Electric stimulation (ES) could induce contraction of intestinal smooth muscle. The aim of this study was to analyze the effects of ES on esophageal motility and the underlying mechanism in vivo. Twenty-eight rabbits were equipped with a pair of subserosa electrodes (connected to an electrical stimulator) in the lower segment of the esophagus. The ES signal consisted of bipolar rectangular pulse trains, lasting for 3 s, with different amplitudes (1 mA, 3 mA, 5 mA and 10 mA), and frequencies (10 Hz, 20 Hz and 50 Hz). The amplitude of the contraction was recognized by high-resolution manometry. The effect of ES was tested under anesthesia and following administration of atropine, phentolamine or L-NAME. ES induced esophageal contraction at the stimulated site. A statistically significant increase in esophageal pressure was observed when the stimulation amplitude was above 3 mA. The increase in esophageal pressure was associated with the amplitude of stimulus as well as the frequency. During stimulation, atropine, phentolamine and L-NAME had no effect on the increase of esophageal pressure induced by ES. These findings implied that ES induced esophageal contraction were not mediated via the NANC, adrenergic or cholinergic pathway. The amplitude of esophageal contraction was current and frequency dependent., L. Zhang, W. Zhao, C. Zhao, H. Jin, B. Wang, B. Wang., and Seznam literatury
We examined the protective effect of radon inhalation on streptozotocin (STZ)-induced type-1 diabetes in mice. Mice inhaled radon at concentrations of 1000, 2500, and 5500 Bq/m3 for 24 hours before STZ administration. STZ administration induced characteristics of type-1 diabetes such as hyperglycemia and hypoinsulinemia; however, radon inhalation at doses of 1000 and 5500 Bq/m3 significantly suppressed the elevation of blood glucose in diabetic mice. Serum insulin was significantly higher in mice pre-treated with radon at a dose of 1000 Bq/m3 than in mice treated with a sham. In addition, superoxide dismutase activities and total glutathione contents were significantly higher and lipid peroxide was significantly lower in mice pre-treated with radon at doses of 1000 and 5500 Bq/m3 than in mice treated with a sham. These results were consistent with the result that radon inhalation at 1000 and 5500 Bq/m3 suppressed hyperglycemia. These findings suggested that radon inhalation suppressed STZ-induced type-1 diabetes through the enhancement of antioxidative functions in the pancreas., Y. Nishiyama, ... [et al.]., and Obsahuje seznam literatury
The effect of suramin, an inhibitor of G protein regulated signalling, was studied on the membrane currents induced by noxious heat and by capsaicin in cultured dorsal root ganglia neurones isolated from neonatal rats. Whole-cell responses induced by a heat ramp (24-52 °C) were little affected by suramin. The noxious heat-activated currents were synergistically facilitated in the presence of 0.3 µM capsaicin 13.2-fold and 6.3-fold at 40 °C and 50 °C, respectively. In 65% of neurones, the capsaicin-induced facilitation was inhibited by 10 µM suramin to 35±6 % and 53±6 % of control at 40 °C and 50 °C (S.E.M., n=15). Suramin 30 µM caused a significant increase in the membrane current produced by a nearly maximal dose (1 µM) of capsaicin over the whole recorded temperature range (2.4-fold at 25 °C and 1.2-fold at 48 °C). The results demonstrate that suramin differentially affects the interaction between capsaicin and noxious heat in DRG neurones and thus suggest that distinct transduction pathways may participate in vanilloid receptor activation mechanisms., V. Vlachová, A. Lyfenko, L. Vyklický, † R.K. Orkand., and Obsahuje bibliografii
The goal of this study is to evaluate if promotion of angiogenesis by systemic treatment with an antagomir against miR-92a, a well established inhibitor of angiogenesis, will maximize the benefits of exercise on bone. Ten week old female C57BL6/J mice were subjected to two weeks of external load by four point bending. During the first week of mechanical loading (ML), mice were injected (2.7 mg/kg of bodyweight) with antagomir against miR-92 or control antagomir (3 alternate days via retro-orbital). No difference in tissues weights (heart, kidney, liver) were found in mice treated with miR-92 vs. control antagomir suggesting no side effects. Two weeks of ML increased tibia TV, BV/TV and density by 6-15 %, as expected, in the control antagomir treated mice. Similar increases in the above parameters (7-16 %) were also seen in mice treated miR-92 antagomir. Administration of miR-92 antagomir was effective in reducing levels of mir-92 in heart, liver and skeletal muscle and in contrast, expression levels of two other microRNA’s miR-93 and miR-20a remain constant, thus suggesting specificity of the antagomir used. Surprisingly, we failed to detect significant changes in the expression levels of vascular genes (VEGF, CD31 and Tie2) in heart, liver or skeletal muscle. Based on these findings, we conclude that systemic administration of antagomir against miR-92 while reduced expression levels of miR-92 in the tissues; it did not significantly alter either angiogenic or osteogenic response, thus suggesting possible redundancy in miR-92 regulation of angiogenesis., A. Sengul, ... [et al.]., and Obsahuje seznam literatury
The association of transcription factor 7-like 2 (TCF7L2) gene variants with the pathogenesis of T2D, gestational diabetes and polycystic ovary syndrome (PCOS) was examined. The study involved 1460 individuals: 347 T2D patients (D); 261 gestational diabetics (G); 147 offspring of T2D (O); 329 women with PCOS, and 376 controls (C). The SNPs: rs7901695; rs7903146; rs12255372 in the TCF7L2 gene were genotyped. Anthropometric and biochemical parameters, oGTT derived indices were assessed. In addition, free fatty acids (FFAs) were evaluated in 183 non-diabetic women. The CTT haplotype showed the strongest association with T2D with OR 1.57, p=0.0003. The frequency of the CTT/CTT haplotype was decreasing in following order: D 10.6, O 9.5, G 6.1, C 5.3 and PCOS 4.9 [%]. Among CTT carriers, significantly decreased levels of oGTT-stimulated insulin and C-peptide as well as proportions of fasting PUFAs were observed. The carriership of CTG/TCG was associated with gestational diabetes, OR 2.59, p=0.036. The association of TCF7L2 haplotypes with T2D and gestational diabetes but not with PCOS was confirmed. Novel association of TCF7L2 with FFAs composition was found., J. Včelák ... [et al.]., and Obsahuje seznam literatury
Metabolic complications are frequent in primary aldosteronism (PA) and adiponectin gene polymorphisms seem to confer a genetic risk for metabolic alterations. Aim of the study was to evaluate the prevalence of metabolic symptoms in patients with PA compared to controls and the prevalence of two single nucleotide polymorphisms (SNPs), T45G and G276T, in the adiponectin gene and their relationship to metabolic syndrome (MS). The study involved 47 patients with PA and 90 controls selected from general population. Body mass index (BMI), and selected biochemical parametres were examined, and the mentioned SNPs were genotyped in all subjects. PA pati ents had a significantly higher BMI (p < 0.0001), blood glucose level (p < 0.01), and triglycerides (p < 0.0005) compared to controls. There were no significant differences in the prevalence of the studied genotypes of adiponectin gene polymorphisms. The 276GT genotype was linked with lower levels of triglycerides (p ≤ 0.05), while 276GG was related to higher levels of triglycerides (p=0.01). A similar but non- significant tendency was observed in relation to cholesterol levels. We can conclude that PA patients with the 276GT genotype have lower triglycerides levels, but there are not significant differences in the distribution of genotypes and alleles among PA patients and controls in an East Slovak population., I. Jochmanová, ... [et al.]., and Obsahuje seznam literatury
The relationship between hippocampal function and aging was explored in Wistar rats using taste aversion learning by comparing the performance of adult dorsal hippocampal lesioned and fifteen-month-old intact rats with that of adult intact rats. In experiment 1 the conditioned blocking phenomenon was absent in the hippocampal and the aging rats. Unlike the adult intact rats, the hippocampal and aging rats were not impaired in acquiring a learned aversion to a cider vinegar solution (3 %) presented as a serial compound with a previously conditioned saccharin solution (0.1 %). In experiment 2 both the hippocampal and the aging rats developed reduced aversions to a saline solution (0.5 %) followed by an i.p. injection of lithium chloride (0.15 M; 2 % b.w.) if the taste solution was previously preexposed without consequences. This latent inhibition effect was similar to that seen in intact adult rats. In both experiments, the aging rats exhibited enhanced conventional learned taste aversions. It is concluded that aging is not a unitary process but induces both hippocampal dependent and hippocampal independent complex changes in the functioning of the neural circuits, implementing taste aversion learning., I. Moron, M.A. Ballesteros, A. Candido, M. Gallo., and Obsahuje bibliografii
We used a rat model to assess the role of nephrin, podocin, and desmin in the pathogenesis of IgA nephropathy (IgAN). A rat IgAN model was established by administration of BSA, CCl4, and lipopolysaccharide (LPS) and compared with healthy control rats. Urinary protein, urine red blood cells, and biochemical parameters were measured for 12 weeks. Renal morphology and ultrastructure were examined by light and electron microscopy. Immunofluorescence was used to assess IgA deposition in the glomeruli and to measure expression of nephrin, podocin, and desmin. Real-time quantitative PCR was used to measure expression of nephrin, podocin, and desmin mRNAs. IgAN rats developed proteinuria at week-6 and this worsened over time. Pathological changes were evident under light microscopy at week-8 and under electron microscopy at week-4. Immunofluorescence analysis showed deposition of IgA in the kidneys of IgAN rats, but not control rats. IgAN rats had increased expression of glomerular podocin, nephrin, and desmin mRNAs and proteins at week-4. The expression of nephrin, podocin and desmin proteins and the expression of podocin and desmin mRNAs preceded the increase in urinary protein. Taken together, our study of a rat model of IgAN indicates that changes in the expression and distribution of nephrin, podocin, and desmin precede and may cause foot process fusion and proteinuria., H.-Y. Lu, ... [et al.]., and Obsahuje seznam literatury
The first trimester of pregnancy is characterized by continuous proliferation, invasion and differentiation of cytotrophoblasts. These processes are precisely controlled both, in space and time by molecules such as endothelin-1 (ET-1). ET-1 is expressed in human first trimester trophoblast and is known to stimulate cytotrophoblast proliferation through endothelin A and B receptor subtypes (ETA and ETB), and cytotrophoblast invasion through ETB. However, temporal changes of the ET system during the first trimester of pregnancy have not been previously studied. This study tested the hypothesis that ET-1 release, ETA and ETB expression are increased towards the end of the first trimester of pregnancy (weeks 10-12 vs. weeks 6-9), resulting in increased cytotrophoblast proliferation and invasion. Tissue samples were obtained from 17 surgical pregnancy interruptions (week 6-9: n=9; week 10-12: n=8). After cytotrophoblast isolation, the invasive and proliferative phenotypes were immune-separated by an α6-integrin antibody. Both proliferative and invasive cytotrophoblasts were cultured separately on plastic or Matrigel for 24 h. ET-1 release into the culture medium of both cytotrophoblast subtypes was measured by radioimmunoassay. ETA and ETB mRNA expression was measured by RT-PCR, and the ET-1 effect on cytotrophoblast proliferation and invasion was determined using proliferation and invasion assays, respectively. ET-1 release increased from early to late first trimester of pregnancy in both proliferative (1.8-4.5 fold) and invasive cytotrophoblasts (9.3-28 fold), especially when cultured on Matrigel. This was paralleled by less ETB mRNA on invasive cytotrophoblasts independent of the time period in first trimester, whereas ETA expression was similar on proliferative an invasive cytotrophoblasts. Proliferation and invasion of cytotrophoblasts under control conditions decreased from early to late first trimester. The ET-1/ET-receptor system changes between weeks 6-9 and 10-12 in pregnancy. Our data suggest an autocrine and endocrine ET-1 effect, which is stronger in late than in early first trimester of pregnancy paralleled by different stimulatory effects on trophoblast invasion and proliferation. In general, this suggests time as an additional effector of the critical processes governing placental development in the first trimester of human pregnancy., A. Majali-Martinez, S. Barth, U. Lang, G. Desoye, M. Cervar-Zivkovic., and Seznam literatury