Effects of Hyperglycemia and Metformin on Expression of Adhesion Molecules on Human Aortic Endothelial Cells

Expression of adhesion molecules on the endothelial cell surface as a response to elevated glucose concentration is considered as a main event in the development of atherosclerosis. The influence of high glucose concentration and metformin, a wide used anti-diabetic drug, on the expression of E-selectin, vascular adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) on human aortic endothelial cells (HAECs) was investigated. HAECs were cultured 4 h in a medium with 5.5, 8.0, 12.0, and 16.5 mmol dm-3 glucose with or without metformin addition. The expression of cell adhesion molecules (CAM) was measured by flow-cytometry. Compared to CAM expression in the medium with 5.5 mmol dm-3 glucose, glucose concentration of 12.0 mmol dm-3 increased expression of E-selectin (62 %), VCAM-1 (four fold) and ICAM-1 (81 %). Metformin administration in the medium with 12.0 mmol dm-3 glucose additionally enhanced E-selectin and VCAM-1 expression compared to effects of corresponding glucose concentration. ICAM-1 expression was only significantly increased in the medium with metformin and 8.0 mmol dm-3 glucose. In conclusion, metformin in condition with elevated glucose concentration additionally increased expression of CAM on HAECs which could contribute to development of macrovascular complications in diabetic patients

9-Deazaguanine and Its Methyl Derivatives: Synthesis, Antitumor Activity in vitro and Effects on Purine Nucleoside Phosphorylase Gene Expression

9-Deazaguanine 9-DG, 1-methyl-9-deazaguanine AG-19-K1 and 1,7-dimethyl-9-deazaguanine AG-3 were synthesized and their antiproliferative activity against five leukemia and four solid tumor cell lines as well as inhibitory properties vs. calf spleen purine nucleoside phosphorylase (PNP) were tested. Synthesis of 9-DG involves reaction of 2-amino-6-methyl-5-nitropyrimidin- 4(3H)-one (2) with DMF-dimethylacetal (amount ratio, n(2) / n(DMF-dimethylacetal) = 1:2.5) and use of the benzyloxymethyl group to protect the N-3 position of 2-(N-dimethylaminomethylene) amino-6-methyl-5-nitropyrimidin-4(3H)-one (4). Reaction of 2 with DMF-dimethylacetal (amount ratio, n(2) / n(DMF-dimethylacetal) = 1:6) gave the N-3 methyl substituted intermediate 3. Dithionite reduction of this product afforded N-methyl derivatives AG-19-K1 and AG-3. AG-19-K1 and AG-3 were inactive vs. calf spleen PNP at a concentration of 75 mmol dm–3. Cytotoxic effects of 9-deazaguanine derivatives on cell growth were determined by the MTT assay. Investigated derivatives showed moderate antiproliferative activity towards examined tumor cells. At a concentration of 10–3 mol dm–3, AG-19-K1 inhibited the growth of JURKAT, K562 and AGS cells by approximately 80 %. At the same concentration, AG-3 and 9-DG inhibited cell proliferation by 40-50 % of all tested lines, except MOLT-4 and HL-60. The PNP gene expression was changed in treated leukemia cells after exposure to AG-19-K1 and 9-DG in a time-dependent manner

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

The role of library in self-evaluation of scientific Institution - University Hospital Centre Osijek

U ovome radu prikazala se uloga knjižnice u sastavu Kliničkoga bolničkog centra Osijek u kojem se obavlja zdravstvena, znanstvena, nastavna, knjižnična i nakladnička djelatnost s posebnim naglaskom na ulogu u postupku mjerenja i vrednovanja produktivnosti znanstvene organizacije upisane u Upisnik znanstvenih organizacija MZOS RH.This paper presents the role of the library at the University Hospital Centre (UHC) Osijek, where health, scientific, teaching, librarian and publishing activities are being conducted with special accent on its role in productivity measurement and evaluation of the scientific organisation registered at Research Organisations Registry of the Republic of Croatia, Ministry of Science and Education

The Expression of T Cell FOXP3 and T-Bet Is Upregulated in Severe but Not Euthyroid Hashimoto’s Thyroiditis

Hashimoto’s thyroiditis (HT) is an organ-specific autoimmune disorder characterized by progressive thyroid failure. Th1 and Treg subset of CD4+ cells have been implicated in the pathogenesis; however, less is known about their respective roles across the spectrum of HT clinical presentations. To shed more light on CD4+ subsets role in HT, we investigated the mRNA expression levels of several Th1/Treg-associated transcription factors (T-bet/ETS1, HIF1α/BLIMP1/FOXP3) in peripheral blood T cells of 10 hypothyroid, untreated HT patients, 10 hypothyroid patients undergoing hormone replacement therapy, 12 euthyroid HT subjects, and 11 healthy controls by the qRT-PCR. Compared to euthyroid HT patients and controls, both hypothyroid (2.34-fold difference versus controls, P<0.01) and thyroxine-supplemented patients (2.5-fold, P<0.001) showed an increased FOXP3 mRNA expression in T cells. Similarly, mRNA expression levels of T-bet were upregulated in severely affected but not in euthyroid HT subjects (2.37-fold and 3.2-fold, hypothyroid and thyroxine-supplemented HT patients versus controls, resp., P<0.01). By contrast, no differences in mRNA expression levels of ETS1, BLIMP1, and HIF1α were observed across the study groups. In summary, severe but not euthyroid HT was associated with robust upregulation of T-bet and FOXP3 mRNA in peripheral T cells, independent of the thyroid hormone status but proportional to disease activity