Trbojevic-Stankovic J.,Clinical Center Dr Dragisa Misovic |
Aleksic M.,University of Belgrade |
Odovic J.,University of Belgrade
Srpski Arhiv za Celokupno Lekarstvo | Year: 2015
Introduction Angiotensin-converting enzyme (ACE) inhibitors represent a significant group of drugs primarily used in the treatment of hypertension and congestive heart failure. Objective Selected ACE inhibitors (enalapril, quinapril, fosinopril, lisinopril, cilazapril) were studied in order to establish a fast and easy estimation method of their plasma protein binding degree based on their lipophilicity data. Methods Chromatographic hydrophobicity data (parameter C0) were obtained on cellulose layers under conditions of normal-phase thin-layer chromatography (NPTLC), using different binary solvent systems. The ACE inhibitors lipophilicity descriptors (logP) values were calculated using the software package Virtual Computational Chemistry Laboratory. The ACE inhibitors plasma protein binding data were collected from relevant literature. Results ACE inhibitors protein binding data varied from negligible (lisinopril) to 99% (fosinopril). The calculated lipophilicity descriptors, logPKOWWIN values ranged from -0.94 (lisinopril) to 6.61 (fosinopril). Good correlations were established between plasma protein binding values and calculated logPCKOWWIN values (R2=0.8026) as well as chromatographic hydrophobicity data, C0 parameters (R2=0.7662). Even though good correlation coefficients (R2) were obtained in both relations, unacceptable probability value with p>0.05 was found in relation between protein binding data and calculated logPKOWWIN values. Subsequently, taking into consideration the request for probability value lower than 0.05, a better relationship was observed between protein binding data and chromatographically obtained hydrophobicity parameters C0 values. Conclusion Cellulose layers are easily available and cost effective sorbent to assess hydrophobicity. Experimentally obtained data on ACE inhibitors hydrophobicity and plasma protein binding estimation are important parameters in evaluating bioavailability of these drugs. © 2015 Serbia Medical Society. All rightsreserved.
Milicevic N.M.,Institute of Histology and Embryology |
Trbojevic-Stankovic J.B.,Clinical Center Dr Dragisa Misovic |
Drachenberg C.B.,University of Maryland Baltimore County |
Milicevic Z.,Institute of Histology and Embryology
Pathology and Oncology Research | Year: 2010
The spleen is composed of several tissue compartments and the respective histoquantitative data are essential for complete understanding of immune or pathological processes in this organ. The aim of our study was to determine and compare the stereologic parameters of all tissue compartments of the gunshot-injured and blunt-injured human spleen. The model-based stereology with point-counting method was utilized to study the volume densities of red pulp, perifollicular zone, marginal zone, white pulp (follicles and periarteriolar lymphoid sheath), and connective tissue. The areal numerical density (the number of follicles per mm2 of tissue section), the numerical density (the number of follicles per mm3 of tissue) of lymphoid follicles and the mean follicle diameter were also determined. Our study provides stereological parameters for all tissue compartments of the human spleen. No morphometric differences were registered between tissue compartments of the blunt-injured and gunshot-injured spleen. As the gunshot-injured spleen was taken as presumably unstimulated in immunological regard, our results suggest that both gunshot-injured and blunt-injured organs may be used as models of the normal human spleen. © 2009 Arányi Lajos Foundation.
Vlahovic Z.,Clinical Center Dr Dragisa Misovic |
Radojkovic D.,University of Belgrade
EPMA Journal | Year: 2010
The main topics of this paper are the socialized healthcare system in former Yugoslavia, the changes in the transition period within the society and the healthcare system. We have separately analyzed the factors of the demographic and socioeconomic situation, the usage of the existing capacities within the system, as well as the comparison of the data related to the healthcare system in Serbia versus the EU countries. The analysis presented has pointed to the usual challenges present in the countries in transition as well as the efforts by the Government and the Ministry of Health of the Republic of Serbia in the way of numerous national and strategic documents, initiatives and projects in order to improve and sustain the healthcare system. © 2010 European Association for Predictive, Preventive and Personalised Medicine.
Brankovic A.,University of Belgrade |
Brajuskovic G.,University of Belgrade |
Nikolic Z.,University of Belgrade |
Vukotic V.,Clinical Center dr Dragisa Misovic |
And 3 more authors.
International Journal of Experimental Pathology | Year: 2013
Summary: Genome-wide association studies (GWAS) have identified over 46 SNPs associated with human prostate cancer (PCa). Some studies have shown correlation of the nitric oxide synthase (NOS) NOS3 gene polymorphisms with the risk and/or progression of PCa. This study aimed to evaluate the association of NOS3 gene polymorphisms (-786T>C, -764A>G, -714G>T, -690C>T, -649G>A and 894G>T) with PCa risk and progression. 150 patients with PCa, 150 patients with BPH and 100 age-matched healthy controls were recruited in this study. Genotyping of promoter polymorphisms was performed by bi-directional DNA sequencing, and for 894G>T by RFLP analysis. There was no significant association between the alleles and genotypes of these genetic variants and PCa risk. For -786T>C polymorphism, we found that C allele is associated with absence of metastases, assuming dominant genetic model (P = 0.049; OR, 0.50; 95% CI, 0.25-1.00). It was found that, compared with NOS3 -690C>T variant CC genotype, CT and TT genotypes confer decreased risk of developing metastases (dominant model, P = 0.015, OR, 0.24; 95% CI, 0.07-0.88) and show association with low clinical tumour stage, compared with stages T3 and T4 (dominant model, P = 0.046, OR, 0.20; 95% CI, 0.04-1.02). Genetic variants -764A>G, -714G>T, -649G>A were not detected in our study group. There is evidence of an inverse correlation of the NOS3 894G>T minor allele with high serum PSA (>20 ng/ml) (dominant model, P = 0.013, OR, 0.37; 95% CI, 0.17-0.82). Our results suggest that NOS3 gene polymorphisms are genetic susceptibility factors for the progression of PCa and patient outcome. © 2013 International Journal of Experimental Pathology.
Krajnovic M.,Vinča Institute of Nuclear Sciences |
Radojkovic M.,University of Belgrade |
Radojkovic M.,Clinical Center Dr Dragisa Misovic |
Davidovic R.,Vinča Institute of Nuclear Sciences |
And 2 more authors.
Medical Oncology | Year: 2013
In this study, methylation-specific polymerase chain reaction was used to investigate the role and potential prognostic significance of the methylation status of p16, p15, MGMT and DAPK genes in 32 specimens of follicular lymphoma (FL). Hypermethylation of p15 gene was associated with lower hemoglobin level (P = 0.020) and MGMT/DAPK comethylation with relapsed disease (P = 0.018). Among all patients with FL, there was no significant difference in the overall survival between those with hypermethylated and unmethylated of any examined genes. Therefore, we analyzed methylation in the different groups according to FL International Prognostic Index (FLIPI) and tumor grade. In the high-risk group, patients with hypermethylated p16 gene had significant lower overall survival than those with unmethylated p16 (P = 0.006) and trend toward shorter failure-free survival (P = 0.068). In the same risk group, there was a trend toward longer overall survival for patients with hypermethylated MGMT gene, compared to those with unmethylated MGMT gene (P = 0.066). p15 methylation had impact on shorter overall survival in grade I group of patients (P = 0.013), and DAPK methylation tended to have impact on shorter failure-free survival in the whole examined group (P = 0.079). Our results suggest that promoter methylation of p16 and MGMT genes could have prognostic value when used in combination with the FLIPI and p15 methylation in combination with tumor grade. Concurrent methylation of MGMT and DAPK genes could be the marker of tumor chemoresistance and disease recurrence. © 2012 Springer Science+Business Media New York.
Petrovic D.,Center for Nephrology and Dialysis |
Obrenovic R.,University of Belgrade |
Trbojevic-Stankovic J.,Clinical Center Dr Dragisa Misovic |
Majkic-Singh N.,University of Belgrade |
Stojimirovic B.,Institute of Urology and Nephrology
Journal of Medical Biochemistry | Year: 2011
Cardiovascular diseases are the leading cause of death in hemodialysis (HD) patients. The annual cardiovascular mortality rate in these patients is 9%, with left ventricular (LV) hypertrophy, ischemic heart disease and heart failure being the most prevalent causes of death. The aim of this study was to determine the cardiovascular mortality rate and estimate the influence of risk factors on cardiovascular mortality in HD patients. A total of 115 patients undergoing HD for at least 6 months were investigated. Initially a cross-sectional study was performed, followed by a two-year follow-up study. Beside the standard biochemical parameters, C-reactive protein (CRP), homocysteine, cardiac troponins (cTn) and the echocardiographic parameters of LV morphology and function (LV mass index, LV fractional shortening, LV ejection fraction) were determined. Results were analyzed using Cox regression analysis, Kaplan-Meier and Log-Rank tests. The average one-year cardiovascular mortality rate was 8.51%. Multivariate Cox regression analysis identified increased CRP, cTn T and I, and LV mass index as independent risk factors for cardiovascular mortality. Patients with cTnT > 0.10 ng/mL and CRP > 10 mg/L had significantly higher cardiovascular mortality risk (p < 0.01) than patients with cTnT > 0.10 ng/mL and CRP ≤ 10 mg/L and those with cTnT ≤ 0.10 ng/mL and CRP ≤ 10 mg/L (p < 0.01). HD patients with high cTnT and CRP have a higher cardiovascular mortality risk.
Nikolic Z.Z.,University of Belgrade |
Savic Pavicevic D.L.,University of Belgrade |
Vukotic V.D.,Clinical Center dr Dragisa Misovic |
Tomovic S.M.,Clinical Center Zvezdara |
And 4 more authors.
Cancer Causes and Control | Year: 2014
Purpose: Two previous studies of association between rs2910164 in miR-146a gene and prostate cancer (PCa) risk have provided opposing results. Furthermore, no evidence of association of this SNP with standard prognostic parameters of PCa progression was obtained in mentioned studies. The main aim of this study was to evaluate the possible association between PCa onset and progression to a more aggressive form, since it has not been assessed in a population of European descent.Methods: In this study, 286 samples of peripheral blood were obtained from patients with PCa, while the control group comprised 199 volunteers derived from general population who gave samples of buccal swabs. For individuals diagnosed with PCa clinicopathological characteristics including serum prostate-specific antigen level at diagnosis, Gleason score (GS), and clinical stage were determined. Genotyping of rs2910164 was performed using Taqman®SNP Genotyping Assay. Analysis of SNP association was done using PLINK and SNPStats software.Results: rs2910164 showed no association with PCa risk. Nevertheless, heterozygous genotype was found to be associated with higher GS, as well as with the presence of distant metastases. rs2910164 was also shown to be associated with cancer aggressiveness (p = 0.0067; ORGC = 2.22, 95 %CI 1.24–3.97; ORCC = 0.47, 95 %CI 0.13–1.68).Conclusions: Our results show no evidence of association between rs2910164 and PCa risk in Serbian population. Conversely, this variant was found to be associated with PCa aggressiveness. © 2014, Springer International Publishing Switzerland.
PubMed | University of Belgrade and Clinical Center Dr Dragisa Misovic
Type: | Journal: Medical science monitor : international medical journal of experimental and clinical research | Year: 2016
BACKGROUND It is still disputable whether negative effects of comorbid depression in diabetics can be diminished by successful treatment of depression. The primary aim of this study was to assess whether addition of antidepressants to existing insulin treatment would further improve glycemic control in these patients. A secondary objective was to assess whether such treatment impairs their lipid and inflammatory status. MATERIAL AND METHODS Total of 192 patients with poorly controlled diabetes (defined as HbA1c 8%) in the absence of any uncontrolled medical condition entered the 6-month run-in phase with optimization of diabetic therapy. Depression status was screened at the end of this phase by BDI-II depression testing. Patients with BDI-II 14 and psychiatric confirmation of depression (58 patients) entered the 6-month interventional phase with SSRI class antidepressants. RESULTS Fifty patients completed the study. During the run-in phase, HbA1c dropped from 10.01.8% to 8.51.2% (p<0.001), and during the interventional phase it dropped from 8.51.2% to 7.70.7% (p<0.001). BDI-II scores improved significantly from 30.413.2 to 23.511.0 (p=0.02) during the interventional phase. A positive linear correlation between improvement in depression scale and improvement in glycemic control was observed (R=0.139, p=0.008). Lipid profile and inflammatory status did not change significantly during the interventional phase. CONCLUSIONS Patients with poorly controlled diabetes and comorbid depression might benefit from screening and treatment of depression with SSRI antidepressants by achieving an incremental effect on glycoregulation. This therapy did not have any adverse effects on lipid profile or inflammatory status.
PubMed | University of Belgrade, Military Medical Academy and Clinical Center dr Dragisa Misovic
Type: Journal Article | Journal: Experimental and molecular pathology | Year: 2015
Due to their potentially functional significance, genetic variants within microRNA genes have been recognized as candidates for cancer-related genetic biomarkers. Among the most extensively studied so far are rs3746444, rs11614913 and rs895819. Nevertheless, only few previous studies in Asian population analyzed the association of rs3746444 and rs11614913 with prostate cancer (PCa) risk, while rs895819 was not evaluated in relation to this issue. The aim of this study was to assess the possible association between these genetic variants and PCa risk and progression in Serbian population. 355 samples of peripheral blood were obtained from the patients with PCa and 353 samples from patients with benign prostatic hyperplasia (BPH). 312 volunteers derived from general population who gave samples of buccal swabs were included in the control group. Genotyping of rs3746444, rs11614913 and rs895819 was performed by using PCR-RFLP method, HRM analysis and allele-specific PCR, respectively. Allelic and genotypic associations were evaluated by unconditional linear (for serum PSA level in PCa patients) and logistic regression method with adjustment for age. Minor allele C of rs895819 was found to be associated with the increased risk of developing PCa under dominant (P=0.035; OR=1.38, 95%CI 1.02-1.86) and overdominant (P=0.04; OR=1.37, 95%CI 1.01-1.85) genetic model. Same genetic variant was found to be associated with the clinical stage of localized PCa, as well as with the presence of distant metastases. Allele G of rs3746444 was also shown to be associated with the decreased risk of PCa progression. According to our data, rs3746444 qualifies for a genetic variant potentially associated with PCa aggressiveness in Serbian population. Furthermore, our study provided the first evidence of association between rs895819 and PCa risk, as well as for its genetic association with the presence of distant metastases among PCa patients.
PubMed | University of Belgrade, Military Medical Academy and Clinical Center dr Dragisa Misovic
Type: | Journal: World journal of urology | Year: 2016
The purpose of this study is to evaluate the potential association between genetic variants in genes encoding the components of RNA-induced silencing complex and prostate cancer (PCa) risk. Genetic variants chosen for this study are rs3742330 in DICER1, rs4961280 in AGO2, rs784567 in TARBP2, rs7813 in GEMIN4 and rs197414 in GEMIN3.The study involved 355 PCa patients, 360 patients with benign prostatic hyperplasia and 318 healthy controls. For individuals diagnosed with PCa, clinicopathological characteristics including serum prostate-specific antigen level at diagnosis, Gleason score (GS) and clinical stage were determined. Genotyping was performed using high-resolution melting analysis, PCR-RFLP, TaqMan SNP Genotyping Assay and real-time PCR-based genotyping assay using specific probes. Allelic and genotypic associations were evaluated by unconditional linear and logistic regression methods.The study provided no evidence of association between the analyzed genetic variants and PCa risk. Nevertheless, allele A of rs784567 was found to confer the reduced risk of higher serum PSA level at diagnosis (P=0.046; Difference=-66.64, 95% CI -131.93 to 1.35, for log-additive model). Furthermore, rs4961280, as well as rs3742330, were shown to be associated with GS. These variants, together with rs7813, were found to be associated with the lower clinical stage of PCa. Also, rs3742330 minor allele G was found to be associated with lower PCa aggressiveness (P=0.036; OR 0.14, 95% CI 0.023-1.22, for recessive model).According to our data, rs3742330, rs4961280 and rs7813 qualify for potentially protective genetic variants against PCa progression. These variants were not shown to be associated with PCa risk.