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

Clinical Characteristics of Patients with Spondyloarthritides and HLA-B27 Positive Antigen

The aim of this study was to present our experiences in diagnosing spondyloarthritides (SpA), and to list the most common clinical features of HLA-B 27 positive patients.The study included 65 HLA-B 27 positive patients with confirmed diagnosis of ankylosing spondylitis(AS) and psoriatic arthritis (PsA) who were analyzed between 2009 and 2010 in Clinic of Internal Medicine in Osijek. The diagnosis of seronegative spondyloarthritides was based on the ASAS (Assessment in AS Working Group) classification criteria for axial and then supplemented with ASAS criteria for peripheral SpA and was confirmed by radiological techniques. For diagnosing the ankylosing spondylitis (AS), there have been applied the modified New York criteria. Radiological criteria for definite sacroiliitis according to the modified New York criteria is bilateral sacroiliitis, grade 2–4 (2) or unilateral sacroiliitis, grade 3–4. For diagnosing the psoriatic arthritis (PsA), there were used CASPAR diagnostic criteria. Other features of SpA are defined within the existing classification criteria. HLA-B27 antigen was determined by direct immune-fluorescence technique using flow cytometer. The average age of patients was 50.34 years, of whom 27 female (41.53%), 38 male (58.46%). Duration of illness was 15.79 years on average.With 75.38% of patients, there had been determined the diagnosis of AS; 24.62% of patients had the diagnosis of PsA. The most common clinical characteristics that patients had were: inflammatory back pain (pain Inflammation along the lumbosacral spine), peripheral arthritis, intermittent pain in the gluteus, sacroiliitis, enthesitis, uveitis, dactilitis

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

Interleukin 17A and Toll-like Receptor 4 in Patients with Arterial Hypertension

BACKGROUND/AIMS: Immune responses are involved in arterial hypertension. An observational cross-sectional case control study was conducted to estimate the association between Toll-like receptor 4 (TLR4) expression and interleukin (IL)-17A serum levels in patients with controlled and non-controlled hypertension. METHODS: We have enrolled 105 non-complicated otherwise healthy hypertensive patients: 53 with well-controlled blood pressure and 52 non-controlled. TLR4 peripheral monocytes expression and serum IL-17A levels were determined by flow cytometry and ELISA, respectively. RESULTS: Non-controlled patients exhibited higher TLR4 expression than well-controlled (25.60 vs. 21.99, P=0.011). TLR4 expression was lower in well-controlled patients who were prescribed beta blockers (18.9 vs. 22.6, P=0.005) and IL-17A concentration was higher in patients using diuretics in either group (1.41 vs. 2.01 pg/ml, P<0.001; well-controlled 1.3 vs. 1.8 pg/ml, P= 0.023; non-controlled 1.6 vs. 2.3 pg/ml, P=0.001). Correlation between IL-17A concentration and hypertension duration was observed in non-controlled patients (Spearman correlation coefficient . ρ=0.566, P<0.001) whereas in well-controlled patients a correlation was found between hypertension duration and TLR4 expression (ρ=0.322, P=0.020). CONCLUSIONS: Arterial hypertension stimulates the immune response regardless of blood pressure regulation status. Prolonged hypertension influences peripheral monocyte TLR4 expression and IL-17A serum levels. Anti-hypertensive drugs have different immunomodulatory effects: diuretics are associated with higher IL-17A concentration and beta-blockers with lower TLR4 expression

Klinička obilježja pacijenata sa spondiloartritisima i hla-b27 pozitivnim antigenom

The aim of this study was to present our experiences in diagnosing spondyloarthritides (SpA), and to list the most common clinical features of HLA-B 27 positive patients.The study included 65 HLA-B 27 positive patients with confirmed diagnosis of ankylosing spondylitis(AS) and psoriatic arthritis (PsA) who were analyzed between 2009 and 2010 in Clinic of Internal Medicine in Osijek. The diagnosis of seronegative spondyloarthritides was based on the ASAS (Assessment in AS Working Group) classification criteria for axial and then supplemented with ASAS criteria for peripheral SpA and was confirmed by radiological techniques. For diagnosing the ankylosing spondylitis (AS), there have been applied the modified New York criteria. Radiological criteria for definite sacroiliitis according to the modified New York criteria is bilateral sacroiliitis, grade 2–4 (2) or unilateral sacroiliitis, grade 3–4. For diagnosing the psoriatic arthritis (PsA), there were used CASPAR diagnostic criteria. Other features of SpA are defined within the existing classification criteria. HLA-B27 antigen was determined by direct immune-fluorescence technique using flow cytometer. The average age of patients was 50.34 years, of whom 27 female (41.53%), 38 male (58.46%). Duration of illness was 15.79 years on average.With 75.38% of patients, there had been determined the diagnosis of AS; 24.62% of patients had the diagnosis of PsA. The most common clinical characteristics that patients had were: inflammatory back pain (pain Inflammation along the lumbosacral spine), peripheral arthritis, intermittent pain in the gluteus, sacroiliitis, enthesitis, uveitis, dactilitis.Cilj ovog rada bio je prikazati naša iskustva u dijagnostici spondiloartritisa (SpA) te navesti najtipičnija klinička obilježja HLA-B27 pozitivnih bolesnika. U istraživanju je uključeno 65 HLA-B 27 pozitivnih bolesnika s potvr|enom dijagnozom ankilozantnog spondilitisa (AS) i psorijatičnog artritisa (PsA) koji su tijekom 2009 i 2010 godine liječeni na Internoj klinici u Osijeku. Dijagnoza seronegativnih spondiloartritisa temeljila se na ASAS (Assessment in AS working group) klasifikacijskim kriterijima za aksijalni i periferni SpA i bila potvr|ena radiološkim metodama. Za dijagnosticiranje ankilozantnog spondilitisa (AS) primijenili su se modificirani New york kriteriji. Radiološki kriterij za definitivni sakroileitis prema modificiranim New York kriterijima je bilateralni sakroiliitis stupnja 2–4 (2) ili unilateralni sakroiliitis stupnja 3–4. Za dijagnozu psorijatičnog artritisa (PsA) korišteni su CASPAR dijagnostički kriteriji. Ostale značajke SpA definirane su u sklopu postojećih klasifikacijskih kriterija. HLA-B27 antigen je određivan je direktnom imunofluorescentnom metodom na protočnom citometru. Prosječna starost pacijenata bila je 50,34 godina, od kojih je 27 žena (41,53%), 38 muških (58,46%). Trajanje bolesti bilo je u prosjeku 15,79 godina. U 75,38 % bolesnika postavljena je dijagnoza AS; 24.62% bolesnika imalo je dijagnozu PSA. Najčešće kliničke karakteristike koje su pacijenti imali bili su: upalna križobolja (inflamatorna bol duž lumbosakralnog dijala kralježnice), periferni artritis, naizmjenična bol u gluteusima, sakroiliitis, entezitis, uveitis, daktilitis. Ovo naše istraživanje je pokazalo da se kliničke značajke HLA B 27 pozitivnih pacijenata sa SpA u Istočnoj Slavoniji ne razlikuju od kliničkih manifestacija pacijenata sa SpA u drugim dijelovima Europe koje su iznesene u različitim studijama