The most important characteristic of calcium channels is selective regulation of slow incoming stream of calcium into the cell tissue providing the slow increasement of action potential. Such tissues include smooth muscles of blood vessels, cardiocytes and heart noduses (AV and SA node). Different calcuim antagonists have different effects on previous tissues due to their different chemical formula. Verapamile, Nifedipin and Diltiazem are the most frequently used of all. Their commonest characteristic is blocking the calcium channels causing vasodilatation of blood vessels as well as negative inotropic and chronotropic influence. By blocking the incoming calcium through slow channels of myofibrils of smooth muscles, the antagonists of calcium decrease the quantity of available calcium for contraction which causes vasodilatation. The most famous and most frequently used calcium antagonist is Verapamile. In terms of electrophysiology, Verapamile inhibits action potentials of heart noduses, especially the AV node, where the slow incoming of calcium is the most important for depolarization. Prolongation of the efective refractory period of SA node causes the heart frequency decreasement while prolongation of the effective refractory period of AV node slows down the work of chambers in case of flater and fibrillation of atriums. The molecules of calcium-bonding protein called kalmodulin are located in synaptic endings. Each kalmodulin can bond four calcium ions providing transfer into active calcium-kalmodulin complex which activates the kinase protein. Activated kinase protein starts the exocytosis of neurotransmitters into synaptic gap. Apart from activating kinase protein, calciumkalmodulin complex also starts the activity of calcium pump presynaptic membrane which pumps calcium out of presynaptic ending stopping the further exocytosis of neurotransmitters into synaptic gap. Taking into consideration the fact that opening the calcium channels on membrane of presynaptic ending is necessary to free the neurotransmitter out of the vesicle, the aim of our work is to study whether Verapamile has effects on the membrane of presynaptic endings of sympathetic nervous system checking the level of catecholamine in serum. The experiment was conducted in 6 healthy dogs which were, after 10-minute- infusion (0.9% NaCl), treated with intravenous bolus veramapile injections in three occasions, in every 5 minutes, until the first signs of intoxication had appeared. This caused bradycardia, heart rhythm disorder and blood pressure drop. In order to determine the level of catecholamine, blood was taken sequentially, in every 5 minutes, before the new dose of verapamile was given. Verapamile (given intravenous) significantly decreases the concentration of adrenaline and noradrenaline in the serum of dogs.

Uz tradicionalne faktore rizika smatra se da i inflamacija doprinosi nastanku ishemičnog moždanog udara (IMU). U toku inflamacije neutrofilni leukociti se degranulišu, kada može doći do oslobađanja njihovog enzima mijeloperoksidze (MPO) u ekstracelularni prostor. Osim peroksidazme MPO poseduje i hlorinišuću aktivnost kojom stvara hipohlornu kiselinu i dugoživeće oksidanse hloramine. U ovoj studiji je određivana hlorinišuća aktivnost MPO i koncentracija ukupnih hloramina u serumu. U studiju je bilo uključeno 29 pacijenata sa akutnim IMU, starosti 69.0 godina (64.2–78.0), i 25 ispitanika kontrolne grupe bez IMU, starosti 69.0 godina (67.0–72.0). Nađeno je da je u grupi sa IMU broj neutrofilnih leukocita u perifernoj krvi značajno veći od kontrolnih vrednosti (4.56±1.76 vs. 7.74±3.35 × 109/L, u kontrolnoj grupi i kod pacijenata; p<0.05). Takođe je i hlorinišuća aktivnost MPO seruma bila veća u grupi sa IMU (67.2 U/L vs. 92.3 U/L, kod kontrole i kod pacijenata; p<0.05). Iako je koncentracija ukupnih hloramina bila nešto veća kod IMU nego u kontrolnoj grupi, razlika nije bila statistički značajna (p=0.178). Aktivnost MPO je značajno korelirala sa koncentracijom triglicerida (p<0.05). Korelacija između hlorinišuće aktivnosti MPO i ukupnih hloramina nije bila značajna (p=0.402), dok su korelacije MPO aktivnosti i broja neutrofila (p=0.071) odnosno MPO aktivnosti i prisustva aritmije (p=0.094) bile nešto veće. Rezultati ove studije ukazuju da MPO verovatno ima ulogu u patogenezi IMU, što se delimično može zasnivati na hlorinaciji biološki značajnih molekula vaskularnog kompartmana.

The aim of this study was to evaluate the diagnostic accuracy of ischemia modified albumin (IMA) alone, or in combination with cardiac troponin T (cTnT) and electrocardiogram (ECG) findings for diagnosis of acute coronary syndrome (ACS). The study included patients with acute chest pain suggestive on ACS, recruited within 6 hours from onset. Patients were classified in ACS group and non-ischemic chest pain group (NICP). Of 84 patients, 49 were diagnosed with ACS and 35 with NICP. IMA was significantly higher in ACS group (p<0.0001). The area under receiver operating curve for IMA in ACS diagnosis was 0.95 (p<0.0001). Sensitivity and specificity of IMA for ACS diagnosis were 89.8% and 91.4%, respectively. IMA significantly (p<0.05) improved the sensitivity of ECG and cTnT, alone, and in combination. Sensitivity and negative predictive value of combination of IMA, ECG and cTnT for diagnosis of ACS were 100%. IMA is useful for diagnosis of ACS, in combination with ECG and cTnT.

Oksidativni stres predstavlja disbalans u homeostazi egzogenih i endogenih oksidanasa. Prisustvo povećanih koncentracija oksidanasa u ćelijama i ekstracelularnim tečnostima dovodi do spntanih post-translacionih modifikacija proteina i utiče na njihove hemijske, biološke, fizičke i imunogene osobine, i predstavlja deo molekulskih mehanizama mnogih bolesti. Do sada su opisane brojne post-translacione modifikacije proteina u uslovima oksidativnog stresa. Pored direktnog oksidantnog dejstva kiseonikovih i azotnih slobodnih radikala, i brojni drugi oksidansi učestvuju u post-translacionim modifikacijama proteina. Tako se glikaciom i glikoksidacijom stvaraju AGE (advanced glycation end-products), reakcijom sa lipidnim aldehidima i ketonima ALE (advanced lipoxidation end-products), oksidacijom i polimerizacijom AOPP (advanced oxidation protein products), a reakcijom sa ureom i/ ili izocijanskom kiselinom nastaju produkti karabmoilacije proteina. U ovom preglednom članku dat je opis hemijskih modifikacija proteina sa posebnim osvrtom na značaj u patogenetskom mehanizmu razvoja pojedinih bolesti kod čoveka.

Oxidative stress and associated oxidative damage are mediators of vascular injury and inflammation in many cardiovascular diseases, including hypertension, atherosclerosis, ischemic heart disease, diabetes. Xanthine oxidoreductase is one of the enzymes producing free radicals in the cardiovascular system, and it can contribute to the increment of the oxidative stress and, consequently, blood pressure. The xanthine oxidase is a molybdoenzyme capable of catalyzing the oxidation of hypoxanthine and xanthine in the process of purine metabolism. Xanthine oxidase can exist in two interconvertible forms, either as xanthine dehydrogenase or xanthine oxidase. The aim of the paper was investigate the activity xanthine oxidoreductase in the plasma patients with age related cataract, with hypertensive, and with heart failure. Clinical and biochemical researches were carried out in 73 patients with age related cataract, mean age 72±7 years, divided into group with hypertensive (N=35), with heart failure (N=22) and group normotensive and without heart failure (N=16). Plasma xanthine oxidoreductase activity was determined spectrophotometrically by measuring the formation of uric acid from hypoxanthine at 293 nm. The concentration of triglycerides (TG), total cholesterol (TC), LDL-C, HDL-C in plasma were determined. Our findings show a significantly increased activity xanthine oxidoreductase in plasma hypertensive patients (XO 9.18±1.5 U/L) (p< 0.001) and patients with heart failure (XO 10.44±1.53U/L) (p< 0.001), compared with values plasma xanthine oxidoreductase activity in normotensive and patients without heart failure (XOD 6.02±1.4 U/L). Concentrations of plasma TG, TC and LDL-C were elevated in groups with hypertensive and with heart failure, and we to find significant differences with group normotensive and without heart failure values. Elevated activity of plasma xanthine oxidoreductase contribute to the increasåd oxidative stress and may play a role in accelerated atherosclerosis. 

Nitric oxide (NO) is a major messenger molecule that plays key roles in many physiological processes. NO is produced by nitric oxide synthase (NOS), which catalyzes the conversion of L-arginine to L-citruline and NO. At least three isoforms of NOS have been identified and characterized, namely, neuronal NOS (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS). Recent evidence indicates that most of the cytotoxicity attributed to NO is rather due to peroxynytrite, produced from the diffusion controlled reaction betwen NO and another free radical, the suproxide anion. Peroxynitrite interacts with protein, DNAand lipids via direct oxidative reactions or via indirect radical mediated mechanisms

Reactive products of oxygen are among the most potent and omnipresent threats faced by the living organism. Intracellular accumulation of reactive oxygen species such as superoxide anion, hydrogen peroxide, hydroxyl radical, and peroxy radical, can arise from toxic insults or normal metabolic processes. These species may perturb the cell's natural antioxidant defence systems, resulting in damage to all of the major classes of biological macromolecules, including nuclear acids, proteins, carbohydrates and lipids. Oxidative stress has been defined as a disturbance in the prooxidant-antioxidant balance, resulting in potential cell damage. It has been implicated in several biological and pathological processes like ageing, inflammation, carcinogenesis, ischemia-reperfusion and in diseases including diabetes mellitus, atherosclerosis, and/or neurodegenerative diseases

Cells continuously produce free radicals and reactive oxygen species as part of metabolic processes. These free radicals are neutralized by antioxidant defense system consisting of enzymes such as catalase, superoxide dismutase, glutathione peroxidase, and numerous non-enzymatic antioxidants, including vitamins A, E and C, glutathione, ubiquinone, and flavonoids. Antioxidants include both water and lipid soluble varieties. The lipid soluble antioxidants are located in the cellular membranes and lipoproteins, whereas the water soluble antioxidants are present in the aqueous environments, such as fluids inside cells and in the blood.