Decades of liver regeneration studies still left the termination phase least elucidated. However regeneration ending mechanisms are clinicaly relevant. We aimed to analyse the timing and transcriptional control of the latest phase of liver regeneration, both controversial. Male Wistar rats were subjected to 2/3 partial hepatectomy with recovery lasting from 1 to 14 days. Time-series microarray data were assessed by innovative combination of hierarchical clustering and principal component analysis and validated by real-time RT-PCR. Hierarchical clustering and principal component analysis in agreement distinguished three temporal phases of liver regeneration. We found 359 genes specifically altered during late phase regeneration. Gene enrichment analysis and manual review of microarray data suggested five pathways worth further study: PPAR signalling pathway; lipid metabolism; complement, coagulation and fibrinolytic cascades; ECM remodelling and xenobiotic biotransformation. Microarray findings pertinent for termination phase were substantiated by real-time RT-PCR. In conclusion, transcriptional profiling mapped late phase of liver regeneration beyond 5th day of recovery and revealed 5 pathways specifically acting at this time. Inclusion of longer post-surgery intervals brought improved coverage of regeneration time dynamics and is advisable for further works. Investigation into the workings of suggested pathways might prove helpful in preventing and managing liver tumours., D. Rychtrmoc, ... [et al.]., and Obsahuje seznam literatury
Repeated postnatal caffeine treatment of rat pups led to transient developmental changes in cortical epileptic afterdischarges. To know if physiological cortical functions are also affected transcallosal evoked potentials were studied. Rat pups of the Wistar strain were injected daily with caffeine (10 or 20 mg/kg s.c.) from postnatal day (P) 7 to P11, control siblings received saline. Cortical interhemispheric responses were tested at P12, 18, 25 and in young adult rats. Amplitude of initial monosynaptic components was evaluated in averaged responses. Single pulses as well as paired and frequency (five pulses) stimulations were used. Developmental rules - highest amplitude of responses in 25-day-old rats, potentiation with paired and frequency stimulation present since P18 - were confirmed. Caffeine-treated rats exhibited transient changes: single responses were augmented in P25 if high stimulation intensity was used, paired-pulse and freque ncy responses were higher in experimental than in control anim als at P12, the opposite change was observed in 18- and more ma rkedly in 25-day-old rats. No significant changes were found in adult animals, monosynaptic transcallosal responses represent a simple and robust system. The developmental profile of described changes did not exactly correspond to changes in epileptic afterdischarges supporting the possibility that afterdischarges did not arise from early monosynaptic components of responses. In spite of transient nature of changes they can reflect delayed or more probably modified brain development., J. Tchekalarova, H. Kubová, P. Mareš., and Obsahuje bibliografii a bibliografické odkazy
Differential pulse voltammetry with a carbon fibre microelectrode (ME) was used in pentobarbital- anaesthetized rats for monitoring the stobadine current (STB.C) on both sides of the blood-brain barrier (BBB) in the arterial bloodstream (BS) and in the corpus striatum (CS). The STB.C exhibited a distinct peak at a polarization voltage 540±30 mV (n=4). The maximum of STB.C in BS attained 2-3 min after the STB administration (2.8 mg/100 g in 1.0 ml saline solution i.a.) was followed by a rapid decrease to about 20 % within next 3 min. The STB readily passed across the BBB: the STB.C peak appeared in the CS in the 3rd minute and continued to rise up to the 30th min. The administration of STB did not prevent a large increase (1347±326 %, n=3) of the catechol-oxidative current (CA.OC) occurring in the CS between the 4th and 5th minute after cardiac arrest. However, a decrease of ME sensitivity to CA.OC in the presence of STB was observed. This fact leads to the speculation whether a similar "quenching" of dopamine by STB could not participate in the protective effects of STB observed in the brain exposed to hypoxia-reoxygenation.
Epileptic afterdischarges induced by electrical stimulation of the sensorimotor cortex as well as minimal metrazol seizures are characterized by EEG spike-and-wave rhythm and nearly the same motor pattern of clonic seizures. The action of ethosuximide on these two models was tested in adult rats with implanted electrodes. Cortical afterdischarges remained practically uninfluenced by ethosuximide (62.5 or 125 mg/kg i.p.) whereas minimal metrazol seizures were suppressed in a dose-dependent manner (doses of 31.25, 62.5 and 125 mg/kg i.p. were used). Present results in connection with recent data on the abolition of spike-and-wave rhythm elicited by low systemic doses of pentylenetetrazol suggest that spike-and-wave rhythm does not represent a single entity.
The effects of transient and sustained hyperthyroidism on vasoactive intestinal polypeptide-like immunoreactivity (VIP-LI) levels were studied in the heart atria of developing and adult rats. Newborn rats were divided into 5 groups. Neo-T animals were treated with thyroxine (T4) during postnatal days 1-8 and sacrificed at the age of 60 days. Neo-S rats were treated with T4 during postnatal days 1-60 and sacrificed one day later. Adult-1 and Adult-2 animals received T4 during days 52-60 and were sacrificed 5-6 days and 1 day later, respectively. Control animals were injected with saline. VIP-LI concentrations were determined in extracts from the left and right atria separately. In Neo-S and Adult-2 rats, spontaneous heart rate, the weight of both atria and total T4 serum levels were significantly enhanced, while their body weight was decreased. The ratio atria weight to body weight was significantly increased in all groups except for Adult-1 animals. Hyperthyroidism led to a significant decrease in VIP-LI levels in both atria of Neo-S and Neo-T rats. Hyperthyroidism induced in adult rats also decreased VIP-LI levels in both atria. However, this change was only transient. In conclusion, our data have provided new evidence that hyperthyroidism induced during the early neonatal period interferes with the development of VIP-ergic innervation in rat atria. The period of the first few postnatal days seems to be essential for this effect, since VIP-LI concentrations in 60-day-old animals did not significantly differ between Neo-S and Neo-T atria., J. Kuncová, J. Slavíková., and Obsahuje bibliografii
The pulmonary vasodilator action of an S-nitrosothiol, S-nitroso acetylpenicillamine (SNAP), was investigated in the rat pulmonary vasculature. The influence of its nitric oxide donator property was studied by comparison with the effect of acetylpenicillamine (AP), SNAP minus the nitroso group, and the blockade of nitric oxide release by the L-arginine analogue, L-NAME. In the isolated rat lung perfused with autologous blood at a constant flow rate (1PL), changes in pulmonary artery pressure (Ppa) reflect changes in pulmonary vascular resistance. Dose-response relationships to both SNAP and AP (0.1, 1, 10 and 100 /ug) were established both during normoxic ventilation (air + 5 % CO2; low Ppa) and when Ppa was raised by alveolar hypoxic vasoconstriction (2 % O2 + 5 % CO2). SNAP caused small dose-dependent fall in normoxic Ppa (mean±S.D. 17.4±3.0 mm Hg). in 11 rat IPL % fall of Ppa was 1, 3 and 4 % for 1, 10 and 100 ¡ug, respectively (p<0.01). This fall was more obvious when Ppa was raised by hypoxia (mean Ppa rise (HPV) 11.5±3.8 mm Hg); there was a 22, 55 and 79 % fall in HPV for 1,10 and 100 /ug in 11 rat IPL. The dilatation after 10 /ig SNAP was not consistently affected by 100/rg L-NAME (% fall in HPV pre L-NAME 45±22 % vs 42±23 % post L-NAME). AP had no significant effect on Ppa, causing only small falls in Ppa, equivalent to solvent (saline). There was occasionally a small rise in Ppa with 10 and 100 /tg AP. Thus, the dilator action of SNAP is most likely due to its NO donator property, and is not consistently affected by blockade of endogenous NO release.
Using a microelectrode with carbon filaments and the voltammctric technique, changes evoked in the catechol oxidation current (CA.OC) and multiple unit activity (MUA) by microinjection of 3-5 ¿ri 03 mol.I'1 KC1 were studied in the reticular formation (RF) of the medulla oblongata of anaesthetized rats; the effect of KC1 stimulation of the RF and corpus striatum (S) on the CA.OC in these structures was compared. The microinjection of KC1 in the vicinity of the working electrode in the RF caused depression of MUA which began 2-3 s after administration, persisted for up to 6 min after and then diminished, reaching control values within 9 min. The voltammctric signal was first recorded in the 1st min after microinjection, when there was an evident decrease in the CA.OC value (59 % of the control value); this effect reached its maximum 7 min after administration (a mean drop to 23 % of the control), while at the end of the experiment (i.e. after 24 min) CA.OC values had risen to 45-80 % of the control value. The response in the S had a biphasic character, however. Immediately after the microinjection (1st min), the mean CA.OC value rose to 626 % of the control, while in the second phase (3-10 min) it was seen to fall below the control values (means 21-63 % of the control). The differences in the changes evoked by K+ depolarization in the concentration of catecholamines in the RF and S microenvironment are discussed from the aspect of the existence of different pools of the transmitter and
other regional differences. The possibility of a relationship between considered.