It has been shown that hypercholesterolemia (HCh) exaggerates the microvascular dysfunction that is elicited by ischemia and reperfusion (I/R). The objective of this study was to determine whether oxidants contribute to the exaggerated inflammatory responses and enhanced albumin leakage observed in HCh rat mesenteric venules exposed to I/R (10 minutes of ischemia and 30 minutes of reperfusion)....

1. The transport of 6-thioguanine and 6-mercaptopurine has been studied with isolated jejunal loops of mouse small intestine. H.p.l.c. was used to identify and quantify the thiopurines and their metabolites in the serosal secretions. 2. When the lumen of the intestinal loops contained either 6-thioguanine or 6-mercaptopurine at a concentration of 1 mmol/l, the concentration of unmetabolized dru...

Lipofuscin was produced when HT29, a colon carcinoma cell line, was cultured in millimolar concentrations of xanthine and guanine but not in the presence of other bases. Using a simple assay developed to quantify the fluorescent pigment, it was found that maximum levels of lipofuscin were developed in 3 days. Methylxanthines that are not substrates of xanthine dehydrogenase, such as caffeine an...

Complement plays an important role in ischemia-reperfusion injury. We recently demonstrated that reoxygenation of hypoxic human umbilical vein endothelial cells (HUVECs) activated the classical complement pathway and augmented iC3b deposition. In the present study, we investigated the potential role of oxygen-derived free radicals, NF-kappaB and new protein synthesis in this model. HUVECs subje...

PURPOSE In addition to the inhibition of xanthine oxidase, allopurinol is known to act, dependent on the dose, as a free radical scavenger, an antioxidant, and a "scavenger" of hypochlorous acid. This activity was investigated using a model of lens-induced uveitis. METHODS Lipid peroxides (LPO) were determined in aqueous humor and in retinal tissue. Reduced and oxidized glutathione (GSH and G...

It has been postulated that oxygen-centered free radicals are produced in significant quantities upon reperfusion of ischemic myocardium and could cause the death of myocytes that are still reversibly injured at the end of ischemia ("reperfusion injury"). However, we have shown previously that anti-free radical therapies including superoxide dismutase (SOD) and inhibitors of xanthine oxidase di...

In this issue of Circulation,' Hori and colleagues report the results of using three antioxidant agents in an attempt to reduce ischemic injury in a coronary microembolization model. Repeated injections of 15-,um microspheres resulted in progressive microvascular obstruction, decreased function , and edema until the extent of embolization decreased flow to nearly zero (less than 0.08 ml/min/ g)...