Coronary heart disease is the leading cause of mortality and morbidity worldwide. The effects of coronary heart disease are usually attributable to the detrimental effects of acute myocardial ischaemia-reperfusion injury. Newer strategies such as ischaemic or pharmacological preconditioning have been shown to condition the myocardium to ischaemia-reperfusion injury and thus reduce the final infarct size. This review investigates the role of calcium channel blockers in myocardial preconditioning. Additionally, special attention is given to nicorandil whose mechanism of action may be associated with the cardioprotective effects of preconditioning. There are still many uncertainties in understanding the role of these agents in preconditioning, but future research in this direction will certainly help reduce coronary heart disease.
Nevena Jeremic, Vladimir Zivkovic, Ivan Srejovic, Jovana Jeremic, Anica Petkovic, Jovana Bradic and Vladimir Jakovljevic
Aim of present study was to determine the participation of various biomarkers of oxidative damage: nitrite (NO2−), superoxide anion radicals (O2−), index of lipid peroxidation (TBARS) and hydrogen peroxide (H2O2) in coronary circulation after application of the different models of preconditioning such as ischemic and preconditioning with proton pump inhibitors.
Examining a biochemical markers of oxidative damage we did not notice any increased production values of any parameter, according to that we can hypothesize that possible occurrence of reperfusion injury after ischemia and PPIs preconditioning is not mediated by this mechanism.
Due to the very difficult and controversial application of ischemic preconditioning in clinical practice, the results of this study suggest that in the future proton pump inhibitors can contribute to the prevention of myocardial damage following ischemia
Branko Stefanovic, Zoran Vukasinovic, Srbobran Stankovic, Jovana Jeremic, Nevena Jeremic and Isidora Stojic
Supracondylar humeral fractures (SCHF) are the most common elbow fractures in children, representing 3% of all paediatric fractures. Treatment options for SCHF in children are based on the Gartland classification. Treatment of non-displaced fractures (type I) is non-operative. Plaster immobilization for 3 to 4 weeks is recommended, depending on the age of the child and fracture healing. Treatments of displaced supracondylar fractures (type II and III) of the humerus in children are still undefined in clinical practice. Because of divided opinions, the aim of this study was to evaluate whether delayed or immediate surgical treatment has an advantage in the treatment of supracondylar fractures in children. This is a prospective – retrospective clinical study. This study included 64 patients from 5 to 15 years old; 47 (73.4%) were boys and 17 (26.6%) were girls. The most common age range (59.4%) in this study was 5-8 years old. All patients were diagnosed with supracondylar fractures at the Institute for Orthopaedic Surgery “Banjica”. We analysed 17 parameters, which were obtained either from direct patient interviews or from their medical history. All patients were divided into two groups with matched characteristics. Group I consisted of 26 patients who had immediate operations. Group II consisted of 38 patients who had delayed operations.
Based on the results of the analysed parameters, consisting primarily of functional results, the absence of subjective symptoms and myositis ossificans one year after surgery suggests that emergency surgical treatment of displaced supracondylar humeral fractures is optimal.
Kristina Radoman, Vesna Vucic, Aleksandra Arsic, Dejan Cubrilo, Nevena Jeremic, Jovana Jeremic and Vladimir Jakovljevic
Considering the limited knowledge regarding the effects of n-3 and n-6 PUFAs on the inflammatory response during physical activity, we aimed to evaluate the level of pro- and anti-inflammatory cytokines in young soccer players before and after a maximal physical load test at the beginning and end of a two-month training process. The study included 75 young footballers from Football School “Kragujevac,” who were followed during the two-month training programme. The subjects were divided into the following groups: 1) control group (consumed a standard diet); 2) group that consumed fish oil (2500 mg of n-3 PUFAs per day); 3) group that consumed nutritional sunflower oil (2500 mg of n-6 PUFAs daily). The maximal progressive exercise test was performed using a treadmill belt. Venous blood samples were drawn 4 times for the determination of cytokine levels (IL-6 and TNF-α): before and after the exercise load test before the two-month training programme (initial measurement) and immediately before and after the exercise load test after the two-month training programme (control measurement). Supplementation with fish oil (n-3) has been associated with reduced levels of IL-6 compared with the initial values. After an acute bout of exercise, n-3 PUFAs did not show a significant effect on inflammatory marker dynamics, whereas n-6 PUFAs slightly stimulated the production of TNF-α.
Slobodan Novokmet, Isidora Stojic, Katarina Radonjic, Maja Savic and Jovana Jeremic
Discovery of the metallopharmaceutical cisplatin and its use in antitumour therapy has initiated the rational design and screening of metal-based anticancer agents as potential chemotherapeutics. In addition to the achievements of cisplatin and its therapeutic analogues, there are significant drawbacks to its use: resistance and toxicity. Over the past four decades, numerous transition metal complexes have been synthesized and investigated in vitro and in vivo. The most studied metals among these complexes are platinum and ruthenium. The key features of these investigations is to find novel metal complexes that could potentially exert less toxicity and equal or higher antitumour potency and to overcome other pharmacological deficiencies. Ru complexes have a different mode of action than cisplatin does, some of which are under clinical trials for treating metastatic or cisplatin-resistant tumours. This review consists of the current knowledge, published and unpublished, related to the toxicity of metallopharmaceuticals, and special attention is given to platinum [Pt(II) and Pt(IV)] and ruthenium [Ru(II) and Ru(III)] complexes.
Aleksandar Juskovic, Goran Pesic, Miroslav Kezunovic, Zarko Dasic, Nikola Bulatovic and Jovana Jeremic
The purpose of the current study was to present the authors’ experiences with the long intramedullary Gamma nail in the treatment of patients with complex femoral fractures. This retrospective study included 48 patients with complex femoral fractures. All patients had received fracture fixation treatments with long intramedullary Gamma nails from January 2007 to December 2015. The complex fractures of all patients were classified into 3 types, according to the anatomical locations of the fractures. Type I included combined fractures of the shaft and the proximal femur. Type II included segmental fractures. Type III included combined fractures of the shaft and distal femur. According to the Harris Hip Score, 85.4% of our patients had excellent and very good functional outcomes of the operative procedure. Complications occurred in 7 (14.58%) patients. The most common complications occurred in patients with combined fractures of the shaft and distal femur (50%). Based on the findings of this study, we conclude that the clinical and radiological results after the treatment of complex femoral fractures with the long intramedullary Gamma nail show good outcomes, with a high rate of bone union and minimal soft tissue damage. Experience with this procedure is important to prevent and minimise technical complications.
Sasa Plecevic, Olga Pechanova, Andrej Barta, Aleksandra Vranic, Jovana Jeremic, Ljiljana Arsenijevic, Nevena Jeremic, Vladimir Jakovljevic, Maja Jevdjevic and Dejan Stanojevic
Increased activity of the renin-angiotensin-aldosterone system (RAAS) plays a significant role in the development and progression of various cardio-metabolic diseases, such as hypertension, atherosclerosis and heart failure. Aliskiren is the newest antihypertensive drug and the first orally active direct renin inhibitor to become available for clinical use. This study investigated the acute and direct effects of Aliskiren on different parameters of oxidative stress on isolated rat heart. The hearts of male Wistar albino rats (n = 24, 8 per experimental group, age 8 weeks, body mass 180–200 g), were excised and retrogradely perfused according to the Langendorfftechnique at a gradually increasing perfusion pressure (40-120 cmH2O). Markers of oxidative stress (NO2−, TBARS, H2O2 and O2−) were measured spectrophotometrically after perfusion with three different concentrations of Aliskiren (0.1 μM, 1 μM, and 10 μM). The results demonstrated possible dose-dependent cardioprotective properties of Aliskiren, particularly with higher CPP. Lipid peroxidation (TBARS) levels decreased with the highest dose of Aliskiren and higher CPP, and the same trend was observed in nitrite (NO2−) and hydrogen peroxide (H2O2) levels. These findings indicate that the acute effects of Aliskiren do not likely promote the production of reactive oxygen species upon higher pressure with the highest dose. Aliskiren may exert beneficial effects on oxidative stress biomarkers.
Ana Popovic, Olga Pechanova, Radoslava Rehakova, Vladimir Zivkovic, Ivan Srejovic, Nevena Jeremic, Jovana Jeremic, Aleksandra Vranic and Vladimir Jakovljevic
Provinols are an alcohol-free extract of red wine that contains a wide range of polyphenols. Polyphenols are a group of chemical compounds found in diverse plants. Polyphenols are considered to protect against cardiovascular disease. Although some older epidemiological studies have indicated that the positive effects of red wine on heart disease can be attributed to the alcohol content alone, there is now powerful evidence that polyphenols present in red wine are responsible for these positive effects. The hearts of male Wistar albino rats (n = 36, 12 in each experimental group, 10 weeks old, body mass 250 ± 30 g) were excised and retrogradely perfused according to the Langendorff technique at a gradually increasing perfusion pressure (40-120 cmH2O). Parameters of cardiac function (dp/dt max, dp/dt min, SLVP, DLVP, HR, CF) were measured after perfusion with three different concentrations of provinols (5 μg/ml, 10 μg/ml and 50 μg/ml). Administration of the highest dose (50 μg/ml) induced a significant increase in dp/dt max, dp/dt min, HR and CF compared with control conditions at CPP = 40 cmH2O, while an intermediate dose increased dp/dt max at the same CPP. Generally viewed, the results of the present study suggest that provinols may have a beneficial effect on the intact myocardium and coronary circulation. These findings could constitute an important step in further investigation of these polyphenols under different representative experimental conditions in the heart, as well as providing a good basis for potential clinical studies in this field.
Goran Pesic, Jovana Jeremic, Isidora Stojic, Aleksandra Vranic, Marija Cankovic, Tamara Nikolic, Nevena Jeremic, Aleksandar Matic, Ivan Srejovic, Vladimir Zivkovic and Vladimir Jakovljevic
The femur transfers the body weight from the pelvic bone to the shinbone. Femur fractures are a significant cause of morbidity and mortality among the group of locomotor apparatus injuries, especially in the elderly population. Considering that oxidative stress occurs as a result of increased production of free radicals that damage cell function and cause numerous pathological conditions and diseases, the aim of this study was to investigate oxidative stress parameters in older patients with femoral neck fractures. This clinical study included 70 patients, of which 35 had femoral neck fractures (26 males and 9 females), while the other half of the patients formed the matched control group. Markers of oxidative stress (NO2−, TBARS, H2O2 and O2-) and anti-oxidative enzymes (SOD, CAT, and GSH) were measured. Results showed that the levels of O2- increased, while levels of NO2-, H2O2 and all the antioxidative enzymes decreased in patients with femoral neck fractures. These findings indicate that fractures cause oxidative stress, probably because of the reduced activity of osteoblasts and the increased activity of osteoclasts.
Tamara Nikolic, Ivan Srejovic, Isidora Stojic, Jovana Jeremic, Marko Folic, Stevan Matic, Milena Rakocevic, Snezana Jancic, Biljana Jakovljevic, Radmila Obrenovic, Dusan Djuric and Vladimir Zivkovic
The strong association among the risk of coronary artery diseases (CAD), high levels of LDL-C and low levels of HDLC is well established. Hyperhomocysteinaemia (HHcy) is an independent risk factor for cardiovascular disease (CVD) and causes endothelial dysfunction, a hallmark of atherosclerosis. In this study, we ascertained the influence of statins on the atherogenic index, as an indicator and a significant adjunct for predicting atherosclerosis in hyperhomocysteinaemic male Wistar albino rats. For 4 weeks, the animals were fed with one of the following diets (Mucedola SRL., Milan, Italy): standard rodent chow; a diet enriched in methionine with no deficiency in B vitamins or a diet enriched in methio-nine and deficient in B vitamins. The animals were simultaneously exposed to a pharmacology treatment with atorvastatin at dose of 3 mg/kg/day i.p. or simvastatin, at dose of 5 mg/kg/day i.p. We measured weight gain, food intake, and FER and determined the concentrations of biochemical parameters of dyslipidaemia (TC, TGs, LDL-C, VLDL-C, and HDL-C), AI, and CRR. A histopathological examination was conducted on portions of the right and left liver lobes from each animal. A connection between Hhcy and dyslipidaemia was indicated by the findings of biochemical and histological analyses, suggesting that Hhcy was a pro-atherogenic state. An improvement in the lipid profile along with a decrease in the atherogenic index by statins suggests that atorvastatin and simvastatin could be useful antiatherogenic agents, with protective activities during hyperhomocysteinaemia.