This study aimed to investigate the anti-fibrotic effects of ghrelin in isoproterenol (ISO)-induced myocardial fibrosis and the underlying mechanism. Sprague-Dawley rats were randomized to control, ISO, and ISO + ghrelin groups. ISO (2 mg/kg per day, subcutaneous) or vehicle was administered once daily for 7 days, then ghrelin (100 microg/kg per day, subcutaneous) was administered once daily for the next 3 weeks. Ghrelin treatment greatly improved the cardiac function of ISO-treated rats. Ghrelin also decreased plasma brain natriuretic peptide level and ratios of heart weight to body weight and left ventricular weight to body weight. Ghrelin significantly reduced myocardial collagen area and hydroxyproline content, accompanied by decreased mRNA levels of collagen type I and III. Furthermore, ghrelin increased plasma level of growth differentiation factor 15 (GDF15) and GDF15 mRNA and protein levels in heart tissues, which were significantly decreased with ISO alone. The phosphorylation of Akt at Ser473 and GSK-3beta at Ser9 was decreased with ISO, and ghrelin significantly reversed the downregulation of p-Akt and p-GSK-3beta. Mediated by GDF15, ghrelin could attenuate ISO-induced myocardial fibrosis via Akt-GSK-3beta signaling.

• MeSH
• agonisté adrenergních beta-receptorů farmakologie   MeSH
• fibróza chemicky indukované   farmakoterapie   patologie   MeSH
• ghrelin aplikace a dávkování   MeSH
• isoprenalin farmakologie   MeSH
• kardiomyopatie chemicky indukované   farmakoterapie   metabolismus   patologie   MeSH
• krysa rodu rattus MeSH
• modely nemocí na zvířatech MeSH
• myokard metabolismus   patologie   MeSH
• potkani Sprague-Dawley MeSH
• protoonkogenní proteiny c-akt metabolismus   MeSH
• růstový diferenciační faktor 15 metabolismus   MeSH
• srdce účinky léků   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The functional antagonism between obestatin and ghrelin in the testis is under investigation. We investigated the ability of obestatin to counteract the inhibitory effect of ghrelin on basal and stimulated testosterone (T) secretion in vitro. Testicular strips from adult rats were incubated with 10 ng/ml and 100 ng/ml of obestatin alone, ghrelin alone and obestatin + ghrelin. Obestatin modulation of stimulated T secretion was evaluated by incubation of testicular samples with 10 ng/ml and 100 ng/ml obestatin, ghrelin and obestatin + ghrelin in the absence and presence of 10 IU of human chorionic gonadotrophin (hCG). T concentrations in the hCG treated groups were significantly (P<0.0001) higher than those in the control groups. Obestatin caused a significant increase in basal T secretion in a dose-dependent manner; however, obestatin at the both 10 ng/ml and 100 ng/ml significantly (P<0.0001) increased hCG-stimulated T secretion. In contrast, ghrelin in a dose-dependent manner significantly (P<0.001) decreased both basal and hCG-induced T secretion by testicular slices. Obestatin opposed the inhibitory effect of ghrelin on T secretion under both basal and hCG-stimulated conditions at all doses tested. In conclusions, administration of obestatin was able to antagonize the inhibitory effect of ghrelin on testosterone secretion in vitro.

• MeSH
• ghrelin aplikace a dávkování   MeSH
• krysa rodu rattus MeSH
• peptidové hormony aplikace a dávkování   MeSH
• potkani Sprague-Dawley MeSH
• synergismus léků MeSH
• testis účinky léků   sekrece   MeSH
• testosteron sekrece   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The aim of the present study was to investigate the effects of Angiotensin II (Ang II) and Arginin-Vasopressin (AVP) on contractility of non-pregnant uterus in diabetic Wistar rats and to explore whether one-week administration of Melatonin (MLT) or Ghrelin (GHR) will change the response of diabetic uterine muscle to AngII and AVP. Uterine horns, prepared by the method of isolated tissues were investigated as well as glycemic profile, blood pressure and body weight. The research of smooth muscle contractions was made by a new method of analysis, characterizing in detail the various phases of the myometrial activity. Differences in the development of the peptide-mediated smooth muscle contractions depending on the phase of the estrous cycle were observed. Experimental diabetes had a pronounced negative effect on force and time-parameters of AngII and AVP-stimulated uterine contractions. Administration of GHR or MLT had a beneficial effect on the glycemic status of diabetic rats and partially improved the response of uterine preparations to the peptides. The application of MLT increased both force and time-parameters of Ang II-and AVP-stimulated uterine contractions while treatment with GHR increased power characteristics and shortened contraction and relaxation of the smooth muscle process.

• MeSH
• angiotensin II farmakologie   MeSH
• děložní kontrakce účinky léků   fyziologie   MeSH
• experimentální diabetes mellitus farmakoterapie   metabolismus   MeSH
• ghrelin aplikace a dávkování   MeSH
• krysa rodu rattus MeSH
• melatonin aplikace a dávkování   MeSH
• potkani Wistar MeSH
• rozvrh dávkování léků MeSH
• vasopresiny farmakologie   MeSH
• výsledek terapie MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

T-2 toxin and its metabolite HT-2 toxin are one of the most toxic mycotoxins of type A-trichothecenes, which are produced mainly by Fusarium species. Therefore, study of Fusarium toxins T-2 toxin and HT-2 toxin is an essential issue because they could also play role in failures of reproductive functions as well as endocrine system of domestic animals. Assessment of the effect of A-trichothecene mycotoxin HT-2 toxin alone or combined with insulin-like growth factor (IGF-I), leptin and ghrelin on estradiol secretion by rabbit ovarian fragments in vitro was done. Rabbit ovarian fragments were incubated without (control group) or with HT-2 toxin, or its combinations with IGF-I, leptin and ghrelin at various concentrations for 24 h. Secretion of 17beta-estradiol was determined by ELISA. Firstly, HT-2 toxin at the doses 10 and 100 ng.ml(-1), but not at 1 ng.ml(-1) decreased 17beta-estradiol secretion by ovarian fragments. Secondly, 17beta-estradiol secretion was not affected by HT-2 toxin exposure combined with growth factor IGF-I, metabolic hormones leptin and ghrelin. In conclusion, HT-2 toxin has potent direct dose-dependent effects on ovarian steroidogenesis in rabbits. These direct effects of HT-2 mycotoxin on ovarian steroidogenesis could impact negatively on the reproductive performance of rabbits.

• MeSH
• estradiol krev   MeSH
• fixní kombinace léků MeSH
• ghrelin aplikace a dávkování   MeSH
• insulinu podobný růstový faktor I aplikace a dávkování   MeSH
• králíci MeSH
• kultivované buňky MeSH
• leptin aplikace a dávkování   MeSH
• ovarium účinky léků   metabolismus   MeSH
• T-2 toxin analogy a deriváty   toxicita   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• diabetes mellitus 2. typu farmakoterapie   MeSH
• dvojitá slepá metoda MeSH
• gastroparéza diagnóza   epidemiologie   etiologie   farmakoterapie   MeSH
• ghrelin agonisté   aplikace a dávkování   farmakokinetika   farmakologie   MeSH
• komplikace diabetu farmakoterapie   MeSH
• lidé MeSH
• placebo terapeutické užití   MeSH
• vyprazdňování žaludku účinky léků   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

Malnutrition is a common complication in patients on dialysis and is strongly associated with poor prognosis. Effective therapy could substantially improve morbidity and mortality, but neither enteral nor parenteral supplementation provide long-term benefit because of the strong appetite suppression seen in such patients. We performed a double-blinded randomized crossover study of a week-long treatment with daily subcutaneous ghrelin, a gut hormone that regulates hunger through the hypothalamus, in a group of 12 malnourished dialysis patients. Ghrelin administration increased ghrelin levels in circulation, modestly reduced blood pressure for up to 2 h, and immediately and significantly increased appetite, with an increase in energy intake noted at the first study meal. Persistence of this effect throughout the week was confirmed with food diaries and final study meals. Energy expenditure, measured with free-living pulse and motion monitors, was unchanged by ghrelin. Our study shows that daily treatment with ghrelin achieves a sustained positive change in energy balance in malnourished dialysis patients. Direct manipulation of appetite with ghrelin or its analogs represents an attractive and promising therapeutic strategy for this difficult clinical problem.

• MeSH
• chronické selhání ledvin komplikace   terapie   MeSH
• chuť k jídlu účinky léků   MeSH
• dialýza ledvin MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• energetický metabolismus účinky léků   MeSH
• energetický příjem účinky léků   MeSH
• financování organizované MeSH
• ghrelin aplikace a dávkování   krev   terapeutické užití   MeSH
• klinické křížové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• podvýživa farmakoterapie   terapie   MeSH
• randomizované kontrolované studie jako téma MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH