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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In vitro studies have demonstrated that gliclazide has free radical scavenging and antiplatelet activities. To assess this clinically, we studied gliclazide in a blinded, randomized, glibenclamide-controlled trial in 30 type II diabetic patients with retinopathy. All patients had been taking glibenclamide for more than 12 months before being randomized to receive either an equipotent dose of gliclazide or to continue on glibenclamide. Diabetic control was not modified. The patients were well matched at randomization (mean age, 58 years; duration of diabetes, 8 years; 20 males; mean hemoglobin A1 [HbA1], 8.6%) and their degree of diabetic control was not altered during the trial. Free radical activity was assessed as oxidative status by plasma thiols (PSH), lipid peroxides (MDA-LM), and red blood cell superoxide dismutase activity (SOD). Platelet aggregation in whole blood to collagen (Plt-ag) was used as the measure of platelet reactivity. There were no differences between these measurements at baseline. At 3 months, the oxidative status and platelet aggregation in the gliclazide group had improved significantly compared with baseline and had also showed significant differences in all parameters when compared with the glibenclamide group. Therefore, comparing gliclazide with glibenclamide-treated patients at 3 months, we found: PSH, 458 +/- 38 versus 414 +/- 34 mumol/L, P less than .004; MDA-LM, 7.0 +/- 0.6 versus 8.3 +/- 0.8 mumol/L, P less than .0002; SOD, 152 +/- 36 versus 123 +/- 15 micrograms/mL, P less than .016; Plt-ag, 50.8 +/- 24 versus 72.3% +/- 15%, P less than .006. These changes were maintained at 6 months.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of gliclazide on platelet reactivity and free radicals in type II diabetic patients: clinical assessment. 157 14

Our previous study indicated that erythrocyte Cu,Zn-superoxide dismutase (Cu,Zn-SOD) undergoes glycation and inactivation in vivo (1) and in vitro (2). The aim of the present study was to assess glycated Cu,Zn-SOD in patients with insulin-dependent diabetes mellitus. Glycated Cu,Zn-SOD, which binds to a boronic acid affinity column, was measured by the enzyme-linked immunosorbent assay. The percentage of the glycated form in 25 insulin-dependent diabetic children was 40.2 +/- 8.2%; this was significantly higher than that in the normal controls (P less than 0.01). The specific activity of the glycated form in the diabetic children was 163,000 +/- 33,000 IU/mg Cu,Zn-SOD protein, significantly lower than that in controls (P less than 0.01). These data indicate that glycated and less active Cu,Zn-SOD is increased in erythrocytes of patients with insulin-dependent diabetes mellitus.
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PMID:Increased glycated Cu,Zn-superoxide dismutase levels in erythrocytes of patients with insulin-dependent diabetis mellitus. 159 80

Lipid peroxidation and the antioxidant status were studied in male patients having stable angina (SA) and unstable angina (UA) pectoris and the results were compared with that of controls. Lipid peroxides (LPx) and conjugated dienes (CD) were found to be elevated in patients with both SA (LPx: 3.96 +/- 1.07, P less than 0.001; CD: 357.09 +/- 66.23, P less than 0.01) and UA (LPx: 4.66 +/- 1.33, CD: 373.33 +/- 49.82, P less than 0.001) than in controls (LPx: 3.22 +/- 0.86, CD: 335.15 +/- 60.27). In SA, the erythrocytes expressed a diminished activity of superoxide dismutase (SOD) (SA: 435.59 +/- 76.02, control: 651.69 +/- 145.90, P less than 0.001) and normal activities of catalase and glutathione peroxidase, whereas in UA it showed enhanced activities of both SOD (UA: 735.72 +/- 145.67, P less than 0.01) and catalase (UA: 21.94 +/- 6.26, control: 18.69 +/- 6.37, P less than 0.01). A significant increase was also noticed in the levels of ceruloplasmin and vitamin E during both types of angina, but not alteration was observed in the levels of transferrin. Further, the patients with diabetes showed maximum levels of lipid peroxides compared to smokers and hypertensives. The level of lipid peroxides was also observed to increase with the severity of disease. This study indicates that free radicals are involved in the pathogenesis and progression of atherosclerotic heart disease.
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PMID:Antioxidant status in relation to free radical production during stable and unstable anginal syndromes. 163 72

The interaction of endothelium-derived relaxing factor (EDRF) and oxygen-derived free radicals may potentially play an important role in the pathophysiology of complications associated with diabetes. In the present study, we investigated spontaneous EDRF release in diabetic rat aorta that is unmasked by the addition of superoxide dismutase (SOD). SOD produced a significantly greater relaxation in diabetic aorta compared with control aorta using both aortic ring and bioassay preparations. This relaxation was unaltered by pretreatment with catalase or indomethacin. Removal of the endothelium or pretreatment with either NG-monomethyl-L-arginine or methylene blue eliminated SOD-induced relaxation in both control and diabetic rings. Measurement of antioxidant enzymes revealed an elevation in catalase in diabetic aorta, with no difference in the SOD or glutathione peroxidase activity. The increase in catalase activity suggests increased exposure of diabetic aorta to hydrogen peroxide. Pretreatment of rings with the catalase inhibitor, 3-amino-1,2,4-triazole, attenuated the SOD-induced relaxation in diabetic aortic rings but had no effect in control aortic rings. In summary, our observations suggest that the diabetic rat aorta releases more spontaneous EDRF than control aorta; however, the activity of EDRF on vascular smooth muscle tone is masked by increased destruction by oxygen-derived free radicals.
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PMID:Regulation of spontaneous EDRF release in diabetic rat aorta by oxygen free radicals. 163 63

The following species; superoxide (O2-.), hydrogen peroxide (H2O2), hydroxyl radical (.OH) and singlet oxygen (1O2), are generally called as reactive oxygen species (ROS). These species have been suggested to play important roles in various diseases caused by oxygen toxicity such as ischemia, carcinogenesis, inflammation, diabetes and aging. During the past two decades, considerable interests have been focused on chemical and biological research of ROS. We have also reported about the research results on ROS, which can be classified as following below; 1) chemical reactivities of O2-., 2) formation and toxicity of 1O2, 3) chemical reactivities of .OH, 4) enzyme mechanism of xanthine oxidase, 5) development of the compounds which induce the formation of O2-. and H2O2 in living cells and 6) development of superoxide dismutase mimics. These studies are reviewed from the standpoint of both chemical and biological interests.
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PMID:[Chemical and biochemical studies on reactivities, formations and toxicities of reactive oxygen species]. 164 54

Two forms of superoxide dismutase, CuZn-SOD and MnSOD, have been investigated in the kidneys of streptozotocin-induced diabetic rats using both radio-immunoassay and immunoenzyme staining. The rats were killed 2, 8 and 12 weeks after the induction of diabetes mellitus and the kidneys excised. Two weeks after the induction of diabetes, the kidneys were hypertrophied because of the proliferation of renal tubular epithelium. However, the total CuZnSOD content of the kidneys did not increase and, because of the epithelial proliferation, the CuZnSOD concentration in each proximal tubular cell was decreased. Armanni-Ebstein lesions were found in the distal tubules 8 and 12 weeks after the induction of diabetes. The cells in these lesions were intensely stained for CuZnSOD, suggesting an adaptive response to the enhanced oxidative stress. The MnSOD staining in the thick ascending limbs of Henle's loops was enhanced in the diabetic kidneys, while that in the cortical tubules was unaltered. MnSOD was assumed to increase in response to hypermetabolism associated with the proliferation of renal tubules. This was most marked in the cells which were rich in mitochondria, again suggesting an adaptive response to enhanced oxidative stress induced by diabetes mellitus. The glomeruli of both the diabetic and control groups were not stained for SODs, and no significant microscopic change was found even 12 weeks after the induction of diabetes mellitus.
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PMID:Effect of diabetes mellitus induced by streptozotocin on renal superoxide dismutases in the rat. A radioimmunoassay and immunohistochemical study. 167 79

Blood antioxidant system parameters were examined in elderly subjects. The authors have developed methods for measurements of catalase, superoxide dismutase, and lipid peroxidation products. They introduce a new factor 'F' that is supposed to characterize the blood antioxidant system; this factor is based on the values of catalase and superoxide dismutase activities and the intensity of lipid peroxidation. The authors come to a conclusion that the blood antioxidant and oxidant systems may be more accurately described with the use of this new factor F. In case of an abdominal tumor whole blood catalase level is elevated and superoxide dismutase activity significantly reduced. Factor F values were found extremely low before death, therefore this factor may be considered an important criterion of a critical state. The blood antioxidant parameters of patients with diabetes mellitus and essential hypertension did not much differ from those of age-matched healthy subjects.
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PMID:[Determination of the antioxidant properties of the blood and their diagnostic significance in the elderly]. 172 48

Lipid peroxide (LPO) values in blood plasma, along with the glutathione peroxidase (GSH-PX) activity in whole blood and superoxide dismutase (SOD) activity in erythrocytes were determined in 50 patients with non-insulin-dependent diabetes mellitus (NIDDM) and in 33 control subjects. The mean LPO value, SOD activity, LPO/GSH-PX and LPO/SOD ratios in the diabetic patients were significantly higher than those in the control subjects. The increases of LPO value, LPO/GSH-PX and LPO/SOD ratios were more pronounced in diabetics with microangiopathy than in those without microangiopathy. Our results suggest that free radicals may be implicated in the pathogenesis of diabetic microangiopathy.
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PMID:[Relationship between free radicals and diabetic microangiopathy]. 175 51

We used acetyl-homocysteine-thiolactone (citiolone) as an enhancer of superoxide dismutase (SOD), a free radical scavenger, in order to assay any possible prevention of the insulitis and subsequent B cell damage caused by streptozotocin (STZ) when given in multiple low doses. Mice were given citiolone (50 mg/kg b.wt.) as a long pretreatment or concomitantly with STZ for a shorter period. Ten days after the last STZ injection, pancreases were processed for SOD assay and morphological observations. Results demonstrate that citiolone increases SOD values, but to a variable degree, after the STZ administration. The highest SOD levels were found in animals treated for the longer period (P less than 0.001 vs saline-treated controls; P less than 0.0001 vs STZ-treated controls) but we did not observe a direct correspondence between high SOD values and morphological integrity of islet beta cells and/or low blood glucose levels. In conclusion, we hypothesize that the onset of type 1 diabetes in mice involves free radical generation but in addition some other factor may be responsible for the beta cell damage.
Diabetes Res Clin Pract 1991 Aug
PMID:Prevention of low dose streptozotocin-induced diabetes by acetyl-homocysteine-thiolactone. 177 19

Increased free radical activity may contribute to thrombosis via effects on platelet aggregation and the prostanoid balance. To investigate this further we studied 15 Type 1 diabetic patients with retinopathy, matched with uncomplicated Type 1 patients for age, duration of diabetes and HbA1, together with matched healthy non-diabetic control subjects. The oxidative effects of free radicals as total diene conjugates and lipid peroxides were measured, together with redox status extracellularly as plasma albumin-thiols and intracellularly as erythrocyte superoxide dismutase activity. Platelet count, aggregation of platelets in whole blood to collagen, thromboxane B2, and prostacyclin stimulating factor (PGI2SF) were also assessed. Free radicals measured as lipid peroxides were significantly higher (9.6 (8.1-11.6) mumol l-1 (median and interquartile range) in diabetic patients with retinopathy than in control subjects (8.1 (7.4-9.2) mumol l-1; p less than 0.05). There were also significant reductions in redox status both extracellularly as plasma albumin thiols (408 (383-473) vs 490 (456-517) mumol l-1, p less than 0.001) and intracellularly as erythrocyte superoxide dismutase activity (34 (27-41) vs 44 (36-51) g l-1, p less than 0.05) between patients with retinopathy and control subjects. Platelet counts were increased in diabetic patients with retinopathy (p less than 0.05), as was collagen-induced platelet aggregation (p less than 0.01). Prostacyclin stimulating factor was reduced in patients with retinopathy (p less than 0.05) and correlated within the plasma with lipid peroxides (r = -0.53, p less than 0.04) and albumin thiols (r = 0.64, p less than 0.01). The results suggest that diabetic patients, particularly with retinopathy, are under oxidative stress and have an increased thrombotic tendency with increased platelet reactivity and a reduction in prostacyclin stimulating factor.
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PMID:The relationship of oxidative stress to thrombotic tendency in type 1 diabetic patients with retinopathy. 183 13


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