Masterclass series in peripheral arterial disease

Abstract

The incidence of type 2 diabetes is increasing at an alarming rate; epidemiological studies indicate that by the year 2010 there will be 300 million people with type 2 diabetes worldwide. The rate of increase is highest in Asia and among young adults with obesity. On average, patients with diabetes live 5À10 years less than their non-diabetic counterparts, mainly because of accelerated atherosclerotic disease.A diagnosis of diabetes confers a two-to fourfold increased risk of intermittent claudication and a 10À16-fold increase in the lifetime risk of a lower limb amputation.

Divergent effects of low-O2tension and iloprost on ATP release from erythrocytes of humans with type 2 diabetes: implications for O2supply to skeletal muscle

“…It is estimated that in 2010 there will be in excess of 300 million cases of DM2 worldwide making this disease a major public health challenge (4). A significant complication of DM2 is impaired vascular function that contributes to a fourfold increased risk for claudication (4) and as much as a 16-fold increased risk for lower limb amputation (12,30,43).…”

“…It is estimated that in 2010 there will be in excess of 300 million cases of DM2 worldwide making this disease a major public health challenge (4). A significant complication of DM2 is impaired vascular function that contributes to a fourfold increased risk for claudication (4) and as much as a 16-fold increased risk for lower limb amputation (12,30,43). Although individuals with DM2 have an increased incidence of atherosclerosis in largeconduit vessels (4,30), there is extensive evidence that microvascular circulatory control is also abnormal in humans with DM2 (23,24,27,35).…”

“…A significant complication of DM2 is impaired vascular function that contributes to a fourfold increased risk for claudication (4) and as much as a 16-fold increased risk for lower limb amputation (12,30,43). Although individuals with DM2 have an increased incidence of atherosclerosis in largeconduit vessels (4,30), there is extensive evidence that microvascular circulatory control is also abnormal in humans with DM2 (23,24,27,35). Although direct studies of the skeletal muscle microcirculation are not possible in humans, such studies have been performed in several animal models of diabetes and reveal reduced convective O 2 delivery and diffusive O 2 transport that could contribute to a failure of the skeletal muscle vasculature to deliver appropriate amounts of O 2 to meet metabolic need both at rest and during exercise (2,13,34).…”

Synthesis and Evaluation of Novel Cyclopropane Nucleoside as Potential Tube Formation Agents

“…Hence, they are used only in treatments administered via injection or gene transfection approaches. [1][2][3] Therefore, we synthesized the first low-molecularweight angiogenesis promoter, 2-chloro-carbocyclic oxetanocin A (2-Chloro-C.OXT-A; COA-Cl, 1a, racemate, Fig. 1), [4][5][6][7][8] with a molecular weight (MW) of 284 that is suitable for pharmaceutical use via percutaneous and transmucosal absorption.…”

Synthesis and Evaluation of Novel Carbocyclic Oxetanocin A (COA-Cl) Derivatives as Potential Tube Formation Agents

“…Hence, they are used only in treatments administered by injection or gene transfection approaches. [1][2][3] We synthesized an angiogenesis promoter 2-chlorocarbocyclic oxetanocin A (COA-Cl), (1a, racemate) ( Fig. 1), which is the first low-molecular weight active compound in this class.…”