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Biomedical subjects

E Motz

Publications and source records attributed to E Motz.

At least 19 recordsLinked to original sources
PubMed2001

Detection of nitrotyrosine in the diabetic plasma: evidence of oxidative stress.

AIMS/HYPOTHESIS: Oxidative stress plays an important role in diabetic vascular complications. It has been shown that an imbalance in the ratio of nitric oxide: superoxide anion, because of a prevalence of superoxide anion, leads to an alteration in vascular reactivity. In this condition peroxynitrite production, resulting from the reaction between nitric oxide and superoxide, could increase. Peroxynitrite is responsible for nitration of tyrosine residues in proteins. Therefore, the presence of nitrotyrosine in plasma proteins is considered indirect evidence of peroxynitrite production. The aim of this study was to demonstrate the presence of nitrotyrosine in the plasma of patients with Type II (non-insulin-dependent) diabetes mellitus and to correlate its concentrations with the plasma concentrations of glucose and antioxidant defenses. METHODS: A total of 40 Type II diabetic patients and 35 healthy subjects were enrolled, and glycaemia, plasma nitrotyrosine, total antioxidant parameter and glycated haemoglobin were measured. Nitrotyrosine was detected by ELISA with a detection limit of 10 nmol/l. RESULTS: Nitrotyrosine was found in the plasma of all diabetic patients (means +/- SD = 0.251 +/- 0.141 micromol/l), whereas it was not detectable in the plasma of healthy control subjects. Nitrotyrosine plasma values were correlated with plasma glucose concentrations (r = 0.38, p < 0.02) but not with total antioxidant parameter or glycated haemoglobin. Total antioxidant parameter was reduced in diabetic patients (p < 0.01). CONCLUSIONS: The presence of nitrotyrosine in the plasma of diabetic patients indicates that peroxynitrite is generated in diabetes, suggesting a possible involvement of peroxynitrite in the development of diabetic complications.

Antioxidants↗
PubMed2001

Red wine protects diabetic patients from meal-induced oxidative stress and thrombosis activation: a pleasant approach to the prevention of cardiovascular disease in diabetes.

BACKGROUND: Oxidative stress and thrombosis have been reported to be increased in diabetic patients and involved in the pathogenesis of cardiovascular complications. It has been demonstrated in diabetic patients that consumption of a meal is accompanied by the generation of an oxidative stress and of a hypercoagulable state. It is well recognized that red wine shows antithrombotic activity and that its ingestion increases plasma antioxidant capacity in man. In this study the possibility that red wine consumption may reduce the oxidative stress and thrombosis produced postprandially in diabetic patients has been evaluated. SUBJECTS AND METHODS: Twenty type 2 diabetic patients were studied during fasting consumption of 300 mL of red wine, or during a meal accompanied, or not, by red wine ingestion. RESULTS: Plasma glucose, insulin, triglycerides, total plasma radical-trapping capacity, activated factor VII and prothrombin fragments 1 + 2 were measured in basal state and at 60, 120 and 180 min after the start of each experiment. Low-density lipoprotein (LDL) oxidation was also evaluated at baseline and after 120 min Plasma glucose, insulin, triglycerides and LDL oxidation significantly increased, while the total plasma radical-trapping parameter significantly decreased during the meal test. Consumption of red wine in the fasting state significantly increased total plasma radical-trapping parameter activity, while wine ingestion with a meal counterbalanced the decrease of total plasma radical-trapping parameter and the increase of LDL oxidation. Meal consumption induced an increase in plasma prothrombin fragments 1 + 2 and activated factor VII in diabetic patients. Wine ingestion with the meal significantly reduced the production of both prothrombin fragments 1 + 2 and activated factor VII. Fasting consumption of red wine alone did not show effects on coagulation or LDL oxidation. CONCLUSION: This finding confirms that in the absorptive phase free radicals are produced in diabetic patients, which reduce serum antioxidant defences, increase LDL oxidation and activate the coagulation system. Red wine consumption during a meal significantly preserves plasma antioxidant defences and reduces both LDL oxidation and thrombotic activation. The consumption of a moderate amount of red wine during meals may have a beneficial effect in the prevention of cardiovascular disease in diabetic patients.

Antioxidants↗
PubMed1999

Meal-induced oxidative stress and low-density lipoprotein oxidation in diabetes: the possible role of hyperglycemia.

Oxidative stress and its contribution to low-density lipoprotein (LDL) oxidation have been implicated in the pathogenesis of vascular diabetic complications. However, the relationship between hyperglycemia, hyperinsulinemia, hyperlipidemia, and oxidative stress is still debated. If plasma glucose and/or insulin and/or lipid are some of the most important determinants of oxidative stress in diabetes, then their typical postprandial elevations in diabetes would be expected to favor oxidative stress and LDL oxidation. To test this hypothesis, in type 2 diabetic patients, we evaluated the effects of two different standard meals designed to produce different levels of postprandial hyperglycemia on the plasma oxidative status and LDL oxidation. The meals were administered in randomized order to each of 10 type 2 diabetic patients. Blood samples were collected at baseline and 60 and 120 minutes after the meals. In every sample, plasma levels of glucose, insulin, cholesterol, triglycerides, nonesterified fatty acids (NEFAs), malondialdehyde (MDA), and the total radical-trapping antioxidant parameter (TRAP) were measured. LDL susceptibility to oxidation was evaluated at baseline and after 120 minutes. Plasma glucose, insulin, triglycerides, and MDA increased and NEFAs and TRAP significantly decreased after either meal. The variations in plasma glucose, MDA, and TRAP were significantly greater and LDL was more susceptible to oxidation after the meal that produced a significantly higher degree of hyperglycemia. These results suggest that postprandial hyperglycemia may contribute to oxidative stress in diabetic patients, providing a mechanistic link between hyperglycemia and diabetic vascular disease.

Cross-Over Studies↗
PubMed1998

Effect of intensive glycaemic control on fibrinogen plasma concentrations in patients with Type II diabetes mellitus. Relation with beta-fibrinogen genotype.

Recent studies show that in diabetic subjects an increase of plasma fibrinogen concentration is associated with a high risk of cardiovascular complications. Environmental and genetic factors contribute to the plasma fibrinogen concentration. Several studies indicate a relation between the polymorphism in the 5' region of the beta-fibrinogen gene and plasma protein concentrations and in diabetes the possible influence of hyperglycaemia on fibrinogen is still debated. In this study we investigated these relations. Hind III polymorphism was evaluated by a polymerase chain reaction-technique. On the basis of the observed allelic combination of fibrinogen beta-gene polymorphism and the existence of poor metabolic control (glycated haemoglobin > or = 7.5%), 50 Type II diabetic patients were selected. They were divided into three groups according to their beta-gene polymorphism (alpha1alpha1: n = 20, alpha1alpha2: n = 15, alpha2alpha2: n = 15) and then intensive insulin therapy was started. After 3 months of intensive treatment, the improvement in glycaemic control was equivalent, in terms of glycated haemoglobin, in all the three groups. A fibrinogen reduction was observed in alpha1alpha2 and alpha2alpha2 but not in alpha1alpha1 subjects. These results underline a possible relation between fibrinogen genotypes and glycaemic control in determining plasma fibrinogen concentrations in diabetic patients.

Blood Glucose↗
PubMed1998

Antioxidant defences are reduced during the oral glucose tolerance test in normal and non-insulin-dependent diabetic subjects.

BACKGROUND: Free radical production has been reported to be increased in patients with diabetes mellitus, and it has been suggested that hyperglycaemia may directly contribute to the generation of oxidative stress. The aim of the present study was to evaluate the effects of an acute increase in glycaemia on plasma antioxidant defences. RESULTS: During the oral glucose tolerance test (OGTT), plasma concentration of protein-bound sulphydryl (SH) groups, vitamin C, vitamin E and uric acid significantly decreased in normal as well as non-insulin-dependent diabetes mellitus (NIDDM) subjects. Total plasma radical-trapping activity, which evaluates plasma antioxidant capacity due to known and unknown antioxidants present in the plasma as well as their mutual co-operation, was also significantly reduced. CONCLUSION: This finding supports the hypothesis that hyperglycaemia may, even acutely, induce an oxidative stress.

Antioxidants↗
PubMed1998

Hyperglycemia-induced circulating ICAM-1 increase in diabetes mellitus: the possible role of oxidative stress.

ICAM-1 is one of the most important intercellular adhesion molecules involved in atherogenesis. Previous studies reported increased circulating ICAM-1 plasma levels in NIDDM patients with or without vascular complications. It has been suggested that an acute increase of plasma glucose may produce an oxidative stress in man, and in vitro studies have demonstrated that high glucose and free radicals induce cellular expression of ICAM-1. In this study, three different experiments were performed in nine NIDDM patients and in seven matched healthy controls: oral glucose tolerance test, antioxidant glutathione i.v. administration for two h, oral glucose tolerance test plus glutathione i.v. administration. Blood samples were drawn at -15 min and every 30 min from 0 to 180 min. During the oral glucose tolerance test, circulating ICAM-1 plasma levels significantly increased in both diabetic and normal subjects. Glutathione administration during the oral glucose tolerance test abolished this phenomenon. Glutathione administered alone significantly decreased circulating ICAM-1 plasma levels in diabetic patients, while no effect was observed in the normal subjects. These data suggest that hyperglycemia may induce an increase of circulating ICAM-1 plasma levels through an oxidative stress, and that the antioxidant glutathione counterbalances this effect. These data support the hypothesis of a causal relationship linking hyperglycemia, oxidative stress and atherogenesis in diabetes mellitus.

Aged↗
PubMed1998

Meal-generated oxidative stress in type 2 diabetic patients.

OBJECTIVE: Free radical production has been reported to be increased in diabetic patients and to be involved in the pathogenesis of diabetic complications. In this study, a standardized meal was administered to 10 type 2 diabetic patients and 10 healthy matched normal subjects to evaluate its effects on plasma oxidative stress generation. RESEARCH DESIGN AND METHODS: In diabetic patients, at baseline and after the meal, plasma malondialdehyde (MDA), vitamin C, protein SH groups, uric acid, vitamin E, and total plasma radical-trapping parameter, which evaluates plasma antioxidant capacity due to known and unknown antioxidants present in the plasma as well as their mutual cooperation, were measured. RESULTS: After the meal, plasma MDA and vitamin C increased, while protein SH groups, uric acid, vitamin E, and total plasma radical-trapping parameter decreased more significantly in the diabetic subjects than in control subjects. CONCLUSIONS: This finding shows that in the absorptive phase, free radicals are produced in diabetic patients. Since plasma glucose, but not insulin, rose significantly more in diabetic subjects than in control subjects, hyperglycemia may play an important role in the generation of postprandial oxidative stress in diabetic patients.

Analysis of Variance↗
PubMed1997

Total plasma antioxidant capacity predicts thrombosis-prone status in NIDDM patients.

OBJECTIVE: To explore the hypothesis that a relationship exists between free radical activity and abnormalities in hemostasis in NIDDM. RESEARCH DESIGN AND METHODS: The use of the total radical-trapping antioxidant parameter (TRAP) has very recently been proposed to explore the antioxidant property of a plasma and their mutual cooperation. In the present study, TRAP, vitamin E, vitamin C, vitamin A, uric acid, protein-bound SH (thiol) groups, fibrinogen, prothrombin fragments F1 + 2, and D-dimer have been evaluated in 46 NIDDM patients and 47 healthy matched control subjects. RESULTS: In NIDDM patients, TRAP, vitamin A, SH groups, and uric acid were significantly reduced, whereas the level of vitamin E was significantly increased. Vitamin C was similar in the two groups. Fibrinogen, prothrombin fragment 1 + 2, and D-dimer were increased in diabetic patients. TRAP, but no single other antioxidant, had a strong inverse association with fibrinogen, prothrombin fragment 1 + 2, and D-dimer. CONCLUSIONS: These findings are consistent with the hypothesis that oxidative stress may condition coagulation activation in diabetics. However, the data suggest that it is the total antioxidant capacity rather than any single plasma antioxidant that is the most relevant parameter.

Antioxidants↗
PubMed1997

Total radical-trapping antioxidant parameter in NIDDM patients.

OBJECTIVE: The existence of an oxidative stress in diabetes is still debated. This is largely due to the lack of good tools to assay the level of oxidative stress. The use of total radical-trapping antioxidant parameter (TRAP) has recently been proposed to explore the antioxidant property of a plasma sample. TRAP may be either directly measured by a fluorescence-based method (TRAPm) or calculated (TRAPc) by a mathematical formula, taking into account the serum levels of four natural antioxidants: protein-bound SH (thiol) groups, uric acid, vitamin E, and vitamin C. The difference between TRAPm and TRAPc is due to antioxidants, which are still unidentified, and to the possible synergism among the antioxidants. RESEARCH DESIGN AND METHODS: In this study, we evaluated malondialdehyde (MDA), TRAPm, TRAPc, protein-bound SH groups, uric acid, vitamin E, and vitamin C in 40 NIDDM patients and 40 matched normal control subjects. RESULTS: TRAPm and TRAPc were significantly lower in diabetic patients. A good correlation between TRAPm and TRAPc was found in both NIDDM patients (r = 0.68, P < 0.0001) and control subjects (r = 0.74, P < 0.0001). Protein-bound SH groups and uric acid were significantly lower in diabetic subjects, while MDA and vitamin E level were significantly higher. After correction for serum triglycerides (MDA) and cholesterol (vitamin E), MDA lost significance, while vitamin E did not. Vitamin C was not different in the two groups. CONCLUSIONS: These data show decreased TRAP levels in NIDDM patients, suggesting the existence of lower antioxidant defenses in diabetes. The decrease appears to be due to various antioxidants, some of them not yet clearly defined. TRAP may represent a more reliable estimation of serum antioxidant capacity than the measurement of each known antioxidants. The correlation found between TRAPm and TRAPc values suggests that TRAPc, easier to measure than TRAPm, might be adequately reliable for routine assessment of oxidative stress in diabetic patients.

Antioxidants↗
PubMed1996

Post-meal coagulation activation in diabetes mellitus: the effect of acarbose.

It has been previously demonstrated that hyperglycaemia activates haemostasis; diabetes mellitus is considered a thrombosis-prone state. Acarbose, by inhibiting dietary carbohydrate absorption, reduces post-meal hyperglycaemia. In this study we evaluated the effect of post-meal hyperglycaemia on two markers of coagulation activation: prothrombin fragments 1 + 2 and D-dimer. Seventeen non-insulin-dependent diabetic patients maintained on diet therapy alone were randomly assigned to receive- with a cross-over study design-acarbose (100 mg orally) or placebo before a standard meal. Blood samples for measurement of plasma glucose, insulin, prothrombin fragments 1 + 2 and D-dimer were drawn at 0, 60, 120 and 240 min. After both placebo and acarbose, hyperglycaemia and hyperinsulinaemia which followed a standard meal were accompanied by a significant increase of plasma concentration of prothrombin fragments 1 + 2 and D-dimer in comparison to their baseline values. Acarbose administration significantly reduced the rise of glucose, insulin, prothrombin fragments 1 + 2 and D-dimer from 0 to 240 min in comparison to placebo. We conclude that post-meal hyperglycaemia, at the level reached by many diabetic patients on diet therapy alone, induces a coagulation activation. Acarbose, by decreasing post-meal hyperglycaemia, may be useful in reducing meal-induced activation of haemostasis in diabetic patients.

Acarbose↗
PubMed1996

Increased circulating intercellular adhesion molecule-1 levels in type II diabetic patients: the possible role of metabolic control and oxidative stress.

Blood levels of the circulating form of the integrin intercellular adhesion molecule-1 (ICAM-1), malondialdehyde (MDA), and hemoglobin A1c (HbA1c) were studied at baseline and 3 months after improved metabolic control in 25 type II diabetic patients without signs of macroangiopathy, and were compared with those in 15 matched healthy normal controls. Circulating ICAM-1 and MDA levels were increased in diabetic patients, both at baseline and 3 months later. However, with improving metabolic control HbA1c, circulating ICAM-1, and MDA significantly decreased. A significant correlation between circulating ICAM-1, HbA1c, and MDA was found in diabetic patients at each time. Multiple regression analysis considering circulating ICAM-1 as the dependent variable and HbA1c and MDA as independent variables, showed a significant correlation between the three variable at each time. Similar correlations were found in control subjects. These data show increased levels of circulating ICAM-1 in type II diabetic patients, independent of the presence of macroangiopathy. Moreover, these results suggest that oxidative stress and metabolic control might participate in determining increased circulating ICAM-1 levels in both type II diabetic patients and normal subjects.

Diabetes Mellitus, Type 2↗
PubMed1995

Hyperglycemia-induced thrombin formation in diabetes. The possible role of oxidative stress.

Diabetes is characterized by the existence of a thrombosis-prone condition, possibly related to hyperglycemia. However, the mechanism linking hyperglycemia to the activation of the coagulation cascade is still unclear. It has been recently suggested that diabetes is accompanied by increased oxidative stress. In this work, the possibility that oxidative stress may be involved in the hyperglycemia-induced coagulation activation has been evaluated. Prothrombin fragment 1 + 2 (F1 + 2), which represents a reliable marker of the amount of thrombin released in the circulation, has been chosen for studying thrombin formation in vivo. In nine type II diabetic patients and in seven healthy control subjects, matched for age and body mass index, three different experiments were performed: oral glucose tolerance test (OGTT), intravenous antioxidant glutathione (GSH) administration for 2 h, and OGTT plus intravenous GSH administration. Samples were drawn at -15 min and every 30 min from 0 to 180 min. During the OGTT, F1 + 2 significantly increased in both diabetic and healthy subjects. GSH administration during OGTT normalized this phenomenon. GSH administration alone significantly decreased F1 + 2 in diabetic patients, while no effect was observed in the normal subjects. These data suggest that hyperglycemia may induce thrombin activation, possibly inducing an oxidative stress, and that antioxidant GSH may counterbalance this effect.

Aged↗
PubMed1994

Fibrinogen plasma levels as a marker of thrombin activation in diabetes.

This study attempted to verify the existence of a correlation between fibrinogen, a major cardiovascular risk factor in diabetes, and indexes of thrombin generation and action, prothrombin fragment 1 + 2 (F1 + 2), and D-dimer (D-D), in a group of diabetic subjects compared with a matched control group. Forty insulin-dependent diabetes mellitus patients and 30 matched healthy control subjects participated in this study. The subjects were tested for the following parameters: fibrinogen, prothrombin F1 + 2, D-D, fasting glycemia, and HbA1c. In addition, 5 diabetic subjects who maintained stable fibrinogen plasma levels > 300 mg/dl for at least 6 months before the study were treated with 12,500 U/day subcutaneous heparin for 7 days. Diabetic subjects showed increased levels of fibrinogen, prothrombin F1 + 2, and D-D plasma levels. Simple linear regression analysis detected a positive correlation between fibrinogen and prothrombin F1 + 2, D-D, and glycosylated HbA1c. In the five diabetic subjects treated with heparin fibrinogen, prothrombin F1 + 2 and D-D levels decreased at the end of the treatment. All these parameters returned to baseline after 7 days of washout. These data indicate that fibrinogen plasma levels are correlated to parameters of thrombin activation in plasma in diabetic patients and suggest that high fibrinogen plasma levels might be a risk marker for cardiovascular disease in diabetes because it is an expression of an existing thrombophilia.

Adult↗