Protective Effects of a Coumarin Derivative in Diabetic Rats. Retinal microvascular cells play a crucial role in the pathogenesis of diabetic retinopathy. The endothelial effects of cloricromene, a novel coumarin derivative, on diabetic retinopathy induced by streptozotocin (STZ) in the rat were investigated. Cloricromene (10 mg/kg intraperitoneally) was administered daily in diabetic rats of cytokines, adhesion molecule, and nitric oxide synthase were observed in retina. Cloricromene treatment significantly lowered retinal TNFalpha, ICAM-1, VEGF, and eNOS. Furthermore, immunohistochemical analysis for VEGF, ICAM-1, nitrotyrosine (a marker of peroxynitrite), and tight junctions revealed positive staining in the retina from STZ-treated rats. The degree of staining for VEGF, ICAM-1
Platelet aggregation, ATP release and cytoplasmic Ca2+ movement: the effects of cloricromene. A placebo-controlled, double-blind, randomized, cross-over study was performed in 24 healthy volunteers. 12 volunteers received Cloricromene (100mg gastroresistant capsules twice a day) for 7 days, the other volunteers received identical placebo capsules. Subsequently, after a 7-day wash-out period , washed platelets stimulated with ADP and collagen, while aggregation in platelet-rich plasma (PRP) was studied using PAF, ADP and adrenaline as agonists. Consistent inhibition of aggregation and release induced by both ADP and collagen was observed in WB after Cloricromene administration. Similarly, Ca2+ flux was also inhibited after drug administration. Platelet aggregation in PRP was inhibited only
Effect of cloricromene on intermittent claudication. A randomized, double-blind, placebo-controlled trial in patients treated with aspirin: effect on claudication distance and quality of life. CRAMPS Investigator Group. Cloricromene Randomized Arteriopath The main aim of medical treatment for intermittent claudication (IC) is the reduction of mortality and morbidity from ischemic cardiovascular disease. However, symptomatic treatment with the aim of improving exercise performance and the overall quality of life may also be an important target of the clinical management of patients with intermittent claudication. Cloricromene, a drug with antithrombotic and anti-ischemic activities, has previously shown some promising results in patients with claudication. We have carried out a clinical trial
Effects of cloricromene, a coumarin derivative, on endotoxin-induced uveitis in Lewis rats. To investigate the effects of cloricromene, a coumarin derivative, in rats subjected to endotoxin-induced uveitis (EIU). Endotoxin uveitis was induced in male Lewis rats by a single footpad injection of 200 microg lipopolysaccharide (LPS). Cloricromene was topically applied to the rat eye twice at 1 hour and TNFalpha levels in the aqueous humor. Nitrite and nitrate production was also measured in the aqueous humor. The histopathology of the iris-ciliary body included inflammatory cell infiltration and nuclear modification of vessel endothelial cells. Cloricromene treatment reduced the inflammatory cell infiltration and improved histologic status of the ocular tissue. Immunohistochemical analysis for P
Inhibition of human monocyte adhesion to endothelial cells by the coumarin derivative, cloricromene. 1. The ability of the coumarin derivative cloricromene (8-monochloro-3-beta-diethylaminoethyl-4-methyl-7-ethoxy- carbonylmethoxycoumarin) to inhibit monocyte adhesion to human cultured umbilical vein endothelial cells (HUVEC) was investigated. 2. Cloricromene (10-200 microM) inhibited , in a concentration-dependent manner, the adhesion of both resting and activated monocytes to HUVEC. Significant inhibition was reached with drug concentrations ranging between 15 to 30 microM. 3. The inhibitory activity was, at least in large part, directed to monocytes since no inhibition was observed after selective preincubation of HUVEC with cloricromene and the drug maintained its effect also on monocyte
Cloricromene, a coumarine derivative, protects against collagen-induced arthritis in Lewis rats 1. The aim of the present study was to investigate the effects of cloricromene, a coumarine derivative, in rats subjected to collagen-induced arthritis. 2. Collagen-induced arthritis (CIA) was induced in Lewis rats by an intradermal injection of 100 microl of the emulsion (containing 100 microg challenged rats and the severity of CIA progressed over a 35-day period with radiographic evaluation revealing focal resorption of bone together with osteophyte formation in the tibiotarsal joint and soft tissue swelling. 4. The histopathology of CIA included erosion of the cartilage at the joint margins. Treatment of rats with cloricromene (10 mg kg(-1) i.p. daily) starting at the onset of arthritis (day
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