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Asija Začiragić, A. Dervišević, N. Avdagić, N. Babic, A. Valjevac, O. Lepara, J. Huskic

Abstract Objective. The present study assessed the impact of type 2 diabetes mellitus (T2DM) duration on the serum asymmetric dimethylarginine (ADMA) and C-reactive protein (CRP) concentration in Bosnian patients. Methods. Participants for this cross-sectional study were randomly selected from the Family Medicine Clinic (Sarajevo, Bosnia and Herzegovina). Serum ADMA concentration was determined by ELISA. Serum high-sensitivity (hs-CRP) was determined by particle-enhanced immunonephelometry. ANOVA test followed by Scheffe post-hoc test or Kruskal-Wallis test followed by Man-Whitney test were used for statistical analysis. Results. The study included 38 patients in up to 10 years diabetes duration (≤10 years T2DM) group, 22 patients in greater than 10 years diabetes duration (>10 years T2DM) group, and 60 controls. Serum ADMA concentration in the >10 years T2DM group (1.81±0.15 μmol/L) was significantly higher compared to serum ADMA concentration in the ≤10 years T2DM group (1.38±0.41 μmol/L; p<0.001) and in controls (0.62±0.15 μmol/L; p<0.001). A significant difference in serum ADMA concentration was found between the <10 years T2DM group and the controls (p<0.001). The serum CRP concentration in the >10 years T2DM group [5.95 (4.20–9.12) mg/L] was significantly higher compared to serum CRP concentration in the <10 years T2DM group [2.35 (1.40–4.30) mg/L; p<0.001] and controls [0.85 (0.50–1.30) mg/L; p<0.001]. Significant difference in serum CRP concentration was observed between the <10 years T2DM group and controls (p<0.001). Conclusions. The present study showed an increase in the serum ADMA and CRP concentrations with the advancement of T2DM. These results suggest that ADMA and CRP may serve as indicators of endothelial dysfunction and chronic low-grade inflammation progression in patients with T2DM. Larger prospective studies are required to confirm the observed findings.

Asija Začiragić, Mehmed Elezovic, N. Avdagić, N. Babic, A. Dervišević, O. Lepara, J. Huskic

Objective The association between the neck circumference (NC) and components of metabolic syndrome in different countries and ethnic groups has been insufficiently investigated. The aim of the present study was to assess the impact of gender on NC values and to determine whether NC correlates with standard anthropometric measures and blood pressure values in Bosnian young adults. Materials and Methods Study participants were recruited by the snowball method. The NC, body mass index (BMI), waist circumference (WC), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were measured by trained personnel. Differences between the means were assessed by a Student's t-test. Coefficients of correlation were determined by Pearson's test. Results In young men (n=49), the value of NC was 37.71±1.79 cm, while in young women, (n=62) the value of NC was 32.23±1.83 cm (p<0.001). A significant positive correlation in both genders between the NC and BMI (r=0.70, p<0.001 in men; r=0.53,p<0.001 in women), and between the NC and WC (r=0.48, p<0.001 in men; r=0.38, p=0.01 in women), was found. A significant correlation between the NC and SBP (r=0.08, p=0.57), and DBP (r=0.20, p=0.17), in young men was not determined. Likewise, in young women, a significant correlation between the NC and SBP (r=0.08, p=0.54), and DBP (r=0.09, p=0.49), was not observed. Conclusion Our results suggest that the NC measurement can be used as a valid method in obesity assessment in young adults. A lack of association between the NC and blood pressure requires additional investigation.

I. Aganović-Mušinović, N. Avdagić, N. Babic, A. Začiragić, O. Lepara, J. Huskic, Maida Todić-Rakanović

Background: Multiple myeloma (MM) is a disease of B cell population with excessive secretion of immunoglobulins and presence of free light chains (FLCs) that are by products of immunoglobulin synthesis. Free light chains play crucial role in causing renal damage. Interleukine-6 (IL-6) supports the survival and/or expansion of MM cells by stimulating cells as well as by preventing programmed cell death. Aims and Objectives: The aim of this study was to evaluate serum and urine free light chains (FLC)measurement and compare with IL-6 levels in patients with different stages of Multiple Myeloma (MM) and control group of subjects and to determine their relevance in acute kidney injury occurrence. Materials and Methods: Recruitment of patients with MM (n=62) made the hematologist that followed clinical Solomon-Durie MM classification. Control group consisted of 20 healthy individuals. Results: Patients with MM and renal function injury had significantly higher concentration of urine κ chains compared to control group and group of MM without renal function injury (p<0.005), whereas this difference was not observed when the patients were divided into disease stages groups. Concentration of IL-6 was significantly higher in patients at MM steady stage compared to control group (p<0.001) and significant difference was also detected in patients with MM at relapse stage and control group (p<0.0005). Concentration of IL-6 in MM patients without renal function and with renal function injury was significantly higher compared to control group (p< 0.001; p<0.0005 respectively). Statistically significant correlation was determined between sera κ and urine κ chains (rho=0.437; p<0.01) as well as between urine λ and sera λ chains (rho=0.505; p<0.01) and between urine κ and urine λ chains (rho=0.364; p<0.01). Conclusion: Results showed that urine κ chains, sera κ chains and IL-6 are constructing a fine tuned net and point to conclusion that FLC and IL-6 are important for an early treatment response detection for patients with potentially reversible renal failure.

M. Vučijak-Grgurević, F. Zvizdić, A. Durak-Nalbantić, Elmedina Jahić, N. Resić, J. Huskic

Introduction: An increase in nitric oxide (NO) synthesis concentration could help alleviate some pathological changes directly related to uremia. Aim: To investigate the concentration of nitric oxide in saliva of patients with terminal stage of chronic renal failure on hemodialysis and to investigate the effect of hemodialysis on concentration of nitric oxide in saliva of the patients with terminal stage of chronic renal failure on hemodialysis. Material and Methods: The study had a prospective character and included 60 respondents of both sexes, at age between 20 and 60 years. The control group included 30 healthy volunteers of both sexes (15 men and 15 women) of the same age, who were based on subjective and objective health status without any manifestations of pathophysiological changes. The group of patients with terminal stage of chronic renal failure on hemodialysis involved 30 patients of both sexes (15 men and 15 women). Inclusion criteria: hemodialysis duration more than 6 months and age between 20 and 60 years. Results: The amount of non-stimulated saliva collected during 15 minutes in patients with chronic renal failure was lower by 31.3% compared to the control group of healthy subjects (p<0.0001). Concentration of NO in saliva in patients with chronic renal failure was higher by 121% than in the control group (p<0.001). Concentration of NO in saliva in patients with chronic renal failure after hemodialysis was 121% lower than in the same subjects prior to hemodialysis (p<0.001). A statistically significant negative correlation (r=-0.381, p<0.05) was found between the hemodialysis duration in months and the level of NO in saliva of the patients with chronic renal failure prior to hemodialysis. There was no statistically significant correlation (r=-0.167, NS) between the hemodialysis duration in months and NO levels in saliva of the patients with chronic renal failure after hemodialysis treatment. Conclusion: Concentration of NO in saliva of the patients on hemodialysis was statistically significantly higher in relation to NO concentration in the saliva of healthy subjects and after hemodialysis was statistically significantly lower in relation to NO values prior to hemodialysis. Monitoring of changes in NO concentration dynamics in saliva of hemodialysis patients will probably be helpful in monitoring hemodialysis efficacy.

Asija Začiragić, A. Valjevac, Almira Hadžović-Džuvo, N. Avdagić, N. Babic, O. Lepara, A. Dervišević, J. Huskic

AN IMPACT OF DIABETES DURATION ON SERUM ASYMMETRIC DIMETHYLARGININE CONCENTRATION

Asija Začiragić, Mehmed Elezovic, N. Babic, N. Avdagić, A. Dervišević, J. Huskic

Background: Neck circumference (NC) is an index of subcutaneous adipose tissue distribution in an area of the upper part of the body. The aim of this study was to assess whether NC can be used as an indicator of central obesity and to determine the prevalence of central obesity in apparently healthy Bosnian young adults. Methods: Participants for this cross-sectional study were recruited using the snowball method. NC was measured in horizontal straight position by placing the top edge of a plastic tape only below the laryngeal prominence and perpendicular to the longitudinal axis of the neck, with the head positioned in the Frankfort horizontal plane. Body mass index, waist circumference (WC), and waist-to-hip ratio were taken following the WHO guidelines. Results: The study included 111 second year University of Sarajevo Dentistry students (49 students of male gender and 62 students of the female gender). Determined the optimal cutoff value of NC in the detection of central obesity based on WC values in healthy young participants of male gender was ≥37.45 cm (P < 0.001), while in healthy young participants of the female gender, it was ≥32.75 cm (P < 0.001). Based on the WHO guidelines for WC, central obesity was determined in 24.49% (n = 12) of male patients, and in 29.03% (n = 18) of female participants included in our investigation (P < 0.05). Conclusions: The results of the present study indicate that NC may be used as a screening tool for central obesity in healthy young adults. Prevalence of central obesity observed among student population suggests that there is a justified need for an implementation of healthy lifestyle programs in this population that would have preventive purposes.

Asija Začiragić, Mehmed Elezovic, N. Avdagić, N. Babic, A. Dervišević, O. Lepara, J. Huskic

Objective: Association between neck circumference (NC) and components of metabolic syndrome in different countries and ethnic groups is still insufficiently investigated. The aim of the present study was to assess an impact of gender on NC values and to determine whether NC correlates with standard anthropometric measures and blood pressure values in Bosnian young adults. Material and Methods: Study participants were recruited by the snowball method. NC, Body Mass Index (BMI), Waist circumference (WC), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were measured by trained personnel. Differences between the means were assessed by a Student t-test. Coefficients of correlation were determined by Pearson’s test. This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as: Zaciragic A, Elezovic M, Avdagic N, et al. Relationship between neck circumference, standard anthropometric measures and blood pressure values in Bosnian young adults. Eurasian J Med 2018; DOI: 10.5152/eurasianjmed.2018.18197. ©Copyright 2018 by Atatürk University School of Medicine Available online at www.eajm.org Results: In young men (n =49) value of NC was 37.71±1.79 cm, while in young women (n=62) value of NC was 32.23±1.83 cm (P<0.001). Significant positive correlation in both gender between NC and BMI (r= 0.70; P<0.001 in men and r= 0.53; P<0.001 in women), and between NC and WC (r= 0.48; P<0.001 in men and r= 0.38; P=0.01 in women) was found. Significant correlation of NC with SBP (r=0.08; P=0.57), and with DBP (r=0.20; P=0.17) in young men was not determined. Likewise, in young women significant correlation of NC with SBP (r=0.08; P=0.54), and with DBP (r=0.09; P=0.49) was not observed. Conclusions: Results of the present study suggest possible use of NC measurement as a valid method of obesity assessment in young adults. Lack of an association between NC and blood pressure values requires additional investigation.

Almir Fajkić, M. Musić, A. Kulenović, Asija Začiragić, N. Avdagić, N. Babic, O. Lepara, E. Pepić et al.

BACKGROUND The aim of the present study was to evaluate serum nitric oxide (NO) and C reactive protein (CRP) concentration in veterans with and without PTSD. Furthermore, we aimed to assess whether there is a correlation between serum NO and CRP concentrations in tested groups. SUBJECTS AND METHODS Cross-sectional study included 90 male individuals, with and without experience of direct war combat, divided into three equal groups (n=30): group 1- included war veterans with PTSD, group 2 - included war veterans without PTSD, and control group - 30 apparently healthy volunteers, without experience of direct war combat. The diagnosis of PTSD was assessed according to the guidelines in the 10th revision of the International Classification of Diseases (ICD-10). High-sensitivity CRP was determined by immunonephelometry. The serum NO level was determined by classic colorimetrical Griess reaction. RESULTS Serum CRP concentration in veterans with (3.54±1.19 mg/L) and without PTSD (3.24±2.04 mg/L), was significantly higher (p<0.05) compared to control group (1.26±1.06 mg/L). Serum NO concentration in veterans with (7.64±4.43 μmol/L) and without PTSD (7.12±2.60 μmol/L) was significantly lower (p<0.05) compared to control group (11.26±7.01 μmol/L). Statistically significant correlation between serum NO and CRP concentration was determined in veterans without PTSD (r=-0.473; p<0.01). No correlation was observed between serum NO and CRP concentration in veterans with PTSD (r=0.118; p=0.534) and in control group (r=-0.067; p=0.727). CONCLUSION The present study has showed significant increase of serum CRP and significant decrease of serum NO concentrations in veterans with and without PTSD. Furthermore, statistically significant negative correlation between serum NO and CRP concentration was determined only in veterans without PTSD. Obtained results indicate that the complex mechanism of the pathogenesis of PTSD requires further research.

A. Husic-Selimovic, A. Sofić, J. Huskic, D. Bulja

Introduction: Renin-angiotenzin system (RAS) is frequently activated in patients with chronic liver disease. Angiotenzin - II (AT-II), produced by angiotenzin converting enzyme (ACE), has many physiological effects, including an important role in liver fibrogenesis. Combined antiviral therapy with PEG-IFN and ribavirin besides its antiviral effect also leads to a reduction in liver parenchyma fibrosis. Aim of the study: Determining the value of ACE in serum of patients with chronic hepatitis C before and after combined antiviral therapy, as well as the value of ACE activities in sera of the control group. Materials and methods: We studied 50 patients treated at Gastroenterohepatology Department, in the time-period of four years. Value of ACE in serum was determined by Olympus AU 400 device, with application of kit “Infinity TN ACE Liquid Stable Reagent”. HCV RNA levels in sera were measured by real time PCR. HCV RNA test was performed with modular analysis of AMPLICOR and COBAS AMPLICOR HCV MONITOR test v2.0, which has proved infection and was used for quantification of the viruses and monitoring of the patients’ response to therapy. Liver histology was evaluated in accordance with the level of necroinflammation activity and stage of fibrosis. Results: Serum activities of ACE in chronic hepatitis C patients is statistically higher than the values in the control group (p=0.02). Antiviral therapy in chronic hepatitis C patients statistically decreases serum activities of ACE (p= 0.02) and indirectly affects fibrogenesis of the liver parenchyma. Correlation between ACE and ALT activity after the therapy was proved (0.3934). Conclusion: Our findings suggest that the activity of ACE in serum is a good indirect parameter of the liver damage, and could be used as an indirect prognostic factor of the level of liver parenchyma damage. Serum activity of ACE can be used as a parameter for non-invasive assessment of intensity of liver damage.

A. Začiragić, J. Huskic, N. Mulabegović, N. Avdagić, A. Valjevac, S. Hasić, R. Jadric

Studies that investigated an association between asymmetric dimethylarginine (ADMA) and glycated haemoglobin (HbA1c) in type 2 diabetes mellitus (T2DM) have given discordant results. The aim of this study was to determine and compare serum ADMA concentration in patients with T2DM and healthy controls, and to assess correlation between ADMA and HbA1c in patients with T2DM. Serum ADMA concentration was determined by ELISA method with the use of ADMA ® - ELISA kit (DLD Diagnostics, Hamburg, Germany) and HbA1c levels were determined by an immunoturbidimetric method in 60 patients with T2DM and 60 healthy individuals matched for age and sex. Results have shown that mean serum ADMA concentration was significantly higher in T2DM patients (1.54±0.06 μmol/L) compared to mean serum ADMA concentration (0.62±0.02 μmol/L; p<0.0001) in healthy subjects. A significant, positive, correlation between serum ADMA concentration and HbA1c levels was observed (r=0.494; p<0.01) in T2DM patients. Our results suggest that there is an association between endothelial dysfunction and glycaemic control in type 2 diabetes mellitus. Possible explanation for obtained results may be oxidative stress that is increased in conditions of hyperglycaemia and it also promotes endothelial dysfunction. Larger, longitudinal studies are required that will evaluate relation between metabolic abnormalities and increased ADMA levels in patients with type 2 diabetes mellitus.

A. Dervišević, N. Babic, J. Huskic, Š. Sokolović, E. Nakas-ićindić, Lejla Causevic

Background: Nitric Oxide (NO) participation is recognized in numerous physiological and pathological processes. Rheumatoid arthritis (RA) is an inflammatory autoimmune disease involving joints and other systems including salivary glands. The role of NO in pathogenesis of development of RA is still unknown. Aim & Objectives: We investigated NO concentration in saliva of 63 patients with RA and in 31 healthy control individuals. The aim of the study was also to investigate the correlation between saliva NO concentration and disease activity score (DAS28) in RA patients and to determine whether the statistically significant difference in saliva NO concentrations exists between RA patients with different stages of disease activity. Methods: Patients with RA in this cross;sectional study have been divided, based on the stage of disease activity evaluated by DAS28score, into three subgroups: low disease activity (n=19), moderate disease activity (n=19) and high disease activity (n=25). NO concentration was determined by measuring nitrite concentration by Griess reaction. Conversion of nitrate (NO ;3 ) to nitrite (NO ;2 ) was done with elementary zinc. Absorbance was measured at 546 nm with the use of spectrophotometer.

INTRODUCTION Infection with hepatitis C is often manifested by a mild clinical course, and in many patients it is revealed incidentally, during routine laboratory ests. Progression of the disease often takes 10-20 years with specified high risk of fibrosis and hepatocellular carcinoma. MATERIAL AND METHODS The group of subjects with chronic liver disease of viral C etiology was consisted of 50 patients of both sexes, 38 (75%) were male and 13 (25%) females, aged 20-65 years. Patients were selected according to genotype hepatitis C viral infection and subsequently treated according to two current therapeutic protocols. All patients had prior therapy and after completion of treatment using standard methods of laboratory tests were done the following: functional hepatic tests, serological analysis, nucleic acid detection of hepatitis C virus polymerase chain reaction (PCR), quantitatively and qualitatively with the genotyping of the virus C, which determines the length of therapy. In determining the stage of chronic liver disease, histopathological examination of liver tissue samples obtained by biopsy of the liver was done and we analyzed the fibrosis and architectural changes. RESULTS By analyzing the HCV RNA PCR values at the beginning and end of treatment we tested the effect of treatment on PCR with paired samples t-test logarithm values of the PCR and came to the conclusion that the values after treatment are significantly lower with threshold of significance of 0.01. The results showed that the value of PCR before and after therapy, or achieved a response at the end of therapy, which achieved 77% of patients. The values of ALT in the group of patients with CHC were significantly higher than the values in the group of patients after the therapy. AST values in the patients with CHC were significantly higher than the values in the group of patients after therapy. There was a moderate correlation between ALT values at baseline and ALT values upon completion of treatment (0.5061). There was no correlation between HCV RNA PCR and ALT and AST. CONCLUSION Upon completion of antiviral treatment response at the end of treatment achieved 77% of patients, regardless of the genotype of the virus. Also, regardless of the genotype of the virus antiviral therapy led to statistically significant reduction of AST and ALT, indicating a direct effect of combination therapy on virological and biochemical response with no significant link between these two studied parameters.

Enes Pašić, A. Dedic, J. Huskic, S. Hadžić

Objective. Th e aim of this paper is to determine the concentration ofnitric oxide (NO) in the saliva of subjects resulting from the presenceof various metal restorative activities in the oral cavity. Patients andmethods. Th e research was conducted on 20 subjects (12 women and8 men), aged 18-30, with no metal fi llings in their oral cavity and 20subjects (11 women and 9 men) aged 18-30 with prosthetic and conservativework in their oral cavities made of various metals. Th e pHof the saliva was established by means of an “Orion” type pH meter atan optimal temperature of 250C. Th e concentration of NO was determinedby conversion of NO3-2 into NO2-2 with the help of elementaryzinc and then by colorimetric testing of the NO2-2 concentration bymeans of the Griess reagent. Results. Our results established that theconcentration of NO in patients with various metals (60.18±10.24) is33.7% higher, which is statistically insignifi cant, in relation to the controlgroup (45.01±6.28). Conclusion. Various metal restorative activitiesstemming from dentistry practice do not cause changes in the pHvalues of saliva and NO concentrations.

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