The Role of Pro-Opiomelanocortin Derivatives in the Development of Type 2 Diabetes-Associated Myocardial Infarction: Possible Links with Prediabetes.

Myocardial infarction is a major contributor to CVD-related mortality. T2DM is a risk factor for MI. Stress activates the HPA axis, SNS, and endogenous OPS. These POMC derivatives increase the blood glucose and cardiovascular response by inhibiting the PI3K/AkT insulin signaling pathway and increasing cardiac contraction. Opioids regulate the effect of the HPA axis and SNS and they are cardioprotective. The chronic activation of the stress response may lead to insulin resistance, cardiac dysfunction, and MI. Stress and T2DM, therefore, increase the risk of MI. T2DM is preceded by prediabetes. Studies have shown that prediabetes is associated with an increased risk of MI because of inflammation, hyperlipidemia, endothelial dysfunction, and hypertension. The HPA axis is reported to be dysregulated in prediabetes. However, the SNS and the OPS have not been explored during prediabetes. The effect of prediabetes on POMC derivatives has yet to be fully explored and understood. The impact of stress and prediabetes on the cardiovascular response needs to be investigated. This study sought to review the potential impact of prediabetes on the POMC derivatives and pathways that could lead to MI.

The role of fibrinolysis in the development of prediabetes-associated coronary heart disease: a focus on the plasminogen activator inhibitor -1 and its potential use as a predictive marker in diet-induced prediabetes.

Introduction: Type 2 diabetes mellitus (T2DM) is associated with an increased risk of cardiovascular diseases (CVD). However, the onset of T2DM is preceded by prediabetes, which is associated with sedentary lifestyles and consumption of high-calorie diets. Studies have shown that impaired glucose homeostasis creates an environment for developing T2DM-related complications. Using a high-fat-high-carbohydrate diet-induced prediabetes animal model, this study sought to assess the risk factors of coronary heart disease (CHD) in diet-induced prediabetes and identify biomarkers that can be used for early detection of prediabetes-associated CHD. Methods: Male Sprague Dawley rats were randomly grouped into two groups and were kept on different diets for 20 weeks (n = 6 in each group). One group was fed standard rat chow to serve as a non-prediabetes (NPD) control, while the other group consumed a high-fat-high-carbohydrate diet to induce prediabetes (PD). Post induction, the homeostasis model assessment- insulin resistance (HOMA-IR) and glycated haemoglobin (HbA1c) was used to test for insulin resistance. Body weight, mean arterial pressure (MAP), resting heart rate (HR), inflammatory cytokines (C-reactive protein (CRP), tumor necrosis factor (TNF-α), interleukin-6 (IL-6)), lipids (total cholesterol (TC), triglyceride (TG), lipoproteins (HDL, LDL, VLDL)), endothelial function (endothelial nitric oxide (eNOS), endothelin -1 (ET-1)), fibrinolysis (plasminogen activator inhibitor-1 (PAI-1)) were all measured to assess the risk of CHD. All data were expressed as means ± S.E.M. Statistical comparisons were performed with Graph Pad. Instat Software using Student's two-sided t-test. The Pearson correlation coefficient and linear regression were calculated to assess the association. The value of p < 0.05 was considered statistically significant. Results: There was significant insulin resistance accompanied by significantly increased HbA1c and body weight in PD compared to NPD. Simultaneously, there was a significant increase in inflammatory cytokines in PD compared to NPD. This was accompanied by significantly increased TG and VLDL and endothelial dysfunction in PD. The association between HOMA-IR and PAI-1 was insignificantly positive in NPD, whereas a significantly strong positive association was observed in PD. Conclusion: There is a positive correlation between insulin resistance and PAI-1 during prediabetes; therefore, suggesting that prediabetes increases the risk of developing vascular thrombosis. The current therefore study warrants further investigation on PAI-1 and other markers of fibrinolysis for the early detection of thrombosis and risk of CHD in prediabetes.

Assessing the risk factors for myocardial infarction in diet-induced prediabetes: myocardial tissue changes.

BACKGROUND: Hyperglycaemia is known to result in oxidative stress tissue injury and dysfunction. Interestingly, studies have reported hepatic and renal oxidative stress injury during prediabetes; however, any injury to the myocardium during prediabetes has not been investigated. Hence this study aims to assess changes in the myocardial tissue in an HFHC diet-induced model of prediabetes. METHODS: Male Sprague Dawley rats were randomly grouped into non-prediabetes and prediabetes (n = 6 in each group) and consumed a standard rat chow or fed a high-fat-high-carbohydrate diet respectively for a 20-week prediabetes induction period. Post induction, prediabetes was confirmed using the ADA criteria. Aldose reductase, NADH oxidase 1, superoxide dismutase, glutathione peroxide, cardiac troponins were analysed in cardiac tissue homogenate using specific ELISA kits. Lipid peroxidation was estimated by determining the concentration of malondialdehyde in the heart tissue homogenate according to the previously described protocol. Myocardial tissue sections were stained with H&E stain and analysed using Leica microsystem. All data were expressed as means ± SEM. Statistical comparisons were performed with Graph Pad instat Software using the Student's two-sided t-test. Pearson correlation coefficient was calculated to assess the association. Value of p < 0.05 was considered statistically significant. RESULTS: The prediabetes group showed a markedly high oxidative stress as indicated by significantly increased NADH oxidase 1 and malondialdehyde while superoxide dismutase and glutathione peroxide were decreased compared to non-prediabetes group. There was no statistical difference between cardiac troponin I and T in the non-prediabetes and prediabetes groups. Cardiac troponins had a weak positive association with glycated haemoglobin. CONCLUSION: The findings of this study demonstrate that prediabetes is associated with myocardial injury through oxidative stress. Future studies are to investigate cardiac contractile function and include more cardiac biomarkers.

Presidential communication approaches and the impact on public health: a comparative analysis of three South African presidents' communication on AIDS and COVID-19.

The HIV response in the African continent over past decades demonstrates the potency that the words and actions of political leaders have in either expediting or impeding the implementation and adoption of preventive measures at the individual and community levels. The article explores the health communication approaches employed by two South African past presidents (Thabo Mbeki and Jacob Zuma) in responding to the HIV epidemic, and contrasts these with the communicative approach of President Cyril Ramaphosa during the COVID-19 pandemic. Approached from this understanding, this article provides a comparative analysis of the communication approaches of these three presidencies across the two pandemics, and considers the variously trusted sources of top-down, government-driven and bottom-up, community-informed approaches to health communication. Critical lessons that emerged in South Africa during the HIV epidemic regarding the need to include communities in communicating about risks and behaviour change have not been adopted into the COVID-19 response. Political leaders are not best placed to communicate about these issues, and, in the context of pandemics, there is a clear need to reconsider top-down communication approaches that are designed without the participation of communities and ignore the interconnected nature of health and other social determinants of health.

MRI characteristics of intracranial masses in the paediatric population of KwaZulu-Natal: A neuroimaging-based study.

BACKGROUND: MRI is the imaging modality of choice for the assessment of intracranial masses in children. Imaging is vital in planning further management. OBJECTIVES: The purpose of this study was to describe the common intracranial masses and their imaging characteristics in the paediatric population referred to Inkosi Albert Luthuli Central Hospital for MRI of the brain. METHOD: We retrospectively reviewed the medical records of paediatric patients (aged from birth to 18 years) who underwent MRI investigations for intracranial masses between January 2010 and December 2016. RESULTS: A total of 931 MRI brain scans were performed. One hundred and seven scans met the inclusion criteria, of which 92 were primary brain tumours and 15 were inflammatory masses. The majority were females (56%). The mean age was 12 ± 4.52 (range of 3-18 years). The most common presenting symptom was seizures (70/107, 65.4%). We categorised the masses according to supra- and infratentorial compartments. The most common site for masses was the supratentorial compartment (n = 56, 52%). The most common masses in the supratentorial compartment were craniopharyngiomas (14/45, 31.1%), whilst in the infratentorial compartment, the most common masses were medulloblastomas (24/47, 51.1%). CONCLUSION: In our series, the supratentorial compartment was the commonest site for intracranial masses. The most common tumour in the infratentorial compartment was medulloblastoma. This information is vital in formulating differential diagnoses of intracranial masses.