The role of TNP-Nucleotides, LYS492 and CA²⁺chelators in the skeletal muscle sarcoplasmic reticulum CA²⁺atpase cycle

In the first part of this study, the kinetics of decay of TNP-nucleotide superfluorescence was investigated with a view to understanding the role of nucleotides and Lys492 in later steps in the catalytic cycle of the skeletal muscle Ca²⁺ATPase. It has been found previously, and verified here, that tethering TNP-8N₃-AMP to the Ca²⁺ATPase via Lys492 retarded the Ca²⁺ initiated decay of Pᵢ-induced superfluorescence 10-fold compared with untethered nucleotide. The rapidity of the decay upon addition of EDTA suggested that the E₂ ↔ E₁ → E₁Ca₂ steps were being monitored rather than dephosphorylation per se. Tethered diand triphospho species did not accelerate the decay. While monophasic kinetics was observed with untethered TNP-AMP and TNP-8N₃-AMP, complex kinetics were observed with the di- and triphospho TNP-nucleotides. This was shown to be due to the utilization of TNP-ADP and -ATP, and the azido derivatives, as coupled substrates of the Ca²⁺ATPase in the forward direction of catalysis in the presence of Ca²⁺. The hydrolysis rates of TNP-ADP, TNP-ATP, TNP-8N₃ -ADP, and TNP-8N₃ -ATP were 10, 5, 15 and 10 nomoles/min/mg of protein, respectively, at room temperature and pH 5.5. Ca²⁺ transport was supported by all four nucleotides. This is the first time that a diphosphonucleotide has been shown to support Ca²⁺ transport. A new nonhydrolysable triphospho TNPnucleotide, TNP-AMP-PCP was synthesized and shown to interact with the Ca²⁺ATPase in a similar way, in terms of superfluorescence, as the other TNP-nucleotides. It did not show the complex kinetics on inhibition of the Pcinduced superfluorescence by Ca²⁺, but neither did it accelerate the kinetics. It was concluded that TNP-nucleotides do not accelerate the E₂ ↔ E₁ transition under these conditions, possibly because of the presence of glycerol in the medium. In the second part of the study, it was shown that addition of small amounts of chelators EGTA, EDTA, BAPTA, DTPA, HEDTA and NTA to a Ca²⁺ transport assay in which the free Ca²⁺ concentration is monitored by Fluo-3 causes the Ca²⁺ATPase to pump to apparently lower levels as seen in the [Ca²⁺] lim fluorescence. Addition of chelator retards pump function in the sense that it takes longer for 50 nmols Ca²⁺ to be accumulated. Increased thermodynamic efficiency of the pump and contaminating heavy metal ions were considered as possible mechanisms. To some extend Zn²⁺ and Cd²⁺, but not Fe²⁺ and Cu²⁺, appeared to reverse the partial inhibition. While interpretation of the results is difficult, it is suggested that heavy metal ions interact with luminal loops of the Ca²⁺ATPase and enhance Ca²⁺ release under conditions of high luminal Ca²⁺ concentrations

Ambient Air Pollution Exposure and Respiratory, Cardiovascular and Cerebrovascular Mortality in Cape Town, South Africa: 2001–2006

Little evidence is available on the strength of the association between ambient air pollution exposure and health effects in developing countries such as South Africa. The association between the 24-h average ambient PM10, SO2 and NO2 levels and daily respiratory (RD), cardiovascular (CVD) and cerebrovascular (CBD) mortality in Cape Town (2001–2006) was investigated with a case-crossover design. For models that included entire year data, an inter-quartile range (IQR) increase in PM10 (12 mg/m3) and NO2 (12 mg/m3) significantly increased CBD mortality by 4% and 8%, respectively. A significant increase of 3% in CVD mortality was observed per IQR increase in NO2 and SO2 (8 mg/m3). In the warm period, PM10 was significantly associated with RD and CVD mortality. NO2 had significant associations with CBD, RD and CVD mortality, whilst SO2 was associated with CVD mortality. None of the pollutants were associated with any of the three outcomes in the cold period. Susceptible groups depended on the cause-specific mortality and air pollutant. There is significant RD, CVD and CBD mortality risk associated with ambient air pollution exposure in South Africa, higher than reported in developed countries

Probing secondary exposure and health data as a tool to improve public health in South Africa

The usefulness of secondary exposure and health data to improve public health in South Africa will be assessed. Given the tremendous health impact of air pollution exposure the focus of this thesis is on primary prevention, that is the identification of outdoor air pollution and the use of dirty fuels (wood, animal dung, crop residues, coal, paraffin) for cooking and heating as risk factors, whilst controlling for confounding. Hourly averaged outdoor PM10 mass, NO2, NO, SO2, O3 data (1 August 1998 - 31 July 2003) from Cape Town were analysed in a nonparametric Spearman’s Rho correlation analysis to determine the seasonal spatial correlation between the monitoring sites. Trend and descriptive analyses were conducted on the outdoor hourly and daily PM10 mass data to investigate the current and future health implications in the Khayelitsha sub-district, Cape Town. The 1998 South African Demographic and Health Survey (SADHS) data were analysed. The survey involved 13 826 individuals in 12763 households. Univariate and multivariate logistic regression analyses generated crude and adjusted odds ratios and 95% confidence intervals in order to assess the influence of dirty fuel use for cooking and heating on adult (> 15 years) respiratory health, childhood (< 59 months) respiratory health and 1-59 month mortality. It was found that outdoor air pollution is not homogenously distributed in Cape Town during all seasons. Elevated PM10 mass concentrations are frequently present in the Khayelitsha sub-district. There is a strong case for acknowledging the large public health risk arising from air pollution exposure in South Africa, despite the limitations of the 1998 SADHS data. Not much progress has been made in air pollution epidemiology in the country during this investigation due to the identified limitations. Secondary exposure and health data are thus only useful in improving public health in South Africa by supplying baseline data for trend analysis or hypotheses generation. It is recommended that the country must develop environmental public health tracking networks, which incorporates various data sources from multi-sectoral collaborative intervention projects with analytic study designs, in all major cities in the country.Thesis (PhD)--University of Pretoria, 2006.School of Health Systems and Public Health (SHSPH)PhDUnrestricte

Heat effects of ambient apparent temperature on all-cause mortality in Cape Town, Durban and Johannesburg, South Africa: 2006-2010

Due to climate change, an increase of 3–4 °C in ambient temperature is projected along the South African coast and 6–7 °C inland during the next 80 years. The objective of this study was to investigate the association between daily ambient apparent temperature (Tapp) and daily all-cause non-accidental mortality (hereafter mortality) in Cape Town, Durban and Johannesburg during a 5-year study period (2006–2010). Susceptibility by sex and age groups (< 15 years, 15–64 years and ≥ 65 years) was also investigated. The associations were investigated with the time-stratified case-crossover epidemiological design. Models were controlled for PM10, public holidays and influenza epidemics. City-specific Tapp thresholds were determined using quasi-Poisson generalised additive models. The pooled estimates by sex and age groups were determined in meta-analyses. The city-specific Tapp thresholds were 18.6 °C, 24.8 °C and 18.7 °C, respectively for Cape Town, Durban and Johannesburg. A 3.3%, 2.6% and 2.8% increase in mortality per IQR increase in Tapp (lag0–1) was observed in Cape Town, Durban and Johannesburg, respectively above the city-specific thresholds. The elderly were more at risk in Cape Town and Johannesburg. No difference in risk was observed for males and females in the three cities. In the meta-analysis an overall significant increase of 0.9% in mortality per 1 °C increase in Tapp (lag0–1) was observed for all age groups combined in the three cities. For the ≥ 65 year group a significant increase of 2.1% in mortality was observed. In conclusion, the risks for all age groups combined and the elderly are similar to those reported in studies from developed and developing countries. The results can be used in present-day early warning systems and in risk assessments to estimate the impact of increased Tapp in the country due to climate change. Future research should investigate the association between Tapp and cause-specific mortality and also morbidity.Statistics South Africa and the South African Weather Service.http://www.elsevier.com/locate/scitotenv2018-06-01hj2017School of Health Systems and Public Health (SHSPH

Does apparent temperature modify the effects of air pollution on respiratory disease hospital admissions in an industrial area of South Africa?

Please read abstract in the article.https://cleanairjournal.org.zaam2022School of Health Systems and Public Health (SHSPH

Is one man’s garbage another’s toxic treasure? A brief look into the informal recycling of waste on landfills and associated health challenges in South Africa

As South African consumerism has risen, the waste being generated has increased. Poor accessibility to recycling infrastructures in communities has resulted in a high influx of reusable waste at landfills. Waste disposal through landfills is the primary form of disposal worldwide. According to the World Bank (2018), South Africans produce 0.50-0.99 kg of waste per capita per day. In 2017, the Department of Environment, Forestry and Fisheries (DEFF), formerly the Department of Environmental Affairs, reported that 75% of this waste is disposed of in landfills across the country. This has, to some degree, created a ‘gold rush’ to landfills as underprivileged and unemployed men and women in urban communities turn to waste recycling as a form of income generation.http://www.occhealth.co.zaam2020School of Health Systems and Public Health (SHSPH

PM2.5 chemical composition and geographical origin of air masses in Cape Town, South Africa

No abstract available.http://www.cleanairjournal.org.zahj2021School of Health Systems and Public Health (SHSPH

Comorbidity of respiratory and cardiovascular diseases among the elderly residing close to mine dumps in South Africa : a cross-sectional study

BACKGROUND. Pollution arising from mine dumps in South Africa (SA) has been a source of concern to nearby communities. OBJECTIVE. To investigate whether comorbidity of respiratory and cardiovascular diseases among elderly persons (≥55 years) was associated with proximity to mine dumps. METHODS. Elderly persons in communities 1 - 2 km (exposed) and ≥5 km (unexposed) from five preselected mine dumps in Gauteng and North West provinces in SA were included in a cross-sectional study. RESULTS. Exposed elderly persons had a significantly higher prevalence of cardiovascular and respiratory diseases than those who were unexposed. Multiple logistic regression analysis indicated that living close to mine dumps was significantly associated with asthma + hypertension (odds ratio (OR) 1.67; 95% confidence interval (CI) 1.22 - 2.28), asthma + pneumonia (OR 1.86; 95% CI 1.14 - 3.04), emphysema + arrhythmia (OR 1.38; 95% CI 1.07 - 1.77), emphysema + myocardial infarction (OR 2.01; 95% CI 1.73 - 2.54), emphysema + pneumonia (OR 3.36; 95% CI 1.41 - 7.98), hypertension + myocardial infarction (OR 1.60; 95% CI 1.04 - 2.44) and hypertension + pneumonia (OR 1.34; 95% CI 1.05 - 1.93). CONCLUSION. Detrimental associations between comorbidity of the health outcomes and proximity to mine dumps were observed among the elderly in SAWe thank everybody who participated in the questionnaire interviews, Mr Moses Kebalepile and all the fieldworkers who assisted in data collection, the data technicians for the data capturing, and Statistics South Africa for providing the population sizes of elderly people in each study community.The Mine Health Safety Council, the National Research Fund – Deutscher Akademischer Austausch Dienst and the University of Pretoria.http://www.samj.org.zaam2016School of Health Systems and Public Health (SHSPH

Biomass fuel use for household cooking in Swaziland : is there an association with anaemia and stunting in children aged 6–36 months?

BACKGROUND : This study is the second to investigate the association between the use of biomass fuels (BMF) for household cooking and anaemia and stunting in children. Such fuels include coal, charcoal, wood, dung and crop residues. METHODS : Data from the 2006–2007 Swaziland Demographic and Health Survey (a cross-sectional study design) were analysed. Childhood stunting was ascertained through age and height, and anaemia through haemoglobin measurement. The association between BMF use and health outcomes was determined in multinomial logistic regression analyses. Various confounders were considered in the analyses. RESULTS : A total of 1150 children aged 6–36 monthswere included in the statistical analyses, of these 596 (51.8%) and 317 (27.6%)were anaemic and stunted, respectively. BMFusewas not significantly associated with childhood anaemia in univariate analysis. Independent risk factors for childhood anaemia were child’s age, history of diarrhoea and mother’s anaemia status. No significant association was observed between BMF use and childhood stunting, after adjusting for child’s gender, age, birth weight and preceding birth interval. CONCLUSION : This study identified the need to prioritize anaemia and stunting as health outcomes and introduction of public health intervention in Swaziland. Further research is needed globallyon the potential effects ofBMFuse on childhood anaemia and stunting.http://www.elsevier.com/locate/trstmhhb201

Allergic rhinitis, rhinoconjunctivitis and hayfever symptoms among children are associated with frequency of truck traffic near residences : a cross sectional study

BACKGROUND : Allergic rhinitis (AR) is an increasing and common condition affecting many people globally, especially children. The aim of the study was to investigate the association between the frequency of truck traffic and allergic rhinitis symptoms, rhinoconjunctivitis and hayfever among 13 to 14 year old school children in Ekurhuleni Metropolitan Municipality, Gauteng Province, South Africa. METHODS : In a cross-sectional study design, 3764 children from 16 randomly selected high schools were eligible to participate, 3468 completed the International Study of Asthma and Allergies in Childhood (ISAAC) Phase I questionnaire of which 3424 were suitable for analysis; the overall response rate was 92 %. Data were analysed using multilevel logistic regression analysis. RESULTS : The prevalence of self-reported rhinitis ever, current rhinitis rhinoconjunctivitis and hayfever was 52, 40, 21 and 37 % respectively. Rhinitis ever, current rhinitis and current rhinoconjunctivitis were significantly associated with the frequency of trucks passing near residences almost all day on weekdays, (OR 1.46 95 % CI: 1.16 − 1.84), (OR 1.60 95 % CI: 1.24–2.02) and (OR 1.42 95 % CI: 1.09–1.84) respectively. No association was observed between truck traffic and hay fever in the multiple analyses. CONCLUSION : The study shows a high prevalence of allergic rhinitis symptoms amongst children. The results support the hypothesis that traffic related pollution plays a role in the prevalence of allergic rhinitis symptoms in children residing in the area.The University of Pretoria, Tshwane University of Technology, Medical Research Council and the National Research Foundation.http://www.ehjournal.netam201