Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0162275 (ketonuria)
 553 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetes mellitus (DM) was produced in 17 neonatal lambs by a single intravenous injection of alloxan monohydrate (150 mg/kg). All developed hyperglycemia (greater than 300 mg/100 ml) and glycosuria after 24 h, but none exhibited ketonuria or acidosis. Plasma insulin levels were reduced to about 20% of those appropriate for the plasma glucose levels. Glucose tolerance tests (intravenous) were also consistent with reduced insulin reserve. Measurements of left ventricular performance were obtained under constant hemodynamic conditions in 16 diabetics and did not differ from those in 10 normal lambs. However, myocardial uptake of glucose was sharply reduced and fatty acid uptake was less. Myocardial O2 consumption (MVO2) was unchanged. Coronary flow (CF) was significantly lower in the diabetics (P less than 0.001). Pressure-flow studies were also done and demonstrated a consistent reduction in CF at a given aortic pressure in DM compared with controls. These findings indicate that coronary vascular resistance is elevated in the lamb with DM, and this is not explained by a change in MVO2. Oxygen requirements of the diabetic hearts were satisfied by increased extraction.
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PMID:Coronary dynamics and myocardial metabolism in the diabetic newborn lamb. 46 2

Whereas short-term cold exposure depletes glycogen reserves, repeated and prolonged moderate exercise in a cold environment creates an energy deficit that is satisfied by an increased metabolism of depot fat. Factors contributing to the fat loss include an exercise-induced hypertrophy of lean tissue, a loss of energy through a cold-induced ketonuria, a stimulation of resting metabolism, increases in the energy cost of movement, and a lower yield of energy per litre of oxygen consumed. Biochemical explanations of the enhanced lipolysis include increased catecholamine secretion, altered sensitivity of catecholamine receptors, and decreases of circulating insulin. The enhanced fat loss with combinations of cold and exercise may be helpful in the therapy of obesity, although the response seems less well developed in women than in men. Moreover, there may be other objections to cold exposure in an older obese population. Short-term glycogen depletion has negative implications for the endurance competitor. Cold acclimation, by favoring an insulative response to cold, reduces glycogen depletion; endurance training may supplement this effect by enhancing the activity of fat-metabolizing enzymes.
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PMID:Fat metabolism, exercise, and the cold. 132 16

Blood oxygen transport, pH, acid-base status, urinary ketone level and urobilinogen were studied in 52 pregnant women in whom pregnancy ran a normal course and in 56 ones with a history of habitual abortions, treated for metabolic disorders. Signs of metabolic acidosis in the presence of respiratory alkalosis at the expense of pulmonary hyperventilation were detected in women with normal pregnancy. Follow-up of acid-base status and gases of blood, aciduria and ketonuria in pregnant women with a history of habitual abortions has revealed in them respiratory alkalosis signs presenting in hypoxemia and reduced oxygen saturation and ketonuria. Metabolic therapy included in combined therapeutic schemes for such patients actively influenced the processes of metabolic acidosis and ketonuria compensation, probably at the expense of its normalizing effect on intracellular metabolism. Metabolic therapy of pregnant women liable to spontaneous abortions, due to ovarian hypofunction had a marked antihypoxic effect, normalized the bicarbonate system status and was therefore conducive to improvement of oxygen transport to maternal tissues and the fetus.
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PMID:[Acid-base equilibrium and blood gases in pregnant women with habitual abortion after metabolic therapy]. 147 19

Iron overload is found clinically in such conditions as hemochromatosis and sideroblastic anemia, and after long term repeated transfusion in aplastic anemia. An animal model of iron overload was successfully developed in rats and rabbits by repeated intraperitoneal injections of ferric nitrilotriacetate (Fe3+-NTA). This procedure induced a diabetic state with hyperglycemia, ketonemia, glycosuria and ketonuria. Blood venesection on these rats reduced the iron load in the liver and pancreas, and ameliorated the general diabetic symptoms. A single injection of Fe3+-NTA in rats induced a temporary elevation in plasma iron concentration, lipid peroxidation in the perfused liver homogenate expressed by malondialdehyde (MDA) formation, blood GOT, GPT, ALP and gamma-GTP sequentially. Fe3+-NTA uptake in the liver caused membrane lipid peroxidation, and subsequently produced a transit liberation of liver cell enzymes, although the incorporated liver Fe3+-NTA was only 1% of the injected dosage (7.5 mg iron/kg BW) at 3 hr after injection. The direct toxic effect of Fe3+-NTA to living cells was examined using cultured normal rat liver parenchymal cells (RL-34). Marked cytolysis was found in cells exposed to more than 25 micrograms of iron through Fe3+-NTA/ml. At 50 micrograms iron of Fe3+-NTA/ml, most cells were lethally injured and the remaining cells were piled up and aggregated at 15 days. They grew on soft agar culture, and when inoculated subcutaneously to five newly born rats a subcutaneous tumor developed in all animals within three weeks. Lung metastases were found in three of five inoculated rats. A spin trapping technique with electron spin resonance (ESR) on Fe3+-NTA employing 5, 5-dimethyl-l-pyrroline-N-oxide (DMPO) yielded a spin adduct with three doublets (DMPO-Z) which corresponded to singlet oxygen. By ESR in the presence of H2O2, the Fe3+-NTA solution strongly generated hydroxyl radical. The production of active oxygen species by Fe3+-NTA solution may explain the toxicity and carcinogenicity of Fe3+-NTA. The majority of stainable iron in the iron overloaded tissue was hemosiderin (Hs). We tried to purify the Hs from multi-transfused human spleen by the method of Weir et al. The purified Hs did not show a DMPO-OH adducts in the presence of H2O2 and DMPO on ESR measurement. The Hs iron was solubilized with several biological ligands in an acidic state in the presence of a reducing reagent like glutathione. Solubilized Hs iron produced iron chelate complexes which resulted in OH radicals production in the presence of H2O2 in acidic conditions below pH 5.5.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Pathogenesis and mechanism of iron overload: ferric nitrilotriacetate, hemosiderin, active oxygen, and carcinogenesis]. 268 76

Oxidative damage plays an important role in the pathophysiology of diabetes and diabetic complications. Feline hemoglobin is uniquely susceptible to oxidative denaturation; therefore, Heinz body formation is a highly sensitive indicator of in vivo oxidative stress in this species. Heinz bodies also contribute to anemia. We investigated hematological and clinical biochemical changes in 30 cats with spontaneous diabetes mellitus (as compared to 15 healthy control cats) and evaluated the relationship of these changes to erythrocyte oxidative damage. Cats were categorized as ketoacidotic or nonketoacidotic based on their clinical presentation and the presence of urine ketones. Ketoacidotic cats had significantly (P = .0009) more Heinz bodies (28.3% +/- 9.1%) than nonketotic diabetic cats (6.5% +/- 1.60%) and healthy control cats (0.6% +/- 0.2%). Percent Heinz bodies in diabetic cats directly correlated with plasma beta-hydroxy-butyrate concentration (r = .622; P = .0002), as well as with serum chloride concentration (r = -0.576; P = 0.0009) and the number of monocytes (r = .536; P = .0023). Percent Heinz bodies were negatively correlated with erythrocyte glutathione concentrations. Erythrocyte membrane lipid peroxidation was slightly but not significantly increased in diabetic cats. There were no significant associations between percent Heinz bodies and degree of anemia, hyperglycemia, or glycohemoglobin. These data indicate that ketones are associated with oxidative hemoglobin damage in cats, and suggest that ketone metabolism, ie by cytochrome P450 2E1, may be a potential source of in vivo oxygen radical generation in animals with ketosis.
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PMID:Heinz body formation associated with ketoacidosis in diabetic cats. 789 59

A unique case of HAPE precipitating diabetic ketoacidosis in a previously undiagnosed Type 2 diabetic is reported. A 39-year-old male, previously well, was admitted at a hospital situated at a height of 3500 m with complaints of increasing breathlessness on effort, cough, and fever of short duration, 5 days after high altitude reascent. Examination at admission revealed a febrile (38 degrees C) patient with tachycardia (104/min), SaO2 was 82% (on supplemental oxygen), chest examination revealed bilateral crackles in all lung fields, and chest radiograph demonstrated bilateral fluffy heterogeneous opacities in all zones. He was diagnosed as suffering from high altitude pulmonary edema. The patient did not show adequate improvement despite conventional treatment for HAPE with supplemental oxygen and rest. Investigations revealed leucocytosis, and urinalysis revealed glycosuria and ketonuria. Subsequent arterial blood gas analysis revealed that acidemia and serum glucose levels were raised. He was thereafter managed as for HAPE and DKA and recovered in 2 weeks. The patient has been on regular follow-up with satisfactory glycemic control with oral hypoglycemic agents.
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PMID:Diabetic ketoacidosis in an undiagnosed diabetic precipitated by high altitude pulmonary edema. 1654 71

Canine diabetes mellitus (DM) is a common metabolic disorder with long term complications, most of which are caused by glycosylation of structural proteins, decreases in antioxidant concentrations, altered osmotic balance and hypoxia due to impaired oxygen transport. Previous studies have demonstrated that under hyperglycemic conditions canine erythrocytes undergo swelling, probably due to activation of the polyol pathway. The present work aimed to assess the plasma concentration of advanced glycation end (AGE) products, stable Amadori-products generated by non-enzymatic glycosylation of proteins and the intracellular concentration of sorbitol, produced by the activation of polyol pathway in 34 blood samples from diabetic dogs and in 14 controls. AGE products were significantly higher (p<0.01) in plasma from diabetic dogs compared with control animals. The sorbitol concentration in erythrocytes was also significantly higher in diabetic dogs and, in particular, in poorly compensated animals and in dogs with ketonuria. In five cases that were analysed before and after clinical improvement, sorbitol concentration was found to correlate with improvement. These results suggest that non-specific glycosylation is increased and that the polyol pathway is activated in diabetic dogs in a manner that is proportionate to the severity of disease. Moreover, the concentration of AGE products and sorbitol may be useful for monitoring the onset of diabetic complications and assessing the most appropriate therapeutic approaches for management of canine DM.
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PMID:Advanced glycation end products and sorbitol in blood from differently compensated diabetic dogs. 1763 69