Chronic allograft nephropathy (CAN) represents a frequent and irreversible cause of long-term renal graft loss. TGF- β 1 is a key profibrogenic cytokine associated with CAN pathogenesis. Because of clinical diagnostic inaccuracy, protocol biopsy has been suggested to be a beneficial method for early CAN detection. Protocol core biopsy was carried out in 67 consecutive cyclosporine-based immunosuppression-treated kidney transplant recipients with stable renal function 12 months after renal transplantation. Biopsy specimens were analyzed morphologically according to Banff-97' criteria and immunohistologically for TGF- β 1 staining. The data obtained were correlated with plasma TGF- β 1 levels and clinical data. CAN (grade I-III) was found in 51 patients (76 %). CAN grade I was found to be the most frequent one (44 %). A normal finding within the graft was made in only 12 patients (18 %). Clinically silent acute rejection Banff IA was present in 4 patients (6 %). In 8 patients (12 %) with CAN, borderline changes were present. We found a significant correlation between CAN grade and creatinine clearance, as measured by the Cockroft-Gault formula (p<0.01) as well as body mass index (p<0.01). There was a significant correlation between chronic vasculopathy (Banff cv) and creatinine clearance, and between the degree of TGF- β 1 staining and chronic vasculopathy (p<0.01). There were no relations between morphological findings and TGF- β 1 plasma levels, cyclosporine levels, plasma lipids, HLA- mismatches, panel reactive antibodies (PRA), proteinuria, and the donor's age. In conclusion, CAN is a frequent finding in protocol kidney graft biopsies 12 months after transplantation. TGF- β 1 tissue expression is linked with chronic vasculopathy., O. Viklický, I. Matl, L. Voska, R. Böhmová, M. Jarešová, J. Lácha, A. Lodererová, I. Stříž, V. Teplan, Š. Vítko., and Obsahuje bibliografii
The activity of antioxidant enzymes, copper-zinc superoxide dismutase (CuZnSOD), manganese superoxide dismutase (MnSOD) and catalase (CAT), as well as that of the mitochondrial FAD-dependent a-glycerophosphate dehydrogenase (a-GPD) in the rat interscapular brown adipose tissue (IBAT) were studied after the treatment with methimazole (MMI) for three weeks or with iopanoic acid (IOP) for five days. Besides, the mitochondrial concentration of uncoupling protein-1 (UCP-1) and the activity of catecholamine degrading enzyme monoamine oxidase (MAO) in the IBAT as well as the activity of the catecholamine synthesizing enzyme, dopamine b-hydroxylase (DBH) in rat serum were examined. Judging by the significantly enhanced level of serum DBH, which is an index of sympathetic activity, and that of IBAT MAO, the increase in MnSOD and CAT activities in the IBAT of hypothyroid (MMI-treated) rats seems to be due to elevated activity of sympathetic nervous system (SNS). However, CuZnSOD activity is not affected by SNS. On the contrary, IOP, which is a potent inhibitor of T4 deiodination into T3 producing "local" hypothyroidism, did not change either SNS activity or activities of IBAT antioxidant enzyme. However, both treatments significantly decreased IBAT UCP-1 content and a-GPD activity suggesting that the optimal T3 concentration in the IBAT is necessary for maintaining basal levels of these key mitochondrial parameters., N. Petrović, G. Cvijić V. Davidović., and Obsahuje bibliografii
The role of the glycocalyx of arterial resistance vessels in regulating blood flow in vivo is not fully understood. Therefore, the effect of glycocalyx damage using two separate compounds, hyaluronidase and N-Formylmethionyl-leucyl-phenylalanine (fMLP), was evaluated in the iliac artery vascular bed of the anaesthetised pig. Blood flow and pressure were measured in the iliac, an adjustable snare was applied to the iliac above the pressure and flow measurement site to induce step decreases (3 occlusions at 3-4 min intervals were performed for each infusion) in blood flow, and hence iliac pressure, and vascular conductance (flow/pressure) was calculated. Saline, hyaluronidase (14 and 28 μg/ml/min), and fMLP (1 μM/min) were infused separately, downstream of the adjustable snare and their effect on arterial conductance assessed. Hyaluronidase at the higher infusion rate and fMLP both caused a reduction in arterial conductance, and hence an increase in blood flow resistance. In conclusion, the results show that glycocalyx damage causes an increase in resistance to blood flow in the iliac artery vascular bed., T. Ruane-O’Hora, F. Markos., and Seznam literatury
Fatty acid (FA) profiles as potentially relevant components of Crohn’s disease (CD) have been insufficiently analysed. We sought to explore the plasma profiles of n-3 and n-6 polyunsaturated fatty acids (PUFAs) in newly diagnosed untreated active CD. We included 26 consecutive CD pediatric patients (<19 years) and 14 healthy controls (HCs). Disease characteristics, including inflammatory markers, dietary histories, and the Pediatric Crohn’s Disease Activity Index (PCDAI), were obtained. The profiles of plasma FAs in plasma lipid classes were analysed by gas chromatography with FID detection of methyl esters. The erythrocyte sedimentation rate, C-reactive protein level and fecal calprotectin level (all p<0.001) were significantly higher in CD patients than in HCs. Most changes were observed in plasma phospholipids (PLs), such as a higher content of n-3 and changes in n-6 long-chain PUFAs in the CD group. The CD group had a lower ratio of n-6/n-3 PUFAs in PLs (p<0.001) and triacylglycerols (TAGs) (p<0.01). Correlations of the FA content in plasma PLs with disease activity scores of CD were also observed, which were positive for the sum of monounsaturated fatty acids (MUFAs) as well as oleic acid (18:1n-9) (both p<0.05). The metabolism of PUFAs is significantly altered even in treatment-naïve newly diagnosed active pediatric CD, and the content of major FAs in PLs correlates with disease activity and inflammatory markers, thus probably contributing to the still unclear early disease pathogenesis., Jan Schwarz, Marek Vecka, František Stožický, Renáta Pomahačová, Barbora Staňková, Eva Tvrzická, Marcela Kreslová, Romana Zahálková, Josef Sýkora., and Obsahuje bibliografii
An oxidant/antioxidant imbalance is thought to play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). We hypothesized that antioxidant capacity reflected by erythrocyte glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) activities, and serum levels of the lipid peroxidation product malondialdehyde (MDA), may be related to the severity of obstructive lung impairment in patients with COPD. Erythrocyte GPx, SOD and CAT activities, and serum levels of MDA were measured in 79 consecutive patients with stable COPD. Pulmonary functional tests were assessed by bodyplethysmography. Moderate COPD (FEV1 50-80 %) was present in 23, and severe COPD (FEV1 < 50 %) in 56 patients. Erythrocyte GPx activity was significantly lower, and serum MDA levels were significantly higher in patients with severe COPD compared to patients with moderate COPD (GPx: 43.1±1.5 vs. 47.7±2.9 U/gHb, p<0.05, MDA: 2.4±0.1 vs. 2.1±0.1 nmol/ml, p<0.05). Linear regression analysis revealed a significant direct relationship between FEV1 and erythrocyte GPx activity (r = 0.234, p<0.05), and a significant inverse relationship between FEV1 and serum MDA levels (r = -0.239, p<0.05). However, no differences were observed in the erythrocyte SOD and CAT activities between the two groups of patients with different severity of COPD. Findings of the present study suggest that antioxidant capacity reflected by erythrocyte GPx activity and serum levels of the lipid peroxidation product MDA are linked to the severity of COPD., Z. Kluchová, D. Petrášová, P. Joppa, Z. Dorková, R. Tkáčová., and Obsahuje bibliografii a bibliografické odkazy