Papers by Milica Prostran
Journal of Pharmacological Sciences, 2011
We aimed to examine the rate of thrombotic events after discontinuation of one year clopidogrel t... more We aimed to examine the rate of thrombotic events after discontinuation of one year clopidogrel therapy in patients with implanted coronary stent, and to determine platelet aggregability by multiple electrode analyzer after cessation of clopidogrel. This prospective, multicenter study enrolled 200 patients subjected to coronary stent implantation and treated with aspirin + clopidogrel one year after the stent placement. Platelet aggregation was measured using 3 agonists [adenosine diphosphate with PGE(1) (ADPHS), arachidonic-acid (ASPI), and thrombin receptor activating peptide (TRAP)] on the day of cessation of clopidogrel and at 10, 45, and 90 days after clopidogrel was stopped. Two thrombotic events were registered during the 6-months follow up (one ischemic stroke and one myocardial infarction; incidence of 1%). The mean values of ADP + PGE(1)- and ASPI-induced aggregation 10 - 90 days after the cessation of clopidogrel were significantly higher than values obtained before the termination of the drug (P < 0.001, all). Cessation of clopidogrel did not influence the TRAP-induced aggregation, which reached the plateau in all measurements. In conclusion, the incidence of thrombotic events after the cessation of one-year clopidogrel treatment might be lower than expected in patients with implanted coronary stent.
European Journal of Pain Supplements, 2011
ABSTRACT Background and Aims: A large number of morphinans have been synthesized so far, both to ... more ABSTRACT Background and Aims: A large number of morphinans have been synthesized so far, both to establish the structureactivity- relationship (SAR) and to find novel, clinically useful antinociceptive drugs. The aim of the present study is to evaluate the analgesic activity and the effect on the body temperature of the newly synthesized morphinan compound: 6,14-Ethenomorphinan-7-methanol, 4,5-epoxy-6-fluoro-3- hydroxy-a,a,17-trimethyl (C22H26FNO3HClH2O). Methods: Analgesic activity was assessed by tail-immersion test and the body temperature by insertion of a thermometer probe 5cm into the colon of unrestrained male Wistar rats (200–250 g). The animals were tested in groups of 6 rats per dose. Results: The novel compound (0.037–0.049 mg/kg free base) is about 55 (32.050–93.684) and 33 times (16.863–66.884) more potent than morphine (1.053–3.570 mg/kg free base) in producing analgesia and hyperthermia, respectively. Also, the mean deviation from baseline colonic temperature was up to 1.5°C for both compounds. The maximum analgesic effect of morphine is achieved 60 minutes after the i.p. injection, and this effect lasted up to 120 minutes. The new compound achieved maximum analgesic effect faster (after 10 minutes), and exhibited shorter duration of action (30 minutes). Naloxone hydrochloride (1 mg/kg; sc) abolished both the effects observed, suggesting that they are mediated via opioid receptors. Conclusions: It is concluded that, in comparison with morphine, the newly synthesized morphinan compound is more potent opioid and exhibits shorter duration of action.
Vojnosanitetski pregled, 2012
Selective serotonin reuptake inhibitors are the most commonly chosen antidepressants in patients ... more Selective serotonin reuptake inhibitors are the most commonly chosen antidepressants in patients with Parkinson's disease (PD). The aim of our study was to assess the influence of fluoxetine (Flu) on motor functions in patients with PD. In this prospective, controlled, open-label study, 18 patients with PD and mild depression [(10 < or = Hamilton Rating Scale for Depression (HDRS) < or = 23)] without dementia [(25 < or = Mini-Mental State Examination (MMSE)] were treated with Flu. Both single and repeated dose effects of Flu were assessed on days 1-80. Plasma concentrations of Flu and norfluoxetine (NORFlu) were correlated with the results of selected motor function performance scores: The Unified Parkinsons Disease Rating Score (UPDRS), Finger Tapping Test (FTT) and Purdue Pegboard Test (PPT). Severity of PD, depression and dementia were evaluated using standard tests [(Hoehn and Yahr stages (HY), activity of daily living (ADL), UPDRS, HDRS, MMSE)]. Steady-state for Flu/NORFlu was reached after 18 days of treatment. Such a plateau correlated with significant improvements in both scores of depression and Parkinson's disability (HDRS, UPDRS and ADL, respectively). In addition, FTT and PPT scores also increased until day 18, with further slight fluctuations around the plateau. Optimal motor performances correlated with Flu concentrations of approximately 60-110 microg/L. Flu (20 mg/day) significantly reduced depression in PD patients while it did not impair their motor performances. Because substantial placebo effects may arise in studies of PD and depression, large, prospective, randomized, placebo-controlled clinical trials are warranted.
Journal of the Neurological Sciences, 2006
Both methylenetetrahydrofolate (MTHFR) C677T genotype and levodopa treatment may give rise to ele... more Both methylenetetrahydrofolate (MTHFR) C677T genotype and levodopa treatment may give rise to elevated serum homocysteine levels in parkinsonian patients. We aimed to clarify the interplay of these factors in pathogenesis of Parkinson's disease (PD)-related hyperhomocysteinemia. Total serum levels of homocysteine (tHcy) and MTHFR C677T genotype were investigated in levodopa-treated and -untreated parkinsonian ("de novo") patients, as well as in control healthy subjects matched by age and gender (N=83, 30 and 53, respectively). MTHFR C677T genotypes were equally distributed in PD patients and control subjects, the T allele homozygosity being observed in app. 12-17% cases. tHcy concentrations were significantly higher in both levodopa-treated and -untreated PD patients than in control subjects, and in TT homozygotes than in CT or CC genotype carriers. tHcy levels significantly correlated with the duration of the disease in PD treated patients only, reaching the maximum after 3-6 years. However, there was no correlation between tHcy levels and total daily intake of levodopa in the same group of PD patients. In conclusion, MTHFR C677T genotype is a significant factor for hyperhomocysteinemia in patients with PD, levodopa-untreated and probably even more in levodopa-treated PD patients.
Vojnosanitetski pregled, 2005
... Eleonora Doljić*, Zorica Neić, Radan Stojanović, Nevena Divac, Zoran Todorović, Sonja V... more ... Eleonora Doljić*, Zorica Neić, Radan Stojanović, Nevena Divac, Zoran Todorović, Sonja Vučković, Vladimir Kostić*, Milica Prostran ... snano inhibie oslobađanje acetilholina iz strijatuma i hiperaktivnost holinergičkih neurona (usled nedostatka dopa-mina) to dovodi ...
International Journal of Antimicrobial Agents, 2009
Hellenic journal of cardiology : HJC = Hellēnikē kardiologikē epitheōrēsē
The aim of our study was to examine blood pressure (BP) changes in hypertensive and nonhypertensi... more The aim of our study was to examine blood pressure (BP) changes in hypertensive and nonhypertensive patients after intravitreal bevacizumab injections and to assess whether intravitreal bevacizumab carries an associated vascular risk in patients with exudative ocular disease. We also aimed to estimate the influence of gender. The study included 57 patients with age-related macular degeneration who received an intravitreal injection of 1.25 mg (0.1 mL) of bevacizumab. We analyzed systolic and diastolic BP values separately. Patients were divided into males and females, and into hypertensives and normotensives based on their BP values. BP was measured before bevacizumab administration, and 10 minutes, 1 hour, 2 days, 7 days and 6 weeks after the injection. Males had a statistically significant decline in systolic BP values 1 hour and 6 weeks after drug administration (p<0.05). The most notable significant decline in diastolic BP values was for males and for normotensive participant...
Psychiatria Danubina
A rapid expansion of new treatment options in recent decades and the increasing volume of scienti... more A rapid expansion of new treatment options in recent decades and the increasing volume of scientific evidence published on a daily basis have been followed by the necessity of introduction of clinical guidelines and therapeutic algorithms. The development of these guidelines and algorithms has also been driven by increased cost-awareness and the increasing pressure to improve cost-efficiency. The Serbian Physicians Society published "Therapeutic Guidelines for the Treatment of Schizophrenia" in 2003 and "Therapeutic Guidelines for the Treatment of Bipolar Affective Disorder" in 2004. The School of Medicine, University of Belgrade published "Therapeutic Guidelines for the Treatment of Depression" in 2004. All of these national guidelines, at the moment of development, were based upon up-to-date scientific evidence. According to the recently conducted survey at the Institute of Psychiatry, Clinical Centre of Serbia, about 65% of psychiatrists stated that ...
Journal of Pharmacological Sciences, 2005
The effect of different frequencies of direct subtetanic electrical stimulation (14, 20, and 30 H... more The effect of different frequencies of direct subtetanic electrical stimulation (14, 20, and 30 Hz) and aminophylline (AMPh) pretreatment on the effect of N(G)-nitro-L-arginine methyl ester (L-NAME) (1 mM) on isolated rat diaphragm was investigated. L-NAME potentiated tension developed (Td) in the diaphragm pretreated with a single concentration of AMPh (1.08 mM) in a frequency-dependent manner. The effect was significantly different in comparison with muscle incubated 30 min with Tyrode solution only. In the muscle pretreated with cumulative concentrations of AMPh (0.36 - 3.60 mM), the frequency-dependent potentiation of Td induced by L-NAME and the difference between L-NAME-treated and untreated muscle were lost.
General Pharmacology-the Vascular System, 2000
Adenosine (0.1–300 μM) induced concentration- and endothelium-dependent relaxation of rat renal a... more Adenosine (0.1–300 μM) induced concentration- and endothelium-dependent relaxation of rat renal artery (RRA). NG-Nitro-l-arginine (l-NOARG, 10 μM) significantly reduced adenosine-elicited dilatation, but not the application of indomethacin (10 μM), ouabain (100 μM) or tetraethylammonium (TEA, 500 μM). In the presence of high concentration of K+ (100 mM) or glibenclamide (1 μM), adenosine-evoked relaxation was almost abolished. 8-(3-Chlorostyril)caffeine (CSC, 0.3–3 μM),
In the placebo-controlled open label randomized study, 104 patients with acute myocardial infarct... more In the placebo-controlled open label randomized study, 104 patients with acute myocardial infarction were observed for a period of seven years: 52 patients with standard therapy (con group) and 52 patients with captopril therapy (cap group), 6.25 mg the first 12 h after the onset of AMI, followed by 6.25 mg to 25 mg two times daily. No differences were observed between the groups at baseline. The seven years period was reached by 80 patients; in the captopril group, there were less patients with cardiovascular events (p<0.05), less patients with clinical signs of heart failure, less mortality, and higher levels (p<0.02) of HDL cholesterol. Despite the small group of patients (n=52), statistically significant increase in HDL cholesterol values and less pronounced mortality and morbidity during the entire period of seven years were observed in the cap group.
Vojnosanitetski pregled. Military-medical and pharmaceutical review
Journal of basic and clinical physiology and pharmacology
The effects of physostigmine, L-arginine and NG-nitro-L-arginine methyl ester (L-NAME) were inves... more The effects of physostigmine, L-arginine and NG-nitro-L-arginine methyl ester (L-NAME) were investigated in urethane-anaesthetized rats. The drugs were chosen because physostigmine has been known to produce an increase in peripheral adrenergic activity, whereas L-arginine and L-NAME have been known to modulate nitric oxide (NO) production. Slow infusion of L-arginine produced significant hypotension, but only in animals pretreated by physostigmine. L-NAME applied in the same way produced a slow developing increase in blood pressure, but not in animals pretreated by physostigmine. The pressor responses to physostigmine were potentiated if the drug was injected during infusion of L-NAME, and depressed if the drug was injected after stopping L-NAME infusion (in rats not pretreated with physostigmine). It is concluded that L-arginine-NO pathways act in vivo to oppose peripheral vasoconstrictor influences coupled with central cholinergically mediated activation of the adrenergic system, ...
Magnesium research : official organ of the International Society for the Development of Research on Magnesium
This study investigated whether systemic magnesium sulfate (an antagonist at the glutamate subtyp... more This study investigated whether systemic magnesium sulfate (an antagonist at the glutamate subtype of N-methyl-D-aspartate receptor) affects inflammatory pain, and whether the nitric oxide pathway is involved. Carrageenan (0.5%, 0.1 mL, intraplantar)-induced mechanical hyperalgesia was evaluated using the electronic von Frey test in male Wistar rats. Magnesium sulfate had no effect when injected locally into the inflamed rat paw. However, subcutaneous magnesium sulfate, at doses of 0.5, 5, 15 and 30 mg/kg, reduced the hyperalgesia by 44.4 ± 8.8, 68 ± 8.4, 24.6 ± 6.9 and 45.3 ± 6.7% respectively. N-nitro-L-arginine methyl ester hydrochloride (L-NAME) (3 and 5 mg/kg, intraperitoneal), a non-selective nitric oxide synthase inhibitor, significantly reduced the effects of magnesium sulfate. Also, L-arginine (0.4 mg/kg, subcutaneously) significantly reversed the effect of L-NAME in the magnesium sulfate-treated rats. A selective inhibitor of neuronal or inducible nitric oxide synthase, N-...
Die Pharmazie, 2006
In this study we determined whether oxcarbazepine (OXC) could produce local peripheral antinocice... more In this study we determined whether oxcarbazepine (OXC) could produce local peripheral antinociceptive effects in a rat model of inflammatory hyperalgesia, and whether adenosine receptors were involved. When coadministered with the pro-inflammatory compound concanavalin A, OXC (1000-3000 nmol/paw) caused a significant dose- and time-dependent anti-hyperalgesia. Caffeine (1000-1500 nmol/paw), a nonselective adenosine receptor antagonist, as well as 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) (10-30 nmol/paw), a selective A1 receptor antagonist, coadministered with OXC, significantly depressed its anti-hyperalgesic effect. Drugs injected into the contralateral hind paw did not produce significant effects. These results indicate that OXC produces local peripheral anti-hyperalgesic effects, which is mediated via peripheral A1 receptors.
Vojnosanitetski pregled. Military-medical and pharmaceutical review, 2005
Vojnosanitetski pregled. Military-medical and pharmaceutical review
Medicinski pregled, 2003
All three isoforms of nitric oxide synthase (NOS) are identified within various tissues of the re... more All three isoforms of nitric oxide synthase (NOS) are identified within various tissues of the respiratory system. Under physiological conditions, small amounts of NO, produced by constitutive isoforms of NOS, appear to be important in regulation of basal pulmonary vascular tone and in mediating transition from fetal to neonatal circulation; also, NO exerts antiinflammatory actions, and modulates the respiratory smooth muscle tone. NO AND RESPIRATORY TRACT DISEASES: Under pathological conditions, inducible NOS-derived NO may produce lung damage. In addition, increased or decreased production of NO is found in chronic obstructive pulmonary disease, cystic fibrosis, asthma and related inflammatory disorders, and exhaled NO level measurement is a useful tool in diagnostics of respiratory disorders. It has been shown that NO modulates contractility of the isolated diaphragm, and there are important interactions between NOS inhibitors and drugs for respiratory disorders (e.g. aminophylli...
Vojnosanitetski pregled. Military-medical and pharmaceutical review
Bioorganic & Medicinal Chemistry Letters
The synthesis of 4-methyl fentanyl, a prototype of a novel class of fentanyl analogues has been e... more The synthesis of 4-methyl fentanyl, a prototype of a novel class of fentanyl analogues has been effected in 5 steps, starting from N-ethoxycarbonyl-4-piperidone (approximately 20% overall yield). In the key step, N-phenylation of secondary aliphatic amide intermediare was achieved by a novel reaction, using diphenyliodonium chloride for the phenyl group transfer. Preliminary pharmacological results indicate that 4-methyl fentanyl is a super potent narcotic analgesic, about four times more potent than fentanyl.
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Papers by Milica Prostran