Andrej Dukat is a Professor of Internal Medicine at Comenius University. He has his expertise in Epidemiology, Prevention and Treatment of Cardiovascular Diseases in Slovakia. His clinical practice included non-invasive cardiac diagnosis, research in the field of Hypertension, Lipids and Diabetes. After years of his experiences in Preventive Cardiology, he wrote articles in the peer-reviewed papers and in the textbooks. He is teaching Internal Medicine to pre-graduate, post-graduate and foreign medical students. He is the past-President of the Slovak Society of Internal Medicine, was member of the boards, and is the fellow and honorary fellow of several scientific societies. He has conducted and is still conducting several clinical trials as the National Coordinator. He is responsible for the accreditation of the universities and teaching schools in the field of Medicine and Pharmacy in Slovakia.
Statement of the Problem: N-terminal pro brain natriuretic peptide (NT-proBNP) levels are useful biomarkers for the diagnosis and prognosis of heart failure (HF) patients. However, the data on association of uric acid (UA) concentrations and NT-pro BNP are still lacking. Methodology & Theoretical Orientation: The relationships of UA, NT-proBNP, clearance of creatinine and NYHA function class and echocardiographic variables in primary care patients with HF were investigated. Results: 848 patients (402 men, 446 women) with the mean age of 70.1±7.5 SD were included in the study. NT-proBNP concentrations correlated with UA levels in both men and women after adjusting for age, body mass index (BMI) and glomerular filtration rate (r=0.096, p<0.0001; r=0.123 p<0.0001). UA concentrations rose with the severity of NYHA class and was significantly higher in patients with moderate and severe both systolic and diastolic dysfunction in a multivariate analysis. Conclusion & Significance: A positive correlation between the concentrations of UA and NT-pro BNP in patients with HF has been observed. UA levels were associated with the severity of the disease. It is suggested that the level of UA, analogically to NT-proBN may be another important biochemical biomarker of severity and prognosis among patients with HF.
To be updated soon...
Background: Vascular calcification is common in chronic kidney disease (CKD), and recognized as surrogate marker for cardiovascular disease (CVD). Indoxyl sulfate (IS) is a protein bound uremic toxin to exacerbate vascular calcification in CKD patients, and its therapeutic target has been searched for. We hypothesized that Notch signal pathway alterations caused by IS is involved in vascular calcification because Notch signal activation increase cell survival of vascular cells in developmental and pathological status. Methods: IS (200 mg/kg/day in drinking water) or vehicle was administered to Dahl salt-resistant normotensive rats (DN) and Dahl salt-sensitive hypertensive rats (DS) to evaluate vascular calcification and the expression of Notch-1 and 3 with immunohistochemistry. Human arterial smooth muscle cells (HASMCs) was culture under various concentration of IS, and the expression of Notch 1 and 3, and apoptosis were assessed with RT-PCR, caspase activity assay, and TUNEL staining. Inorganic phosphate-induced calcification in HASMCs was also evaluated with or without IS and pharmacological inhibition of Notch and apoptosis signaling (gamma-secretase inhibitor, DAPT; 20 μM; caspase inhibitor, ZVAD 100 μM). Results: Aortic calcification was observed solely in IS-administered DS rats. The expression of Notch-1 and 3 was slightly increased in aortic SMCs from vehicle-treated DS rats compared to vehicle treated DN mice. IS induced the expression of Notch-1 and 3 in aorta from both DN and DS rats, and strong signal was especially observed in IS-administered DS rats. Notably the expression of Notch-1 and 3 was fainted in vascular calcification in IS-treated DS rats. In cultured HASMCs, the expression of Notch1 and 3 was peaked at 24 h after administration of IS (1000 μM), and fainted within 72 h. The expression of Notch-1 and 3 was also peaked at the concentration of 500 μM of IS and fainted less than 1000 μM. Exposure to IS increased TUNEL -positive cells and caspase 3/7 activity in a dose- and time- dependent manner. IS accelerated inorganic phosphate-induced calcification in HASMCs, and the effect was canceled by pharmacological inhibition of Notch and apoptotic signal. Conclusion: IS transiently activates Notch signal in vascular smooth muscle cells, but the effect was fainted in accordance to higher concentration and longer duration of exposure to IS. The decreased Notch activity induced formation of apoptotic body and calcified lesions. Thus, Notch signal would be a novel therapeutic target for vascular calcification in CKD patients.