Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous work has shown a reduction in cephaloridine nephrotoxicity in a diabetic rat model. The following studies examined in vitro cephaloridine toxicity in renal slices from normoglycemic and diabetic Fischer 344 rats. Diabetes was induced by acute intraperitoneal injection of 35 mg/kg streptozotocin. Renal cortical slices were isolated from normoglycemic and diabetic animals. Tissues were exposed to 0-5 mM cephaloridine for 15-120 min. Pyruvate-directed gluconeogenesis was diminished in all groups exposed to 2-5 mM cephaloridine for 60-120 min. Leakage of lactate dehydrogenase (LDH) was apparent only in the normoglycemic group in the presence of 4-5 mM cephaloridine for 120 min. LDH leakage was not increased at any cephaloridine concentration in the diabetic tissue. Total glutathione levels were compared in renal cortical slices exposed to cephaloridine for 30-120 min. Baseline values for glutathione were comparable between normoglycemic and diabetic tissue suggesting that the mechanism for reduced toxicity was not due to higher glutathione levels in diabetic tissue. Total glutathione levels were diminished more rapidly in normoglycemic than diabetic tissue by incubation with 5 mM cephaloridine. Comparison of cephaloridine accumulation indicated that diabetic tissue accumulated less cephaloridine than the normoglycemic group when tissues were incubated with 0-2 mM cephaloridine. However, renal slice accumulation was similar between normoglycemic and diabetic groups following in vitro incubation with 4-5 mM cephaloridine. These results suggest that the mechanism for reduced in vitro cephaloridine toxicity in diabetic tissue cannot be limited to differences in accumulation and must include an unidentified cellular component.
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PMID:Cephaloridine in vitro toxicity and accumulation in renal slices from normoglycemic and diabetic rats. 929 92

Changes of enzyme activities in the myocardium of rats from 6 different experimental groups (normal rats, diabetic rats, hypoxic diabetic rats, each with and without Ginkgo biloba extract treatment) were measured by using both cytophotometric and biochemical methods. The activity of succinate dehydrogenase, a marker of oxidative capacity, and of menadione-dependent glycerol-3-phosphate dehydrogenase and total lactate dehydrogenase, both markers of glycolytic capacity were measured to characterize changes of the metabolic profile in myocardium. A strong correlation between cytophotometric and biochemical data were found by linear regression analysis, justifying the use of cytophotometrical enzyme activity measurements in cells of organized tissue, where biochemistry cannot provide topographical information. The comparison of the results obtained from the different groups revealed the following: Enzyme activities in the myocardium of rats with streptozotocin-induced diabetes were significantly increased by 10-30% as compared to the normal myocardium. This effect was interpreted as a metabolic compensation of the diabetic heart with reduced performance. When diabetic rats were exposed to acute hypoxia of 20 min duration, enzyme activities decreased under the normal level, to 56% of the succinate dehydrogenase activity, to 87% of glycerol-3-phosphate dehydrogenase activity and to 69% of lactate dehydrogenase activity. Treatment of rats with the oxygen radical scavenger Ginkgo biloba extract (EGb 761) over 3 months resulted primarily in an increase by 10% of oxidative capacity and in a decrease by 30% of glycolytic capacity. Under diabetic conditions a shift to more glycolytic metabolism was observed by increasing the glycolytic activity by 39% and remaining the oxidative activity.
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PMID:The correlation of cytophotometrically and biochemically measured enzyme activities: changes in the myocardium of diabetic and hypoxic diabetic rats, with and without Ginkgo biloba extract treatment. 938 12

Aminoguanidine, a nucleophilic hydrazine, has been shown to be capable of blocking the formation of advanced glycation end products. It reduces the development of atherosclerotic plaques and prevents experimental diabetic nephropathy. We have found that aminoguanidine is also quite potent at inhibiting semicarbazide-sensitive amine oxidase (SSAO) both in vitro and in vivo. The inhibition is irreversible. This enzyme catalyses the deamination of methylamine and aminoacetone, which leads to the production of cytotoxic formaldehyde and methylglyoxal, respectively. Serum SSAO activity was reported to be increased in diabetic patients and positively correlated with the amount of plasma glycated haemoglobin. Increased SSAO has also been demonstrated in diabetic animal models. Urinary excretion of methylamine is substantially increased in the rats following acute or chronic treatment with aminoguanidine. Urinary methylamine levels were substantially increased in streptozotocin (STZ)-induced diabetic rats following administration of aminoguanidine. The non-hydrazine SSAO inhibitor (E)-2-(4-fluorophenethyl)-3-fluoroallylamine hydrochloride (MDL-72974A) has been shown to reduce urinary excretion of lactate dehydrogenase (an indicator of nephropathy) in STZ-induced diabetic rats. Formaldehyde not only induces protein crosslinking, but also enhances the advanced glycation of proteins in vitro. The results support the hypothesis that increased SSAO-mediated deamination may be involved in structural modification of proteins and contribute to advanced glycation in diabetes. The clinical implications for the use of aminoguanidine to prevent glycoxidation have been discussed.
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PMID:Aminoguanidine inhibits semicarbazide-sensitive amine oxidase activity: implications for advanced glycation and diabetic complications. 938 14

Recent studies suggest that Alzheimer's disease and non-insulin-dependent (type 2) diabetes mellitus may share a common cell death mechanism, related to the toxicity of beta-amyloid (Abeta) and amylin, respectively. Both Abeta and amylin cause apoptosis in different cell culture systems, which may be related to the amyloidogenic properties of these peptides. We have further characterized the actions of a variety of Abeta peptides (Abeta25-35, Abeta1-40, Abeta1-42), human amylin and rat amylin (which does not form fibrils) on undifferentiated PC12 cells. Although all peptides except rat amylin compromised mitochondrial function as assessed by MTT reduction, only human amylin decreased cell viability at a concentration of 10 microM, as measured by lactate dehydrogenase release or trypan blue exclusion assay. The cell death caused by human amylin was determined to be predominantly of an apoptotic nature, with a possibility of a portion of necrotic cell death, which was not accompanied by increased expression of c-Jun or c-Fos inducible transcription factors.
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PMID:Acute application of human amylin, unlike beta-amyloid peptides, kills undifferentiated PC12 cells by apoptosis. 946 71

Rapid progress in the molecular technology has stimulated attempts to establish DNA diagnosis of human diseases. However, advances in technology have led to improvements at the research level but not in routine laboratory work because only few laboratory tests are covered by medical insurance; the methodologies cannot be easily applied to routine work; and the equipment and reagents are relatively expensive. This paper provides an overview of recent progress in DNA diagnosis and my experience in the DNA diagnostic field. I started working in the DNA diagnostic field in January 1988 with research on mutation analysis of lactate dehydrogenase subunit deficiency. I worked in Dr. Steven Li's laboratory at the National Institutes of Health in North Carolina and discussed with him about screening the patient's genomic library instead of using PCR because PCR was not adequate for mutation analysis. We successfully completed the mutation analysis and I returned to Japan. Thereafter, PCR has been increasingly improved and is now applicable to mutation analysis. Currently, amplification is essential for many DNA diagnostic technologies. The Human Genome Project has progressed and will be finished around 2002. In this process, DNA diagnosis will play an important role in the clinical laboratory. Common diseases, such as atherosclerosis, diabetes mellitus, hypertension and so on, have also been analyzed and the responsible genes will have been identified. Each laboratory should have a specialty and characteristic, and should be ready to help and assist each other via a network. Network communication is clearly needed by laboratories in the future.
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PMID:[The recent progress and future prospects of diagnostic DNA testing--experience in DNA analysis of serum enzymes]. 952 32

Oligo-elements such as zinc (Zn), selenium (Se) and copper (Cu) have a significant influence on the function of the immune system. Various immunological and inflammatory changes are known to occur in patients undergoing cardiopulmonary bypass. The aim of this study was to evaluate changes in serum oligo-elements levels during and following cardiopulmonary bypass. The serum levels of Zn, Se and Cu were determined in 67 consecutive patients, with coronary artery disease admitted for coronary artery bypass grafting. Blood samples for oligo-elements, analysis were withdrawn into metal-free tubes just prior to the start of cardiopulmonary bypass; at 30, 60 and 90 min into cardiopulmonary bypass; following weaning from cardiopulmonary bypass; 30 min after termination of cardiopulmonary bypass; at 24 h; and on the 5th postoperative day. Trace elements analyses were performed using atomic absorption spectrophotometry. Interleukin 6 and 8, as well as serum albumin, creatine phosphokinase, lactate dehydrogenase and creatine phosphokinase-MB fractions were also analyzed. The mean age was 63 +/- 9 years and 91% (61) were men. The mean preoperative left ventricular function was 52 +/- 12%, Canadian Cardiovascular Society (CCS) angina class was 3.7 +/- 0.5 and 30% (20) of the operations were re-do's. All patients had normothermic cardiopulmonary bypass. Mean cardiopulmonary bypass-time was 85 +/- 31 min. One patient was lost for the recovery sampling (hospital mortality, 1.5%). Nine patients had a postoperative cardiac index < 2.0 liter/min per m2, which required pharmacological support and additional intra-aortic balloon pump in two of them. Other postoperative complications were few. There was a rapid depletion of S-selenium and S-Zn levels, which were halved at 30 min after cardiopulmonary bypass and remained low throughout the study period. The Cu/Zn ratio increased significantly at the start of cardiopulmonary bypass, which indicated an inflammatory reaction and was not normalized until the 5th postoperative day. Length of ischemia time, presence of diabetes. hypertension and hyperlipidemia did not influence the results, while a prolonged cardiopulmonary bypass-time > 120 min resulted in a higher Cu/Zn ratio than observed for shorter cardiopulmonary bypass-times. This indicates a more profound inflammatory response. Inflammatory parameters responded in the same manner as described earlier by others. These data indicate that severe loss of various oligo elements occur in patients undergoing coronary artery bypass grafting and suggests that a supplementary administration of zinc and perhaps also selenium could be appropriate during cardiopulmonary bypass.
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PMID:Inflammatory response and oligo-element alterations following cardiopulmonary bypass in patients undergoing coronary artery bypass grafting. 972 21

The study was aimed at evaluating changes in lens antioxidant status, glucose utilization, redox state of free cytosolic NAD(P)-couples and adenine nucleotides in rats with 6-week streptozotocin-induced diabetes, and to assess a possibility of preventing them by DL-alpha-lipoic acid. Rats were divided into control and diabetic groups treated with and without DL-alpha-lipoic acid (100 mg x kg body weight(-1) x day(-1), i.p.). The concentrations of glucose, sorbitol, fructose, myo-inositol, oxidized glutathione, glycolytic intermediates, malate, alpha-glycerophosphate, and adenine nucleotides were assayed in individual lenses spectrofluorometrically by enzymatic methods, reduced glutathione and ascorbate--colorimetrically, and taurine by HPLC. Free cytosolic NAD+:NADH and NADP+:NADPH ratios were calculated from the lactate dehydrogenase and malic enzyme systems. Sorbitol pathway metabolites were found to increase, and antioxidant concentrations were reduced in diabetic rats compared with controls. The profile of glycolytic intermediates (increase in glucose 6-phosphate and fructose 6-phosphate, decrease in fructosel,6-diphosphate, increase in dihydroxyacetone phosphate, 3-phosphoglycerate, phosphoenolpyruvate, pyruvate, and no change in lactate), and 5.9-fold increase in alpha-glycerophosphate suggest diabetes-induced inhibition of glycolysis. Free cytosolic NAD+:NADH ratios, ATP levels, ATP/ADP x inorganic phosphate (Pi), and adenylate charge were reduced in diabetic rats while free cytosolic NADP+:NADPH ratios were elevated. Diabetes-induced changes in the concentrations of antioxidants, key glycolytic intermediates, free cytosolic NAD+:NADH ratios, and energy status were partially prevented by DL-alpha-lipoic acid, while sorbitol pathway metabolites and free cytosolic NADP+:NADPH ratios remained unaffected. In conclusion, diabetes-induced impairment of lens antioxidative defense, glucose intermediary metabolism via glycolysis, energy status and redox changes are partially prevented by DL-alpha-lipoic acid. The findings support the important role of oxidative stress in lens metabolic imbalances in diabetes.
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PMID:Diabetes-induced changes in lens antioxidant status, glucose utilization and energy metabolism: effect of DL-alpha-lipoic acid. 986 11

About 50 mg of silver leaf (metallic silver) was given daily by mouth to 30 healthy volunteers for 20 days. A statistically significant hypophospholipidemic, hypotriglyceridemic, hypocholesterolemic and hypoglycemic effect was observed. This was accompanied by a less marked fall in total lipids and significant rise in HDL-cholesterol. In addition, a decrease in plasma enzymes - alkaline phosphatase (ALP), glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), creatine phosphokinase (CPK), gamma glutamyl transpeptidase (GGT) and lactate dehydrogenase (LDH) was noted. This was statistically significant for all enzymes except CPK. The safety of ingested silver foil is indicated by absence of pathology in urine and unaltered levels of protein and albumin in the plasma. These observations suggest that silver could be beneficial in conditions like diabetes mellitus, obesity and atherosclerosis.
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PMID:Effect of silver leaf on circulating lipids and cardiac and hepatic enzymes. 1023 75

Urinalysis was carried out in 231 inpatients with alcohol dependence syndrome (215 males and 16 females). Fifty-nine patients (25.5%) showed proteinuria, 97 (42.0%) showed glucosuria, and 62 patients (26.8%) showed hematuria on admission. A total of 135 out of 231 patients (58.4%) showed abnormal urinalysis. Proteinuria was related to high blood pressure, high serum glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, lactate dehydrogenase, uric acid, and triglyceride levels, and high urinary amylase concentration. Glucosuria was related to high serum glutamic-oxaloacetic transaminase concentration and a history of gastrectomy. Hematuria was related to high age and high urinary amylase levels. By chi-square test, there was a significant correlation between proteinuria and hematuria (p < 0.001) and between hematuria and glucosuria (p < 0.001), but no correlation was found between proteinuria and glucosuria. The incidence of diabetes mellitus was 10.8% (25 out of 231 patients), but transient hyperglycemia was observed in some patients without diabetes mellitus on admission. Elevated hemoglobin A1, hemoglobin A1c, and fructosamine concentrations were observed in patients with either impaired glucose tolerance or transient hyperglycemia, which suggested the presence of persistent hyperglycemia before admission. On discharge, only 12 out of 198 patients (6.1%) showed abnormal urinalysis. We report that heavy ethanol consumption induces transient abnormal urinalysis results in Japanese alcoholics.
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PMID:Induction of transient proteinuria, hematuria, and glucosuria by ethanol consumption in Japanese alcoholics. 1039 97

The protective effect of taurine in model in vitro diabetic cataract and the mechanism of this effect were investigated in isolated rat lenses. Isolated rat lenses were incubated in medium 199 in elevated glucose (55.6 m m) with taurine (5 m m). Taurine concentrations in the lenses were determined by amino acid analysis. Accumulative leakage of the intracellular enzyme lactate dehydrogenase (LDH) was used to estimate damage to the lens, as previously reported. In the clear lenses, prior to vacuole formation, after 1 or 2 days of incubation, the taurine and amino acids in lenses decreased progressively in concentration. In lenses incubated with 5 m m taurine, the level of taurine was increased towards that of control lenses. In taurine-treated lenses LDH leakage was significantly decreased, and lens clarity was maintained, similarly to that found previously for vitamin C and lipoic acid. To test whether taurine has similar antioxidant activity, we tested its ability to decrease luminol luminescence generated by (1) superoxide from hypoxanthine/xanthine oxidase and (2) peroxide from diluted glucose/glucose oxidase. For either superoxide or peroxide, the luminescence was decreased to zero, as a function of increasing taurine concentration, at 30 m m, approximately the physiological concentration of taurine in the lens. Spin trapping confirmed that taurine scavenged superoxide. This is consistent with a role for taurine as an important antioxidant protecting the lens against oxidative insults. Amino acids also had antioxidant activity in this assay, and as a group, when all activities were summed, their loss also contributed significantly to the antioxidant loss. Taken in conjunction with Wolff and Crabbe's observation of increased free radical generation by glucose auto-oxidation in diabetes, this suggests a push-pull mechanism for increased oxidative stress in diabetic cataract, involving both increased free radicals and decreased radical scavenging antioxidants.
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PMID:Modelling cortical cataractogenesis 22: is in vitro reduction of damage in model diabetic rat cataract by taurine due to its antioxidant activity? 1047 37


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