A biochemical assessment of Ochratoxin A stress responses in vitro, with resveratrol as a possible therapeutic intervention.

Doctor of Philosophy Medical Biochemistry. University of KwaZulu-Natal. Durban, 2017.Abstract available in PDF file

Firm Financial Performance in The Global 1000: Does Human Capital Effectiveness Matter?

Organisations worldwide spend a substantial proportion of revenue on salaries and benefits (compensation) as an investment in employees who are regarded as human capital. The justification behind this investment is the theoretical assertion that investments in human capital predict financial performance but empirical support for this relationship is limited. The present study contributes to the extant literature by examining the relationship between human capital effectiveness (HCE) and financial performance. A further contribution of the research is to consider alternative criteria of financial performance as findings may be dependent on operationalisation of the criterion. The relationships we tested were between Human Capital Return on Investment (HCROI) and (1) Return on Assets and (2) Return on Equity. Drawing on the Resource Based View theory, we conducted a study using 10 years of data from a sample that comprised the Global 1000 (highest revenue, listed firms domiciled across 45 countries). We used a retrospective correlational study. Spearman Correlation (rs) analysis revealed significant effects for the relationships we investigated in all years. Moreover, meta-analysis showed these effects to be significant on average across the 10 years, showing moderate strength and relative stability. A corollary of the study is that we established global benchmarks for HCROI and provided the first empirical evidence that supports a positive relationship between HCE and financial performance. These findings may be useful to investors who seek possible indicators of expected financial performance from HCE. In doing so, the study suggests we should expand financial reporting to include HCE indicators. Implications of findings and study limitations are noted

The phytoalexin, resveratrol ameliorates ochratoxin A genotoxicity in human embryonic kidney (HEK293) cells.

M. Med. Sc. University of KwaZulu-Natal, Durban 2014.Background: Ochratoxin A (OTA) is a mycotoxin produced by fungal species of Aspergillus and Penicillium. OTA is nephrotoxic and carcinogenic in several animal models; it frequently contaminates human and animal food products. Chronic exposure is associated with progressive renal fibrosis in humans (Balkan endemic nephropathy). Resveratrol is a phytoalexin that possesses both anti-cancer and antioxidant properties. We investigated the mechanism of cellular oxidative stress induced by OTA in the human embryonic kidney (HEK293) cell line. Methods: An IC50 value of 1.5μM was determined from a dose-dependent cell viability curve using the methylthiazol tetrazolium (MTT) assay on HEK293 cells treated with a range of OTA concentrations (0.25μM–50μM) for 24hrs. Glutathione levels were quantified by luminometry and gene expression of Nrf2, OGG1, CAT, SOD and GPx was determined by qPCR. Protein expression of Nrf2 and phosphorylated SIRT1 (pSIRT1) was assessed by western blot, DNA damage was determined using the comet assay, and flow cytometry was employed for intracellular ROS detection. Results: Resveratrol decreased mRNA expression of OGG1 (p<0.05) and OTA significantly increased OGG1 expression (p<0.05). The comet assay proved that while OTA induced DNA damage, resveratrol protected the DNA against strand breaks. Both resveratrol and OTA significantly increased antioxidant defence gene expression (Nrf2, CAT, GPx and SOD) (p<0.05). OTA decreased intracellular ROS, while resveratrol-treated cells exhibited the lowest percentage of intracellular ROS. Luminometry analysis showed the OTA+Resveratrol co-treatment to have a synergistic effect on the concentration of GSH and GSSG. Western blot analysis of protein showed that resveratrol significantly increased the levels of pSIRT1 while concomitantly decreasing the protein levels of Nrf2 (p<0.05) and OTA significantly decreased pSIRT1 protein levels

The phytoalexin resveratrol ameliorates ochratoxin a toxicity in human embryonic kidney (HEK293) cells

Ochratoxin A (OTA) is a nephrotoxic mycotoxin produced by Aspergillus and Penicillium fungi. It contaminates human and animal food products, and chronic exposure is associated with renal fibrosis in humans (Balkan endemic nephropathy). Resveratrol, a phytoalexin, possesses anti-cancer and antioxidant properties. We investigated the mechanism of cellular oxidative stress induced by OTA, and the effect of resveratrol in human embryonic kidney (HEK293) cells over 24 and 48 h. Cells were exposed to OTA [IC50¼1.5 mM (24 h) and 9.4 mM (48 h) determined using MTT assay] and 25mM resveratrol. Glutathione was quantified by luminometry and gene expression of Nrf2 and OGG1 was determined by qPCR. Protein expression of Nrf2, LonP1, SIRT3, and pSIRT1 was assessed by Western blot, DNA damage (comet assay), and intracellular reactive oxygen species (flow cytometry). At 24 h, resveratrol increased mRNA expression of the DNA repair enzyme, OGG1 (P<0.05), whereas OTA and OTAþresveratrol significantly decreased OGG1 expression (P<0.05). OGG1 expression increased during 48-h exposure to resveratrol and OTAþresveratrol (P<0.05). Comet tail lengths doubled in 48-h OTA-treated cells, whereas at both time periods, OTAþresveratrol yielded shorter comet tails (P<0.0001). During 24- and 48-h exposure, OTA, resveratrol, and OTAþresveratrol significantly decreased mRNA expression of Nrf2 (P<0.05). Luminometry analysis of GSH revealed an increase by OTAþresveratrol for 24 and 48 h (P<0.05 and P<0.001, respectively). Western blot analysis showed decreased Nrf2 protein expression during 24-h exposure, but increased Nrf2 expression during 48 h. LonP1 protein expression increased during 24-h exposure to OTA (P<0.05) and OTAþresveratrol (P<0.0011) and during 48-h exposure to resveratrol (P<0.0005).http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1097-46442016-12-31hb201

Methylenetetrahydrofolate (MTHFR), the One-Carbon Cycle, and Cardiovascular Risks

The 5-10-methylenetetrahydrofolate reductase (MTHFR) enzyme is vital for cellular homeostasis due to its key functions in the one-carbon cycle, which include methionine and folate metabolism and protein, DNA, and RNA synthesis. The enzyme is responsible for maintaining methionine and homocysteine (Hcy) balance to prevent cellular dysfunction. Polymorphisms in the MTHFR gene, especially C677T, have been associated with various diseases, including cardiovascular diseases (CVDs), cancer, inflammatory conditions, diabetes, and vascular disorders. The C677T MTHFR polymorphism is thought to be the most common cause of elevated Hcy levels, which is considered an independent risk factor for CVD. This polymorphism results in an amino acid change from alanine to valine, which prevents optimal functioning of the enzyme at temperatures above 37 &deg;C. Many studies have been conducted to determine whether there is an association between the C677T polymorphism and increased risk for CVD. There is much evidence in favour of this association, while several studies have concluded that the polymorphism cannot be used to predict CVD development or progression. This review discusses current research regarding the C677T polymorphism and its relationship with CVD, inflammation, diabetes, and epigenetic regulation and compares the evidence provided for and against the association with CVD

The value of electrocardiography in predicting inpatient mortality in patients with acute pulmonary embolism: A cross sectional analysis

Introduction: Pulmonary embolism (PE) is a significant global cause of mortality, ranking third after myocardial infarction and stroke. ECG findings may play a valuable role in the prognostication of patients with PE, with various ECG abnormalities proving to be reasonable predictors of haemodynamic decompensation, cardiogenic shock, and even mortality. This study aims to assess the value of electrocardiography in predicting inpatient mortality in patients with acute pulmonary embolism, as diagnosed with computed tomography pulmonary angiogram. Method: This study was a cross sectional analysis based at Tygerberg Hospital, Cape Town, South Africa. Eligible patients were identified from all CT-PA performed between 1 January 2017 and 31 December 2019 (2 years). The ECGs were independently screened by two blinded emergency physicians for predetermined signs that are associated with right heart strain and higher pulmonary artery pressures, and these findings were analysed to in-hospital mortality. Results: Of the included 81 patients, 61 (75 %) were female. Of the 41 (51 %) patients with submassive PE and 8 (10 %) with massive PE, 7 (17 %) and 3 (38 %) suffered inpatient mortality (p = 0.023) respectively. Univariate ECG analysis revealed that complete right bundle branch block (OR, 8.6; 95 % CI, 1.1 to 69.9; p = 0.044) and right axis deviation (OR, 5.6; 95 % CI, 1.4 to 22.4; p = 0.015) were significant predictors of inpatient mortality. Conclusion: Early identification of patients with pulmonary embolism at higher risk of clinical deterioration and in-patient mortality remains a challenge. Even though no clinical finding or prediction tool in isolation can reliably predict outcomes in patients with pulmonary embolism, this study demonstrated two ECG findings at presentation that were associated with a higher likelihood of inpatient mortality. This single-centre observational study with a small sample precludes concrete conclusions and a large follow-up multi-centre study is advised

Diagnosis and Treatment of MODY: An Updated Mini Review

Maturity-Onset Diabetes of the Young (MODY) is the most common form of monogenic diabetes resulting from a single gene mutation. It is characterized by mild hyperglycemia, autosomal dominant inheritance, early onset of diabetes (&lt;25 years), insulin resistance, and preservation of endogenous insulin secretion. Currently, 14 MODY subtypes have been identified, with differences in incidence, clinical features, diabetes severity and related complications, and treatment response. This type of diabetes is mostly misdiagnosed as either type 1 or type 2 diabetes mellitus because it is difficult to differentiate between these forms of diabetes due to clinical similarities, the high cost of genetic testing, and lack of awareness. As a result, thousands of patients are not receiving appropriate treatment. Accurate diagnosis would allow for more effective therapeutic management and treatment strategies that are distinct from those used for type 1 and type 2 diabetes. This review serves to explore MODY subtypes, diagnosis, and treatment, and increase awareness of MODY incidence