Although there are abundant data on ischemic postconditioning (IPoC) in the adult myocardium, this phenomenon has not yet been investigated in neonatal hearts. To examine possible protective effects of IPoC, rat hearts isolated on days 1, 4, 7 and 10 of po stnatal life were perfused according to Langendorff. Developed force (DF) of contraction was measured by an isometric force transducer. Hearts were exposed to 40 or 60 min of global ischemia followed by reperfusion up to the maximum recovery of DF. IPoC wa s induced by three cycles of 10, 30 or 60 s periods of global ischemia/reperfusion. To further determine the extent of ischemic injury, lactate dehydrogenase (LDH) release was measured in the coronary effluent. Tolerance to ischemia did not change from day 1 to day 4 but decreased to days 7 and 10. None of the postconditioning protocols tested led to significant protection on the day 10. Prolonging the period of sustained ischemia to 60 min on day 10 did not lead to better protection. The 3x30 s protocol wa s then evaluated on days 1, 4 and 7 without any significant effects. There were no significant differences in LDH release between postconditioned and control groups. It can be concluded that neonatal hearts cannot be protected by ischemic postconditioning during first 10 days of postnatal life. and J. Doul, Z. Charvátová, I. Ošťádalová, M. Kohutiar, H. Maxová, B. Ošťádal.
The endothelin (ET) and prorenin/renin/prorenin receptor (PRR) systems have opposing physiological effects on collecting duct (CD) salt and water reabsorption. It is unknown if the CD ET and renin/PRR systems interact, hence we examined the effects of deleting CD renin or nephron PRR on CD ET system components. PRR knockout (KO) mice were polyuric and had markedly increased urinary ET-1 and inner medullary CD (IMCD) ET-1 mRNA. PRR KO mice had greatly increased IMCD ETA receptor mRNA and protein, while ETB mRNA and protein were decreased. Water loaded wild-type mice with similar polyuria as PRR KO mice had modestly increased urinary ET-1 excretion and inner medullary ET-1 mRNA, while inner medullary ETA and ETB mRNA or protein expression were unaffected. In contrast to PRR KO, CD prorenin/renin KO did not alter ET system components. Taken together, these results suggest that the nephron PRR is involved in regulating CD ET system expression, but this effect may be independent of CD-derived renin., N. Ramkumar, D. Stuart, N. Abraham, D. E. Kohan., and Seznam literatury
We used a model of tibial lengthening in rabbits to study the postoperative pain pattern during limb-lengthening and morphological changes in the dorsal root ganglia (DRG), including alteration of substance P (SP) expression. Four groups of animals (naïve; OG: osteotomized only group; SDG/FDG: slow/fast distraction groups, with 1 mm/3 mm lengthening a day, respectively) were used. Signs of increasing postoperative pain were detected until the 10th postoperative day in OG/SDG/FDG, then they decreased in OG but remained higher in SDG/FDG until the distraction finished, suggesting that the pain response is based mainly on surgical trauma until the 10th day, while the lengthening extended its duration and increased its intensity. The only morphological change observed in the DRGs was the presence of large vacuoles in some large neurons of OG/SDG/FDG. Cell size analysis of the S1 DRGs showed no cell loss in any of the three groups; a significant increase in the number of SP-positive large DRG cells in the OG; and a significant decrease in the number of SP-immunoreactive small DRG neurons in the SDG/FDG. Faster and larger distraction resulted in more severe signs of pain sensation, and further reduced the number of SP-positive small cells, compared to slow distraction., K. Pap, Á. Berta, G. Szöke, M. Dunay, T. Németh, K. Hornok, L. Marosföi, M. Réthelyi, M. Kozsurek, Z. Puskár., and Obsahuje bibliografii
The present study investigated the effects of nesfatin-1 on gastric distension (GD)-responsive neurons via an interaction with corticotropin-releasing factor (CRF) receptor signaling in the ventromedial hypothalamic nucleus (VMH), and the potential regulation of these effects by hippocampal projections to VMH. Extracellular single-unit discharges were recorded in VHM following administration of nesfatin-1. The projection of nerve fibers and expression of nesfatin-1 were assessed by retrograde tracing and fluoro-immunohistochemical staining, respectively. Results showed that there were GD-responsive neurons in VMH; Nesfatin-1 administration and electrical stimulation of hippocampal CA1 sub-region altered the firing rate of these neurons. These changes could be partially blocked by pretreatment with the non-selective CRF antagonist astressin-B or an antibody to NUCB2/nesfatin-1. Electrolytic lesion of CA1 hippocampus reduced the effects of nesfatin-1 on VMH GD-responsive neuronal activity. These studies suggest that nesfatin-1 plays an important role in GD-responsive neuronal activity through interactions with CRF signaling pathways in VMH. The hippocampus may participate in the modulation of nesfatin-1-mediated effects in VMH., H. Feng, Q. Wang, F. Guo, X. Han, M. Pang, X. Sun, Y. Gong, L. Xu., and Obsahuje bibliografii
In previous studies, it has been shown that recombinant human neuregulin-1(rhNRG-1) is capable of improving the survival rate in animal models of doxorubicin (DOX)-induced cardiomyopathy; however, the underlying mechanism of this phenomenon remains unknown. In this study, the role of rhNRG-1 in attenuating doxorubicin-induce apoptosis is confirmed. Neonatal rat ventricular myocytes (NRVMs) were subjected to various treatments, in order to both induce apoptosis and determine the effects of rhNRG-1 on the process. Activation of apoptosis was determined by observing increases in the protein levels of classic apoptosis markers (including cleaved caspase-3, cytochrome c, Bcl-2, BAX and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining). The activation of Akt was detected by means of western blot analysis. The study results showed that doxorubicin increased the number of TUNEL positive cells, as well as the protein levels of cleaved caspase-3 and cytochrome c, and reduced the ratio of Bcl-2/Bax. However, all of these effects were markedly antagonized by pretreament with rhNRG-1. It was then further demonstrated that the effects of rhNRG-1 could be blocked by the phosphoinositole-3-kinase inhibitor LY294002, indicating the involvement of the Akt process in mediating the process. RhNRG-1 is a potent inhibitor of doxorubicin-induced apoptosis, which acts through the PI3K-Akt pathway. RhNRG-1 is a novel therapeutic drug which may be effective in preventing further damage from occurring in DOX-induced damaged myocardium., T. An, ... [et al.]., and Obsahuje seznam literatury
Depression is a complex disorder related to chronic inflammatory processes, chronic stress changes and a hippocampal response. There is a increasing knowledge about the role of glial cells in nutrient supply to neurons, maintenance of synaptic contacts and tissue homeostasis within the CNS. Glial cells, viewed in the past as passive elements with a limited influence on neuronal function, are becoming recognized as active partners of neurons and are starting to be discussed as a possible therapeutic target. Their role in the pathogenesis of depressive disorders is also being reconsidered. Attention is devoted to studies of the different types of antidepressants and their effects on transmembrane signaling, including levels of α subunits of G proteins in C6 glioma cells in vitro as a model of postsynaptic changes in vivo. These models indicate similarities in antidepressant effects on G proteins of brain cells and effector cells of natural immunity, natural killers and granulocytes. Thus, an antidepressant response can exhibit certain common characteristics in functionally different systems which also participate in disease pathogenesis. There are, however, differences in the astrocyte G-protein responses to antidepressant treatment, indicating that antidepressants differ in their effect on glial signalization. Today mainstream approach to neurobiological basis of depressive disorders and other mood illnesses is linked to abnormalities in transmembrane signal transduction via G-protein coupled receptors. Intracellular signalization cascade modulation results in the activation of transcription factors with subsequent increased production of a wide array of products including growth factors and to changes in cellular activity and reactivity., M. Páv, H. Kovářů, A. Fišerová, E. Havrdová, V. Lisá., and Obsahuje bibliografii a bibliografické odkazy
Neurogenic pulmonary edema (NPE), which is induced by acute spinal cord compression (SCC) unde r the mild (1.5 %) isoflurane anesthesia, is highly dependent on baroreflex-mediated bradycardia because a deeper (3 %) isoflurane anesthesia or atropine pretreatment comple tely abolished bradycardia occurrence and NPE development in rats subjected to SCC. The aim of the present study was to evaluate whether hypertension- associated impairment of baroreflex sensitivity might exert some protection against NPE developmen t in hypertensive animals. We therefore studied SCC-induced NPE development in two forms of experimental hypertension - spontaneously hypertensive rats (SHR) and salt hypertensive Dahl rats, which were reported to have reduced baroreflex sensitivity. SCC elicited NPE in both hypertensive models irrespective of their baroreflex sensitivity. It is evident that a moderate impairment of baroreflex sensitivity, which was demonstrated in salt hypertensive Dahl rats, does not exert sufficient protective effects against NPE development., J. Šedý, J. Kuneš, J. Zicha., and Obsahuje bibliografii a bibliografické odkazy
Neurohumoral substances and their receptors play a major part in the complex regulation of gastrointestinal motility and have therefore been the predominant targets for drug development. The numerous receptors involved in motility are located mainly on smooth muscle cells and neuronal structures in the extrinsic and intrinsic parts of the enteric nervous system. Within this system, receptor agonists and antagonists interacts directly to modify excitatory or inhibitory signals. In view of this complexity it is not surprising that our knowledge about the mechanisms of actions of the various neurohormones and drugs affecting gut motility has been rather fragmented and incomplete. However, recently substantial progress has been achieved, and drug therapy for gut dysmotility is emerging, based primarily on neurohumoral receptors. This paper presents a selective review of the neurohumoral regulatory mechanisms of gastrointestinal motility. In this context, the physiology and pharmacology of the smooth muscle cells, gastrointestinal motility and dysmotility, the enteric nervous system, gastrointestinal reflexes, and serotonin is presented. Further investigation and understanding of the transmitters and receptors involved in especially the reflex activation of peristalsis is crucial for the development of novel therapies for motility disorders., M. B. Hansen., and Obsahuje bibliografii
Neuromedin beta (NMB) is a member of the bombesin-like peptide family expressed in brain, gastroin testinal tract, pancreas, adrenals and adipose tissue. The aim of our study was to compare the frequency of P73T polymorphism in overweight and obese patients (37 men: age 50.6±11.7 years, BMI 41.1±7.8 kg/m2; 255 women: age 49.0±11.9 years, BMI 37.9±6.8 kg/m2) with that of healthy normal weight subjects (51 men: age 28.2±7.1 years, BMI 22.3±2.0 kg/m2; 104 women: age 29.1±9.1 years, BMI 21.5±1.9 kg/m2) and to investigate the polymorphism’s influence on anthropometric, nutritional and psychobehavioral parameters in overweight/obese patients both at the baseline examination and at a control visit carried out 2.5 years later, regardless of the patient́s compliance with the weight reduction program. No significant differences in the genotype distribution were demonstrated between normal weight and overweight/obese subjects. Male T allele non-carriers compared to T allele carriers had higher energy (p=0.009), protein (p=0.018) and fat (p=0.002) intakes and hunger score (p=0.015) at the beginning of treatment. Male T allele non-carriers had a more favorable response to weight management at the follow-up, as they exhibited a significant reduction in waist circumference, energy intake and depression score as well as a significant increase in dietary restraint. No significant differences between carriers and non-carriers were demonstrated in women at the baseline examination. Both female T allele carriers and non-carriers demonstrated similar significant changes in nutritional parameters and in restraint score at the follow-up. Nevertheless, only female non-carriers showed a significant decrease in the hunger score., J. Spálová, H. Zamrazilová, J. Včelák, M. Vaňková, P. Lukášová, M. Hill, K. Hlavatá, P. Šrámková, M. Fried, B. Aldhoon, M. Kunešová, B. Bendlová, V. Hainer., and Obsahuje bibliografii a bibliografické odkazy