Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A study was made of changes in the activity of erythrocyte antioxidant enzymes (superoxide dismutase and catalase) with regard to the blood level of glucose in children with insulin dependent diabetes mellitus and in vitro. A total of 83 children aged 3 to 14 with insulin dependent diabetes mellitus and 10 healthy adults were investigated. Catalase activity did not change whereas superoxide dismutase activity in decompensation of disease was significantly lower than that in its compensation. Experiments in vitro revealed that glucose, added to erythrocytes of donors in the concentration of 20 mumol/l, caused a double decrease in the activity of both enzymes at 37 degrees C for 2 h as compared to control test values. Thus glucose was shown to be able to act as a modifier of enzymes, and the state of antioxidant protection of erythrocytes depended on its blood level.
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PMID:[Effect of hyperglycemia on the status of antioxidant protection of erythrocytes in children with diabetes mellitus and in vitro]. 194 99

The aim of our research was elucidation of a relationship between red cell membrane lipid peroxidation (LPO) and antioxidant defense enzymes, on the one hand, and the age, disease duration, and presence of vascular complications in patients with type I diabetes mellitus, on the other. The possibility of correcting red cell peroxide status with human insulin preparations was investigated. Red cell membrane LPO was found increased more than twofold and antioxidant defense enzymes activities virtually unchanged vs. controls in 16 patients with diabetes aged 20 to 43. These characteristics of red cell peroxidation status do not depend on patients' age, disease standing, or presence of vascular complications. A twelve-week therapy with biosynthetic insulin resulted in complete normalization of LPO processes in patients with angiopathies aged under 35 and with disease standing of less than 10 years. In diabetics with angiopathies aged over 35 and disease standing of more than 10 years red cell MDA level reduced under the effect of therapy with human insulin preparations but was still increased vs. that in healthy donors by 1.5 times. Red cell GP and SOD activities reduced in the course of insulin therapy in all the examined groups of diabetics. Catalase activity increased by approximately 50% in patients with angiopathies, those aged over 35, and a disease standing of more than 10 years under the effect of insulin. In the rest groups of patients catalase activity did not differ from its initial level. Our results permit us recommending besides human insulin preparations antioxidant therapy for patients with vascular complications, those aged over 35, and a disease standing of more than 10 years.
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PMID:[Effect of biosynthetic insulin on lipid peroxidation in erythrocyte membranes in patients with type I diabetes mellitus]. 807 92

Oxygen free radicals produced during normal aerobic metabolism have been implicated in several pathophysiological mammalian processes. The importance of free radical-mediated fatty acid oxidation has received much attention. The generation of active oxygen species may lead to lipid peroxidation and formation of reactive products, which may be involved in severe damage of cell molecules and structures. Free radical metabolism in pregnancy and in diabetes mellitus is still unclear. To add new insights to the question, changes in lipid peroxidation products and activities of three antioxidant enzymes: catalase (CAT), glutathione peroxidase (GPX) and superoxide dismutase (SOD) in maternal red blood cells haemolysates were evaluated in pregnant women with insulin-dependent diabetes mellitus (IDDM-PW) and in healthy pregnant women (HPW). Healthy non-pregnant women were the control group for IDDM-PW and HPW, respectively. Pregnancy provoked an increase of lipoperoxidation products and an high SOD activity since early pregnancy, while CAT and GPX activities did not change during gestation. IDDM-PW showed higher content of lipoperoxidation breakdown products and lower SOD activity at each trimester, if compared with HPW; moreover, a slight increase of CAT and SOD activity is reported during late diabetic pregnancy. IDDM-PW were in very good metabolic control at time of sampling. The variations reported suggest an easier membrane lipoperoxidability and, consequently, an easier membrane damage during diabetic gestation.
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PMID:Lipid peroxidation products and antioxidant enzymes in red blood cells during normal and diabetic pregnancy. 811 55

In vivo and in vitro data obtained in rodents indicate that beta-cells can trigger efficient repair mechanisms following non-lethal injury. Recent observations suggest that human pancreatic islets are more resistant than rodent islets to damage by alkylating agents, free oxygen radicals, nitric oxide and cytokines. This increased resistance to injury is associated with higher expression of heat shock protein 70, catalase and superoxide dismutase. These findings emphasise the potential relevance of beta-cell repair and/or defence mechanisms in the development of human IDDM.
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PMID:Beta-cell defence and repair mechanisms in human pancreatic islets. 881 35

The condition was studied on the antioxidant system (AOS)--the activities of catalase, concentration of tocoferoli and reduced glutathione--in 112 patients with type I diabetes mellitus during the course of treatment. It has been established that in decompensation of diabetes mellitus there is a striking deterioration of AOS the degree of which depends upon duration and severity of the illness as well as the presence of angiopathies. Employment in the combined treatment of the donator of sulphhydric groups unithiol and a naturally occurring antioxidant tocopheroli promoted normalization of parameters associated with AOS, diabetic angiopathies included.
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PMID:[Antioxidant system disorder in diabetic patients and the means for its normalization]. 907 82

In our present work we attempt to clarify the pro-, antioxidant status (redox status) of blood and the red blood cell (RBC) filtration changes in type 1 (insulin dependent diabetes mellitus = IDDM) diabetic patients, broadening our biochemical knowledge about the mechanism of disease. Further on we try to apply our observations in therapy. Our studies on enzymes and the pro- and antioxidant status in type 1 diabetes are closely related to earlier works. Our studies on antioxidants have been extended deeper on redox conditions for example on the reduced and oxidized glutathione (GSH and GSSG) and glutathione reductase activity. The properties and changes of antioxidant enzyme activities (superoxide dismutase, glutathione peroxidase and catalase) as well as lipid peroxidation (LP) have been studied earlier without selecting the different type of human diabetics. At the same time the red blood cell filtration characteristics are compared also with normal values. The results of our studies confirmed the earlier findings that human diabetes is accompanied by a strong oxidative predominance (oxidative stress) in blood.
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PMID:Pro-, antioxidant and filtration changes in the blood of type 1 diabetic patients. 970 3

This study showed that citiolone (CIT), a free radical scavenger, significantly increased superoxide dismutase (P < 0.001 vs. untreated NOD, NMMA-treated, and silica-treated animals), catalase (P < 0.01 vs. untreated NOD), and glutathione peroxidase (P < 0.001 vs. untreated NOD and C57BL6/J) values. Silica treatment was capable of counteracting the plasma antioxidant capacity (TRAP) decrease observed in untreated NOD mice, although it did not block the blood glucose rise and insulitis progression in type 1 diabetes significantly. Conversely, early silica administration was able to deplete macrophages (as demonstrated by immunocytochemistry) and to block the rise in blood glucose levels and insulitis progression significantly. Silica-treated animals in this study showed the highest TRAP levels, demonstrating that depletion of macrophages also was able to improve the antioxidant status. This study suggested that macrophages are essential for type 1 diabetes development and showed that they also are involved when the antioxidant status is affected. The reported findings are significant in view of previous studies indicating that oxygen and/or nitrogen free radicals contribute to the islet beta-cell destruction in type 1 diabetes animal models.
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PMID:Macrophages and antioxidant status in the NOD mouse pancreas. 982 94

Pancreatic beta cells are sensitive to reactive oxygen species and this may play an important role in type 1 diabetes and during transplantation. Beta cells contain low levels of enzyme systems that protect against reactive oxygen species. The weakest link in their protection system is a deficiency in the ability to detoxify hydrogen peroxide by the enzymes glutathione peroxidase and catalase. We hypothesize that the deficit in the ability to dispose of reactive oxygen species is responsible for the unusual sensitivity of beta cells and that increasing protection will result in more resistant beta cells. To test these hypotheses we have produced transgenic mice with increased beta cell levels of catalase. Seven lines of catalase transgenic mice were produced using the insulin promoter to direct pancreatic beta cell specific expression. Catalase activity in islets from these mice was increased by as much as 50-fold. Northern blot analysis of several tissues indicated that overexpression was specific to the pancreatic islet. Catalase overexpression had no detrimental effects on islet function. To test whether increased catalase activity could protect the transgenic islets we exposed them to hydrogen peroxide, streptozocin, and interleukin-1beta. Fifty-fold overexpression of catalase produced marked protection of islet insulin secretion against hydrogen peroxide and significantly reduced the diabetogenic effect of streptozocin in vivo. However, catalase overexpression did not provide protection against interleukin-1beta toxicity and did not alter the effects of syngeneic and allogenic transplantation on islet insulin content. Our results indicate that in the pancreatic beta cell overexpression of catalase is protective against some beta cell toxins and is compatible with normal function.
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PMID:Overexpression of catalase provides partial protection to transgenic mouse beta cells. 1051 87

Most viral gene delivery syslems utilized to date have demonstrated significant limitations in practicality and safety due to the level and duration of recombinant transgene expression as well as their induction of host immunogenicity to vector proteins. Recombinant adeno-associated virus (rAAV) vectors appear to offer a vehicle for safe, long-term therapeutic gene transfer; factors afforded through the propensity of rAAV to establish long-term latency without deleterious effects on the host cell and the relative non-immunogenicity of the virus or viral expressed transgenes. The principal historical limitation of this vector system, efficiency of rAAV-mediated transduction, has recently observed a dramatic increase as the titer, purity, and production capacity of rAAV preparations have improved. In terms of systems that could benefit from such improvements, rAAV gene therapy to enhance solid organ transplantation would appear an obvious choice with islet transplantation forming a promising candidate due to the ability to perform viral transductions ex vivo. Currently, islet transplantation can be used to treat type 1 diabetes yet persisting alloimmune and autoimmune responses represent major obstacles to the clinical success for this procedure. The delivery of transgenes capable of interfering with antigenic recognition and/or cell death [e.g., Fas ligand (FasL), Bcl-2, Bcl-XL] as well as imparting tolerance/immunoregulation [e.g., interleukin(IL)-4, IL-10, transforming growth factor (TGF)-beta], or cytoprotection [e.g., heme oxygenase-1 (HO-1), catalase, manganese superoxide dismutase (MnSOD)] may prevent recurrent type 1 diabetes in islet transplantation and offer a promising form of immunotherapy. Research investigations utilizing such systems may also provide information vital to understanding the immunoregulatory mechanisms critical to the development of both alloimmune and autoimmune islet cell rejection mechanisms and recurrent type 1 diabetes.
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PMID:Adeno-associated virus (AAV) as a vehicle for therapeutic gene delivery: improvements in vector design and viral production enhance potential to prolong graft survival in pancreatic islet cell transplantation for the reversal of type 1 diabetes. 1189 74

Increased lipid peroxidation (LPO) and reduced antioxidant activity may contribute to the development of complications in pregnancy. The present study discusses the possibility of LPO and antioxidant activity in both maternal and umbilical cord blood as an indicator of oxygen radical activity. For this aim, pregnancies with hypertension and pre-eclampsia, diabetes mellitus (insulin dependent diabetes mellitus and gestational diabetes mellitus), oligohydramnios and abruptio placentae, as well as a healthy control group, were subjected in the present study. Simultaneous determination of glutathione S-transferase (GST), selenium dependent glutathione peroxidase (Se-GPx), catalase (CAT) activities and thiobarbituric acid reactive-substances (TBARs) levels were carried out in maternal erythrocyte and plasma in the antenatal period (in the third trimester) and immediately after the delivery. The same oxidative stress-related parameters were determined in umbilical cord blood as well. Erythrocyte GST activity was significantly increased in insulin-dependent diabetic pregnancy (IDDP) when compared to the control (P<0.05). Erythrocyte Se-GPx activity was found to be significantly increased in hypertensive preeclamptic pregnancy (HPP) (P<0.05) and in IDDP (P<0.05). Alterations in enzyme activities were accompanied by a simultaneous significant increase in the levels of TBARs in plasma samples of HPP (P<0.05), and IDDP (P<0.05). Enzyme activities were found to be significantly lower in cord blood samples than the maternal values, except GST. This enzyme represents about two- to threefold higher activity than those of the maternal activity in uncomplicated and complicated groups. Cord blood erythrocyte and plasma Se-GPx and CAT activities were decreased significantly in the HPP group when compared to the maternal value (P<0.05). Cord blood erythrocyte CAT activity was significantly decreased in the HPP group compared to the control (P<0.05). Cord blood TBARs levels were significantly lower than the before deliveries maternal value in the HPP group (P<0.05). No difference was detected between umbilical cord blood and maternal blood TBARs levels after delivery. The results of the present study suggest that oxidative stress and subsequent lipid peroxidation accompany the complications of hypertension, preeclampsia and diabetes mellitus in pregnancy. Maternal erythrocyte GST activity seems to be a sensitive indicator of oxidative stress in IDDP before delivery. The same enzyme can be used in cord blood as a biomarker of oxidative stress upon a sudden increase in oxygenation during delivery. These multiparameter biomarkers can also be used in monitoring the efficiency of antioxidant supplementation in complicated pregnant women, as has recently been suggested for diabetic and preeclamptic pregnancies.
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PMID:Circulating biomarkers of oxidative stress in complicated pregnancies. 1259 16


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