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Thrombin, also known as an active plasma coagulation factor II, belongs to the family of serine proteases and plays a crucial role in blood coagulation process. The process of thrombin generation is the central event of the hemostatic process and regulates blood coagulant activity. For this reason, thrombin inhibition is key to successful novel antithrombotic pharmacotherapy. The aim of our present study was to examine the effects of the well-known polyphenolic compounds on the activity of thrombin, by characterization of its interaction with selected polyphenols using different biochemical methods and biosensor BIAcore analyses. Only six compounds, cyanidin, quercetin, silybin, cyanin, (+)-catechin and (−)-epicatechin, of all examined in this study polyphenols caused the inhibition of thrombin amidolytic activity. But only three of the six compounds (cyanidin, quercetin and silybin) changed thrombin proteolytic activity. BIAcore analyses demonstrated that cyanidin and quercetin caused a strong response in the interaction with immobilized thrombin, while cyanin and (−)-epicatechin induced a low response. Lineweaver-Burk curves show that used polyphenol aglycones act as competitive thrombin inhibitors. Our results suggest that polyphenolic compounds might be potential structural bases and source to find and project nature-based, safe, orally bioavailable direct thrombin inhibitors. [ABSTRACT FROM AUTHOR]

A systematic study of crystal lattice reorientation in early stages of recrystallization has been carried out to correlate the orientations of recrystallization nuclei with the deformation microtexture and with slip systems. Microstructure and texture of Al–1 wt.% Mn single crystals of unstable initial orientations of {112}〈111〉, {100}〈001〉 and {001}〈110〉 have been examined by high-resolution field-emission gun scanning electron microscope local orientation measurements. All single crystals were channel-die deformed at room temperature and then annealed for a short time. It was shown that often observed presence of the 〈112〉 directions as rotation axes in the formation of new nuclei orientation directly suggested a close link with the deformation process. [ABSTRACT FROM AUTHOR]

Our understanding of the effects of long-term denervation on skeletal muscle is heavily influenced by an extensive literature based on the rat. We have studied physiological and morphological changes in an alternative model, the rabbit. In adult rabbits, tibialis anterior muscles were denervated unilaterally by selective section of motor branches of the common peroneal nerve and examined after 10, 36, or 51 wk. Denervation reduced muscle mass and cross-sectional area by 50–60% and tetanic force by 75%, with no apparent reduction in specific force (force per cross-sectional area of muscle fibers). The loss of mass was associated with atrophy of last fibers and an increase in fibrous and adipose connective tissue; the diameter of slow fibers was preserved. Within fibers, electron microscopy revealed signs of ultrastructural disorganization of sarcomeres and tubular systems. This, rather than the observed transformation of fiber type from IIx to IIa, was probably responsible for the slow contractile speed of the muscles. The muscle groups denervated for 10, 36, or 51 wk showed no significant differences. At no stage was there any evidence of necrosis or regeneration, and the total number of fibers remained constant. These changes are in marked contrast to the necrotic degeneration and progressive decline in mass and force that have previously been found in long-term denervated rat muscles. The rabbit may be a better choice for a model of the effects of denervation in humans, at least up to 1 yr after lesion. [ABSTRACT FROM AUTHOR]

The crystallography of recrystallization has been investigated in channel-die deformed pure aluminium bicrystals with {100}<011>/{110}<001> orientations. The microstructural and microtextural changes during the early stages of recrystallization were followed by systematic local orientation measurements using scanning and transmission electron microscopes. In particular, orientation mapping combined with in situ sample heating was used to investigate the formation and growth of new grains at very early stages of recrystallization. Grain boundary migration and ‘consumption’ of the as-deformed areas was always favoured along directions parallel to the traces of the {111} slip planes that had been most active during deformation. [ABSTRACT FROM AUTHOR]

Seven paraplegic Functional Electrical Stimulation (FES) experienced users volunteered to test a newly developed eight channel stimulation system. The goal was to discover the influence of various stimulation parameters on the gait quality. As additional task the usability should be improved and simplified as much as possible. Commercially available hydrogel electrodes were attached to quadriceps and gluteus muscles to achieve hip and knee extension, to peroneal nerve to elicit flexion reflex and later also to adductor muscles. All patients were positive about the handling of the stimulation system. Especially the wireless remote control was highly approved. First results demonstrate the importance of an amplitude ramp during stimulation onset (0.1-0.4 s) resulting in a smooth and more 'natural' movement. For an adequate step length and walking speed the timing of quadriceps and peroneal nerve stimulation at the end of the swing phase are crucial. Experienced patients with a higher walking speed require a short swing phase and an overlap of quadriceps decay and peronaeus onset (0-0.2 s). Activation of the adductor muscles reduces knee abduction and lead to a better knee trajectory during standing up and better leg movement during the swing phase. Patients can perform 15-25 steps per minute with a step length of 20-30 cm. The walking distance until exhaustion or muscle fatigue occurs is 4-60 m. The analysis of the used stimulation sequences brought up guidelines for a fast and effective parameter optimization procedure. [ABSTRACT FROM AUTHOR]

Evidence suggests that metabotropic glutamate receptors (mGluR) are involved in mediating seizures and epileptogenesis. In the present experiments, the selective, group II mGluR agonist (+)-2-aminobicyclo-[3.1.0]hexane-2,6-dicarboxylic acid (LY354740, 0.1–1.0 µM) inhibited spontaneous epileptiform discharges which developed in rat cortical slices in Mg2+- free medium. LY354740 (4–16 mg/kg) administered prior to an injection of pentylenetetrazol (80 mg/kg) or picrotoxin (3.2 mg/kg) produced a dose-dependent decrease in the number of mice exhibiting clonic convulsions, but had no effect on N-methyl-d-aspartate (NMDA, 150 mg/kg)-induced convulsions. LY354740 (4–16 mg/kg) did not affect lethality induced in mice by pentylenetetrazol, picrotoxin or NMDA. LY354740 potentiated the anticonvulsant activity of the conventional antiepileptic drug diazepam, significantly decreasing the ED50 for that drug's effect on pentylenetetrazol-induced convulsions by 30%, but had no influence on anticonvulsant activity of ethosuximide and valproic acid. A pharmacokinetic interaction between LY354740 and diazepam, leading to the lowering of the plasma level of free diazepam, was also demonstrated. Our data suggest that the group II mGluR agonist LY354740 possesses anti-seizure activity and may modify the effects of some conventional antiepileptic drugs. [ABSTRACT FROM AUTHOR]

The effect of repeated treatment with various antidepressant drugs on the reactivity of CA1 neurons to the 5-HT receptor agonist zacopride was examined. Zacopride decreased the calcium-activated afterhyperpolarization and adaptation, it also elicited a slow membrane depolarization associated with an increase in input resistance. All those effects may have contributed to the zacopride-induced increase in the amplitude of population spikes, evoked in the CA1 cell layer by stimulation of the Schaffer collateral/commissural pathway. The later effect of zacopride was concentration-dependent and was antagonized by the 5-HT receptor antagonist DAU 62805. Repeated (14 days, twice daily), but not single, administration of the antidepressant drugs imipramine, citalopram, fluvoxamine and paroxetine (10 mg/kg) attenuated the effect of zacopride on population spikes. Because inhibitory 5-HT and excitatory 5-HT receptors are colocalized on pyramidal neurons, and our previous data demonstrated an increase in the 5-HT receptor-mediated inhibition after repeated treatment with antidepressants, we conclude that treatment with antidepressant drugs may enhance the inhibitory effect of 5-HT directly, by increasing the 5-HT receptor responsiveness, and indirectly, by inducing subsensitivity to the 5-HT receptor activation. [ABSTRACT FROM AUTHOR]