From Pulsing Headache to Pheochromocytoma: The First Application of 123I-MIBG in the Scintigraphy in Croatia – A Case Report

This case report presents a patient with pheocromocytoma and the first use of 123I-MIBG scintigraphy in the diagnostic workup of an adrenal gland tumor with elevated metanephrine and normetanephrine levels in Croatia. The patient had intensive pulsing headaches for a year. A tumour of the right suprarenal gland has been observed by ultrasound, by CT scan, and by MRI of the abdomen. A comprehensive endocrinological observation revealed significantly increased values of metanephrine, normetanephrine, epinephrine and noreinephrine. 123I-MIBG scintigraphy excluded multiple tumours and metastases of malignant pheochromocytoma. After surgery, diagnosis of pheochromocytoma was proven histologically. Three weeks after surgery, the values of metanephrine and normetanephrine were within the normal range

Tumor markers for prostate cancer

Karcinom prostate je u većini zemalja zapadne hemisfere najčešći oblik karcinoma u muškaraca i drugi vodeći uzrok smrti od karcinoma. U otkrivanju i praćenju karcinoma prostate važno mjesto ima određivanje koncentracije tumorskoga markera prostata specifičnoga antigena (PSA) u serumu. Glavni je nedostatak PSA niža specifičnost jer njegova koncentracija u serumu raste i kod benigne hiperplazije prostate i prostatitisa. Kako bi se smanjio broj nepotrebnih biopsija, nastoji se poboljšati specifičnost PSA uvođenjem različitih varijanti njegovoga određivanja u serumu i kombinacijom određivanja s drugim specifičnim humanim kalikreinima prostate. U dijagnostici karcinoma prostate istražuju se novi molekularni markeri, čimbenici rasta i inhibicije rasta karcinoma prostate. Dok se ne dokažu, većina njih u svakodnevnoj praksi ostaje nedostupna. 1 nadalje se koristi etablirani PSA s kontroverzama oko određivanja granice njegove pouzdanosti.Prostate cancer is the leading malignancy and the second leading cause of cancer death in men in the majority of countries of the Western Hemisphere. Extremely useful marker for early detection of prostate cancer and in monitoring patients for disease is serum prostate-specific antigen (PSA). The main limitation of serum PSA detection is a low specificity since enhanced PSA serum concentration could be found in patients with benign prostate hyperplasia and prostatitis. In order to reduce the number of unnecessary biopsies there is a strong tendency to improve the PSA specificity by introducing various methods of serum PSA determination as well as implementation of other specific human glandular prostate kallikreins measurements in combination with PSA. The introduction of new tumor markers, growth factors and inhibitors of the prostate cancer is the novel approach in the diagnostics of prostate cancer. Until those biomarkers become validated, the majority of them stay unavailable in daily clinical practice. Furthermore, the established PSA is still widely used, with its controversial questions regarding the limits of its reliability

Importance of Interleukin 6 in Pathogenesis of Inflammatory Bowel Disease

Inflammatory bowel disease (IBD), encompassing ulcerative colitis (UC) and Crohn’s disease (CD), is an uncontrolled chronic inflammation of the gastrointestinal tract caused by an interaction of diverse genes and environmental factors. There is growing evidence that cytokine production plays an important role in IBD. One of the key roles in signaling pathway in development of IBD is performed by interleukin 6 (IL-6), although molecular mechanism of this pathway is not yet fully understood. In order to assess the clinical relevance of IL-6 serum concentration in patients with CD and UC we performed cross-sectional, case-control study of IL-6 levels in patients’ and healthy blood donors’ sera. A total of 100 CD and UC patients and 71 healthy blood donors were investigated. Clinical activity of CD and UC was evaluated using the Crohn\u27s disease activity index and Truelove-Witt\u27s criteria, respectively. Quantitative assessment of serum IL-6 was performed with solid-phase, enzyme-labeled, chemiluminescent sequential immunometric assay. Our results indicate that serum IL-6 is a clinically relevant parameter for CD and UC that strongly correlates with inflammatory activity of disease. We confirmed and extended the role of cytokine production patterns for IBD presentation in Croatian population

Polymorphisms of Interleukin-23 Receptor in Patients with Inflammatory Bowel Disease in a Croatian Tertiary Center

The Interleukin-23 signalling pathway is important for the differentiation of TH17 lymphocytes and is involved in the pathogenesis of Inflammatory bowel disease. Polymorphisms in the IL-23 receptor gene were previously found to be associated with Inflammatory bowel disease in various populations. The aim of this study was to determine whether the specific rs11209026 and rs7530511 single-nucleotide polymorphisms in the Interleukin-23 receptor gene are associated with Crohn’s disease and ulcerative colitis in a Croatian patient population. A total of 50 patients with Crohn’s disease and 93 patients with ulcerative colitis, as well as 99 healthy control subjects were included in the study. The results deter- mined a significantly higher occurrence of rs11209026 in control group compared to patients with inflammatory bowel disease, suggesting a protective effect of this polymorphism. The rs11209026 variant was strongly associated with Crohn’s disease, but it was absent in ulcerative colitis. However, there was no significant association between the rs7530511 poly- morphism with either ulcerative colitis or Crohn’s disease. Associations presented in this study give potentially impor- tant insight into the roles of specific Interleukin-23 receptor polymorphisms in Crohn’s disease pathogenesis in the Cro- atian population

Interakcija između interleukina-6, C-reaktivnog proteina i interleukina-6 (-174) G/C polimorfizma u patogenezi Crohnove bolesti i ulceroznog kolitisa

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. Analysis of the promoter region of the interleukin-6 rs1800795 gene polymorphism showed no statistically significant difference in allele frequency either between inflammatory bowel disease patients and healthy controls or between the two inflammatory bowel disease phenotypes and healthy controls. Associations presented in this study give a potentially important insight into the role of interleukin-6 and C-reactive protein signaling and interleukin-6 polymorphism in the pathogenesis of Crohn’s disease and ulcerative colitis disease.Upalne bolesti crijeva predstavljaju multifaktorski poremećaj klinička manifestacija kojega ovisi o interakciji imunog odgovora te genetskih i okolišnih čimbenika. Rezultati više novijih istraživanja upućuju na ulogu citokina i polimorfizama gena u patogenezi bolesti u različitim populacijama, iako molekularni mehanizmi njihova singaliziranja i interakcije još nisu dovoljno poznati. Cilj ovoga istraživanja bio je ispitati učinke interleukina-6, C-reaktivnog proteina i interleukin-6 rs1800795 na razvoj Crohnove bolesti, ulceroznoga kolitisa i upalnih bolesti crijeva općenito te utvrditi razlike između skupine ispitanika oboljelih od upalnih bolesti crijeva i kontrolne skupine ispitanika. U istraživanje je uključeno ukupno 132 oboljela od upalnih bolesti crijeva i 71 zdravi davatelj krvi. Serumska koncentracija interleukina-6 određena je kemiluminiscentnom sekvencijskom imunometričnom, a koncentracija C-reaktivnog proteina imunoturbidimetrijskom metodom. Analiza polimorfizma rs1800795 provodila se na uređaju LightCyclerTM PCR 1.2 u stvarnome vremenu temeljem prijenosa energije uslijed fluorescentne rezonancije. Serumske koncentracije interleukina-6 i C-reaktivnoga proteina bile su povišene i u oboljelih od Crohnove bolesti i oboljelih od ulceroznoga kolitisa. Utvrđene su pozitivne korelacije između serumskih koncentracija C-reaktivnoga proteina i interleukina-6 i indeksa aktivnosti ulceroznoga kolitisa mjerenoga prema ljestvici MTWSI. Serumska koncentracija C-reaktivnog proteina bila je viša u oboljelih od Crohnove bolesti bez prethodne resekcije crijeva u usporedbi s oboljelima od Crohnove bolesti s prethodnom resekcijom crijeva. U oboljelih od ulceroznoga kolitisa serumske koncentracije interleukina-6 i C-reaktivnog proteina bile su statistički značajno više kod CC genotipa interleukina-6 u usporedbi s genotipom GG+GC. Analizom polimorfizma promotorske regije IL-6 rs1800795 nisu uočene razlike u učestalosti alela između oboljelih od Crohnove bolelsti, oboljelih od ulceroznoga kolitisa i kontrolne skupine ispitanika, ni razlike između kontrolne skupine ispitanika i oboljelih od upalnih bolesti crijeva općenito. Rezultati ove studije pružaju potencijalno važan uvid u ulogu signaliziranja interleukina-6 i C-reaktivnoga proteina te polimorfizma interleukina-6 u patogenezi Crohnove bolesti i ulceroznoga kolitisa

Polymorphisms of Vitamin D Receptor Gene in the Population of Eastern Croatia with Psoriasis vulgaris and Diabetes mellitus

The aim of this study was to evaluate the possible association between polymorphisms in the Vitamin D receptor gene (VDR gene) and tendency for development of psoriasis vulgaris and diabetes mellitus in the population of Slavonia, which is a region in the Eastern Croatia. In order to conduct the mentioned evaluation the restriction fragment length polymorphisms (ApaI, BsmI and TaqI) in the Vitamin D receptor gene were researched in three groups of patients: patients suffering only from psoriasis vulgaris, patients suffering only from diabetes mellitus, and patients suffering at the same time from both diseases. Four most common genotypes were found in all standardized control patients: triple heterozygotes BbAaTt (in 29.3% of the studied patients), bbAaTT (in 18.6% of the studied patients), bbaaTT (in 12.9% of the studied patients) and BbAATt (in 8.6% of the studied patients). Three most common VDR 3’-RFLP haplotypes determined in this study were: three-component baT, Bat and bAT haplotype. Results of the Hardy-Weinberg equilibrium showed presence of BsmI polymorphism genotype frequencies disequilibrium in the group of patients suffering from psoriasis and ApaI polymorphism in the group of patients suffering from both diseases. According to the same statistical test all conditions for TaqI polymorphism genotype frequency were fulfilled in all groups of studied patients. There was no significant difference in distribution of BsmI, ApaI or TaqI polymorphism genotype frequencies between control patients and any of the subgroup of studied patients. In studied population none of analysed polymorphisms individually was associated with the risk of development of psoriasis, diabetes or combined phenotype

An Overexpression of Icam-1 in Mild Hyperhomocysteinemia and Hyperglycemia − A Study of Antidiabetics Administration Effect

Elevated plasma homocysteine is connected to atherosclerosis and increased cerebrovascular and ischemic heart disease especially in the patients with type 2 diabetes. Effects of metformin (10 μg mL−1), insulin (1 mUI mL−1), and their combination administration in condition of mild hyperhomocysteinemia (30 μmol dm−3) and hyperglycemia (12 mmol dm−3) on human aortic endothelial cells (HAEC) was investigated. HAEC were cultured 4 h in a medium with homocysteine (7 and 30 μmol dm−3) and glucose (5.5 and 12.0 mmol dm−3). E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular adhesion molecule-1 (VCAM-1) expressions were analysed by flow-cytometry. Controls were CAMs expression on HAEC in medium with physiological concentration of homocysteine and glucose. HAEC, incubated additionally with 30 μmol dm−3 homocysteine, increased expression of ICAM-1 for 65 % (p = 0.07) and decreased of E-selectin for 30 % (p = 0.07) and VCAM-1 for 13 % (0.06). In condition of mild hyperhomocysteinemia and hyperglycemia there was a statistically significant increase of ICAM- 1 expression (for 22 %, p = 0.04), while administration of metformin and insulin did not statistically significantly influence adhesion molecules expression. Observed significant overexpression of ICAM-1, leads us to conclude that combination of mild hyperhomocisteinemia and hyperglycemia could have significant influence on development of inflammation and atherosclerosis in diabetic patients.(doi: 10.5562/cca1810