Chronic systemic inflammation is associated with increased cardiovascular mortality in patients with rheumatoid arthritis (RA). The aim of our study was to investigate association of glucose metabolism and inflammatory markers in a group of patients with rheumatoid arthritis free of other metabolic risk factors. Twenty-two premenopausal RA females (11 patients on low-dose GC (<8.5 mg/day of prednisone or equivalent), 11 patients without glucocorticoid therapy) and 15 age- and BMImatched healthy females underwent the oral glucose tolerance test. The insulin sensitivity indices according Matsuda (ISIMAT) and Cederholm (ISICED) as well as HOMA2 %S were calculated. Cytokines, lipid profile, non-esterified fatty acids (NEFA) and plasminogen activator inhibitor-1 (PAI-1) were measured in baseline blood samples. Despite elevated interleukin IL-6 and TNF alpha, glucose, insulin and C-peptide responses to oral glucose load as well as ISIMAT, ISICED, PAI-1 and NEFA were comparable in both RA groups and healthy controls. HOMA 2 %S correlated with disease activity. In conclusions, low-dose glucocorticoid treatment does not lead to glucose metabolism impairment in RA patients without other metabolic risk factors. Increased cardiovascular mortality and morbidity is probably due to a direct effect of systemic inflammation on myocardium and/or blood vessels., A. Penesová, ... [et al.]., and Obsahuje seznam literatury
Circulating lipopolysaccharide-binding protein (LBP), a metabolic endotoxemia marker, was identified as an independent predictor of atherosclerosis. Although increases in carotid intima-media thickness (CIMT) were repeatedly reported in obstructive sleep apnea (OSA), neither the role of OSA in metabolic endotoxemia nor of LBP in early atherosclerosis were explored in patients with OSA. At a tertiary university hospital we investigated the relationships between OSA, LBP and CIMT in 117 men who underwent full polysomnography and CIMT assessment by B-mode ultrasound. Circulating LBP concentrations and average CIMT increased from patients without OSA to those with mild-moderate and severe OSA (from 32.1±10.3 to 32.3±10.9 to 38.1±10.3 μg.ml-1, p=0.015; from 0.52±0.09 to 0.58±0.06 to 0.62±0.10 mm, p=0.004, respectively). Oxygen desaturation index (ODI) was a predictor of serum LBP levels independent of age, waist-to-hip ratio (WHR), smoking, hypertension, HDL cholesterol, triglycerides and fasting glucose [p (ANOVA)=0.002, r 2=0.154], with no independent effect of the ODI*WHR interaction term on LBP. Furthermore, serum LBP predicted CIMT independently of known risk factors of atherosclerosis including obesity (p<0.001, r 2=0.321). Our results suggest that OSA severity contributes to metabolic endotoxemia in patients with OSA independently of obesity, and that LBP might represent a contributing factor promoting early atherosclerosis in such patients., I. Trojová, M. Kozarová, D. Petrasová, Z. Malachovská, I. Paranicová, P. Joppa, R. Tkacová., and Seznam literatury
Increases in resting energy expenditure (REE) likely contribute to weight loss in various chronic diseases. In chronic obstructive pulmonary disease (COPD), relationships between the ventilatory impairment and increased REE, and between disturbances in adipokines and weight loss were previously described. Therefore, we investigated serum levels and adipose tissue expression of leptin and adiponectin, and their relationships to REE in patients with COPD. In 44 patients with stable COPD (38 male; age 62.3±7.2 years), REE was assessed using indirect calorimetry. Subcutaneous adipose tissue samples were analyzed using realtime PCR. From underweight [n=9; body mass index (BMI) <20.0 kg.m−2 ], to normal weight-overweight (n=24, BMI=20.0- 29.9 kg.m−2 ) and obese patients (n=11; BMI≥30 kg.m−2 ), REE adjusted for body weight decreased (32.9±6.1 vs. 26.2±5.8 vs. 23.9±6.6 kcal.kg−1 .24 h−1 , p=0.006), serum levels and adipose tissue expression of leptin increased (p<0.001 for both), and serum and adipose tissue adiponectin decreased (p<0.001; p=0.004, respectively). REE was inversely related to serum and adipose tissue leptin (R=−0.547, p<0.001; R=−0.458, p=0.002), and directly to serum adiponectin (R=0.316, p=0.039). Underweight patients had increased REE compared to normal weight-overweight patients, in association with reductions in serum and adipose tissue leptin, and increased serum adiponectin, suggesting a role of adipokines in energy imbalance in COPD-related cachexia, M. Brúsik ... [et al.]., and Obsahuje seznam literatury
Selective serotonine reuptake inhibitors (SSRI) are believed to be less dangerous in the treatment of depressive disorder in comparison with tricyclic antidepressants (TCA) due to their relative lack of cardiotoxicity. Thus, we investigated the effect of citalopram (SSRI) on membrane electrophysiology in rat cardiomyocytes in tissue culture. The results were compared with those from amitriptyline (TCA). The whole-cell configuration patch-clamp technique was used. Both citalopram and amitriptyline exhibited the concentration-dependent inhibition of the L-type calcium channel current (ICa). Citalopram in concentrations of 3 mM and 10 mM inhibited peak calcium current by 2.7 % and 8 %, respectively. We demonstrated the same potency of citalopram and amitriptyline to inhibit ICa. These observations led us to conclude that citalopram and amitriptyline are drugs, which exhibit a similar potency for causing concentration-dependent inhibition of ICa., J. Hamplová-Peichlová, J. Krůšek, I. Paclt, J. Slavíček, V. Lisá, F. Vyskočil., and Obsahuje bibliografii
Erythromycin has a well-known dual effect on the contractility of the gastrointestinal system and recently has also been shown to inhibit contractions of the rat myometrium. The aim of the present study was to investigate the effects of clarithromycin on oxytocin, prostaglandin F2a (PGF2a) and KCl-induced contractions of human myometrium in vitro. Myometrial strips were obtained from pregnant women undergoing elective Cesarean section and the strips were suspended in a jacketed organ bath filled with Krebs solution at 37 oC (pH 7.4) and continuously aired with 95 % oxygen and 5 % carbon dioxide. Isometric contractions were measured using a force displacement transducer. Oxytocin, PGF2a, KCl and clarithromycin were applied to the tissue bath and the amplitude and frequency of contractions were evaluated at 20-min intervals. Freidmann analysis of variance, Kruskal Wallis and Wilcoxon Rank tests were used for statistical analysis of the data. Clarithromycin dose dependently inhibited the amplitude of contractions independent of the stimulus. Pre-treatment with apamin prevented clarithromycin-induced effects on amplitude and frequency of contractions. We conclude that the macrolide antibiotic clarithromycin may have a direct inhibitory effect on contractions of human myometrium., H. Celik, A. Ayar., and Obsahuje bibliografii
Rat liver myofibroblasts (MFB) were isolated by repeated passaging of nonparenchymal liver cell fraction. They were cultured on polystyrene Petri dishes, on fibrin or on type I collagen gels for 5 days. Quantitative RT-PCR, Western blotting, zymography and immunocytochemistry were used to study differences in cell morphology and protein expression. MFB were large and spread on plastic substrate, with prominent α-smooth muscle (α-SMA) fibres. They turned much smaller and elongated on collagen which was accompanied by the rearrangement of the cytoskeleton and a decrease in α-SMA and β-actin content. Collagen gel induced the expression of a group of metalloproteinases (MMP-2, -3, -9, -13), on mRNA and protein level which resulted in the degradation of the gel. This response was accompanied by changes in the mRNA expression of cytokines of TGF-β family, CTGF and interleukin-6, as well as of osteopontin and thrombospondin-2 that are involved in metalloproteinases (MMPs) regulation. The expression of MMPs substrates, collagen types I, IV and XII did not change or decreased. The effects of fibrin gels on MFB were milder than those of collagen. MFB assumed to deposit collagen and other ECM components in fibrotic liver, besides hepatic stellate cells, also possess a great collagenolytic potential., A. Jiroutová, ... [et al.]., and Obsahuje seznam literatury
Decrease of arterial wall shear stress (WSS) is associated with higher probability of atherosclerotic plaque development in many disease conditions. End-stage renal diseases (ESRD) patients suffer from vascular disease frequently, but its nature differs from general population. This study was aimed at proving an association between common carotid wall shear stress and the presence of carotid bifurcation plaques in a group of ESRD patients. ESRD subjects, planned for the creation of a dialysis access and therapy were included. Wall shear rate (WSR) was used as a surrogate of WSS and was analyzed in the common carotid arteries by duplex ultrasonography. Intima media thickness (IMT) was measured at the same site. The presence/absence of carotid bifurcation plaques was recorded. The endothelial function was estimated by the levels of von Willebrand factor (vWf). 35 ESRD patients were included (19 females, 17 diabetics). Atherosclerotic plaque was present in 53 % of bifurcations. Wall shear rate was lower in arteries with plaques (349±148 vs. 506±206 s-1, p=0.005) and was directly related to the height of IMT and inversely to the activity of vWf (r= –0.65, p=0.016). Lower wall shear rate in the common carotid arteries is linked to the endothelial dysfunction and to the presence of atherosclerotic plaques in carotid bifurcations in ESRD subjects. Faster arterial dilatation may facilitate this process in ESRD subjects., J. Malík ... [et al.]., and Obsahuje seznam literatury
Gum acacia (GA) is used in pharmaceutical, cosmetic and food industries as an emulsifier and stabilizer, and in some countries in the traditional treatment of patients with chronic kidney disease (CKD). We have previously found that GA ameliorates adenine -induced chronic renal failure (CRF) in rats. Different brands of GA are commercially available, but their comparative efficacy against adenine-induced CKD is unknown. Here, we explored the effects of three different brands of GA (Sudanese GA, SupergumTM and GA from BDH) on some physiological, biochemical, and histological effects of adenine-induced CRF in rats. Adenine (0.75 %, w/w in feed, four weeks) reduced body weight, and increased urine output. It also induced significant increases in blood pressure, and in creatinine, urea, several inflammatory cytokines in plasma, and indices of oxidative stress, and caused histological damage in kidneys. Treatment of rats concomitantly with any of the three GA brands, significantly, and to a broadly similar extent, mitigated all the signs of CRF. The results suggested equivalent efficacy of these brands in antagonizing the CRF in this animal model. However, to enable standardization of different brands between laboratories, the use of the chemically well-characterized GA preparation (such as SupergumTM) is recommended., B. H. Ali, ... [et al.]., and Obsahuje seznam literatury
Previously, the changes in phagocyte functions such as adherence, chemotaxis or TNFa production were found to be associated with oxidative stress in endotoxin-induced septic shock. However, in this type of oxidative stress the lymphocyte involvement has rarely been studied. In the present report, we analyzed the above functions in peritoneal lymphocytes from male and female BALB/c mice with a lethal endotoxic shock caused by intraperitoneal injection of E. coli lipopolysaccharide (LPS) (100 mg/kg), male and female Swiss mice with lethal endotoxic shock caused by intraperitoneal injection of LPS (150 and 250 mg/kg, respectively) or non-lethal endotoxic shock (100 mg/kg). In peritoneal lymphocytes obtained at 0, 2, 4, 12 or 24 h after LPS injection, the first two functions of these cells in the immune response, i.e. adherence to tissues and directed migration (chemotaxis), were studied. At 0, 0.5, 1, 1.5, 2, 4, 12 and 24 h after LPS injection, TNFa released by lymphocytes was also analyzed. The results show that endotoxic shock increases the adherence and TNFa release, and decreases the chemotaxis of peritoneal lymphocytes. These changes were more significant in mice with lethal than with non-lethal endotoxic shock, a fact that confirms the important role of lymphocytes during endotoxic shock., V. M. Víctor, D. Rubio, M. De la Fuente., and Obsahuje bibliografii
Although male rats generally outperform females in many spatial tasks, sometimes gender differences are not present. This preliminary study examined gender effects in the Enemy avoidance task, in which a rat on a stable circular arena avoids approaching a small mobile robot while collecting randomly dispersed small pellets. Whenever distance between robot and the rat dropped below 25 cm, animal was punished by a mild footshock. Female rats showed thigmotaxis, hypolocomotion and avoidance of robot in the habituation phase, when approaches were not punished. No statistically significant differences in avoidance learning under reinforcement training sessions were observed; but females still spent significantly more time at periphery of the arena and foraged less than males. We conclude that females were able to perform at the same level as males under reinforcement despite different behavioral strategy. The thigmotaxic behavior appears to function as innate escape strategy in female rats triggered by the stressing effect of the moving robot rather then the presence of shocks., J. Svoboda, ... [et al.]., and Obsahuje seznam literatury