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Volume 53, Issue 4, 2025

Online ISSN: 2560-3310

ISSN: 0350-8773

Volume 53 , Issue 4, (2025)

Published: 30.06.2025.

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01.12.2014.

Professional paper

DESKRIPTIVNO-EPIDEMIOLOŠKE KARAKTERISTIKE KARCINOMA GRLIĆA MATERICE

Karcinom grlića materice je ozbiljan javno zdravstveni problem kako u svetu tako i kod nas. Kontrola karcinoma grlića materice pored prevencije podrazumeva ranu dijagnostiku i lečenje, ali i preciznu registraciju i praćenje obolelih žena. Da bi bila obezbeđena dobra kontrola bolesti, svi ovi delovi sistema moraju funkcionisati paralelno. Cilj rada je sagledavanje osnovnih deskriptivno-epidemioloških karakteristika obolelih i umrlih žena od raka grlića materice u svetu, Evropi i Srbiji. Poseban osvrt i detaljan epidemiološki prikaz usmeren je na područje centralne Srbije za period od 1999. do 2011. godine. U radu je primenjen deskriptivno-epidemiološki metod. Kao izvor podataka korišćeni su podaci Globocan-a (softver za procenu opterećenja bolesti populacije, pokrenut od strane WHO), kao i podaci Registra za rak centralne Srbije za analizirani period. U svetu, broj novoobolelih slučajeva za 2012. g. je 527624 (standardizovana stopa incidencije je 14,0 na 100000 žena). U pogledu mortaliteta, za dotičnu godinu broj umrlih žena je 265653 (standardizovana stopa mortaliteta je 6,8 na 100000 žena). Od karcinoma grlića materice na svaka 2 minuta u svetu umre jedna žena (720 dnevno). U Evropi, ukupan broj novoobolelih žena za 2012. g. je 58348 (11,44 na 100000 žena). Ukupan broj umrlih žena je 24378 (3,75 na 100000 žena). U Srbiji, ukupan broj novoobolelih žena za 2012. g. je 1501 (23,8 na 100000 žena). Ukupan broj umrlih žena je 609 (7,7 na 100000 žena). Pozicija Srbije u Svetu u pogledu obolevanja je 62 (od 182. zemlje), dok je 84. u pogledu mortaliteta, što nas svrstava u gornju polovinu liste svih zemalja u svetu. Prema podacima Registara za rak za centralnu Srbiju, prosečna standardizovana stopa incidencije od 23,9/100000 žena i mortaliteta od 7,2/100000 za period 1999-2011. godine ukazuju na nepovoljnu epidemiološku situaciju ovog malignoma u centralnoj Srbiji. Mada se analizom pomenutog vremenskog intervala registruje blagi pad trenda obolevanja u centralnoj Srbiji (y=27,13-0,47x; p>0,05, otprilike jedan slučaj karcinoma grlića materice na 100000 žena manje za sledeće dve godine). Naprotiv, za isti analizirani period, beleži se porast umiranja (y=7,16+0,01x; p>0,05).

D. Vukicevic, R. Mitic, M. Mijovic, N. Mitic, L. Vitkovic, B. Djerkovic, V. Nedeljkovic

01.01.2011.

Original scientific paper

EFFECTS OF DIFFERENT DOSES OF ZINC PREPARATION ON GLYCEMIA AND ANTIOXIDANT PARAMETERS IN EXPERIMENTALLY INDUCED DIABETIC RABBITS

Researches with micronutrients are getting more and more important in science and also in practice. In this view zinc, chromium, copper and selenium are having a special role in preventing micro- and macrovascular diabetic complications, as integral components of antioxidant enzymes (superoxide dismutase and glutathione peroxidase) and also as cofactor of enzymes and hormones involved in the metabolism of glucose and lipid. The aim of this study was to evaluate the effects different doses of zinc on glycemia and parameters of antioxidative defense: superoxide dismutase (SOD) and total antioxidant status (TAS), and correlation glycoregulation with antioxidant system of the alloxan-induced diabetic rabbits. The study was conducted on fourteen New Zealand rabbits of both sexes, weighing 2 to 3.5 kg. Experimental diabetes was induced in rabbits by intravenous injection of alloxan (80 mg /kg BW). Three weeks after induced experimental diabetes, rabbits were treated orally appropriate doses of chelated zinc: I dose - 15 mg, after a washout period (10 t ), II dose - 25 mg, af- 1/2 ter a washout period, III dose - 50 mg. Blood samples were taken at specific time intervals: before alloxan induced diabetes, after alloxan induced diabetes, after application the first dose of 15 mg of zinc, after application of a second dose of 25 mg of zinc, after application of third dose of 50 mg of zinc. The zinc preparation did not cause a statistically significant reduction in serum glucose level when administered in single doses 15, 25 and 50 mg in experimentally induced diabetic rabbits. However, the activity of superoxide dismutase (SOD) was significantly increased after single dose preparations of zinc at a dose 15 mg (p<0,05), 25 mg (p<0,001) and 50 mg (p<0,001) in relation to the activity recorded before the application of zinc. Also, after the application first, second, and than third dose of zinc in diabetic rabbits was recorded statistically significant increase of TAS in relation to the value recorded before the application of zinc (p<0,001). Glucose concentrations negatively correlated with superoxide dismutase activity. This indicates that oral application of zinc preparation can reduce the harmful effects of oxidative stress in diabetes.

Z. Stanojević, R. Mitić, M. Stanić, M. Miletić, D. Valjarević, S. Hadžistević, M. Dejanović

01.01.2011.

Original scientific paper

CEPHALOSPORINS AND NEPHROTOXICITY

Cephalosporins are bactericidal antibiotics that are active against a wide variety of Gram(+) and Gram(-) aerobic bacteria, along with a few anaerobic species. Adverse effects of cephalosporins are uncommon and reversible. Cefalotin and cefaloridine exhibit a nephrotoxic effect and might cause renal tubule necrosis. No data about the nephrotoxicity of cefotaxime and ceftriaxone has been presented in literature so far. When cephalosporins are applied via intramuscular injection a local reaction is possible, whereas with IV administration thrombophlebitis develops in about 5% of all cases. Hypersensitivity reactions, as well as some hematological disorders (thrombocytosis, leukopenia, neutropenia) might also occur. Cephalosporins were found to sometimes cause an augmentation of transaminase (AST, ALT), alkaline phosphatase, and, less frequently, bilirubin levels, too. The goal of this study was to evaluate the creatinine values in the serum of patients hospitalised in Kosovska Mitrovica Health Centre. The values were determined before, within and after 7 days of cephalosporin administration (cefotaxime 2x1000mg IM; ceftriaxone 2x1000mg IV). Data concerning certain hematological and biochemical variables will be presented as well. Creatinine levels were measured by the Jaffe reaction method. Both cefotaxime and ceftriaxone yielded a statistically significant increase of the serum creatinine values. As these cephalosporins do not show a nephrotoxic effect, the increase can be explained by the interference of sodium picramate, a byproduct of the Jaffe reaction which is produced regardless of whether the process is manual or automated.

M. Stanić, R. Mitić, S. Pajović, V. Adžić, K. Bulatović

01.01.2011.

Professional paper

THE PROSPECT OF UTILIZING SPREADSHEET SOFTWARE IN PHARMACOKINETICS

This article aims to promulgate the use of Microsoft Excel, one of the predominant spreadsheet applications, in the calculation of approximate functions by the method of spline polynomial interpolation. Cubic spline functions have demonstrated a remarkable suitability for the analysis of pharmacokinetic data of drugs with non-linear kinetic behavior or an unknown kinetic model, as well as general kinetic analysis, regardless of pharmacokinetic and compartmental models. It should be noted that cubic spline polynomials can be employed in determining a highly significant pharmacokinetic parameter - the area under curve (AUC), especially when the area measurement is not the principal intention, and the data is to be used for further research. Spreadsheet software is exceptionally pertinent to this kind of computation, as it delivers high precision and virtually instantaneous availability of the results. Moreover, this type of software possesses conspicuous flexibility, characterized by a real-time graphical representation and the capability to sustain user-created functions through a macro-language (VBA - Visual Basic for Applications) implemented in the program itself. 

R. Mitić, J. Damjanović

01.12.2010.

Original scientific paper

THE EFFECT AND INTERACTION ASPIRIN AND TICLOPIDINE ON HEMATOLOGICAL VARIABLES IN RATS

The combination of aspirin and ticlopidine has been proven to reduce the frequency of haemorrhagic and vascular complications after coronary artery stenting, but also can cause serious hematological side effects. The purpose of this study was to evaluate the effect and interactions aspirin and ticlopidine on hematological variables. Thirty two Wistar rats were divided in four groups and they received intraperitoneal one of the following treatments for 4 days: group I - control, group II aspirin (50 mg/kg BM), group III - ticlopidine (125 mg/kg/day) and group IV - aspirin+ticlopidine combination (50 mg/kg/day+125 mg/kg/day). Hematological variables were determined at once after taking the sample of blood. Relationship between measured variables was determined by calculating linear correlation coefficient (r). The hematocrit, haemoglobin and red blood cell were significantly decreased in group treated with aspirin+ticlopidine combination compared to control (p< 0,05). Neutrophil and platelet count weren't significantly different in treated groups, but were slightly decreased in groups treated with ticlopidine and aspirin+ticlopidine combination. Between hematocrit and platelet count in control group of rats was noticed negative and medium correlation (r=-0,41), in groups treated with ticlopidine and aspirin+ticlopidine combination positive and medium correlation (r=0,52; r=0,69). Based on obtained results it can be observed significant decreased hematocrit, haemoglobin and red blood cell in group treated with aspirin+ticlopidine combination. The negative correlation between hematocrit and platelet count in control group becomes positive after the treatment with ticlopidine alone and aspirin+ticlopidine combination.

Z. Stanojević, R. Mitić, V. Nestorović, D. Valjarević, S. Hadžistević

01.12.2010.

Professional paper

THE ASSESSMENT OF BIOLOGICAL EQUIVALENCE (BIOEQUIVALENCE) OF DRUGS BASED ON THEIR PHARMACODYNAMIC VARIABLES

Biological equality assessments are carried out by means of: a) comparative pharmacokinetic study; b) comparative pharmacodynamic study; c) controlled comparative clinical experimentation; d) comparative in vitro assay (dissolution test). The first method mentioned, i.e. determining the concentration of a drug in the blood of healthy volunteers, is the most accurate and most frequently employed. In this paper, a study conducted on healthy volunteers that displays the possibility of evaluating biological equality using pharmacodynamic variable data, giving the example of such assay of retard tablets of verapamil produced by two different companies, is presented. Taking into account the effects of this drug, biological equivalence was proved by comparing pharmacodynamic variables such as PR interval, systolic and diastolic blood pressure and heart rate.

R. Mitić, Z. Stanojević, J. Popović

01.12.2010.

Professional reviews

METABOLISM AND INHALED ANESTHETIC ELIMINATION

In this review paper, metabolism of most used inhaled halogenated anesthetics (halothane, enflurane, isoflurane, desulfurane and sevoflurane) is shown Only part of the anesthetics is metabolized, while the remainder is eliminated unchanged. They are metabolized by mixed function oxidases (reductive or oxidative pathways). 

J. Plačkić, Lj. Gvozdenović, M. Vojnović, M. Popović, R. Mitić

01.01.2009.

Original scientific paper

THE EFFECT OF VERAPAMIL ON TRACHEA RESPONSE CAUSED BY HISTAMINE AND ACETILCHOLINE

In the study with experimental animals in vitro conditions, the aim of the research was to examine the effect of verapamil on the even brawniness of the isolated organ of the respiratory ways (tracheas) in guinea-pigs on acetylcholine and histamine, and in that way, to examine local mechanisms of smooth muscle system but also to exclude the rest of the neurohumoral influences. The guinea-pigs of both sexes (average weight of 500-700 gr), were used for this experiment. 10 guinea-pigs were included in the experimental research; the trachea was taken from them after the immolation. The preparations of isolated organs of trachea were divided into two groups (A and B). The previous incubation of trachea -5 isolated by verapamil (1 minute) in concentration 10 M significantly reduced the contraction caused by acetylcholine -4 (ascent 21.49±9.63, r=0.97, p<0.05). Concentration of verapamil 10 M also caused significant fall of contraction (ascent -5 21.3±12.63, r=0.95, p<0.05). Verapamil in concentration 10 M significantly reduces the response of isolated trachea cau- -6 -5 -4 sed by histamine in concentrations 10 M and 10 M (slope 21.3±10.6, r=0.96, p<0.05).Concentration of verapamil 10 M significantly reduced the contraction of smooth muscles of isolated trachea caused by histamine (slope 15.46±10.47, r= 0.94, p < 0.05).

R. Mitić, B. Biševac, Z. Stanojević, M. Bursać, T. Đokić

01.01.2009.

Original scientific paper

CORRELATIONS BIOCHEMICAL VARIABLES OF ASPIRIN AND TICLOPIDINE ADMINISTERED ALONE AND IN COMBINATION IN RATS

A combination of aspirin and ticlopidine has been proven to reduce the frequency of haemorrhagic and vascular complications after coronary artery stenting. Also, ticlopidine is often associated with hyperbilirubinemia and abnormal liver function test values. The purpose of this study was to evaluate the correlations between biochemical variables (serum total cholesterol levels, total bilirubin concentration, serum activities of alkaline phosphatase and alanine- ALT and aspartate- AST aminotransferases) of aspirin and ticlopidine administered alone and in combination. The experiment was conducted on white laboratory rats, type Wistar. Thirty-two rats were divided in four groups and they received one of the following treatments for three days: group I - control, saline (1 ml/kg, i.p.); group II - aspirin (50 mg/kg/day i.p.); group III - ticlopidine (125 mg/kg/day i.p.) and group IV - aspirin+ticlopidine combination (50 mg/kg/day+125 mg/kg/day i.p.). Biochemical variables were determined at once after taking the sample of blood. Relationship between two measured variables was determined by calculating linear correlation coefficient (r). Between total cholesterol level and AST activity in control group of rats was noticed negative and low correlation (r=-0,27); in group treated with aspirin negative, high and significant correlation (r=-0,86); in group treated with ticlopidine negative and low correlation (r=-0,24); and in group treated with aspirin+ticlopidine combination positive, high and significant correlation (r=0,79). Between other investigated variables were not noticed significant correlation in all treated groups. Based on obtained results it can be noticed that negative correlation between serum total cholesterol level and AST activity in control, aspirin and ticlopidine groups becomes positive and significant only after the treatment with aspirin+ticlopidine combination.

Z. Stanojević, R. Mitić, V. Nestorović, S. Stević, Z. Bukumirić, S. Bulajić

01.01.2009.

Professional reviews

ALPHA LIPOIC LIPOIC ACID IN CLINICAL ACID IN CLINICAL APPLICA APPLICATION

Alpha lipoic acid is the most efficient of all known antioxidants for its lipo and hydrosolubility which enable easy penetrability in cytoplasm making its protection of free reactive radicals, energetic metabolism, regulation of genetic expresion etc. It has wide application in prevention and in therapy of diabetic angiopathy, neuropathy, cardiovascular, cerebrovascular, neurodegenerative disease, lesion, (insufficiency) of liver, HIV, intoxication with hard metals, mycotoxins etc. An important proprety of lipoic acid is its possibility to prevent or remove lesions which are caused by application aminogycosides and haloperidol (ototoxicity, nephrotoxicity) according to its wide application. R isomer of lipoic acid is physiological substance presented in organism which synthesize in in liver enabling its its application in relatively high dose for a longer period of time.

B. Vučinić, R. Mitić, S. Dimić, Z. Milanović, S. Sovtić

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