The present investigation was directed to study the effect of in vitro or ex vivo NO donors, sodium nitroprusside and molsidomine, using isolated sliced adipose tissue or in the form of immobilized and perfused adipocytes on the basal and isoprenaline-stimulated lipolysis. The results demonstrated that 1) in vitro application of sodium nitroprusside to perfused adipocytes or molsidomine to sliced adipose tissues affects isoprenaline-induced lipolysis in two ways, an increase in lipolysis at low isoprenaline concentrations (which means the sensitization of adipose tissues to adrenergic effect by NO) and decreased adrenergic agonist-stimulated lipolysis at higher concentration of isoprenaline (a decrease in the maximum lipolytic effect of isoprenaline), 2) low concentrations of molsidomine alone induced lipolysis from adipose tissue which attained more than 60 % of that by isoprenaline (pD2 value for molsidomine = 11.2, while pD2 for isoprenaline = 8.17) while sodium nitroprusside did not affect the basal lipolysis significantly, 3) in vivo administration of molsidomine for 2 days reduced the maximum lipolytic effect of isoprenaline and (only non-significantly) increased the sensitivity to low doses of isoprenaline. In conclusion the present data demonstrate that NO plays an important role in adrenergic lipolysis in adipose tissues and further investigations are needed to unravel the exact role of NO in lipolysis., D. Lincová, D. Mišeková, E. Kmoníčková, N. Canová, H. Farghali., and Obsahuje bibliografii
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
We investigated the impact of a high-fat (HF) diet during pre- and post-weaning periods on the intestinal microbiota and alkaline phosphatase (AP) activity in male rats. Nutrition from birth was influenced by feeding rat dams with either a standard or HF diet. After weaning male pups nursed by control dams continued on a standard diet (CC) or HF diet (C-HF), while offspring nursed by HF dams continued on HF diet (HF) or standard diet (HF-C). The numbers of Bacteroides/Prevotella (BAC) and Lactobacillus/Enterococcus (LAB) in the gut were determined by FISH technique. HF pups displayed enhanced adiposity and increased AP activity (19 %), as well as higher LAB (P<0.001) and lower numbers of BAC (P<0.001) in the jejunum and colon than controls. In HF-C rats, post-weaning lower fat intake resulted in decreased fat deposition accompanied by reduced AP activity (20 %) compared to HF rats. Composition of the intestinal microbiota in these rats was not influenced. In contrast, in comparison with controls, C-HF rats displayed higher LAB (P<0.001) and lower BAC (P<0.001) together with increased adiposity and AP activity (14 %). These results indicate that consumption of diet with different fat content could modulate gut microbial/functional conditions depending on the period when the nutritional manipulation occurs., Z. Šefčíková, D. Bujňáková., and Obsahuje bibliografii
Cancer therapy with daunorubicin is limited by its cardiotoxicity. It has been suggested that daunorubicin-induced free radical generation can be involved. The precise molecular mechanism of daunorubicin-induced cardiotoxicity is still not well understood but it is believed that mitochondria play an important role in this process. It has been reported that flavonoids with antioxidant properties may prevent anthracycline-induced cardiotoxicity. In this work, we investigated the effects of daunorubicin and quercetin on mitochondrial enzyme activities such as ATPase, glutathione peroxidase (GPx) and glutathione reductase (GR). Moreover, we also studied the changes of outer mitochondrial membrane using synchronous fluorescence spectra. The actitivity of ATPase and GR were significantly increased after daunorubicin application. Pretreatment with quercetin significantly alleviated this increase. On the other hand, GPx activity was significantly decreased and quercetin prevented this decrease. Treatment with quercetin alone had no significant effect on the enzyme activity studied. Quercetin also completely prevented daunorubicin-induced changes in fluorescence of the outer mitochondrial membrane. In conclusion, our data indicate that quercetin may be useful in mitigating daunorubicin-induced cardiotoxicity., J. Guzy, J. Kušnír, M. Mareková, Z. Chavková, K. Dubayová, G. Mojžišová, L. Mirossay, J. Mojžiš., and Obsahuje bibliografii
Reoxygenation following hypoxic episodes can increase the risk for the development of ventricular arrhythmias, which, in addition to circadian aspects of reoxygen ation arrhythmias has not been studied extensively. The aim of the present study was to evaluate circadian changes in the electrical stability of the rat heart during reoxygenation following a hypovent ilatory episode. The electrical stability of the heart, defined in the present study as the ventricular arrhythmia threshold (VAT), was measured at 3 h intervals at clock times 09:00, 12:00, 15:00, 18:00, 21:00, 24:00, 03:00, 06:00 and 09:00 during 20 min hypoventilation (20 breaths/min, tidal volume = 0.5 ml/100 g body weight [n=17]) and subsequent 20 min reoxygenation (50 breaths/min, tidal volume = 1 ml/100 g body weight [n=4]) intervals. The experiments were performed usin g pentobarbital-anesthetized (40 mg/kg intraperitoneally) female Wistar rats that first underwent a four-week adaptation to a 12 h light:12 h dark regimen. Detailed analysis show ed that circadian VATs changed to biphasic rhythms at 10 min of hypoventilation. The VAT circadian rhythms were observed immediately following the commencement of reoxygenation, with the highest values measured between 12:00 and 15: 00, and the lowest values between 24:00 and 03:00. These resu lts suggest that myocardial vulnerability is dependent on the light:dark cycle and characteristics of pu lmonary ventilation., P. Švorc ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Resveratrol, which is a polyphenol present in red wines and vegetables included in human diets, exerts many biological effects. The aim of the present study was to investigate its effect on some activities of polymorphonuclear leukocytes, particularly the generation of superoxide anion (O2-) in whole blood, hypochlorous acid (HOCl) and nitric oxide (NO) production by isolated cells, and chemotaxis. Resveratrol showed significant dose-dependent inhibitory effect on all these activities. In particular, it inhibited O2- generation in stimulated but not in resting neutrophils, decreased HOCl much more than O2- production indicating an effect on myeloperoxidase secretion since HOCl production is directly and proportionally dependent on O2- generation and reduced cell motility. The small dose of resveratrol (4.38 nM) used is attainable with a diet including red wine and vegetables confirming its protective role against some pathological processes such as inflammation, coronary heart disease, and cancer., A. Cavallaro, T. Ainis, C. Bottari, V. Fimiani., and Obsahuje bibliografii
The physiological significance of serotonin released into the intestinal lumen for the regulation of motility is unknown in humans. The aim of this study was to evaluate the effect of serotonin infused into the lumen of the gastric antrum, duodenum or the jejunum, on antro-duodeno-jejunal contractility in healthy human volunteers. Manometric recordings were obtained and the effects of either a standard meal, continuous intravenous infusion of serotonin (20 nmol/kg/min) or intraluminal bolus infusions of graded doses of serotonin (2.5, 25 or 250 nmol) were compared. In addition, platelet-depleted plasma levels of serotonin, blood pressure, heart rate and electrocardiogram were evaluated. All subjects showed similar results. Intravenous serotonin increased migrating motor complex phase III frequency 3-fold and migrating velocity 2-fold. Intraluminal infusion of serotonin did not change contractile activity. Platelet-depleted-plasma levels of serotonin increased 2-fold following both intravenous and high doses of intraluminal infusions of serotonin. All subjects reported minor short-lived adverse effects following intravenous serotonin stimulation, while only half of the subjects reported minor short-lived adverse effects following intraluminal serotonin stimulations. We conclude that exogenous serotonin in the lumen of the upper part of the small intestine does not seem to change antro-duodeno-jejunal contractility significantly in healthy adult volunteers., M. B. Hansen, F. Arif, H. Gregersen, H. Bruusgaard, L. Wallin., and Obsahuje bibliografii a bibliografické odkazy
The effects of 8-days treatment with 17α-estradiol (33.3 μg/kg) and progesterone (1.7 mg/kg) on plasma lipids and fatty acid composition of plasma phospholipids were examined in intact (INT) and bilaterally common carotid arteries occluded (BCO) male Wistar rats. Significant decrease of triglyceride level was found in BCO rats after the estradiol treatment. Both hormones elevated proportion of 18:1n-7 fatty acid in INT, but they failed to have such an effect in BCO. Estradiol increased 22:5n-3 and total n-3 polyunsaturated fatty acids (PUFA) in intact, and decreased 18:2n-6 in BCO rats. Significantly lower level of total n-3 was found in progesterone-treated than in estradiol-treated BCO rats. Given that n-3 PUFA have many beneficial effects on cell and tissue function, while n-6 PUFA have mostly the opposite effects, estradiol, rather than progesterone, was seen to improve plasma lipids and phospholipids FA profiles in INT and BCO animals. Estradiol significantly elevated the estimated activity of Δ9-desaturases and progesterone of Δ5-desaturase in BCO group, with no effects in INT rats., S. Petrović, M. Takić, A. Arsić, V. Vučić, D. Drakulić, M. Milošević, M. Glibetić., and Obsahuje bibliografii
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
Many studies documented the relationship between elevated plasma concentrations of natriuretic peptides and cardiovascular diseases, especially heart failure. However, it is still uncertain whether physical exercise leads to a significant release of natriuretic peptide in healthy subjects. The aim of this study was to determine the effect of maximal physical activity on plasma BNP concentrations in healthy individuals within 3 hours after the short-term exercise. BNP plasma concentrations were measured in 15 healthy volunteers before, immediately after as well as 1 hour and 3 hours after bicycle spiroergometry. Maximal workload and exercise capacity were assessed in watts, wattseconds, metabolic equivalents and VO2max. Mean BNP plasma levels before, immediately after, 1 hour and 3 hours postexercise were 19.4±2.5; 30.6±4.7; 17.9±2.5 and 18.7±3.1 pg/ml, respectively. The increase of BNP concentrations immediately after exercise was statistically significant (p=0.0017) compared to baseline values. We did not find any correlation between the post-exercise increase of BNP levels and age, body mass index, maximal workload or exercise capacity. In conclusion, short-term maximal physical exercise in healthy individuals led to a fast and transient rise of plasma BNP concentrations, which remained well within normal range and far below the cut-off value for heart failure (100 pg/ml)., J. Krupička ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy