The first-line effector mechanisms of immune defence, including inflammation and oxidative burst, contribute significantly to host-pathogen resistance. Whether these immune responses undergo age-related changes in birds remains unknown. Here, we tracked selected inflammatory parameters in 54 free-living great tits (Parus major) of known age, captured repeatedly over three consecutive years, with the aims to investigate long-term repeatability and age-dependent changes in cellular oxidative burst responsiveness upon in vitro stimulation with bacterial lipopolysaccharide (LPS), and to identify its relationships with leukotriene B4 (LTB4) levels and haematological traits. In addition, we linked these immunological traits to selected physiological markers (antioxidants and oxidative stress markers). LTB4 levels increased with age and we have shown a similar non-significant tendency also for absolute granulocyte counts, indicating propagating chronic inflammation over the bird's lifetime, consistent with the inflammaging hypothesis. In contrast, cellular oxidative burst followed a quadratic trend of dependency on age with a peak in midlife individuals, in line with the immunosenescence hypothesis. Interestingly, LTB4 levels were positively associated with general oxidative damage, but negatively with antioxidant glutathione peroxidase activity, indicating links to redox balance. This longitudinal study demonstrates the contrasting patterns of age-related changes in background and acute markers of pro-inflammatory immunity contributing to immunosenescence in birds and thus provides basis for interpretation of the tested inflammatory markers in cross-cohort datasets.

• MeSH
• imunosenescence * MeSH
• lidé MeSH
• longitudinální studie MeSH
• oxidační stres MeSH
• stárnutí MeSH
• zánět MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The endocannabinoid/CB1R system as well as the central ghrelin signalling with its growth hormone secretagogoue receptors (GHS-R1A) are importantly involved in food intake and reward/reinforcement processing and show distinct overlaps in distribution within the relevant brain regions including the hypothalamus (food intake), the ventral tegmental area (VTA) and the nucleus accumbens (NAC) (reward/reinforcement). The significant mutual interaction between these systems in food intake has been documented; however, the possible role of ghrelin/GHS-R1A in the cannabinoid reinforcement effects and addiction remain unclear. Therefore, the principal aim of the present study was to investigate whether pretreatment with GHS-R1A antagonist/JMV2959 could reduce the CB1R agonist/WIN55,212-2-induced dopamine efflux in the nucleus accumbens shell (NACSh), which is considered a crucial trigger impulse of the addiction process. The synthetic aminoalklylindol cannabinoid WIN55,212-2 administration into the posterior VTA induced significant accumbens dopamine release, which was significantly reduced by the 3 mg/kg i.p. JMV2959 pretreatment. Simultaneously, the cannabinoid-increased accumbens dopamine metabolic turnover was significantly augmented by the JMV2959 pretreament. The intracerebral WIN55,212-2 administration also increased the endocannabinoid arachidonoylethanolamide/anandamide and the 2-arachidonoylglycerol/2-AG extracellular levels in the NACSh, which was moderately but significantly attenuated by the JMV2959 pretreatment. Moreover, the cannabinoid-induced decrease in accumbens γ-aminobutyric acid/gamma-aminobutyric acid levels was reversed by the JMV2959 pretreatment. The behavioural study in the LABORAS cage showed that 3 mg/kg JMV2959 pretreatment also significantly reduced the systemic WIN55,212-2-induced behavioural stimulation. Our results demonstrate that the ghrelin/GHS-R1A system significantly participates in the rewarding/reinforcing effects of the cannabinoid/CB1 agonist that are involved in cannabinoid addiction processing.

• MeSH
• benzoxaziny aplikace a dávkování   MeSH
• dopamin metabolismus   MeSH
• endokanabinoidy metabolismus   MeSH
• GABA metabolismus   MeSH
• ghrelin metabolismus   MeSH
• glyceridy metabolismus   MeSH
• glycin aplikace a dávkování   analogy a deriváty   MeSH
• kyseliny arachidonové metabolismus   MeSH
• morfoliny aplikace a dávkování   MeSH
• naftaleny aplikace a dávkování   MeSH
• nucleus accumbens účinky léků   metabolismus   MeSH
• polynenasycené alkamidy metabolismus   MeSH
• potkani Wistar MeSH
• preklinické hodnocení léčiv MeSH
• triazoly aplikace a dávkování   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The extended occurrence of fentanils abuse associated with the dramatic increase in opioid fatal overdoses and dependence strongly emphasizes insufficiencies in opioid addiction treatment. Recently, the growth hormone secretagogue receptor (GHS-R1A) antagonism was proposed as a promising mechanism for drug addiction therapy. However, the role of GHS-R1A and its endogenous ligand ghrelin in opioid abuse is still unclear. Therefore, the aim of our study was to clarify whether the GHS-R1A antagonist JMV2959 could reduce the fentanyl-induced conditioned place preference (CPP), the fentanyl intravenous self-administration (IVSA), and the tendency to relapse, but also whether JMV2959 could significantly influence the fentanyl-induced dopamine efflux in the nucleus accumbens (NAC) in rats, that importantly participates in opioids' reinforcing effects. Following an ongoing fentanyl self-administration, JMV2959 3 mg/kg was administered intraperitoneally 20 minutes before three consequent daily 360-minute IVSA sessions under a fixed ratio FR1, which significantly reduced the number of active lever-pressing, the number of infusions, and the fentanyl intake. Pretreatment with JMV2959 also reduced the fentanyl-seeking/relapse-like behaviour tested in rats on the 12th day of the forced abstinence period. Pretreatment with JMV2959 significantly and dose-dependently reduced the manifestation of fentanyl-CPP. The fentanyl-CPP development was reduced after the simultaneous administration of JMV2959 with fentanyl during conditioning. The JMV2959 significantly reduced the accumbens dopamine release induced by subcutaneous and intravenous fentanyl. Simultaneously, it affected the concentration of byproducts associated with dopamine metabolism in the NAC. Our findings suggest that GHS-R1A importantly participates in the rewarding/reinforcing effects of fentanyl.

• MeSH
• autoaplikace MeSH
• dopamin metabolismus   MeSH
• fentanyl aplikace a dávkování   škodlivé účinky   MeSH
• ghrelin metabolismus   MeSH
• glycin analogy a deriváty   farmakologie   MeSH
• intravenózní podání MeSH
• krysa rodu rattus MeSH
• narkotika aplikace a dávkování   škodlivé účinky   MeSH
• nucleus accumbens účinky léků   MeSH
• operantní podmiňování účinky léků   MeSH
• potkani Wistar MeSH
• receptory ghrelinu antagonisté a inhibitory   MeSH
• triazoly farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Chronic stress is considered as a risk factor for developing insulin resistance and diabetes mellitus. Pheochromocytoma is a useful model for studying the influence of long-term catecholamines overproduction on cardiometabolic disorders in humans. Catecholamines induce a hypermetabolic state with various metabolic abnormalities. The exact mechanisms of their action remain unclear. The aim of the study is to determine the mechanism of action of catecholamines on energy and glucose metabolism in relation to insulin resistance and diabetes mellitus in pheochromocytoma and to clarify the role of adipose tissue in this process. The project will thus by using the modern methods of molecular biology, metabolomics and flow cytometry aim to clarify the exact mechanisms behind the interactions of catecholamines, glucose metabolism and adipose tissue and to identify novel factors responsible for pathophysiological consequences of these interactions. The results could contribute to better understanding the effects of sympathoadrenal system in the development of insulin resistance.

Chronický stres je považován za rizikový faktor v patogenezi inzulinorezistence a rozvoji diabetes mellitus. Feochromocytom může sloužit jako vhodný model pro sledování vlivu dlouhodobé nadprodukce katecholaminů na metabolické a kardiovaskulární změny u lidí. Katecholaminy navozují hypermetabolický stav provázený řadou metabolických abnormalit. Přesné mechanizmy působení včetně vlivu na tukovou tkáň zůstávají neobjasněny. Záměrem studie je porozumět mechanizmu působení katecholaminů na energetický a glukózový metabolismus ve vztahu k rozvoji inzulinorezistence a diabetes mellitus u nemocných s feochromocytomem a současně objasnit úlohu tukové tkáně v rozvoji metabolických změn. Cílem studie je objasnit mechanizmy interakce mezi nadprodukcí katecholaminů, metabolismem glukózy a tukovou tkání s využitím moderních metod molekulární biologie, metabolomiky a průtokové cytometrie a současně identifikovat nové faktory zodpovědné za patofyziologické důsledky těchto interakcí. Výsledky mají přinést nové poznatky o vlivu sympatoadrenálního systému v rozvoji inzulinorezistence.

• MeSH
• diabetes mellitus etiologie   MeSH
• energetický metabolismus MeSH
• feochromocytom MeSH
• glukosa metabolismus   MeSH
• inzulinová rezistence MeSH
• katecholaminy škodlivé účinky   MeSH
• lidé MeSH
• metabolické nemoci etiologie   MeSH
• psychický stres MeSH
• tuková tkáň MeSH
• Check Tag
• lidé MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• onkologie
• vnitřní lékařství
• NLK Publikační typ
• závěrečné zprávy o řešení grantu AZV MZ ČR

• Publikační typ
• abstrakt z konference MeSH

• Publikační typ
• abstrakt z konference MeSH

• Publikační typ
• abstrakt z konference MeSH

Adipose tissue and its dysfunction in obesity and type 2 diabetes play an important role in the development of cardiovascular complications. The aim of the project is to elucidate the role and the mechanism of action of epicardial adipose tissue in the development of heart disease and cardiovascular complications with special focus on its endocrine dysfunction, local and systemic subclinical inflammation and the changes in local immunocompetent cells composition. The close proximity of epicardial fat to myocardium and coronary arteries opens the possibility of close paracrine and cellular interactions among these tissues. The project will utilize modern methods of molecular biology, metabolomics, proteomics, flow cytometry and immunohistochemistry to identify exact mechanisms behind the interactions of epicardial fat and myocardium in cardiac surgery and heart transplantation patients and to identify novel factors that might be directly responsible for pathophysiological consequences of these interactions.

Tuková tkáň a její dysfunkce u pacientů s obezitou a diabetem 2. typu má zásadní význam při rozvoji kardiovaskulárních komplikací. Cílem projektu je objasnit význam a mechanizmus působení epikardiální tukové tkáně při rozvoji onemocnění srdce a kardiovaskulárních komplikací s důrazem na endokrinní dysfunkci epikardiálního tuku, jeho subklinický zánět a změny složení imunokompetentních buněk. Těsná blízkost epikardiálního tuku, myokardu a koronárních arterií otvírá možnost těsných parakrinních a buněčných interakcí mezi epikardiálním tukem a myokardem. V rámci projektu budou použity moderní metody molekulární biologie, metabolomiky, proteomiky, průtokové cytometrie a imunohistochemie k ozřejmění mechanizmů interakce epikardiálního tuku a myokardu u pacientů podstupujících kardiochirurgickou operaci respektive transplantaci srdce a k identifikaci nových faktorů zodpovědných za patofyziologické důsledky těchto interakcí.

• MeSH
• diabetes mellitus 2. typu etiologie   MeSH
• imunokompetence MeSH
• nemoci srdce komplikace   MeSH
• obezita etiologie   MeSH
• perikard patologie   MeSH
• rizikové faktory MeSH
• tuková tkáň MeSH
• zánět MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• kardiologie
• NLK Publikační typ
• závěrečné zprávy o řešení grantu AZV MZ ČR

OBJECTIVES: With over 35 million cases worldwide, Alzheimer's disease (AD) represents the main cause of dementia. The differentiation of AD from other types of dementia is challenging and its early diagnosis is complicated. The established biomarkers are not only based on the invasive collection of cerebrospinal fluid, but also lack sufficient sensitivity and specificity. Therefore, much current effort is aimed at the identification of new biomarkers of AD in peripheral blood. DESIGN AND METHODS: We focused on blood-based analyses using chiroptical spectroscopy (Raman optical activity, electronic circular dichroism) supplemented with conventional vibrational spectroscopy (infrared, Raman) and metabolomics (high-performance liquid chromatography with a high-resolution mass detection). RESULTS: This unique approach enabled us to identify the spectral pattern of AD and variations in metabolite levels. Subsequent linear discriminant analysis of the spectral data resulted in differentiation between the AD patients and control subjects. CONCLUSIONS: It may be stated that this less invasive approach has strong potential for the identification of disease-related changes within essential plasmatic biomolecules and metabolites.

• MeSH
• Alzheimerova nemoc krev   diagnóza   MeSH
• biologické markery krev   MeSH
• cirkulární dichroismus MeSH
• diskriminační analýza MeSH
• krevní proteiny analýza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metabolomika MeSH
• Ramanova spektroskopie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH

• Publikační typ
• abstrakt z konference MeSH