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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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01.01.2011.

Original scientific paper

UTILIZATION OF ANTIBIOTICS FOR SYSTEMIC USE AT THE SURGICAL CLINIC OF THE CHC - PRISTINA IN GRACANICA

In our work we analyzed utilisation of antibiotics for systemic use at the Surgical Clinic of the Clinical Hospital Centre - Pristina in Gracanica in 2007. and 2008. Data on antibiotic utilization were delivered on the basis of drug dispensing records from the Central Hospital Pharmacy during the two-years period. Antibiotics were distributed inside the ATC/DDD system in accordance with WHO guidelines. Quantitative antibiotics' utilisation was expressed as number of defined daily doses per 100 patient-days (DDDs/100 PD). Overall use of antibiotics in 2007 was 123.37 DDDs/100 PD, and 125.09 DDDs /100 PD in 2008. Three most utilized antibiotics in 2007. were cefuroxime 24.26 DDDs/100 PD (19.66 % of total antibiotics' use), ceftriaxone 16.65 DDDs/100 PD (13.49 %), and cephalexin 15.78 DDDs/100 PD (12.79 %). In 2008. the most utilized were ceftriaxone 23.23 DDDs/100 PD (18.57 %), cefuroxime 22.53 DDDs/100 PD (18.01 %), and co-trimoxazole 19,55 DDDs/100 PD (15.63 %). Qualitative and quantitative part of the consumed antibiotics was mainly in accordance with the results of similar researches in our country.

S. Bulajić, S. Hadžistević, D. Milovanović, G. Trajković, N. Vujačić, Z. Stanojević

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

01.12.2010.

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

01.01.2009.

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

01.01.2006.

Original scientific paper

DRUG TRANSITION THROUGH THE BLOOD-BRAIN BARRIER AFTER THE RETROGRADE INTRAARTERIAL APPLICATIO

Transition of xenobiotics from blood into brain tissue is limited by the blood-brain barrier (BBB), a very selective functional barrier that excludes penetration of various substances, while allowing essential nutrients to enter into CNS. Transport of drugs through the intact BBB depends of their physico-chemical characteristics, the way of drug application and of anatomical and functional integrity of the barrier. The aim of this work was to examine penetration of quinine and lysinacetylsalicilate in vivo through the rat BBB, after the intraarterial injection via the a. axillaris in the course to CNS. The
experiment was done on anaesthetized Wistar rats, body weight 200-300 g. Test animals received injection of quinine (25 mg/kg) or LAS (90 mg/kg). Blood from the left jugular vein and brain samples (brain stem, cerebellum, right and left cerebral hemispheres) were taken in four minutes period. Quinine concentrations in rat brain were higher than in blood (ratio between blood/brain concentration was <1) while LAS concentrations in blood were permanently higher, according to their liposolubility. Maximal concentration in the brain tissue of both drugs are time dependent which indicated the useness of an active transport

S. Stević, V. Jakovljević, R. Mitić, L. Žorić, Z. Stanojević, Z. Bukumirić, S. Bulajić, M. Bursać, L. Vitković

01.01.2006.

Professional reviews

MONITORING THE ADVERSE ADVERSE DRUG REACTIONS REACTIONS TODAY

One the of most importante charactersistics of drug is a drug safety. However, there is no absolute safety. Medicines are troughly tested in controlled clinical trials with limiting population and short duration. Experience has shown that much of our knowledge about a medicine becomes available during the subsequent prescribing practice. Therefore there is a need for continued monitoring medicines after granting of product licence for a new drug (phrmacovigilance). WHO international system for drug safety monitoring as maintained by the Upsala Monitoring Centre (UMC) in Sweden, has built up vastedatabase of reports of suspect adverse drug reactions, coming from national centres in 75 countries in all of the world. The international system products valuable information from countries around the world, to support regulatory follow-up and decision-making. Emphasis is on those signals that may remain at the national level, because of small numbers or absence of local reports. The aim of the WHO's international pharmacovigilance program is a safe and rational medicines evrywhere. In Serbia as of 2005. National Medical Devices Agency is acting on behalf of the Ministry of Health as National Centre for Adverse Drug Reactions. The form for reporting adverse effects of medicines, in both pre-marketing and post-marketing phase can be found and downloaded in Word format on the Agency`s web site www.alims.sr.gov.yu.

S. Janićijević-Hudomal, J. Rašić, R. Mitić, Z. Stanojević

01.01.2006.

Professional reviews

PLACE OF ZINK PREPARATION AS DIETETIC SUPPLEMENT IN NON-INSULIN-DEPENDENT DIABETES MELLITUS

Considering its importance in cell replication and differentiation, programmed cell death, DNA transcription, function of hormones, biological membranes and immunological system, zinc probably has a major role in enabling a proper
function of different tissues, organs and organic system in general. As an essential micronutrient wich is directly involved in metabolizm of insulin, zinc play important role in pathogenesis of diabetes mellitus and its complications. On the other hand, low zinc absorption and hyperzincuria in diabetic animals and humans have indicated that diabetics are more susceptibile to zinc deficiency compared to healthy persons. Inasmuch as zinc plays an important role in syntesis, storage and secretion of insulin as well as conformational integrity of insulin in the hexameric form, zinc deficiency may adversely affect the ability of the islet Numerous studies suggested that urinary zinc excretion was higher in diabetes mellitus, probably as result of hyperglycemia. In contribution, there are findings about correlation between urinary zinc excretion and blood glycosylated hemoglobin (HbA1c) levels in non-insulin dependent diabetic patients. Recent experimental investigations showed that zinc supplementation inhibited NF-kB activation in the pancreas and decreased the expression of inducibile nitric oxide synthase, a downstream target gene of NF-kB. The ability of zinc to modulate NF-kB activation in the diabetogenic pathway may be the key mechanism for zinc's protective effect and important criterion for choosing nutritional strategies for diabetes mellitus prevention.

Z. Stanojević, R. Mitić, S. Stević, Z. Bukumirić, B. Biševac, M. Miletić, S. Bulajić

01.12.2006.

Professional reviews

THE USE OF THE USE OF ANTITUBERCULOSIS DRUGS (A ANTITUBERCULOSIS DRUGS (ATD) TODAY

The World Health Organization (WHO) declared tuberculosis (TB) a global emergensy in recognition of its growing importance as public health problem. In response to this situation WHO in 1990 was developed new strategy and framework for effective TB control, wich was called „DOTS“. The aims of treatment of TB are: to cure the pation of TB, to prevent death from active TB or its late effects, to prevent relapse of TB, to decrease transmission of TB to others, and to prevent
the development of acqured drug resistance. Antituberculosis drugs (ATD) are antibiotics and synthetic drugs used in the
treatment of tuberculosis and other deases caused by microorganisms of the genus Mycobacterium. The essential ATD are:
isoniazid (H), rifampicin (R), pyrazinamid (Z), streptomycin (S), ethambutol (E), and thioacetazone (T). The reserve ATD
are: amikacin (Am), kanamycin (Km), capreomycin (Cm), ciprofloxacin (Cx), ofloksacin (O), cycloserine (Cs), ethionamide (Et), protionamide (Pt), and p-aminosalycilic acid (PAS). The regimen recommended for each patient depends on the
diagnostic category for each patient. There are several possible regimens. ATB treatment regimens consists of two phases:
an initial phase and a continuation phase

J. Rašić, S. Janićijević-Hudomal, D. Radišić, Z. Bukumirić, Z. Stanojević

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