Evidence for an Independent and Cumulative Effect of Postprandial Hypertriglyceridemia and Hyperglycemia on Endothelial Dysfunction and Oxidative Stress Generation

Background— Postprandial hypertriglyceridemia and hyperglycemia are considered risk factors for cardiovascular disease. Evidence suggests that postprandial hypertriglyceridemia and hyperglycemia induce endothelial dysfunction through oxidative stress; however, the distinct role of these two factors is a matter of debate. Methods and Results— Thirty type 2 diabetic patients and 20 normal subjects ate 3 different meals: a high-fat meal; 75 g glucose alone; and high-fat meal plus glucose. Glycemia, triglyceridemia, nitrotyrosine, and endothelial function were assayed during the tests. Subsequently, diabetics took 40 mg/d simvastatin or placebo for 12 weeks. The 3 tests were performed again at baseline, between 3 to 6 days after the start, and at the end of each study. High-fat load and glucose alone produced a decrease of endothelial function and an increase of nitrotyrosine in normal and diabetic subjects. These effects were more pronounced when high fat and glucose were combined. Short-term simvastatin treatment had no effect on lipid parameters but reduced the effect on endothelial function and nitrotyrosine observed during each different test. Long-term simvastatin treatment was accompanied by a lower increase in postprandial triglycerides, which was followed by smaller variations of endothelial function and nitrotyrosine during the tests. Conclusions— This study shows an independent and cumulative effect of postprandial hypertriglyceridemia and hyperglycemia on endothelial function, suggesting oxidative stress as common mediator of such effect. Simvastatin shows a beneficial effect on oxidative stress and endothelial dysfunction, which may be ascribed to a direct effect as well as the lipid-lowering action of the drug

Procédé de correction auditive utilisant un modèle paramétrique du signal de parole

Cet article présente un nouveau procédé de correction auditive utilisant un modèle paramétrique du signal de parole. Ce procédé permet, en plus des opérations classiques de compression et d'amplification, d'effectuer des transformations élaborées (modification du rythme temporel, modification de l'enveloppe spectrale, etc.) tout en conservant la structure naturelle du signal de parole. Les premiers résultats d'une série de tests cliniques montrent que ce procédé est bien accueilli par les personnes atteintes de surdités intermédiaires (moyennes ou sévères) et pour lesquelles il n'existe pas véritablement de traitement prothétique adapté

Prunella vulgaris Suppresses HG-Induced Vascular Inflammation via Nrf2/HO-1/eNOS Activation

Vascular inflammation is an important factor which can promote diabetic complications. In this study, the inhibitory effects of aqueous extract from Prunella vulgaris (APV) on high glucose (HG)-induced expression of cell adhesion molecules in human umbilical vein endothelial cells (HUVEC) are reported. APV decreased HG-induced expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. APV also dose-dependently inhibited HG-induced adhesion of HL-60 monocytic cells. APV suppressed p65 NF-κB activation in HG-treated cells. APV significantly inhibited the formation of intracellular reactive oxygen species (ROS). HG-stimulated HUVEC secreted gelatinases, however, APV inhibited it. APV induced Akt phosphorylation as well as activation of heme oxygenase-1 (HO-1), eNOS, and nuclear factor E2-related factor 2 (Nrf2), which may protect vascular inflammation caused by HG. In conclusion, APV exerts anti-inflammatory effect via inhibition of ROS/NF-κB pathway by inducing HO-1 and eNOS expression mediated by Nrf2, thereby suggesting that Prunella vulgaris may be a possible therapeutic approach to the inhibition of diabetic vascular diseases

Increased Glycemic Variability Is Independently Associated With Length of Stay and Mortality in Noncritically Ill Hospitalized Patients

OBJECTIVE To investigate the association between glycemic variability (GV) and both length of stay (LOS) and 90-day mortality in noncritically ill hospitalized patients. RESEARCH DESIGN AND METHODS This study retrospectively analyzed 4,262 admissions to the general medicine or surgery services during a 2 year period. Patients with point-of-care glucose monitoring and a minimum of two glucose values per day on average were selected. GV was assessed by SD and coefficient of variation (CV). Data were analyzed with linear and logistic multivariate regression analysis in separate models for SD and CV. Analysis was performed with generalized estimating equations to adjust for correlation between multiple admissions in some individual cases. RESULTS After exclusions, 935 admissions comprised the sample. Results of adjusted analysis indicate that for every 10 mg/dL increase in SD and 10–percentage point increase in CV, LOS increased by 4.4 and 9.7%, respectively. Relative risk of death in 90 days also increased by 8% for every 10-mg/dL increase in SD. These associations were independent of age, race, service of care (medicine or surgery), previous diagnosis of diabetes, HbA1c, BMI, the use of regular insulin as a sole regimen, mean glucose, and hypoglycemia occurrence during the hospitalization. CONCLUSIONS Our results indicate that increased GV during hospitalization is independently associated with longer LOS and increased mortality in noncritically ill patients. Prospective studies with continuous glucose monitoring are necessary to investigate this association thoroughly and to generate therapeutic strategies targeted at decreasing GV. Inpatient hyperglycemia is common, and it has been associated with increased morbidity and mortality in patients with and without diabetes (1–7). In the intensive care unit (ICU) setting, hypoglycemia has also been independently associated with a significant increase in mortality (8–10). Recently, a third metric of glucose control, known as glycemic variability (GV), has been proposed to be additionally implicated in the disease-associated process of dysglycemia (11). GV refers to fluctuations of blood glucose values around the mean and has been posited as a novel marker for poor glycemic control (12,13). In vitro and human studies suggest that high GV leads to greater oxidative stress than does sustained hyperglycemia (14,15). Studies of ICU patients have consistently demonstrated that increased GV is independently associated with higher mortality (16–19). Notably, results from a large multicenter study concluded that GV was a stronger predictor of ICU mortality than was mean glucose concentrations (20). Although there is no consensus as to the best method to determine GV in hospitalized patients, the use of SD of glucose values has been well validated by previous ICU studies (16,20). Coefficient of variation (CV) has also been suggested as a strong independent index for measuring GV because it corrects for mean glucose levels (21,22). Despite substantial scientific evidence from the ICU, no previous studies have investigated the association between GV and clinical outcomes in patients admitted to the general medical and surgical wards. The purpose of this study was therefore to investigate the association between GV and length of stay (LOS) and 90-day mortality in noncritically ill hospitalized patients. We hypothesize that increased GV in this setting is associated with increased LOS and mortality

Age-related impairment of mesenchymal progenitor cell function

In most mesenchymal tissues a subcompartment of multipotent progenitor cells is responsible for the maintenance and repair of the tissue following trauma. With increasing age, the ability of tissues to repair themselves is diminished, which may be due to reduced functional capacity of the progenitor cells. The purpose of this study was to investigate the effect of aging on rat mesenchymal progenitor cells. Mesenchymal progenitor cells were isolated from Wistar rats aged 3, 7, 12 and 56 weeks. Viability, capacity for differentiation and cellular aging were examined. Cells from the oldest group accumulated raised levels of oxidized proteins and lipids and showed decreased levels of antioxidative enzyme activity. This was reflected in decreased fibroblast colony-forming unit (CFU-f) numbers, increased levels of apoptosis and reduced proliferation and potential for differentiation. These data suggest that the reduced ability to maintain mesenchymal tissue homeostasis in aged mammals is not purely due to a decline in progenitor cells numbers but also to a loss of progenitor functionality due to the accumulation of oxidative damage, which may in turn be a causative factor in a number of age-related pathologies such as arthritis, tendinosis and osteoporosis. © 2006 The Authors Journal compilation © Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland 2006

A1C Variability and the Risk of Microvascular Complications in Type 1 Diabetes: Data from the Diabetes Control and Complications Trial

OBJECTIVE—Debate remains as to whether short- or long-term glycemic instability confers a risk of microvascular complications in addition to that predicted by mean glycemia alone. In this study, we analyzed data from the Diabetes Control and Complications Trial (DCCT) to assess the effect of A1C variability on the risk of retinopathy and nephropathy in patients with type 1 diabetes

Piper sarmentosum inhibits ICAM-1 and Nox4 gene expression in oxidative stress-induced human umbilical vein endothelial cells

<p>Abstract</p> <p>Background</p> <p>Aqueous extract of <it>Piper sarmentosum </it>(AEPS) is known to possess antioxidant and anti-atherosclerotic activities but the mechanism responsible for it remains unclear. In early part of atherosclerosis, nuclear factor-kappa B (NF-κB) induces the expression of cellular adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1) and E-selectin. NADPH oxidase 4 (Nox4) is the predominant source of superoxide in the endothelial cells whereas superoxide dismutase 1 (SOD1), catalase (CAT) and glutathione peroxidase (GPx) are the antioxidant enzymes responsible for inactivating reactive oxygen species. The present study aimed to investigate the effects of AEPS on the gene expression of NF-κB, VCAM-1, ICAM-1, E-selectin, Nox4, SOD1, CAT and GPx in cultured human umbilical vein endothelial cells (HUVECs).</p> <p>Methods</p> <p>HUVECs were divided into four groups:- control; treatment with 180 μM hydrogen peroxide (H₂O₂); treatment with 150 μg/mL AEPS and concomitant treatment with AEPS and H₂O₂for 24 hours. Total RNA was extracted from all the groups of HUVEC using TRI reagent. Subsequently, qPCR was carried out to determine the mRNA expression of NF-κB, VCAM-1, ICAM-1, E-selectin, Nox4, SOD1, CAT and GPx. The specificity of the reactions was verified using melting curve analysis and agarose gel electrophoresis.</p> <p>Results</p> <p>When stimulated with H₂O₂, HUVECs expressed higher level of ICAM-1 (1.3-fold) and Nox4 (1.2-fold) mRNA expression. However, AEPS treatment led to a reduction in the mRNA expression of ICAM-1 (p < 0.01) and Nox4 (p < 0.05) in the H₂O₂-induced HUVECs. AEPS also upregulated the mRNA expression of SOD1 (p < 0.05), CAT (p < 0.01) and GPx (p < 0.05) in oxidative stress-induced HUVECs. There was no significant change in the mRNA expression of VCAM-1 and E-selectin.</p> <p>Conclusion</p> <p>The expressional suppression of ICAM-1 and Nox4 and induction of antioxidant enzymes might be an important component of the vascular protective effect of AEPS.</p

Oxidative stress in type 2 diabetes: the role of fasting and postprandial glycaemia

Oxidative stress, through the production of reactive oxygen species (ROS), has been proposed as the root cause underlying the development of insulin resistance, β-cell dysfunction, impaired glucose tolerance and type 2 diabetes mellitus (T2DM). It has also been implicated in the progression of long-term diabetes complications, including microvascular and macrovascular dysfunction. Excess nourishment and a sedentary lifestyle leads to glucose and fatty acid overload, resulting in production of ROS. Additionally, reaction of glucose with plasma proteins forms advanced glycation end products, triggering production of ROS. These ROS initiate a chain reaction leading to reduced nitric oxide availability, increased markers of inflammation and chemical modification of lipoproteins, all of which may increase the risk of atherogenesis. With the postulation that hyperglycaemia and fluctuations in blood glucose lead to generation of ROS, it follows that aggressive treatment of fasting and postprandial hyperglycaemia is important for prevention of micro and macrovascular complications in T2DM