circulation. These findings indicate that placental hypoxia and ER stress are contributory factors to the pathogenesis of PE and may be a key contributory factor in placental cell apoptosis and the consequent release of placental derived debris into the maternal circulation. Key words: HIF-1α; CHOP; Syncytiotrophoblast Microvesicles; Pre- eclampsia; Endoplasmic Reticulum Stress; Hypoxia
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    The relationship between age and diabetes control in patients living with diabetes mellitus in low-to-middle income countries.
    (2021) Chetty, Rushern Ruvashin.; Pillay, Somasundram.
    Diabetes Mellitus (DM) is a chronic, metabolic disease characterised by raised blood glucose levels. In 2019, there were an estimated 463 million adult patients living with diabetes (PLWD), with this figure expected to reach around the 700 million mark by 2045. Patients living in low-income and middle-income countries comprise approximately 79% of global adult PLWD figures, with approximately 20% of these PLWD being older than 65 years. This illustrates that the burden of DM rests on the younger working-age population in low-to-middle-income (LMIC) countries. These patients living with type 1 and type 2 diabetes have reduced life expectancies of approximately 20 and 10 years, respectively. Unfortunately, this compounds the problem of further decreasing the life expectancy of the population of LMIC countries which are already being affected by communicable diseases like HIV infection. South Africa has the highest prevalence of human immuno-deficiency virus (HIV) in the world at 13% with many PLWD also being HIV-infected. With the effective roll-out of anti-retroviral treatment (ART), patients are also able to live longer and can develop diabetes mellitus as a result of longevity, ART and the HIV-infection itself. With the prevalence of both these conditions and the numbers of DM expected to rise, determining relationships in PLWD in an HIV-endemic area would offer better knowledge and allow for better strategies to be implemented to effectively manage a significant proportion of patients in our setting. A scoping review was conducted globally to identify associations between ‘age’ and ‘glycaemic control’ in HIV-infected PLWD. The review concluded that “varying data exists on the associations between glycaemic control and age in PLWD in the context of HIV infection (PLWDH). Further studies are recommended to determine associations in this regard, especially in LMIC where HIV and DM have a higher prevalence.” The lack of conclusive associations identified from the scoping review suggested that another study was warranted in an HIV-endemic region. A retrospective study was conducted among 957 PLWD of whom 146 patients were HIV-infected from the Edendale Hospital Diabetes Clinic, Pietermaritzburg, South Africa from 1 January 2019 to 31 December 2019. Statistical analysis was performed with a p value<0.05 being considered statistically significant. Our study showed that younger PLWD had poorer glycaemic control and were likely to develop diabetes-related complications later in life. Of note, older age was associated with improved mean glycated haemoglobin (HbA1c) levels after adjusting for glomerular filtration rate (GFR) [r=-0.141, p<0.001; (before adjustment: r=-0.108; p=0.001)]. In addition to this, PLWD with an HIV-infection who had a mean HbA1c>7% were significantly younger than those with HbA1c≤7% (47.38 years vs. 52.77 years, p=0.013). viii From this study, we evaluated associations between age and glycaemic control in PLWD has served to highlight that “more emphasis, in terms of diabetes education and management, needs to be placed in the younger age category of both PLWD and PLWDH”. This study, as well as future prospective studies, will assist with providing patients, healthcare workers and government with improved knowledge, thereby managing patients more effectively at any given age. Some of our recommendations from this study include: screening all patients for DM and implementing strategies to optimise glycaemic control and prevent complications; healthy diet to be implemented by patients of all ages; exercise as well as optimal pharmacological management and self-monitoring of glucose levels.
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    The prevalence and risk factors for genital mycmoplasmas in Human immunodeficiency virus infected pregnant women from King Edward Vlll hospital.
    (2021) Nundlall, Nikita.; Abbai, Nathlee Samantha.; Singh, Ravesh.
    Background: Genital mycoplasmas can be found amongst the normal human flora mostly in the respiratory, reproductive and urinary tracts as commensal or pathogenic organisms. These bacteria are sexually transmitted and can be linked to sexually transmitted diseases and other conditions. There are a limited number of studies conducted in South African pregnant women especially from KwaZulu-Natal which have assessed the prevalence, co-infection rates and risk factors for genital mycoplasmas. In this study, the prevalence, co-infection rates and risk factors for Mycoplasma genitalium, M. hominis, Ureaplasma urealyticum and U. parvum were investigated in a cohort of Human immunodeficiency virus (HIV) infected pregnant women. The data generated in this study, therefore adds to the growing body of knowledge on these pathogens. Methods: This study included 264 HIV infected pregnant women attending the King Edward VIII antenatal clinic in eThekwini, South Africa. The women were recruited between October 2020 and April 2021. Each enrolled women provided self-collected vaginal swabs (dry swabs) for detection of the vaginal infections. The consenting women had also completed a questionnaire on socio-demographic, behavioural and clinical factors. DNA was extracted from the vaginal samples using the PureLink Microbiome kit. The individual pathogens were detected using the TaqMan Real-time PCR assays using commercially available primers and probes on a QuantStudio 5 Real-time polymerase chain reaction (PCR) platform. The statistical data analysis was conducted in a freely available Statistical Computing Environment, R software, version 3.6.3 using the RStudio platform. Results: The most prevalent infection in the study population was U. urealyticum, 236/264 (89.4%), followed by M. hominis, 215/264 (81.4%), U. parvum, 203/264 (76.9%) and lastly M. genitalium, 7/264 (2.70%). A total of five women (1.90%) were coinfected with all four microorganisms. Within the group of women who tested positive for Mycoplasma genitalium (M. genitalium), partner having other partners was the only significant behavioral factor in relation with being positive, p=0.031. However, a smaller proportion of positive women reported that their partner had other partners (28.6%) when compared to 57.1% who reported that their partner did not have other partners and 14.3% who did not know if their partner had other partners. Within the group of women who tested positive for Mycoplasma hominis (M. hominis), partner having STI symptoms was a significant clinical factor in relation with being positive, p=0.027. Women that experienced current symptoms of STIs was significantly associated with being positive, p<0.001. In addition, of the M. hominis positive women, a higher proportion, 80.5% tested positive for U. parvum infection compared to 19.5% who tested negative and this was significant, p=0.004. Partner being circumcised was a significant clinical factor in relation with being positive for Ureaplasma urealyticum (U. urealyticum), p=0.028. In addition, partner having symptoms of STIs was a significant clinical factor in relation with being positive, p=0.027. The majority of the positive women were in the third trimester of pregnancy and trimester of pregnancy was significantly associated with being positive for infection, p=0.040. Of the women who tested positive for U. urealyticum, a higher proportion of women also tested positive for M. hominis and this association was significant, p=0.051. Within the group of women who tested positive for Ureaplasma parvum (U. parvum), partners HIV status was significant in relation with being positive, p=0.049. Lifetime number of sex partners was significantly associated with being positive, p=0.012. Partner having other partners was also a significant factor in relation with being positive, p=0.023. Of the U. parvum positive women, a higher proportion of women (85.2%) tested positive for M. hominis. This association was significant, p=0.004. In the adjusted analysis, being employed increased the risk of getting infected with M. hominis p=0.012. In the adjusted analysis, current STI symptoms increased the risk for M. hominis by 95.27 fold, p<0.001. Being U. parvum positive increased the risk for M. hominis by 8.19 fold, p=0.001. Being U. urealyticum positive also increased the risk for M. hominis, p=0.039. In the adjusted analysis, having >4 lifetime sex partners increased the risk of infection with U. parvum by 88.02 fold. This factor was significant, p<0.001. Partner having other partners increased the risk of infection with U. parvum, p=0.008. In the adjusted analysis, being M. hominis positive increased the risk for U. parvum by 4.33 fold, p=0.008. Conclusion: The present study provides information on the risk factors associated with genital mycoplasma infections. The identification of risk factors provides the foundation for the development of prevention interventions. In this study, clinical and behavioral factors were shown to be significantly associated with the risk for infection. Based on this finding, it is evident that a single prevention strategy will not be sufficient, what will be needed is a combination prevention strategy for this vulnerable population.
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    Renal and metabolic effects of tulbaghia violacea harv. and captopril in fructose-fed streptozotocin induced diabetic rats.
    (2017) Joseph, Kimane Megan.; Mackraj, Irene.; Moodley, Kogilambal.
    Background: Diabetes mellitus has rapidly emerged as a worldwide epidemic resulting in significant morbidity and mortality. The incidence of type 2 diabetes mellitus, induced by a high carbohydrate diet, a sedentary lifestyle as well as obesity, is increasing rapidly. Despite the availability of current conventional drugs, the complications of diabetes mellitus continue to progress. Therefore the search for alternate therapies that are antidiabetic in nature and elicit minimal side effects is essential. This study investigated the effects of the medicinal plant Tulbaghia violacea. Harv and angiotensin converting enzyme inhibitor, Captopril in a fructose-fed streptozotocin induced diabetic rat model. Methods: Thirty-six, male Sprague-Dawley rats (six-week old) were randomly divided into six groups’ namely non-diabetic control, diabetic control, diabetic treated with Tulbaghia violacea Harv. (60 mg/kg bw), diabetic treated with captopril (50 mg/kg bw), diabetic treated with metformin (250 mg/kg bw) and diabetic treated with glibenclamide (10 mg/kg bw). Diabetes was induced by fructose feeding for 1 week followed by a single intraperitoneal injection of 40 mg/kg.bw streptozotocin. Animals with a fasting blood glucose concentration >25mmol/L were considered diabetic and included in the study. Thereafter, respective doses of Tulbaghia violacea and conventional drugs were daily administered to the diabetic groups by oral gavage for seven weeks. At week six, an oral glucose tolerance test was performed. At the end of week 7, the animals were euthanized by halothane overdose. Blood was collected and organs were harvested for further biochemical analyses. Results: Tulbaghia violacea treatment significantly increased plasma insulin and liver glycogen content. Tulbaghia violacea treatment also reduced liver thiobarbituric acid reactive substances levels, increased liver superoxide dismutase concentration and increased plasma nitric oxide levels. Furthermore, Tulbaghia violacea administration reduced serum triglycerides, total cholesterol, VLDL cholesterol, LDL cholesterol and increased HDL cholesterol. The plant treated group showed increased pancreatic islet counts as well as improved glomerular morphology. The angiotensin converting enzyme inhibitor captopril showed a significant increase in angiotensin converting enzymeactivity as well as increased angiotensin type 1 receptor expression compared to the diabetic controls and Tulbaghia violacea. Conclusion: Tulbaghia violacea did not decrease fasting blood glucose levels or improve glucose tolerance. However, in this study, the data obtained demonstrated the ability of Tulbaghia violacea to elicit antioxidant and hypolipidemic effects, augment plasma insulin levels, improve pancreatic and glomerular morphology and positively impact β- cell function in a fructose-fed streptozotocin induced diabetic rat model.
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    “Sugars”: the chemical characterization of a prevalent illicit drug cocktail in South Africa.
    (2016) Chetty, Yvette Yolanda.; Nadar, Anand.
    ABSTRACT Introduction “Sugars” is an illicit drug cocktail that is thought to be a mixture of heroin, cocaine and other substances in order to add bulk to the final product. Since its emergence in a local KwaZulu-Natal community known as Chatsworth in 2006, the use of the drug has spread to other provinces in South Africa and has currently become a popular drug amongst the youth. The affordability of the cocktail has allowed it to become rampant in low income communities and this coupled with its accessibility further reinforces “Sugars” as the preferred drug of choice. The use of the drug allows the user to experience euphoria, however once the effects wear off, the pain of the resulting withdrawal or “roster” drives the individual to continue using the drug. The withdrawal symptoms range from common cold and flu-like symptoms to extreme bone pain, stomach cramps, constipation and nausea. There have been attempts at rehabilitating “Sugars” addicts however, due to the lack of knowledge of a precise chemical composition of the cocktail, it is difficult to effectively maintain therapeutic interventions. Aim The aim of this study was therefore to chemically characterize the composition of “Sugars”, thereby allowing for the development of targeted treatment options for rehabilitation centres. Method Batches of samples of the mixture were sourced from 3 independent suppliers in the Durban South area of KwaZulu-Natal, South Africa. Chromatographic techniques were used to separate the individual constituents of the mixture and determine molecular weights of these compounds. Nuclear magnetic imaging was used to identify the compounds. Results and discussion The tests confirmed the presence of heroin, papaverine and noscapine in the “Sugars” samples analysed. However, there was variance noted in the composition between the different sources of the drug. We hypothesize that “Sugars” was therefore not heroin that is bulked up with other substances, but may be the waste product of the final purification process in the illicit heroin manufacturing process. Conclusion It was concluded that “Sugars” contained heroin, noscapine and papaverine. The variance in composition of heroin in the samples suggests independence between suppliers. The presence of papaverine and noscapine, which are impurities that are usually removed during the final purification of heroin, supports the hypothesis that “Sugars” is the waste product of the manufacture of heroin. Noscapine and papaverine are costly pharmaceutical products and we therefore speculate that it would not be economically viable to bulk up a cheap low grade drug cocktail with these compounds.
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    Anatomic study of the morphologic relationship between the proximal left and right coronary arteries.
    (2016) Singh, Sadhna.; Satyapal, Kapil Sewsaran.; Lazarus, Lelika.; Ajayi, Nasirudeen Oladipupo.
    Arising from the aorta, the right (RCA) and left (LCA) coronary arteries provide the arterial supply to the heart. An extensive literature review revealed that most studies have either evaluated the morphology of the RCA or the LCA independently. This study aimed to document the relationship between the morphology of the RCA and LCA using coronary angiograms and fetal dissections. In addition, variations such as split or double RCA and absence of the LCA was documented. A review of 500 coronary angiograms and a fetal dissection of 41 heart specimens was conducted. The RCA and LCA were classified according to their branching patterns and arterial dominance. The embryologic relationship between the RCA and the LCA was also documented including their lengths and diameters. The angiographic review showed that the most prevalent branching pattern of the LCA was bifurcation in 65.8%, while trifurcation and quadrifurcation occurred in 20.4% and 1.6%, respectively. The splitting of the RCA and absence of the LCA occurred in 4.2% and 11.8%, respectively. A significant correlation was found between the split RCA and absent LCA showing that the split RCA was more prevalent in the absence of the LCA. The dissection of the fetal heart specimens (age range 13.13 - 26.95 weeks) found that the RCA arose from the right aortic sinus and provided arterial dominance in all the specimens. The LCA was classified into types according to their branching pattern. The bifurcation, trifurcation and quadrifurcation of the LCA occurred in 68.3%, 29.3% and 2.4% of hearts, respectively. The mean lengths of the RCA and LCA were 0.98 ± 0.54mm and 1.83 ± 0.77mm, respectively. The mean diameters of the RCA and LCA were 0.38 ± 0.12mm and 0.49 ± 0.17mm, respectively. A significant correlation was found between the RCA and LCA length and the fetal age indicating changes in the development of the coronary vasculature with fetal development. A knowledge of the distribution of the RCA and LCA assists in providing information on the area of the myocardium supplied. With the advent of coronary angiography, a comprehensive understanding of coronary arterial anatomy and their variations is necessary.
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    Evaluation of teixobactin derivatives as potential antimicrobial agents.
    (2017) Ramchuran, Estelle Juanita.; Bester, Linda Antionette.
    Methicillin resistant Staphylococcus aureus (MRSA) and vancomycin resistant Enterococcus (VRE) are on the World Health Organization (WHO) high priority list of pathogens that require serious attention. Therefore, the need for novel class of compounds is vital in overcoming this problem. Teixobactin is a new class of antibiotic that has exhibited antimicrobial activity against resistant bacteria. In this study we are expanding the investigation of teixobactin derivatives against clinically relevant bacterial isolates from South African patients. The minimum inhibitory concentration (MIC), the minimal bactericidal concentration (MBC), the serum effect on the MIC’s and the time kill kinetics studies of three of our synthesized teixobactin derivatives 3, 4 and 5 were ascertained by broth microdilution according to the CLSI 2017 guidelines. Haemolysis on red blood cells (RBCs) and cytotoxicity on peripheral blood mononuclear cells (PBMCs) were performed to investigate the safety of these derivatives. MIC’s of the teixobactin derivatives against ATCC reference strains were between 4-64 µg/ml (3), 2-64 µg/ml (4) and 0.5-64 µg/ml (5). The MIC’s for MRSA were 32 µg/ml for (3), 2-4 µg/ml for (4) and 2-4 µg/ml for (5) whilst the MIC’s obtained for VRE’s were 8-16 μg/ml for (3), 4 μg/ml for (4) and 2-16 μg/ml for (5). 50% human serum had no effect on the MIC’s. All these derivatives did not show any effect on cell viability at their effective concentration. Teixobactin derivatives (3, 4 and 5) were capable of inhibiting bacterial growth in drug resistant bacteria and thus serve as potential antimicrobial agents.
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    Identification of mutations in genes associated with metronidazole resistance and susceptibility in Trichomonas vaginalis.
    (2021) Mzenda, Tumelo.; Abbai, Nathlee Samantha.
    Trichomonas vaginalis is the most common non-viral, sexually transmitted pathogen worldwide. Although, metronidazole cure rates are high for T. vaginalis infection, resistance has been reported. Mutations in the nitroreductase genes of T. vaginalis have also been implicated in metronidazole resistance. Therefore, the aim of this study was to detect mutations in the nitroreductase genes and link the mutations to metronidazole resistance patterns in T. vaginalis isolated from South African pregnant women, a currently under-researched area. Vaginal swabs were collected from 362 pregnant women recruited from the King Edward VIII hospital antenatal clinic in Durban from October 2018 to March 2019. The swabs were cultured in Diamonds TYM medium to obtain pure isolates of T. vaginalis. Pure isolates were sub-cultured and subjected to metronidazole susceptibility assays. The susceptibility assays were conducted under aerobic and anaerobic conditions. DNA was extracted from the pure isolates to perform the polymerase chain reaction (PCR) assays for the detection of the nitroreductase genes and the PFOR gene. The PCR amplicons were sequenced using the Sanger approach in order to identify mutations associated with resistance. A total of 21/362 (5.8%) pregnant women tested positive for T. vaginalis infection. Of the 21 T. vaginalis isolates tested for anaerobic metronidazole susceptibility, 9.5% (2/21) had an MIC of 4 μg/ml (resistant), 38.1% (8/21) had an MIC of 2 μg/ml (intermediate) and 52.4% (11/21) had an MIC ≤ 1 μg/ml (susceptible). For the ntr2 gene, susceptible and resistant isolates carried mutations which were absent in the intermediate isolates. The susceptible isolates carried mostly insertion mutations and the resistant isolate carried substitution mutations. Some deletion mutations were also observed in the ntr2 gene. For the ntr3 gene, two substitution mutations were observed in the intermediate isolate only. In the ntr4 gene, substitution mutations were only observed in the susceptible and resistant isolate. For the ntr5 gene, substitution and insertion mutations were observed in the resistant isolate and not in the intermediate or susceptible isolates. For the ntr6 gene, insertion and deletion mutations were observein the intermediate isolate and a single deletion mutation in the resistant isolate. For the PFOR gene, a single substitution mutation was observed in the intermediate and resistant isolate. In this study, mutations in the ntr2, ntr3, ntr4, ntr5 and ntr6 genes were observed across metronidazole susceptibility profiles. Previous studies have not identified mutations in the ntr2, ntr3 and ntr5 genes, so there is not enough data to support the functions of those genes and their association with metronidazole resistance. Future studies aimed at identifying the function of these mutations are needed.
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    Local experience of patients with connective tissue associated interstitial lung disease who were treated with cyclophosphamide.
    (2021) Singh, Swasti Gitesh.; Nyamande, Kennedy.; Mitha, Mohammed.
    Introduction: Interstitial lung disease (ILD) is a major cause of death amongst individuals with connective tissue diseases (CTD). Although there is no cure for CTD-ILD the need to retard disease progression is vital, hence early detection and treatment is necessary. Cyclophosphamide (CYC) is a potent immunosuppressant that has efficacy in inducing and maintaining remission in autoimmune diseases. Objectives: The purpose of this study was to assess the clinical, radiological and pulmonary function responses of patients who received intravenous CYC for CTD-ILD at Inkosi Albert Luthuli Central Hospital (IALCH) in Durban, Kwa-Zulu Natal, South Africa over a ten year period from January 2009 to December 2018. Methodology: This was a retrospective electronic chart review conducted at IALCH, the main quaternary public sector hospital in the province of Kwa-Zulu Natal, South Africa. Patients 18 years and older with CTD-ILD treated with CYC were included. Patients were given CYC every 2 weeks for 9 months with a total of 18 doses. Demographic and clinical data, as well as data from special investigations, were captured from medical records. Treatment outcomes were assessed using symptoms, pulmonary function and HRCT changes. Results: There were 62 subjects, 88.7% being female with the majority between the ages of 40-59 years old (64.5%). Approximately 50% were black Africans followed by ethnic Indians at 43.5% and then Whites at 6.5%. Most patients had Systemic Sclerosis, followed by Mixed Connective Tissue disease and then Systemic Lupus Erythematosus. There was no significant difference in pre and post treatment, symptoms, lung function and HRCT in those who were treated with CYC. Conclusion: In our setting, the use of 18 doses of CYC every 2 weeks, did not have a significant impact on disease progression.
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    The impact of semen exposure on cytokine response and bacterial vaginosis in the female genital tract.
    (2018) Mngomezulu, Khanyisile Happiness.; Ngcapu, Sinaye.; Baxter, Cheryl.
    Background: Diverse microbial communities and inflammatory cytokine responses in the lower female genital tract (FGT) are closely associated with increased human immunodeficiency virus (HIV-1) risk, possibly through increasing mucosal HIV target cell frequency and T-cell activation. The presence of semen in the vagina during unprotected sex has been associated with short-term activation of mucosal immunity. Here, we investigated the extent to which partner semen impacts on cytokine and microbial profiles measured in 248 HIV-uninfected women at high risk for HIV infection. Methods: We assessed the semen exposure in SoftCup supernatants by quantifying prostate specific antigen (PSA) levels using enzyme-linked immunosorbent assay (ELISA). Luminex was used to measure 48 cytokines in SoftCup supernatants and the vaginal swabs were used for diagnosis of bacterial vaginosis by Nugent score. Results: PSA, which denotes semen exposure within 48 hours prior to sampling, was detected in 19% (43/248) of SoftCup supernatants. Of the 43 PSA positive women, 70% (30/43) had self-reported condom use at their last sex act and 84% (36/43) had non-Lactobacillus dominant microbiota (Nugent score >7). In addition, PSA was significantly associated with prevalent bacterial vaginosis (Relative Risk (RR), 2.609; 95% Confidence Interval (CI), 1.104 - 6.165; p = 0.029), after adjusting for potential confounders such as age, STIs, current contraceptive use and condom use. Furthermore, women with detectable PSA had high median concentrations of Macrophage inflammatory protein- beta (MIP-1β) (p=0.047) compared to those without PSA. Conclusion: These findings suggest that the presence of semen has a potential to alter the inflammatory response and microbial communities of the FGT, which may facilitate recruitment of HIV susceptible cells, resulting in increased susceptibility to HIV-1 infection.
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    The role of immunoglobulin isotypes (IgG1-IgG4, IgA AND IgM) in HIV preeclamptics on highly active anti-retroviral therapy, in South Africa.
    (2018) Moodley, Mikaila.; Naicker, Thirusha.
    Background: The epicentre of a successful pregnancy lies within the placenta and is nurtured by suppressed immune responses. However, the fragile balance between maternal inflammatory responses and the regulation of maternal immunoglobulins is distorted by HIV and Preeclampsia (PE). Preeclampsia and co-morbid diseases such as HIV infections are major contributors to maternal morbidity and mortality, worldwide. Furthermore, the effects of Highly Active Antiretroviral therapy (HAART) on the reconstitution of immunity in HIV preeclamptics remain obscure. Therefore, the current study aims to investigate the role of immunoglobulins in HIV infected preeclamptics and elucidate the effects of HAART on immunoglobulin levels in HIV infected PE. Method: Ethical clearance was granted by the Biomedical Research Ethics Committee (BREC). Serum samples of 38 normotensive and 38 preeclamptic pregnancies were collected at a regional hospital and further categorized based on HIV status. The serum samples were then subjected to the analysis of immunoglobulin (IgG1-IgG4, IgA and IgM) concentration (ng/dl). The Bio-Plex immunoassay technique of analysis was used to investigate the concentration of immunoglobulin isotypes in the sample population. Immunoglobulin concentrations were considered significant when p < 0.05. Results: Immunoglobulin concentration was evaluated in pregnancy type irrespective of HIV status. A non-significant down-regulated trend of IgG1, IgG3 and IgG4 was observed, whilst IgG2 and IgM showed a non-significant up-regulation. On the contrary, IgA levels presented a significant increase in preeclamptics irrespective of HIV status. However, in HIV infected pregnancies irrespective of pregnancy type IgG1 presented a non-significant up-regulated trend, whilst IgG3 and IgG4 showed non-significant down-regulatory trends. Nonetheless, IgG2, IgA and IgM demonstrated a significant down-regulation in HIV infected pregnancies, irrespective of pregnancy type. Furthermore, IgG1, IgG3, IgG4 and IgM showed a non-significant difference when analysed according to pregnancy type and HIV status. However, IgG2 and IgA presented a significant up-regulation in HIV negative PE. Conclusion: This study highlights the importance of the maternal-fetal transfer of immunoglobulins (IgG subclass) in pregnancy. We report a significant up-regulation of IgG2, indicating its role in activating the classical complement pathway thereby, exacerbating the inflammatory response in PE. The up-regulation of IgA is an ingenerate anti-inflammatory response, which inhibits the exacerbated inflammatory cascade via classical complement activation in PE. In HIV infection the down-regulation of IgG2, IgA and IgM maybe due to HAART. In addition, IgA showed an up-regulation in HIV associated PE, suggesting that the reconstitution of HAART is insufficient in neutralizing the exaggerated inflammatory response in PE. To further understand the role of IgG2 and IgA in HIV associated PE, larger studies are warranted.
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    The role of vitamin A (retinol palmitate) and beta-carotene on B- lymphocytes and natural killer cells in HIV-1 seropositive pregnant women.
    (1998) Doorasamy, Trevor.; Coovadia, Hoosen Mahomed.
    Abstract available in PDF.