The aim of this study was to investigate the reaction of the hypothalamo-pituitary-adrenocortical (HPA) system to various stressors (fasting, crowding, cold and heat) by measuring blood ACTH and corticosterone (CORT) concentration as well as the cholesterol (CHOL) content in the adrenals. To examine the effects of stress termination, the rats were returned and kept under control conditions for the same period as that of stress duration (supposed recovery period). According to our results HPA system was activated by all the stressors applied. Heat seems to be the strongest stressor since the exposure of animals to a high ambient temperature resulted in the greatest rise of plasma ACTH concentration as well as CORT synthesis and secretion. These values remained elevated after the stress termination i.e. after the rats had been returned to room temperature. Fasting seems to be the weakest stressor given because it causes the smallest increase in blood ACTH and CORT concentrations. Moreover, in refed rats the HPA function was fully recovered. In conclusion, the various stressors applied seem to induce a different response of the HPA system as judged by quantitative changes in ACTH and CORT release., J. Djordjević, G. Cvijić, V. Davidović., and Obsahuje bibliografii
Increased oxidative stress is indisputably an important mechanism of doxorubicin side effects, especially its cardiotoxicity. To prevent impairment of non-tumorous tissue and to improve the specificity in targeting the tumor tissue, new drug nanotransporters are developed. In many cases preclinical therapeutic advantage has been shown when compared with the administration of conventional drug solution. Three forms of doxorubicin - conventional (DOX), encapsulated in liposomes (lipoDOX) and in apoferritin (apoDOX) were applied to Wistar rats. After 24 h exposition, the plasma level of 4-hydroxy-2- nonenal (4-HNE) as a marker of lipoperoxidation and tissue gene expression of thioredoxin reductase 2 (TXNRD2) and aldehyde dehydrogenase 3A1 (ALDH3A1) as an important part of antioxidative system were determined. Only conventional DOX significantly increases the level of 4-HNE; encapsulated forms on the other hand show significant decrease in plasma levels of 4-HNE in comparison with DOX. They also cause significant decrease in gene expression of ALDH3A1 and TXNRD2 in liver as a main detoxification organ, and a mild influence on the expression of these enzymes in left heart ventricle as a potential target of toxicity. Thus, 4-HNE seems to be a good potential biomarker of oxidative stress induced by various forms of doxorubicin., M. Hlaváčová, J. Gumulec, T. Stračina, M. Fojtů, M. Raudenská, M. Masařík, M. Nováková, H. Paulová., and Obsahuje bibliografii
We evaluated the effects of N G -nitro-L-arginine methylester (L-NAME) (50 mg/kg/day) and 7-nitroindazole (7NI) (10 mg/kg/day) administered from 10th-16th week of age either individually or together on cardiovascular system of Wistar rats and SHR. Systolic blood pressure (sBP) was measured weekly by the plethysmographic method. For morphological studies, the animals (n=10) were perfused with a fixative (120 mm Hg), and thoracic aorta and carotid and co ronary arteries were processed for electron microscopy. For functional investigation (n=10), aortic rings were used in an or gan bath. In Wistar rats, L-NAME evoked an increase of sBP; hype rtrophy of the heart and arterial walls; an increase in cross-sectional areas (CSA) of endothelial cells (EC), muscle cells (SMC), extracellular matrix (ECM), and a decrease in acetylcholin e-induced endothelial-dependent relaxation (EDR). 7NI evoked sBP-independent hypotrophy of the heart and arterial walls, a decrease in CSA of EC and SMC without affecting the CSA of ECM, and a mild decrease in acetylcholine-induced EDR. 7NI and L-NAME administered together evoked lower effect on BP and trophicity of the heart and all arteries, and a similar de crease in acetylcholine-induced EDR compared to L-NAME alone. In SHR, 7NI did not evoke any effect on the studied parameters., F. Kristek, M. Drobna, S. Cacanyiova., and Obsahuje bibliografii
Under physiological conditions the mammalian circadian system is synchronized to a cyclic environment. The central oscillator in the suprachiasmatic nuclei (SCN) responds predominantly to an external light (L) dark (D) cycle. Peripheral oscillators are more efficiently synchronized by metabolic cues. When the circadian system is exposed to opposing synchronizing cues, peripheral oscillators uncouple from the SCN. To consider influence of phase advances and delays in light regimens mimicking shift work, we analyzed the expression of clock genes (per2, bmal1) and natriuretic peptides (anp, bnp) in the heart of male rats. Experimental groups were exposed to a rotating LD regimen with either 8 h phase advance or delay for 11 weeks. Samples were taken for a 24 h cycle in 4 h intervals. Peripheral oscillators responded to rotating phase advance by decreasing rhythm robustness, while phase delay mostly influenced the phase angle between the acrophase of rhythmic gene expression and the external LD cycle. The expression of anp was arrhythmic in the heart of control rats and was not influenced by rotating LD regimens. The expression of bnp showed a daily rhythm with a nadir during the active phase. The daily rhythm in bnp expression diminished under rotating LD regimen conditions., I. Herichová, J. Ambrušová, L'. Molčan, A. Veselá, P. Svitok, M. Zeman., and Obsahuje bibliografii
Tissue renin-angiotensin systems are known to behave differently from the circulating renin-angiotensin system (RAS). It has already been proposed that not only the circulating RAS, but also RAS localized in the cardiac tissue plays an important role in the heart failure. The objective of this study was to compare the gene expression of individual components of the renin-angiotensin system in hearts of normotensive and hypertensive rats. Two genetically hypertensive rat strains - spontaneously hypertensive rats (SHR) and hereditary hypertriglyceridemic rats (HTG) - were compared with Wistar-Kyoto (WKY) and Lewis (LEW) normotensive controls. In addition, developmental changes in gene expression of individual components of cardiac RAS were studied in 20-day-old fetuses, 2-day-old newborns and 3-month-old HTG and LEW rats. In our study, the angiotensinogen gene expression did not differ either among adult normotensive and hypertensive strains, or during development. In contrast, the renin gene expression was significantly increased in hearts of hypertensive compared to normotensive rats. Moreover, a 5-fold increase of renin mRNA was observed in hearts of HTG rats between day 2 and the third month of age. There was also an age-dependent increase of ACE gene expression in both HTG and LEW rats which was substantially delayed in HTG hearts. In conclusion, the results of our study suggest that overexpression of the cardiac renin gene in hypertensive strains could participate in the structural and functional changes of the heart during the development of hypertension., D. Jurkovičová, Z. Dobešová, J. Kuneš, O. Križanová., and Obsahuje bibliografii
The influence of long-term hypodynamy on the calcium and phosphorus levels was studied in the bones of Japanese quails. The hypodynamy evoked different changes in the calcium and phosphorus content in males and females. The calcium content in the marrow of femurs was only changed in the hens, while in cockerels it was significantly decreased in the upper part and marrow of the tibia. Furthermore, changes in the phosphorus content were observed only in the tibia of cockerels., J. Antalíková, M. Baranovská, I. Mravcová, V. Sabo, P. Škrobánek., and Obsahuje bibliografii
Administration of anti-tumor necrosis factor antibody (anti-TNF, infliximab) down-regulates T helper 1 (Th 1) cytokines production in intestinal mucosa of patients with Crohn´s disease (CD). Interleukin 10 (IL-10) is thought to be involved in CD pathogenesis through regulation of the Th 1 response. The aim of this study was to determine the IL-10 response in CD patients treated with anti-TNF. Fourteen patients with active CD received 5 mg/kg of infliximab; clinical activity assessed by Crohn´s Disease Activity Index (CDAI), α1-acid glycoprotein and serum IL-10 were determined before and after treatment, in month 0, 1 and 5. In the group with a good clinical response, IL-10 levels diminished significantly in month 1 (p<0.05) and remained decreased in month 5. The group with a lower response showed a significant increase in IL-10 levels in month 1 (p<0.05). α1-acid glycoprotein levels obtained before treatment were significantly elevated in the group with a good clinical response (p<0.05) and a significant decrease in month 1 was observed in this group (p<0.05). These observations suggest that a pattern of IL-10 response might be related to the clinical response to anti-TNF treatment in CD., Z. Detková, V. Kupčová, M. Príkazská, L. Turecký, S. Weissová, E. Jahnová., and Obsahuje bibliografii
Derivative of 6-methyluracil, selective cholinesterase inhibitor C-547 potentiates miniature endplate currents (MEPCs) in rat external intercostal muscles (external ICM) more effectively than in internal intercostal muscles (internal ICM). Effect of the C-547 on intercostal muscles was compared with those on extensor digitorum longus (EDL) and diaphragm muscles. Half-effective concentrations for τ of MEPC decay arranged in increasing order were as follows: EDL, locomotor muscle, most sensitive = 1.3 nM, external ICM, inspiration muscle = 6.8 nM, diaphragm, main inspiration muscle = 28 nM, internal ICM, expiration muscle = 71 nM. External ICM might therefore be inhibited, similarly as the limb muscles, by nanomolar concentrations of the drug and do not participate in inspiration in the presence of the C-547. Moreover, internal ICM inhibition can hinder the expiration during exercise-induced fast breathing of C-547-treated experimental animals., K. Petrov ... [et al.]., and Obsahuje seznam literatury
Microvessels respond to metabolic stimuli (e.g. pO2) and hemodynamic forces (e.g. shear stress and wall stress) with structural adaptations including angiogenesis, remodeling and pruning. These responses could be mediated by differential gene expression in endothelial and smooth muscle cells. Therefore, rat mesenteric arteries and veins we reexcised by microsurgery, and mRNA expression of four angioadaptation-related genes was quantified by real time duplex RT-PCR in equal amounts of total RNA, correlated to two different house keeping genes (ß-actin, GAPDH). The results show higher expression of VEGFA, TIE2, and ANG2 in arteries than in veins, but equal expression of ADAMTS1. Higher availability of VEGFA mRNA in endothelial cells of arteries shown here could contribute to the maintenance of mechanically stressed blood vessels and counteract pressure-induced vasoconstriction., N. Mecha Disassa ... [et al.]., and Obsahuje seznam literatury
Despite the demonstrated exercise -induced increase in reactive oxygen species (ROS) production, growing epidemiological evidence indicates that habitual, moderate physical activity reduces the incidence of several oxidative stress-based diseases. This apparent paradox can be explained taking into account that ROS produced during repeated ex ercise bouts may act as mild stressors able to trigger physiological and biomolecular hormetic responses through a number of redox-sensitive transcription pathways. Unfortunately, much more limited information is available from general population-based research, which could better reflect the condition of common people interested in achieving and maintaining good fitness levels. The present work aimed at investigatin g whether and how exercise-related habits in non-professional regular runners (n=33) can affect the systemic anti-oxidative capacity, and the resting serum levels of typical lipid peroxidation-related by-products and oxidatively- damaged proteins, in comparison with untrained sedentary individuals (n=25). We also anal yzed in both groups the redox response elicited by a modified Bruce-based maximal exercise test on the same parameters. Our findings indicated that long- term regular and moderate practice of aerobic physical activity can increase antioxidant defense systems, lower the resting protein oxidation processes and reduce the immediate up- regulation of lipid-targeting oxidative stress in response to an acute bout of exercise., S. Falone, A. Mirabilio, A. Pennelli, M. Cacchio, A. Di Baldassarre, S. Gallina, A. Passerini, F. Amicarelli., and Obsahuje bibliografii