International journal of clinical pharmacology research
-
Int J Clin Pharmacol Res · Jan 2003
ReviewRole of advanced glycation end products (AGEs) and their receptor (RAGE) in the pathogenesis of diabetic microangiopathy.
Diabetic vascular complication is a leading cause of acquired blindness, end-stage renal failure, a variety of neuropathies and accelerated atherosclerosis, which could account for disabilities and high mortality rates in patients with diabetes. Chronic hyperglycemia is essentially involved in the pathogenesis of diabetic micro- and macrovascular complications via various metabolic derangements. In this review, we discuss the molecular mechanisms of diabetic retinopathy and nephropathy, especially focusing on advanced glycation end products (AGEs) and their receptor (RAGE) system. Several types of AGE inhibitors and their therapeutic implications in diseases, including diabetic microangiopathy, will be discussed in the next review article.
-
Repeated colics from urinary calculosis produce referred muscle hyperalgesia whose extent is proportional to the number of colics. The pathophysiology of this hyperalgesia was investigated in electrophysiological studies (spinal cord recordings) on an animal model of artificial ureteral calculosis. Stone-implanted rats show both visceral pain episodes and muscle hyperalgesia of the ipsilateral lumbar musculature; the extent of hyperalgesia is a function of the number of episodes. ⋯ These findings were proportional in extent to the number of visceral episodes presented by the rats before recordings; in cases of an extremely high number (> 50), several neurons also displayed abnormal activity, i.e. permanent short rhythmic bursts. These changes reflect a state of central sensitization and are probably due to the abnormal inflow from the affected ureter which facilitates the central effect of muscular input, thus accounting for the referred hyperalgesia. The degree of sensitization appears to be a function of the repetition of the visceral afferent barrage.