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M Nedeljkovic

Publications and source records attributed to M Nedeljkovic.

13 recordsLinked to original sources
PubMed2004

Differential effects of NMDA and AMPA/kainate receptor antagonists on superoxide production and MnSOD activity in rat brain following intrahippocampal injection.

The involvement of NMDA and AMPA/kainate receptors in the induction of superoxide radical production in the rat brain was examined after injection of kainate, non-NMDA receptor agonist, kainate plus 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), selective AMPA/kainate receptor antagonist, or kainate plus 2-amino-5-phosphonopentanoic acid (APV), selective NMDA receptor antagonist. Competitive glutamate receptor antagonists were injected with kainate unilaterally into the CA3 region of the rat hippocampus. We investigated superoxide production and mitochondrial MnSOD activity after injection. The measurements took place at different times (5, 15 min, 2, 48 h and 7 days) in the ipsi- and contralateral hippocampus, forebrain cortex, striatum, and cerebellum homogenates. Used glutamate antagonists APV and CNQX both expressed sufficient neuroprotection in sense of decreasing superoxide production and increasing MnSOD levels, but with differential effect in mechanisms and time dynamics. Our findings suggest that NMDA and AMPA/kainate receptors are differentially involved in superoxide production. Following intrahippocampal antagonists injection they, also, interpose different neuroprotection effect on the induction of MnSOD activity in distinct brain regions affected by the injury, which are functionally connected via afferents and efferents. It suggests that MnSOD protects the cells in these regions from superoxide-induced damage and therefore may limit the retrograde and anterograde spread of neurotoxicity.

2-Amino-5-phosphonovalerate↗
PubMed2003

Prognostic value of myocardial viability determined by a 201Tl SPECT study in patients with previous myocardial infarction and mild-to-moderate myocardial dysfunction.

The prognostic meaning of myocardial viability is most important in patients with severe left ventricular dysfunction and ischaemic heart disease, but its prognostic significance in patients with previous myocardial infarction and mild-to-moderate myocardial dysfunction is uncertain. The aim of this study was to assess the prognostic value of a 201Tl single photon emission computed tomography (SPECT) rest-redistribution study in patients with previous myocardial infarction, ischaemic heart disease and mild-to-moderate myocardial dysfunction. Myocardial viability was assessed in 55 patients (50 male; mean age 58+/-9 years) by 201Tl SPECT rest-redistribution (after 4 h) scintigraphy. All patients had previous myocardial infarction (>3 months) and angiographically documented coronary artery disease, with the mean ejection fraction of 43+/-10%. Out of 55 patients, 20 were medically treated and 35 were revascularized. The follow-up period for adverse cardiac events, including death and non-fatal myocardial infarction, was 12 months. 201Tl SPECT study was positive for myocardial viability in 36 patients (65%) and negative in 19 patients (35%). Sensitivity, specificity, positive and negative predictive values for functional improvement in the follow-up period were 85%, 75%, 92% and 60%. Out of seven (13%) cardiac events in the follow-up period (four cardiac deaths and three reinfarctions), five occurred in 20 medically treated patients and two in 35 revascularized patients (25% vs 6%, P <0.05). Absence of myocardial viability was the only variable associated with adverse cardiac events (P =0.02). Survival at 12 months, as determined by using Kaplan-Meier analysis, was 56% for medically treated and non-viable patients, 80% for revascularized and non-viable patients, 91% for medically treated and viable patients, and 100% for revascularized and viable patients (P =0.0034). These findings suggest that in patients with previous myocardial infarction and mild-to-moderate myocardial dysfunction, the absence of myocardial viability as determined by the 201Tl SPECT study was the only variable associated with adverse cardiac events. The best 12 month survival was observed in revascularized viable patients, whereas the worse prognosis was found in non-viable, medically treated patients.

Female↗
PubMed2002

Chlamydia trachomatis infections in eastern Europe: legal aspects, epidemiology, diagnosis, and treatment.

OBJECTIVES: Knowledge concerning genital Chlamydia trachomatis infections in eastern Europe is scarce. Data on the legal aspects, epidemiology, diagnosis, and treatment of the infection have never been collected, summarised, and presented to the international scientific community. The aim of this study was to present the current situation on the main aspects of chlamydial infections in the countries of eastern Europe. METHODS: Written questionnaires concerning legal aspects, epidemiology, diagnosis, and treatment of the infection were distributed among national STI operating administrators as well as researchers who had presented papers at earlier meetings of European chlamydia or STI societies. RESULTS: Most of the countries have not legalised reporting of chlamydial infections and in those who have done so, the quality of the reporting system is poor. Contact tracing is mostly done on a voluntary basis. Reported chlamydia incidence varies from 21 to 276 per 100000 inhabitants. The most commonly used diagnostic test remains the direct immunofluorescence test; however, some tendencies towards nucleic acid amplification are in evidence. Diagnostic services are paid for by the patient himself, while treatment in many countries is partially or completely covered by public insurance. CONCLUSIONS: This is the first report summarising data concerning the situation on C trachomatis infections in eastern Europe. The reporting system and diagnosis of C trachomatis infections remain suboptimal, which allows neither control of the epidemiological situation nor optimal treatment of the patients. The most urgent work currently necessary is the education of professionals and the general population.

Anti-Bacterial Agents↗
PubMed2000

Pharmacological radionuclide ventriculography for detection of myocardial contractile reserve in patients after myocardial infarction: head-to-head comparison of low dose dobutamine and low dose dipyridamole.

BACKGROUND: Low dose pharmacological stress echocardiography with either dobutamine or dipyridamole infusion has been proposed for recognition of myocardial viability. However, dependence on adequate acoustic window, observer experience, and the mild degree of wall motion changes make the viability assessment by stress echocardiography especially bothersome. The objective of the study was to evaluate the ability of low dose dobutamine and low dose dipyridamole radionuclide ventriculography to detect contractile reserve in patients after myocardial infarction and functional recovery after coronary angioplasty. METHODS: The study group consisted of 20 consecutive patients (52 +/- 10 years, 17 male, 3 female) with previous myocardial infarction and resting regional dyssynergy, in whom diagnostic cardiac catheterization revealed significant one-vessel coronary artery stenosis suitable for angioplasty. Each patient underwent equilibrium 99m-Tc radionuclide ventriculography which was performed at rest and during low dose dipyridamole (0.28 mg/kg over 2 minutes) and low dose dobutamine infusion (up to 10 mcg/kg/min). Left ventricular global and regional ejection fractions were determined. Increase of regional ejection fraction for > 5% (inferoapical and posterolateral regions) or > 10% (anteroseptal regions) during low dose dobutamine and dipyridamole in infarcted regions, as well as in the followup period, was considered as index of contractile reserve. After 8 weeks of successful angioplasty, resting radionuclide ventriculography was repeated in all patients in order to identify functional recovery of the infarct zone. RESULTS: Out of the 180 analyzed segments (20 x 9), 90 regional ejection fractions have shown depressed contractility. The mean of the regional ejection fractions showing depressed contractility increased from the resting value of 34 +/- 12% to 42 +/- 14% in the follow-up period (p = 0.06). Of the 90 with baseline dyssynergy, 46 were responders during low-dose dobutamine (51%), whereas 32 segments were responders (36%, p = 0.05 vs. dobutamine) during low dose dipyridamole. Positive predictive value of dobutamine and dipyridamole for predicting functional recovery was 72% and 75% (p = ns), respectively. Negative predictive value of dobutamine and dipyridamole was 48% and 69% (p = 0.05), respectively. In the group of patients with most severe dyskinesia (regional ejection fraction < 35%, 42 segments) positive predictive value was 73% and 82%, while negative predictive value was 42% and 64% for low dose dobutamine and low dose dipyridamole respectively (p = ns). CONCLUSION: Although low dose dobutamine induced higher rate of positive responses during radionuclide ventriculography imaging, dipyridamole radionuclide ventriculography has shown superior, particularly negative, prognostic value for predicting functional recovery of infarcted regions.

Journal Article↗
PubMed1999

Integrated evaluation of relation between coronary lesion features and stress echocardiography results: the importance of coronary lesion morphology.

OBJECTIVES: The aim of this study was to analyze, in the same group of patients, the relationship between multiple variables of coronary lesion and results of exercise, dobutamine and dipyridamole stress echocardiography tests. BACKGROUND: Integrated evaluation of the relation between stress echocardiography results and angiographic variables should include not only the assessment of stenosis severity but also evaluation of other quantitative and qualitative features of coronary stenosis. METHODS: Study population consisted of 168 (138 male, 30 female, mean age 51+/-9 years) patients, on whom exercise (Bruce treadmill protocol), dobutamine (up to 40 mcg/kg/min) and dipyridamole (0.84 mg/kg over 10 min) stress echocardiography tests were performed. Stress echocardiography test was considered positive for myocardial ischemia when a new wall motion abnormality was observed. One-vessel coronary stenosis ranging from mild stenosis to complete obstruction of the vessel was present in 153 patients, and 15 patients had normal coronary arteries. The observed angiographic variables included particular coronary vessel, stenosis location, the presence of collaterals, plaque morphology according to Ambrose classification, percent diameter stenosis and obstruction diameter as assessed by quantitative coronary arteriography. RESULTS: Covariates significantly associated with the results of physical and pharmacological stress tests included for all three stress modalities presence of collateral circulation, percent diameter stenosis and obstruction diameter, as well as lesion morphology (p < 0.05 for all, except collaterals for dobutamine stress test, p = 0.06). By stepwise multiple logistic regression analysis, the strongest predictor of the outcome of exercise echocardiography test was only percent diameter stenosis (p = 0.0002). However, both dobutamine and particularly dipyridamole stress echocardiography results were associated not only with stenosis severity - percent diameter stenosis (dobutamine, p = 0.04; dipyridamole, p = 0.003) - but also, and even more strongly, with lesion morphology (dobutamine, p = 0.006; dipyridamole, p = 0.0009). As all of stress echocardiography results were significantly associated with percent diameter stenosis, the best angiographic cutoff in relation to the results of stress echocardiography test was: exercise, 54%; dobutamine, 58% and dipyridamole, 60% (p < 0.05 vs. exercise). CONCLUSIONS: Integrated evaluation of angiographic variables have shown that the results of dobutamine and dipyridamole stress echocardiography are not only influenced by stenosis severity but also, and even more importantly, by plaque morphology. The results of exercise stress echocardiography, although separately influenced by plaque morphology, are predominantly influenced by stenosis severity, due to a stronger exercise capacity in provoking myocardial ischemia in milder forms of coronary stenosis.

Adult↗
PubMed1997

Coronary vasodilation without myocardial erection. Simultaneous haemodynamic, echocardiographic and arteriographic findings during adenosine and dipyridamole infusion.

AIM: The aim of this study was to evaluate simultaneously echocardiographic, haemodynamic and angiographic changes that occur during adenosine and dipyridamole infusion, in patients with one-vessel coronary artery stenosis. This would assess whether deterioration in left ventricular haemodynamics during vasodilator agent infusion is influenced by vasodilation per se, or the development of myocardial ischaemia. METHODS AND RESULTS: We performed adenosine (140 micrograms.kg-1.min-1 over 4 min) and dipyridamole (up to 0.84 mg.kg-1 over 10 min) stress echocardiography tests, together with angiographic and haemodynamic assessment, in 26 patients undergoing elective coronary angioplasty. In 12 of 26 patients, adenosine and dipyridamole tests were repeated 24 h after angioplasty. The criterion for echocardiography test positivity was the appearance of a new transient regional wall motion abnormality. Coronary angiograms were analysed with quantitative coronary arteriography. Adenosine and dipyridamole induced regional dysfunction in 18/26 (69%) and 14/26 (54%) patients before angioplasty, respectively (P = ns). In the echocardiography-positive patients, the percent diameter stenosis was significantly (P < 0.05) tighter stenosis than in the echocardiography-negative patients (adenosine, 66.6 +/- 8.3% vs 58.0 +/- 8.9%; dipyridamole, 69.2 +/- 7.1% vs 57.7 +/- 7.6%). During both tests, left ventricular end-diastolic pressure significantly increased (P < 0.05) in echocardiography-positive patients (adenosine, 9.8 +/- 2.7 mmHg to 13.5 +/- 4.1 mmHg; dipyridamole, 10.1 +/- 2.8 mmHg to 14.1 +/- 4.3 mmHg), but not in echocardiography-negative patients. In the patients who had undergone successful angioplasty (reduction to < 50% diameter stenosis), both adenosine and dipyridamole confirmed the arteriographic success of the procedure (echocardiography negative in all patients). In this group of patients, no significant change was observed in left ventricular end-diastolic pressure during adenosine or dipyridamole infusion. CONCLUSIONS: Intravenous infusion of either adenosine or dipyridamole was accompanied by an obvious increase in left ventricular end-diastolic pressure only in patients with induced wall motion abnormalities. Coronary vasodilation per se has no significant effect on left ventricular end-diastolic pressure when no ischaemia is induced, disproving any clinically significant 'erectile' and adverse effects of coronary vasodilation per se.

Adenosine↗
PubMed1996

High dose adenosine stress echocardiography for noninvasive detection of coronary artery disease.

OBJECTIVES: The aim of this study was to assess the tolerability and incremental diagnostic value of high adenosine doses in stress echocardiography testing in patients with coronary artery disease (CAD). BACKGROUND: In comparison with other pharmacologic stress echocardiography tests, standard dose adenosine stress has sub-optimal sensitivity for detecting milder forms of CAD. METHODS: Adenosine stress echocardiography was performed in 58 patients using a starting dose of 100 micrograms/kg body weight per min over 3 min followed by 140 micrograms/kg per min over 4 min (standard dose). If no new wall motion abnormality appeared, the dose was increased to 200 micrograms/kg per min over 4 min (high dose). All patients underwent coronary angiography. Significant CAD was defined as > or = 50% diameter stenosis in at least one major coronary artery. Thirty-three patients had one-vessel and seven had multivessel CAD. Coronary angiographic findings were normal in 18 patients. RESULTS: The high adenosine dose caused a slight but significant increase over baseline values in rate-pressure product. Limiting side effects occurred in two patients during the standard dose protocol and in one patient receiving the high dose regimen. The test was stopped in 30 patients after the standard adenosine dose regimen because of a provoked new wall motion abnormality. The sensitivity of adenosine echocardiography with the standard dose was 75% (95% confidence interval [CI] 63% to 87%). After completion of the standard dose protocol, 28 patients continued testing with the high dose adenosine protocol. The overall sensitivity of adenosine echocardiography, calculated as cumulative, increased to 92% (95% CI 84% to 100%) with the high dose (p < 0.05). The specificity of adenosine testing was 100% and 88%, respectively, with the standard and high dose regimen (p = 0.617). CONCLUSIONS: We believe that use of a higher than usual adenosine dose protocol for stress testing may improve the diagnostic value of adenosine echocardiography, mainly by increasing sensitivity in patients with single-vessel disease without deterioration of the safety profile and with only a mild reduction in specificity.

Adenosine↗
PubMed1995

Dipyridamole and dobutamine: competitors or allies in pharmacological stress echocardiography?

Stress echocardiography has become an accepted and cost-effective method for diagnosing coronary artery disease. However, as exercise stress echocardiography is a demanding technique, difficult to reproduce, pharmacological stress echocardiography has become very popular in recent years. The two most popular tests from the pharmacological stress echocardiography arena are dipyridamole and dobutamine. They have enabled the technical limitations inherent in exercise echocardiography to be overcome, and have provided the opportunity to obtain, during stress, images of unchanged quality in comparison to baseline. However, the sensitivity of both pharmacological stresses applied separately is less than ideal in patients with milder forms of coronary artery disease and in patients under therapy. To overcome this, a new generation of pharmacological stress tests, the combined dipyridamole-dobutamine tests were introduced. A combined dipyridamole-dobutamine echocardiography stress test should suggest that the agents are natural allies rather than competitors but in some instances they are applicable only in selected patients, and each pharmacological agent may be clinically contraindicated for administration. This is the message from a large scale study of recent years.

Cardiotonic Agents↗
PubMed1994

Dipyridamole-dobutamine echocardiography: a novel test for the detection of milder forms of coronary artery disease.

OBJECTIVES: This study was designed to assess the clinical, hemodynamic and diagnostic effects of the addition of dobutamine to dipyridamole echocardiography. BACKGROUND: Pharmacologic stress echocardiography with either dipyridamole or dobutamine has gained acceptance because of its safety, feasibility, diagnostic accuracy and prognostic power. The main limitation of the two tests is a less than ideal sensitivity in some patient subsets, such as those with limited coronary artery disease. We hypothesized that two pharmacologic stresses might act synergistically in the induction of ischemia by combining the mechanisms of inappropriate coronary vasodilation (with dipyridamole) and an increase in myocardial oxygen consumption (with dobutamine). METHODS: One hundred fifty patients (mean [+/- SD] age 51 +/- 11 years) referred for stress echocardiography were initially studied by dipyridamole-dobutamine echocardiography. The test was stopped during the dipyridamole step in 95 patients for achievement of a predetermined end point (obvious dyssynergy induced by lower or higher dipyridamole dose), and dipyridamole-dobutamine tests were performed in 55 patients (negative dipyridamole echocardiographic test). In the same 150 patients the dobutamine echocardiographic test (up to 40 micrograms/kg body weight per min) was performed on a separate day. RESULTS: Significant coronary artery disease (> 50% diameter stenosis of at least one major coronary vessel by quantitative coronary arteriography) was present in 131 patients (one vessel in 115; two vessels in 10, three vessels in 6), with normal coronary arteriography in 19. The feasibility of the dipyridamole-dobutamine test was 96%. Self-limiting side effects occurred in 5% of patients. The peak rate-pressure product was lowest during the dipyridamole test (132 +/- 30) and was comparable during the dobutamine (186 +/- 59) and dipyridamole-dobutamine tests (179 +/- 45, p = NS vs. dobutamine; p < 0.01 vs. dipyridamole). Sensitivity was 71% for dipyridamole, 75% for dobutamine and 92% for dipyridamole-dobutamine echocardiography (dipyridamole vs. dipyridamole-dobutamine, p < 0.01; dobutamine vs. dipyridamole-dobutamine, p < 0.01; dipyridamole vs. dobutamine, p = NS), whereas specificity was 89% for dipyridamole, 79% for dobutamine and 89% for dipyridamole-dobutamine echocardiography (p = NS for all). CONCLUSIONS: Routine dobutamine addition to dipyridamole stress testing is clinically useful and well tolerated. It expands the spectrum of the disease detectable by pharmacologic stress echocardiography and allows documentation of milder forms of coronary artery disease that can be missed by conventional dipyridamole or dobutamine stress echocardiography.

Adult↗
PubMed1994

Stress echocardiography in the detection of myocardial ischemia. Head-to-head comparison of exercise, dobutamine, and dipyridamole tests.

BACKGROUND: Exercise and pharmacological stress echocardiography have emerged as convenient alternatives to myocardial scintigraphy. The objective of this study was to compare in the same patients the diagnostic values of exercise, dobutamine, and dipyridamole stress echocardiography tests for detection of myocardial ischemia. METHODS AND RESULTS: We performed exercise (maximal treadmill Bruce protocol), dobutamine (up to 40 micrograms/kg per minute) and dipyridamole (up to 0.84 mg/kg over 10 minutes) stress echocardiography tests, in random sequence and on separate days, in 136 consecutive patients. All patients underwent coronary angiography. Significant coronary artery disease was defined by quantitative coronary angiography as a lesion with a diameter stenosis > or = 50%. A stress echocardiogram was considered positive when new or worsening of preexisting wall motion abnormality was observed. Most of the patients (94%) were receiving the same antianginal medication for each stress test; 59 patients were receiving concomitant beta-blocker therapy. The prevalence of coronary artery disease was 87.5%, with 108 patients having one-vessel coronary artery disease. Peak heart rate and systolic blood pressure were higher with exercise than with dobutamine or dipyridamole (P < .01). Sensitivity of exercise, dobutamine, and dipyridamole stress echocardiography was 88%, 82%, and 74% (dipyridamole versus exercise, P < .01), respectively. Specificity was 82%, 77%, and 94%, respectively. The overall accuracy was 87%, 82%, and 77% (dipyridamole versus exercise, P < .01), respectively. The accuracy of dipyridamole was higher (P = .02) in the group of patients not receiving beta-blockers (84%) than in the patients receiving beta-blocker therapy (66%), whereas the accuracy of exercise and dobutamine were only slightly higher in the patients not receiving beta-blockers. Significant side effects occurred in 3%, 11%, and 1% of patients during exercise, dobutamine, and dipyridamole tests, respectively. CONCLUSIONS: Despite the different hemodynamic effects, exercise, dobutamine, and dipyridamole echocardiography have high overall diagnostic values. In this group of patients with a predominance of one-vessel coronary artery disease, the overall diagnostic accuracy of stress echocardiography tests was higher for exercise than for dobutamine or dipyridamole. Concomitant beta-blocker therapy significantly decreased the accuracy of the dipyridamole stress echocardiography test. Pharmacological stress testing (dipyridamole without beta-blockers) can therefore be used as an efficient option for detection of myocardial ischemia in patients who are unable or poorly motivated to exercise adequately.

Adrenergic beta-Antagonists↗
PubMed1986

Effects of capsaicin on molluscan neurons: an intracellular study.

Effects of capsaicin (CAP) on membrane properties and action potentials (AP) were studied (30-300 microM, at 22 degrees C, pH 7.4) in Helix and Aplysia neurons. CAP (100-300 microM) depolarized the cell membrane and increased the slope resistance. The neuronal firing increased and/or the spike threshold decreased. CAP differentially affected the APs generated in A- and B-cells in Helix or S- and F-cells in Aplysia. Plateau-like prolongation of the APs with a concomitant increase of the hump duration was observed in A-cells, while a significant prolongation of the spike duration was at 90% repolarization time in B-cells. The electrophysiological changes proved to be similar when CAP acted in homologous Helix and Aplysia neurons, but were less pronounced in the latter animal. CAP decreased the rate of rise and the rate of fall of the APs and shortened the action potential duration (APD) in Na-free (TEA) solution. CAP-induced events were dose-dependent and reversible.

Action Potentials↗