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

Long-term complications of diabetes mellitus have been ascribed to both the effects of prolonged hyperglycemia and to increased oxidative stress. In an attempt to identify the mechanisms underlying the acute effects of hyperglycemia on oxidative stress, we investigated the hypothesis that high glucose might lead to an insufficiency in reducing equivalents (such as NADPH) and thus to a disruption in the glutathione-dependent antioxidant defences and to an incapacity to deal with oxidant attack. For this purpose, erythrocytes from diabetic patients were incubated for 0-90 min in 5.55 or 33.3 mM D-glucose containing tertbutyl hydroperoxide 0.5 and 1 mM, Menadione 100 microM, or glucose oxidase. The time course of the changes in non-protein bound glutathione (reduced and oxidised), lactate and pyruvate, alanine and fluorescent products of oxidative proteolysis, hemolysis and methemoglobin was monitored. The results show that although glucose utilisation was unaffected, all oxidants caused a persistent decrease in total non-protein-bound glutathione suggesting binding to proteins. However, changes in glutathione and redox status differed between the various oxidants and were not directly related to the extent of oxidative cellular damage. In these experimental conditions, with short incubations and using the erythrocyte as the simplest cellular model of glucose metabolism, neither high glucose nor the diabetic condition worsened the susceptibility of erythrocytes to acute in vitro oxidative damage.
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PMID:Divergent effects of different oxidants on glutathione homeostasis and protein damage in erythrocytes from diabetic patients: effects of high glucose. 1171 65

Vitamin K-dependent proteins, including matrix Gla-protein, have been shown to inhibit vascular calcification. Activation of these proteins via carboxylation depends on the availability of vitamin K. We examined whether dietary intake of phylloquinone (vitamin K-1) and menaquinone (vitamin K-2) were related to aortic calcification and coronary heart disease (CHD) in the population-based Rotterdam Study. The analysis included 4807 subjects with dietary data and no history of myocardial infarction at baseline (1990-1993) who were followed until January 1, 2000. The risk of incident CHD, all-cause mortality, and aortic atherosclerosis was studied in tertiles of energy-adjusted vitamin K intake after adjustment for age, gender, BMI, smoking, diabetes, education, and dietary factors. The relative risk (RR) of CHD mortality was reduced in the mid and upper tertiles of dietary menaquinone compared to the lower tertile [RR = 0.73 (95% CI: 0.45, 1.17) and 0.43 (0.24, 0.77), respectively]. Intake of menaquinone was also inversely related to all-cause mortality [RR = 0.91 (0.75, 1.09) and 0.74 (0.59, 0.92), respectively] and severe aortic calcification [odds ratio of 0.71 (0.50, 1.00) and 0.48 (0.32, 0.71), respectively]. Phylloquinone intake was not related to any of the outcomes. These findings suggest that an adequate intake of menaquinone could be important for CHD prevention.
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PMID:Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study. 1551 82

Atherosclerosis is characterized by inflammatory metabolic change with lipid accumulation in the artery. Atherosclerotic plaque occurs at discrete locations in the arterial system and involves the proliferation of smooth muscle cells (SMCs) together with imbalance of the extracellular matrix elements, elastic fiber in particular. The role of elastin in arterial development and disease was confirmed by generating mice that lack elastin. Thus, elastin is a critical regulatory molecule that regulates the phenotypic modulation, proliferation and migration of SMCs. We estimated that elastin expression and SMC proliferation are coupled inversely: potent stimulators of cell proliferation may potentially inhibit elastin expression and potent inhibitors of cell proliferation can stimulate elastin expression. Moreover, elastin was found to be expressed maximally at the G(0) and minimally at the G(2)/M phase during the cell cycle, suggesting that its expression is regulated by the cell growth state. The elastin peptide VPGVG enhanced SMC proliferation, resulting in the reduction of elastin expression. The inhibition of elastin expression by elastin fragments may be reflected in the negative feedback regulatory mechanism. The relationship between cell proliferation and elastin expression may be changed in atherosclerosis. Areas of atherosclerotic plaque show abnormality of elasticity and permeability from the viewpoint of the physiological function of the arterial wall. The etiology was estimated to be that cholesterol and calcium are deposited on the elastic fiber, resulting in decreased elastin synthesis and cross-linking formation. In addition, these dysfunctions of elastin fiber are also associated, in that the down-regulation of elastin and its related components (fibrillin-1 and lysyl oxidase) are directly related to calcification in SMCs. The denatured arterial elastin by cholesterol and calcium accumulation was also susceptible to proteolytic enzymes such as elastase and matrix metalloproteinase (MMP). Therefore, metabolic change in elastic fiber induces decreased elasticity and is associated with essential hypertension. Vitamin K(2) is used in drug therapy against atherosclerosis, or calcification in diabetes mellitus or dialysis, due to its promotion of the carboxylation of the matrix Gla protein.
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PMID:Atherosclerosis and matrix dystrophy. 1555 5

Diabetes is the major cause of autonomic neuropathy in humans. Sympathetic neurons from the celiac/superior mesenteric ganglia (CG/SMG) develop neuropathic changes in diabetes whereas sympathetic superior cervical ganglion (SCG) neurons do not. Glucose-induced oxidative stress is proposed as a major factor in the development of diabetic neuropathy. The aim of this study was to investigate whether sympathetic neurons that develop neuropathy in diabetes are more susceptible to oxidative stress. Explants of CG/SMG and SCG from control adult rats were cultured in media free of serum and NGF, exposed to menadione for 48 h to induce oxidative stress and assessed for neuronal viability, TUNEL-positive nuclei and tyrosine hydroxylase- (TH)-immunoreactivity. TH-immunoreactivity was also assessed in ganglia from control and 8 week streptozotocin-diabetic rats. Menadione caused a concentration-dependent loss of neuronal viability and increase in TUNEL staining in both ganglia. However, at low concentrations, menadione had a significantly greater effect (p<0.01) on CG/SMG neurons than SCG neurons. At 1 nM, menadione caused a significant increase (p<0.05) in the number of CG/SMG neurons containing intense TH-immunoreactivity without affecting SCG neurons. Similarly, 8 weeks streptozotocin-induced diabetes resulted in a significant increase (p<0.05) in intensely fluorescent TH-containing CG/SMG neurons but not SCG neurons. This is the first demonstration that oxidative stress in vitro causes the same accumulation of TH in CG/SMG neurons as is observed following streptozotocin-induced diabetes in vivo. Furthermore, the selective vulnerability of CG/SMG neurons to diabetes is reflected by increased sensitivity to oxidative stress.
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PMID:Selective susceptibility of different populations of sympathetic neurons to diabetic neuropathy in vivo is reflected by increased vulnerability to oxidative stress in vitro. 1697 73

Atrial fibrillation (AF) requires anticoagulation for prevention of arterial embolism, especially in the presence of defined risk factors summarized in the CHADS (2) score (congestive heart disease, hypertension, age >75 years, diabetes, history of ischemic stroke or transient cerebral ischemia). Vitamin K antagonists as drugs of choice have several limitations. International normalized ratio (INR) adjustment to 2.0 to 3.0 may be difficult to maintain, and doses vary widely between patients. Inherited variations of the vitamin K epoxide reductase C1 enzyme and of the cytochrome P450 2C9 system influence the dosage as well as exogenous factors such as food and drug intake or intercurrent diseases. Increasing age and risk of falling are the main factors behind the underuse of anticoagulation in AF. Anticoagulants with a lack of all or most of these characteristics and without need of regular monitoring for dose adjustment may improve the adherence to the indication for anticoagulation. Indirect systemic and oral direct factor Xa and oral direct thrombin inhibitors are currently being developed for the prevention of embolism in patients with AF.
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PMID:New anticoagulants in atrial fibrillation. 1978 62

Atrial fibrillation (AF) is the most commonly encountered arrhythmia in clinical practice and is associated with substantial morbidity and mortality. Its prevalence increases with age, affecting about 1% of patients aged <60 years and almost 10% of patients >80 years. AF is associated with a fivefold increasing risk of embolism or stroke with absolute risk ranging from less than 1% to 20% per year, depending on patient age and the presence of clinical risk factors including congestive heart failure, systemic hypertension, diabetes mellitus and prior history of cardioembolic events. Vitamin K antagonists (VKAs) and acetyl salicylic acid are currently the only licensed antithrombotic therapies for stroke prevention in patients with AF. Anticoagulants are very effective for stroke prevention in patients with AF, overall a 64% relative risk reduction. Nonetheless, approximately 50% of patients with AF who have an indication for VKA receive anticoagulant therapy, of which only 50% maintain adequate therapeutic ranges. Furthermore, 50% will discontinue VKAs within 3 to 5 years regardless of appropriate international normalized ratio control. Underutilization of VKAs is related, in part, to their numerous limitations and difficulty in maintaining adequate therapeutic control, prompting the development of new antithrombotic strategies that are equally effective and safer, and easier to manage than VKAs. This review focuses on new antithrombotic therapies for stroke prevention in patients with AF.
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PMID:New pharmacotherapy for stroke prevention in atrial fibrillation: update 2010. 2012 14

The growing incidence of Atrial Fibrillation (AF) induces an increasing morbimortality, particularly thromboembolism (TE). Vitamin K Antagonists (VKA) reduce of 62 % the stroke rate in case of AF and are more efficient with INR between 2 and 3 than aspirin or the association aspirin-VKA with INR<2. The only place for clopidogrel could be its association with aspirin if VKA are contra-indicated. But VKA increase of 1.4 to 3.36 %/year the major bleedings, whereas the risk with aspirin is less important. The TE risk factors validated in case of AF are: previous TE, heart failure, hypertension, age over 75, diabetes mellitus, rhumatismal valvulopathy or mechanical valvular prosthesis. Ischemic cardiomyopathy, age between 65 and 75 and the female gender represent intermediate risks. Guidelines suggest to anticoagulate patients with previous TE or CHADS(2) score > or = 2 and to discuss VKA for a score equal to 1. Lone AF must not be anticoagulated but the continuous follow-up of occurring risk factors remains essential. Paroxysmal and persistant/permanent AF present the same TE risk. VKA are preferable if patients are older than 75 unless a major bleeding risk is present. If AF occurs on an ischemic cardiomyopathy, VKA are often essential and reduce the total mortality even if they increase the bleeding risk due to the association with antiplatelet therapy. However no precise guidelines are available on this topic. After a successful AF ablation, guidelines recommend not to modify the antithrombotic strategy. The bleeding risk score called "HEMORR2HAGE" allows to establish an individual balance of risk/benefit of VKA. The utility of transoesophagial echocardiography could be recognized in case of intermediate TE risk to suggest VKA if thrombotic criteria are identified. At least, new antithrombotic therapy will probably modify our perception of the risk/benefit ratio.
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PMID:[Atrial fibrillation: who should be anticoagulated?]. 2047 91

Atrial fibrillation is the most frequent cardiac arrhythmia and its prevalence increases with age. It is essential to prevent the thromboembolic events, stroke in particular, considered as its most serious complication. Vitamin K antagonists are currently the most effective drugs to prevent them. However, despite their proven efficacy, they carry a risk of bleeding complications. Consequently, it is essential to balance individual thromboembolic risk with the hemorrhagic risk, taking into consideration age, cardiac diseases, hypertension, diabetes, history of cerebral vascular accident, history of hemorrhagic disease and also patient's compliance. The CHADS2 score is a stratification model for stroke risk in patients with non-valvular atrial fibrillation that is the easiest score to use in clinical practice and the most used one.
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PMID:[Which patients with atrial fibrillation need anticoagulation?]. 2096 18

The stroke rate in atrial fibrillation is 4.5% per year, with death or permanent disability in over half. The risk of stroke varies from under 1% to over 20% per year, related to the risk factors of congestive heart failure, hypertension, age, diabetes, and prior stroke or transient ischemic attack (TIA). Major bleeding with vitamin K antagonists varies from about 1% to over 12% per year and is related to a number of risk factors. The CHADS(2) index and the HAS-BLED score are useful schemata for the prediction of stroke and bleeding risks. Vitamin K antagonists reduce the risk of stroke by 64%, aspirin reduces it by 19%, and vitamin K antagonists reduce the risk of stroke by 39% when directly compared with aspirin. Dabigatran is superior to warfarin for stroke prevention and causes no increase in major bleeding. We recommend that all patients with atrial fibrillation or atrial flutter, whether paroxysmal, persistent, or permanent, should be stratified for the risk of stroke and for the risk of bleeding and that most should receive antithrombotic therapy. We make detailed recommendations as to the preferred agents in various types of patients and for the management of antithrombotic therapies in the common clinical settings of cardioversion, concomitant coronary artery disease, surgical or diagnostic procedures with a risk of major bleeding, and the occurrence of stroke or major bleeding. Alternatives to antithrombotic therapies are briefly discussed.
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PMID:Canadian Cardiovascular Society atrial fibrillation guidelines 2010: prevention of stroke and systemic thromboembolism in atrial fibrillation and flutter. 2132 65

Atrial fibrillation (AF) is the most common form of cardiac arrhythmia, and its incidence is rising as the population ages. AF is therefore a growing source of cardiovascular morbidity and mortality due to thromboembolic complications and heart failure. The risk of embolic stroke is multiplied by about 5.6-fold in non rheumatic AF and by 17.6-fold in rheumatic AF Strokes due to AF are often fatal or disabling. Paroxysmal and permanent fibrillation are associated with a similar thromboembolic risk. Embolic complications arise from the left atrium or the left atrial appendage. Known risk factors in patients with AF include a history of thromboembolism or stroke, age > 75 years, heart failure, rheumatic valve disease, mechanical prosthetic valves, arterial hypertension and diabetes mellitus. Ischemic cardiomyopathy, female gender and atherosclerotic vascular disease are associated with an intermediate risk of thromboembolism. Vitamin K antagonist therapy targeting an INR of 2 to 3 reduces the risk of stroke by two-thirds in patients with AF, and causes bleeding in 1.4 % to 3.6 % of patients. The bleeding risk can be evaluated with the CHADS2 scale. Aspirin (75/300 mg per day) reduces the risk of cerebral thromboembolism by about 21%. Current guidelines recommend vitamin K antagonist or dabigatran anticoagulation for patients with a CHADS2 score of 2. Patients with a score of 0 should receive either aspirin or no drug therapy, while patients with a score of 1 may receive either a vitamin K antagonist or aspirin. After successful AF ablation, the existing antithrombotic strategy should be pursued New strategies based on antithrombin or anti-Xa medications will probably have a better risk-benefit ratio.
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PMID:[Thrombotic risk factors and antithrombotic treatment in atrial fibrillation]. 2237 63


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