Ljubinka Jankovic Velickovic

University of Niš, Nisch, Central Serbia, Serbia

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Publications (21)17.39 Total impact

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    ABSTRACT: Primary acinic cell carcinoma (ACC) is an uncommon malignant neoplasm of the salivary gland (SG), which usually presents as slow growing tumor. We reported a 69-year-old woman with tumor in the right parotid gland with a 5-year progress. Biopsy sections revealed a hybrid form of ACC with a low- and high-grade component and prominent lymphoid tissue in tumor stroma. Immunohistochemistry was performed to define the molecular profile of this unusual ACC, with special interest for stromal influence on to the proliferative activity of ACC with dedifferentiation. We detected that the level and the type of stromal lymphoid reaction (particularly CD8+/CD4+ ratio) had a significant influence on to Ki-67 index in the high-grade component of ACC, as well as the involvement of the CXCR4 signaling axis in the stromal reaction influence. We suggest that tumor stroma may be a source of potential new tumor biomarkers which can determine the aggressivity of this tumor.
    Vojnosanitetski pregled. Military-medical and pharmaceutical review 12/2013; 70(12):1155-8. · 0.21 Impact Factor
  • Ljubinka Jankovic Velickovic, Vladisav Stefanovic
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    ABSTRACT: This review mainly focuses on our understanding of spermatogenesis in physiological and pathological hypoxic condition. Real hypoxia is closely related to vascular changes and an increase in testicular temperature. Both induce a reduction in sperm count and can be related to the increase in germ cell apoptosis. On the other hand, change in the temperature, and oxygen levels in the microenvironment have influence on spermatogonial stem cell function and differentiation. The initial connection between hypoxia and a factor critical for stem cell maintenance is alteration in Oct-4 expression, and these data may be a useful strategy for modulating stem cell function. Unilateral testicular ischemia-induced cell death can be accompanied by an increase in germ cell apoptosis in the contralateral testis. The injury of contralateral testis following unilateral testicular damage is controversial, and it can contribute to the reduction in fertility.
    International Urology and Nephrology 11/2013; · 1.33 Impact Factor
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    ABSTRACT: Upper tract urothelial carcinoma (UTUC) associated with Balkan endemic nephropathy (BEN) is characterized by a number of aberrations in cell-cycle regulation and apoptosis. The aim of this study was to detect angiogenesis-related marker(s) specific for BEN UTUC, and to examine the influence of HIF 1α upon angiogenesis and apoptosis in UTUC. Present investigation included 110 patients with UTUC, 50 from BEN region and 60 control tumors. Altered expression of VEGFR1 was more often present in control UTUC than in BEN tumors (p<0.005). It was associated with high grade, low and high stage, solid growth, and metaplastic change of control UTUC. Microvessel density assessed by CD31 (MVD CD31) was significantly higher in UTUC with lymphovascular invasion (p<0.05), and in BEN tumors with papillary growth (p<0.05). Discriminant analysis indicated that BEN and control tumors do not differ significantly in expression of angiogenesis related markers. The most important discriminant variable that determined control UTUC was expression of VEGFR1 (p=0.002). HIF 1α in UTUC significantly correlated with the low stage, papillary growth and expression of Bcl-2, Caspase-3 index, and MVD CD34 (p<0.001; 0.0005; 0.01; 0.005; 0.01, respectively). HIF-1α may be helpful marker in evaluation of UTUC, especially when combined with angiogenesis and apoptosis.
    International journal of clinical and experimental pathology 01/2012; 5(7):674-83. · 2.24 Impact Factor
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    ABSTRACT: Gentamicin (GM) is a widely used antibiotic against serious, life-threatening infections, but its usefulness is limited by the development of nephrotoxicity. The present study was designed to determine the protective effect of selenium (Se) in GM-induced nephrotoxicity in rats. Experiments were done on 32 adult Wistar rats divided into four groups of 8 animals each. The GM group received gentamicin (100 mg/kg), whereas the GM+Se group received the same dose of GM and selenium (1 mg/kg) by intraperitoneal (i.p.) injections on a daily basis. Animals in the Se group, serving as a positive control, received only selenium (1 mg/kg) and the control group received saline (1 mL/day), both given i.p. All groups were treated during 8 consecutive days. Quantitative evaluation of GM-induced structural alterations and degree of functional alterations in the kidneys were performed by histopathological and biochemical analyses in order to determine potential beneficial effects of selenium coadministration with GM. GM was observed to cause a severe nephrotoxicity, which was evidenced by an elevation of serum urea and creatinine levels. The significant increases in malondialdehyde levels and protein carbonyl groups indicated that GM-induced tissue injury was mediated through oxidative reactions. On the other hand, simultaneous selenium administration protected kidney tissue against oxidative damage and the nephrotoxic effect caused by GM treatment. Exposure to GM caused necrosis of tubular epithelial cells. Necrosis of tubules was found to be prevented by selenium pretreatment. The results from our study indicate that selenium supplementation attenuates oxidative-stress-associated renal injury by reducing oxygen free radicals and lipid peroxidation in GM-treated rats.
    Drug and Chemical Toxicology 11/2011; 35(2):141-8. · 1.29 Impact Factor
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    ABSTRACT: Deregulation of the normal cell cycle is common in upper urothelial carcinoma (UUC). The aim of this study was to investigate the expression of regulatory proteins of the cell cycle (p53, p16, cyclin D1, HER-2) and proliferative Ki-67 activity in UUC, and to determine their interaction and influence on the phenotypic characteristics of UUC. In 44 patients with UUC, histopathological and immunohistochemical analyses (p53, p16, cyclin D1, HER-2, and Ki-67) of tumors were done. Overexpression/altered expression of p53, p16, cyclin D1 or HER-2 was detected in 20%, 57%, 64%, and 57% of tumors, respectively. Eleven (25%) UUC had a high proliferative Ki-67 index. Forty patients (91%) had at least one marker altered, while four (9%) tumors had a wild-type status. Analysis of relationship between expressions of molecular markers showed that only high expression of p53 was significantly associated with altered p16 activity (p < 0.05). High Ki-67 index was associated with the high stage (p < 0.005), solid growth (p < 0.01), high grade (p < 0.05), and multifocality p < 0.05) of UUC, while high expression of p53 was associated with the solid growth (p < 0.05). In regression models that included all molecular markers and phenotypic characteristics, only Ki-67 correlated with the growth (p < 0.0001), stage (p < 0.01), grade (p < 0.05) and multifocality (p < 0.05) of UCC; (Ki-67 and HER-2 expression correlated with the lymphovascular invasion (p < 0.05). This investigation showed that only negative regulatory proteins of the cell cycle, p53 and p16, were significantly associated in UUC, while proliferative marker Ki-67 was in relation to the key phenotypic characteristics of UUC in the best way.
    Vojnosanitetski pregled. Military-medical and pharmaceutical review 07/2011; 68(7):567-74. · 0.21 Impact Factor
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    Ana Ristić, Ljubinka Janković Velicković, Dragana Stokanović
    Vojnosanitetski pregled. Military-medical and pharmaceutical review 06/2011; 68(6):511-4. · 0.21 Impact Factor
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    ABSTRACT: Patients with severe traumatic brain injury are at a risk of developing ventilator-associated pneumonia. The aim of this study was to describe the incidence, etiology, risk factors for development of ventilator-associated pneumonia and outcome in patients with severe traumatic brain injury. A retrospective study was done in 72 patients with severe traumatic brain injury, who required mechanical ventilation for more than 48 hours. Ventilator-associated pneumonia was found in 31 of 72 (43.06%) patients with severe traumatic brain injury. The risk factors for ventilator-associated pneumonia were: prolonged mechanical ventilation (12.42 vs 4.34 days, p < 0.001), longer stay at intensive care unit (17 vs 5 days, p < 0.001) and chest injury (51.61 vs 19.51%, p < 0.009) compared to patients without ventilator-associated pneumonia. The mortality rate in the patients with ventilator-associated pneumonia was higher (38.71 vs 21.95%, p = 0.12). The development of ventilator-associated pneumonia in patients with severe traumatic brain injury led to the increased morbidity due to the prolonged mechanical ventilation, longer stay at intensive care unit and chest injury, but had no effect on mortality.
    Medicinski pregled 01/2011; 64(7-8):403-7.
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    ABSTRACT: Upper urothelial carcinoma (UUC) has a plasticity to demonstrate divergent differentiation with squamous metaplastic elements. There was no previous study exploring profiling of molecular markers in metaplastic squamous upper urothelial carcinoma (SUUC) and conventional upper urothelial carcinoma (CUUC). The aims of this study was to compare expression of the phenotypic characteristics of tumors and molecular markers (p53, p16, cyclin D1, E-cadherin, HER-2, Ki-67, Bcl-2, Bax) in SUUC and CUUC. SUUC was detected in 20% of 44 patients. There was significant difference between SUUC and CUUC in the pathological stage, grade, growth and presence of lymphovasular invasion (p < 0.05; 0.05; 0.05; 0.01 respectively). The mean Ki-67 and p53 labeling index was significantly higher in SUUC than in CUUC (p < 0.05; 0.05). There was no significant difference in the expression of p16, cyclin D1, E-cadherin, HER-2, Bcl-2 and Bax between SUUC and CUUC. Univariant model showed that SUUC was significantly associated with lymphovascular invasion (p = 0.007), Ki-67 activity (p = 0.016) and growth (p = 0.026). Exploration of UUC with squamous divergent differentiation showed changes in phenotypic characteristics and Ki-67, as well as similar molecular profile with CUUC.
    Pathology & Oncology Research 12/2010; 17(3):535-9. · 1.56 Impact Factor
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    ABSTRACT: There is a high incidence of upper urothelial carcinoma (UUC) in regions affected by Balkan Endemic Nephropathy (BEN). The aim of this study was to compare E-cadherin expression in UUC, in regions affected by BEN, and in control rural and city populations free of BEN. Another aim was to determine the influence of some morphological parameters on the E-cadherin status. In the samples of 85 UUC patients, of whom 40 lived in BEN settlements and 45 served as control subjects, immunoreactions were performed using monoclonal anti-human E-cadherin antibody. Aberrant expression of E-cadherin was more frequent in BEN tumors than in control tumors (p<0.01). Decreased E-cadherin expression was linked to high grade and solid growth in control and BEN tumors (p<0.0001 and <0.05 versus p<0.05 and <0.05, respectively), and to the stage in control tumors (p<0.01). However, BEN low grade and low stage tumors showed aberrant expression more often than did control tumors (p<0.05 and <0.005, respectively). In control tumors, using univariate analysis, E-cadherin status was found to be influenced by grade, stage, and tumor growth (p=0.001, 0.017, 0.015, respectively). In the same group, only the grade was significant according to multistep logistic regression analysis (Wald=6.429 and p=0.011). The growth pattern had a predominant influence on E-cadherin expression in BEN tumors (p=0.005). A significant influence on normal membranous or abnormal cytoplasmic expression of E-cadherin in UUC is exerted by tumor grade, stage, growth, and metaplastic change (p=0.002, 0.048, 0.019, 0.011, respectively), but only by tumor grade in the multistep logistic regression model. These results suggest that decreased expression of E-cadherin in BEN tumors may be linked to tumor growth, while expression of E-cadherin in control tumors may be associated with tumor grade.
    Pathology - Research and Practice 06/2009; 205(10):682-9. · 1.21 Impact Factor
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    ABSTRACT: Mammary phyllodes tumors (MPT) are uncommon fibroepithelial (biphasic) neoplasms whose clinical behavior is difficult to predict on the basis of histological criteria only. They are divided into benign, borderline malignant and malignant groups. Sometimes it appears difficult to distinguish these tumors from other types of soft tissue sarcomas. Because of the relatively scant data on the role of biological markers in MPT histogenesis, we have decided to undertake the following study, trying to shed more light on the issue by investigating the following elements that make up MPT: their histological patterns, biological behavior, enzymohistochemical, histochemical and immunohistochemical characteristics (ICH) together with the mast cell analysis. We examined the biopsy material of 35 MPT in our laboratory. Enzymohistochemistry was performed on frozen sections (method of Crowford, Nachlas and Seligman). The used methods were classical hematoxylin-eosin (H & E); histochemical Massontrichrome, Alcian-blue, Periodic acid Schiff and immunohistochemical LSAB2 method (DacoCytomation). Ki-67, c-kit, vimentin, estrogen receptor (ER), progesterone receptor (PR) and Her-2 oncoprotein immunohistochemistry was performed on all tumors. The patients were ranged per age from 30--62 years (mean 43.3 years, median 39 years). A total of 35 cases of MPT were included: 20 benign (57%), 6 borderline malignant (17%) and 9 malignant (26%). Twenty-two patients (62.8%) underwent segmental mastectomy, while 13 (37.2%) had total mastectomies. Twenty-eight patients had negative surgical margins at original resection. The mean size of malignant MPT (7.8 cm) was larger than that of benign MPT (4.5 cm). Significant features of the malignant MPT were: stromal cellularity, stromal cellular atypism, high mitotic activity, atypic mitoses, stromal overgrowth, infiltrative tumor contour and heterologous stromal elements. Benign MPT showed strong enzymohistochemical Leucine Amino Peptidase (LAP) activity in both epithelial and stromal components while it was weak or absent in the epithelial parts of the malignant tumors. Acid mucopolysacharides were present in the stromal component of all types of these tumors. Benign MPT had a lower Ki-67 than did borderline malignant MPT (4 versus 28). Malignant MPT had a greater than 8-fold higher Ki-67 activity than did benign tumors (35 versus 4). Intracyto-plasmatic c-kit expression was associated with a pathological diagnosis of malignant MPT, correlating with increasing grade (p < 0.05). In hypercellular stroma of borderline malignant and especially malignant forms of MPT, high activity of ER in mast cells was confirmed. Oncoprotein Her-2 activity, mostly in epithelial components, correlated with the degree of malignant progression of MPT (p < 0.05). Besides the well-known malignant features additional parameters have been found to be high Ki-67 and c-kit stromal expressions, and weak LAP activity in the epithelial part of malignant MPT, as well as mast cells with a high expression of ER.
    Vojnosanitetski pregled. Military-medical and pharmaceutical review 05/2009; 66(4):277-82. · 0.21 Impact Factor
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    ABSTRACT: An increasing number of patients suffering from renal diseases and limitations in standard diagnostic and therapeutic approaches has created an intense interest in applying genomics and proteomics in the field of nephrology. Genomics has provided a vast amount of information, linking the gene activity with disease. However, proteomic technologies allow us to understand proteins and their modifications, elucidating properties of cellular behavior that may not be reflected in analysis of gene expression. The application of these innovative approaches has recently yielded the promising new urinary biomarkers for acute kidney injury and chronic kidney disease, thus providing a better insight in renal pathophysiology and establishing the basis for new therapeutic strategies. Despite significant improvements in therapeutics, the mortality and morbidity associated with acute renal failure (ARF) remain high. The lack of early markers for ARF causes an unacceptable delay in initiating therapy. These biomarker panels will probably be useful for assessing the duration and severity of ARF, and for predicting progression and adverse clinical outcomes. Kidney failure leads to the uremic syndrome characterized by accumulation of uremic toxins, which are normally cleared by the kidneys. Proteomics has gained considerable interest in this field, as a new and promising analytical approach to identify new uremic toxins. The urinary proteome as a tool for biomarker discovery is still in its early phase. A major challenge will be the integration of proteomics with genomics data and their functional interpretation in conjunction with clinical results and epidemiology.
    Renal Failure 01/2009; 31(8):765-72. · 0.94 Impact Factor
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    Irena Dimov, Ljubinka Jankovic Velickovic, Vladisav Stefanovic
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    ABSTRACT: Exosomes are nanovesicles of endocytic origin that are secreted into the extracellular space or body fluids when a multivesicular body (MVB) fuses with the cell membrane. Interest in exosomes intensified after their description in antigen-presenting cells and the observation that they can significantly moderate immune responses in vivo. In the past few years, several groups have reported on the secretion of exosomes by almost all cell types in an organism. In addition to a common set of membrane and cytosolic molecules, exosomes harbor unique subsets of proteins, reflecting their cellular source. Major research efforts were put into their surprisingly various biological functions and in translating knowledge into clinical practice. Urine provides an exciting noninvasive alternative to blood or tissue samples as a potential source of disease biomarkers. Urinary exosomes (UE) became the subject of serious studies just a few years ago. A recent large-scale proteomics-based study of normal UE revealed a myriad of proteins, including disease-related gene products. Thus, UE have valuable potential as a source of biomarkers for early detection of various types of diseases, monitoring the disease evolution and/or response to therapy. As a relatively new field of research, it still faces many challenges, but UE have already shown some straightforward potential.
    The Scientific World Journal 01/2009; 9:1107-18. · 1.73 Impact Factor
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    Ljubinka Jankovic Velickovic, Takanori Hattori, Vladisav Stefanovic
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    ABSTRACT: The role of aristolochic acid in the etiology of Balkan endemic nephropathy (BEN) and associated upper urothelial carcinoma (UUC) was recently confirmed. The aim of this study was to determine the marker(s) specific for BEN-associated UUC. A total of 82 patients with UUC (38 from the BEN region and 44 control tumors) were included in the study. The Ki-67 index in BEN tumors correlated with the grade and multifocality (p < 0.05), but in regression analysis, only the grade of BEN tumor. The p53 index was significantly higher in BEN than in control tumors (p < 0.05), as well as the alteration of p53 (p < 0.05). BEN low-stage tumors, tumors without limphovascular invasion (LVI), and tumors of the renal pelvis had a higher p53 index than the control tumors (p < 0.05, 0.01, 0.05, respectively). The Ki-67 index was higher in control tumors with high-stage and solid growth than in BEN UUC (p < 0.050, 0.005). The Ki-67 correlated with the grade, growth, stage, LVI, and multifocality of UUC on the best way, but not with the group. In regression analysis, only multifocality of UUC had predictive influence on Ki-67 activity (p < 0.001). P53 correlated with the grade, growth, and group (p < 0.05). This investigation identifies the p53 pathway as the specific cell cycle marker involved in BEN-associated UUC.
    The Scientific World Journal 01/2009; 9:1360-73. · 1.73 Impact Factor
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    ABSTRACT: Upper urothelial carcinoma (UUC), a rare neoplasm, occurs more frequently in some regions of Balkan countries than in other areas in the world. The aim of this study is to compare phenotypic morphological characteristics of UUC in Balkan endemic nephropathy (BEN) region and control rural and city populations free of BEN, and to determine the characteristic(s) that could discriminate tumors in endemic and non-endemic regions. The authors analyzed biopsies from 88 patients with UUC, 40 patients who live in Balkan endemic (BEN) settlements and 48 control subjects. The histological sections were used to assess morphological variables: histologic grade, pathologic stage (pT), growth pattern, pattern of invasion, lympho-vascular invasion (LVI), presence of necrosis and metaplastic changes (squamous or glandular) within the tumor. Statistically significant differences between the groups were found concerning tumor grade, pattern of invasion, growth pattern and metaplastic changes. High-grade tumors and trabecular/infiltrative patterns of invasion were more frequent in the group of BEN tumors (chi(2)=4.583, p<0.05; chi(2)=8.064, p<0.05). Moreover, solid growth and metaplastic changes are significant in BEN tumor, chi(2)=9.696, p<0.01; chi(2)=9.35, p<0.01, respectively. Discriminant analysis of morphological variables had indicated that BEN and control tumors are significantly different (Wilks' lambda=0.833, chi(2)=15.044 and p<0.05). The best characteristic that differentiated them was growth pattern; i.e., solid growth for BEN tumors and papillary for control tumors.
    Pathology - Research and Practice 12/2008; 205(2):89-96. · 1.21 Impact Factor
  • Dimov Irena, Ivana Pesic, Ljubinka Jankovic Velickovic
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    ABSTRACT: Current explosion of „omics“ technologies within functional genomics and proteomics promises to take a central place in the understanding of pathogenesis, diagnosis, monitoring and treatment of (pre)cancers of many different sites. Urothelial cancer is a common malignant disease characterized by multiple localisations and frequent recurrences. Proteomics is expected to play the key role in early diagnosis and distinction of biological potential among the low grade urothelial cancers, with the long-term goal of predicting their evolution in terms of outcome, avoiding invasive diagnostic procedures. This review covers a selection of advances of proteomics application and its promise for transitional cell carcinoma research. Proteomics offers an attractive approach to biomarker discovery. Protein profiling of urine could provide us with low-cost and noninvasive diagnostic approach for transitional cell carcinoma. Tissue protein profiling is far more complicated than the analysis of fluids, but it could provide more accurate information of healthy and malignant urothelium.
    Acta Facultatis Medicae Naissensis. 01/2008;
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    ABSTRACT: The aim of this study was to assess renal function in different stages of type 1 diabetes mellitus by radionuclide methods. Additionally, glomerular and tubular functions were correlated with urinary albumin (UAER) and N-acetyl-beta-D-glucosaminidase (NAGA) excretion rates. Fifty-three patients with diabetes mellitus were classified into four groups: normoalbuminuric (NA, 18 patients), microalbuminuric (MiA, 12 patients), macroalbuminuric (MaA, 13 patients), and chronic renal failure group (CRF, 10 patients). Glomerular filtration rate (GFR) was estimated by diethylenetriamine pentaacetic acid-technetium 99m ((99m)Tc-DTPA) clearance rate while tubular function was calculated as a percentage of net injected activity fixed in both kidneys, 4 h after intravenous injection of dimercaptosuccinate acid-technetium 99m ((99m)Tc-DMSA). Additionally, (99m)Tc-DTPA clearance was correlated with estimated GFR (eGFR) by using modified Modification of Diet in Renal Disease (MDRD) Study Group formula. (99m)Tc-DTPA clearance and (99m)Tc-DMSA fixation were found significantly higher in normoalbuminuric group (p < 0.05 and p < 0.02, respectively), unchanged in microalbuminuric group (p > 0.05, p > 0.05), and decreased in both macroalbuminuric (p < 0.0001, p < 0.00001) and chronic renal failure group (p < 0.0001, p < 0.00001). Renal function was denoted as normal, increased (hyperfunction), or decreased (hypofunction). It was found normal in a high percentage of patients with normalbuminuria (filtration 44.4%, fixation 72.2% pts) and microalbuminuria (66.7% and 66.7%). Renal hyperfunction was not only found frequent in normalbuminuric group (55.6% and 27.8%), but was also recorded in microalbuminuric group (8.3% and 8.3%). Renal hypofunction was present in all macroalbuminuric patients and in one-quarter of those with microalbuminuria as well. Such distribution of renal function conditions indicated normalbuminuric and microalbuminiric groups functionally heterogeneous. Regression analysis showed a significant correlation between (99m)Tc-DTPA clearance and eGFR in MaA and CRF groups only. Although urinary NAGA excretion rate was shown as a less sensitive staging parameter, being significantly increased when compared to control group only in MaA and CRF groups (p < 0.05), it significantly correlated with (99m)Tc-DTPA clearance rate (r = -0.485, p = 0.0004) and (99m)Tc-DMSA tubular fixation (r = -0.526, p = 0.0002). The results of this study favor the performance of radionuclide studies together with the determination of urinary albumin excretion rate in patients with type 1 diabetes mellitus in order to achieve more reliable staging of diabetic kidney disease. The demonstration of glomerular hyperfiltration and tubular hyperfunction by radiopharmaceuticals contributes to the early detection of diabetic kidney disease, while the quantification of renal function enables the follow-up of the progressive function loss in the later course of the disease.
    Renal Failure 02/2007; 29(6):685-91. · 0.94 Impact Factor
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    ABSTRACT: A wide spectrum of glandular epithelial metaplastic changes may be seen in the bladder. Cystitis glandularis (CG) is a well-known metaplastic lesion occurring in the presence of chronic inflammation, but there are a few data about mucin expression in its two subtypes (typical and intestinal). The purpose of the present study was to determine the expression of mucin core proteins and CD10 in the different types of CG. For this examination, we used a panel of monoclonal-specific antibodies for MUC1, MUC2, MUC5AC, and MUC6. CG of the intestinal type expressed MUC5AC both in goblet and columnar cells, and strongly expressed intestinal mucin MUC2 only in goblet cells in all cases. There was no expression of MUC1, MUC6, and CD10 in the metaplastic cells. CG of the typical type showed an expression of MUC1 similar to normal urothelium, but the CD10 expression was more intensive than in the control. The mucin expression profile in the different types of CG allows the identification of "gastric mucin" (MUC5AC) together with intestinal mucin (MUC2), while typical CG (CGTP) retains MUC1. Different and contrasting immunoprofiles were evident in various forms of CG. The absence of CD 10 in CG of the intestinal type is a finding that points towards an incomplete form of urinary bladder metaplasia.
    Pathology - Research and Practice 02/2007; 203(9):653-8. · 1.21 Impact Factor
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    Zana Dolićanin, Ljubinka Janković Veličković, Vuka Katić
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    ABSTRACT: Currently, there is no perfect test for the detection of bladder cancer. Even the gold standard cystoscopy is increasingly being demonstrated to miss both Tis and papillary bladder cancer. The oldest urine-based biomarker, cytology, has high specificity but has low sensitivity and significant variability in performance. Stage and grade of transitional cell carcinoma are currently the most useful tools for taking therapeutic decisions and evaluating the prognosis of bladder cancer patients. During the last two decades, the better understanding of the molecular mechanisms involved in carcinogenesis and tumor progression has provided a large number of molecular markers of bladder cancer, with a potential diagnostic and prognostic value. Markers that distinguish among bladder cancer, normal urothelium, and benign urothelial conditions are potentially diagnostic, prognostic, and therapeutic targets. Currently, there are many research bladder tumor markers, but only a few are commercially available. The ideal urinary bladder tumor test is still unavailable, but the eventual "gold standard" will consist of multiple assays that analyze nucleic acids and proteins for detection. In addition, these tests would also reveal to the clinician both prognostic information and therapeutic targets for personalized medical treatment.
    Medicine and Biology. 01/2007; 14:61-6.
  • Jugoslovenska Medicinska Biohemija-yugoslav Medical Biochemistry - JUGOSLAV MED BIOHEM. 01/2006; 25(4):317-323.
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    ABSTRACT: Acquired factor VIII (FVIII) inhibitor causes a rare but life-threatening form of bleeding disorder, owing to the formation of autoantibodies against FVIII. Treatment modalities include the use of immunosuppressive drugs, such as cyclophosphamide and corticosteroids, plasmapheresis, and i.v. immunoglobulin. The case of a 67-year-old patient with acquired FVIII inhibitor and psoriasis presented us with a serious bleeding complication. Bleeding reacted poorly to therapy with corticosteroids and cyclophosphamide. Treatment with cyclosporin, however, resulted in a prompt and complete response. The lack of side effects and the relatively quick response suggest that cyclosporin A should be tried as a frontline treatment for patients with acquired FVIII inhibitor.
    Srpski arhiv za celokupno lekarstvo 01/2006; 133 Suppl 2:134-6. · 0.23 Impact Factor