Ghrelin is a new endogenous peptide, discovered in 1999 by Kojima et al., as the result of a search for an endogenous ligand for an orphan receptor of known structure and function. Ghrelin is composed of 28 amino acids and is produced mostly by cells of the stomach, hypothalamus, and hypophysis, but it has also been detected in other tissues. Its discovery is related to the development of a new hypothesis regarding the regulation of growth hormone secretion. It is an antagonist of somatostatin. Ghrelin activates the release of growth hormone from the somatotrophic cells of the hypophysis. It participates in the regulation of energy homeostasis, increases food intake, decreases energy output and exerts a lipogenetic effect. Its metabolic effects do not depend on the GH/IGF-I system, but are mediated by the NPY/Y1 and AGRP receptor system. Ghrelin influences the secretion and motility of the gastrointestinal tract, especially the stomach. The presence of ghrelin and its receptors has also been demonstrated in many other tissues. Its function in these tissues has not yet been studied, thus providing many possibilities for further research., M. Rosická, M. Kršek, Z. Jarkovská, J. Marek, V. Schreiber., and Obsahuje bibliografii
Ghrelin and agonists of its re ceptor GHS-R1a are potential substances for the treatment of cachexia. In the present study, we investigated the acute and lo ng-term effects of the GHS-R1a agonist JMV 1843 (H-Aib-DTrp-D-gTrp -CHO) on food intake, body weight and metabolic parameters in lean C57BL/6 male mice. Additionally, we examined stability of JMV 1843 in mouse blood serum. A single subcutaneous injection of JMV 1843 (0.01-10 mg/kg) increased food intake in fed mice in a dose- dependent manner, up to 5-times relative to the saline-treated group (ED 50 =1.94 mg/kg at 250 min). JMV 1843 was stable in mouse serum in vitro for 24 h, but was mostly eliminated from mouse blood after 2 h in vivo . Ten days of treatment with JMV 1843 (subcutaneous administration, 10 or 20 mg/kg/day) significantly increased food intake, body weight and mRNA expression of the orexigenic neuropeptide Y and agouti-related peptide in the medial basal hy pothalamus and decreased the expression of uncoupling protein 1 in brown adipose tissue. Our data suggest that JMV 1843 could have possible future uses in the treatment of cachexia., M. Holubová, ... [et al.]., and Obsahuje seznam literatury
Single unit recordings were made from the motor cortex of conscious cats with glass micropipettes that allowed ionophoretic application of 0.5 M glutamate in 2 M NaCl or 0.5 M ACPD (1S,3R-1-amino-cyclopentane-1,3-dicarboxylic acid, a mGluR agonist) in 2 M NaCl. Activity in response to a 70 dB click (1 ms rectangular pulse to loudspeaker) was studied before, during, and immediately after applying each agent locally as a paired US (90 nA current 570 ms after click for 300 ms in combination with glabella tap). A 70 dB hiss sound was presented 4.4 sec after the click as a discriminative stimulus (DS). CS and DS were presented 10 times initially (adaptation); then CS, US plus tap, and DS (approximately 10 times as conditioning); and then CS and DS (2-10 times to test post-conditioning). Glutamate potentiated the mean, early, 8-16 ms response to the click after conditioning (t=18.2, p<0.0001), but not the baseline activity which decreased from a mean of 17 spk/sec to 7 spk/sec (t=3.71, p<0.001). Baseline activity increased to 31 spk/sec when glutamate was applied during conditioning (t=3.30, p<0.005). ACPD reduced the intermediate, 64-72 ms response to the click after conditioning (t=8.18, p<0.0001), and potentiated the late 104-112 ms response (t=15.4, p<0.0001). Baseline activity was slightly increased after conditioning with ACPD. Saline did not potentiate the response to click. The results indicate that glutamate agonists that differ in their receptor affinities can induce different CRs when used as locally applied USs to condition neuronal responses to a click CS in the motor cortex of cats., Ch. D. Woody., and Obsahuje bibliografii
Primary aldosteronism (PA) is the most common cause of endocrine hypertension with a high frequency of cardiovascular complications. We found in our previous study higher occurrence of metabolic disturbances in patients with idiopathic hyperaldosteronism (IHA) compared to subjects with aldosterone-producing adenoma (APA). The aim of our present study is to evaluate potential differences in the frequency of endorgan damage (arterial stiffness and microalbuminuria) between two main types of PA. The diagnosis of the particular form of PA was based on adrenal venous sampling and/or histopathological examination. We analyzed clinical and laboratory data from 72 patients with PA (36 with IHA, 36 with APA). The arterial stiffness was expressed as the carotid-femoral pulse wave velocity (PWV) and the renal damage as urinary albumin excretion levels (UAE). Patients with IHA had significantly (p<0.03) higher prevalence of metabolic syndrome (17 % in APA, 35 % in IHA), higher triglycerides (1.37±0.71 mmol/l in APA, 1.85±0.87 mmol/l in IHA), lower HDL cholesterol (1.25±0.28 mmol/l in APA, 1.06±0.25 mmol/l in IHA), higher PWV (7.91±1.61 m/s in APA, 8.99±1.77 m/s in IHA) and higher UAE (12.93±2.21 mg/l in APA, 28.09±6.66 mg/l in IHA). It seems that patients with IHA may have a slightly different phenotype compared to APA., Z. Šomlóová ... [et al.]., and Obsahuje seznam literatury
The most frequent hereditary hearing loss is caused by mutations in the GJB2 gene coding for the gap junction beta 2 protein Connexin 26 (Cx26). In contrast to many studies performed in patients with bi-allelic mutations, audiometric studies on heterozygotes are sparse and often contradictory. To evaluate hearing function in heterozygous carriers of the GJB2 c.35delG mutation, audiometry over the extended frequency range and the recording of otoacoustic emissions (OAEs), i.e., transient-evoked OAEs (TEOAEs) and distortion product OAEs (DPOAEs), were performed in a group of parents and grandparents of deaf children homozygous for the GJB2 c.35delG mutation. The comparison of audiograms between control and heterozygous subjects was enabled using audiogram normalization for age and sex. Hearing loss, estimated with this procedure, was found to be significantly larger in GJB2 c.35delG heterozygous females in comparison with controls for the frequencies of 8-16 kHz; the deterioration of hearing in heterozygous men in comparison with controls was not statisticaly significant. A comparison of TEOAE responses and DPOAE levels between GJB2 c.35delG heterozygotes and controls did not reveal any significant differences. The results prove the importance of using audiometry over the extended frequency range and audiogram normalization for age and sex to detect minor hearing impairments, even in a relatively small group of subjects of different ages., D. Groh, ... [et al.]., and Obsahuje seznam literatury
Positive effects of repeated administration of diclofenac, an inhibitor of prostaglandin synthesis, in terms of prevention of tumor development and stimulation of hematopoiesis have been observed in C3H mice transplanted subcutaneously with G:5:113 fibrosarcoma cells. Fourteen-day treatment with diclofenac (3.75 mg/kg/day) started from day 5 after tumor cell transplantation. Measurements of tumors and hematological examinations were performed on day 30. The results strongly suggest the possibility that inhibitors of prostaglandin synthesis (non-steroidal anti-inflammatory drugs) may be used in oncological practice where the observed effects are highly desirable., M. Hofer, Z. Hoferová, P. Fedoročko, N. O. Macková., and Obsahuje bibliografii
Extracorporeal membranous oxygenation (ECMO) is increasingly used in the management of refractory cardiac arrest. Our aim was to investigate early effects of ECMO after prolonged cardiac arrest. In fully anesthetized swine (48 kg, N=18) ventricular fibrillation (VF) was induced and untreated period (20 min) of cardiac arrest commenced, followed by 60 min extracorporeal reperfusion (ECMO flow 100 ml/kg.min). Hemodynamics, arterial blood gasses, plasma potassium, tissue oximetry (StO2) and cardiac (EGM) and cerebral (BIS) electrophysiological parameters were continuously recorded and analyzed. Within 3 minutes of VF hemodynamic and oximetry parameters fall abruptly while metabolic parameters destabilize gradually over 20 minutes peaking at pH 7.04±0.05, pCO2 89±14 mmHg, K+ 8.5±1.6 mmol/l. During reperfusion most parameters restore rapidly: within 3-5 minutes mean arterial pressure reaches >40 mmHg, StO2 >50 %, paO2 >100 mmHg, pCO2 <50 mmHg, K+ <5 mmol/l. EGMs mean amplitude peaks at 4.5±2.4 min. Cerebral activity (BIS>60) reappeared in 5 animals after 87±21 min. In 12/18 animals return of spontaneous circulation was achieved. In conclusions, ECMO provides rapid restitution of internal milieu even after prolonged arrest. However, despite normalization of global parameters full recovery was not guaranteed since cardiac and cerebral electrical activities were sufficiently restored only in some animals. More sensitive and organ specific indicators need to be identified in order to estimate adequacy of cardiac support devices., M. Mlček, ... [et al.]., and Obsahuje seznam literatury
Heterologous expression of Kir channels offers a tool to modulate excitability of neurons which provide insight into Kir channel functions in general. Inwardly-rectifying K+ channels (Kir channels) are potential candidate proteins to hyperpolarize neuronal cell membranes. However, heterologous expression of inwardly-rectifying K+ channels has previously proven to be difficult. This was mainly due to a high toxicity of the respective Kir channel expression. We investigated the putative role of a predominantly glial-expressed, weakly rectifying Kir channel (Kir4.1 channel subunit; KCNJ10) in modulating electrophysiological properties of a motoneuron-like cell culture (NSC-34). Transfection procedures using an EGFP-tagged Kir4.1 protein in this study proved to have no toxic effects on NSC-34 cells. Using whole cell-voltage clamp, a substantial increase of inward rectifying K+ currents as well as hyperpolarization of the cell membrane was observed in Kir4.1-transfected cells. Na+ inward currents, observed in NSC-34 controls, were absent in Kir4.1/EGFP motoneuronal cells. The Kir4.1-transfection did not influence the NaV1.6 sodium channel expression. This study demonstrates the general feasibility of a heterologous expression of a weakly inward-rectifying K+ channel (Kir4.1 subunit) and shows that in vitro overexpression of Kir4.1 shifts electrophysiological properties of neuronal cells to a more gliallike phenotype and may therefore be a candidate tool to dampen excitability of neurons in experimental paradigms., J. Zschüntzsch, ... [et al.]., and Obsahuje seznam literatury
Our aim was to investigate the influence of microgravity on the sensitivity of the skin to mechanical stimulation, epidermal thickness, peripheral nerve density in the upper dermis, and serum levels of a stress marker in a rat hindlimb suspension (HS) model. Thirty 8-week-old male Wistar rats were randomly divided into 3 groups: HS, n=10; sham HS, n=10; control, n=10. The suspension system was attached to rat tails in both the HS and sham-HS groups, but the hindlimbs were suspended only in the HS group. The HS and sham-HS groups were treated for 4 weeks. In behavioral tests using von-Frey filaments (n=5 in each group), mechanical hypersensitivity developed in the HS and sham HS groups. Serum corticosterone levels increased significantly in the HS and sham HS groups compared to the control group, and no changes in epidermal thickness or peripheral nerve density were observed immediately after the removal of HS (n=5 in each group). These data indicated that the mechanical hypersensitivity observed in the HS group was not caused by microgravity or inactivity, but rather by restraint stress. We suggest that microgravity does not affect skin sensitivity and histology in these animals., Y. Tanaka, ... [et al.]., and Obsahuje seznam literatury
The use of reversible lesion techniques in memory research was pioneered in the laboratory of Jan Bureš and Olga Burešova. We use the occasion of Jan’s 75th birthday to briefly review the experimental utility of this approach. Two experiments from our current research are reported in which reversible lesioning methods are used to ask otherwise experimentally untenable questions about memory retrieval. The first experiment used intra-hippocampal injections of tetrodotoxin to temporarily inactivate the hippocampus during retrieval of a well-learned place avoidance navigation memory. This revealed that the hippocampus is necessary for place avoidance retrieval but that the extinction of place avoidance can occur independently of retrieving the memory and intact hippocampal function. The second experiment used KCl-induced cortical spreading depression in an interhippocampal transfer paradigm to demonstrate that a Y-maze memory that is learned by only one cortical hemisphere can be made to transfer to the other hemisphere by forcing the rat to swim, a unique stressful experience that occurred in a different apparatus, different behavioral context, and involved different behaviors than the Y-maze training. This demonstrates, we believe for the first time behaviorally, that memories can be activated outside of the behavioral context of their acquisition and expression in rats., K. Ježek, M. Wesierska, A. A. Fenton., and Obsahuje bibliografii