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Aldose Reductase Inhibitor (aldose + reductase_inhibitor)
Selected AbstractsStratified analyses for selecting appropriate target patients with diabetic peripheral neuropathy for long-term treatment with an aldose reductase inhibitor, epalrestatDIABETIC MEDICINE, Issue 7 2008N Hotta Abstract Aims The long-term efficacy of epalrestat, an aldose reductase inhibitor, in improving subjective symptoms and nerve function was comprehensively assessed to identify patients with diabetic peripheral neuropathy who responded to epalrestat treatment. Methods Stratified analyses were conducted on data from patients in the Aldose Reductase Inhibitor,Diabetes Complications Trial (ADCT). The ADCT included patients with diabetic peripheral neuropathy, median motor nerve conduction velocity , 40 m/s and with glycated haemoglobin (HbA1c) , 9.0%. Longitudinal data on HbA1c and subjective symptoms of the patients for 3 years were analysed (epalrestat n = 231, control subjects n = 273). Stratified analyses based on background variables (glycaemic control, grades of retinopathy or proteinuria) were performed to examine the relationship between subjective symptoms and nerve function. Multiple logistic regression analyses were conducted. Results Stratified subgroup analyses revealed significantly better efficacy of epalrestat in patients with good glycaemic control and less severe diabetic complications. In the control group, no improvement in nerve function was seen regardless of whether symptomatic benefit was obtained. In the epalrestat group, nerve function deteriorated less or improved in patients whose symptoms improved. The odds ratio of the efficacy of epalrestat vs. control subjects was approximately 2 : 1 (4 : 1 in patients with HbA1c , 7.0%). Conclusion Our results suggest that epalrestat, an aldose reductase inhibitor, will provide a clinically significant means of preventing and treating diabetic neuropathy if used in appropriate patients. [source] The effect of sorbinil, an aldose reductase inhibitor, on aortic function in control and streptozotocin-induced diabetic ratsAUTONOMIC & AUTACOID PHARMACOLOGY, Issue 1 2000D. J. Sellers 1 The present study investigates the effect of treatment of 14-day streptozotocin-diabetic rats with the aldose reductase inhibitor, sorbinil, on changes ex vivo in aortic vasoconstriction and vasodilation. 2 Maximum contractile responses and aortic sensitivity to phenylephrine were significantly enhanced in aortae from 14-day diabetic rats, in accordance with our previous data. 3 Endothelium-dependent relaxations to carbachol were, in contrast, depressed, although endothelium-independent relaxations to forskolin and sodium nitroprusside were unaltered. 4 Sorbinil treatment of diabetic animals failed to prevent any of these diabetes-induced alterations in aortic function, and indeed exacerbated some of these alterations. In addition, sorbinil treatment caused altered aortic responses in control animals, which sometimes mirrored those found in diabetic animals. 5 It can be concluded that sorbinil may have actions in addition to, and independent of, polyol pathway inhibition. Thus, sorbinil may not be an effective tool for the investigation of aldose reductase inhibition within the vascular system of the rat. [source] The role of taurine in diabetes and the development of diabetic complicationsDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 5 2001Svend Høime Hansen Abstract The ubiquitously found ,-amino acid taurine has several physiological functions, e.g. in bile acid formation, as an osmolyte by cell volume regulation, in the heart, in the retina, in the formation of N -chlorotaurine by reaction with hypochlorous acid in leucocytes, and possibly for intracellular scavenging of carbonyl groups. Some animals, such as the cat and the C57BL/6 mouse, have disturbances in taurine homeostasis. The C57BL/6 mouse strain is widely used in diabetic and atherosclerotic animal models. In diabetes, the high extracellular levels of glucose disturb the cellular osmoregulation and sorbitol is formed intracellularly due to the intracellular polyol pathway, which is suspected to be one of the key processes in the development of diabetic late complications and associated cellular dysfunctions. Intracellular accumulation of sorbitol is most likely to cause depletion of other intracellular compounds including osmolytes such as myo -inositol and taurine. When considering the clinical complications in diabetes, several links can be established between altered taurine metabolism and the development of cellular dysfunctions in diabetes which cause the clinical complications observed in diabetes, e.g. retinopathy, neuropathy, nephropathy, cardiomyopathy, platelet aggregation, endothelial dysfunction and atherosclerosis. Possible therapeutic perspectives could be a supplementation with taurine and other osmolytes and low-molecular compounds, perhaps in a combinational therapy with aldose reductase inhibitors. Copyright © 2001 John Wiley & Sons, Ltd. [source] Diabetic neuropathy: therapies on the horizonJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 9 2009Danish Mahmood Abstract Objectives This is a review of emerging interventions from the recent preclinical and clinical literature that demonstrate the potential for effectiveness in the therapy of diabetic neuropathy (DN). DN is the most common complication of diabetes mellitus and up to 50% of patients with type 1 and type 2 forms have some or other form of neuropathy. The pathology of DN is characterized by progressive nerve fibre loss that gives rise to positive and negative clinical signs and symptoms such as pain, paraesthesiae and loss of sensation. Key findings There are very few drugs available to directly treat DN. Those that are clinically indicated provide symptomatic relief but do not repair or reverse underlying nerve damage. However, some agents are in clinical development that may support adult neurons and direct reparative processes after injury stages. Several disease modifying drugs such as aldose reductase inhibitors and protein kinase C inhibitors are in phase III development. Agents on the horizon include neurotrophic factors, growth factors, gene therapy, immunotherapy, poly(ADP-ribose) polymerase inhibitors and non-immunosuppressive immunophilin ligands. Summary Progress has been made toward understanding the biochemical mechanisms leading to diabetic neuropathy, and as a result, new treatment modalities are being explored. The pathogenesis, types and approaches for treating DN together with the newer therapeutic interventions on the horizon are discussed. [source] | ||||||||||