Vignjević S

University of Belgrade, Beograd, Central Serbia, Serbia

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Publications (40)27.67 Total impact

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    ABSTRACT: The aim of our study was to investigate the appearance, density and distribution of ghrelin cells and GHS-R1a and GHS-R1b in the human stomach and duodenum during prenatal and early postnatal development. We examined chromogranin–A and ghrelin cells in duodenum, and GHS-R1a and GHS-R1b expression in stomach and duodenum by immunohistochemistry in embryos, fetuses, and infants. Chromogranin-A and ghrelin cells were identified in the duodenum at weeks 10 and 11 of gestation. Ghrelin cells were detected individually or clustered within the base of duodenal crypts and villi during the first trimester, while they were presented separately within the basal and apical parts of crypts and villi during the second and third trimesters. Ghrelin cells were the most numerous during the first (∼11%) and third (∼10%) trimester of gestation development. GHS-R1a and GHS-R1b were detected at 11 and 16 weeks of gestation, showed the highest level of expression in Brunner's gland and in lower parts of duodenal crypts and villi during the second trimester in antrum, and during the third trimester in corpus and duodenum. Our findings demonstrated for the first time abundant duodenal expression of ghrelin cells and ghrelin receptors during human prenatal development indicating a role of ghrelin in the regulation of growth and differentiation of human gastrointestinal tract.
    Peptides 01/2014; · 2.52 Impact Factor
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    ABSTRACT: Psychological stress affects different physiological processes including haematopoiesis. However, erythropoietic effects of chronic psychologi-cal stress remain largely unknown. The adult spleen contains a distinct microenvironment favourable for rapid expansion of erythroid progeni-tors in response to stressful stimuli, and emerging evidence suggests that inappropriate activation of stress erythropoiesis may predispose to leukaemic transformation. We used a mouse model to study the influence of chronic psychological stress on erythropoiesis in the spleen and to investigate potential mediators of observed effects. Adult mice were subjected to 2 hrs daily restraint stress for 7 or 14 consecutive days. Our results showed that chronic exposure to restraint stress decreased the concentration of haemoglobin in the blood, elevated circulating levels of erythropoietin and corticosterone, and resulted in markedly increased number of erythroid progenitors and precursors in the spleen. Western blot analysis revealed significantly decreased expression of both erythropoietin receptor and glucocorticoid receptor in the spleen of restrained mice. Furthermore, chronic stress enhanced the expression of stem cell factor receptor in the red pulp. Moreover, chronically stressed animals exhibited significantly increased expression of bone morphogenetic protein 4 (BMP4) in the red pulp as well as substantially enhanced mRNA expression levels of its receptors in the spleen. These findings demonstrate for the first time that chronic psychological stress activates BMP4-dependent extramedullary erythropoiesis and leads to the prolonged activation of stress erythropoiesis pathways. Prolonged activation of these pathways along with an excessive production of immature erythroid cells may predispose chronically stressed subjects to a higher risk of leukaemic transformation.
    11/2013;
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    ABSTRACT: Psychological stress affects different physiological processes including haematopoiesis. However, erythropoietic effects of chronic psychological stress remain largely unknown. The adult spleen contains a distinct microenvironment favourable for rapid expansion of erythroid progenitors in response to stressful stimuli, and emerging evidence suggests that inappropriate activation of stress erythropoiesis may predispose to leukaemic transformation. We used a mouse model to study the influence of chronic psychological stress on erythropoiesis in the spleen and to investigate potential mediators of observed effects. Adult mice were subjected to 2 hrs daily restraint stress for 7 or 14 consecutive days. Our results showed that chronic exposure to restraint stress decreased the concentration of haemoglobin in the blood, elevated circulating levels of erythropoietin and corticosterone, and resulted in markedly increased number of erythroid progenitors and precursors in the spleen. Western blot analysis revealed significantly decreased expression of both erythropoietin receptor and glucocorticoid receptor in the spleen of restrained mice. Furthermore, chronic stress enhanced the expression of stem cell factor receptor in the red pulp. Moreover, chronically stressed animals exhibited significantly increased expression of bone morphogenetic protein 4 (BMP4) in the red pulp as well as substantially enhanced mRNA expression levels of its receptors in the spleen. These findings demonstrate for the first time that chronic psychological stress activates BMP4-dependent extramedullary erythropoiesis and leads to the prolonged activation of stress erythropoiesis pathways. Prolonged activation of these pathways along with an excessive production of immature erythroid cells may predispose chronically stressed subjects to a higher risk of leukaemic transformation.
    Journal of Cellular and Molecular Medicine 11/2013; · 4.75 Impact Factor
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    ABSTRACT: The aim of our study was to investigate HER-2 and TOP2A gene status and their correlation with Bcl-2, p53, Ki67, ssDNA, and clinicopathological parameters in four molecular subtypes of breast cancer. Seventy-four paraffin-embedded samples are immunohistochemically studied for the expression of estrogen receptor (ER), progesterone receptor (PR), HER-2, p53, Bcl-2, ssDNA, and Ki67, while HER-2 and TOP2A gene status by fluorescence in situ hybridization was investigated in 60 samples. Luminal A and B subtypes were characterized with small tumor size, intermediate histological grade, negative lymph node, and metastatic status, while triple negative and HER-2 positive subtypes were associated with larger tumor size, poorly differentiated tumors, and positive lymph node status. p53, Ki67, and ssDNA expression was higher in triple negative and HER-2 positive than in luminal subtypes, while ER, PR, and Bcl-2 dominated in luminal subtypes. HER-2 gene status was higher in luminal B and HER-2 positive than in luminal A and triple negative subtypes, while TOP2A gene status was similar. HER-2 gene status positively correlated with TOP2A gene status, HER-2 receptor, and histological grade, while negative correlation characterized relationship between HER-2 gene status and ER, PR, and Bcl-2. The shortened overall survival period characterized patients from triple negative breast cancer subtype (18.7 months). HER-2 and TOP2A gene amplification showed a tendency to be associated with larger tumor size, positive lymph node status, high level of apoptotic and proliferative indexes, and low level of p53 and Bcl-2 expression, which all together indicate group of patients with similar outcome during the progression of the disease.
    Targeted Oncology 11/2013; · 3.46 Impact Factor
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    ABSTRACT: INTRODUCTION TOP2A gene aberration, TOP2A and BRCA1 expression are very significant prognostic and predictive markers in breast cancer, however their correlation in four molecular subtypes have not yet been evaluated. OBJECTIVES The aim of our study was to investigate TOP2A gene aberration (using FISH methods), TOP2A and BRCA1 protein over-expression (immunohistochemistry) in four molecular subtypes of breast cancer and to compare them with clinicopathological parameters. MATERIAL The 67 tissue samples were analyzed by immunohistochemistry and 53 patients by FISH methods. RESULTS Of the 67 patients, 33 showed TOP2A and 39 patients demonstrated BRCA1 over-expression. Significant difference in TOP2A expression was found between Luminal A and B, Luminal B and triple negative, Luminal B and HER-2 positive subtypes. Of 22 patients with TOP2A amplification, 15 (68.2 %) over-expressed TOP2A: 4 (26.7 %) cases in Luminal A, 9 (60 %) cases in Luminal B, 2 (13.3 %) cases in HER-2 positive subgroup. Of 11 Luminal B tumors with TOP2A amplification, 9 (81.8 %) over-expressed TOP2A. BRCA1 over-expression showed a significant positive correlation with TOP2A expression in Luminal A, Luminal B, triple negative and HER-2 positive subtypes (p=0.05). TOP2A, BRCA1 over-expression and TOP2A gene aberrations in Luminal A, B and triple negative subtypes was associated with a small tumor size, moderately differentiated tumors, negative lymph node status and no distant metastases. CONCLUSIONS We demonstrate for the first time a similar pattern of BRCA1 and TOP2A expression and a significant correlation between these proteins in Luminal A, B, triple negative and HER-2 positive subtypes.
    Polskie archiwum medycyny wewnȩtrznej 06/2013; · 2.05 Impact Factor
  • 18th Congress of the European Hematology Association, June 13-16, 2013, Stockholm, Sweden, Haematologica 2013:98, Page 615-616 (B1594), Stockholm, Sweden; 06/2013
  • IX International Conference on HFRS HPS & Hantaviruses, Beijing, China, June 5-7, 2013. (P3-2), Beijing, China,; 06/2013
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    Medicinski Casopis 01/2013; 47(1):7-11.
  • Treći kongres endokrinologa Srbije sa međunarodnim učešćem, Beograd, 6-9 decembar, 2012. godine, Abstract book, str. 33, Beograd, Srbija; 12/2012
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    ABSTRACT: AIMS: We showed previously that the acute effect of ethanol on intestinal immunoglobulin A (IgA) expression might be mediated by endogenous nitric oxide (NO). To extend these findings, this study was designed to investigate a possible role of neuronal NO synthase (nNOS) in the observed phenomenon, using 7-nitroindazole (7-NI), a selective inhibitor of its activity. METHODS: Adult male Wistar rats were treated with: (a) ethanol (4 g/kg, intraperitoneally, i.p.), (b) 7-NI (25 mg/kg, i.p.) followed by ethanol (4 g/kg, i.p.) 30 min later and (c) 7-NI (25 mg/kg, i.p.) followed by saline 30 min later. Untreated rats were used as controls. The concentrations of serum and intestinal IgA were measured by enzyme-linked immunosorbent assay, while the expression of nNOS was determined using western blot and immunohistochemistry. RESULTS: Acute ethanol treatment significantly increased the concentration of IgA in the ileal extracts, whereas it decreased its serum level. Inhibition of nNOS activity by 7-NI abolished this action of alcohol on IgA. Additionally, western blot analysis revealed that the acute alcohol administration induced an increase in the expression of intestinal nNOS. Furthermore, nNOS-immunoreactive cells, observed within the lamina propria of small intestine, were numerous in ethanol-treated rats. CONCLUSION: Taken together, these results extended our previous findings suggesting that nNOS mediates the acute effect of ethanol on IgA and supported an immunomodulatory role of this enzyme isoform.
    Alcohol and Alcoholism 10/2012; · 1.96 Impact Factor
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    ABSTRACT: Background: This study was performed to investigate expression and distribution of glucocorticoid receptor (GR) in the rat adrenal cortex, acute effect of ethanol on its expression and possible role of endogenous nitric oxide (NO) in this phenomenon. Methods: Adult female Wistar rats showing diestrus day 1 were treated with: a) ethanol (2 or 4 g/kg body weight (b.w.), ip), b) N(ω)-nitro-L-arginine methyl ester (L-NAME), well-known competitive inhibitor of all isoforms of NO synthase (NOS), (30 mg/kg b.w., sc) followed by ethanol (4 g/kg, ip) 3 h later and c) L-NAME (30 mg/kg b.w., sc) followed by saline (ip) 3 h later. Untreated rats were used as controls. Adrenocortical expression of GR was estimated by immunohistochemistry. Results: Strong nuclear GR staining was observed throughout the cortex of control rats. Acute ethanol treatment significantly decreased the expression of GR in the zona fasciculata and zona reticularis. Blockade of NO formation had no influence on this effect of ethanol, whereas L-NAME itself induced significant decline in GR immunoreactivity. Conclusions: Obtained findings are the first to demonstrate localization and distribution of the GR throughout the rat adrenal cortex and to suggest that ethanol as well as endogenous NO may modulate adrenocortical expression of this steroid receptor.
    Pharmacological reports: PR 07/2012; 64(4):896-901. · 1.97 Impact Factor
  • 17 th Congress of the European Hematology Association, Amsterdam, June 14–17, 2012, Hematologica, page 389, Ab. No. 0940., Amsterdam; 06/2012
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    ABSTRACT: BACKGROUND: Since reports on endocrine cells and their kinetics in the corpus of the human stomach are limited, the aim of this study was to examine the appearance, localization, density, and the relationship among the endocrine cell types in the corpus of the human stomach during prenatal and early postnatal development. METHODS: We examined chromogranin A, somatostatin, ghrelin, glucagon, and serotonin expression by immunohistochemistry in 2 embryos, 38 fetuses, and 3 infants in the corpus of human stomach. RESULTS: Chromogranin A secreting endocrine cells were identified in the corpus at week 10 of gestation. Somatostatin cells were present from the 10th week, ghrelin and serotonin cells from the 11th week, and glucagon cells from the 12th week of gestation. Endocrine cells were present individually or clustered within the glandular base and body during the first trimester, and were present separately within the basal and central parts of glands during the second and third trimesters. Somatostatin cells were the most common type of cells (~46 %) during the first trimester, while ghrelin cells were the most numerous during the second trimester (~34 %), and in infants (~28 %). The percentage of glucagon cells was significant only during the first trimester of pregnancy (5.5 %), and the percentage of serotonin cells was only significant just before birth (4.8 %). CONCLUSIONS: These results show, for the first time, that the largest number of endocrine cells are present in the corpus during the first trimester of prenatal development. Also, these results suggest that secretory products of endocrine cells play a role in the regulation of homeostasis, growth, and differentiation, and in human stomach function.
    Journal of Gastroenterology 04/2012; · 3.79 Impact Factor
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    ABSTRACT: The pancreas appears to be a major source of ghrelin during fetal development, but the ontogeny of ghrelin cells in the human pancreas and their developmental relationship with α- and β-cells remain largely unknown. In the present study, we examined the dynamics of ghrelin cell growth, colocalization of ghrelin with major pancreatic hormones and defined the similarities and differences among developmental patterns of ghrelin-, glucagon- and insulin-expressing cells in the human pancreas. To this end, paraffin-embedded pancreatic tissue sections from human embryos and fetuses were assessed by immunohistochemistry. Ghrelin-positive cells were first detected in the pancreas of 11-week-old fetuses. With advancing gestational age, both ghrelin- and glucagon-expressing cells were increasingly observed at the periphery of the developing islets, whereas insulin-containing cells were typically found in the islet core. Double immunohistochemistry showed that ghrelin-expressing cells were clearly separate from insulin-, somatostatin- and pancreatic polypeptide-containing cells. In contrast, cells coexpressing ghrelin and glucagon were sporadically detected during both the early and late fetal periods. Furthermore, morphometric analysis revealed a similar trend in the volume density of ghrelin- and glucagon-positive cells, and a contrasting pattern in β-cell density at specific time points during the development of the human pancreas. This study demonstrates that the developmental pattern of ghrelin cells, although clearly distinct, is quite similar to that of glucagon-expressing cells. The obtained findings indicate a close lineage relationship between these cell populations, a functional relationship between their secretory products and an auto/paracrine mode of ghrelin-glucagon interaction in pancreatic development.
    Cells Tissues Organs 04/2012; 196(4):362-73. · 1.96 Impact Factor
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    ABSTRACT: Numerous studies were aimed to detect and characterize various tumor markers in patients with oral planocellular carcinoma in order to reduce moratlity and mobidity rates of these patients, as well as to establish the correlation between the expression of specific tumor marker and prognostic outcome. The aim of this study was to determine patohistological characteristics of tumor and peritumor tissue in patients with oral planocellular carcinoma, with special regard to the expression of Bcl-2, as well as to point out the significance of clinicomorphological correlations for clinical use. Sixty-two patients with oral planocellular carcinoma, stage II and III, were examined. The patients were surgically treated for this condition at the Clinic for Maxillofacial Surgery, Military Medical Academy, Belgrade. Surgical specimens were obtained from both tumor and peritumoral tissues. Patohistologic degree of tumor differentiation and the immunohistochemical expression of Bcl-2 were determinated for each specimens. Twenty-four (39%) patients had tumor dimension T1, while six (9%) and thirty-two (52%) patients had tumor dimension T2 and T3, respectively. Patohistologic analysis of peritumor connective, fat, muscle and bone tissue samples confirmed the presence of tumor infiltration. The expression of Bcl-2 in peritumor tissue samples correlated significantly with tumor's histologic grade (rho = 0.468; p < 0.001), nuclear grade (rho = 0.430; p < 0.001) and nucleocytoplasmic ratio (rho = 0.410; p = 0.001). This results suggest that the expression of Bcl-2 in combination with patohistologic findings could have a prognostic value in patients with oral planocellular carcinoma.
    Vojnosanitetski pregled. Military-medical and pharmaceutical review 04/2012; 69(4):314-9. · 0.21 Impact Factor
  • 53th ASH Annual Meeting and Exposition, December 10-13, 2011, San Diego, USA, 3847, Session: 634, Myeloproliferative Syndromes: Poster III. Blood, 2011; 118:1645-1645., San Diego, USA,; 12/2011
  • 13 Kongres farmakologa Srbije i 3. kongres kliničke farmakologije Srbije. Palić, 5-8. oktobra. 2011. godine, Zbornik sažetaka, str.144., Palić; 10/2011
  • 3th International Symposium of Clinical and Applied Anatomy, July 22-24, 2011, Maribor, Slovenia, p20, Maribor, Slovenia; 07/2011
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    ABSTRACT: The present study was designed to investigate a possible role of endogenous nitric oxide (NO) in the adrenal response to an acute alcohol administration in female rats. To this end, N(ω)-nitro-L-arginine-methyl ester (L-NAME), a competitive inhibitor of all isoforms of NO synthase, was used. Adult female Wistar rats showing diestrus Day 1 were treated with: (a) ethanol (2 or 4 g/kg, intraperitoneally); (b) L-NAME (30 or 50 mg/kg, subcutaneously) followed by either ethanol or saline 3 h later. Untreated and saline-injected rats were used as controls. The animals were killed 30 min after last injection. Adrenal cortex was analyzed morphometrically, and plasma levels of adrenocorticotropic hormone (ACTH) and serum concentrations of corticosterone were determined. Acute ethanol treatment enhanced the levels of ACTH and corticosterone in a dose-dependent manner. Stereological analysis revealed that acute alcohol administration induced a significant increase in absolute volume of the cortex and the zona fasciculata (ZF). In addition, ethanol at a dose of 4 g/kg increased volume density and length of the capillaries in the ZF. However, other stereological parameters were unaffected by alcohol exposure. Pretreatment with both doses of L-NAME had no effect on ethanol-induced changes. Obtained findings indicate that acute ethanol treatment stimulates the activity of the adrenal cortex and that this effect is not mediated by endogenous NO in female rats under these experimental conditions.
    Alcohol and Alcoholism 05/2011; 46(5):523-8. · 1.96 Impact Factor
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    ABSTRACT: The aim of this study was to investigate the appearance, localization and density of ghrelin cells in the human stomach during prenatal development. For this purpose the antrum and corpus of embryos, fetuses and infants are stained immunohistochemically by the streptavidin-biotin technique. The presence of P/D1 cells at 11 weeks of fetal development, their highest density during the first detection and higher density in the corpus than in antrum, and their localization in the glandular base of stomach gland, all suggest that ghrelin plays a major role in the early stages of the developing stom-ach.
    Archives of Biological Sciences 01/2011; 63(1):21-28. · 0.79 Impact Factor

Publication Stats

14 Citations
27.67 Total Impact Points

Institutions

  • 2010–2014
    • University of Belgrade
      • Institute for Medical Research
      Beograd, Central Serbia, Serbia
  • 2008
    • Institute for Medical Research - Belgrade
      Beograd, Central Serbia, Serbia