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Although surgical revascularization of the myocardium is routine and one of the most performed procedures in cardiac surgery, complications that occur during and after surgery, such as systemic inflammation and sepsis, as well as bleeding due to impaired platelet function, have a high share in such high mortality. The extracorporeal bloodstream system has a special role in these processes. Determination of levels of new biomarker for detection infectious complications - presepsin, with CRP and leukocyte formula, is just one of these diagnostic combinations of tests that allow assessment of the immune status of a cardiac patient and the need for further examination and / or therapy of patients who may potentially develop systemic inflammatory response syndrome (SIRS) or sepsis. On the other hand, the application of aggregometry gives precise data on the functional changes of platelets, which enables adequate care of complications in terms of increased postoperative bleeding or thrombosis. The study included 100 patients of both sexes, 22 women (21.6%) and 78 men (76.5%), mean age 64.63 ± 7.48 years. Patients were divided into two groups in relation to the use of extracorporeal blood circulation device. Postoperatively, there was a decrease in the number of erythrocytes (p 1800ml) was present in 15 patients (15 in the group where the extracorporeal circulatory system was applied, 17.64% of patients (9/51) met the clinical criteria for SIRS with elevated presepsin values of 600 pg / ml and more, while in the second group of patients 2 of 49 (4.08%) met the clinical and laboratory criteria for SIRS.The ECC system significantly affects the development of SIRS and inhibition of platelet function in patients where it was applied during surgery.

A possibility to develop sever systemic complications of acute pancreatitis(AP) demands timely assessment of the severity of the disease in order to make an optimal therapeutic approach and a correct prognosis of the disease. The aim of the study was to establish the role of certain individual inflammatory biomarkers and coagulation parameters in the prediction of AP severity, and also to propose a mathematical formula which allows there combined use for the same purpose. Methods. The prospective study included 92 patients with AP. The patients were divided into groups: mild, moderate and severe AP. Results. Based on the results of Mann-Whitney,s test, it can be concluded that a statistically significant difference between groups A(mild) and B(moderate and severe) for CRP (p

In classical Hodgkin’s lymphoma (cHL) the existing prognostic scoring systems do not include markers that adequately reflect the interaction of malignant Hodgkin and Reed-Sternberg (HRS) cells and tumor environment. The research objective is to determine the relationship between serum Galectin-1 (Gal-1) and soluble CD163 (sCD163) and the clinical status of patients with cHL, with special emphasis on the presence of relapse, progression, or resistance to the therapy applied. The research included 79 patients. Of this number, 63 were patients with cHL, and the control group consisted of 16 healthy volunteers. The study group of 63 patients with cHL included a subgroup of newly diagnosed patients without therapy, newly diagnosed patients with therapy, patients with relapse and progression of the disease, and primary refractory patients during 2014 and 2015. Analysis of the levels of sCD163 and sGal-1 within a group of patients suffering from cHL has shown that the values of both molecules were higher in relapsed patients and the subgroup with progressive disease comparing the subgroup of newly diagnosed patients without therapy or patients with therapy onset. Determination of Gal-1 and sCD163 levels is simple and reliable analysis that can contribute to the identification of high-risk patients with cHL, and deserves inclusion in current prognostic scoring systems.

Patients with diffuse large B cell non Hodgkin lymphoma (DLBCL) have a very heterogeneous clinical course and prognosis. There is a constant need to find new prognostic factors to assess risk in patients. Immunohistochemical biomarkers correlated with clinical and biochemical parameters, as well as prognostic scores may be predictors of risk patients. The main aim of this study was to analyze the survival of patients with diffuse large B- cell non Hodgkin lymphoma according to clinical prognostic factors and expression of proteins involved in the activation of immune response, cell cycle regulation and programmed cell death (Ki-67, Bcl-2, Bcl-6 , CD10, CD5, CD138, MUM1 and the presence of mutations L265P MyD88), by classifying patients according to current prognostic scoring systems comparing the clinical and immunological factors prognosis in patients with DLBCL, make a proposal for a prognostic scoring system that would unite the two groups of parameters. All patients was determined by clinical stage of the disease. During the study were collected and processed by clinical and laboratory parameters, that are known to have a prognostic value and that it was possible to collect for all patients included in the study. It is about gender, age, Ann Arbor clinical stage of disease, extranodal number of cities affected processes, performance status, presence of "B" symptoms, hemoglobin, platelet count, erythrocyte sedimentation rate, C-reactive protein levels, beta 2 microglobulin, serum albumin and serum LDH. Histopathological material consisted of 68 paraffin blocks. From immunohistochemical parameters were analyzed: CD5, CD10, Ki- 67, Bcl-2, Bcl-6, MUM1 by EnVision procedure. Molecular-genetic study of gene polymorphism MyD88 L265P was used genomic DNA isolated from fixed tissue in paraffin patients with DLBCL. Polymerization chain reaction were amplified by DNA segments within which the SNP is tested gene MyD88 L265P. Statistical analyzes included the use of nonparametric methods and parametric tests. Period of OS (overall survival), was studied using Kaplan-Meier analysis. A statistically significant difference in overall survival (OS) exists in relation to the age (the benefit under the age of 60 years), compared with gender (in favor of women) and the albumin concentration in serum (lower serum albumin levels in patients with DLBCL are associated with shorter OS, as they showed the greatest predictive value). In the prediction of the risk significance showed recategorized performance status (category : ≤2; > 2), recategorized clinical stage of the disease (limited and advanced DLBCL) and R- IPI. The analysis of restriction fragment length is determined homozygous, normal wild type genotype polymorphisms tested. All other clinical, biochemical and immunohistochemical parameters showed no predictive value in patients with DLBCL. in relation to the applied therapeutic protocol there is a strong statistical significance in overall survival in favor of the patients treated at R- CHOP protocol. We standardized PCR-RFLP method for Myd 88 L265P DNA samples isolated from paraffin molds. According to our knowledge there are no data available on the study Myd 88 L265P polymorphism in a population of patients with DLBCL in Serbia. In the population of patients with areas of southeast Serbia pathological signaling pathway which achieves mutation Myd 88 L265, is not responsible for the development DLBCL.Male gender, age over 60, low levels of serum albumin were negative predictor factors in patients with DLBCL. R-IPI score is in the era imunochemotherapy, useful prognostic score in relation to the IPI.

Interferons (IFN) are first described in the late fifties of the twentieth century as special proteins in the family of cytokines and induced by the host, after invasion virus. If you are transferred to the fresh tissue was observed antiviral activity, thanks to inhibit replication of the virus. In this appearance immunology known as "interference". Under normal conditions in the human body concentration of IFN-a was below detectable levels or because cells synthesize IFN or contain as its constituent element. IFN was divided in three classes: IFN-, IFN- and IFN-. Most mammalian cells formed in unequal quantities of IFN- and IFN- after stimulation with viruses or other agents, or inducers of the synthesis of IFN. In many countries, is still detained biotechnological process for the production of human IFN (hlFN) for the clinical application of human leukocytes allocated from canned whole blood units, not older than 6 hours. After centrifugation the procedure centrifugation devotes a buffy coat (leukocyte suspension) as a "side" -produkat. Further processing of "buffy coat" (BC) was purified from the red cell contamination, in order to obtain as pure substrate of human leukocytes, which is subjected to viral infection in order to stimulate the synthesis of hIFN-. Different viruses are used as inductors synthesis hIFN-, but in practice most often used "Sendai" virus, cultivated in horion-alantoic membrane of chicken embryos. Induction of synthesis hIFN- played on temperature of +37 ° C and lasts 18 hours. Refined suspension of human tal and practical. In fundamental respects got the time sequence data on the morphology, viability and induction capabilities of leucocytes, or their ability under the influence of the inductor synthesis hIFN- (or lyophilized virus hemagglutinin) higher yields of interferon, in the new proposed terms. In practical terms should consolidate that, when using a total amount of BC and from all transfusion centers in the Republic of Serbia as a raw material for the production of IFN-, in order to produce sufficient quantities IFN-, as biotherapeutic products, to cover not only needs Republic of Serbia, but to ensure the export of certain quantities of these products in countries with insufficient financial resources. Conclusions: 1. Learn yield and enhanced the antiviral activity of hIFN- in the compositions prepared from the suspension of leukocytes obtained from the pools "buffy coat"s which are added to dissolve dextran and 10% 6% hydroxy ethyl starch high molecular weight compared to the leukocyte suspension prepared in the conventional (current) method. 2. Better and more efficient biotechnological production process hIFN-, compared to the current procedure of obtaining hIFN- according to the modified "Cantell's" method. 3. The human leukocytes used for the production of hIFN- move more and have a greater ability to induction, while the same suspension of leukocytes is used for the production of hIFN- according to the modified "Cantell's" method has a stronger capacity of cell viability and induction ability of human leukocytes. 4. The lyophilized phytohemagglutinin - PHA-P, used as an inductor for the synthesis of hIFN- , although weaker than inductor "Sendai" virus, is a good inducer of the synthesis of which has been successfully induced human leukocytes in purified suspension.

PURPOSE: Research aim of this dissertation is to examine and determine the rates of cytogenetic and molecular responses in patients with chronic myeloid leukemia as well as identification of clinical and laboratory parameters that influence clinical course of the disease and achievement of complete cytogenetic and major molecular response to therapy. Also, the goal of this dissertation is determination and comparison of the basic morphometric parameters of bone marrow angiogenesis for studied groups of patients in order to prove the difference in the degree of angiogenesis, as well as identification of prognostic morphometric parameters of angiogenesis affecting the achievement of complete cytogenetic and major molecular responses. Thesis also includes development and comparison of regression predictive models in which single morphometric parameters of angiogenesis were added to the basic clinical parameters in order to increase the accuracy of prediction of complete cytogenetic and major molecular responses to therapy. METHODOLOGY: This research included 40 patients with chronic myeloid leukemia Philadelphia positive in chronic phase and 20 patients with Hodgkin's and non-Hodgkin's lymphoma in which there was no evidence of lymphoma infiltration of the bone marrow, which were treated at the Clinic of Hematology and Clinical Immunology of the Clinical Center Niš. Morphometric analysis of the microvascular structure of the bone marrow has been performed on biopsy specimens of all patients. Immunohistochemical CD34 stained microscopic preparations have been analyzed on Leica DMR microscope with a digital camera using the direct digitization. Quantification of the digital images was performed using software (ImageJ software, National Institutes of Health, USA) on a personal computer. Firstly total number of microvascular structures by optical field has been determined. For every countable microvascular structure that has been identified, the size dependent and shape dependent morphometric parameters have been evaluated: major axis, minor axis, area, perimeter, feret diameter, circularity, aspect ratio, roundness and solidity. 9 RESULTS: In the study group of patients the cumulative rate of complete cytogenetic response was 75%, and of major molecular response 57.14%. Clinically positive prognostic factors for achieving a complete cytogenetic response have been indentified: the presence of less than 3% of peripheral blasts, less than 4% of the peripheral basophils and less than 4% of basophils in the bone marrow, while the presence of less than 4% of the peripheral basophils was positive prognostic factor for reaching major molecular response (p

Introduction: Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS) characterized by episodic neurological defects, disseminated in time and neuroanatomical localization. The central role in the development of inflammatory mediated lesions in MS is now attributed to autoreactive, myelin-specific CD4+ T lymphocytes, which are thought to regulate all immune mechanisms that lead to the myelin sheath damage. It was originally thought that these cells belong to the subpopulation of Th-1 cells, however, a number of nowadays studies indicate the importance Th-17 cells in the pathogenesis of the disease. In addition to demyelination, which is still considered to be the main pathological feature of the disease, in the last few years special attention in MS research has been given to neurodegenerative processes, considering that it has been shown that the clinical symptoms of the disease are directly related to the degree of axonal damage and loss. Recently, glutamate excitotoxicity is considered as a possible mechanism of neurodegeneration in MS. This is a phenomenon that occurs when the excessive amount of excitatory neurotransmitter glutamate, overactivates its receptors on the membranes of neurons and oligodendrocytes, which leads to the intracellular accumulation of Ca2+ ions and the consequent cell death. Aims of the Thesis: To examine the association of Th-17 mediated inflammation and glutamate excitotoxicity in the development of MS. To determine the potential molecular mechanisms by which inflammation stimulates glutamate excitotoxicity and the consequent neurodegeneration with special emphasis on the role of astrocytes. Materials and Methods: The study had two integral parts: a clinical part conducted on the human material and experimental part conducted on the primary cultures of rat astrocytes. The clinical study enrolled 79 patients, divided into two groups: a control group and a group of MS patients. The presence of a Th-17 cells in the CNS of the studied subjects was monitored by IL-17A levels in the cerebrospinal fluid (CSF) determined by ELISA (Enzyme Immunosorbent Assay) method; while glutamate level was used to estimate excitotoxic damage by HPLC (High Performance Liquid Chromatography) method. The experimental Тh-17 имунски одговор и глутаматска ексцитотоксичност у патогенези МС др Милош Костић 10 study was carried out on the primary cultures of rat astrocytes. In order to investigate the effects of IL-17A on astrocyte ability to uptake and metabolize glutamate, cell cultures were stimulated with increasing concentrations of recombinant rat IL-17A protein, and then used for gene expression analysis of glutamate transporter (GLAST and GLT-1) and the enzyme glutamine synthetase, by PCR (Polymerase Chain Reaction). Investigation of IL-17A effect on astrocyte ability to release glutamate, was conducted in basal conditions and under conditions of elevated and reduced extracellular Ca2+. Astrocyte cultures were stimulated with the rising concentrations of recombinant rat IL-17A protein, and then glutamate secretion was followed up by the level of glutamate in the cell supernatants by HPLC. Results: Patients suffering from MS had a significantly higher level of IL-17A in the CSF compared to the control subjects (P