Metabolic syndrome, dysglycaemia and vascular disease: making sense of the evidence

" 'Diagnosis' of metabolic syndrome by any current criteria is not needed and adds little to clinical practice. Attention and resources should be focused on the major modifiable risk factors and more should be done to engender sustainable lifestyle changes in all with vascular disease."     

Cardiac Manifestations of Exhaustive Exercise in Nonathletic Adults: Does Cardiac Fatigue Occur?

The aim of the study was to examine the impact of prolonged exercise leading to physical exhaustion on left ventricular (LV) systolic and diastolic function in untrained healthy subjects, and to examine cardiovascular determinants of exercise performance. Twenty-four nonathletic healthy adults (14 males, 10 females; mean age 42 +/- 11 years) were exercised on a treadmill at 70% of maximal oxygen consumption until physical exhaustion occurred after an average of 84 +/- 39 minutes. Two-dimensional and Doppler echocardiography was performed before and 15 minutes after exercise to assess LV function and geometry, and right ventricular (RV) systolic function. After prolonged exercise, LV ejection fraction and geometry were unchanged, but LV end-diastolic volume, end-systolic volume, and stroke volume decreased. However, due to a higher heart rate (HR), cardiac output increased at 15 minutes post exercise. RV fractional shortening was unchanged. LV peak early to atrial filling velocity ratio decreased post exercise, with an increase in percent atrial contribution. However, less preload-dependent variables of LV diastolic function such as deceleration time, LV inflow propagation rate, mitral annular tissue Doppler and myocardial performance index were unchanged. Preexercise stroke volume and HR were the only predictors (r = 0.86, P < 0.01) of exercise duration. However, age, resting blood pressure, indices of systolic and diastolic function, and LV geometry were not predictors. Prolonged exercise leading to physical exhaustion is not associated with systolic or diastolic dysfunction. Reduced early LV diastolic filling and the relative increase in left atrial contribution seen with prolonged exercise are likely due to preload reduction rather than true diastolic dysfunction.     

Impaired angiotensin II AT(1) receptor function and enhanced Na, K-ATPase affinity for sodium in proximal tubule of streptozotocin-treated diabetic rats

We determined angiotensin II (Ang II) AT(1) receptor function in terms of Na-K-ATPAse (NKA) stimulation in the proximal tubule (PTs) of streptozotocin-induced diabetic rats. Ang II (10 pM) stimulated NKA activity in PTs of control rats but not diabetic rats. The AT(1) receptor expression was similar, but the expression of G-proteins (G(i)alpha2 and G(i)alpha3) in the PTs was decreased in diabetic compared with control rats. Kinetic studies revealed an increase in NKA affinity, low K(0.5,) for Na, with no changes in V(max) of the enzyme in diabetic compared with control rats. Basal Ser-phosphorylation of NKA alpha1-subunit was lower in diabetic compared with control rats. This data suggest that the higher basal NKA affinity for Na, possibly due to lower Ser-phosphorylaion of alpha1-subunit and not the AT(1) receptor function, in the PTs may be responsible for increased renal Na reabsorption associated with early stage of streptozotocin-induced diabetes.     

Craniocerebral aspergillosis in immunocompetent hosts: surgical perspective

Craniocerebral aspergillosis is a rare but dangerous variety of central nervous system infections. Surgery is being widely recognized as the cornerstone of management. Due to the rarity of the disease, difficulty and delay in diagnosis and poor outcome, there is very little in the literature regarding the various surgical strategies that may be adopted in these patients. Early aggressive surgery followed by chemotherapy offers the best chances. Surgical planning would depend upon the type and location of the disease process as well as the condition of the patient. Perioperative care holds immense importance and knowledge of possible complications is essential. Aspergillosis of the central nervous system is difficult to diagnose and equally difficult to treat. Surgery remains the cornerstone of management followed by systemic antifungal medications. Results are better in immunocompetent patients as compared to those who are immunocompromised.     

Development and characteristics of a human cell assay for screening agents for melanoma prevention

This paper describes the development and initial evaluation of a human cell assay to identify potentially efficacious agents for preventing melanoma. Four human cell lines were used: normal melanocytes, a radial growth-phase-like melanoma cell line (WM3211), a vertical growth-phase-like melanoma cell line (Lu1205), and 83-2c, a cell strain cloned from metastatic melanoma. Four endpoints were evaluated in ultraviolet B-treated cells: annexin V, human leukocyte antigen-DR; E-cadherin, and N-cadherin. Annexin V was induced by nimesulide, 4-hydroxyphenylretinamide, and difluoromethylornithine in ultraviolet-B-treated radial growth-phase-like melanoma cells. None of the agents inhibited human leukocyte antigen-DR expression in ultraviolet-B-treated radial growth-phase-like melanoma cells, the only cells that strongly expressed human leukocyte antigen-DR. E-cadherin was overexpressed only in radial growth-phase-like melanoma cells relative to melanocytes, and ultraviolet B exposure dramatically reduced this expression. E-cadherin was only induced by difluoromethylornithine in ultraviolet-B-treated radial growth-phase-like melanoma cells. N-cadherin was over- expressed in all melanoma cell lines relative to melanocytes. In this study, all candidate preventive agents inhibited N-cadherin in ultraviolet B-treated radial growth-phase-like melanoma cells. Four agents inhibited N-cadherin in ultraviolet B-treated vertical growth-phase-like melanoma cells. The mean ratios of N-cadherin to E-cadherin levels and specific endpoint responses for both the radial growth-phase-like melanoma and vertical growth-phase-like melanoma cells were used to rank the agents. Agents were evaluated at clinically relevant concentrations. The rankings were difluoromethylornithine>4-hydroxyphenylretinamide>nimesulide>9-cis-retinoic acid>polyphenon E. Diphenylhydramine, D-mannitol, and nordihydroguaiaretic acid were inactive. The results of these initial studies suggest that ultraviolet-B-treated radial growth-phase-like melanoma cells are the most responsive to chemopreventive agents, and may be the cell line of choice for screening melanoma prevention agents.     

Cytoprotective effect of Podophyllum hexandrum against gamma radiation is mediated via hemopoietic system stimulation and up-regulation of heme-oxygenase-1 and the prosurvival multidomain protein Bcl-2

The radioprotective effect of a hydroalcoholic extracted material (REC-2000) from the rhizome of Podophyllum hexandrum was studied in mice exposed to lethal gamma radiation (10 Gy). The extract (REC-2000) was found to restore the hemoglobin content (14.73 +/- 0.33) and total leukocyte count (TLC) (4166.66 +/- 0.02) in lethally (10 Gy) gamma-irradiated mice on the 15th day in comparison to the radiation control mice. The hemoglobin content of the drug + radiation group was observed to be significantly (21.25%) higher than the radiation control group on the 10th day. Similarly, the TLC was significantly increased (83.33 times) in the drug + radiation group as compared to a radiation (10 Gy) only group on the 10th day. Enhanced expression of heme-oxygenase-1 and Bcl-2 protein observed by Western blotting further supports the observation of hemopoietic recovery in irradiated mice. These findings indicate that the bioactive constituents present in REC-2000 exert the radioprotective effect by modulating the hemopoietic system.     

CVD risk factors and ethnicity--a homogeneous relationship?

Current understanding of cardiovascular disease risk (CVD) is derived largely from studies of Caucasians of European origin. However, people of certain ethnic groups experience a disproportionately greater burden of CVD including coronary heart disease (CHD) and stroke. Adoption of a Westernised lifestyle has different effects on metabolic and vascular dysfunction across populations, e.g. South Asians have a higher prevalence of coronary heart disease (CHD) and cardiovascular mortality compared with Europeans. African-Americans demonstrate higher rates of CHD and stroke while African/Caribbeans in the UK have lower CHD rates and higher stroke rates than British Europeans. Other non-European groups such as the Chinese and Japanese exhibit consistently high rates of stroke but not CHD, while Mexican Americans have a higher prevalence of both stroke and CHD, and North American native Indians also have high rates of CHD. While conventional cardiovascular risk factors such as smoking, blood pressure and total cholesterol predict risk within these ethnic groups, they do not fully account for the differences in risk between ethnic groups, suggesting that alternative explanations might exist. Ethnic groups show differences in levels of visceral adiposity, insulin resistance, and novel risk markers such as C-reactive protein (CRP), adiponectin and plasma homocysteine. The marked differences across racial and ethnic groups in disease risk are likely due in part to each of genetic, host susceptibility and environmental factors, and can provide valuable aetiological clues to differences in patterns of disease presentation, therapeutic needs and response to treatment. Ongoing studies should increase understanding of ethnicity as a potential independent risk factor, thus enabling better identification of treatment targets and selection of therapy in specific populations.     

Flexible sigmoidoscopy and colonoscopy during pregnancy

More than 6000 pregnant women each year have an indication that warrants a flexible sigmoidoscopy or colonoscopy. In addition to the potential complications inherent in the risk of sedation and the procedures themselves, the endoscopist who performs these procedures in pregnant women must be aware of the potential to do harm to the fetus. This article reviews the existing literature as it pertains to flexible sigmoidoscopies and colonoscopies performed during pregnancy, including indications and diagnostic usefulness, safety, use of medications, and therapeutic interventions.