The role of melatonin in preventing amiodarone-induced rat liver damage.

Long-term exposure to amiodarone, an antiarrhythmic drug, can induce different organ damage, including liver. Cell damage included by amiodarone is a consequence of mitochondrial damage, reactive oxygen species production, and cell energy depletion leading to programmed cell death. In the present study, hepatoprotective potential of neurohormone melatonin (50 mg/kg/day) was evaluated in a chronic experimental model of liver damage induced by a 4-week application of amiodarone (70 mg/kg/day). The obtained results indicate that amiodarone induces an increase in xanthine oxidase activity, as well as the content of the lipid and protein oxidatively modified products and p53 levels. Microscopic analysis further corroborated the biochemical findings revealing hepatocyte degeneration, apoptosis, and occasional necrosis, with the activation of Kupffer cells. Coadministration of melatonin and amiodaron prevented an increase in certain damage associated parameters, due to its multiple targets. In conclusion, the application of melatonin together with amiodarone prevented an increase in tissue oxidative damage parameters and moderately prevented liver cell apoptosis, indicating that the damage of hepatocytes provoked by amiodarone supersedes the protective properties of melatonin in a given dose.

Association of Plasma Renalase and Left Ventricle Mass Index in Heart Failure Patients Stratified to the Category of the Ejection Fraction: A Pilot Study.

Heart failure represents a growing health problem, with increasing morbidity and mortality globally. According to the mechanisms involved in the pathogenesis of heart failure, many biomarkers have been proposed for the timely diagnosis and prognostication of patients with heart failure, but other than natriuretic peptides, none of them has gained enough clinical significance. Renalase, a new protein derived from kidneys was demonstrated to metabolize catecholamines and to have a cardioprotective role. The aim of the study was to determine whether renalase and brain natriuretic peptide (BNP) concentration could be used to differentiate heart failure patients stratified to the category of the ejection fraction and whether plasma renalase could be used as a biomarker for left ventricle hypertrophy in all subgroups of heart failure patients. We included patients diagnosed with heart failure and stratified them to the three subgroups according to the ejection fraction. Regarding echocardiographic parameters, HFmrEF had an intermediate profile in between HFrEF and HFpEF, with statistical significance in most evaluated parameters. BNP concentration was significantly different in all three subgroups (p < 0.001), and renalase was statistically higher in HFrEF (p = 0.007) compared to the HFmrEF and HFpEF, where its results were similar, without statistical significance. Renalase plasma concentration was demonstrated to be highly and positively associated with left ventricle mass index in HFrEF (p = 0.029), as well as increased plasma concentration of BNP (p = 0.006). In the HFmrEF group of patients, body mass index was positively associated with LVMI (p = 0.05), while in the patients with HFpEF, diabetes mellitus was demonstrated to have a positive association with LVMI (p = 0.043). These findings suggest that renalase concentration may be measured in order to differentiate patients with reduced ejection fraction. Plasma renalase concentrations positively correlated with left ventricle hypertrophy in patients with reduced ejection fraction, being strongly associated with increased left ventricular mass index.

Detrimental effects of a bout of physical exercise on circulating endogenous inhibitors of endothelial function in patients with coronary artery disease.

BACKGROUND: A bout of intense physical activity has been shown to transiently impair endothelial function; however, the underlying mechanisms are unclear. AIM: The purpose of the review was to assess the impact of a bout of physical exercise induced by exercise stress echocardiography, on blood concentration of the endogenous inhibitors of nitric oxide synthase, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA), in patients with atherosclerosis. METHODS: Overall, 83 study participants were enrolled, 25 coronary artery disease (CAD) patients, 20 age and sex-matched asymptomatic study participants with at least one risk factor for CAD, and 38 healthy controls. RESULTS: Patients with CAD developed symptoms and/or left ventricular wall motion abnormalities during exercise; no changes were seen in study participants with risk factors, or in healthy controls. At baseline, in CAD patients and in study participants with risk factors, both ADMA and SDMA were higher than healthy controls (P < 0.001). However, a further large increase occurred during exercise stress echocardiography in both groups, regardless of development of symptoms (P < 0.001). CONCLUSION: Basal concentrations of ADMA and SDMA are high in CAD patients and in study participants with risk factors, consistent with impaired nitric oxide synthase activity in atherosclerosis. Large increase of these endogenous inhibitors of nitric oxide during intense exercise provide support to the hypothesis that in patients with atherosclerosis endothelial function may further deteriorate as a consequence of a bout of physical activity.

Crosstalk of Various Biomarkers That Might Provide Prompt Identification of Acute or Chronic Cardiorenal Syndromes.

INTRODUCTION: Pathophysiological interaction between the heart and kidneys represents the basis for clinical entities called cardiorenal syndromes. The purpose of the study was to assess the relations between acute and chronic cardiorenal syndromes and biomarkers [advanced oxidation protein products, brain natriuretic peptide, malondialdehyde, xanthine oxidoreductase (XOD), xanthine oxidase, xanthine dehydrogenase, interleukin 8, cystatin C, plasminogen activator inhibitor-1, high-sensitive troponin T, C-reactive protein and glomerular filtration rate, measured by the Modification of Diet in Renal Disease (MDRD) formula], to hypothesize biomarkers that might provide a prompt identification of acute or chronic cardiorenal syndromes, and to distinguish acute versus chronic types of these syndromes. METHODS: A total of 114 participants were enrolled in this study, i.e. 79 patients divided into subgroups of acute and chronic cardiorenal syndromes and 35 volunteers. RESULTS: Nonadjusted odds ratio (OR) showed that there was a significant risk for acute cardiorenal syndrome with increased XOD activity (p = 0.037), elevated cystatin C concentration (p = 0.038) and MDRD (p = 0.028). Multivariable adjusted OR, on the other hand, revealed that only glomerular filtration rate measured by the MDRD formula had a significance for acute cardiorenal syndrome (p = 0.046). Nonadjusted OR showed a significant risk for chronic cardiorenal syndrome only in elderly (p = 0.002). Multivariable adjusted OR exhibited that age was the only risk factor for chronic cardiorenal syndrome (p = 0.012). CONCLUSION: Cystatin C, glomerular filtration rate measured by the MDRD equation and XOD were independent risk factors for acute cardiorenal syndrome, while age remained an independent risk factor for chronic cardiorenal syndrome. When comparing ORs of evaluated parameters, the highest significance for acute cardiorenal syndrome was plasma concentration of cystatin C.

Microinflammation factors in the common diseases of the heart and kidneys.

AIM: To determine levels of interleukin-8 (IL-8) and plasminogen activator inhibitor-1 (PAI-1) in different cardiorenal syndrome (CRS) modalities and to compare findings to some already investigated direct and indirect parameters of inflammation and atherosclerosis. MATERIALS AND METHODS: Testing involved 114 examinees, divided into control and clinical groups suffering from different modalities and were formed according to the basis of a valid classification for CRS. RESULTS: C-reactive protein (CRP) was significantly higher in all CRSs in comparison to the control group (P < 0.05). PAI-1 in CRSs was statistically higher than in the control group. IL-8 was increased in all CRSs, and especially in CRS-5, where no significance was found. PAI-1 correlated with IL-8 in all CRSs, with significant value in CRS-2 and CRS-5. Correlation for PAI-1 and high-density lipoproteins (HDL) was found in CRS-4, while IL-8 was found to be related to CRP level in all CRSs, with significance only in CRS-1 (P < 0.001). CONCLUSIONS: C-reactive protein, IL-8, and PAI-1 could be useful for clinical differentiation of chronic modalities of CRSs. Inflammation was the most pronounced in CRS-4. Lipid status parameters could be useful for differentiation of CRSs. Furthermore, HDL in chronic primary kidney diseases and triglycerides and total cholesterol in CRS-5 could be valuable.

[Level of job satisfaction among employees working at healthcare facilities in Nisava and Toplica district].

INTRODUCTION: The product of health system and its employees is health service whose quality is related to the satisfaction and motivation of people working in health system. The objective of this study was to assess and compare satisfaction with different aspects of work among different categories of employees in healthcare facilities on primary, secondary and tertiary level of health care in Nisava and Toplica districts. MATERIALS AND METHODS: The study was conducted as a one-day study in 15 healthcare facilities on primary level, in two public hospitals and 27 clinics of Clinical Centre of Nis, using anonymous questionnaire. Out of 3,892 employees, who took part in this study, 2,227 were from primary and 1,665 were from secondary and tertiary level. RESULTS: All employees on primary level are more satisfied with the majority of aspects of job comparing with employees on secondary and tertiary level of health care. Administrative staff is in general more satisfied with all aspects of job comparing with other categories of employees. All employees on secondary and tertiary level are more physically and psychically exhausted than employees on primary level of health care. Health workers on secondary and tertiary level are most psychically exhausted. CONCLUSION: There is a difference in satisfaction with different aspects ofjob in different categories of employees, and on different levels of health, in healthcare facilities in Nisava and Toplica districts. Employees of healthcare facilities on primary level of health care are in general more satisfied than employees on se-condary and tertiary level of health care.

Frequency and characteristics of myocardial ischemia recorded during stress echocardiography in patients with high coronary risk.

BACKGROUND/AIM: Ischemic heart disease is the major cause of morbidity and mortality in the world as well as in our country. Ischemic heart disease has the multifactorial origin and the presence of several risk factors increases the risk of myocardial ischemia. The aim of the study was to evaluate the frequency and characteristics of myocardial ischemia in asymptomatic subjects with two or more risk factors for coronary artery disease during stress echocardiography. METHODS: In 240 high risk asymptomatic subjects (an absolute risk of fatal cardiovascular disease of more than 5%, according to the Systemic Coronary Risk Evaluation Chart), the exercise stress echocardiography test was performed. The criterion for myocardial ischemia was the appearance of transient segmental wall motion abnormality (WMA). The wall motion score index was calculated before and after the exercise stress echocardiography. RESULTS: During exercise stress echocardiography, in 36 (15%) subjects WMA occurred. Out of 36 subjects with myocardial ischemia, in 10 (27.8%) subjects WMA and ST segment depression were accompanied with the first occurrence of chest pain (the subgroup with symptomatic myocardial ischemia), in 20 (55.6%) subjects WMA and ST segment depression were detected and in 6 (16.6%) subjects only WMA occurred (the subgroup with silent myocardial ischemia). There were no significant differences between the subgroups with symptomatic and silent myocardial ischemia with regard to exercise tolerance, heart rate at the onset of WMA, and time to the onset of WMA, but the wall motion score index was significantly higher in the subjects with symptomatic myocardial ischemia (p < 0.01). In all the individuals with symptomatic myocardial ischemia, significant stenosis of the coronary arteries was found by coronary angiography. Out of 26 subjects with asymptomatic myocardial ischemia, coronary angiography was performed in 18 and significant stenosis of the coronary arteries was diagnosed in all of them. The number and grade of coronary stenosis in subjects with symptomatic and silent myocardial ischemia were similar. CONCLUSION: The obtained results presented the incidence of myocardial ischemia in 15% of asymptomatic subjects with high coronary risk during stress echocardiography. Silent myocardial ischemia was markedly more frequent than symptomatic one, but in the subjects with symptomatic ischemia, the wall motion score index was significantly higher.

Impact of reversible myocardial ischaemia on nitric oxide and asymmetric dimethylarginine production in patients with high risk for coronary heart disease.

BACKGROUND: The aim of the present study was to assess the impact of reversible myocardial ischemia, provoked by acute physical activity during an exercise stress echocardiography (ESE), on nitric oxide (NOx) and asymmetric dimethylarginine (ADMA) production in patients with high risk for coronary heart disease (CHD). MATERIAL/METHODS: An overall of 45 patients (27 men, 18 women; mean age, 55.87+/-6.39 years), was enrolled in the study and assigned into groups according to sex, CHD risk factors (RF), wall motion score (WMS), and diabetes mellitus (DM). An ESE was performed on an ergocycle, using a standardized protocol. The modified Saville-Griess method was used to determine NOx concentration. Production of ADMA was evaluated by high-performance liquid chromatography with fluorescent detection. RESULTS: A significant increase of NOx was observed in men (P<.05) and patients with stable WMS (P<.01), as well as its decrease in patients with increased WMS, whereas ADMA significantly increased in both sexes (P<.001 and P<.01 in men and women, respectively), independently of CHD risk (P<.05 and P <.001 in 1-2 RF and > or =3 RF groups, respectively), presence of DM (P<.001 and P<.01 in no-DM and DM groups, respectively), and WMS dynamic (P<.05 and P<.001 in WMS stable and WMS increased groups, respectively). The WMS was significantly higher in the > or =3 RF group (P<.01) after ESE and significantly increased in both sexes (P<.001 and P<.01 in men and women, respectively), with no regard to DM (P<.001 and P<.01 in no-DM and DM groups, respectively). CONCLUSIONS: The results of the present study clearly demonstrated a significant increase of NOx in patients with stable WMS and its decrease in patients with increased WMS after ESE, compared with the resting condition, as well as a significant increase of ADMA both in patients with stable WMS and those with increased WMS, irrespective of sex and CHD risk. A significant increase of WMS was observed in the > or =3 CHD RF group, in both sexes, with no regard to the presence of DM.

[Prevalence and prognostic significance of silent myocardial ischemia in patients after myocardial infarction].

BACKGROUND/AIM: Silent myocardial ischemia (MI) can be detected in subjects with any symptoms, in patients after myocardial infarction and in coronary patients who have episodes of symptomatic, as well as of silent MI. This study was carried out to evaluate the frequency, characteristics and prognostic significance of silent MI detected in stress echocardiography test in patients after myocardial infarction. METHODS: In 210 patients within three months after myocardial infarction exercise test was performed. In those patients with ischemic ST depression on exercise electrocardiogram, in order to confirm MI stress echocardiography was additionally performed. To assess the incidence of major cariovascular events, all the patients were followed at least five years after the first myocardial infraction. RESULTS: Out of 210 patients 88 (42%) had ischemic response during stress echocardiography test. Out of 88 patients with MI 54 (61%) had anginal pain (patients with symptomatic MI), while 34 (39%) were free of symptoms (patients with silent MI). Level of exercise test, heart rate, time to the onset of ST segment depression, and the magnitude of ST segment depression were similar in both subgroups of the patients with MI. Duration of exercise test was longer in patients with silent MI (p < 0.05). Wall motion score index during stress echocardiography was higher in patients with symptomatic MI (p < 0.05). Coronary angiography findings were similar in patients with silent and those with symptomatic MI. During a five-yearsfollow-up period the occurrence of major cardic events (cardiac mortality and recurrent myocardial infarction) was similar in both subgroups of the patients with MI. CONCLUSION: In more than one third of patients after myocardial infarction silent MI during stress echocardiography was detected. The patients with silent ischemia had longer duration of exercise test and smaller wall motion score index on stress echocardiography. There was no difference in coronary angiography finding between patients with silent and those with symptomatic MI. The incidence of major cardiac events during a five- years- follow-up was similar in the patients with silent and those with symptomatic MI.