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Open access

DD Milovanovic, JR Milovanovic, M Radovanovic, I Radosavljevic, S Obradovic, S Jankovic, D Milovanovic and N Djordjevic

Abstract

The aim of the present study was to investigate the distribution of CYP2C8 variants *3 and *5, as well as their effect on carbamazepine pharmacokinetic properties, in 40 epileptic pediatric patients on carbamazepine treatment. Genotyping was conducted using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and allele-specific (AS)-PCR methods, and steady-state carbamazepine plasma concentrations were determined by high performance liquid chromatography (HPLC). The CYP2C8 *3 and *5 polymorphisms were found at frequencies of 17.5 and 0.0%, respectively. After dose adjustment, there was a difference in daily dose in CYP2C8*3 carriers compared to non carriers [mean ± standard deviation (SD): 14.19 ± 5.39 vs. 15.46 ± 4.35 mg/kg; p = 0.5]. Dose-normalized serum concentration of carbamazepine was higher in CYP2C8*3 (mean ± SD: 0.54 ± 0.18 vs. 0.43 ± 0.11 mg/mL, p = 0.04), and the observed correlation between weight-adjusted carbamazepine dose and carbamazepine concentration after dose adjustment was significant only in CYP2C8*3 non carriers (r = 0.52, p = 0.002). However, the population pharmacokinetic analysis failed to demonstrate any significant effect of CYP2C8 *3 polymorphism on carbamazepine clearance [CL L/h = 0.215 + 0.0696*SEX+ 0.000183*DD]. The results indicated that the CYP2C8*3 polymorphism might not be of clinical importance for epilepsy treatment in pediatric populations.

Open access

Olivera M. Knezevic, Dragan M. Mirkov, Marko Kadija, Darko Milovanovic and Slobodan Jaric

The novel test based on isometric alternating consecutive maximal contractions performed by two antagonistic muscles has been recently proposed as a test of muscle function in healthy subjects. The aim of this study was to evaluate reliability and sensitivity of a novel test as a test of knee muscles function in athletes recovering from anterior cruciate ligament reconstruction. Fifteen male athletes with recent ligament reconstruction (4.0 ± 0.1 months following the surgery) and 15 sport and physical education students participated in the study. Peak torques of the quadriceps and hamstring muscles assessed both through the alternating consecutive maximal contractions and standard isokinetic test performed at 60 º/s and 180 º/s served for calculation of the hamstrings-to-quadriceps ratio and the bilateral difference in strength. When applied on individuals recovering from anterior cruciate ligament reconstruction, the novel test revealed a high within-day reliability and sensitivity for detecting imbalances both between antagonistic and between contralateral muscles. The present findings suggest that alternating consecutive maximal contractions could be used as a test of muscle function that is either complementary or alternative to the isokinetic test, particularly in the laboratories where the isokinetic devices are not available. Potential advantages of the novel test could be both a brief testing procedure and a possibility to conduct it using relatively inexpensive devices such as custom made kits containing a single one-axis force transducer.

Open access

Aleksandar Arsenijevic, Jelena Milovanovic, Bojana Stojanovic, Marija Milovanovic, Eric M. Gershwin, Patrick Leung, Nebojsa Arsenijevic and Miodrag L. Lukic

Abstract

Primary biliary cirrhosis (PBC) is an autoimmune disease of the liver that is, characterised by destruction of the intrahepatic bile ducts and the presence of antimitochondrial antibodies (AMAs). Several murine models of PBC, with similar serological, biochemical, and histological features to human PBC, have been developed in recent years. These animal models enable investigators to study the etiology and pathophysiologic mechanism of PBC. Immune response in PBC is directed towards E2 components of the 2-oxo-acid dehydrogenase family of enzymes, which is in located in mitochondria and is an immunodominant epitope (a lipoylated peptide sequence shared by enzymes). Immunisation of mice with 2-octynoic acid coupled to bovine serum albumin (2-OA-BSA) (which is an antigen that is structurally related to the E2 subunit of the pyruvate dehydrogenase complex [PDC-E2]) produces histologic features similar to those found in human PBC. Th is model of xenobiotic induced PBC is suitable for studying the early events in PBC pathogenesis and for developing new therapeutics in PBC.

Open access

P. Sovilj, M. Milovanović, D. Pejić, M. Urekar and Z. Mitrović

Abstract

Measurement methods, based on the approach named Digital Stochastic Measurement, have been introduced, and several prototype and small-series commercial instruments have been developed based on these methods. These methods have been mostly investigated for various types of stationary signals, but also for non-stationary signals. This paper presents, analyzes and discusses digital stochastic measurement of electroencephalography (EEG) signal in the time domain, emphasizing the problem of influence of the Wilbraham-Gibbs phenomenon. The increase of measurement error, related to the Wilbraham-Gibbs phenomenon, is found. If the EEG signal is measured and measurement interval is 20 ms wide, the average maximal error relative to the range of input signal is 16.84 %. If the measurement interval is extended to 2s, the average maximal error relative to the range of input signal is significantly lowered - down to 1.37 %. Absolute errors are compared with the error limit recommended by Organisation Internationale de Métrologie Légale (OIML) and with the quantization steps of the advanced EEG instruments with 24-bit A/D conversion

Open access

Danijela Jakšić-Gvozdić, Slobodan M. Janković, Danka Pajović, Sandra Vidojević, Srđan Stefanović and Jasmina R. Milovanović

Abstract

The aim of this study was to investigate the possible potential of preschool staff through a newly designed questionnaire and evaluate their role in the prevention of early childhood caries (EEC) in Serbia where extremely high prevalence of this preventable disease was recorded.

We preformed a cross-sectional study of 268 preschool staff using specially prepared semi-structured questionnaire for measuring potential of secondary children’s caregivers to prevent EEC. The questionnaire was tested on a pilot sample and after that all collected data were analyzed trough construction of correlation matrix with the evaluation of the value of each question, reliability testing, factorial analysis and estimating of its validity using SPSS software.

The tested questionnaire had good internal consistency based on the Cronbach’s alpha coefficient value of 0.873 calculated directly and similar value (0.899) after applied Spearman-Brown “prediction” formula. Using exploratory factorial analysis and orthogonal rotation, we identified two domains that emerged with similar loadings (4.043 and 3.183). The first factor (domain) reflected attitudes of the study participants towards prevention of EEC, and the second factor (domain) showed behaviour of the study participants, which includes preventive actions against EEC.

The total score of the questionnaire was correlated positively with oral health knowledge (Spearman’s correlation coefficient 0.331, p=000) and inversely with the length of employment, where each additional year of employment decreased the total score of the questionnaire by 1.20.

These findings could partially explain an extremely high prevalence of EEC in young children and indicate that preschool teachers should be more engaged in health education activities and motivation programs.

Open access

Jasmina R. Milovanovic, Katerina Dajic, Anđelka Stojkovic, Aleksandra Tomic Lucic, Slobodan M. Jankovic and Sandra Matovic

Abstract

The aim of this study was to perform screening for anxiety disorders among children with asthma and to reveal factors associated with general anxiety disorder and its specific forms. This was a cross-sectional study conducted among outpatients with asthma during routine visits to pediatricians. They were screened for anxiety disorders using SCARED self-reported questionnaire. Additional data were collected using specially designed questionnaire as well as the patient files. Statistical analysis was performed by the SPPS software using descriptive statistics and logistic regression. Study population consisted mostly of schoolchildren (n=58), 8-12 years old, and adolescents (13-17 years) (n=13). Approximately 33.8% respondents were positive for general anxiety disorder. The most common were separation anxiety and social anxiety, recorded among 49.3% and 32.4% of patients, respectively. Generalized anxiety and panic/somatic disorder were recorded in the same percentage of patients (21.3%), while avoiding school was the least frequent (14.08%). Influence of numerous factors was tested, but only the following showed significant effects: peak expiratory flow test was associated with general anxiety disorder, patient’s age and gender with PD, and living place, asthma control according to GINA and age on GAD. Parent’s smoking was associated with SAD, age and patient’s weight status with SPH, and GINA asthma control with SA. These findings suggest that anxiety disorders are common among children and adolescents with asthma. Various factors can be associated with general anxiety disorder and its specific forms, but some of them being preventable as avoiding smoking in the family.

Open access

Zorica C. Milosevic, Mirjan M. Nadrljanski, Zorka M. Milovanovic, Nina Z. Gusic, Slavko S. Vucicevic and Olga S. Radulovic

Abstract

Background

We aimed to analyse the morphokinetic features of breast fibrocystic changes (nonproliferative lesions, proliferative lesions without atypia and proliferative lesions with atypia) presenting as a non-mass enhancement (NME)in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) examination.

Patients and methods

Forty-six patients with histologically proven fibrocystic changes (FCCs) were retrospectively reviewed, according to Breast Imaging Reporting and Data System (BI-RADS) lexicon. Prior to DCE-MRI examination, a unilateral breast lesion suspicious of malignancy was detected clinically, on mammography or breast ultrasonography.

Results

The predominant features of FCCs presenting as NME in DCE-MRI examination were: unilateral regional or diffuse distribution (in 35 patients or 76.1%), heterogeneous or clumped internal pattern of enhancement (in 36 patients or 78.3%), plateau time-intensity curve (in 25 patients or 54.3%), moderate or fast wash-in (in 31 patients or 67.4%).Nonproliferative lesions were found in 11 patients (24%), proliferative lesions without atypia in 29 patients (63%) and lesions with atypia in six patients (13%), without statistically significant difference of morphokinetic features, except of the association of clustered microcysts with proliferative dysplasia without atypia.

Conclusions

FCCs presenting as NME in DCE-MRI examination have several morphokinetic features suspicious of malignancy, therefore requiring biopsy (BI-RADS 4). Nonproliferative lesions, proliferative lesions without atypia and proliferative lesions with atypia predominantly share the same predefined DCE-MRI morphokinetic features.

Open access

S. Đorđe Marjanović, Danica Bogunović, Mirjana Milovanović, Darko Marinković, Nemanja Zdravković, Vladimir Magaš and M. Saša Trailović

Abstract

In the present study we tested the dose andh time dependence of the antinematodal effects of carvacrol and tyhmol on Caenorabditis elegans, and the efficacy of carvacrol, thymol, p-cymene and cinnamaldehyde,which were administrated in the drinking water of rats naturally infected with the pinworm Syphacia muris. The control treatment of the infected rats was carried out with piperazine. Thymol caused a dose and time-dependent mortality in adult C. elegans. The value of the Median Lethal Concentration (LC50) of thymol was 117.9nM after 24h and 62.89 nM after 48h of exposure. Carvacrol exhibited a higher antinematodal efficiency than thymol. The LC50 of carvacrol, after 24 hours of exposure, was 53.03 nM, while after 48 hours it was 33.83 nM. On the other hand, piperazine showed an extremely high efficacy against S. muris infection in rats. Piperazine, at a dose of 625 mg/kg bw, administered in drinking water continuously for 10 days, eliminates the infection completely. However, none of the investigated active ingredients of essential oils were effective against S. muris. The reason for the lack of efficiency may be due to their pharmacokinetic properties. A relatively low amount of, orally administered, active ingredients of essential oils reaches the distal segments of the gastrointestinal tract, where S. muris inhabits the gut (colon and cecum). The obtained results, on C. elegans, indicate a clear dose and time-dependent antinematodal effect of thymol and carvacrol. However, for clinical application, it is necessary to examine the efficacy of microencapsulated formulations with a controlled release of active ingredients of essential oils in certain parts of the gastrointestinal tract.

Open access

Mirjana Milovanović, Miloš Milosavljević, Marjanović S Đorđe, Saša Trailović M, Marijana Vučinić, Jelena Nedeljković Trailović, Maja Marković and Dragan Đurđević

Abstract

Carvacrol is a monoterpenic phenol and an active ingredient of the plant essential oils of the family Lamiaceae. We have investigated the analgesic effect of carvacrol, the possible dependence of the effect in relation to animal sex, and the impact of carvacrol on motor coordination in rats. Hyperalgesia was induced by formalin (1.5%), which was administered SC in the upper lip of rat. Hyperalgesia and effects of carvacrol and indomethacin were measured by using the orofacial formalin test. The influence on motor coordination in animals treated with carvacrol was investigated by using the rota-rod test. Carvacrol administered PO in pre-treatment (45 min. prior to formalin) at a single dose of 50, 75 and 100 mg /kg BW, in the male, 50 and 100 mg /kg BW, in female rats caused a dose-dependent antinociceptive effect. This effect of carvacrol was significantly higher (P<0.01, P<0.001) in male rats. Compared with indomethacin administered during pre-treatment (2 mg/kg, PO), carvacrol (100 mg/kg) exhibits significantly higher (P <0.05 and P <0.001) antinociceptive effect on formalininduced hyperalgesia in male rats. In the rota-rod test carvacrol did not disturb the motor coordination in male rats, nor the dose of carvacrol with clear antinociceptive properties exhibited depressive effect on the CNS of treated rats. Keeping in mind that the monoterpene carvacrol is of plant origin, with potentially less side effects and without residues, it is realistic to expect the possibility of its therapeutic use in the treatment of inflammatory pain in animals.

Open access

Martin B. Popević, Srđan M. Janković, Srđan S. Borjanović, Slavica R. Jovičić, Lazar R. Tenjović, Aleksandar P.S. Milovanović and Petar Bulat

Summary

A frequently encountered exposure profile for hand-arm vibration in contemporary occupational setting comprises workers with a long history of intermittent exposure but without detectable signs of hand-arm vibration syndrome (HAVS). Yet, most of the published studies deal with developed HAVS cases, rarely discussing the biological processes that may be involved in degradation of manual dexterity and grip strength when it can be most beneficial - during the asymptomatic stage. In the present paper, a group of 31 male asymptomatic vibration-exposed workers (according to the Stockholm Workshop Scale) were compared against 30 male controls. They were tested using dynamometry and dexterimetry (modelling coarse and fine manual performance respectively) and cold provocation was done to detect possible differences in manual performance drop on these tests. The results showed reduced manual dexterity but no significant degradation in hand grip strength in the exposed subjects. This suggests that intermittent exposure profile and small cumulative vibration dose could only lead to a measurable deficit in manual dexterity but not hand grip strength even at non-negligible A(8) levels and long term exposures.