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Jasenko Karamehić

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S. Arslanagic, J. Karamehić

Introduction: Burns, depending on the degree of severity, induce a significant pathophysiological response in the body. The complement system participates in the body's defenses as well as in immune responses after burn-induced trauma. Objectives: The main objective of the study was to examine how burn severity affects serum C3 and serum C4 complement values; whether burn severity correlates with serum C3 and C4 complement, and establish the predictive value of the serum C3 complement and serum C4 complement for assessing the severity of the burn.  Patients and methods: According to the degree of TBSA, patients were classified into three groups: group with %TBSA<15% (30 patients), group with %TBSA >15% -25% (30 patients), and group with %TBSA > 25% to 40% (30 patients). According to the depth of burns, patients were classified into two groups partial-thickness burns (39 patients) and full-thickness burns (51 patients). We followed laboratory parameters: value serum C3 complement and serum C4 complement on the first and seventh day after burn trauma. Results: Serum C3 complement was significantly lower in patients with %TBSA>25%-40% and in the group with %TBSA>15%-25% compared to patients with %TBSA<15% on the first and seventh day after burn trauma. Serum C3 complement was significantly lower in patients with %TBSA >15%-25% compared to patients with %TBSA<15% on day one and day seven after burn trauma. Serum complement C4 was not significantly different between burn groups on the first and seventh day. Full-thickness burns have significantly lower levels of serum complement C3, compared to partial-thickness burns, on the 1st and 7th day. Full-thickness burns result in a decrease in serum C4 complement compared to partial-thickness burns on the 7th day after burn trauma, but this decrease is not significant. On the 1st day after burn trauma, we found a negative correlation between %TBSA with serum C3 complement. Serum C4 complement was not correlated with %TBSA on the day 1st. Conclusions: %TBSA and depth of burn result in a significant decrease in serum C3 complement but not serum C4 complement. There is a negative correlation of %TBSA and C3 complement but not serum C4 complement on the 1st day after burn trauma. Serum C3 complement is a significant predictor of burn severity. The predictory significance of the C4 complement is not statistically significant.

S. Arslanagic, J. Karamehić

Introduction: Burn, depending on the degree of severity and depth, induces significant pathophysiological  response of the body. Our study is the  prospective study  for  assessment of  T lymphocyte  immunological changes in patients with burns, with different degrees of  %TBSA  and depth of burns. Research objectives : Objectives of this study were to assess %CD3+Ly, % CD4+Ly,  %CD8+Ly, %CD3+HLA-DR+Ly, %CD4+Ly /CD8+Ly), of burned body with different   %TBSA degrees, different depth burns and to establish predictive value of of immune suppression  these  parameters. Patients and methods: According  to %TBSA, patients were classified into three groups:  mild  burns with TBSA% 25% to 40%  (30 patients).  According to the depth of burns, patients were classified into two groups, partial-thickness burns, (39 patients), and full-thickness burns (51 patients). We followed laboratory  parameters :  % CD3+Ly , % CD3+ CD4+Ly,  % CD3+CD8+Ly,  % CD3+HLA-DR+Ly, CD4 / CD8 (%) lymphocytes (on    day 7th and on   day 14th). Results: Percentage of CD3+ lymphocytes was significantly lower in severe  burns compared to the moderate  heavy  burns  andsignificantly lower compared to the mild  burns . Percentage of CD3+CD4+ lymphocytes was significantly lower in severe burns   compared to moderate  heavy burns   and  in relation to  mild burns  (results on day 14th );  also  are lower in moderate severe burn compared  to  mild burns. On day 14th, the% CD4 / CD8 ratio was not significantly lower in the severe burns versus the moderate  burns. On day 14th, the  % CD4 / CD8 ratio wassignificantly lower in severe burns compared to mild burns; significantly lower in moderateburns  compared  to  mild  burns. % CD3+HLA-DR + cells was significantly lower   in severe   burn and moderately  severe  burns  compared to the mild burns  on day 7th, and also on day 14th .  Full- thickness burns have significantly lower  %CD3+lymphocytes, %CD3+CD4+ lymphocytes,  %CD3+HLA-DR+ lymphocytes, ratio of % CD4/CD8 lymphocytes compared to partial-thickness burns  . Conclusions : Peripheral blood T lymphocytes are one of the key indicators of immunosuppression of patients with burns of different % TBSA and different degrees of burn depth.   Larger %TBSA and full- thickness burns injected stronger systemic immunosuppresion,   compared to smaller %TBSA and partial-thickness burns.

E. Fejzić, Izet Eminovic, J. Karamehić, A. Šahović, Sanela Šišić, Damir Suljevic

Objectives This study aims to investigate the low-resolution human leukocyte antigen (HLA)-B locus polymorphisms between unrelated healthy individuals and patients with diagnosis of seronegative spondyloarthropathies and determine risky and protective allelic groups and genotypes. Patients and methods The study included 104 healthy control individuals (52 males, 52 females; median age 43 years; range 2 to 76 years) and 96 patients (43 males, 53 females; median age 28.5 years; range 2 to 67 years) diagnosed with: ankylosing spondylitis (AS) (n=19), reactive arthritis (n=19), psoriatic arthritis (n=28) and undifferentiated spondyloarthropathies (n=30). Genomic deoxyribonucleic acid was extracted from peripheral blood to detect allelic groups of HLA class I and II. Single-specific-primer polymerase chain reaction was used for HLA genotyping and visualization of products after their separation on 1.5% agarose gel for horizontal gel electrophoresis. Results Significantly increased frequency was found for HLA-A*02 and HLA-B*27 allelic variants in all groups of patients. The increased frequency of the HLA-B*35 allelic group in the control group represents the protective gene variant for the occurrence of AS. The predisposing genotype (HLA-B*27/B*44 and B*27/B*51) for the onset of disease was only found in AS patients. Conclusion This study shows the strong association of HLA-B*27 antigen with spondyloarthropathies, which is considered a risk variant of the gene for the onset of disease. Protective and risky allelic variants and genotypes are rare and their detection as well as increased frequency are possible if larger numbers of patients are involved.

Lamija Zečević, J. Karamehić, J. Ćorić, D. Štubljar, N. Avdagić, K. Selmanovic, T. Jukić, S. Savic

Summary Background: There is still no reliable, specific biomarker for precision diagnosis and clinical monitoring of systemic lupus erythematosus. The aim of this study was to investigate the importance of the determination of immunofenotypic profiles (T, B lymphocytes and NK cells) and serum cytokine concentrations (IL-17 and IFN-alpha) as potential biomarkers for this disease. Methods: The study included 55 patients with SLE and 25 healthy controls. The proportion of T, B, NK cells were assessed in peripheral blood using flow cytometric assays while the serum cytokine concentration (IL-17 and IFNalpha) was determined by ELISA test. Results: ROC curve analysis showed good accuracy to distinguish between patients and healthy individuals for activated T cells (AUC=0.798; p<0.001), Treg (AUC= 0.651; p=0.036), and memory B cells (AUC=0.285; p=0.002). We found statistically significant difference (p=0.036) in the levels of serum IL-17 between patients with SLE (IL-17=49.27 pg/mL) and controls (IL-17= 28.64 pg/mL). Conclusions: Significant increase in the relative number of Treg lymphocytes, and decrease in memory B cells, as well as decrease level of IL-17, in SLE patients may be implicated in the pathogenesis of the disease. These parameters, as biomarkers, could distinguish SLE patients and no-SLE patients. Monitoring subpopulations of immune cells in peripheral blood using flow cytometry provides insight into abnormal T and B cell function in SLE. Progress in understanding the immunity at SLE, results in concrete benefits for the SLE patients, which include new clinical management and therapeutic strategies.

E. Fejzić, J. Karamehić, Izet Eminovic, Damir Suljevic, A. Alijagic, Semir Bećirević, A. Šahović, Sanela Šišić

AIM: The research was conducted by genotyping two Human Leukocyte Antigen (HLA) gene classes. The main objective of this research was to investigate distribution and frequency of the allelic groups, genotypes and haplotypes in the gene loci of HLA class I (HLA-A*, -B*, -C*) and HLA class II (HLA-DRB1*, -DQB1*) in patients included in the program of cadaveric renal transplantation. MATERIAL AND METHODS: Our study covered 186 blood samples of patients who are registered on the list for cadaveric renal transplantation in Federation of Bosnia and Herzegovina and included 59 control, healthy unrelated individuals. For the HLA typing, we have used three different methods: micro lymphocyte cytotoxicity test (MLCT), Polymerase Chain Reaction (PCR) – Sequence Specific Primers (SSP) and PCR – Sequence-Specific Oligonucleotides (SSO) or Luminex technology. All patients and cadaveric donors were tested using the three methods because the system is polymorphic. RESULTS: Analysis of the results of genotyping HLA class I gene loci identified dominant HLA-A*02, HLA-B*35, HLA-C*07 allelic groups. Analysis of the HLA class II gene loci genotyping showed that HLA-DRB1*11 and HLA-DQB1*03 loci had the highest incidence in HLA class II. CONCLUSION: Based on our results and previous research, there were no observed differences between allelic frequencies and genotypes of healthy people and people with ESRD. Differences between allelic groups occurred, but they were not statistically significant, except HLA-C*01 (p = 0.020).

Marina Delić-Šarac, S. Mutevelic, J. Karamehić, D. Subasic, T. Jukić, J. Ćorić, Ognjen Ridjić, Mirsad Panjeta, Lejla Zunic

Introduction: Anti GAD (antibodies on glutamic acid decarboxylase) and anti-IA2 antibodies (against tyrosine phosphatase), today, have their place and importance in diagnosis and prognosis of Type 1 diabetes. Huge number of patients with diabetes mellitus type 1 have these antibodies. Insulin antibodies are of critical importance in diagnosis of diabetes mellitus type 1 for pediatric population. Materials and methods: During 2014, the samples of 80 patients from Clinical Center University Sarajevo (CCUS) Pediatrics clinic’s, Endocrinology department were analyzed on anti-GAD and IA2 antibodies. The samples of serums of all patients were analyzed with ELISA tests using Anti GAD ELISA (IgG) kites from EUROIMMUN company. These are quantitative in vitro tests for human antibodies against decarboxylase of glutamine acid (GAD) and IA2, in serum or EDTA plasm. Results: During the period of one year, in CCUS’s Organizational unit, Institute for Clinical Immunology, 80 samples of patients with anti GAD and IA2 antibodies were analyzed. Out of total number of samples, 41 were male patients, or 51% and 39 female, or 49%. The youngest patient was born in 2012, and the oldest in 1993. Age average was represented by the patients born in 2001. Share of positive results for IA2 antibodies and GAD antibodies was 37% for IA2 antibodies, and 63% for GAD antibodies. Discussion: During an autoimmune – mediated Diabetes mellitus type 1 leads to T-cell mediated destruction of beta cells of pancreatic islets, reduced production of insulin and glucose metabolism. Studies have shown that these bodies are the most intense single marker for identifying persons with increased risk for diabetes development.

O. Ridic, S. Bušatlić, Edita Dapo, T. Jukić, Sahrudin Sarajčić, J. Karamehić

In today’s modern society innovating in every organization be- comes a key of its competitive advantage and survival in the highly competitive market. This rule, sooner or later will have to be accepted by our primary sector health care organizations. All institutions must strive that by constant innovating, using in the best manner possible the limited and available resources, to, in the long term, ensure continuing business and better future. The scope of innovating activities must be all segments of the health care organizations. All employees must be involved in innovating process, and not only the research and development departments (R&D). The health care institutions, which constantly innovate, enjoy the permanent advantage in the competition with their competitors. They are able to produce products and services that are cheaper and of better quality. The innovation type, which the particular health care institution chooses, represents, in its essence, the nature of the innovation. It also includes the influence of change on the value chain participants, competence and firms’ inclination in tedious fields of innovation and innovative management. The modern markets require from the health care organizations to be more dynamic, and the environmental changes demand comprehensive innovative orientations. The people who kick start innovations in health care field are in principle leaders. The leadership variables become very important having in mind that almost all organizations, to a certain extent are built based on the hierarchical structure. As the result of this fact, the decision making centers tend to be concentrated in the hands of the leading individuals. The science has found the relationship between leaders’ motivations and the frequencies of the innovations. The health care in Federation of Bosnia and Herzegovina (F.B&H), and its entry and Primary care sector are faced with the serious challenges. Thus, innovating in this sensitive service field becomes the imperative for society. Innovating and at the same time, managing these processes is necessary for more reasons. Financial resources allocated for health care in B&H are limited, and are expect- ed to remain so in the future. The second part of the challenges the health care sector is facing is represented in the aging of the population. The people live longer, and as the consequence, for the health maintenance of population over 65, more and more re- sources are spent. By innovating, best practice checking and waste reducing the immense savings can be achieved in the health care. These actions, as well as the quality applications of best practices will enable that health care outlays, (which exceed ten percent of gross domestic product (GDP) for B&H for 2011), shall, either remain stable or decline.

Mirsad Panjeta, I. Tahirović, J. Karamehić, E. Sofić, O. Ridic, J. Ćorić

Introduction: Hypoxia is a basic stimulant in production of erythropoietin (EPO). The primary function of erythrocytes is the transport of oxygen to tissues. Erythropoietin stimulates erythropoiesis which leads to increased production of erythrocytes- their total mass. This increases the capacity of the blood to carry oxygen, reduces the hypoxic stimulus and provides a negative feedback of stopping EPO production. The aim of this study was to establish a quantitative relationship between the concentration of erythropoietin, hemoglobin and hematocrit in different values of renal insufficiency. Material and methods: The survey was conducted on 562 subjects divided into two groups: with and without renal insufficiency. EPO, hemoglobin, hematocrit, serum creatinine and additional parameters iron, vitamin B12, and folic acid were determined by using immunochemical and spectrophotometric methods and glomerular filtration rate (GFR) was calculated as well. Results: EPO values (median) grow to the first degree of renal insufficiency, as compared to EPO values of healthy subjects, this increase is statistically significant, p=0.002. With further deterioration of renal function the values of EPO between all pathological groups are decreasing, and this decrease is statistically significant between first and second degree of renal insufficiency (RI) p<0.001. In the group of healthy subjects EPO is correlated rho = -0.532, p <0.0005 with hematocrit. The correlations are negative and strong and can be predicted by regression line (EP0 = 41.375- Hct * .649; EPO = 61.41–Hb * 0.355). In the group of subjects with the first degree of renal insufficiency EPO is in correlation with hematocrit rho=-0.574, p<0, 0005. It is also correlated with hemoglobin rho=-0.580, p< 0.0005. The correlation is negative (EP0= 42.168- Hct * 0.678). In the group of subjects with the third degree of renal insufficiency EPO is in correlation with hemoglobin rho=0.257, p=0.028. The correlation is medium strong and positive. In the group of subjects with third and fourth degree of renal insufficiency EPO is not in correlation with hemoglobin and hematocrit p>0.05. Conclusion: Renal dysfunction, depending on the level of RI effects differently on the biosynthesis of EPO in a diseased kidney, and consequently it also has a different effect on biosynthesis of HB in bone marrow and its content in the blood.

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