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Effect of VULM 1457, an ACAT inhibitor, on serum lipid levels and on real time red blood cell flow in diabetic and non-diabetic hamsters fed high cholesterol-lipid diet.
Gen Physiol Biophys
December 2007
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, Kalinciakova 8, 832 32 Bratislava, Slovakia.
Acyl-coenzyme A: cholesterol O-acyltransferase (ACAT) catalyzes the formation of cholesterol/fatty acyl-coenzyme A esters. Accumulation of cholesterol esters leads to pathological changes connected with atherosclerosis. We have evaluated effects of a newly synthesized ACAT inhibitor, 1-(2,6-diisopropyl-phenyl)-3-[4-(4'-nitrophenylthio)phenyl] urea (VULM 1457), on serum lipid (cholesterol and triglycerides) levels and velocity of red blood cells (RBC) in non-diabetic and diabetic hamsters fed on high cholesterol-lipid (HCHL) diet during 3 months.
View Article and Find Full Text PDFThe myocardial infarct size-limiting and antiarrhythmic effects of acyl-CoA:cholesterol acyltransferase inhibitor VULM 1457 protect the hearts of diabetic-hypercholesterolaemic rats against ischaemia/reperfusion injury both in vitro and in vivo.
Eur J Pharmacol
December 2007
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, Odbojarov 10, 832 32 Bratislava, Slovak Republic.
The study was designed to characterise the influence of a novel acyl-CoA:cholesterol acyltransferase inhibitor, VULM 1457, on the severity of myocardial ischaemia-reperfusion injury in a model of diabetes mellitus and hypercholesterolaemia induced by co-administration of streptozotocin and a high fat-cholesterol diet. We used Langendorff-perfused rat hearts to measure the size of myocardial infarction after 30 min of regional ischaemia, followed by a 2-h reperfusion period, and open-chest rats were exposed to 6 min of ischaemia and 10 min of reperfusion to analyse ventricular arrhythmias. In addition to the high fat-cholesterol diet, VULM 1457 was administered to the diabetic-hypercholesterolaemic rats for 5 days.
View Article and Find Full Text PDFAdverse effects of herbicide MCPA on dogs in a 90 day toxicological study.
Neuro Endocrinol Lett
December 2006
Department of Toxicology and Pathology, VULM, a.s., Modra, Slovakia.
Objectives: This study was performed to investigate the toxicity of the herbicide MCPA after repeated treatment according to OECD No 409.
Methods: The herbicide MCPA was administrated to dogs of both sexes in daily doses: 0, 1, 5 and 15 mg/kg per os during 90 days. Clinical observations were recorded, opthalmoscopic, haematological, clinical chemistry parameters were investigated.
Protective effect of simvastatin and VULM 1457 in ischaemic-reperfused myocardium of the diabetic-hypercholesterolemic rats.
Pharmazie
September 2006
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, Bratislava, Slovak Republic.
This study examined the effects of simvastatin (10 mg/ kg) and VULM 1457 (50 mg/kg), an ACAT inhibitor, in the heart model of 6 min ischemia followed by 10 min reperfusion injury in the diabetic-hypercholesterolaemic (DM-HCH) rats. In the DM-HCH rats, the incidence of ventricular tachycardia (VT) had a tendency to be increased, while ventricular fibrillation (VF) occurred in all diseased rats (p < 0.01).
View Article and Find Full Text PDFThe ACAT inhibitor VULM1457 significantly reduced production and secretion of adrenomedullin (AM) and down-regulated AM receptors on human hepatoblastic cells.
Gen Physiol Biophys
December 2005
Institute of Experimental Pharmacology, Slovak Academy of Sciences, Dúbravská cesta 9, 841 04 Bratislava 4, Slovakia.
Acyl-CoA:cholesterol acyltransferase (ACAT) is an important enzyme in the pathways of cholesterol esterification. It has been shown that new ACAT inhibitor 1-(2,6-diisopropyl-phenyl)-3-[4-(4'-nitrophenylthio)phenyl] urea (VULM1457) significantly reduced atherogenic activity in animal experimental atherosclerosis. Proliferative hormone adrenomedullin (AM) has been shown to be released in response to hypoxia, however, its role in cellular protection has remained elusive.
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