-Inflammatory bowel diseases are multifactorial disorders the clinical manifestation of which depends on the interaction among immune response, genetic and environmental factors. There is growing evidence that cytokines and gene polymorphisms have an important role in disease pathogenesis in various populations although molecular mechanism of their signaling and interactions is not fully understood yet. The present study aimed at exploring the effects of interleukin-6, C-reactive protein and interleukin-6 rs1800795 polymorphism on the development of Crohn's disease, ulcerative colitis and inflammatory bowel diseases overall and at determining differences between inflammatory bowel disease patients and healthy controls. A total of 132 inflammatory bowel disease patients and 71 healthy blood donors were investigated. In order to assess the clinical relevance of interleukin-6 and C-reactive protein serum concentration and interleukin-6 rs1800795 single nucleotide polymorphism in patients with Crohn's disease and ulcerative colitis, we performed a cross-sectional, case-control study. Quantitative assessment of serum interleukin-6 and C-reactive protein was performed with solid-phase, enzyme-labeled, chemiluminescent sequential immunometric and immunoturbidimetric assay, respectively. A real-time fluorescence resonance energy transfer-based method on a LightCyclerTM PCR 1.2 was used for genotyping of IL-6 rs1800795 polymorphism. Both interleukin-6 and C-reactive protein serum levels were elevated in Crohn's disease and ulcerative colitis patients. Positive correlations were observed between C-reactive protein and interleukin-6 serum concentration and ulcerative colitis activity index as measured by modified Truelove-Witt's severity index scale. C-reactive protein serum level was higher in Crohn's disease patients without intestinal resection than in Crohn's disease patients with prior intestinal resection. In ulcerative colitis patients, interleukin-6 and C-reactive protein serum levels were statistically significantly higher in CC interleukin-6 genotype in comparison to GG+GC genotype.

SUMMARY – Interleukin (IL)-10 is an anti-inflammatory cytokine, and a decrease in its secretion is associated with obesity, metabolic syndrome and type 2 diabetes. However, it has not been established whether the intensity of the immune response during diabetes-associated chronic inflammation affects the development and/or progression of type 2 diabetes and its microvascular complications. The aim of this study was to investigate the role of single nucleotide polymorphism (SNP)-1082G/A for IL-10 gene in development of diabetes type 2 and its complications. DNA was extracted from blood cells of 240 overweight/obese subjects for IL-10 genotyping. Based on the presence of diabetes type 2, patients were divided in two groups: experimental group of 144 patients with diabetes type 2 and control group of 96 age- and gender-matched subjects without diabetes. Compared to control group, diabetic group had higher levels of leukocytes (p=0.012), fibrinogen (p=0.049) and plasminogen activator inhibitor-1 (PAI-1) (p=0.009), and lower levels of albumin (p=0.001). There were no differences in the frequency of SNP-1082G/A for IL-10 gene between the two groups (p=0.654). When considering diabetes related traits in all subjects in relation to specific genotype, a group with homozygous (AA) genotype had higher values of the mean fasting glucose (p<0.000001), HbA1c (p<0.000001) and HOMA-IR (p=0.003632), while the mean HOMA-B value (p=0.000178) was lower when compared to the groups with GG and GA genotypes. There was no difference in development of diabetic nephropathy, retinopathy and polyneuropathy between the IL-10 polymorphism genotypes. In conclusion, obese diabetes type 2 patients had an increased inflammation activity compared to obese non-diabetic individuals. There was no association of the investigated polymorphisms and development of type 2 diabetes and its microvascular complications. However, diabetes related traits clearly depended on the presence of specific IL-10 genotype.

The present study investigates the etiological roles of premilitary risk factors, military entry conditions, war zone experiences, dissociative reactions to war zone experiences and homecoming reception in the development of chronic posttraumatic stress disorder (PTSD) among Croatian veterans. A total of 150 Croatian war veterans with the diagnosis of chronic combat-related PTSD, who sought treatment at Psychiatric Clinic, Osijek, Croatia, in the period 1993-1998, and who provided complete data, were selected as the sample for the present study from the treatment-seeking group of the ex-soldier population. Structural equation modeling is used to develop an etiological model concerning the relationships of premilitary risk factors, military entry conditions, war zone experiences, dissociative reactions, and homecoming reception with current symptoms of PTSD. An etiological model with satisfactory fit and parsimony was developed. In terms of the magnitude of variables' total contributions to the development of PTSD, war zone experiences are the most influential contributor which is followed by dissociative reactions, homecoming reception, military entry conditions and premilitary risk factors. Statistical significant direct effects to the development of PTSD were found for dissociative reactions and low family postwar support. The etiology of combat-related PTSD among Croatian veterans remains largely unexplained. Partial explanations are omission of other etiological factors, retrospective nature of the data and small study sample. The results are the source of questions for further research.

The placement of the diagnostic category of post-traumatic stress disorder (PTSD) among anxiety disorders reflects the recognition that anxiety is a predominant reaction to trauma. Indeed, the symptoms of PTSD overlap considerably with those of other anxiety disorders. The nosological criteria render PTSD as quite a heterogeneous diagnosis. Two individuals with no common symptoms can be diagnosed as having PTSD. In this report we provide information on the phenomenology and psychiatric comorbidity in a sample of 33 patients with combat-related PTSD. The finding of clinical heterogeneity in subjects with combat-related PTSD and the therapy implications are discussed.

Interleukin-23 receptor (IL-23R) and signal transducer and activator of transcription 3 (STAT3) polymorphisms are common risk factors for a number of T helper (Th) 17-mediated autoimmune diseases. However, the importance of genetic variations in Th17 pathways to thyroid autoimmunity, and particularly Hashimoto's thyroiditis (HT), is not fully understood. In this study, we genotyped three single nucleotide polymorphisms (SNPs) within the IL-23R (rs11209026/p.Arg381Gln, rs7530511) and STAT3 (rs744166) genes in 217 Croatian patients with HT and 161 healthy controls using fluorescence resonance energy transfer technology and melting curve analysis of polymerase chain reaction products. None of the tested SNPs or IL-23R haplotypes was associated with HT susceptibility or disease severity. These results suggest that the studied IL-23R/STAT3 polymorphisms affecting Th17 signaling efficiency are not major determinants of HT risk in the Croatian population. Further work is necessary to determine if these loci contribute modestly or conditionally to the risk of HT.