- MeSH
- ekonomika a organizace zdravotní péče MeSH
- počítače MeSH
- socialismus MeSH
- veřejné zdravotnictví MeSH
- Geografické názvy
- Československo MeSH
Závěrečná zpráva o řešení grantu Agentury pro zdravotnický výzkum MZ ČR
nestr.
The balance and interaction between anorexigenic and orexigenic signals originating from the gut and brain appears to play an important role in the regulation of food intake and behavior. Existence of microbiota-gut-brain axis was recently suggested to play a critical role in mediating the effect of gut microorganisms on behavior. Certain components of gut microbiota were described to trigger the production of autoantibodies cross-reacting with appetite-regulating hormones. The regulation of appetite, emotion, and nutritional status is also under the control of immunoregulatory mechanisms which could lead to autoimmune reactions directed to neuronal autoantigens. We will study the effect of renutrition on anti-?-MSH and other antineuronal autoantibody formation, changes in gut microbiota composition and intestinal barrier function in patients with anorexia nervosa (AN). Simultaneously, we will determine the microbiota composition using DNA extraction and HTS before and during renutrition and after therapy in AN.The present project will have a high impact on clinical practice of AN.
Rovnováha a interakce mezi anorexigenními a orexigenními signály produkovanými gastrointestinálním traktem a centrálním nervovým systémem mají zásadní význam v řízení příjmu potravy a chování. Nedávno byla ukázána klíčová úloha osy střevní mikrobiota-gastrointestinální trakt-centrální nervový systém zprostředkující vliv střevních mikroorganismů na chování. Byly popsány určité komponenty střevní mikrobioty, které spouští produkci autoprotilátek zkříženě reagujících s hormony ovlivňujícími příjem potravy. Regulace příjmu potravy, emocí a nutričního stavu je také pod kontrolou imunoregulačních mechanismů, které by mohly vést k autoimunitním reakcím zaměřeným proti neuronálním autoantigenům. Budeme zkoumat vliv realimentace na tvorbu autoprotilátek proti ?-MSH a dalších antineuronálních autoprotilátek, změny ve složení střevní mikrobioty a funkci střevní bariéry u pacientek s mentální anorexií (AN). Zároveň budeme zjištovat složení střevní mikrobioty pomocí extrakce DNA a HTS před, během realimentace a po léčbě u AN. Předkládaný projekt bude mít dopad pro klinickou praxi u AN.
- Klíčová slova
- autoimmunity, gut microbiota, nutriční stav, nutritional status, mentální anorexie, Anorexia Nervosa, autoprotilátky, autoantibodies, autoimunita, Střevní mikrobiota, chování, behavior, ?-MSH, neuronální autoantigeny, realimentace, extrakce DNA, vysoce výkonné sekvenování (HTS), funkce střevní bariéry, příjem potravy, poruchy příjmu potravy, ?-MSH, neuronal autoantigens, refeeding, DNA extraction, high throughput sequencing (HTS), intestinal barrier function, food intake, eating disorders,
- NLK Publikační typ
- závěrečné zprávy o řešení grantu AZV MZ ČR
Asthma poses an increased risk for cardiovascular disorders, suggesting that allergy, which is an underlying process in asthma, causes atypical functioning of organs other than lungs. In a previous study in a guinea pig asthma model, we concluded that allergic sensitization increased aorta contractile responses to 5-HT. To further characterize these responses, here we explored the role of the 5-HT2 receptors family. We found that TCB-2 (5-HT2A agonist) and WAY161503 (5-HT2C agonist) induced aorta contractions resembling those elicited by 5-HT but less intense (~43 % and ~25 %, respectively). In these experiments, aortas from sensitized guinea pigs showed increased contractions to TCB-2, but not to WAY161503. In turn, MDL 100907 (5-HT2A antagonist) and RS-102221 (5-HT2C antagonist) caused a notably and a mild reduction of the 5-HT-induced contractions, respectively, with no differences seen between sensitized and non-sensitized tissues. BW723C86 (5-HT2B agonist) did not induce contractile responses and RS-127445 (5-HT2B antagonist) did not modify the contractile responses to 5-HT. In non-sensitized aortas, the pattern of protein expression of receptors was 5HT2B>5-HT2A=5-HT2C, which did not change in sensitized animals. In conclusion, we found that allergic sensitization increased the aorta contractile responses to 5-HT, partly mediated by enhanced responses of 5-HT2A receptors, which was unrelated to changes in the expression of these receptors.
- MeSH
- aorta MeSH
- bronchiální astma * MeSH
- morčata MeSH
- receptory serotoninové 5-HT2 MeSH
- receptory serotoninové metabolismus MeSH
- serotonin * MeSH
- zvířata MeSH
- Check Tag
- morčata MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Epidemiological and clinical studies suggest that asthma is associated with adverse cardiovascular outcomes, but its mechanism is uncertain. 5-Hydroxytryptamine (5-HT) is a mediator involved in asthma and in cardiovascular functioning. Thus, in the present study, we explored whether allergic sensitization in guinea pigs modifies 5-HT-induced contractile responses and 5-HT2A receptor expression in thoracic aorta rings. We found that sensitization produced a significant increase of 100 microM 5-HT-induced contractions of aorta rings (~27 % greater contraction than in non-sensitized animals, p<0.05). Preincubation with 10 nM ketanserin (a 5-HT2A receptor antagonist) reduced by ~30 % (p=0.003) and ~36 % (p=0.005) the area under the curve of 5-HT-induced contractions in aortas from non-sensitized and sensitized animals, respectively. There were no differences between sensitized and non-sensitized animals with respect to mRNA (qPCR) and protein (Western blot) expression of 5-HT2A receptor in thoracic aortas. We concluded that in this guinea pig model of asthma, allergic sensitization is not confined to airways, but also affects arterial contractile responses to 5-HT; changes in the expression of the 5-HT2A receptor appear not to be involved in this phenomenon.
- MeSH
- aorta patofyziologie MeSH
- bronchiální astma patofyziologie MeSH
- modely nemocí na zvířatech MeSH
- morčata MeSH
- receptor serotoninový 5-HT2A fyziologie MeSH
- serotonin fyziologie MeSH
- svaly hladké cévní patofyziologie MeSH
- zvířata MeSH
- Check Tag
- morčata MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- acetylmuramyl-alanyl-isoglutamin farmakologie MeSH
- adjuvancia imunologická farmakologie MeSH
- ileum fyziologie účinky léků MeSH
- metergolin farmakologie MeSH
- receptory serotoninové účinky léků MeSH
- serotonin analogy a deriváty farmakologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
We examined the relationship of two neurohormones with neuroendocrine impact (serotonin /5-HT/ and adiponectin) under standardized clinical conditions in an overweight cohort. Adiponectin was measured in serum and Serotonin was determined in the second morning urine samples. Serotonin correlated positively with adiponectin in our investigation Srho (+0.303; p=0.03). As high adiponectin level corresponds with a low risk of Insulin resistance our findings refer to possible improvement of prediabetic conditions in overweight patients tracking peripheral serotonin circulation. Further clinical evidence is mandatory to verify the effects of 5-HT in patients with metabolic syndrome
The type B trichothecenes pollute food crops and have been associated to alimentary toxicosis resulted in emetic reaction in human and animal. This group of mycotoxins consists deoxynivalenol (DON) and four structurally related congeners: 3-acetyl-deoxynivalenol (3-ADON), 15-acetyl deoxynivalenol (15-ADON), nivalenol (NIV) and 4-acetyl-nivalenol (fusarenon X, FX). While emesis induced by intraperitoneally dosed to DON in the mink has been related to plasma up-grading of 5-hydroxytryptamine (5-HT) and neurotransmitters peptide YY (PYY), the impact of oral dosing with DON or its four congeners on secretion of these chemical substances have not been established. The aim of this work was to contraste emetic influence to type B trichothecene mycotoxins by orally dosing and involve these influence to PYY and 5-HT. All five toxins attracted marked emetic reaction that are relevant to elevated PYY and 5-HT. The reduction in vomiting induced by the five toxins and PYY was due to blocking of the neuropeptide Y2 receptor. The inhibition of the induced vomiting response by 5-HT and all five toxins is regulated by the 5-HT3 receptor inhibitor granisetron. In a word, our results indicate that PYY and 5-HT take a key role in the emetic reaction evoked by type B trichothecenes.
- MeSH
- emetika škodlivé účinky MeSH
- lidé MeSH
- mykotoxiny * škodlivé účinky MeSH
- norek MeSH
- peptid YY MeSH
- serotonin MeSH
- trichotheceny typu B * škodlivé účinky MeSH
- trichotheceny * toxicita MeSH
- zvířata MeSH
- zvracení chemicky indukované MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- acetylmuramyl-alanyl-isoglutamin farmakologie MeSH
- adjuvancia imunologická farmakologie MeSH
- finanční podpora výzkumu jako téma MeSH
- morčata MeSH
- osmium metabolismus účinky léků MeSH
- receptory serotoninové metabolismus MeSH
- techniky in vitro MeSH
- zvířata MeSH
- Check Tag
- morčata MeSH
- zvířata MeSH
