Mitochondria are involved in cellular functions that transcend the traditional role of these organelles as the energy factory of the cell. Their relative inaccessibility and the difficulties involved in attempts to study them in their natural environment - the cytosol - has delayed much of this understanding and they still have many secrets to yield. One of the relatively new fields in this respect is undoubtedly the analysis of mitochondrial membrane potential. The realization that its alteration may have important pathophysiological consequences has led to an increased interest in measuring this variable in a variety of biological settings, including cardiovascular diseases. Measurements of mitochondrial membrane potential tell us much about the role of mitochondria in normal cell function and in processes leading to cell death. However, we must be aware of the limitations of using isolated mitochondria, single cells and different fluorescent indicators., L. Škárka, B. Ošťádal., and Obsahuje bibliografii
We investigated how selected electromorphological parameters of myelinated axons influence the preservation of interspike intervals when the propagation of action potentials is corrupted by axonal intrinsic noise. Hereby we tried to determine how the intrinsic axonal noise influences the performance of axons serving as carriers for temporal coding. The strategy of this coding supposes that interspike intervals presented to higher order neurons would minimally be deprived of information included in interspike intervals at the axonal initial segment. Our experiments were conducted using a computer model of the myelinated axon constructed in a software environment GENESIS (GEneral NEural SImulation System). We varied the axonal diameter, myelin sheath thickness, axonal length, stimulation current and channel distribution to determine how these parameters influence the role of noise in spike propagation and hence in preserving the interspike intervals. Our results, expressed as the standard deviation of spike travel times, showed that by stimulating the axons with regular rectangular pulses the interspike intervals were preserved with a microsecond accuracy. Stimulating the axons with pulses imitating postsynaptic currents, greater changes of interspike intervals were found, but the influence of implemented noise on the jitter of interspike intervals was approximately the same., E. Kuriščák, S. Trojan, Z. Wünsch., and Obsahuje bibliografii
The pattern-reversal (P-VEPs) and the motion-onset (M-VEPs) of visual evoked potentials were modeled by means of three damped oscillators (O1, O2, O3) of identical construction. The O1, assumed to simulate the response of primary visual area (V1), was driven by the firing density of the lateral geniculate nuclei. O1 contributed mainly to the N75 and P100 peaks of the P-VEPs. The O2, driven by the O1 output, mimics the activity of V2, V3a, and MT. It contributed to the negative peak N145 of the P-VEPs or to the N160 in the M-VEPs. The O3 was suggested to model late slow processes probably of an attentive origin. The model parameters were set by optimization to follow the P-VEPs and M-VEPs obtained as a grand average of four young volunteers (PZ - A2 lead). The evoked potentials were described with normalized root mean square error lower than 13 %., J. Kremláček, M. Kuba, J. Holčík., and Obsahuje bibliografii
Models of basic types of epileptic seizures are elaborated not only in adult but also in immature rodents. It is important because at least half of human epilepsies starts during infancy and childhood. This paper presents a review of chemically and electrically induced models of generalized convulsive and nonconvulsive (absence) seizures as well as models of partial simple (neocortical) and complex (limbic) seizures in immature rats. These models can also serve as a tool for study the development of central nervous system and motor abilities because the level of maturation is reflected in seizure semiology. Age-dependent models of epileptic seizures (absences and flexion seizures) are discussed. Models of seizures in immature animals should be used for testing of potential antiepileptic drugs., P. Mareš., and Obsahuje seznam literaury
Baroreflex sensitivity (BRS) is abnormal in the prediabetic state. This study was conducted to determine effects of chronic rosiglitazone (RSG), an insulin sensitizer, on BRS in prediabetic hyperglycemic (PDH) rats induced by nicotinamide and streptozotocin. The fasting and postprandial blood glucose levels were 5.6–6.9 and 7.8–11.0 mmol/l, respectively. Rats were treated with RSG or saline for 12 weeks. BRS response to phenylephrine (PE-BRS) or sodium nitroprusside (NP-BRS) was determined by linear regression method. Cardiac sympathetic and parasympathetic influences were determined by autonomic blockades. In the saline-treated PDH rats, PE-BRS was enhanced early at week 4 and became greater at week 12. Abnormalities in NP-BRS and cardiac autonomic influences were found only after week 12. Four weeks of RSG treatment normalized blood glucose levels but not PE-BRS. All altered cardiovascular variables were completely restored by 12 weeks of RSG treatment. The correlation between BRS and blood glucose levels in salinetreated PDH rats was significant at week 12, but no correlation was found in RSG-treated rats. In conclusion, hyperglycemia, even in the prediabetic state, may play a role in BRS abnormalities. RSG treatment early in the prediabetic state may normalize BRS via cardiac autonomic modulation, besides its antihyperglycemic action., L.-Z. Hong ... [et al.]., and Obsahuje seznam literatury
Hypericin is a photosensitizing plant pigment from Hypericum perforatum with multiple modes of light-induced biological activities due to production of singlet oxygen and/or excited-state proton transfer with consequent pH drop in the hypericin environment. In the present work, we studied the effects of three inhibitors of crucial mechanisms responsible for intracellular pH (pHi) regulation on hypericin phototoxicity: N-ethylmaleimide (NEM), an inhibitor of H+-ATPase, 5'-(N,N-dimethyl)-amiloride (DMA), an inhibitor of Na+/H+ exchanger, and omeprazole (OME), an inhibitor of H+K+-ATPase. Our experiments show that the effect of hypericin at 1x10-5 and 1x10-6 mol.l-1 was significantly potentiated by NEM (1x10-7-1x10-9 mol.l-1) and DMA (1x10-6 and 1x10-7 mol.l-1) in leukemic CEM cell line. On the other hand, OME had no significant effect on hypericin cytotoxicity. Our results support the hypothesis that the excited-state proton transfer and the consequent acidification of hypericin environment could play a role in the biological activity of hypericin., A. Miroššay, L. Mirossay, M. Šarišský, P. Papp, J. Mojžiš., and Obsahuje bibliografii
Our study explored the role of extrapituitary prolactin (PRL) and toll-like receptors (TLR)2 and TLR4 in defense reaction of immune system to bacterial infection. Forty-two patients diagnosed with sepsis were recruited and blood samples were withdrawn after patients’ admission to hospital, after the end of acute phase of sepsis and after the sepsis has been resolved, respectively. Seventeen patients died of sepsis; thus, only one sample collected just before death could be processed. PRL and TLR2/4 mRNA levels were measured in CD14+ blood monocytes by QPCR and PRL -1149 G/T SNP genotyped. The TLRs mRNA expression was markedly elevated in all patients groups in comparison to healthy controls mRNA levels; the highest upregulation of monocytic TLR2 in sepsis (16.4 times, P<0.0001) was detected in patients who did not survive septic complications. PRL mRNA expression in monocytes from nonsurvivors tended to be lower (4.5 fold decrease, P=NS) compared to control levels and it was 6.2 times reduced compared to PRL mRNA expression in second blood sample from survivors (P<0.05). The PRL -1149 G/T SNP had no effect on PRL mRNA response during sepsis. Our data suggest that increased prolactin mRNA expression in monocytes is associated with better outcome and improved survival rate in sepsis with no apparent effect of PRL -1149 G/T SNP on monocytic prolactin response., P. Čejková ... [et al.]., and Obsahuje seznam literatury
Using histochemical analysis (NADPH-diaphorase, Fluoro-Jade B dye and bis-benzimide 33342 Hoechst) we studied the influence of intraperitoneal administration of nicotine (NIC), kainic acid (KA) and combination of both these substances on hippocampal neurons and their changes. In experiments, 35-day-old male rats of the Wistar strain were used. Animals were pretreated with 1 mg /kg of nicotine 30 min prior to the kainic acid application (10 mg/kg). After two days, the animals were transcardially perfused with 4 % paraformaldehyde under deep thiopental anesthesia. Cryostat sections were stained to identify NADPH-diaphorase positive neurons that were then quantified in the CA1 and CA3 areas of the hippocampus, in the dorsal and ventral blades of the dentate gyrus and in the hilus of the dentate gyrus. Fluoro-Jade B positive cells were examined in the same areas in order to elucidate a possible neurodegeneration. In animals exposed only to nicotine the number of NADPH-diaphorase positive neurons in the CA3 area of the hippocampus and in the hilus of the dentate gyrus was higher than in controls. In contrast, KA administration lowered the number of NADPH-diaphorase positive cells in all studied hippocampal areas and in both blades of the dentate gyrus. Massive cell degeneration was observed in CA1 and CA3 areas of the hippocampus and in the hilus of the dentate gyrus after kainic acid administration. Animals exposed to kainic acid and pretreated with nicotine exhibited degeneration to a lesser extent and the number of NADPH-diaphorase positive cells was higher compared to rats, which were exposed to kainic acid only., V. Riljak, M. Milotová, K. Jandová, J. Pokorný, M. Langmeier., and Obsahuje bibliografii a bibliografické odkazy
Motion artefact (MA) in voltage-sensitive fluorescent signals causes significant debasement of action potential. During ischemia and reperfusion in isolated rabbit heart, this artefact develops in a manner which may be described by the time of its onset, level, and shape. The MA during ischemia: (a) may become substantial with approximately two minutes delay after establishing global ischemia; (b) may be almost twice as high as the physiological action potential and decreases both with time and repetition of ischemia; (c) the MA shape is unpredictable and depends on individual rabbit., O. Janoušek, ... [et al.]., and Obsahuje seznam literatury
Growth of the A549 cell line in a perfusion system suitable for use in a magnetic resonance study has been characterized and shown to be stable physiologically and hence appropriate for serial observations. Several methods of monitoring cell growth were compared to assess the behavior of the cells in this system. Comparison between NMR metabolite data and cell growth via cell counting showed that 31P NMR signals accurately reported cell doubling time. In contrast to most NMR cell culture systems, viable cells can be recovered from the perfusion system after the NMR measurements for further biochemical studies. These data further suggest that this system will be useful for studying the physiology and biochemistry of exponentially growing cells for at least two days in NMR tube culture., E. G. Shankland, J. C. Livesey, R. W. Wiseman, K. A. Krohn., and Obsahuje bibliografii