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Latest Paper:
Immunol Res. 2012 Mar 15;:
22418727
Gordana Radosavljevic,
Vladislav Volarevic,
Ivan Jovanovic,
Marija Milovanovic,
Nada Pejnovic,
Nebojsa Arsenijevic,
Daniel K Hsu,
Miodrag L Lukic
Center for Molecular Medicine and Stem Cell Research, Faculty of Medicine, University of Kragujevac, Svetozara Markovica 69, 34000, Kragujevac, Serbia.
Galectin-3, a unique chimera-type member of the β-galactoside-binding soluble lectin family, is widely expressed in numerous cells. Here, we discuss the role of Galectin-3 in T-cell-mediated inflammatory (auto) immunity and tumor rejection by using Galectin-3-deficient mice and four disease models of human pathology: experimental autoimmune encephalomyelitis (EAE), Con-A-induced hepatitis, multiple low-dose streptozotocin-induced diabetes (MLD-STZ diabetes) and metastatic melanoma. We present evidence which suggest that Galectin-3 plays an important pro-inflammatory role in Con-A-induced hepatitis by promoting the activation of T lymphocytes, NKT cells and DCs, cytokine secretion, prevention of M2 macrophage polarization and apoptosis of mononuclear cells, and it leads to severe liver injury. In addition, experiments in Galectin-3-"knock-out" mice indicate that Galectin-3 is also involved in immune-mediated β-cell damage and is required for diabetogenesis in MLD-STZ model by promoting the expression of IFN-gamma, TNF-alpha, IL-17 and iNOS in immune and accessory effector cells. Next, our data demonstrated that Galectin-3 plays an important disease-exacerbating role in EAE through its multifunctional roles in preventing cell apoptosis and increasing IL-17 and IFN-gamma synthesis, but decreasing IL-10 production. Finally, based on our findings, we postulated that expression of Galectin-3 in the host may also facilitate melanoma metastasis by affecting tumor cell adhesion and modulating anti-melanoma immune response, in particular innate antitumor immunity. Taken together, we discuss the evidence of pro-inflammatory and antitumor activities of Galectin-3 and suggest that Galectin-3 may be an important therapeutic target.
Clinical Centre Nis, Eye Clinic, Nis, Serbia. sonjaziv@yahoo.com
BACKGROUND Idiopathic polypoidal choroidal vasculopathy (IPCV) is uncommon condition. It is considered to be a variant of neovascular age-related macular degeneration, but it can be also found in younger patients. CASE REPORT We presented a case of otherwise healthy, 36-year-old women, with sudden unilateral visual impairment in the left eye and metamorphosia. Slit lamp biomicroscopy examination of the eye anterior segment was normal. Intraocular pressure determined by aplanation tonometry was 16 mmHg in both eyes. Indirect slit lamp biomicroscopy examination showed signs of serosanquinous detachments of the retinal pigment epithelium. Fluorescein angiography showed a subretinal vessel network through the pigment epithelial atrophy with hyperfluorescence in superior part of serohemorrhagic pigment epithelial detachment and the inferior hypofluorescence, caused by hemorrhage. Optical coherence tomography proved detachment of the retinal pigment epithelium. CONCLUSION In patients with IPCV a mild, natural course with spontaneous resorption of exudations and hemorrhage and improvement in visual acuity can be observed. There is no approved treatment at present.
Immunol Res. 2012 Mar 6;:
22392053
Marija Milovanovic,
Vladislav Volarevic,
Gordana Radosavljevic,
Ivan Jovanovic,
Nada Pejnovic,
Nebojsa Arsenijevic,
Miodrag L Lukic
Faculty of Medicine, Center for Molecular Medicine and Stem Cell Research, University of Kragujevac, Svetozara Markovica 69, 34000, Kragujevac, Serbia.
Interleukin-33 (IL-33), a member of the IL-1 family of cytokines, binds to its plasma membrane receptor, heterodimeric complex consisted of membrane-bound ST2L and IL-1R accessory protein, inducing NFkB and MAPK activation. IL-33 exists as a nuclear precursor and may act as an alarmin, when it is released after cell damage or as negative regulator of NFκB gene transcription, when acts in an intracrine manner. ST2L is expressed on several immune cells: Th2 lymphocytes, NK, NKT and mast cells and on cells of myeloid lineage: monocytes, dendritic cells and granulocytes. IL-33/ST2 axis can promote both Th1 and Th2 immune responses depending on the type of activated cell and microenvironment and cytokine network in damaged tissue. We previously described and discuss here the important role of IL-33/ST2 axis in experimental models of type 1 diabetes, experimental autoimmune encephalomyelitis, fulminant hepatitis and breast cancer. We found that ST2 deletion enhance the development of T cell-mediated autoimmune disorders, EAE and diabetes mellitus type I. Disease development was accompanied by dominantly Th1/Th17 immune response but also higher IL-33 production, which suggest that IL-33 in receptor independent manner could promote the development of inflammatory autoreactive T cells. IL-33/ST2 axis has protective role in Con A hepatitis. ST2-deficient mice had more severe hepatitis with higher influx of inflammatory cells in liver and dominant Th1/Th17 systemic response. Pretreatment of mice with IL-33 prevented Con A-induced liver damage through prevention of apoptosis of hepatocytes and Th2 amplification. Deletion of IL-33/ST2 axis enhances cytotoxicity of NK cells, production of IFN-γ in these cells and systemic production of IFN-γ, IL-17 and TNF-α, which leads to attenuated tumor growth. IL-33 treatment of tumor-bearing mice suppresses activity of NK cells, dendritic cell maturation and enhances alternative activation of macrophages. In conclusion, we observed that IL-33 has attenuated anti-inflammatory effects in T cell-mediated responses and that both IL-33 and ST2 could be further explored as potential therapeutic targets in treatment of immune-mediated diseases.
University Clinical Hospital Center Zemun, Faculty of Medicine, University of Belgrade, Vukova 9, 11070 Belgrade, Serbia.
Klaus Mönkemüller, Department of Internal Medicine, Gastroenterology and Infectious Diseases, Marienhospital Bottrop, Bottrop 46236, Germany.
AIM To study the endoscopic and radiological characteristics of patients with hepaticojejunostomy (HJ) and propose a practical HJ stricture classification. METHODS In a retrospective observational study, a balloon-assisted enteroscopy (BAE)-endoscopic retrograde cholangiography was performed 44 times in 32 patients with surgically-altered gastrointestinal (GI) anatomy. BAE-endoscopic retrograde cholangio pancreatography (ERCP) was performed 23 times in 18 patients with HJ. The HJ was carefully studied with the endoscope and using cholangiography. RESULTS The authors observed that the hepaticojejunostomies have characteristics that may allow these to be classified based on endoscopic and cholangiographic appearances: the HJ orifice aspect may appear as small (type A) or large (type B) and the stricture may be short (type 1), long (type 2) and type 3, intrahepatic biliary strictures not associated with anastomotic stenosis. In total, 7 patients had type A1, 4 patients A2, one patient had B1, one patient had B (large orifice without stenosis) and one patient had type B3. CONCLUSION This practical classification allows for an accurate initial assessment of the HJ, thus potentially allowing for adequate therapeutic planning, as the shape, length and complexity of the HJ and biliary tree choice may mandate the type of diagnostic and therapeutic accessories to be used. Of additional importance, a standardized classification may allow for better comparison of studies of patients undergoing BAE-ERCP in the setting of altered upper GI anatomy.
Dig Dis. 2011 ;29 Suppl 1 :27-31
22104749
Ivan Jovanovic,
Klaus Vormbrock,
Lars Zimmermann,
Srdjan Djuranovic,
Milenko Ugljesic,
Peter Malfertheiner,
Lucia C Fry,
Klaus Mönkemüller
Clinic for Gastroenterology and Hepatology, Clinical Center of Serbia, Belgrade, Serbia.
Background/Aims: There are few reports focusing on therapeutic small bowel endoscopy. The aim of this study was to analyze the results of therapeutic small bowel endoscopy in a large cohort of patients. Methods: A retrospective study of a prospectively collected database comprising all patients undergoing diagnostic and therapeutic small bowel endoscopy in three centers. Results: A total of 614 double-balloon enteroscopies were performed in 534 patients. The most common pathological findings were angiodysplasias and vascular lesions (n = 98, 18%), mucosal ulcers and erosions (n = 95, 17.8%), polyps and tumors (including patients with familiar polyposis syndrome such as Peutz-Jeghers syndrome, familiar adenomatous polyps syndrome, neurofibromatosis, adenocarcinoma, neuroendocrine tumors and gastrointestinal stromal tumors)(n = 52, 9.7%), and strictures (Crohn's disease, ischemia, tumors)(n = 12, 2.2%). The mean duration of therapeutic small bowel enteroscopy was 67 min (range 30-115) compared to 50 min (range 25-105) for diagnostic procedures (p < 0.05). A therapeutic small bowel endoscopy was performed in 121 patients (22%). Therapeutic procedures included argon plasma coagulation of vascular lesions (n = 73), polypectomy (n = 49), mucosectomy (n = 5), stricture dilation (n = 7), foreign body extraction (n = 7), injection of fibrin glue (n = 10), and clip placement (n = 5). There were a total of 5 complications (0.9%; paralytic ileus, n = 2, pancreatitis, n = 1, bleeding n = 2). No perforations or deaths occurred. Conclusion: Endoscopists performing double-balloon enteroscopy should be trained and prepared to provide therapeutic interventions for small bowel disorders including argon plasma coagulation, injection, hemoclipping, polypectomy, mucosectomy and foreign body extraction. Therapeutic small bowel endoscopy, albeit associated with complications in about 1% of cases, can be considered a relatively safe procedure.
Dig Dis. 2011 ;29 (5):491-3
22095016
Clinical Center of Serbia, Gastroenterology and Hepatology Clinic, University of Belgrade, Faculty of Medicine, Belgrade, Serbia.
There are four major complications of peptic ulcer disease (PUD): bleeding, perforation, penetration, and obstruction. Complications can occur in patients with peptic ulcer of any etiology. Despite improvements in the medical management and the lower overall incidence of PUD, there are conflicting data about the incidence of potentially life-threatening ulcer complications. There are important time trends embedded within this stable overall rate of complications: the dramatic decline in the prevalence of Helicobacter pylori (comparing the cohort born from 1900 to 1920 to cohorts born after 1940); an increased use of nonsteroidal anti-inflammatory drugs, and an increased rate of ulcer complications related to such drug use, especially in the elderly. As a result of these trends, ulcer complications are on the rise in older patients but on the decline in younger individuals. Hemorrhage is the most frequent PUD complication and its incidence is increasing in comparison to perforation and stenosis. Therapeutic endoscopy is considered the treatment of choice for bleeding ulcers, reducing the need for emergent surgical procedures to 10-20% of the cases. In recent years, besides the success of angiographic embolization, the containment of massive hemorrhage must also be taken into account. Transcatheter arterial embolization is also an effective and safe treatment in patients with duodenal ulcers re-bleeding after therapeutic endoscopy or surgery.
Ljiljana Vasović,
Ivan Jovanović,
Slađana Ugrenović,
Slobodan Vlajković,
Predrag Jovanović,
Vesna Stojanović
Department of Anatomy, Faculty of Medicine, University of Niš, Blvd. Dr Zoran Đinđić 81, 18000 Niš, Serbia. likica@medfak.ni.ac.rs
OBJECTS Carotid-vertebrobasilar anastomoses-the trigeminal, otic, hypoglossal, and proatlantal intersegmental arteries-serve as transitory channels between primitive internal carotid arteries and bilateral longitudinal neural arterial plexus, which is the precursor of future basilar artery, when the human embryo reaches about 4-mm length. MATERIAL AND METHODS Normal and/or abnormal morphofunctional aspects of the prenatal and postnatal forms of the trigeminal artery are described according to personal and literature data. Many arteries of similar origin and course are also noted in the differential diagnosis of the trigeminal artery. CONCLUSIONS The persistent primitive trigeminal artery, as the most commonly carotid-vertebrobasilar anastomosis, has a reported incidence of 0.03-2.2% in the literature. There is female sex predilection, and it may be discovered in patients of any age, on either side, and in association with many vascular variants. Although the significance of persistent primitive trigeminal artery regarding the development of an aneurysm or association with another pathological condition may not be clear, its (ab)normal morphology is the inspiration for anatomists, especially for neurosurgeons, before planning diagnostic and therapeutic procedures.
Faculty of Veterinary Medicine, University of Belgrade, Department of Physiology and Biochemistry, Bulevar Oslobodjenja 18, 11000 Belgrade, Serbia. olja@vet.bg.ac.rs
The objective of this experiment was to compare the efficiencies of sodium selenite (SS) and selenized yeast (SY) supplemented at different doses (0.05 and 0.30 mg Se/kg feed) with respect to plasma glutathione peroxidase (Gpx) activity, extent of oxidative lipid injury, and thyroid hormone activation in broilers during the first four weeks of growth. Results indicate a significant increase in plasma Gpx activity and reduction in thiobarbituric acid reactive substances (TBARS) in all supplemented groups at 4 weeks of age compared to 2-week-old chicks. Plasma thyronine activation was highest in SY supplemented broilers. It can be concluded that in the first 4 weeks of broiler life selenite has a more efficient antioxidative effect which is reflected in lower plasma and liver TBARS values. However, broiler feed supplementation with selenized yeast results in a more proficient conversion of T4 to T3.
Pharmacol Rep. ;63 (3):808-814
21857092
Maja Milojkovic,
Slavica Stojnev,
Ivan Jovanovic,
Srdjan Ljubisavljevic,
Vladisav Stefanovic,
Raute Sunder-Plassman
Institute of Pathophysiology, University School of Medicine Zorana Djindjica 81, 18000 Nis, Serbia. maja@medfak.ni.ac.rs.
The multi-drug resistance 1 (MDR1) gene encodes for a P-glycoprotein (PGP), which acts as a gate-keeper against various kinds of xenobiotics. Several single nucleotide polymorphisms (SNPs) in the MDR1 gene that may influence PGP level and function have been identified. The aim of this study was to simultaneously analyze the three most important MDR1 SNPs, C3435T, G2677T/A and C1236T, in the Serbian population and to compare the results with those published for other ethnic groups. A group of 158 unrelated, healthy subjects was included in the present study. For determination of MDR1 SNPs, a multiplexed mutagenically separated PCR was performed. The genotype frequency of the analyzed MDR1 SNPs was as follows: 3435 nt - 0.19 (CC), 0.54 (CT) and 0.27 (TT); 2677 nt - 0.26 (GG), 0.52 (GT), 0.15 (TT), 0.03 (GA) and 0.064 (TA), and 1236 nt - 0.23 (CC), 0.61 (CT) and 0.16 (TT). Our results for the Serbian population could be relevant for further investigation of drugs that are substrates of PGPand for studies of interethnic diversity in MDR1 polymorphism frequency.
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