In the horse, the inflammation response to various pathologies (intestinal strangulations, laminitis, etc.) involves an excessive stimulation of the polymorphonuclear neutrophils releasing reactive oxygen species (ROS) and myeloperoxidase (MPO). The aim of the present work was to study the effect of natural polyphenols, curcumin oids and tetrahydrocurcuminoids (THC) on isolated stimulated equine neutrophils and on the activity of purified MPO. The ROS production and the release of MPO by activated neutrophils were measured by chemiluminescence and ELISA techniques, respectively. The activity of purified MPO was measured by studying its nitration, chlorination or oxidation capacity and by using an original method called SIEFED allowing the study of drug interaction with the enzyme without interferences of the medium. Curcuminoids and THC had dose-dependent inhibitory effects on ROS production and MPO release by activated neutrophils and on purified MPO activity. We suggest that the higher efficacy of curcuminoids versus THC could be explained, at least partially, by its chemical structure: the conjugated double bounds and the plane structure of curcuminoids made easier the neutralization of the radical species generated by activated neutrophils and the interaction of the drug with the active site of MPO. These inhibitory effects of curcuminoids on the oxidant activity of equine neutrophils and on MPO activity open therapeutic perspectives in equine pathologies with excessive inflammatory reactions., T. Franck, S. Kohnen, S. Grulke, P. Neven, Y. Goutman, F. Peters, B. Pirotte, G. Deby-Dupont, D. Serteyn., and Obsahuje bibliografii a bibliografické odkazy
Metformin is widely used in the treatment of Type 2 diabetes, however, mechanisms of its antihyperglycemic effect were not yet fully elucidated. Complex I of mitochondrial respiration chain is considered as one of the possible targets of metformin action. In this paper, we present data indicating that the inhibitory effect of metformin can be tested also in liver homogenate. Contrary to previous findings on hepatocytes or mitochondria under our experimental conditions, lower metformin concentrations and shorter time of preincubation give significant inhibitory effects. These conditions enable to study the mechanism of the inhibitory effect of metformin in small samples of biological material (50-100 mg wet weight) and compare more experimental groups of animals because isolation of mitochonria is unnecessary., E. Páleníčková ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Vitamin D status and the relationship between serum 25(OH) vitamin D concentrations and the components of insulin resistance were examined in 120 patients with chronic kidney disease stage 2 and 3. Insulin sensitivity/resistance was calculated by the quantitative insulin sensitivity check index (QUICKI). In this analysis, the prevalence of insulin resistance was 42 %. Only 17 % of patients had serum 25(OH) vitamin D concentration in the recommended range ( ≥ 30 ng/ml), 42 % suffered from vitamin D insufficiency and 41 % had moderate vitamin D deficiency. Insulin resistance significantly correlated with serum 25(OH)D and 1,25(OH) 2 D concentrations, renal function and protein excretion rate. Our results support the increasing evidence that vitamin D deficiency may be one of the factors participating in the development of insulin resistance already in the early stages of chronic kidney disease. and K. Štefíková ... [et al.].
Numerous studies concerning the cardiovascular system in SHR often yield controversial data. The background of this diversity has various roots, ranging from different vascular segments or areas studied up to the different age of experimental animals. Our study aimed to follow the BP as an integrated response of vascular system. This approach was justified since stabilized cardiac output in SHR was proved till 1 year of age. The groups of male SHR (aged 3, 5, 9, 17 and 52 weeks) and age-matched Wistar rats were used. Significant basal BP difference between SHR and Wistar rats was found at 9 weeks of age and continued till the age of 52 weeks, reaching 189.6±11.9 mm Hg in SHR and 117.3±6.9 mm Hg in Wistar rats (P<0.01). The significant difference in BP increase to two doses of noradrenaline (0.1μg and 1 μg) between SHR and control rats was also found at the age of 9 weeks. At 52 weeks the BP increment to two doses of noradrenaline was in SHR 19.7±2.0 mm Hg and 60.5±3.9 mm Hg and in Wistar rats 7.4±1.9 mm Hg and 40.5±3.2 mm Hg (P<0.01). The hypotensive response to acetylcholine (0.1 μg, 1 μg and 10 μ) in SHR was enhanced at 17 weeks of age only and this amplification persisted till the age of 52 weeks. In 52-week-old SHR the hypotensive response to three doses was 69.9±10.2 mm Hg, 87.5±11.8 mm Hg and 103.4±10.6 mm Hg, while in Wistar rats it was 37.4 4.2 mm Hg P<0.0), 62.3±3.5 mm Hg (P<0.01) and 73.5±2.8 mm Hg (P<0.05). In conclusion, the efficiency of cardiovascular system of SHR to respond to noradrenaline was already enhanced from 9 weeks of age, whereas the response to acetylcholine was not augmented before the age of 17 weeks., M. Gerová, F. Kristek., and Obsahuje bibliografii a bibliografické údaje
The two i nferior colliculi (IC) are paired structures in the midbrain that are connected to each other by a bundle of commissural fibers. The fibers play an important role in coordinating sound signal processing between the two inferior colliculi. This study examined inter-collicular suppression on sound signal processing in amp litude domain of mice by measuring the rate-amplitude functions (RAFs) of neurons in one IC during the electrical stimulation of the opposite IC. Three types (monotonic, saturated and non-monotonic) RAFs of collicular neurons were measured before and durin g inter-collicular suppression. Inter-collicular suppression significantly increased the slope, decreased the dynamic range and narrowed down the responsive amplitude of all RAFs to high amplitude level but did not change the type of most (36/43, 84 % ) RAFs. As a result, all types of RAFs were compressed at a greater degree at low than at high sound amplitude during inter-collicular suppression. These data indicate that inter-collicular suppression improve sound processing in the high amplitude domain., Liang Cheng, Hui-Xian Mei, Yun Huang., and Obsahuje bibliografii
In a frog neuromuscular preparation of m. sartorius, glutamate had a reversible dose-dependent inhibitory effect on both spontaneous miniature endplate potentials (MEPP) and nerve stimulation-evoked endplate potentials (EPP). The effect of glutamate on MEPP and EPP is caused by the activation of metabotropic glutamate receptors, as it was eliminated by MCPG, an inhibitor of group I metabotropic glutamate receptors. The depression of evoked EPP, but not MEPP frequency was removed by inhibiting the NO production in the muscle by L-NAME and by ODQ that inhibits the soluble NO-sensitive guanylyl cyclase. The glutamate-induced depression of the frequency of spontaneous MEPP is apparently not caused by the stimulation of the NO cascade. The particular glutamate-stimulated NO cascade affecting the evoked EPP can be down-regulated also by adenosine receptors, as the glutamate and adenosine actions are not additive and application of adenosine partially prevents the further decrease of quantal content by glutamate. On the other hand, there is no obvious interaction between the glutamatemediated inhibition of EPP and inhibitory pathways triggered by carbacholine and ATP. The effect of glutamate on the evoked EPP release might be due to NO-mediated modulation (phosphorylation) of the voltage-dependent Ca2+ channels at the presynaptic release zone that are necessary for evoked quantal release and open during EPP production., S. Adámek ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Leptin is a hormone primarily secreted by adipocytes and participating in the regulation of food intake and energy expenditure. Its blood levels usually correlate with adiposity. The secretion of this hormone is affected, among others, by food consumption, insulin, fasting and cold exposure. Regulation of leptin secretion depends on many intracellular events. It is known that the activation of mTOR (the mamma lian target of rapamycin) as well as increase in ATP and malonyl-CoA content in adipocytes enhance secretion of leptin. The rise in intracellular cAMP and fatty acids is thought to evoke the opposite effect. Moreover, the undisturbed action of endogenous adenosine in adipocytes and the proper intracellular Ca2+ concentration in these cells were also found to have an important function in leptin release. The role of mTOR, ATP, cAMP, fatty acids, malonyl-CoA, adenosine and Ca2+ in the regulation of leptin secretion from adipocytes is discussed., T. Szkudelski., and Obsahuje bibliografii a bibliografické odkazy
Production of superoxide anions in the incubation medium of hippocampal slices can induce long-term potentiation (LTP). Other reactive oxygen species (ROS) such as hydrogen peroxide are able to modulate LTP and are likely to be involved in aging mechanisms. The present study explored whether intracerebro-ventricular (ICV) injection of oxidant or antioxidant molecules could affect LTP in vivo. With this aim in mind, field excitatory post-synaptic potentials (fEPSPs) elicited by stimulation of the perforant pathway were recorded in the dentate gyrus of the hippocampal formation in urethane-anesthetized rats. N-acetyl-L-cysteine, hydrogen peroxide (H2O2) or hypoxanthine/xanthine-oxidase solution (a superoxide producing system) were administrated by ICV injection. The control was represented by a group injected with saline ICV. Ten minutes after the injection, LTP was induced in the granule cells of the dentate gyrus by high frequency stimulation of the perforant pathway. Neither the H2O2 injection or the N-acetyl-L-cysteine injection caused any variation in the fEPSP at the 10-min post-injection time point, whereas the superoxide generating system caused a significant increase in the fEPSP. Moreover, at 60 min after tetanic stimulation, all treatments attenuated LTP compared with the control group. These results show that ICV administration of oxidant or antioxidant molecules can modulate LTP in vivo in the dentate gyrus. Particularly, a superoxide producing system can induce potentiation of the synaptic response. Interestingly, ICV injection of oxidants or antioxidants prevented a full expression of LTP compared to the saline injection., A. Viggiano, E. Viggiano, M. Monda, A. Viggiano, S. Ascione, S. Amaro, B. de Luca., and Obsahuje bibliografii a bibliografické odkazy