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.
- ItemThe adrenal cortex in hypercholesterolaemic rabbits. Histochemical and electron microscopical changes(Health & Medical Publishing Group, 1978-2) Rossouw, D. J.; Chase, C. C.; Engelbrecht, F. M.The adrenals of rabbits on a cholesterol-rich diet for 35 days showed histopathological changes, a marked increase in weight and a lowering in the ascorbate content. A focal increase in the neutral lipid and cholesterol content was noted mostly in the inner cortical zones; and a characteristic acid phosphatase-positive pattern in areas of infiltrating cells, and an alkaline phosphatase-positive reaction in heterophils in the infiltrated areas. Electron microscopy confirmed that the zona glomerulosa cells were relatively normal in hypercholesterolaemic rabbits, while necrosis and fibrosis were very obvious in the inner two zones. The cellular infiltrate was shown to consist of large, granular mononuclear cells, heterophils, eosinophils, stromal phagocytes, lymphocytes and plasma cells. The possibility that the reaction was of an immunological nature is considered. The morphology of the adrenals of rabbits which were on a cholesterol-rich diet for 35 days and on a normal diet for 6 weeks afterwards, was indistinguishable from that of those rabbits killed after 35 days on a cholesterol-rich diet.
- 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(http://www.cvja.co.za/index.php, 2010-03) Webster, Ingrid; Huisamen, Barbara; Lochner, Amanda; Friedrich, Sven O; Biomedical Sciences: Medical Physiology
- 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.
- 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.
- ItemAspalathin-enriched green rooibos extract reduces hepatic insulin resistance by modulating PI3K/AKT and AMPK pathways(MDPI, 2019-02-01) Mazibuko-Mbeje, Sithandiwe E.; Dludla, Phiwayinkosi V.; Roux, Candice; Johnson, Rabia; Ghoor, Samira; Joubert, Elizabeth; Louw, JohanWe previously demonstrated that an aspalathin-enriched green rooibos extract (GRE) reversed palmitate-induced insulin resistance in C2C12 skeletal muscle and 3T3-L1 fat cells by modulating key effectors of insulin signalling such as phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B (PI3K/AKT) and AMP-activated protein kinase (AMPK). However, the effect of GRE on hepatic insulin resistance is unknown. The effects of GRE on lipid-induced hepatic insulin resistance using palmitate-exposed C3A liver cells and obese insulin resistant (OBIR) rats were explored. GRE attenuated the palmitate-induced impairment of glucose and lipid metabolism in treated C3A cells and improved insulin sensitivity in OBIR rats. Mechanistically, GRE treatment significantly increased PI3K/AKT and AMPK phosphorylation while concurrently enhancing glucose transporter 2 expression. These findings were further supported by marked stimulation of genes involved in glucose metabolism, such as insulin receptor (Insr) and insulin receptor substrate 1 and 2 (Irs1 and Irs2), as well as those involved in lipid metabolism, including Forkhead box protein O1 (FOXO1) and carnitine palmitoyl transferase 1 (CPT1) following GRE treatment. GRE showed a strong potential to ameliorate hepatic insulin resistance by improving insulin sensitivity through the regulation of PI3K/AKT, FOXO1 and AMPK-mediated pathways.
- ItemAspalathin-rich green rooibos extract lowers LDL-cholesterol and oxidative status in high-fat diet-induced diabetic vervet monkeys(2019-05-02) Orlando, Patrick; Chellan, Nireshni; Louw, Johan; Tiano, Luca; Cirilli, Ilenia; Dludla, Phiwayinkosi; Joubert, Elizabeth; Muller, Christo J. F.Type 2 diabetic patients possess a two to four-fold-increased risk for cardiovascular diseases (CVD). Hyperglycemia, oxidative stress associated with endothelial dysfunction and dyslipidemia are regarded as pro-atherogenic mechanisms of CVD. In this study, high-fat diet-induced diabetic and non-diabetic vervet monkeys were treated with 90 mg/kg of aspalathin-rich green rooibos extract (Afriplex GRT) for 28 days, followed by a 1-month wash-out period. Supplementation showed improvements in both the intravenous glucose tolerance test (IVGTT) glycemic area under curve (AUC) and total cholesterol (due to a decrease of the low-density lipoprotein [LDL]) values in diabetics, while non-diabetic monkeys benefited from an increase in high-density lipoprotein (HDL) levels. No variation of plasma coenzyme Q10 (CoQ10) were found, suggesting that the LDL-lowering effect of Afriplex GRT could be related to its ability to modulate the mevalonate pathway differently from statins. Concerning the plasma oxidative status, a decrease in percentage of oxidized CoQ10 and circulating oxidized LDL (ox-LDL) levels after supplementation was observed in diabetics. Finally, the direct correlation between the amount of oxidized LDL and total LDL concentration, and the inverse correlation between ox-LDL and plasma CoQ10 levels, detected in the diabetic monkeys highlighted the potential cardiovascular protective role of green rooibos extract. Taken together, these findings suggest that Afriplex GRT could counteract hyperglycemia, oxidative stress and dyslipidemia, thereby lowering fundamental cardiovascular risk factors associated with diabetes.
- ItemAssessment of the 2,4 km run as a predictor of aerobic capacity(Health & Medical Publishing Group, 1990-09) Burger, S. C.; Bertram, S. R.; Stewart, R. I.ENGLISH ABSTRACT: Since the 2,4 km run time test is routinely used in military training programmes as an indicator of aerobic capacity and its possible improvement, an atemtp was made to: (i) establish a regression equation of VO2(max) v. 2,4 km run time in a group of 20 young military volunteers; and (ii) determine whether this equation could be used to predict VO2(max) reliably from the 2,4 km time obtained from another group. Before and after training, VO2(max) was measured in all subjects using a treadmill test, and 2,4 km run time was determined in the field. Linear regression equations using the 2,4 km run time as the independent variable accounted for 76-92% of the variance in VO2(max), while the standard error of the estimate varied from 2,24-2,91 ml/kg/min. In the second test group, the directly measured VO2(max) was 59,89 ± 0,99 ml/kg/min, while the mean values estimated from the regression equation of the first group was 59,61 ± 1,16 ml/kg/min (P< 0.001). It was concluded that, in the population studied, the 2,4 km run time in the field reliably predicts VO2(max) measured during treadmill exercise in the laboratory.
- 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.
- ItemThe beneficial role of Anchomanes difformis in STZ-induced reproductive dysfunction in male Wistar rats(Dove Press, 2020-11) Alabi, Toyin Dorcas; de Villiers, Charon; du Plessis, Stephan S.; Monsees, Thomas K.; Brooks, Nicole L.; Oguntibeju, Oluwafemi OmoniyiBackground: Progression of diabetes mellitus has increasingly led to several diabetic complications. Diabetes is one of the major factors implicated in male reproductive system damage. Recent approaches such as the use of medicinal plants have been explored in the management of diabetes and associated complications. Anchomanes difformis (common name: children’s umbrella) has been shown to possess anti-diabetic ability in animal model. Therefore, this study seeks to investigate the potency of Achomanes difformis in ameliorating diabetes-induced reproductive dysfunction. Method: Type 2 diabetes was induced in male Wistar rats with 10% fructose administration for 2 weeks and an intraperitoneal injection of 40mg/kgBW of streptozotocin. Aqueous extract (200mg and 400mg/kgBW) of Anchomanes difformis leaves was administered daily for 6 weeks. The rats were randomly divided into 7 groups with a minimum of eight rats in each (8 rats in normal groups and 10 in diabetic groups). The impact of diabetes and treatment was investigated by estimating sperm concentration, motility indices, viability and morphological parameters in the normal, treatment controls and diabetic rats using CASA-SCA system. Histological examination of the testes and epididymis was performed. Results: Diabetes induction resulted in significant decrease in sperm concentration, viability and some motility parameters with 40% abnormalities in sperm morphology. The administration of Anchomanes difformis significantly increased sperm concentration and sperm viability, while it significantly improved the percentage of morphologically normal sperm in diabetic rats. Anchomanes difformis ameliorated testicular damage such as vacuolization and loss of germinal epithelium in the diabetic-treated rats when compared to the diabetic controls. Conclusion: The potency Anchomanes difformis displayed against diabetic-induced damage in the reproductive system might be a new and promising tool in the management of male reproductive dysfunctions and associated complications in diabetes mellitus.
- ItemBiochemiese en Hematologiese Veranderinge Tydens Eksperimentele Hipercholesterolemie(Health & Medical Publishing Group, 1973-11) Rossouw, D. J.; Engelbrecht, F. M.ENGLISH ABSTRACT: Various biochemical and hematological parameters were investigated during experimentally induced hypercholesterolemia in rabbits. A close correlation between the total serum cholesterol concentration and the changes in body mass and β globulin concentration was observed. The initial increase in these parameters was followed by a reduction in body mass and β globulin concentration and was accompanied by a simultaneous decline in the total serum cholesterol values. The slight increase in total serum protein levels could be attributed to an elevation in the globulin fraction. Both the relative and absolute α and γ globulin concentrations increased progressively during the course of the study. The significance of these findings is discussed. Anemia of a biphasic character (the second phase being hemolytic) was associated with the hypercholesterolemia. The increased fragility of the red blood corpuscles, however, was not related to the total serum cholesterol concentrations. The marked mononuclear leucocytosis and basophilia which were observed, may be a response to chronic inflammatory processes in the tissues.
- ItemBiological effect of asbestos dust on the peritoneal viscera of rats(Health & Medical Publishing Group, 1973-09) Engelbrecht, F. M.; Burger, B. F.ENGLISH ABSTRACT: Crocidolite and chrysotile asbestos suspensions were ip injected into rats. Peritoneal mesotheliomas were induced in 90% of the crocidolite group and in 30% of the chrysotile group. The pathology and possible pathogenesis are described and discussed. It is postulated that the asbestos fibers are encapsulated by fibrous tissue and that a soluble carcinogen then diffuses from these fibers to the mesothelial cells, causing anaplastic changes.
- 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.