Research Articles (Medical Physiology)
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- ItemAdipose tissue as a possible therapeutic target for polyphenols : a case for Cyclopia extracts as anti-obesity nutraceuticals(Elsevier, 2019) Jack, Babalwa U.; Malherbe, Christiaan J.; Mamushi, Mokadi Peggy; Muller, Christo J. F.; Joubert, Elizabeth; Louwa, Johan; Pheiffer, CarmenENGLISH ABSTRACT: Obesity is a significant contributor to increased morbidity and premature mortality due to increasing the risk of many chronic metabolic diseases such as type 2 diabetes, cardiovascular disease and certain types of cancer. Lifestyle modifications such as energy restriction and increased physical activity are highly effective first-line treatment strategies used in the management of obesity. However, adherence to these behavioral changes is poor, with an increased reliance on synthetic drugs, which unfortunately are plagued by adverse effects. The identification of new and safer anti-obesity agents is thus of significant interest. In recent years, plants and their phenolic constituents have attracted increased attention due to their health-promoting properties. Amongst these, Cyclopia, an endemic South African plant commonly consumed as a herbal tea (honeybush), has been shown to possess modulating properties against oxidative stress, hyperglycemia, and obesity. Likewise, several studies have reported that some of the major phenolic compounds present in Cyclopia spp. exhibit anti-obesity effects, particularly by targeting adipose tissue. These phenolic compounds belong to the xanthone, flavonoid and benzophenone classes. The aim of this review is to assess the potential of Cyclopia extracts as an anti-obesity nutraceutical as underpinned by in vitro and in vivo studies and the underlying cellular mechanisms and biological pathways regulated by their phenolic compounds.
- ItemAmeliorative potentials of quercetin against cotinine-induced toxic effects on human spermatozoa(Hainan Medical University Journal Publisher, 2016) Goss, Dale; Oyeyipo, Ibukun P.; Skosana, Bongekile T.; Ayad, Bashir M.; Du Plessis, Stefan S.Objectives: Cotinine, the principal metabolite of nicotine found in smokers' seminal plasma, has been shown to adversely affect sperm functionality while quercetin, a flavonoid with diverse properties is associated with several in vivo and in vitro health benefits. The aim of this study was to investigate the potential benefits of quercetin supplementation against damage caused by the by-products of tobacco smoke in human sperm cells. Methods: Washed human spermatozoa from 10 normozoospermic donors were treated with nutrient medium (control), quercetin (30 mmol/L) and cotinine (190 mg/mL, 300 ng/mL) with or without quercetin for 60 and 180 min incubation periods. Computer-aided sperm analysis was used to assess sperm motility while acrosomereacted cells were identified under a fluorescent microscope using fluorescein isothiocyanate-labelled Pisum Sativum Agglutinin as a probe, viability was assessed by means of a dye exclusion staining technique (eosin/nigrosin) and oxidative stress by flow cytometry using dihydroethidium as a probe. Values were expressed as mean ± S.E.M. as compared by ANOVA. Results: Higher cotinine concentrations reduced the number of viable cells after 60 and 180 min of exposure while viability of cells was increased in the cotinine aliquots supplemented with quercetin after 180 min of exposure when compared with cotinine only treated group. Conclusion: This study indicates that the ameliorating ability of quercetin on cotinineinduced decline in sperm function is associated with increased number of viable cells.
- ItemAMP kinase activation and glut4 translocation in isolated cardiomyocytes(Clinics Cardive Publishing, 2010-04) Webste, Ingrid; Friedrich, Sven O.; Lochner, Amanda; Huisamen, BarbaraActivation of AMP-activated protein kinase (AMPK) results in glucose transporter 4 (GLUT4) translocation from the cytosol to the cell membrane, and glucose uptake in the skeletal muscles. This increased activation of AMPK can be stimulated by a pharmacological agent, AICAR (5’-aminoimidazole-4-carboxamide ribonucleoside), which is converted intracellularly into ZMP (5’-aminoimidazole-4-carboxamideribonucleosidephosphate), an AMP analogue. We utilised AICAR and ZMP to study GLUT4 translocation and glucose uptake in isolated cardiomyocytes. Adult ventricular cardiomyocytes were treated with AICAR or ZMP, and glucose uptake was measured via [3H]-2-deoxyglucose accumulation. PKB/Akt, AMPK and acetyl-CoA-carboxylase phosphorylation and GLUT4 translocation were detected by Western blotting or flow cytometry. AICAR and ZMP promoted AMPK phosphorylation. Neither drug increased glucose uptake but on the contrary, inhibited basal glucose uptake, although GLUT4 translocation from the cytosol to the membrane occurred. Using flow cytometry to detect the exofacial loop of the GLUT4 protein, we showed ineffective insertion in the membrane under these conditions. Supplementing with nitric oxide improved insertion in the membrane but not glucose uptake. We concluded that activation of AMPK via AICAR or ZMP was not sufficient to induce GLUT4-mediated glucose uptake in isolated cardiomyocytes. Nitric oxide plays a role in proper insertion of the protein in the membrane but not in glucose uptake.
- ItemAMP kinase activation and glut4 translocation in isolated cardiomyocytes(http://www.cvja.co.za/index.php, 2010-03) Webster, Ingrid; Huisamen, Barbara; Lochner, Amanda; Friedrich, Sven O; Biomedical Sciences: Medical Physiology
- ItemAntioxidant activities of Basella alba aqueous leave extract in blood, pancreas, and gonadal tissues of diabetic male Wistar rats(Wolters Kluwer, 2018) Arokoyo, Dennis Seyi; Oyeyipo, Ibukun Peter; Du Plessis, Stefan Simon; Aboua, Yapo GuillaumeBackground: Oxidative stress is frequently identified as a key element in the pathophysiology of many complications of diabetes mellitus, including reproductive complications. The antioxidant potential of medicinal plants have been suggested for therapeutic focus of diseases in recent reports. Objective: To investigate the effect of Basella alba (Ba) aqueous leave extract on diabetes‑induced oxidative stress. Materials and Methods: Forty male Wistar rats (8–10 weeks) were randomly divided into four groups (n = 10) and treated as follows; Control (C + Ns) and Diabetic (D + Ns) animals received oral normal saline 0.5 ml/100 g body weight daily, while Healthy Treatment (H + Ba) and Diabetic Treatment (D + Ba) rats were given Ba extract at an oral dose of 200 mg/kg body weight daily. Treatment was by gavage and lasted 4 weeks in all groups. Diabetes was induced in D + Ns and D + Ba rats by single intraperitoneal injection of streptozotocin (55 mg/kg) and fasting blood sugar (FBS) recorded weekly in all rats afterwards. Animals were euthanized at the end of the experiment and blood samples, pancreas, testes, and epididymis were preserved for analysis of oxidative stress biomarkers. Results: Oral administration of aqueous leave extract of Ba significantly (P < 0.0001) lowered FBS in D + Ba rats. There was significantly higher blood superoxide dismutase activity and serum ferric reducing antioxidant power, but lower serum concentration of conjugated dienes and thiobarbituric acid reactive substances in D + Ba compared to D + Ns rats (P < 0.05). Conclusion: Ba exerts antioxidant effects in the gonads by enhancing antioxidant parameters in circulating blood, but not necessarily in the gonadal tissues.
- ItemAscorbic acid causes spuriously low blood glucose measurements(Health & Medical Publishing Group, 1993-01) Strijdom J. G.; Marais B. J.; Koeslag J. H.[No abstract available]
- ItemAspalathin reverts doxorubicin-induced cardiotoxicity through increased autophagy and decreased expression of p53/mTOR/p62 signaling(MDPI, 2017-11-01) Johnson, Rabia; Shabalala, Samukelisiwe; Louw, Johan; Kappo, Abidemi Paul; Muller, Christo John FrederickENGLISH ABSTRACT: Doxorubicin (Dox) is an effective chemotherapeutic agent used in the treatment of various cancers. Its clinical use is often limited due to its potentially fatal cardiotoxic side effect. Increasing evidence indicates that tumour protein p53 (p53), adenosine monophosphate-activated protein kinase (AMPK), nucleoporin p62 (p62), and the mammalian target of rapamycin (mTOR) are critical mediators of Dox-induced apoptosis, and subsequent dysregulation of autophagy. Aspalathin, a polyphenolic dihydrochalcone C-glucoside has been shown to activate AMPK while decreasing the expression of p53. However, the role that aspalathin could play in the inhibition of Dox-induced cardiotoxicity through increased autophagy flux remained unexplored. H9c2 cardiomyocytes and Caov-3 ovarian cancer cells were cultured in Dulbecco’s Modified Eagle’s medium and treated with or without Dox for five days. Thereafter, cells exposed to 0.2 µM Dox were co-treated with either 20 µM Dexrazozane (Dexra) or 0.2 µM aspalathin (ASP) daily for 5 days. Results obtained showed that ASP mediates its cytoprotective effect in a p53-dependent manner, by increasing the Bcl-2/Bax ratio and decreasing apoptosis. The latter effect was diminished through ASP-induced activation of autophagy-related genes (Atgs) with an associated decrease in p62 through induction of AMPK and Fox01. Furthermore, we showed that ASP was able to potentiate this effect without decreasing the anti-cancer efficacy of Dox, as could be observed in Caov-3 ovarian cancer cells. Taken together, the data presented in this study provides a credible mechanism by which ASP co-treatment could protect the myocardium from Dox-induced cardiotoxicity.
- ItemAspalathin, a C-glucosyldihydrochalcone from rooibos improves the hypoglycemic potential of metformin in type 2 diabetic (db/db) mice(Institute of Physiology, The Czech Academy of Sciences, 2018-07-25) Dludla, P. V.; Gabuza, K. B.; Muller, C. J. F.; Joubert, E.; Louw, J.; Johnson, R.ENGLISH ABSTRACT: Metformin is the first line therapy of type 2 diabetics, but continued reduction of their life expectancy warrants further investigation into alternative treatment strategies. This study reports on the combinational use of metformin with aspalathin, a C-glucosyl dihydrochalcone with known glucose lowering and antioxidant properties, as an effective hypoglycemic therapy in a type 2 diabetic (db/db) mouse model. When tested as a monotherapy, a low dose of aspalathin (13 mg/kg) showed no effect, while a high dose (130 mg/kg) has already displayed a better potential than metformin in protecting against diabetes associated symptoms in db/db mice. Thus, it remains of interest to determine whether this dihydrochalcone can improve the efficacy of metformin. The results showed that this combination therapy was more effective than the use of metformin as a monotherapy in ameliorating diabetes associated symptoms, including abnormal raised fasting plasma glucose levels, impaired glucose tolerance, as well as excessively increased body weights and fat content. The treated mice also had reduced food and water consumption when compared to untreated controls, with a pronounced effect evident in the last week of treatment. Therefore, this study supports further investigations into the ameliorative effect of combination therapy of metformin and aspalathin against diabetes associated symptoms.
- ItemAspalathin, a natural product with the potential to reverse hepatic insulin resistance by improving energy metabolism and mitochondrial respiration(Public Library of Science, 2019) Mazibuko-Mbeje, Sithandiwe E.; Dludla, Phiwayinkosi V.; Johnson, Rabia; Joubert, Elizabeth; Louw, Johan; Ziqubu, Khanyisani; Tiano, Luca; Silvestri, Sonia; Orlando, Patrick; Opoku, Andy R.; Muller, Christo J. F.ENGLISH ABSTRACT: Aspalathin is a rooibos flavonoid with established blood glucose lowering properties, however, its efficacy to moderate complications associated with hepatic insulin resistance is unknown. To study such effects, C3A liver cells exposed to palmitate were used as a model of hepatic insulin resistance. These hepatocytes displayed impaired substrate metabolism, including reduced glucose transport and free fatty acid uptake. These defects included impaired insulin signaling, evident through reduced phosphatidylinositol-4,5-bisphosphate 3-kinase/ protein kinase B (PI3K/AKT) protein expression, and mitochondrial dysfunction, depicted by a lower mitochondrial respiration rate. Aspalathin was able to ameliorate these defects by correcting altered substrate metabolism, improving insulin signaling and mitochondrial bioenergetics. Activation of 5´-adenosine monophosphate-activated protein kinase (AMPK) may be a plausible mechanism by which aspalathin increases hepatic energy expenditure. Overall, these results encourage further studies assessing the potential use of aspalathin as a nutraceutical to improve hepatocellular energy expenditure, and reverse metabolic disease-associated complications.
- ItemAtaxia telangiectasia mutated protein kinase : a potential master puppeteer of oxidative stress-induced metabolic recycling(Hindawi, 2021) Blignaut, Marguerite; Harries, Sarah; Lochner, Amanda; Huisamen, BarbaraENGLISH ABSTRACT: Ataxia Telangiectasia Mutated protein kinase (ATM) has recently come to the fore as a regulatory protein fulfilling many roles in the fine balancing act of metabolic homeostasis. Best known for its role as a transducer of DNA damage repair, the activity of ATM in the cytosol is enjoying increasing attention, where it plays a central role in general cellular recycling (macroautophagy) as well as the targeted clearance (selective autophagy) of damaged mitochondria and peroxisomes in response to oxidative stress, independently of the DNA damage response. The importance of ATM activation by oxidative stress has also recently been highlighted in the clearance of protein aggregates, where the expression of a functional ATM construct that cannot be activated by oxidative stress resulted in widespread accumulation of protein aggregates. This review will discuss the role of ATM in general autophagy, mitophagy, and pexophagy as well as aggrephagy and crosstalk between oxidative stress as an activator of ATM and its potential role as a master regulator of these processes.
- ItemAtaxia-Telangiectasia Mutated is located in cardiac mitochondria and impacts oxidative phosphorylation(Springer Nature, 2019) Blignaut, Marguerite; Loos, Ben; Botchway, Stanley W.; Parker, Anthony W.; Huisamen, BarbaraThe absence of Ataxia-Telangiectasia mutated protein kinase (ATM) is associated with neurological, metabolic and cardiovascular defects. The protein has been associated with mitochondria and its absence results in mitochondrial dysfunction. Furthermore, it can be activated in the cytosol by mitochondrial oxidative stress and mediates a cellular anti-oxidant response through the pentose phosphate pathway (PPP). However, the precise location and function of ATM within mitochondria and its role in oxidative phosphorylation is still unknown. We show that ATM is found endogenously within cardiac myocyte mitochondria under normoxic conditions and is consistently associated with the inner mitochondrial membrane. Acute ex vivo inhibition of ATM protein kinase significantly decreased mitochondrial electron transfer chain complex I-mediated oxidative phosphorylation rate but did not decrease coupling efficiency or oxygen consumption rate during β-oxidation. Chemical inhibition of ATM in rat cardiomyoblast cells (H9c2) significantly decreased the excited-state autofluorescence lifetime of enzyme-bound reduced NADH and its phosphorylated form, NADPH (NAD(P)H; 2.77 ± 0.26 ns compared to 2.57 ± 0.14 ns in KU60019-treated cells). This suggests an interaction between ATM and the electron transfer chain in the mitochondria, and hence may have an important role in oxidative phosphorylation in terminally differentiated cells such as cardiomyocytes.
- ItemBeneficial effects of adenosine triphosphate-MgC12 administered intravenously to rabbits subjected to haemorrhagic shock(Health & Medical Publishing Group, 1986-10) Engelbrecht, F. M.; Mattheyse, F. J.ENGLISH ABSTRACT: The beneficial effects of adenosine triphosphate (ATP)-MgCl2 administered as a bolus following fluid infusion or in combination with the infusion fluid were investigated in rabbits subjected to severe but reversible haemorrhagic shock. ATP-MgCl2 treatment led to a significant improvement of the metabolic functions of lung and liver tissue. Kidney tissue showed the same tendency, but the improvement did not reach significant levels. The release of lysosomal enzymes in vivo was retarded after treatment but not stopped. The mean arterial pressure was kept at a relatively constant level when ATP-MgCl2 was infused slowly. Administration as a bolus resulted in an immediate dramatic drop in pressure, followed by recovery and then a gradual decrease to levels which appeared to be incompatible with survival.
- ItemBlood-based DNA methylation biomarkers for type 2 diabetes : potential for clinical applications(Frontiers Media, 2018) Willmer, Tarryn; Johnson, Rabia; Louw, Johan; Pheiffer, CarmenENGLISH ABSTRACT: Type 2 diabetes (T2D) is a leading cause of death and disability worldwide. It is a chronic metabolic disorder that develops due to an interplay of genetic, lifestyle, and environmental factors. The biological onset of the disease occurs long before clinical symptoms develop, thus the search for early diagnostic and prognostic biomarkers, which could facilitate intervention strategies to prevent or delay disease progression, has increased considerably in recent years. Epigenetic modifications represent important links between genetic, environmental and lifestyle cues and increasing evidence implicate altered epigenetic marks such as DNA methylation, the most characterized and widely studied epigenetic mechanism, in the pathogenesis of T2D. This review provides an update of the current status of DNA methylation as a biomarker for T2D. Four databases, Scopus, Pubmed, Cochrane Central, and Google Scholar were searched for studies investigating DNA methylation in blood. Thirty-seven studies were identified, and are summarized with respect to population characteristics, biological source, and method of DNA methylation quantification (global, candidate gene or genome-wide). We highlight that differential methylation of the TCF7L2, KCNQ1, ABCG1, TXNIP, PHOSPHO1, SREBF1, SLC30A8, and FTO genes in blood are reproducibly associated with T2D in different population groups. These genes should be prioritized and replicated in longitudinal studies across more populations in future studies. Finally, we discuss the limitations faced by DNA methylation studies, which include including interpatient variability, cellular heterogeneity, and lack of accounting for study confounders. These limitations and challenges must be overcome before the implementation of blood-based DNA methylation biomarkers into a clinical setting. We emphasize the need for longitudinal prospective studies to support the robustness of the current findings of this review.
- ItemBody composition in women with HIV/AIDS : the relevance of exercise(Health and Medical Publishing Group (HMPG), 2008-07) Myburgh, Kathryn H.; De Bruto, Petro C.Untreated infection with the human immunodeficiency virus (HIV) leads to severe physical debilitation, culminating in the acquired immune deficiency syndrome (AIDS). Multiple infections, body mass loss, physical weakness and wasting are characteristic manifestations of each of the four stages of HIV/AIDS, respectively (Table I). The latter two impact especially on the affected person’s ability to function, as well as on social and economic levels. However, even though antiretroviral treatment (ART) is now available at many selected public clinics in South Africa, it only complicates the issues surrounding body composition and physical function.
- ItemCardiac glucolipotoxicity and cardiovascular outcomes(MDPI, 2018) Cerf, Marlon E.Cardiac insulin signaling can be impaired due to the altered fatty acid metabolism to induce insulin resistance. In diabetes and insulin resistance, the metabolic, structural and ultimately functional alterations in the heart and vasculature culminate in diabetic cardiomyopathy, coronary artery disease, ischemia and eventually heart failure. Glucolipotoxicity describes the combined, often synergistic, adverse effects of elevated glucose and free fatty acid concentrations on heart structure, function, and survival. The quality of fatty acid shapes the cardiac structure and function, often influencing survival. A healthy fatty acid balance is therefore critical for maintaining cardiac integrity and function.
- ItemCardiomyocyte differentiation : experience and observations from 2 laboratories(South African Heart Association, 2017) Patten, Victoria; Chabaesele, I.; Sishi, Balindiwe; Van Vuuren, DerickThe undifferentiated clonal cell line, H9c2, derived from left ventricular rat heart tissue, has been extensively used in cardiovascular research. In the present study, 2 independent laboratories aimed to investigate the cells’ capacity to differentiate into distinct cardiac-like cells. Undifferentiated H9c2 cells were supplemented daily for a period of 6 - 12 days, with varying concentrations of retinoic acid (RA) (10nM, 30nM and 1μM), in standard cell culture medium containing either 1% foetal bovine, or horse serum, in order to stimulate differentiation of the cells into a more cardiac-specific phenotype. Light microscopy confirmed some degree of morphological change associated with differentiation, and a significant increase in oxidative phosphorylation following RA treatment was observed. However, Western blot probing for the cardiac-specific markers Cardiac Troponin T (cTnT) and Myosin Light Chain-2v (MLC2v) indicated little to no differentiation, although immunocytochemistry indicated the presence of cTnT expression. Thus, it was found that the differentiation protocol induced differentiation in some, but not all cells, thereby generating a heterogeneous cell population. Our findings suggest that the H9c2 cell line may display some degree of resistance to differentiation. This should be kept in mind when considering to use this model for cardiovascular research.
- ItemCardioprotection conferred by rooibos (Aspalathus linearis) : a mini review to highlight a potential mechanism of action(Academy of Science of South Africa, 2019) Maarman, Gerald J.ENGLISH ABSTRACT: A number of cardioprotective interventions have been identified throughout the years, and these include the use of natural antioxidants in sources like rooibos (Aspalathus linearis) tea. Recent studies have demonstrated that rooibos (either its isolated components or the crude rooibos extract/tea) confers cardioprotection in diabetic cardiomyopathy and myocardial ischaemic injury. In addition, a clinical study has shown that regular rooibos consumption reduces the risk for cardiovascular disease in adults. However, rooibos is currently not considered an official treatment against cardiac disease, mainly because the underlying mechanisms for rooibos-induced cardioprotection are not fully elucidated. Physiological actions of rooibos must be well investigated before rooibos can be used in a clinical setting as adjunct treatment for patients with heart disease. Thus, research to delineate the underlying mechanisms of rooibos-induced cardioprotection is key. In the light of the aforementioned, the available literature on rooibos-induced cardioprotection is reviewed here, highlighting the fact that rooibos preserves and maintains cardiac energy homeostasis. It is postulated that rooibos activates an AMPK-GLUT-4 glucose oxidation (cardiac energy-shortage sensing) pathway to shift cardiac energy usage, thereby conferring cardioprotection.
- ItemCardioprotective potential of N-acetyl cysteine against hyperglycaemia-induced oxidative damage : a protocol for a systematic review(BMC (part of Springer Nature), 2017) Dludla, Phiwayinkosi V.; Nkambule, Bongani B.; Dias, Stephanie C.; Johnson, RabiaBackground: Hyperglycaemia-induced oxidative damage is a well-established factor implicated in the development of diabetic cardiomyopathy (DCM) in diabetic individuals. Some of the well-known characteristics of DCM include increased myocardial left ventricular wall thickness and remodelling that result in reduced cardiac efficiency. To prevent this, an increasing number of pharmacological compounds such as N-acetyl cysteine (NAC) are explored for their antioxidant properties. A few studies have shown that NAC can ameliorate hyperglycaemia-induced oxidative damage within the heart. Hence, the objective of this review is to synthesise the available evidence pertaining to the cardioprotective role of NAC against hyperglycaemia-induced oxidative damage and thus prevent DCM. Methods: This systematic review protocol will be reported in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) 2015 statement. We will perform a comprehensive search on major databases such as EMBASE, Cochrane Library, PubMed and Google scholar for original research articles published from January 1960 to March 2017. We will only report on literature that is available in English. Two authors will independently screen for eligible studies using pre-defined criteria, and data extraction will be done in duplicate. All discrepancies will be resolved by consensus or consultation of a third reviewer. The quality of studies will be checked using Cochrane Risk of Bias Assessment Tool and The Joanna Briggs Institute (JBI) Critical Appraisal tools for non-randomised experimental studies. Heterogeneity across studies will be assessed using the Cochrane Q statistic and the inconsistency index (I2). We will use the random effects model to calculate a pooled estimate. Discussion: Although several studies have shown that NAC can ameliorate hyperglycaemia-induced oxidative damage within the heart, this systematic review will be the first pre-registered synthesis of data to identify the cardioprotective potential of NAC against hyperglycaemia-induced oxidative damage. This result will help guide future research evaluating the cardioprotective role of NAC against DCM and better identify possible mechanisms of action for NAC to prevent oxidative damage with a diabetic heart.
- ItemCardiovascular risk and endothelial function in people living with HIV/AIDS: design of the multi-site, longitudinal EndoAfrica study in the Western Cape Province of South Africa(BioMed Central, 2017-01-07) Strijdom, Hans; De Boever, Patrick; Walzl, Gerhard; Essop, M. Faadiel; Nawrot, Tim S.; Webster, Ingrid; Westcott, Corli; Mashele, Nyiko; Everson, Frans; Malherbe, Stephanus T.; Stanley, Kim; Kessler, Harald H.; Stelzl, Evelyn; Goswami, NanduBackground: There is growing evidence of an interaction between HIV-infection, anti-retroviral therapy (ART) and cardiovascular diseases (CVD). Epidemiological studies in Europe and North America have been observing a shift towards an increased incidence of coronary heart disease and acute myocardial infarctions in HIV-infected populations compared to the general population even after adjusting for traditional cardiovascular risk factors. Despite South Africa (and sub-Saharan Africa, SSA) being regarded as the epicentre of the global HIV epidemic, very little is known about the prevalence of cardiovascular risk factors and precursors of vascular disease in HIV-infected populations in this region. The knowledge gap is further widened by the paucity of data from prospective studies. We present the rationale, objectives and key methodological features of the EndoAfrica study, which aims to determine whether HIVinfection and ART are associated with altered cardiovascular risk and changes in vascular endothelial structure and function in adults living in the Western Cape Province of South Africa. Methods: In this longitudinal study, comprehensive cardiovascular assessments of HIV-negative and HIV-positive (with and without ART) study participants are performed by clinical and biochemical screening for traditional cardiovascular risk factors and biomarkers of CVD. Vascular and endothelial function is determined by brachial artery flow-mediated dilatation (FMD), carotid-intima-thickness (IMT) measurements and quantitative retinal blood vessel analyses, complemented by vascular endothelial biomarker assays. Finally, we aim to statistically determine whether HIVinfection and/or ART are associated with increased cardiovascular risk and vascular endothelial dysfunction, and determine whether there is progression/regression in these endpoints 18 months after the baseline assessments. Discussion: The EndoAfrica study provides a unique opportunity to recruit a cohort of HIV-infected patients and HIVnegative controls who will be comprehensively and longitudinally assessed for cardiovascular risk and disease profile with vascular endothelial function as a potentially important intermediate cardiovascular phenotype. To our knowledge, it is the first time that such a systematic study has been established in the context of SSA and South Africa.
- ItemCombination of radiosensitizers and hyperthermia in tumour radiotherapy(1981) Brueckner, V.Specific metabolic properties of hypoxic (and therefore radio-resistant) tumour cells are responsible for the selective effect of radiosensitizers (such as misonidazole) and hyperthermia upon these cells in respect of radiosensitization as well as cytotoxicity. Radiosensitizers and hyperthermia should therefore be used to improve the results of tumour radiotherapy; enhancement ratios of 2-4 have already been attained experimentally with this combined treatment. In spite of these good results, certain problems exist, and up to now the combination of radiosensitizers and hyperthermia has not been used to any great extent for tumours in humans.