The functional aversive stimulus properties of several IP doses of (±)-amphetamine (1.25-10 mg.kg-1), 2-phenylethylamine (PEA, 2.5-10 mg.kg-1, following inhibition of monoamine oxidase with pargyline 50 mg.kg-1) and phenylethanolamine (6.25-50 mg.kg 1) were measured with the conditioned taste aversion (CTA) paradigm. A two bottle choice procedure was used, water vs. 0.1 % saccharin with one conditioning trial and three retention trials. (±)-Amphetamine and phenylethanolamine induced a significant conditioned taste aversion but PEA did not. (±)-Amphetamine and PEA increased spontaneous locomotor activity but phenylethanolamine had no effects on this measure. Measurement of whole brain levels of these drugs revealed that the peak brain elevation of PEA occurred at approximately 10 min whereas the peak elevations of (±)-amphetamine and phenylethanolamine occurred at approximately 20 min. The present failure of PEA to elicit conditioned taste aversion learning is consistent with previous reports for this compound. The differential functional aversive stimulus effects of these three compounds are surprising since they exhibit similar discriminative stimulus properties and both (±)-amphetamine and PEA are self-administered by laboratory animals. The present data suggest that time to maximal brain concentrations following peripheral injection may be a determinant of the aversive stimulus properties of PEA derivatives., A.J. Greenshaw, S. Turkish, B.A. Davis., and Obsahuje bibliografii
It is well known that the training level of a muscle belongs to the parameters that affect the H-reflex response amplitude. The aim of this study was to investigate the effects of training type on H- and T-reflex response parameters. For this purpose, 20 long-distance athletes (group I, test group), 18 short-distance athletes (group II, test group) and 20 non-trained subjects (group III, control group) were involved in this study in which the H- and T-reflex amplitude and latency values were measured. The H-reflex amplitude and latency values found in groups I, II and III were 3.64±0.28 mV and 26.88±1.45 ms, 3.17±0.26 mV and 26.19±1.89 ms, and 6.07±0.34 mV and 26.77±1.32 ms, respectively. The T-reflex amplitude and latency values of the groups I, II and III were 3.30±0.18 mV and 32.01±1.02 ms, 3.11±0.20 mV and 31.47±1.16 ms, 4.24±0.21 mV and 31.47±1.16 ms, respectively. There was no statistically significant difference between the groups with respect to latencies of H- and T-reflexes (p>0.05). In both test groups, the amplitudes of the H-reflex and T-reflex were significantly smaller than the control group (p<0.05). The results of this study suggest that training of muscles affect the H- and T-reflex response parameters., R. Ozmerdivenli, S. Bulut, T. Urat, A. Ayar., and Obsahuje bibliografii
C-reactive protein (CRP) is a marker of arterial inflammation while lipoprotein-associated phospholipase A2 (Lp-PLA2) is related to plaque instability. The aim of this study was to evaluate the correlation between the risk of unstable plaque presenting as acute coronary syndrome (ACS) and Lp-PLA2, and to assess the influence of statins on interpretation of Lp-PLA2. A total of 362 consecutive patients presenting to the emergency department (ED) with acute chest pain suggestive of ACS were evaluated by cardiologists as STEMI, NSTEMI, or unstable angina, and non- ACS. Serum biomarkers measured on admission: troponin I, Creactive protein (Abbott), and Lp-PLA2 (DiaDexus). Four groups were defined according to the final diagnos-; non- ACS/statin+. Lp-PLA2 was highest in ACS/statin- group; statins decreased Lp-PLA2 both in ACS and non-ACS of about 20 %. Lp- PLA2 was higher in ACS patients in comparison with non-ACS patients group without respect to statin therapy (p<0.001). Lp- PLA2 predicted worse outcome (in terms of acute coronary syndrome) effectively in patients up to 62 years; limited prediction was found in older patients. C-reactive protein (CRP) failed to discriminate four groups of patients. Statin therapy and age should be taken into consideration while interpreting Lp-PLA2 concentrations and lower cut-off values should be used for statintreated persons., J. Franeková, J. Kettner, Z. Kubíček, A. Jabor., and Obsahuje bibliografii
To further investigate the role of insulin during preimplantation embryo development, we compared the effects of insulin on the development of mouse and bovine preimplantation embryos and on cell proliferation during culture in vitro in simplex media. The influence of insulin on the development of mouse zygotes was determined during cultivation in mSOF medium, alone or supplemented with glucose. Similarly, the effects of insulin on the bovine preimplantation embryo development were studied in mSOF medium. The addition of insulin into mSOF medium enhanced significantly the number of cells per mouse blastocyst. Moreover, when mSOF medium was supplemented with insulin and 0.2 mmol.l-1 glucose, the percentage of hatched blastocysts and the mean cell number of mouse blastocysts were significantly higher. Insulin had no significant effect on the development of bovine embryos, produced by in vitro fertilization of in vitro matured oocytes. Neither the rates of developing embryos nor the mean number of cells in blastocysts were different in comparison with control embryos. Our results suggest that the in vitro development of mouse embryos could be enhanced by the addition of insulin to the culture medium and is further improved by the addition of glucose. In contrast to this our results indicate that insulin has no detectable beneficial effect on the preimplantation development of bovine embryos in mSOF medium., J. Mihalik, P. Rehák, J. Koppel., and Obsahuje bibliografii
The pathophysiological processes underlying the development of diabetic osteopenia has not hitherto been elucidated. Induction of streptozotocin diabetes leads in our experiments to decrease of bone density, ash, mineral content and to thinner cortical width compared to control male rats. In order to investigate the pathogenetic role of bone resorption by osteoclasts in streptozotocin-induced diabetes, we determined the circulating levels of tartrate-resistant acid phosphatase (TRAP), a biochemical marker for bone resorption. Plasma TRAP values in diabetic rats did not differ from their corresponding controls. Streptozotocin diabetes by itself did not have any effect on the weight of seminal vesicles which are highly testosterone-dependent. Low doses of nitric oxide cause bone resorption, but higher doses of NO inhibit bone resorbing activity. We examined the effect of L-NAME (inhibitor of nitric oxide production) after six weeks of administration to diabetic rats. There was no further significant loss of bone mineral density, ash and mineral content or tibia weight in diabetic rats treated with L-NAME. L-NAME itself did not decrease bone metabolism. In our study no evidence of an increased bone resorption was found. Our results have indicated that a predominance of bone resorption over bone formation is not involved in the pathogenesis of diabetes-associated osteopenia. Inhibition of NO neither increased osteoclastic activity (TRAP) nor induced osteopenia in L-NAME-treated rats. This suggests a possibility that NO is not involved in the pathogenesis of diabetic osteopenia., P. D. Broulík, M. Haluzík, J. Škrha., and Obsahuje bibliografii
We investigated the actions of dantrolene Ca2+-induced on Ca2+-release (CICR) evoked by action potentials in cultured rat sensory neurons. The effect of dantrolene on action potential after-depolarization and voltage-activated calcium currents was studied in cultured neonatal rat dorsal root ganglion cells (DRG) using the whole-cell patch-clamp technique. Depolarizing current injection evoked action potentials and depolarizing after-potentials, which are activated as a result of CICR following a single action potential in some cells. The type of after-potentials was determined by inducing action potentials from the resting membrane potential. Extracellular application of dantrolene (10 mM) abolished after-depolarizations without affecting action potential properties. Furthermore, dantrolene significantly reduced repetitive action potentials after depolarizing current injection into these neurons, but had no significant effect on the steady-state current voltage relationship of calcium currents in these neurons. We conclude that dantrolene inhibits the induction of action potential after depolarizations by inhibiting CICR in cultured rat sensory neurons., A. Ayar, H. Kelestimur., and Obsahuje bibliografii
Acetylcholinesterase inhibitors (AChEIs) are used in the treatment of myasthenia gravis (MG). We investigated the effects of AChEIs on peripheral nicotinic receptors (nAChR), which play a crucial role in the treatment of MG symptoms. The positive modulation of those receptors by AChE inhibitors could have an added value to the anti-AChE activity and might be useful in the therapy of MG. Furthermore, to estimate the potential drawbacks of the compounds, cytotoxicity has been assessed on various cell lines. The whole-cell mode of the patch-clamp method was employed. The experiments were performed on medulloblastoma/rhabdomyosarcoma cell line TE671 expressing human embryonic muscle-like receptor with subunits α2βγδ. The effect of the compounds on cell viability was measured by standard MTT assay (Sigma Aldrich) on ACHN (renal cell adenocarcinoma), HeLa (immortal cell line derived from a cervical carcinoma), HEPG2 (hepatocellular carcinoma) and BJ (skin fibroblasts) cell lines. No positive modulation by the tested AChE inhibitors was observed. Moreover, the compounds exhibited antagonistic activity on the peripheral nAChR. Standard drugs used in MG treatment were shown to be less potent inhibitors of muscle-type nAChR than the newly synthesized compounds. The new compounds showed very little effect on cell viability, and toxicities were comparable to standards. Newly synthesized AChEIs inhibited peripheral nAChR. Furthermore, the inhibition was higher than that of standards used for the treatment of MG. They could be used for the study of nAChR function, thanks to their high antagonizing potency and fast recovery of receptor activity after their removal. However, since no positive modulation was observed, the new compounds do not seem to be promising candidates for MG treatment, even though their cytotoxic effect was relatively low., V. Sepsova, J. Krusek, J. Zdarova Karasova, F. Zemek, K. Musilek, K. Kuca, O. Soukup., and Obsahuje bibliografii
Paola Bertoli, Veronica Grembi., Obsahuje bibliografii a bibliografické odkazy., České resumé, and Vydává: Univerzita Karlova, Centrum pro ekonomický výzkum a doktorské studium, Národohospodářský ústav AV ČR
Alloxan and streptozotocin are widely used to induce experimental diabetes in animals. The mechanism of their action in B cells of the pancreas has been intensively investigated and now is quite well understood. The cytotoxic action of both these diabetogenic agents is mediated by reactive oxygen species, however, the source of their generation is different in the case of alloxan and streptozotocin. Alloxan and the product of its reduction, dialuric acid, establish a redox cycle with the formation of superoxide radicals. These radicals undergo dismutation to hydrogen peroxide. Thereafter highly reactive hydroxyl radicals are formed by the Fenton reaction. The action of reactive oxygen species with a simultaneous massive increase in cytosolic calcium concentration causes rapid destruction of B cells. Streptozotocin enters the B cell via a glucose transporter (GLUT2) and causes alkylation of DNA. DNA damage induces activation of poly ADP-ribosylation, a process that is more important for the diabetogenicity of streptozotocin than DNA damage itself. Poly ADP-ribosylation leads to depletion of cellular NAD+ and ATP. Enhanced ATP dephosphorylation after streptozotocin treatment supplies a substrate for xanthine oxidase resulting in the formation of superoxide radicals. Consequently, hydrogen peroxide and hydroxyl radicals are also generated. Furthermore, streptozotocin liberates toxic amounts of nitric oxide that inhibits aconitase activity and participates in DNA damage. As a result of the streptozotocin action, B cells undergo the destruction by necrosis., T. Szkudelski., and Obsahuje bibliografii
Recent studies have demonstrated that some microRNAs (miRNAs) inhibit bone formation by inhibiting the translation of specific genes. Several in vitro studies have suggested that miR - 23a inhibits osteogenic differentiation by suppressing the translation of Runx2, a transcription factor essential for osteoblastogenesis, and of Sa tb2, a member of the special AT-rich binding protein family. In the pr esent study, we used a gain -of-function approach to determine the roles of miR -23a in bone formation and homeostasis in vivo . The miR -23a transgenic (Tg) mice grew normally and their body size and weight were similar to those of wild -type (WT) littermates. Bone structure and morphology were similar in Tg and WT mice. Furthermore, the numbers of osteoblasts and osteoclasts, as well as their activities in bone were similar between Tg and WT mice. Our results indicate that miR -23 has limited roles in bone form ation and maintenance in vivo in mice., J. Park, S. Wada, T. Ushida, T. Akimoto., and Obsahuje bibliografii