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
Altered Ca2+ handling may be responsible for the development of cardiac contractile dysfunctions with advanced age. In the present study, we investigated the roles of oxidative damage to sarcoplasmic reticulum (SR) and expression of Ca2+-ATPase (SERCA 2a) and phospholamban in age-associated dysfunction of cardiac SR. SR vesicles were prepared from hearts of 2-, 6-, 15-, and 26-month-old Wistar rats. Although activity of Ca2+-ATPase decreased with advancing age, no differences in relative amounts of SERCA 2a and phospholamban protein were observed. On the other hand, significant accumulation of protein oxidative damage occurred with aging. The results of this study suggest that agerelated alteration in Ca2+-ATPase activity in the rat heart is not a consequence of decreased protein levels of SERCA 2a and phospholamban, but could arise from oxidative modifications of SR proteins. Cellular oxidative damage caused by reactive oxygen species could contribute to age-related alternations in myocardial relaxation., E. Babušíková ... [et al.]., and Obsahuje seznam literatury
Age-associated changes in large blood vessels were characterized by increased arterial wall thickness, luminal dilation and impaired endothelial function. But little is known about the effect of age on structural and functional changes in small resistance arteries. The mechanisms underlying age-associated endothelial dysfunction in rat mesenteric resistance arteries were investigated in the present study. Small rat mesenteric arteries were excised and cannulated, and vascular endothelial functions were tested by acetylcholine (ACh). Our experiments showed (1) endotheliumdependent vasorelaxation induced by ACh was reduced in aged mesenteric arteries; (2) blockade of Kca channels markedly reduced the vasodilation in young and adult rats, the resultant reduction in aged rats was much smaller compared with young and adult rats; (3) inhibition of endothelial nitric oxide synthase (NOS) resulted in a significant reduction of vasodilation in young and adult, but there was a smaller reduction in aged rats. The results suggest that (1) endothelial function was impaired in mesenteric arteries of aged rats; (2) both Kca channels and nitric oxide (NO) contribute together to the ACh-induced vasorelaxation in small mesenteric arteries, and (3) both the impairment of Kca channel function and decreased NO account for the age-related endothelial dysfunction., E. Zhou, D. Qing, J. Li., and Obsahuje bibliografii a bibliografické odkazy
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
a1_Fifty years ago, Lewis K. Dahl has presented a new model of salt hypertension – salt-sensitive and salt-resistant Dahl rats. Twenty years later, John P. Rapp has published the first and so far the only comprehensive review on this rat model covering numerous aspects of pathophysiology and genetics of salt hypertension. When we summarized 25 years of our own research on Dahl/Rapp rats, we have realized the need to outline principal abnormalities of this model, to show their interactions at different levels of the organism and to highlight the ontogenetic aspects of salt hypertension development. Our attention was focused on some cellular aspects (cell membrane function, ion transport, cell calcium handling), intra- and extrarenal factors affecting renal function and/or renal injury, local and systemic effects of reninangiotensin-aldosterone system, endothelial and smooth muscle changes responsible for abnormal vascular contraction or relaxation, altered balance between various vasoconstrictor and vasodilator systems in blood pressure maintenance as well as on the central nervous and peripheral mechanisms involved in the regulation of circulatory homeostasis. We also searched for the age-dependent impact of environmental and pharmacological interventions, which modify the development of high blood pressure and/or organ damage, if they influence the saltsensitive organism in particular critical periods of development (developmental windows). Thus, severe self-sustaining salt hypertension in young Dahl rats is characterized by pronounced dysbalance between augmented sympathetic hyperactivity and relative nitric oxide deficiency, attenuated baroreflex as well as by a major increase of residual blood pressure indicating profound remodeling of resistance vessels. Salt hypertension development in young but not in adult Dahl rats can be attenuated by preventive increase of potassium or calcium intake., a2_On the contrary, moderate salt hypertension in adult Dahl rats is attenuated by superoxide scavenging or endothelin-A receptor blockade which do not affect salt hypertension development in young animals., J. Zicha, ... [et al.]., and Obsahuje seznam literatury
The aim of the study was to investigate age-related changes in postural responses to platform translation with 3 various velocities. We focused on the influence of linear velocity using the smoothed profile of platform acceleration (till 100 cm.s−2 ). Eleven healthy young (20-31 years) and eleven healthy elderly (65-76 years) subjects were examined. The subjects stood on the force platform with their eyes closed. Each trial (lasting for 8 sec) with different velocity (10, 15, 20 cm.s−1 ) of 20 cm backward platform translation was repeated 4 times. We have recorded displacements of the centre of pressure (CoP) and the EMG activity of gastrocnemius muscle (GS) and tibialis anterior muscle (TA). The results showed increased maximal values of CoP responses to the platform translation. There was also observed a scaling delay of CoP responses to platform translation with different velocities in elderly. The EMG activity of GS muscle during backward platform translation was of about similar shape in both groups during the slowest platform velocity, but it increased depending on rising velocity. EMG activity of TA was not related to the platform velocity. Early parts of postural responses showed significant co-activation of TA and GS muscles of elderly. It is likely that elderly increased body stiffening in order to help their further balance control., Z. Halická ... [et al.]., 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
Vascular aging is associated with both structural and functional changes that can take place at the level of the endothelium, vascular smooth muscle cells and the extracellular matrix of blood vessels. With regard to the endothelium, reduced vasodilatation in response to agonists occurs in large conduit arteries as well as in resistance arteries with aging. Reviews concerning the different hypotheses that may account for this endothelial dysfunction have pointed out alterations in the equilibrium between endothelium-derived relaxing and constricting factors. Thus, a decreased vasorelaxation due to nitric oxide and, in some arteries, endothelium-derived hyperpolarizing factor as well as an increased vasoconstriction mediated by cyclooxygenase products such as thromboxane A2 are likely to occur in age-induced impairment of endothelial vasodilatation. Furthermore, enhanced oxidative stress plays a critical role in the deleterious effect of aging on the endothelium by means of nitric oxide breakdown due to reactive oxygen species. The relative contribution of the above phenomenon in age-related endothelial dysfunction is highly dependent on the species and type of vascular bed., R. L. Matz, C. Schott, J. C. Stoclet, R. Andriantsitohaina., and Obsahuje bibliografii
Mechanisms underlying atrial fibrillation (AF), the most common cardiac arrhythmia, particularly in aged population, are not fully elucidated. We have previously shown an increased propensity of old guinea pigs (GPs) heart to inducible AF when comparing to young animals. This study aimed to verify our hypothesis that susceptibility of aged heart to AF may be attributed to abnormalities in myocardial connexin-43 (Cx43) and extracellular matrix that affect cardiac electrical properties. Experiments were conducted on male and female 4-week-old and 24-week-old GPs. Atrial tissue was processed for analysis of Cx43 topology using immunohistochemistry, expression of Cx43 protein using immunobloting, and expression of mRNA of Cx43 and extracellular matrix metalloproteinase-2 (MMP-2) using real time PCR. Immunohistochemistry revealed uniform Cx43 distribution predominantly on lateral sides of the cardiomyocytes of young male and female GP atria. In contrast, non-uniform distribution, mislocalization and reduced immunolabeling of Cx43 were detected in atria of old GPs. In parallel, the atrial tissue levels of Cx43 mRNA were significantly decreased, while mRNA expression of MMP-2 was significantly increased in old versus young GPs. The changes were more pronounced in old GPs males comparing to females. Findings indicate that age-related down-regulation of atrial Cx43 and up-regulation of MMP-2 as well as disordered Cx43 distribution can facilitate development of AF in old guinea pig hearts., V. Nagibin, T. Egan Benova, C. Viczenczova, B. Szeiffova Bacova, I. Dovinova, M. Barancik, N. Tribulova., and Obsahuje bibliografii
Chronic airflow limitation, caused by chronic obstructive pulmonary disease (COPD) or by asthma, is believed to change the shape and the position of the diaphragm due to an increase in lung volume. We have made a comparison of magnetic resonance imaging (MRI) of diaphragm in supine position with pulmonary functions, respiratory muscle function and exercise tolerance. We have studied the differences between patients with COPD, patients with asthma, and healthy subjects. Most interestingly we found the lung hyperinflation leads to the changes in diaphragmatic excursions during the breathing cycle, seen in the differences between the maxim al expiratory diaphragm position (DPex) in patients with COPD and control group (p=0.0016) . The magnitude of the diaphragmatic dysfunction was significantly related to the airflow limitation expressed by the ratio of forced expiratory volume in 1 s to slow vital capacity (FEV 1 /SVC) , (%, p=0.0007); to the lung hyperinflation expressed as the ratio of the residual volume to total lung capacity (RV/TLC), (%, p=0.0018) and the extent of tidal volume constrain expressed as maximal tidal volume (V Tmax ), ([l], p=0 .0002); and the ratio of tidal volume to slow vital capacity (VT/SVC), (p=0.0038) during submaximal exercise. These results suggest that diaphragmatic movement fails to contribute sufficiently to the change in lung volume in emphysema. Tests of respiratory muscle function were related to the position of the diaphragm in deep expiration, e.g. neuromuscular coupling (P 0.1 /VT) (p=0.0232). The results have shown that the lung volumes determine the position of the diaphragm and function of the respiratory muscles. Chronic airflow limitation seems to change the position of the diaphragm, which thereafter influences inspiratory muscle function and exercise tolerance. There is an apparent relationship between the position of the diaphragm and the pulmonary functions and exercise tolerance., L. Hellebrandová, J. Chlumský, P. Vostatek, D. Novák, Z. Rýznarová, V. Bunc., and Obsahuje bibliografii