Antiendothelial cell antibodies (AECA) have been detected by flow cytometry analysis in 23 out of 80 patients with connective tissue diseases. Ten out of 19 serum samples from patients with systemic lupus erythematosus (SLE) were positive. These antibodies were not detectable in healthy donors. We examined the capacity of serum samples to induce endothelial cell activation by modulating cell adhesion molecule expression on human umbilical vein endothelial cells. We found that sera from both AECA-positive and AECA-negative patient groups induced a significantly higher expression of E-selectin compared to healthy controls (P<0.05). There were no differences in the ICAM-1 on VCAM-1 expression. Our data suggest that increased E-selectin expression in activated endothelium in patients with various connective tissue disorders is not related to the production of AECA., M. Horváthová, E. Jahnová, Š. Nyulassy., and Obsahuje bibliografii
a1_The wide chemical diversity of estrogenic compounds precludes an accurate prediction of estrogenic activity on the basis of chemical structure or radioimmunological assay and thus requires that the potency of these compounds is defined by bioassay. The mammary duct growth response in intact prepubertal and adult gonadectomized female and male mice of the C3H/Di strain was used to assess the estrogenicity of synthetic compounds or their derivatives. The vehicle for tested compounds should be free of estrogenic and other hormonal effects. Olive oil or sunflower oil exerted estrogenic activities and were thus unsuitable as vehicles for the tested compounds. The absence of estrogenic activity, high solubility of different steroid hormones, and the low incidence of the inflammatory reactions at the injection site were achieved by using a vehicle containing benzyl alcohol, benzyl benzoate, butylhydroxyanisole, butylhydroxytoluene, ethyl oleate and ethanol. The bioassay was primarily designed to examine the effect of tested compounds on mammogenesis. The duration of hormone treatment was chosen to be long enough for induction of duct growth but too short to induce lobuloalveolar differentiation. Females were treated for 10 days, males for 15 days. The proportional volume occupied by mammary epithelial structures was estimated by the modified Chalkley's technique. The mean coefficient of variation of quantitative evaluation of 10 different mammary glands obtained by two operators varied between 3.2 and 17.4 %. The mean coefficient of variation of quintuplicate determinations of each mammary gland by one operator was 10.1 %, and 11.1 % by the other. The correlation coefficient between results of two operators was 0.994. Estrogens are primarily defined by their ability to increase the mitotic activity of female secondary sex organs., a2_However, our results have shown that progesterone alone, if administered in a high dose, stimulates mammary growth in both intact prepubertal and OV-X female mice similarly as the synthetic progestatial steroid norethindrone with inherent estrogenic properties. In contrast, progesterone alone had no effect, in young intact or adult castrated males, but norethindrone did stimulate mammary growth. These results demonstrated that the mammary gland of males is a suitable model for estrogen screening., J. Škarda., and Obsahuje bibliografii
The aim of our study was to investigate adrenocortical function in the context of disease activity and inflammatory status in premenopausal RA females. Adrenal glucocorticoid and androgen responses to the 1 μg ACTH 1-24 test were investigated in 23 premenopausal RA and in 15 age- and BMI-matched healthy females. Twelve RA patients were on low-dose prednisone (<8.5 mg/day). Patients with DAS28>3.2 had lower (p<0.05) total plasma cortisol, 17-hydroxyprogesterone, dehydroepiandrosterone and androstenedione responses in the ACTH test compared to healthy controls. Patients with DAS28>3.2 had lower (p<0.05) dehydroepiandrosterone response in the ACTH test compared to patients with DAS28≤3.2. C-reactive protein (CRP), DAS28, and interleukin (IL)-6 negatively correlated with androstenedione response to ACTH 1-24. Responses of all measured adrenal steroids were lower (p<0.05) in patients on low-dose glucocorticoids compared to healthy controls. RA patients not treated with glucocorticoids had lower total cortisol response (p=0.038) but did not differ in free plasma cortisol in the ACTH test. The results indicate an association of increased disease activity with a decrease in adrenal androgen production in RA and normal cortisol bioavailability in patients not treated with glucocorticoids., R. Imrich, M. Vlcek, J. Kerlik, M. Vogeser, F. Kirchhoff, A. Penesova, Z. Radikova, J. Lukac, J. Rovensky., and Obsahuje bibliografii
Diabetes mellitus type 2 ranks among the strongest predictors of cardiovascular diseases (CVD) while the association of type 1 diabetes with CVD is more complex. We studied differences between type 1 and 2 diabetic women regarding association of cardiovascular risk factors with preclinical atherosclerosis expressed as intima-media thickness of common carotid (IMT CCA) and femoral arteries (IMT CFA) measured by high resolution ultrasound. Women with type 1 (n=203) and type 2 diabetes (n=123) were examined with regard to the presence of cardiovascular risk factors. In type 1 diabetic women strong association between IMT CCA and body mass index, waist circumference, and total body fat was found in contrast to type 2 diabetic women. In type 2 diabetic women strong association between IMT CCA and fasting glucose, glycated hemoglobin, and atherogenic index of plasma (log TG/HDL cholesterol) was observed in contrast to type 1 diabetic women. In type 1 diabetic women, IMT CFA was associated with body fat in contrast to type 2 diabetic women. Preclinical atherosclerosis in type 1 diabetic women was strongly associated with factors reflecting body fat and its distribution, while in type 2 diabetic women preclinical atherosclerosis was associated with markers reflecting glucose and lipid metabolic disorders., P. Piťhová, K. Štechová, J. Piťha, V. Lánská, M. Kvapil., and Obsahuje bibliografii
Cardiovascular disease is a major cause of morbidity and mortality in young adults with end-stage renal disease (ESRD), but its basis is still not well understood. We therefore evaluated the determinants of atherosclerosis in children with ESRD. A total of 37 children with ESRD (with 31 who had undergone transplantation) were examined and compared to a control group comprising 22 healthy children. The common carotid intimamedia thickness (CIMT) was measured by ultrasound as a marker of preclinical atherosclerosis. The association of CIMT with anthropometrical data, blood pressure, plasma lipid levels, and other biochemical parameters potentially related to cardiovascular disease was evaluated. Children with ESRD had significantly higher CIMT, blood pressure, and levels of lipoprotein (a), urea, creatinine, ferritin, homocysteine, and serum uric acid as well as significantly lower values of apolipoprotein A. The atherogenic index of plasma (log(triglycerides/HDL cholesterol)) was also higher in patients with ESRD; however, this difference reached only borderline significance. In addition, a negative correlation was found between CIMT and serum albumin and bilirubin in the ESRD group, and this correlation was independent of age and body mass index. In the control group, a significant positive correlation was observed between CIMT and ferritin levels. Factors other than traditional cardiovascular properties, such as the antioxidative capacity of circulating blood, may be of importance during the early stages of atherosclerosis in children with endstage renal disease., H. M. Dvořáková ... [et al.]., and Obsahuje seznam literatury
Increased homocysteine levels in serum are typical features of neurodegenerative brain diseases including hydrocephalus. The most frequent therapeutic approach consists of the insertion of a shunt, connecting the brain ventricles to an alternative drainage site. To decide whether the patient should undergo this, the lumbar drainage test is usually carried out to distinguish patients who can benefit from the shunt insertion. In searching for other potential biochemical markers for shunt indication we determined homocysteine levels in CSF during the lumbar drainage test. Homocysteine in CSF was measured during the 5-day lumbar drainage test in 27 patients with normal-pressure hydrocephalus (NPH) and in 25 patients with excluded hydrocephalus. A novelized gas chromatography method with flame ionization detection (GC-FID) was developed and evaluated. During the first two days of lumbar drainage, the levels of CSF homocysteine in NPH patients were significantly higher compared to the controls, while on the fifth day, the homocysteine levels in patients with hydrocephalus reached the level of controls. Determination of CSF homocysteine in patients with confirmed or suspected hydrocephalus may serve as an independent marker for deciding on their further treatment strategy., L. Sosvorová, J. Bešťák, M. Bičíková, M. Mohapl, M. Hill, J. Kubárová, R. Hampl., and Obsahuje bibliografii
Many physiological and pathological processes in the cardiac tissue have been shown to be associated with a release of endothelin (ET) peptides and with induction of specific ET-receptors and G-protein-coupled ion channels. However, the exact mechanism regulating ET-receptors in the myocardium is controversial. The response to ET-1, the most important member of the ET family, is rapidly attenuated by down-regulation of ET-receptors. The internalization of ET-1 bound to two subclasses of specific receptors (ETA and ETB) that are abundant in the myocardium has been hypothesized to activate and/or inhibit a variety of intracellular signal transducing systems. The [125I]ET-1, BQ-3020 and selective ET-antagonists were used to study the subtype-selective component of regulation of ET-1 receptors in myocardial membranes. We determined the characteristics of [125I]ET-1 binding and [3H]thymidine incorporation in whole cell saturation studies and measured Ca 2+ channel induction and the total number of inactive Ca2+ channels in photoaffinity studies with [3H]azidopine. Here we demonstrate four important components of the complex ET-1 response in human, porcine and rat myocardium, leading to aberrant responses of cells. After ET-1 induction, adaptive subtype-ETB selective down-regulation predominated in human embryonic fibroblasts, in porcine membrane vesicles and in microsomal membranes of renal hypertensive rats, with preferential high affinity ET-1 binding to ETA receptors and with the resultant ETA mediated proliferative and mitogenic activation of human fibroblasts. The ET-1 induction was also accompanied by profound inactivation of Ca2+ channels in myocardial membranes., J. Dřímal, M. Mislovičová, A. Ismail, F. Monček., and Obsahuje bibliografii
Systolic blood pressure (SBP) changes control the cardiac interbeat intervals (IBI) duration via baroreflex. Conversely, SBP is influenced by IBI via non- baroreflex mechanisms. Both causal pathways (feedback - baroreflex and feedforward - non- baroreflex) form a closed loop of the SBP- IBI interaction. The aim of this study was to assess the age -related changes in the IBI - SBP interaction. We have non -invasively recorded resting beat -to- beat SBP and IBI in 335 healthy subjects of different age, ranging from 11 to 23 years. Using a linear autoregressive bivariate model we obtained gain (Gain SBP,IBI, used traditionally as baroreflex sensitivity) and coherence (CohSBP,IBI) of the SBP-IBI interaction and causal gain and coherence in baroreflex (Gain SBP → IBI , Coh SBP → IBI ) and coherence in non- baroreflex (CohIBI→SBP) directions separately. A non -linear approach was used for causal coupling indices evaluation (C SBP → IBI , C IBI → SBP ) quantifying the amount of information transferred between signals. We performed a correlation to age analysis of a ll measures. CohIBI→SBP and CIBI→SBP were higher than CohSBP→IBI and CSBP→IBI, respectively. Gain SBP,IBI increased and Coh SBP → IBI decreased with age. The coupling indices did not correlate with age. We conclude that the feedforward influence dominated at rest. The increase of Gain SBP,IBI with age was not found in the closed loop model. A decrease of Coh SBP → IBI could be related to a change in the cardiovascular control system complexity during maturation., J. Svačinová, M. Javorka, Z. Nováková, E. Závodná, B. Czippelová, N. Honzíková., and Obsahuje bibliografii
The aim of this study was to examine whether threshold to heat stimuli, and expression of transient receptor potential vanilloid1 (TRPV1) and nerve growth factor (NGF) in dorsal root ganglion (DRG) altered under conditions of long-term limb immobilization. A plastic cast was wrapped around the right limb from the forearm to the forepaw to keep wrist joint at 90° of flexion for 5 weeks. Heat hyperalgesia was tested using the plantar test at 6 h after removing cast. The rats were perfused transcardially with 4 % paraformaldehyde and DRGs were excised at 24 h after removing cast. For size distributions of the TRPV1-IR and NGF-IR neuronal profile, the DRG area measurements over 1000 DRG neurons per animal were measured in each side, on both the immobilized (ipsilateral) and contralateral sides. Ipsilateral withdrawal latency was significantly shorter than contralateral sides. Ipsilateral percentage of immunoreactive neurons in the total DRG neurons was significantly higher than contralateral sides in TRPV1-IR and NGF-IR. Long-term casting induced heat hyperalgesia, and up-regulation and phenotypic change of TRPV1-IR and NGF-IR in DRGs on the immobilized side. These DRG alterations may involve heat hyperalgesia after long-term limb immobilization., T. Nishigami, ... [et al.]., and Obsahuje seznam literatury