Thiazolidinediones are insulin-sensitizing drugs acting through peroxisome proliferator- activated receptor (PPAR)-γ. The aim of our study was to evaluate the effect of 5-month treatment with PPAR-γ agonist – rosiglitazone (4 mg/day), on the circulating markers of endothelial dysfunction and to evaluate the role of changes in endocrine function of adipose tissue in this process. Biochemical and metabolic parameters, circulating adiponectin, resistin, ICAM-1, VCAM-1, E-selectin, P-selectin, PAI-1, myeloperoxidase (MPO), and matrix metalloproteinase-9 (MMP-9) concentrations were assessed in 10 women with type 2 DM before and after rosiglitazone treatment and in a control group of healthy women. At baseline, diabetic group had significantly higher serum concentrations of glucose, glycated hemoglobin, V-CAM and PAI-1 compared to control group. Adiponectin levels tended to be lower in diabetic group, while resistin concentrations did not differ from control group. Rosiglitazone treatment improved diabetes compensation, significantly reduced VCAM-1, PAI-1 and E-selectin concentrations and increased adiponectin levels, while it did not affect serum resistin concentrations. Adiponectin concentrations at baseline were inversely related to E-selectin and MPO levels, this correlation disappeared after rosiglitazone treatment. We conclude that 5-month rosiglitazone treatment significantly reduced several markers of endothelial dysfunction. This effect could be at least in part attributable to marked increase of circulating adiponectin levels., R. Doležalová, M. M. Haluzík, L. Bošanská, Z. Lacinová, Z. Kasalová, T. Štulc, M. Haluzík., and Obsahuje bibliografii a bibliografické odkazy
Autophagy-lysosomal pathway is a cellular mechanism ensuring degradation of various macromolecules like proteins or triacylglycerols (TAG). Its disruption is related to many pathological states, including liver steatosis. We compared the effect of short- and long-established steatosis on the intensity of autophagy-lysosomal pathway in rat liver. The experiments were carried out on 3-month old Wistar rats fed standard (SD) or highfat diet for 2 (HF-2) or 10 (HF-10) weeks. HF diet administered animals accumulated an increased amount of TAG in the liver (HF-2→HF-10). Autophagy flux was up-regulated in HF-2 group but nearly inhibited after 10 weeks of HF administration. The expression of autophagy related genes was up-regulated in HF-2 but normal in HF-10. In contrast, total activities of two lysosomal enzymes, lysosomal lipase (LAL) and acid phosphatase, were unaffected in HF-2 but significantly increased in HF-10 groups. mRNA expression of lysosomal enzymes was not affected by the diet. We conclude that in a state of metabolic unbalance (steatosis), autophagy machinery and lysosomal enzymes expression are regulated independently. The accumulation of TAG in the liver is associated with the increase of total LAL activity and protein expression. In contrast, the autophagy response is bi-phasic and after rapid increase it is significantly diminished. This may represent an adaptive mechanism that counteracts the excessive degradation of substrate, i.e. TAG, and eliminate over-production of potentially hazardous lipiddegradation intermediates., Z. Papáčková, ... [et al.]., and Obsahuje seznam literatury
Transthoracic echocardiography (TTE) has become an important modality for the assessment of cardiac structure and function in animal experiments. The acquisition of echocardiographic images in rats requires sedation/anesthesia to keep the rats immobile. Commonly used anesthetic regimens include intraperitoneal or inhalational application of various anesthetics. Several studies have compared the effects of anesthetic agents on echocardiographic parameters in rats; however, none of them examined the effects of different concentrations of inhalational anesthetics on echocardiographic parameters. Accordingly, the aim of this study was to examine the effects of different concentrations of isoflurane used for anesthesia during TTE examination in rats on basic echocardiographic parameters of left ventricular (LV) anatomy and systolic function. TTE examinations were performed in adult male Wistar rats (n=10) anesthetized with isoflurane at concentrations of 1.5-3 %. Standard echocardiograms were recorded for off-line analysis. An absence of changes in basic echocardiographic parameters of LV anatomy and systolic function was found under isoflurane anesthesia using concentrations between 1.5-2.5 %. An isoflurane concentration of 3 % caused a small, but statistically significant, increase in LV chamber dimensions without a concomitant change in heart rate or fractional shortening. For the purpose of TTE examination in the rat, our results suggest that isoflurane concentrations ≤ 2.5 % can be safely recommended., H. Říha ... [et al.]., and Obsahuje seznam literatury
Chronic smoking can cause imbalance in endocrine homeostasis and impairment of fertility in both sexes. The male reproductive system is more resilient, still the literature provides conflicting results about the influence of smoking on the steroid hormone levels. The data about smoking cessation are limited; there has not yet been a study primarily focused on changes in steroids levels. In our study, we analyzed levels of testosterone, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphate (DHEAS), cortisol and sex hormone-binding globulin (SHBG) in male smokers and during smoking cessation. Monitored analytes were determined by RIA. The free testosterone index was calculated. Basal samples of men successful and unsuccessful in smoking cessation did not differ and monitored hormones could hardly predict success of smoking cessation. After one year without smoking, a significant BMI increase and SHBG decrease in former smokers was observed. The decrease in total testosterone was non-significant. Changes in SHBG and testosterone did not correlate with BMI, presumably due to the direct effect of smoking cessation., H. Hruškovičová, ... [et al.]., and Obsahuje seznam literatury
Influence of the regulatory system mediated by adenosine A3 receptors on the functioning of erythropoiesis and thrombopoiesis was studied by means of evaluation of the numbers and attributes of peripheral blood erythrocytes and platelets, as well as of erythroid bone marrow progenitor cells in adenosine A3 receptor knock-out (Adora3tm1Jbsn/Adora3tm1Jbsn, A3AR(-/-)) mice and their wild-type C57BL/6 counterparts, both males and females. Minor but statistically significant disturbances in the properties of erythrocytes, namely in the parameters of mean erythrocyte volume and mean erythrocyte hemoglobin were observed in A3AR(-/-) mice. In addition, adenosine A3 receptor knock-out mice were found to exhibit an expressive, statistically significant decrease of their blood platelet count, amounting to 17 % and 21 % in males and females, respectively. This decrease in platelet levels was accompanied by a significant 17 % decline in the plateletcrit in both sexes. The obtained data can help to define therapeutic applications based on the principle of adenosine receptor signaling., M. Hofer, ... [et al.]., and Obsahuje seznam literatury
Clinical studies showed that GABAB receptor agonists improve symptoms in patients with gastroesophageal reflux disease. One proposed mechanism of this effect is direct inhibition of the gastroesophageal vagal tension mechanosensors by GABAB agonists leading to reduction of reflux. In addition to tension mechanosensors, the vagal nodose ganglion supplies the esophagus with nociceptive C-fibers that likely contribute to impairment of esophageal reflex regulation in diseases. We hypothesized that GABAB agonists inhibit mechanically-induced activation of vagal esophageal nodose C-fibers in baseline and/or in sensitized state induced by inflammatory mediators. Ex vivo extracellular recordings were made from the esophageal nodose C-fibers in the isolated vagally-innervated guinea pig esophagus. We found that the selective GABAB agonist baclofen (100- 300 μM) did not inhibit activation of esophageal nodose C-fibers evoked by esophageal distention (10-60 mmHg). The mechanical response of esophageal nodose C-fibers can be sensitized by different pathways including the stimulation of the histamine H1 receptor and the stimulation the adenosine A2A receptor. Baclofen failed to inhibit mechanical sensitization of esophageal nodose Cfibers induced by histamine (100 μM) or the selective adenosine A2A receptor agonist CGS21680 (3 nM). Our data suggest that the direct mechanical inhibition of nodose C-fibers in the esophagus is unlikely to contribute to beneficial effects of GABAB agonists in patients with esophageal diseases., M. Brozmanová, ... [et al.]., and Obsahuje seznam literatury
Strenuous exercise induces delayed-onset muscle damage including oxidative damage of cellular components. Oxidative stress to muscle cells impairs glucose uptake via disturbance of insulin signaling pathway. We investigated glucose uptake and insulin signaling in relation to oxidative protein modification in muscle after acute strenuous exercise. ICR mice were divided into sedentary and exercise groups. Mice in the exercise group performed downhill running exercise at 30 m/min for 30 min. At 24 hr after exercise, metabolic performance and insulin-signaling proteins in muscle tissues were examined. In whole body indirect calorimetry, carbohydrate utilization was decreased in the exercised mice along with reduction of the respiratory exchange ratio compared to the rested control mice. Insulin-stimulated uptake of 2-deoxy-[3 H]glucose in damaged muscle was decreased after acute exercise. Tyrosine phosphorylation of insulin receptor substrate (IRS)-1 and phosphatidyl-3-kinase/Akt signaling were impaired by exercise, leading to inhibition of the membrane translocation of glucose transporter 4. We also found that acute exercise caused 4-hydroxy-nonenal modification of IRS-1 along with elevation of oxidative stress in muscle tissue. Impairment of insulin-induced glucose uptake into damaged muscle after strenuous exercise would be related to disturbance of insulin signal transduction by oxidative modification of IRS-1., W. Aoi ... [et al.]., and Obsahuje seznam literatury
a1_We have investigated expression of skeletal calsequestrin (CSQ1) and fiber type composition in normal and regenerated fast and slow skeletal muscles and in the left heart ventricles of euthyroid (EU), hypothyroid (HY) and hyperthyroid (TH) adult inbred Lewis strain rats. The CSQ1 level was determined by SDS-PAGE followed by Western blot analysis. CSQ1 gene expression was assessed using reverse transcription and subsequent real time polymerase chain reaction. Muscle regeneration was achieved by intramuscular grafting of either soleus or extensor digitorum longus (EDL) from 3- to 4-week-old rats to either EDL or soleus muscle of 2-month-old rats. The fiber type composition was assessed by a stereological method applied to stained muscle cross sections. We found that the protein and mRNA levels for CSQ1 were highest in the EDL muscle, the relative CSQ1 protein levels in the soleus muscle were two times lower and the transcript levels more than 5 times lower compared to the EDL. In the left heart ventricle, protein isoform and CSQ1 transcript were also present, although at protein level, CSQ1 was hardly detectable. TH status increased and HY status decreased the expression of CSQ1 in the EDL, but its relative levels in the soleus and in the heart did not change. The regenerated soleus transplanted into EDL, as well as EDL transplanted into soleus exhibited protein and mRNA levels of CSQ1 corresponding to the host muscle and not to the graft source. TH status increased the percentages of the fastest 2X/D and 2B fibers at the expense of slow type 1 and fast 2A fibers in the EDL and that of fast 2A fibers in the soleus at the expense of slow type 1 fibers. HY status led to converse fiber type changes., a2_We suggest that the observed changes in CSQ1 levels in TH and HY compared to EU rats can be related to fiber type changes caused by alteration of the thyroid status rather than to the direct effect of thyroid hormones on CSQ1 gene expression., T. Soukup ... [et al.]., and Obsahuje seznam literatury
Fatty acid composition of adipose tissue changes with weight loss. Palmitoleic acid as a possible marker of endogenous lipogenesis or its functions as a lipokine are under debate. Objective was to assess the predictive role of adipose triglycerides fatty acids in weight maintenance in participants of the DIOGENES dietary intervention study. After an 8-week low calorie diet (LCD) subjects with > 8 % weight loss were randomized to 5 ad libitum weight maintenance diets for 6 months: low protein (P)/low glycemic index (GI) (LP/LGI), low P/high GI (LP/HGI), high P/low GI (HP/LGI), high P/high GI (HP/HGI), and a control diet. Fatty acid composition in adipose tissue triglycerides was determined by gas chromatography in 195 subjects before the LCD (baseline), after LCD and weight maintenance. Weight change after the maintenance phase was positively correlated with baseline adipose palmitoleic (16:1n-7), myristoleic (14:1n-5) and trans-palmitoleic acid (16:1n-7t). Negative correlation was found with baseline oleic acid (18:1n-9). Lower baseline monounsaturated fatty acids (14:1n-5, 16:1n-7 and trans 16:1n-7) in adipose tissue triglycerides predict better weight maintenance. Lower oleic acid predicts lower weight decrease. These findings suggest a specific role of monounsaturated fatty acids in weight management and as weight change predictors., M. Kunešová, ... [et al.]., and Obsahuje seznam literatury
Aluminofluoride complexes (AlFx) form spontaneously in aqueous solutions containing fluoride and traces of aluminum ions and appear to act as phosphate analogs. These complexes have become widely utilized in laboratory investigations of various guanine nucleotide-binding proteins. Reflecting on many laboratory studies, a new mechanism of fluoride and aluminum action on the cellular level is being suggested. The long-term synergistic effects of these ions in living environment and their hidden danger for human health are not yet fully recognized., A. Strunecká, O. Strunecký, J. Patočka., and Obsahuje bibliografii