dinoprost and Diabetes-Mellitus

Topics: Biomarkers; Diabetes Mellitus; Diabetic Angiopathies; Diabetic Neuropathies; Dinoprost; Electron Transport; Endothelial Cells; Glycation End Products, Advanced; Humans; Hyperglycemia; Mitochondria; NADPH Oxidases; Oxidative Stress; Polymers; Receptor for Advanced Glycation End Products; Receptors, Immunologic; Superoxides

Most of the traditional methods used to assess oxidative stress in clinical setting are non specific, unreliable or inaccurate. Recently, a novel family of prostaglandin F2 isomers, called F2-isoprostanes, produced in vivo by a free radical peroxidation of arachidonic acid, has been described. These compounds may produce physiological or pathological effects due to their ability to alter smooth muscle and platelet functions. The quantification of the two major isoforms (isoprostaglandin F2 alpha type-III and VI) in biological fluids and tissues as markers of lipid peroxidation appears to be an important advance in our ability to explore the role of free radicals in the pathogenesis of human disease.. Urinary excretion of F2-isoprostanes is correlated with age, indicating increased oxidative stress during the normal aging process. High F2-isoprostanes concentration has been described in diseases such as ischemic heart disease, diabetes, Alzheimer's disease and hepatic cirrhosis. The correlation of F2-isoprostane concentrations and human diseases severity in hepatic cirrhosis, cardiac failure and diabetes suggest that these compounds may be of interest as predictive markers.. Preliminary studies suggest the use of F2-isoprostanes as prognosis markers. In addition, F2-isoprostanes quantification offers promising potential as intermediate endpoints for clinical studies of antioxidant therapies.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antioxidants; Biomarkers; Cardiovascular Diseases; Child; Diabetes Mellitus; Dinoprost; Female; Free Radicals; Humans; Hypercholesterolemia; Infant, Newborn; Kidney Transplantation; Lipid Peroxidation; Liver Diseases; Lung Diseases; Male; Middle Aged; Nervous System Diseases; Oxidative Stress; Prognosis; Risk Factors; Smoking

Long-term vascular complications still represent the main cause of morbidity and mortality in diabetic patients. Although randomized long-term clinical studies comparing the effects of conventional and intensive therapy have demonstrated a clear link between hyperglycemia and the development of complications of diabetes, they have not defined the mechanism through which excess glucose results in tissue damage. Evidence has accumulated indicating that oxidative stress may play a key role in the etiology of diabetic complications. Isoprostanes are emerging as a new class of biologically active products of arachidonic acid metabolism of potential relevance to human vascular disease. Their formation in vivo seems to reflect primarily, if not exclusively, a nonenzymatic process of lipid peroxidation. Enhanced urinary excretion of 8-iso-PGF(2alpha) has been described in association with both type 1 and type 2 diabetes mellitus, and correlates with impaired glycemic control. Besides providing a likely noninvasive index of lipid peroxidation in this setting, measurements of specific F(2) isoprostanes in urine may provide a sensitive biochemical end point for dose-finding studies of natural and synthetic inhibitors of lipid peroxidation. Although the biological effects of 8-iso-PGF(2alpha) in vitro suggest that it and other isoeicosanoids may modulate the functional consequences of lipid peroxidation in diabetes, evidence that this is likely in vivo remains inadequate at this time.

Topics: Animals; Antioxidants; Arachidonic Acids; Arteriosclerosis; Biomarkers; Coronary Disease; Diabetes Complications; Diabetes Mellitus; Dietary Supplements; Dinoprost; F2-Isoprostanes; Humans; Hyperglycemia; Lipid Peroxidation; Oxidative Stress; Protein Isoforms; Vitamin E

Isoprostanes are emerging as a new class of biologically active products of arachidonic acid metabolism of potential relevance to human vascular disease. Their formation in vivo seems to reflect primarily, if not exclusively, a nonenzymatic process of lipid peroxidation. Enhanced urinary excretion of 8-iso-PGF2 alpha has been described in association with cardiac reperfusion injury and with cardiovascular risk factors, including cigarette smoking, diabetes mellitus, and hypercholesterolemia. Besides providing a likely noninvasive index of lipid peroxidation in these settings, measurements of specific F2 isoprostanes in urine may provide a sensitive biochemical end point for dose-finding studies of natural and synthetic inhibitors of lipid peroxidation. Although the biological effects of 8-iso-PGF2 alpha in vitro suggest that it and other isoeicosanoids may modulate the functional consequences of lipid peroxidation, evidence that this is likely in vivo remains inadequate at this time.

Topics: Antioxidants; Arteriosclerosis; Biomarkers; Cardiovascular Diseases; Diabetes Mellitus; Dinoprost; F2-Isoprostanes; Free Radicals; Gas Chromatography-Mass Spectrometry; Humans; Hyperlipidemias; Immunoassay; Indicator Dilution Techniques; Lipid Peroxidation; Oxidative Stress; Platelet Aggregation; Prostaglandins F; Risk Factors; Thrombosis; Vasoconstrictor Agents

Topics: Animals; Diabetes Mellitus; Dinoprost; F2-Isoprostanes; Hepatorenal Syndrome; Humans; Vasoconstrictor Agents

Oxidative stress is a key driver of vascular dysfunction in diabetes mellitus. Ebselen is a glutathione peroxidase mimetic. A single-site, randomized, double-masked, placebo-controlled, crossover trial was carried out in 26 patients with type 1 or type 2 diabetes to evaluate effects of high-dose ebselen (150 mg po twice daily) administration on oxidative stress and endothelium-dependent vasodilation. Treatment periods were in random order of 4 wk duration, with a 4-wk washout between treatments. Measures of oxidative stress included nitrotyrosine, plasma 8-isoprostanes, and the ratio of reduced to oxidized glutathione. Vascular ultrasound of the brachial artery and plethysmographic measurement of blood flow were used to assess flow-mediated and methacholine-induced endothelium-dependent vasodilation of conduit and resistance vessels, respectively. Ebselen administration did not affect parameters of oxidative stress or conduit artery or forearm arteriolar vascular function compared with placebo treatment. There was no difference in outcome by diabetes type. Ebselen, at the dose and duration evaluated, does not improve the oxidative stress profile, nor does it affect endothelium-dependent vasodilation in patients with diabetes mellitus.

Topics: Adult; Antioxidants; Azoles; Brachial Artery; Case-Control Studies; Cross-Over Studies; Diabetes Mellitus; Dinoprost; Double-Blind Method; Endothelium, Vascular; Female; Forearm; Glutathione; Humans; Isoindoles; Male; Methacholine Chloride; Middle Aged; Organoselenium Compounds; Oxidative Stress; Parasympathomimetics; Plethysmography; Tyrosine; Ultrasonography; Vasodilation

We have reported that repeated sauna therapy improves impaired vascular endothelial function in a patient with coronary risk factors. We hypothesized that sauna therapy decreases urinary 8-epi-prostaglandin F(2alpha) (PGF(2alpha)) levels as a marker of oxidative stress and conducted a randomized, controlled study. Twenty-eight patients with at least one coronary risk factor were divided into a sauna group (n = 14) and non-sauna group (n = 14). Sauna therapy was performed with a 60 degrees C far infrared-ray dry sauna for 15 minutes and then bed rest with a blanket for 30 minutes once a day for two weeks. Systolic blood pressure and increased urinary 8-epi-PGF(2alpha) levels in the sauna group were significantly lower than those in the non-sauna group at two weeks after admission (110 +/- 15 mmHg vs 122 +/- 13 mmHg, P < 0.05, 230 +/- 67 pg/mg x creatinine vs 380 +/- 101 pg/mg x creatinine, P < 0.0001, respectively). These results suggest that repeated sauna therapy may protect against oxidative stress, which leads to the prevention of atherosclerosis.

Topics: Adult; Body Mass Index; Coronary Disease; Diabetes Mellitus; Dinoprost; Endothelium, Vascular; Female; Heart Rate; Hematocrit; Humans; Hypercholesterolemia; Hypertension; Male; Middle Aged; Nitric Oxide Synthase; Oxidative Stress; Risk Factors; Steam Bath

Cigarette smoking, a key risk factor for the development of vascular disease, is associated with an increased 8-epi-prostaglandin (PG) F(2alpha). Elevated 8-epi-PGF(2alpha) has been found in vascular tissue, blood and urine as well. We examined the influence of quitting cigarette smoking in 71 patients (38 males, 33 females; aged 32-67 a) with clinically manifested atherosclerosis and various risk factors. In addition, in eight patients with hypercholesterolemia without clinical manifestation of atherosclerosis quitting smoking was monitored as well. Twenty-six of the patients with manifested atherosclerosis and five with hypercholesterolemia restarted and the isoprostanes in plasma, serum and urine were monitored in these patients as well. Quitting cigarette smoking induces an immediate decline becoming significant after 1 or 2 weeks. Restarting smoking results in an increase in 8-epi-PGF(2alpha) reaching prevalues within almost 1 week. These findings indicate that the in vivo oxidation injury associated with cigarette smoking quickly decreases after quitting but increases soon after restarting immediately.

Topics: Adult; Aged; Arteriosclerosis; Biomarkers; Diabetes Complications; Diabetes Mellitus; Dinoprost; F2-Isoprostanes; Female; Humans; Hypercholesterolemia; Hypertension; Male; Middle Aged; Risk Factors; Smoking; Smoking Cessation; Time Factors

Our objective was to evaluate whether isocaloric replacement of refined rice with whole grains and other plant products as a form of powder reduces coronary artery disease (CAD) risk factors, such as insulin demand and lipid peroxidation in CAD patients. Seventy-six male patients with CAD were randomly assigned to either a group ingesting a whole-grain meal daily or a control group for 16 weeks. In the whole-grain group, serum concentrations of glucose and insulin decreased by 24% and 14%, respectively, without altering body weight and energy intake, whereas daily intakes of fiber and vitamin E increased by 25% and 41%, respectively. Consumption of whole grains and legume powder in CAD patients without diabetes decreased fasting levels of glucose and insulin. The areas under the curve for insulin and glucose during the oral glucose tolerance test were also decreased. CAD patients with diabetes in the whole-grain group also showed reductions in fasting glucose and in the area under the curve for glucose. In the whole-grain group, plasma malondialdehyde and homocysteine and urinary 8-epi-prostaglandin F(2alpha) concentrations decreased by approximately 28%. Also, lipid-corrected concentrations of alpha-carotene, retinol, tocopherols, and lycopene increased by 11% to 40%, and the percentage composition of n-6 fatty acids of serum phospholipid increased by 14% in the whole-grain group. The replacement of refined rice with whole grain and legume powder as a source of carbohydrate in a meal showed significant beneficial effects on glucose, insulin, and homocysteine concentrations and lipid peroxidation in CAD patients. These effects are likely to substantially reduce the risk factors for CAD and diabetes.

Topics: Area Under Curve; Blood Glucose; Carotenoids; Cholesterol, HDL; Coronary Disease; Diabetes Complications; Diabetes Mellitus; Dinoprost; Edible Grain; F2-Isoprostanes; Fabaceae; Glucose Tolerance Test; Homocysteine; Humans; Insulin; Lipid Peroxidation; Male; Malondialdehyde; Middle Aged; Powders; Risk Factors

Urinary 8-isoprostane provides a significantly heritable measure of oxidative stress. Prior reports suggest that genetic variants may modulate oxidative stress due to smoking, other environmental factors, and disease. Alternatively, these apparent modulations may reflect a dependence of genetic effects on 8-isoprostane concentrations.. Spouse 8-isoprostane concentrations were weakly concordant (r. Heritability of oxidative stress as measured by 8-isoprostane is quantile-dependent, which may contribute to the larger reported effects on oxidative stress by UCP2 -866G > A, IL6 -572C > G and LTA 252A > G polymorphisms in smokers than nonsmokers, by the UCP2 -866G > A polymorphism in coronary heart disease patients, by the ESRRG rs1890552 A > G polymorphism in type 2 diabetics, by the CYBA 242C > T polymorphism after exercise training, by the PLIN 11482G > A/14995A > T haplotype before weight loss, and by the CYBA -930A > G and GSTP1 I105V haplotypes in patients with pulmonary edema.

Topics: Cardiovascular Diseases; Diabetes Mellitus; Dinoprost; Humans; Oxidative Stress; Smoking

Urinary excretion of 8-iso-prostaglandin F

Topics: Acute Coronary Syndrome; Aged; China; Coronary Vessels; Diabetes Mellitus; Dinoprost; Female; Humans; Male; Middle Aged; Necrosis; Oxidative Stress; Plaque, Atherosclerotic; Predictive Value of Tests; Prognosis; Risk Assessment; ROC Curve; Ultrasonography, Interventional

Chronic oxidative stress is one of the key mechanisms responsible for disease progression in non-alcoholic fatty liver disease. However, so far, few studies reported increased circulating levels of oxidative stress markers in patients with non-alcoholic fatty liver and no study has been performed with newer markers of systemic oxidative stress. The aim was to assess the relationship between urinary 8-iso-prostaglandin F2α and serum soluble NOX2-derived peptide and the severity of liver steatosis in subjects with non-alcoholic fatty liver.. The study was performed in 264 consecutive patients referred for suspected metabolic disease. Steatosis was defined according to Hamaguchi ultrasonographic criteria. Oxidative stress was assessed by urinary 8-iso- prostaglandin F2α and serum soluble NOX2-derived peptide levels.. Patients with non-alcoholic fatty liver had higher (p < 0.001) mean values of urinary 8-iso-PGF2α and of serum soluble NOX2-derived peptide, alanine aminotransferase, Cytokeratin-18 and homeostasis model of insulin resistance and lower values of serum adiponectin as compared to those without. Prevalence of metabolic syndrome and of its clinical features was significantly higher in patients with non-alcoholic fatty liver. Same findings were also observed after the exclusion of obese subjects, or subjects with diabetes or with metabolic syndrome and in those not taking statin medication. In addition, the levels of urinary 8-iso-PGF2α were independent predictors of non-alcoholic fatty liver and a strong association of urinary 8-iso-PGF2α and of serum soluble NOX2-derived peptide with the severity of steatosis at ultrasound was also observed.. We demonstrated increased markers of oxidative stress in subjects with non-alcoholic fatty liver. Urinary 8-iso-PGF2α and serum soluble NOX2-derived peptide levels were independent from obesity, diabetes and metabolic syndrome and increased with the severity of liver steatosis at ultrasound.

Topics: Adult; Aged; Biomarkers; Case-Control Studies; Cohort Studies; Diabetes Mellitus; Dinoprost; Female; Humans; Linear Models; Male; Membrane Glycoproteins; Metabolic Syndrome; Middle Aged; NADPH Oxidase 2; NADPH Oxidases; Non-alcoholic Fatty Liver Disease; Obesity; Oxidative Stress; Severity of Illness Index; Ultrasonography

The methylenetetrahydrofolate reductase (MTHFR) 677 C→T polymorphism may be associated with elevated total homocysteine (tHcy) levels, an independent risk factor for cardiovascular disease. It was the study objective to evaluate in vivo lipid peroxidation and platelet activation in carriers of the MTHFR 677 C→T polymorphism and in non-carriers, in relation to tHcy and folate levels. A cross-sectional comparison of urinary 8-iso-prostaglandin (PG)F(2α) and 11-dehydro-thromboxane (TX)B(2) (markers of in vivo lipid peroxidation and platelet activation, respectively) was performed in 100 carriers and 100 non-carriers of the polymorphism. A methionine-loading test and folic acid supplementation were performed to investigate the causal relationship of the observed associations. Urinary 8-iso-PGF(2α) and 11-dehydro-TXB(2) were higher in carriers with hyperhomocysteinaemia than in those without hyperhomocysteinaemia (p<0.0001). Hyperhomocysteinaemic carriers had lower folate levels (p=0.0006), higher urinary 8-iso-PGF(2α) (p<0.0001) and 11-dehydro-TXB(2) (p<0.0001) than hyperhomocysteinaemic non-carriers. On multiple regression analysis, high tHcy (p<0.0001), low folate (p<0.04) and MTHFR 677 C→T polymorphism (p<0.001) independently predicted high rates of 8-iso-PGF(2α) excretion. Methionine loading increased plasma tHcy (p=0.002), and both urinary prostanoid metabolites (p=0.002). Folic acid supplementation was associated with decreased urinary 8-iso-PGF(2α) and 11-dehydro-TXB2 excretion (p<0.0003) in the hyperhomocysteinaemic group, but not in the control group, with substantial inter-individual variability related to baseline tHcy level and the extent of its reduction. In conclusion, hyperhomocysteinaemia due to the MTHFR 677 C→T polymorphism is associated with enhanced in vivo lipid peroxidation and platelet activation that are reversible, at least in part, following folic acid supplementation. An integrated biomarker approach may help identifying appropriate candidates for effective folate supplementation.

Topics: Biomarkers; Cardiovascular Diseases; Comorbidity; Cross-Sectional Studies; Diabetes Mellitus; Dinoprost; Dyslipidemias; Folic Acid; Homocystinuria; Humans; Hyperhomocysteinemia; Lipid Peroxidation; Methionine; Methylenetetrahydrofolate Reductase (NADPH2); Muscle Spasticity; Oxidative Stress; Platelet Activation; Polymorphism, Single Nucleotide; Psychotic Disorders; Smoking; Thromboxane B2

The purpose of this study was to determine the effects of diabetic complications on oxidation of proteins, lipids, and DNA and to investigate the relationship between oxidative damage markers and clinical parameters.. The study group consisted of 69 type 2 diabetic patients (20 patients without complication, 49 patients with complication) who attended internal medicine outpatient clinics of Istanbul Education and Research Hospital and 19 healthy control subjects. In serum samples of both diabetic patients and healthy subjects, 8-hydroxy-2'deoxyguanosine (8-OHdG), as a marker of oxidative DNA damage, N(ε)-(hexanoyl)lysine (HEL) and 15-F2t-iso-prostaglandin (15-F2t-IsoP). as products of lipooxidative damage, advanced oxidation protein products (AOPP), as markers of protein damage, and paraoxonase1 (PON1) as antioxidant were studied.. 15-F2t-IsoP (p < 0.005) and AOPP (p < 0.001) levels were significantly higher in diabetic group than control group while there were no significant differences in levels of 8-OHdG and HEL between the two groups. AOPP (p < 0.001) and 8-OHdG (p < 0.001) were significantly higher in diabetic group with complications compared to diabetic group without complications.. Increased formation of free radicals and oxidative stress, under conditions of hyperglycaemia, is one of the probable causes for evolution of complications in diabetes mellitus. Our study supports the hypothesis that oxidant/antioxidant balance is disturbed in diabetic patients.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aryldialkylphosphatase; Deoxyguanosine; Diabetes Mellitus; Dinoprost; DNA Damage; Enzyme-Linked Immunosorbent Assay; Female; Humans; Isoprostanes; Male; Middle Aged; Oxidative Stress; Proteins

Topics: Cross-Sectional Studies; Diabetes Mellitus; Dinoprost; Glucose; Humans; Hypoglycemia; Hypoglycemic Agents; Inflammation; Insulin; Models, Biological; Oxidative Stress; Research Design

It has been reported that urinary oxidative stress markers are higher in diabetic patients with proteinuria. We performed the present study to elucidate the relationship between urinary excretion of oxidative stress markers, albumin excretion, and histological changes, and to confirm the potential utility of oxidative stress markers for clinical treatment.. Diabetic db/db mice or nondiabetic db/m mice were administered candesartan (10 mg/kg/day) or hydralazine (50 mg/kg/day) for 18 weeks.. Thirty-week-old male db/db mice treated with control vehicle revealed elevated urinary excretion and immunohistological levels of 8-hydroxydeoxyguanosine in glomeruli when compared to db/m mice. Treatment with candesartan, but not hydralazine, reduced these values to levels in db/m mice. Increased mesangial expansion, urinary excretion of albumin and 8-isoprostane, and glomerular immunohistological levels of nitrotyrosine in db/db mice were also decreased markedly by candesartan but not hydralazine. Interestingly, correlations between levels of albumin and oxidative stress markers in urine were very high, even when groups undergoing long-term (44 weeks) treatment were included (correlation coefficient 0.767 with respect to 8-hydroxydeoxyguanosine, 0.888 with respect to 8-isoprostane).. It is anticipated that urinary concentrations of oxidative stress markers will be direct barometers of glomerulus-derived oxidative stress and glomerular injury in diabetic nephropathy.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Albuminuria; Angiotensin II Type 1 Receptor Blockers; Animals; Antihypertensive Agents; Benzimidazoles; Biomarkers; Biphenyl Compounds; Deoxyguanosine; Diabetes Mellitus; Diabetic Nephropathies; Dinoprost; Disease Models, Animal; Hydralazine; Kidney Glomerulus; Male; Mice; Mice, Inbred C57BL; Oxidative Stress; Tetrazoles; Treatment Outcome; Tyrosine

Systemic oxidative stress causes insulin resistance in rodents. We tested the hypothesis that oxidative stress and insulin resistance are associated in humans.. We used cross-sectional data from 2,002 nondiabetic subjects of the community-based Framingham Offspring Study. We measured insulin resistance with the homeostasis model and defined categorical insulin resistance as homeostasis model assessment of insulin resistance (HOMA-IR) > 75th percentile. We measured oxidative stress using the ratio of urine 8-epi-prostaglandin F2alpha (8-epi-PGF2alpha) to creatinine and used age- and sex-adjusted regression models to test the association of oxidative stress with insulin resistance in individuals without diabetes and among subgroups at elevated risk of diabetes.. Across 8-epi-PGF2alpha/creatinine tertiles, the prevalence of insulin resistance increased (18.0, 27.5, and 29.4% for the first, second, and third tertiles, respectively; P < 0.0001), as did mean levels of HOMA-IR (3.28, 3.83, and 4.06 units; P < 0.0001). The insulin resistance-oxidative stress association was attenuated by additional adjustment for BMI (P = 0.06 across tertiles for insulin resistance prevalence; P = 0.004 for mean HOMA-IR). Twenty-six percent of participants were obese (BMI > or = 30 kg/m2), 39% had metabolic syndrome (according to the Adult Treatment Panel III definition), and 37% had impaired fasting glucose (IFG) (fasting glucose 5.6-6.9 mmol/l). Among 528 obese participants, respectively, insulin resistance prevalence was 41.3, 60.6, and 54.2% across 8-epi-PGF2alpha/creatinine tertiles (P = 0.005); among 781 subjects with metabolic syndrome, insulin resistance prevalence was 41.3, 56.7, and 51.7% (P = 0.0025); and among 749 subjects with IFG, insulin resistance prevalence was 39.6, 47.2, and 51.6% (P = 0.04).. Systemic oxidative stress is associated with insulin resistance in individuals at average or elevated risk of diabetes even after accounting for BMI.

Topics: Aged; Biomarkers; Body Mass Index; Body Size; Cardiovascular Diseases; Creatinine; Diabetes Mellitus; Dinoprost; Female; Health Surveys; Humans; Insulin Resistance; Male; Massachusetts; Middle Aged; Nuclear Family; Oxidative Stress; Phenotype; Prediabetic State; Prevalence

Pressure-induced vasodilation (PIV) allows skin blood flow to increase in response to locally applied pressure and may be protective against pressure ulcers. We previously showed that PIV was absent in 1-week diabetic mice exhibiting no neuropathy. Our aim was to determine whether the diabetes-induced PIV alteration could be prevented.. Diabetic mice received no treatment or a daily treatment with either sorbinil, alagebrium or alpha-lipoic acid (LPA) for 1 week. Laser Doppler flowmetry was used to evaluate PIV as well as endothelium-dependent vasodilation following iontophoretic delivery of acetylcholine (ACh). The effect of each treatment on oxidative stress was examined by plasma 8-isoprostane assay. LPA was the sole treatment to prevent both PIV and ACh vasodilation alterations, with a significant reduction of oxidative stress in diabetic mice. Both PIV and ACh-vasodilation were abolished in LPA-treated diabetic mice following injection of Nomega-nitro-L-arginine (p<0.05). In contrast, alagebrium and sorbinil prevented neither diabetes-induced PIV abolition nor endothelial alteration.. LPA treatment significantly reduced the oxidative stress and was able to preserve endothelial nitric oxide availability in the cutaneous microcirculation and then to preserve the PIV response in diabetic mice. LPA treatment could play a key role in limiting the risk of pressure-induced cutaneous ulcer during diabetes.

Topics: Acetylcholine; Aldehyde Reductase; Animals; Antioxidants; Biomarkers; Diabetes Mellitus; Dinoprost; Imidazolidines; Laser-Doppler Flowmetry; Male; Mice; Microcirculation; Nitric Oxide Synthase; Nitroarginine; Oxidative Stress; Pressure; Pressure Ulcer; Regional Blood Flow; Skin; Thioctic Acid; Vasodilation; Vasodilator Agents

Topics: Blood Glucose Self-Monitoring; Diabetes Complications; Diabetes Mellitus; Dinoprost; Glycated Hemoglobin; Humans; Hyperglycemia; Oxidative Stress

The objective of this study was to establish if diabetes in the presence of polyneuropathy (PN) and/or cardiovascular autonomic neuropathy (CAN) is associated with alterations in the amounts of 8-epi-PGF2alpha (IP) and its metabolites including 2, 3-dinor-8-epi-PGF2alpha (dinor-IP) and 2, 3-dinor-5, 6 dihydro-8-epi-PGF2alpha (dinor-dihydro-IP) in urine. Mass spectrometric separation showed that excretion of IP was similar in the PN + /CAN- and PN+/CAN+ groups but higher than in the PN-/CAN- group (n = 103, 22 and 60, respectively; P < 0.05). By contrast, excretion of dinor-IP or dinor-dihydro-IP were similar in the PN-/CAN- and PN+/CAN- groups but higher than in PN+/CAN+ group. Correlations were obtained between IP and dinor-IP or dinor-dihydro-IP (r = 0.30; P < 0.001 and r = 0.31; P < 0.001, respectively). A significant association was also observed between dinor-IP and dinor-dihydro-IP (r = 0.48; P < 0.001). In conclusion, these biomarkers should prove useful in studies evaluating the impact of therapeutic drugs or antioxidant interventions aimed at delaying the onset of diabetic complications.

Topics: Adult; Aged; Cardiovascular Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Dinoprost; F2-Isoprostanes; Female; Humans; Male; Middle Aged; Oxidation-Reduction; Polyneuropathies

Oxidative stress plays a role in cardiovascular dysfunction. This is of interest in diabetes, a clinical condition characterized by oxidative stress and increased prevalence of cardiovascular disease. The role of p66(shc) in oxidative stress-related response has been demonstrated by resistance to and reduction of oxidative stress and prolonged lifespan in p66(shc-/-) mice. In this study we assess p66(shc) gene expression in peripheral blood mononuclear cells (PBM) from type 2 diabetic patients and healthy subjects. The p66(shc) mRNA level was assessed using RT-PCR with two sets of primers mapping for different p66(shc) regions. p66(shc) is expressed in both monocytes and lymphocytes. The level of p66(shc) mRNA was significantly higher in type 2 diabetic patients compared with controls (0.38 +/- 0.07 densitometric units vs. 0.13 +/- 0.08; P < 0.0001). In addition, total plasma 8-isoprostane levels, a marker of oxidative stress, were higher in type 2 diabetics (0.72 +/- 0.04 ng/ml) than in normal subjects (0.43 +/- 0.04, P < 0.001) and were significantly correlated to the p66(shc) mRNA level in PBM from type 2 diabetics (r(2) = 0.47; P = 0.0284). In conclusion, diabetes induces p66(shc) gene expression in circulating PBM; this up-regulation in expression is significantly associated with markers of oxidative stress. p66(shc) gene expression in PBM may represent a useful tool to investigate the oxidative stress involved in the pathogenesis of long-term diabetic complications.

Topics: Adaptor Proteins, Signal Transducing; Animals; Diabetes Mellitus; Diabetes Mellitus, Type 2; Dinoprost; Gene Expression Regulation; Humans; Leukocytes, Mononuclear; Mice; Mice, Knockout; Middle Aged; Oxidative Stress; Reference Values; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Shc Signaling Adaptor Proteins; Src Homology 2 Domain-Containing, Transforming Protein 1

Oxidative stress is involved in the pathophysiology of atherosclerosis, diabetes mellitus, hypertension, obesity, and cigarette smoking, all of these being risk factors for coronary heart disease (CHD). We tested the hypothesis that risk factors of CHD are associated with abundant systemic oxidative stress.. We conducted a case-control study with 93 CHD patients and 93 control subjects frequency-matched by age and sex. Urinary excretion of the F2-isoprostane 8-iso-prostaglandin (PG) F2alpha and its major urinary metabolite, 2,3-dinor-5,6-dihydro-8-iso-PGF2alpha, were measured by gas chromatography-tandem mass spectrometry. Body mass index, systolic blood pressure, and C-reactive protein were elevated in CHD patients (P<0.01). Urinary 8-iso-PGF2alpha and 2,3-dinor-5,6-dihydro-8-iso-PGF2alpha also differed, from 77 (interquartile range, 61-101) to 139 (93-231) pmol/mmol creatinine and from 120 (91-151) to 193 (140-275) pmol/mmol in control subjects and case subjects, respectively (P<0.001). 8-iso-PGF2alpha and its metabolite were highly correlated (Spearman's rho=0.664, P<0.001). HDL cholesterol was diminished in CHD patients (P<0.001). All of these characteristics predicted CHD in univariate analysis. In a multivariate model, the odds ratios were increased only for 8-iso-PGF2alpha (> or =131 pmol/mmol, P<0.001) and C-reactive protein (>3 mg/L, P<0.01), ie, by 30.8 (95% CI, 7.7-124) and 7.2 (1.9-27.6), respectively. 8-iso-PGF2alpha was found to be a novel marker in addition to known risk factors of CHD, ie, diabetes mellitus, hypercholesterolemia, hypertension, and smoking. Urinary excretion of 8-iso-PGF2alpha correlated with the number of risk factors for all subjects (P<0.001 for trend).. 8-iso-PGF2alpha is a sensitive and independent risk marker of CHD.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Case-Control Studies; Comorbidity; Coronary Disease; Diabetes Mellitus; Dinoprost; Female; Gas Chromatography-Mass Spectrometry; Germany; Humans; Hypercholesterolemia; Hypertension; Male; Middle Aged; Obesity; Oxidative Stress; Risk Factors; Sensitivity and Specificity; Smoking

To determine the clinical conditions associated with systemic oxidative stress in a community-based cohort. Information regarding cardiovascular risk factors associated with systemic oxidative stress has largely been derived from highly selected samples with advanced stages of vascular disease. Thus, it has been difficult to evaluate the relative contribution of each cardiovascular risk factor to systemic oxidative stress and to determine whether such risk factors act independently and are applicable to the general population.. We examined 2828 subjects from the Framingham Heart Study and measured urinary creatinine-indexed levels of 8-epi-PGF2alpha as a marker of systemic oxidative stress. Age- and sex-adjusted multivariable regression models were used to assess clinical correlates of oxidative stress. In age- and sex-adjusted models, increased urinary creatinine-indexed 8-epi-PGF2alpha levels were positively associated with female sex, hypertension treatment, smoking, diabetes, blood glucose, body mass index, and a history of cardiovascular disease. In contrast, age and total cholesterol were negatively correlated with urinary creatinine-indexed 8-epi-PGF2alpha levels. After adjustment for several covariates, decreasing age and total/HDL cholesterol ratio, sex, smoking, body mass index, blood glucose, and cardiovascular disease remained associated with urinary 8-epi-PGF2alpha levels.. Smoking, diabetes, and body mass index were highly associated with systemic oxidative stress as determined by creatinine-indexed urinary 8-epi-PGF2alpha levels. The effect of body mass index was minimally affected by blood glucose, and diabetes and may suggest an important role of oxidative stress in the deleterious impact of obesity on cardiovascular disease.

Topics: Adult; Aged; Aged, 80 and over; Body Mass Index; Comorbidity; Diabetes Mellitus; Dinoprost; F2-Isoprostanes; Female; Humans; Male; Middle Aged; Multivariate Analysis; Obesity; Oxidative Stress; Risk Factors; Sex Factors; Smoking

The relationship between oxidative stress in vivo and insulin resistance was examined.. This study included 87 patients, 46 males and 41 females (mean age 63 +/- 10 years), without coronary artery disease. The homeostasis assessment insulin resistance (HOMA-IR) (fasting blood sugar x fasting immunoreactive insulin/405), a marker for insulin resistance, was measured. The patients were divided into three groups: the noninsulin resistance group (N-IR group) without diabetes mellitus (DM) and with fasting blood glucose level of 126 mg/dl and HOMA-IR < or = 1.73 (n = 44), the insulin resistance group (IR group) without diabetes mellitus and with fasting blood glucose level of 126 mg/dl and HOMA-IR > 1.73 (n = 29), and the DM group (type 2 diabetes mellitus) (n = 14). Urinary 8-iso-prostaglandin F2 alpha (U-8-iso-PGF2 alpha) excretion was measured as a marker of in vivo oxidative stress.. There were significantly more obese patients in the IR group than in the N-IR group (62% vs 25%, p = 0.001), and the remnant-like particle cholesterol level was significantly higher in the IR group than in the N-IR group (7.6 +/- 5.2 vs 4.6 +/- 1.5 mg/dl, p < 0.01). Patients in the IR group had a significantly larger number of coronary risk factors. U-8-iso-PGF2 alpha excretion was significantly higher in the IR group and DM groups (201 +/- 86, 191 +/- 136 vs 129 +/- 50 pg/mg. Cr, p < 0.0001, p = 0.01), and there was a significantly positive correlation between the number of coronary risk factors, fasting blood sugar and U-8-iso-PGF2 alpha concentration (correlation coefficient = 0.32, 0.37, p = 0.002, p = 0.0003). Multiple regression analysis showed that remnant-like particle cholesterol, fasting blood sugar and insulin resistance were independent factors for U-8-iso-PGF2 alpha concentration (p < 0.0001, p = 0.0007, p = 0.02).. Insulin resistance, remnant lipoprotein and hyperglyceridemia are deeply involved in oxidative stress in vivo.

Topics: Blood Glucose; Cholesterol; Diabetes Mellitus; Dinoprost; F2-Isoprostanes; Female; Homeostasis; Humans; Insulin Resistance; Lipoproteins; Male; Middle Aged; Oxidative Stress; Regression Analysis

Diabetes mellitus (DM) is associated with enhanced lipid peroxidation and persistent platelet activation. We tested the hypothesis that the in vivo formation of the F2-isoprostane 8-iso-prostaglandin (PG)F2alpha, a bioactive product of arachidonic acid peroxidation, is enhanced in DM and contributes to platelet activation.. Urine samples were obtained from 85 diabetic patients and 85 age- and sex-matched healthy subjects for measurement of immunoreactive 8-iso-PGF2alpha and 11-dehydro-thromboxane B2 (TXM), an in vivo index of platelet activation. Sixty-two had non-insulin-dependent (NID)DM, and 23 had insulin-dependent (ID) DM. Vitamin E supplementation, metabolic control, and cyclooxygenase inhibitors were used to investigate the mechanisms of formation of 8-iso-PGF2alpha in this setting. Urinary 8-iso-PGF2alpha excretion was significantly higher (P=0.0001) in NIDDM patients (419+/-208 pg/mg creatinine; range 160 to 1014) than in age-matched control subjects (208+/-92; 41 to 433). Urinary 8-iso-PGF2alpha was linearly correlated with blood glucose and urinary TXM. 8-iso-PGF2alpha excretion was also significantly (P=0. 0001) higher in IDDM patients (400+/-146; 183 to 702) than in control subjects (197+/-69; 95 to 353). Vitamin E supplementation (600 mg/d for 14 days) was associated with a statistically significant reduction in both urinary 8-iso-PGF2alpha (by 37%) and TXM (by 43%) in 10 NIDDM patients. Improved metabolic control was associated with a significant (P=0.0001) reduction in 8-iso-PGF2alpha and TXM excretion by 32% and 41%, respectively, in 21 NIDDM patients. 8-iso-PGF2alpha was unchanged after 2-week dosing with aspirin and indobufen despite profound suppression of TXM excretion.. We conclude that DM is associated with increased formation of F2-isoprostanes, as a correlate of impaired glycemic control and enhanced lipid peroxidation. This may provide an important biochemical link between impaired glycemic control and persistent platelet activation. These results provide a rationale for dose-finding studies of antioxidant treatment in diabetes.

Topics: Adult; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dinoprost; F2-Isoprostanes; Female; Humans; Lipid Peroxidation; Male; Middle Aged; Platelet Activation; Thromboxane B2; Vitamin E

Topics: Adult; Aged; Alprostadil; Connective Tissue Diseases; Diabetes Mellitus; Dinoprost; Factor Analysis, Statistical; Female; Humans; Kidney Failure, Chronic; Lung Diseases, Obstructive; Male; Medicine, Chinese Traditional; Medicine, East Asian Traditional; Middle Aged; Neoplasms; Prostaglandins E; Prostaglandins F

In our ongoing studies of the interrelationship between platelets and the vascular wall we found that an accurate estimate could be made of the clinical condition and more effective therapy prescribed when we monitored alterations in the plasma levels of TXB2. For this purpose we devised a radioimmunoassay with I125-TXB2-Tyramide. Patients with ischemic heart disorders, cerebral apoplexy, diabetes mellitus, Buerger's disease, Takayasu disease etc., all had statistically high levels of TXB2 as compared with healthy controls. In particular, patients with myocardial infarction, cerebral thrombosis and/or hemorrhage all revealed increases in levels of TXB2 and these levels increased in parallel with a worsening of the clinical condition, and there was always a re-increase in TXB2 level before a recurrence of an attack. As plasma TXB2 levels clearly reflect thrombogenic disorders, the assessment of these levels on a routine basis, enables a more accurate diagnosis, an indication of possible recurrences, and more effective chemotherapy and rehabilitation.

Topics: Adolescent; Adult; Arteriosclerosis; Arteriosclerosis Obliterans; Child; Chromatography, Gel; Circadian Rhythm; Coronary Disease; Diabetes Mellitus; Dinoprost; Female; Humans; Intracranial Embolism and Thrombosis; Male; Middle Aged; Prostaglandins F; Takayasu Arteritis; Thromboangiitis Obliterans; Thromboxane B2; Thromboxanes