We hypothesized that hypertension-related myocardial remodeling characterized by hypertrophy and fibrosis might be accompanied by cell-to-cell gap junction alterations that may account for increased arrhythmogenesis. Intercellular junctions and expression of gap junction protein connexin-43 were analyzed in rat heart tissues from both spontaneous (SHR) and L-NAME model of hypertension. Isolated heart preparation was used to examine susceptibility of the heart to lethal ventricular fibrillation induced by low potassium perfusion. Ultrastructure observation revealed enhanced neoformation of side-to-side type while internalization of end-to-end type (intercalated disc-related) of gap junctions prevailed in the myocardium of rats suffering from either spontaneous or L-NAME-induced hypertension. In parallel, immunolabeling showed increased number of connexin-43 positive gap junctions in lateral cell membrane surfaces, particularly in SHR. Besides, focal loss of immunopositive signal was observed more frequently in hearts of rats treated with L-NAME. There was a significantly higher incidence of hypokalemia-induced ventricular fibrillation in hypertensive compared to normotensive rat hearts. We conclude that adaptation of the heart to hypertension-induced mechanical overload results in maladaptive gap junction remodeling that consequently promotes development of fatal arrhythmias., M. Fialová, K. Dlugošová, L. Okrouhlicová, F. Kristek, M. Manoach, N. Tribulová., and Obsahuje bibliografii a biblioigrafické údaje
GABA exhibits depolarizing action in the immature neurons due to high intracellular activity of chloride ions. It is maintained by cation-chloride cotransporter NKCC1 which is present in immature brain. Bumetanide is a specific inhibitor of this cotransporter. We studied possible anticonvulsant activity of bumetanide in pentyl enetetrazol-induced seizures in three age groups of rat pups (7, 12, and 18 days old). Pretreatment with bumetanide (0.2-1 mg/kg i.p.) resulted in dose-dependent decrease of incidence of the tonic phase of generalized tonic-clonic seizures in 12-day-old rats only. No effect was observed in younger and older animals. Higher dose of bumetanide (2.5 mg/kg) did not affect tonic convulsions but, on the contrary, decreased latencies of generalized seizures in 12-day-old animals. Lack of marked anticonvulsant effect is probably due to relative maturity of neurons in the brainstem where the generator of generalized seizures is localized. Age- and dose-specific suppression of the tonic phase needs further analysis. and Obsahuje seznam literatury
The growth of the prostate gland is androgen-dependent. Testosterone is converted to the most potent dihydrotestosterone (DHT) by 5α-reductase within the prostate. Androgen interacts with androgen receptors (AR) to regulate normal growth of the prostate and has also been implicated in both the progression of benign prostate hyperplasia and prostate cancer. This study was conducted to compare the mRNA expression of AR and 5α-reductase by the prostate gland from three age categories: immature, young-mature and old dogs. Quantitative gene expression was assessed by the real-time PCR and the results were expressed as a relative mRNA expression of the target gene. This study revealed that there was no significant difference in the mRNA expression of the AR gene by the prostate gland of immature, young and old dogs. In contrast, there is a highly significant (P<0.001) down-regulation in 5α-reductase gene by the prostate of young and old dogs as compared with immature dogs. However, there is no significant difference in mRNA expression of the 5α-reductase gene by the prostate gland from young and old dogs. This differential expression of AR and 5α-reductase genes, which are involved in the regulation of androgen effect on prostate gland, might reflect an age-dependent growth requirement of the gland for androgens., F. Shidaifat., and Obsahuje seznam literatury
Certain aspects of balance control change with age, resulting in a slight postural instability. We examined healthy subjects between 20-82 years of age during the quiet stance under static conditions: at stance on a firm surface and/or on a compliant surface with eyes either open or closed. Body sway was evaluated from centre of foot pressure (CoP) positions during a 50 sec interval. The seven CoP parameters were evaluated to assess quiet stance and were analyzed in three age groups: juniors, middle-aged and seniors. The regression analysis showed evident increase of body sway over 60 years of age. We found that CoP parameters were significantly different when comparing juniors and seniors in all static conditions. The most sensitive view on postural steadiness during quiet stance was provided by CoP amplitude and velocity in AP direction and root mean square (RMS) of statokinesigram. New physiological ranges of RMS parameter in each condition for each age group of healthy subjects were determined. Our results showed that CoP data from force platform in quiet stance may indicate small balance impairment due to age. The determined physiological ranges of RMS will be useful for better distinguishing between small postural instability due to aging in contrast to pathological processes in the human postural control., D. Abrahamová, F. Hlavačka., and Obsahuje bibliografii a bibliografické odkazy
Nitrogen-containing bisphosphonates were found to inhibit farnesyl diphosphate synthase - an essential enzyme in the cholesterol biosynthesis pathway, but their effect on cholesterol synthesis per se in the central nervous system (CNS) remains unknown. The aim of the present study was to examine possible influence of a representative agent alendronate on cholesterol synthesis rates in selected parts of rat CNS and on plasma cholesterol level. Two groups of rats were orally administered either alendronate (3 mg/kg b.w. ) or vehicle for 9 days. At the end of experiment, brain (basal ganglia, frontal cortex and hippocampus) and spinal cord were isolated and cholesterol synthesis was determined using the technique of deuterium incorporation from deuterated wa ter. In the alendronate group significant reductions of choleste rol synthesis rates were detected in frontal cortex, hippocampus and spinal cord (p<0.001). However, the experimental treatment did not produce a significant alteration in the levels of plasma cholesterol. In conclusion, this study brings the first experimental evidence of the inhibition of cholesterol biosynthesis with alendronate in central nervous system., Ľ. Cibičková, R. Hyšpler, N. Cibiček, E. Čermáková, V. Palička., and Obsahuje bibliografii
STR/N is an inbred strain of mice which is known to exhibit extreme polydipsia and polyuria. We previously found central administration of angiotensin II enhanced cardiovascular responses in STR/N mice than normal mice, suggesting that STR/N mice might exhibit different cardiovascular responses. Therefore, in this study, we investigated daily mean arterial blood pressure and heart rate, and changes in the baroreceptor-heart rate reflex in conscious STR/N mice and control (ICR) mice. We found that variability in daily mean arterial blood pressure and heart rate was significantly larger in STR/N mice than in ICR mice (p<0.05). There was a stronger response to phenylephrine (PE) in STR/N mice than in ICR mice. For baroreceptor reflex sensitivity, in the rapid response period, the slopes of PE and sodium nitroprusside (SNP) were more negative in STR/N mice than in ICR mice. In the later period, the slopes of PE and SNP were negatively correlated between heart rate and blood pressure in ICR mice, but their slopes were positively correlated in STR/N mice. These results indicated that STR/N mice exhibited the different cardiovascular responses than ICR mice, suggesting that the dysfunction of baroreceptor reflex happened in conscious STR/N mice., C. P. Chu, B. R. Cui, H. Kannan, D. L. Qiu., and Obsahuje bibliografii
Metabotropic glutamate receptors (mGluRs) represent a potential therapeutic target. Possible anticonvulsant action of AMN 082, an agonist of mGluR7 subtype, was studied in immature rats using pentylenetetrazol (PTZ)-induced seizures as a model. Five age groups of rats (7-, 12-, 18-, 25-day-old and adult animals) were pretreated with AMN 082 in doses of 0.5, 1, 2, and 5 mg/kg i.p. and 30 min later PTZ was administered (100 mg/kg s.c.). Controls received saline instead of the agonist. AMN 082 did not exhibit clear anticonvulsant action with the exception of suppression of the tonic phase of generalized tonic-clonic seizures (GTCS) in 12-day-old rats. Shorter latencies of GTCS after AMN 082 pretreatment indicate a proconvulsant action. Involuntary movements (mostly tremor) appeared after AMN 082 before PTZ administration, therefore we performed another experimental series with AMN 082 only (1, 2, 5, and 10 mg/kg i.p.). During 60-min observation period tremor appeared in all age groups; sensitivity to this action decreased with age from the 2 mg/kg dose in 7- and 12-day-old rats to the 10 mg/kg dose in adult rats. Mixed anti- and proconvulsant actions of AMN 082 together with unwanted motor effects makes clinical use of this drug highly improbable., Pavel Mareš., and Obsahuje bibliografii a bibliografické odkazy
a1_Using magnetic resonance imaging (MRI) in conjunction with synchronized spirometry we an alyzed and compared diaphragm movement during tidal breathing and voluntary movement of the diaphragm while breath holding. Breathing cycles of 16 healthy subjects were examined using a dynamic sequence (77 slices in sagittal plane during 20 s, 1NSA, 240x256, TR4.48, TE2.24, FA90, TSE1, FOV 328). The amplitude of movement of the apex and dorsal costophren ic angle of the diaphragm were measured for two test conditions: tidal breathing and voluntary breath holding. The maximal inferior and superior positions of the diaphragm were subtracted from the corresponding positions during voluntary movements while breath holding. The average amplitude of inferio-superior mo vement of the diaphragm apex during tidal breathing was 27.3±10.2 mm (mean ± SD), and during voluntary movement while breath holding was 32.5±16.2 mm. Movement of the costophrenic angle was 39±17.6 mm during tidal breathing and 45.5±21.2 mm during voluntary movement while breath holding. The inferior position of the diaphragm was lower in 11 of 16 subjects (68.75 %) and identical in 2 of 16 (12.5 %) subj ects during voluntary movement compared to the breath holding. Pearson’s correlation coefficient was used to demonstrate that movement of the costophrenic angle and apex of the diaphragm ha d a linear relationship in both examined situations (r=0.876). A correlation was found between the amplitude of diaphragm movement during tidal breathing and lung volume (r=0.876). The amplitude of movement of the diaphragm with or without breathing showed no correlation to each other (r=0.074). The moveme nt during tidal breathing shows a correlation with the changes in lung volumes. Dynamic MRI demonstrated that individuals are capable of moving their diaphragm voluntarily, but the amplitude of movement differs from person to person., a2_In this study, the movements of the diaphragm apex and the costophr enic angle were synchronous during voluntary movement of the diaphragm while breath holding. Although the sample is small, this study confirms that the function of the diaphragm is not only respiratory but also postural and can be voluntarily controlled., P. Kolář, J. Neuwirth, J. Šanda, V. Suchánek, Z. Svatá, J. Volejník, M. Pivec., and Obsahuje bibliografii
Neuroactive steroids represent potential antiepileptic drugs. We tested a newly synthesized analogue of allopregnanolone 3α- hydroxy-21ξ,22-oxido-21-homo-5α-pregnan-20-on (HOHP) against two types of pentylenetetrazol-induced seizures (100 mg/kg s.c.) in 12- and 25-day-old rats. Ganaxolone, a neuroactive steroid in clinical trials, served as a reference drug. Pretreatment with either steroid suppressed generalized tonicclonic seizures in both age groups, their efficacy was comparable. HOHP as well as ganaxolone were more active in 12- than in 25-day-old rats (effective doses were 40 and 60 mg/kg, respectively). Minimal clonic seizures, which can be elicited only in 25-day-old rats, were not influenced by any drug. Very short duration of anticonvulsant action of HPOP demonstrated in 12-day-old animals indicates that this drug might be used only in acute treatment in epileptology., P. Mareš, H. Kubová, A. Kasal., and Obsahuje bibliografii a bibliografické odkazy