Current Medicinal Chemistry - Volume 10, Issue 15, 2003

Diabetic complications including nephropathy, neuropathy and cataract are the leading causes of end stage renal diseases and neurological disorders, respectively. The annual cost for patients with diabetes-related renal diseases and neurological disorder exceeds several billion dollars. Recent epidemiologic studies suggest that genetic factors play an important role in the pathogenesis of diabetic complications. Indeed, Read More

In spite of the significant developments in antidiabetic therapy, diabetic complications, particularly seen in long-term diabetes, continue to be seriously deleterious. Various types of diabetic complications affecting different systems in the body have been reported. The clinical course of the disease is largely determined by those complications. Therefore, an important area is obviously prevention or treatment of the disabling Read More

Aldose reductase [ALR2; EC 1.1.1.21], a key enzyme of polyol pathway, catalyzes NADPH-dependent reduction of glucose to sorbitol (Sorbitol pathway), and an excessive accumulation of intracellular sorbitol found in various tissues of diabetic animals and in cells cultured under high glucose conditions has been proposed to be an important factor for the pathogenesis of diabetic complications. The only strategy shown Read More

Aldose reductase (AR) is an NADPH-dependent enzyme that catalyses the reduction of the aldehyde to the corresponding alcohols. Diabetic complications including neuropathy, nephropathy, cataracts and retinopathy are considerately caused by accumulation of sorbitol, which is produced from glucose by AR in polyol pathway. The aim of AR inhibitor therapy is to normalize the elevated flux of blood and sorbitol th Read More

Diabetes Mellitus is an increasing concern, worldwide in terms of health. Long-term diabetes often leads to secondary diseases such as cataract, retinopathy, neuropathy, nephropathy, and cardiovascular diseases. The enzyme aldose reductase (AR) has been implicated in the pathogenesis of some of these diseases and inhibitors of AR (ARIs) were effective in preventing some of the diabetic complications in animal models. Ho Read More

Diabetes is a major cause of mortality and morbidity due to the long term microvascular complications of this disease. There is now convincing evidence to show that genetic factors together with elevated blood glucose play an important role in the susceptibility to diabetic nephropathy as well as retinopathy. The polyol pathway is thought to play an important role in the pathogenesis of diabetic microvascular complications. Read More

Aldose-, aldehyde and renal specific oxido reductase (RSOR) belong to the family of aldo-keto reductases (AKRs). They are monomeric (α / β)8-barrel proteins with a molecular weight ranging from 30 to 40 kDa, and at present include more than 60 members. Except for RSOR, they are expressed in a wide variety of animal and plant species and in various tissues. They catalyze NADPHdependent reduction of various alip Read More

Protein tyrosine phosphatase 1B (PTP1B) has been implicated as one of the key negative regulators of insulin and leptin signal transduction pathways. PTP1B deficient mice are more sensitive to insulin, and have improved glycemic control and resistance to diet-induced obesity than the wild-type control mice. Inhibiting PTP1B action using antisense oligonucleotides and small molecule inhibitors represents novel therapeut Read More

A clear understanding of the mechanism of function of immune stimulatory adjuvants, which commonly accompany vaccines, is beginning to emerge. Recent investigations have demonstrated that Toll-like receptors (TLRs) are the critical link between the innate and the adaptive immunity. This link, which is normally activated as a result of collaboration between adjuvants and TLRs in triggering adaptive immunity, has been Read More

Preterm labour is a major cause of perinatal mortality and morbidity. However, during the past 40 years of clinical studies and despite the use of multiple therapeutic agents, the rate of preterm birth has not drastically declined. In 1991, it was estimated that in the US approximately 116,000 women admitted with acute episodes of preterm labour were treated each year with ritodrine, which is the first drug approved by the U Read More