UMLS:C0011849 - FACTA Search

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

Periodontal disease, a frequent complication of diabetes mellitus, is the major cause of tooth loss. However, studies on neutrophil function in patients with this condition have yielded contradictory findings. The NADPH oxidase activity of 40 diabetic patients with periodontosis who were on metabolic control was evaluated and compared with that in 40 healthy subjects. Superoxide anion production was measured by a photometric method, with NBT reduction at 490 nm in a microplate reader and by a microscopic method, with a percentage of positive PMNs with granules of formazan in the cytoplasm. When the PMN respiratory burst was activated by phorbol myristate acetate (PMA), a protein kinase C (PKC) soluble activator, superoxide production of diabetics (4.31 +/- 1.67 A x 10(-3)/min) and normal subjects (4.25 +/- 1.25 A x 10(-3)/min) was comparable by photometric method, whereas a significantly defective response to opsonized zymosan was observed when the microscopic method was used (58 +/- 17% in diabetics and 66 +/- 18% in controls; p = 0.05). Therefore in patients with diabetes the impact on PMN function is of multifactorial origin, and is probably correlated to the glucose level and to glycation of PMN protein, such as NADPH oxidase or myeloperoxidase. Alternatively, glucose in PMN may be reduced by aldose reductase to polyols, and this pathway requires NADPH, the coenzyme for the respiratory burst. Moreover, we found that superoxide production in response to opsonized zymosan was reduced in diabetic patients. The activation of protein tyrosine kinase (PTK) is an important mechanism underlying transmembrane signaling and, moreover, protein tyrosine phosphorylations, stimulated by zymosan receptor-mediated activation, might be caused by the activation of specific PTK, whereas activation by PMA is probably mediated through another PKC type.
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PMID:Respiratory burst of neutrophils in diabetic patients with periodontal disease. 970 64

The etiology of Dupuytren's disease is still unknown in spite of significant recent advances in identifying the type of cell responsible for initiating the process. Associated factors such as alcoholism, smoking, work, diabetes, and epilepsy are discussed. The course of the disease in men as compared with women is also discussed. Recent evidence has shown that there may be genetic and immunologic factors involved. Superoxide free radicals and their effect on fibroblast proliferation may play a significant role in the disease process.
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PMID:Etiology of Dupuytren's disease. 1005 Feb 41

Generation of oxygen free radicals by glycated proteins is widely believed to be one of the causes of oxidative stress in diabetes and aging. Metal ion catalysis is regarded as an essential part of the oxidative mechanism. In this work, we also considered an alternative "metal-free" superoxide radical formation by a number of fructose-amino acids (Amadori compounds) derived from glycine and lysine, which represent the simplest models for early glycated proteins. In the superoxide dismutase-dependent cytochrome c assay, 1 mM Chelex-treated aqueous solutions of monofructose-amino acids 4-6 generated 0.9-3.6 x 10(-10) M s-1 O2*- at pH 7. Surprisingly, the rates of superoxide radical formation in the solutions of difructose-amino acids 7-9 were significantly higher (0.75-5.8 x 10(-9) M s-1 O2*-). The percentage of acyclic sugar anomers (</=0. 8-85%) and their "enolization" rate constants (5 x 10(-6) to 2 x 10(-3) s-1) varied broadly for the compounds studied and positively correlated with the rates of superoxide radical formation. The presence of Cu2+ markedly increased the rate of superoxide radical formation at metal concentrations higher than 1 microM, while Fe3+ did not accelerate the reaction even at 100 microM. Therefore, in addition to the metal ion-catalyzed oxygen free radical formation, metal-free enol oxidation of fructosyl groups on glycated amino acid residues may contribute to the generation of oxygen free radicals and their subsequent oxidative damage to proteins.
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PMID:Superoxide free radical generation by Amadori compounds: the role of acyclic forms and metal ions. 1007 85

Antioxidant enzymes in liver and small intestine were investigated using control and streptozotocin diabetic rats fed diets with 5% olive, sunflower or fish oil for five weeks. In liver, Glutathione Peroxidase and Superoxide Dismutase decreased and in intestine Glutathione-S-transferase (GST) increased by diabetes. In isolated jejunum and ileum, this increase in GST activity was due to an increase in GST-alpha and -mu isoenzymes in jejunum and GST-alpha, mu and -pi in ileum. Since GST plays an important role in protecting tissues from oxidative damage, our results highlight the role of the intestine against free radicals in physiological or pathological situations.
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PMID:Modulation of hepatic and intestinal glutathione S-transferases and other antioxidant enzymes by dietary lipids in streptozotocin diabetic rats. 1023 44

The effect of superoxide dismutase, catalase, metal-chelating agents and hydroxyl radical scavengers on the toxicity of alloxan to isolated ob/ob mouse pancreatic islets in vitro has been compared with the reported ability of such substances to protect against alloxan diabetes in vivo. Superoxide dismutase and catalase protected beta-cells of isolated pancreatic islets against alloxan cytotoxicity, as did the hydroxyl radical scavengers dimethyl sulfoxide (DMSO) and butanol. However, 1,3-dimethylurea and thiourea, that are recognised as effective hydroxyl radical scavengers and that protect animals against the diabetogenic effects of alloxan, were without effect. Similarly, desferrioxamine, that inhibits hydroxyl radical formation from alloxan in chemically defined systems, did not protect against alloxan toxicity. Diethylenetriamine pentaacetic acid, which does not inhibit hydroxyl radical formation from alloxan, also gave no significant protection. The results indicate a role for superoxide radical and hydrogen peroxide in the mechanism of toxicity of alloxan but do not support the involvement of the hydroxyl radical in this process. Alternative explanations must be sought for the ability of hydroxyl radical scavengers and metal-chelating agents to protect against alloxan toxicity in vivo.
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PMID:Effect of superoxide dismutase, catalase, chelating agents, and free radical scavengers on the toxicity of alloxan to isolated pancreatic islets in vitro. 1038 Dec 3

Adenosine, an intercellular messenger that is a product of the metabolism of ATP, plays a major role in neuronal and vascular responses of the retina to alterations in oxygen delivery. Significant changes in adenosine concentration have been measured in the retina during both ischemia and during the subsequent reperfusion period which result in important, but complex, functional effects. Adenosine A1 receptor stimulation produces a protective effect during ischemia, whereas overstimulation of the A2a receptor has deleterious effects. The mechanisms underlying these findings have not been completely determined, but most likely are the result of alterations in excitotoxicity, gene expression, and blood flow. Paradoxically, prolonged increases in adenosine concentration may be injurious to the retina, a consequence of superoxide radical formation secondary to adenosine catabolism. Adenosine is a critical mediator of blood flow changes in response to ischemia. It is a significant component of the retina's compensatory hyperemic response to ischemia, hypoxia, and hypoglycemia. Increasing endogenous adenosine concentrations may be useful in ameliorating post-ischemic hypoperfusion. Overall, current evidence suggests that adenosine is a vital component of the endogenous retinal response to substrate deprivation. Additionally, in vitro studies provide strong evidence that adenosine is a mediator of the formation and effects of vascular endothelial growth factor, which in turn promotes neovascularization. Finally, the ability of the retina to develop an ischemia-tolerant state by ischemic preconditioning is an intriguing phenomenon that reveals yet another essential role for adenosine in the retina's endogenous response to ischemia. The experimental results described in this review suggest that continued investigation into the role of adenosine in the retina may lead to important clinical applications for adenosine-based therapies that could decrease the incidence of retinal damage in ischemic vasculopathies such as diabetes, glaucoma, and retinal vascular occlusion.
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PMID:The purine nucleoside adenosine in retinal ischemia-reperfusion injury. 1039 21

Alloxan is a diabetogenic agent which apparently acts through formation of superoxide radicals formed by redox cycling. Superoxide radicals are also formed by a variety of mechanisms in hyperglycemia. We exposed extracellular-superoxide dismutase (EC-SOD) null mutant and wild-type mice to alloxan, and followed up both the initial diabetes induction and the long-term course of the hyperglycemia. The null mutant mice responded with a modestly enhanced hyperglycemia compared to the wild type controls. In the long-term follow-up all mice eventually regained glycemic control, although it took longer for individuals with higher initial hyperglycemia. This delaying effect of the hyperglycemia was much more pronounced in the null mutant mice. These data suggest that the difference in initial diabetes induction between the groups is due to interception by EC-SOD of extracellular superoxide radicals produced by alloxan. The delayed recovery in the null mutant mice suggests that superoxide radicals released as a result of hyperglycemia impair beta-cell regeneration and that EC-SOD provides some protection. Mouse islets were found to contain little EC-SOD, whereas the content of the cytosolic Cu- and Zn-containing SOD was very high. This low EC-SOD activity may contribute to the high alloxan susceptibility of beta-cells, and may also cause a high susceptibility to superoxide radicals produced by activated inflammatory leukocytes and in hyperglycemia.
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PMID:Enhanced alloxan-induced beta-cell damage and delayed recovery from hyperglycemia in mice lacking extracellular-superoxide dismutase. 1051 83

The role of reactive oxygen species in diabetes and its complications are well known. Two therapeutic agents commonly used in the treatment of diabetes are the sulfonylureas gliclazide and glibenclamide. These drugs effectively reduce blood sugar in non-insulin-dependent diabetes mellitus, by augmenting insulin release. Gliclazide is known to be a general free radical scavenger as shown by its inhibition of o-dianisidine photo-oxidation. In this study, the effects of gliclazide and glibenclamide on free radicals were examined in vitro, using electron spin resonance spectroscopy. Superoxide radical (O2*-) generated from the hypoxanthine-xanthine oxidase system or hydroxyl radical (OH*) generated via the Fenton reaction were analyzed as spin adducts of 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). Gliclazide scavenged O2*- and OH* in a dose-dependent manner whereas glibenclamide was without effect. These findings suggest that gliclazide is not only effective in reducing blood sugar, but may also be beneficial as a result of inhibition of lipid and protein denaturation, which is believed to lead to the development of diabetic complications.
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PMID:Gliclazide scavenges hydroxyl and superoxide radicals: an electron spin resonance study. 1069 14

Both reactive oxygen species (ROS) and endothelin-1 (ET- 1) have been implicated in the pathophysiology of diabetic nephropathy. The interrelationship between them, however, has not been documented in this disease. To determine whether ROS regulates ET-1 production in diabetic kidneys, we examined the in vitro and in vivo effects of ROS donors and scavengers on ET-1 production of diabetic rat glomeruli. For in vitro study, the glomeruli were isolated with a sieving method from streptozotocin-induced diabetic rats and killed at 1 week, 1 month, and 3 months, respectively. Superoxide was measured by a spectrophotometer, and ET-1 was measured by radioimmunoassay. The results demonstrated that the basal production levels of superoxide and ET-1 were higher in diabetic glomeruli than in normal glomeruli in vitro. There was a positive correlation between the production of superoxide and ET-1 in diabetic glomeruli. The basal ET-1 production was markedly attenuated by ROS scavengers including superoxide dismutase, catalase, dimethyl sulfoxide, and deferoxamine in diabetic glomeruli. Exogenous ROS generated by xanthine/xanthine oxidase significantly enhanced ET-1 generation by both diabetic and normal glomeruli. A high glucose concentration (500 mg/dL) in vitro increased ET-1 production by normal glomeruli but not diabetic glomeruli, and insulin partly suppressed ET- 1 production by diabetic glomeruli. The in vivo study demonstrated that when diabetic rats were injected daily with superoxide dismutase or catalase after diabetes was induced, the basal production of ET-1 was markedly attenuated after 1 week and 1 month, respectively. These results indicate that exogenously or endogenously derived ROS can enhance ET-1 production by diabetic rat glomeruli and that ROS scavengers suppress ET- 1 production both in vitro and in vivo. The effects of ROS on ET-1 production of diabetic glomeruli may be partly caused by the effect of hyperglycemia or insulin deficiency.
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PMID:Reactive oxygen species enhances endothelin-1 production of diabetic rat glomeruli in vitro and in vivo. 1077 44

Superoxide anion plays important roles in vascular disease states. Increased superoxide production contributes to reduced nitric oxide (NO) bioactivity and endothelial dysfunction in experimental models of vascular disease. We measured superoxide production by NAD(P)H oxidase in human blood vessels and examined the relationships between NAD(P)H oxidase activity, NO-mediated endothelial function, and clinical risk factors for atherosclerosis. Endothelium-dependent vasorelaxations and direct measurements of vascular superoxide production were determined in human saphenous veins obtained from 133 patients with coronary artery disease and identified risk factors. The predominant source of vascular superoxide production was an NAD(P)H-dependent oxidase. Increased vascular NAD(P)H oxidase activity was associated with reduced NO-mediated vasorelaxation. Furthermore, reduced endothelial vasorelaxations and increased vascular NAD(P)H oxidase activity were both associated with increased clinical risk factors for atherosclerosis. Diabetes and hypercholesterolemia were independently associated with increased NADH-dependent superoxide production. The association of increased vascular NAD(P)H oxidase activity with endothelial dysfunction and with clinical risk factors suggests an important role for NAD(P)H oxidase-mediated superoxide production in human atherosclerosis. The full text of this article is available at http://www.circresaha.org. Key Words:atherosclerosis endothelium superoxide nitric oxide diabetes Two Distinct Congenital Arrhythmias Evoked by a Multidysfunctional Na(+) Channel Marieke W. Veldkamp, Prakash C. Viswanathan, Connie Bezzina, Antonius Baartscheer, Arthur A.M. Wilde, Jeffrey R. Balser Abstract-The congenital long-QT syndrome (LQT3) and the Brugada syndrome are distinct, life-threatening rhythm disorders linked to autosomal dominant mutations in SCN5A, the gene encoding the human cardiac Na(+) channel. It is believed that these two syndromes result from opposite molecular effects: LQT3 mutations induce a gain of function, whereas Brugada syndrome mutations reduce Na(+) channel function. Paradoxically, an inherited C-terminal SCN5A mutation causes affected individuals to manifest electrocardiographic features of both syndromes: QT-interval prolongation (LQT3) at slow heart rates and distinctive ST-segment elevations (Brugada syndrome) with exercise. In the present study, we show that the insertion of the amino acid 1795insD has opposite effects on two distinct kinetic components of Na(+) channel gating (fast and slow inactivation) that render unique, simultaneous effects on cardiac excitability. The mutation disrupts fast inactivation, causing sustained Na(+) current throughout the action potential plateau and prolonging cardiac repolarization at slow heart rates. At the same time, 1795insD augments slow inactivation, delaying recovery of Na(+) channel availability between stimuli and reducing the Na(+) current at rapid heart rates. Our findings reveal a novel molecular mechanism for the Brugada syndrome and identify a new dual mechanism whereby single SCN5A mutations may evoke multiple cardiac arrhythmia syndromes by influencing diverse components of Na(+) channel gating function. The full text of this article is available at http://www.circresaha.org. Key Words: Na(+) channel inactivation long-QT syndrome Brugada syndrome
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PMID:UltraRapid communications : vascular superoxide production by NAD(P)H OxidaseAssociation with endothelial dysfunction and clinical risk factors 1080 75

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