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

Antioxidants were administered to diabetic rats and experimentally galactosemic rats to evaluate the ability of these agents to inhibit the development of diabetic retinopathy. Alloxan diabetic rats and nondiabetic rats that were fed 30% galactose randomly received standard diets or the diets supplemented with ascorbic acid and alpha-tocopherol (vitamins C+E diet) or a more comprehensive mixture of antioxidants (multi-antioxidant diet), including Trolox, alpha-tocopherol, N-acetyl cysteine, ascorbic acid, beta-carotene, and selenium. Diabetes or galactose feeding of at least 12 months resulted in pericyte loss, acellular capillaries, and basement membrane thickening. Compared with diabetic controls, the development of acellular capillaries was inhibited by 50% (P < 0.05) in diabetic rats that received supplemental vitamins C+E, and the number of pericyte ghosts tended to be reduced. The vitamins C+E supplement had no beneficial effect in galactosemic rats, but these rats consumed only approximately half as much of the antioxidants as the diabetic rats. The multi-antioxidant diet significantly inhibited ( approximately 55-65%) formation of both pericyte ghosts and acellular capillaries in diabetic rats and galactosemic rats (P < 0.05 vs. controls), without affecting the severity of hyperglycemia. Parameters of retinal oxidative stress, protein kinase C activity, and nitric oxides remained elevated for at least 1 year of hyperglycemia, and these abnormalities were normalized by multi-antioxidant therapy. Thus, long-term administration of antioxidants can inhibit the development of the early stages of diabetic retinopathy, and the mechanism by which this action occurs warrants further investigation. Supplementation with antioxidants can offer an achievable and inexpensive adjunct therapy to help inhibit the development of retinopathy in diabetes.
Diabetes 2001 Aug
PMID:Abnormalities of retinal metabolism in diabetes and experimental galactosemia. VII. Effect of long-term administration of antioxidants on the development of retinopathy. 1147 58

The reference ranges of the trace elements Al, As, Be, B, Cd, Co, Cu, Fe, Mn, Mo, Ni, Pb, Li, Rb, Se, Sr, and Zn were determined by inductively coupled plasma-mass spectrometry (ICP-MS) in sera of a group of free-ranging plains viscachas of the pampa grasslands of Argentina. The values were compared with those of a small group of captive plains viscachas of the Zurich Zoo with diabetes and bilateral cataracts. In addition, a method for digestion of whole-blood samples is described for the trace element determination. Significant differences in the concentration of trace elements in the two groups of animals are discussed. No correlation was found between the levels of selenium and of other trace elements compared to the formation of cataracts.
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PMID:Concentration of 17 trace elements in serum and whole blood of plains viscachas (Lagostomus maximus) by ICP-MS, their reference ranges, and their relation to cataract. 1150 31

Selenium in serum and selenium and glycogen in erythrocytes were determined in diabetic patients divided into noninsulin-dependent (n = 50) and insulin-dependent (n = 31) groups according to the etiopathogenesis of their diabetes. Selenium was determined by the method of atomic absorption spectrometry. Serum level of selenium was statistically significantly different in patients with either noninsulin-dependent (59.23 +/- 12.2 microg/L) or insulin-dependent (58.23 +/- 16.7 microg/L) diabetes mellitus as compared with the control group of 62 subjects (64.2 +/- 11.5 microg/L; p < 0.05). There was no statistically significant difference in the serum levels of selenium between the groups of patients with noninsulin-dependent and insulin-dependent diabetes mellitus. The levels of erythrocyte glycogen were 2.0580 +/- 1.326, 2.0380 +/- 1.735, and 2.0036 +/- 1.3537 microg/g Hb in the control group, noninsulin-dependent group, and insulin-dependent group, respectively, with no statistically significant between-group difference. The decreased levels of selenium in serum and erythrocytes of diabetic patients suggest the possible role of glutathione peroxidase activity.
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PMID:Selenium and glycogen levels in diabetic patients. 1179 14

Cereal grains and their products provide around 30% of total energy intake in British adults, (much more than any of the other major food groups). Coronary heart disease (CHD) is the largest single cause of death in Britain and many other Western countries. This review examines the question whether there is a relation between cereal consumption and CHD. Several of the nutrients in cereals have known potential for reducing risk factors for CHD: the linoleic acid, fibre, vitamin E, selenium and folate. Cereals also contain phytoestrogens of the lignan family and several phenolic acids with antioxidant properties. Processing generally reduces the content of these nutrients and bioprotective substances. Although cereals at the farm gate are very low in salt, processed cereal foods, eg bread and some breakfast cereals, are high-salt foods and thus could contribute to raising blood pressure. Human experiments have clearly shown that oat fibre tends to lower plasma total and LDL cholesterol but wheat fibre does not. Rice bran and barley may also lower cholesterol but most people do not eat enough barley to have an effect. Cereal foods with low glycaemic index such as pasta and oats are beneficial for people with diabetes and might lower plasma lipids. Between 1996 and 2001 an accumulation of five very large cohort studies in the USA, Finland and Norway have all reported that subjects consuming relatively large amounts of whole grain cereals have significantly lower rates of CHD. This confirms an earlier report from a small British cohort. The protective effect does not seem to be due to cholesterol-lowering. While cohort studies have shown this consistent protective effect of whole grain cereals, there has been (only one) randomised controlled secondary prevention trial of advice to eat more cereal fibre. In this there was no reduction of the rate of reinfarction. The trial had some weaknesses, eg there were eight different diets, compliance was not checked objectively, and duration was for only 2 y. It appears valid to make health claims (as now permitted by the US FDA) that whole grain cereal foods and oat meal or bran may reduce the risk of CHD.
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PMID:Cereal grains and coronary heart disease. 1184 Jan 74

There is growing evidence that suggests that brain injury after amphetamine and methamphetamine (METH) administration is due to an increase in free radical formation and mitochondrial damage, which leads to a failure of cellular energy metabolism followed by a secondary excitotoxicity. Neuronal degeneration caused by drugs of abuse is also associated with decreased ATP synthesis. Defective mitochondrial oxidative phosphorylation and metabolic compromise also play an important role in atherogenesis, in the pathogenesis of Alzheimer's disease, Parkinson's disease, diabetes, and aging. The energy deficits in the central nervous system can lead to the generation of reactive oxygen and nitrogen species as indicated by increased activity of the free radical scavenging enzymes like catalase and superoxide dismutase. The METH-induced dopaminergic neurotoxicity may be mediated by the generation of peroxynitrite and can be protected by antioxidants selenium, melatonin, and selective nNOS inhibitor, 7-nitroindazole. L-Carnitine (LC) is well known to carry long-chain fatty acyl groups into mitochondria for beta-oxidation. It also plays a protective role in 3-nitropropioinc acid (3-NPA)-induced neurotoxicity as demonstrated in vitro and in vivo. LC has also been utilized in detoxification efforts in fatty acid-related metabolic disorders. In this study we have tested the hypothesis that enhancement of mitochondrial energy metabolism by LC could prevent the generation of peroxynitrite and free radicals produced by METH. Adult male C57BL/6N mice were divided into four groups. Group I served as control. Groups III and IV received LC (100 mg/kg, orally) for one week. Groups II and IV received 4 x 10 mg/kg METH i.p. at 2-h intervals after one week of LC administration. LC treatment continued for one more week to groups III and IV. One week after METH administration, mice were sacrificed by decapitation, and striatum was dissected to measure the formation of 3-nitrotyrosine (3-NT) by HPLC/Coularry system. METH treatment produced significant formation of 3-NT, a marker of peroxynitrite generation, in mice striatum. The pre- and post-treatment of mice with LC significantly attenuated the production of 3-NT in the striatum resulting from METH treatment. The protective effects by the compound LC in this study could be related to the prevention of the possible metabolic compromise by METH and the resulting energy deficits that lead to the generation of reactive oxygen and nitrogen species. These data further confirm our hypothesis that METH-induced neurotoxicity is mediated by the production of peroxynitrite, and LC may reduce the peroxynitrite levels and protect against the underlying mechanism of METH toxicity, which are models for several neurodegenerative disorders like Parkinson's disease.
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PMID:The protective role of L-carnitine against neurotoxicity evoked by drug of abuse, methamphetamine, could be related to mitochondrial dysfunction. 1210 98

The syntheses of two selenium analogues (10 and 11) of the naturally occurring sulfonium ion, salacinol (3), are described. Salacinol is one of the active principles in the aqueous extracts of Salacia reticulata that are traditionally used in Sri Lanka and India for the treatment of diabetes. The synthetic strategy relies on the nucleophilic attack of a 2,3,5-tri-O-benzyl-1,4-anhydro-4-seleno-D-arabinitol at the least hindered carbon of benzyl- or benzylidene-protected D- or L-erythritol-1,3-cyclic sulfate. The use of 1,1,1,3,3,3-hexafluoro-2-propanol as a solvent in the coupling reaction proves to be beneficial. Enzyme inhibition assays indicate that 10 is a better inhibitor (K(i) = 0.72 mM) of glucoamylase than 3, which has a K(i) value of 1.7 mM. In contrast, 11 showed no significant inhibition of glucoamylase. Compounds 10 and 11 showed no significant inhibition of barley-alpha-amylase or porcine pancreatic-alpha-amylase.
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PMID:Synthesis of selenium analogues of the naturally occurring glycosidase inhibitor salacinol and their evaluation as glycosidase inhibitors. 1210 2

In the 21st century, patients suffering from diabetes mellitus (DM), a lifestyle-related disease, will increase more than in the 20th century. DM is threatening because of the development of many severe secondary complications, including atherosclerosis, microangiopathy, renal dysfunction and failure, cardiac abnormalities, diabetic retinopathy, and ocular disorders. Generally, DM is classified as either insulin-dependent type 1 or noninsulin-dependent type 2 DM. Type 1 DM is treated only by daily insulin injections; type 2 DM is treated by several types of synthetic therapeutic substances together with a controlled diet and physical exercise. Even with these measures, the daily necessity for several insulin injections can be painful both physically and mentally, whereas the synthetic therapeutic substances used over the long term often have side effects. For those reasons, the creation and development of a new class of pharmaceuticals for treatment of DM in the 21st century would be extremely desirable. In the last half of the 20th century, investigations of the relationships among diseases and micronutrients, such as iron, copper, zinc, and selenium, have been numerous. Research into the development of metallopharmaceuticals involving the platinum-containing anticancer drug, cisplatin, and the gold-containing rheumatoid arthritis drug, auranofin, has also been widespread. Such important findings prompted us to develop therapeutic reagents based on a new concept to replace either insulin injections or the use of synthetic drugs. After many trials, we noticed that vanadium might be very useful in the treatment of DM. Before the discovery of insulin by Banting and Best in 1921 and its clinical trial for treating DM, the findings in 1899, in which orally administered sodium vanadate (NaVO(3)) was reported to improve human DM, gave us the idea to use vanadium to treat DM. However, it has taken a long time to obtain a scientific explanation as to why the metal ion exhibits insulin-mimetic or blood-glucose lowering effects in in vitro and in vivo experiments. After investigations from many perspectives involving biochemistry and bioinorganic chemistry, vanadyl sulfate (VOSO(4)) and its complexes with several types of ligands have been proposed as useful for treating DM in experimental diabetic animals. On the basis of a mechanistic study, this article reports on recent progress regarding the development of antidiabetic vanadyl complexes, emphasizing that the vanadyl ion and its complexes are effective not only in treating or relieving both types of DM but also in preventing the onset of DM.
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PMID:A new concept: the use of vanadium complexes in the treatment of diabetes mellitus. 1220 6

In the treatment of diabetes-induced pathologies, beneficial results have been obtained with administration of antioxidants. Selenium is an antioxidant and essential trace element in living organisms. The aim of this study was to investigate the possible effects of selenium on the structural alterations of the mandible due to diabetes. In this study thirty-nine Wistar rats were used and a control, a selenium given control, a diabetic and a selenium given diabetes groups were formed. Experimental diabetes was induced by a single i.p. injection (50 mg/kg) of streptozotocin (STZ). The diabetic + selenium and the control + selenium groups were injected with a daily dose of 5 micro mol/kg/day sodium selenite (i.p.) for 4 weeks while the diabetic and the control groups were injected with distilled water. Mandibles of all the animals were excised and examined at the 5th week. High blood glucose level and low body weight in the diabetic group were not significantly affected by selenium administration. Furthermore, a negligible increase in blood glucose level was observed in the selenium given control group. Densitometric analysis revealed a significant reduction in bone density and presence of resorption in the diabetic and the selenium given control groups as compared to the selenium given diabetes and the control groups. In X-ray diffraction analysis, the reduction in peak intensity of the reflected light in both the diabetic and the selenium given control groups indicated a possible alteration in the crystallinity or a poor crystalline substance. Histological investigation showed that there was progressive resorption, trabecular and cortical irregularity and vascular proliferation in the diabetic and the selenium given control groups, whereas a more healthy appearance was detected in the selenium given diabetes group. The results of this study suggest the positive effects of selenium on diabetes-induced structural alterations in the mandible. However, the unexpected results in the selenium given control group necessitate further studies on the mechanism of selenium effects in organisms.
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PMID:Effects of selenium on the structure of the mandible in experimental diabetics. 1222

Radiation hazards in outer space present an enormous challenge for the biological safety of astronauts. A deleterious effect of radiation is the production of reactive oxygen species, which result in damage to biomolecules (e.g., lipid, protein, amino acids, and DNA). Understanding free radical biology is necessary for designing an optimal nutritional countermeasure against space radiation-induced cytotoxicity. Free radicals (e.g., superoxide, nitric oxide, and hydroxyl radicals) and other reactive species (e.g., hydrogen peroxide, peroxynitrite, and hypochlorous acid) are produced in the body, primarily as a result of aerobic metabolism. Antioxidants (e.g., glutathione, arginine, citrulline, taurine, creatine, selenium, zinc, vitamin E, vitamin C, vitamin A, and tea polyphenols) and antioxidant enzymes (e.g., superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidases) exert synergistic actions in scavenging free radicals. There has been growing evidence over the past three decades showing that malnutrition (e.g., dietary deficiencies of protein, selenium, and zinc) or excess of certain nutrients (e.g., iron and vitamin C) gives rise to the oxidation of biomolecules and cell injury. A large body of the literature supports the notion that dietary antioxidants are useful radioprotectors and play an important role in preventing many human diseases (e.g., cancer, atherosclerosis, stroke, rheumatoid arthritis, neurodegeneration, and diabetes). The knowledge of enzymatic and non-enzymatic oxidative defense mechanisms will serve as a guiding principle for establishing the most effective nutrition support to ensure the biological safety of manned space missions.
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PMID:Free radicals, antioxidants, and nutrition. 1236 82

Apoptosis of retinal endothelial cells and pericytes is postulated to contribute to the development of retinopathy in diabetes. The goal of this study is to investigate diabetes-induced activation of retinal caspase-3, an apoptosis executer enzyme, in retina, and examine the effects of antioxidants on the activation. Caspase-3 activation was determined in the retina of alloxan diabetic rats (2-14 months duration) and in the isolated retinal capillary cells (endothelial cells and pericytes) by measuring cleavage of caspase-3 specific fluorescent substrate, and cleavage of caspase-3 holoenzyme and poly (ADP ribosyl) polymerase. Effect of antioxidants on the activation of caspase-3 was determined by feeding a group of diabetic rats diet supplemented with a comprehensive mixture of antioxidants, including Trolox, alpha-tocopherol, N-acetyl cysteine, ascorbic acid, beta-carotene and selenium for 2-14 months, and also under in vitro conditions by incubating isolated retinal capillary cells with antioxidants with wide range of actions. Caspase-3 was activated in the rat retina at 14 months of diabetes (P < 0.05 vs. normal), but not at 2 months of diabetes, and administration of antioxidants for the entire duration inhibited this activation. In the isolated retinal capillary cells incubated in 25 mM glucose medium, caspase-3 activity was increased by 50% compared to the cells incubated in 5 mM glucose (P < 0.02), and antioxidants or caspase-3 inhibitor inhibited this increase. Our results suggest that increased oxidative stress in diabetes is involved in the activation of retinal caspase-3 and apoptosis of endothelial cells and pericytes. Antioxidants might be inhibiting the development of diabetic retinopathy by inhibiting microvascular apoptosis.
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PMID:Diabetes-induced activation of caspase-3 in retina: effect of antioxidant therapy. 1244 25


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