IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide. Current studies have shown that the Th17/Treg immune balance may be involved in the occurrence of IgAN, but the exact mechanism is still unclear. Indoleamine 2,3-dioxygenase (IDO) is an enzyme that catalyses degradation of tryptophan (Trp) through the kynurenine (Kyn) pathway; it can control inflammation and immune response by inducing Trp starvation. IDO may be a key molecule in regulating the Th17/Treg immune balance. However, it is not clear whether IDO is involved in the IgAN disease occurrence by regulating the Th17/Treg immune balance. In this study, an IgAN mouse model was established. The mice were intraperitoneally inoculated with IDO inhibitor 1-MT or agonist ISS-ODN to observe whether the IDO signalling pathway participates in the occurrence and development of IgAN by regulating the Th17/Treg immune balance. The results showed that IDO inhibitor 1-MT significantly increased renal injury and glomerular IgA accumulation and up-regulated Th17/Treg and Th17-related cytokine expression in IgAN mice, while ISS-ODN significantly decreased renal injury and glomerular IgA accumulation, down-regulated Th17/Treg expression and inhibited Th17-related cytokine expression in IgAN mice. In conclusion, IDO was involved in the occurrence and progress of IgAN by regulating the Th17/ Treg balance.

• MeSH
• buňky Th17 imunologie   MeSH
• cytokiny metabolismus   MeSH
• IgA nefropatie enzymologie   imunologie   MeSH
• imunita * MeSH
• indolamin-2,3,-dioxygenasa metabolismus   MeSH
• ledviny zranění   metabolismus   patologie   MeSH
• myši inbrední BALB C MeSH
• regulační T-lymfocyty imunologie   MeSH
• signální transdukce MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Tumor-initiating cells (TICs) often survive therapy and give rise to second-line tumors. We tested the plausibility of sphere cultures as models of TICs. Microarray data and microRNA data analysis confirmed the validity of spheres as models of TICs for breast and prostate cancer as well as mesothelioma cell lines. Microarray data analysis revealed the Trp pathway as the only pathway upregulated significantly in all types of studied TICs, with increased levels of indoleamine-2,3-dioxygenase-1 (IDO1), the rate-limiting enzyme of Trp metabolism along the kynurenine pathway. All types of TICs also expressed higher levels of the Trp uptake system consisting of CD98 and LAT1 with functional consequences. IDO1 expression was regulated via both transcriptional and posttranscriptional mechanisms, depending on the cancer type. Serial transplantation of TICs in mice resulted in gradually increased IDO1. Mitocans, represented by α-tocopheryl succinate and mitochondrially targeted vitamin E succinate (MitoVES), suppressed IDO1 in TICs. MitoVES suppressed IDO1 in TICs with functional mitochondrial complex II, involving transcriptional and posttranscriptional mechanisms. IDO1 increase and its suppression by VE analogues were replicated in TICs from primary human glioblastomas. Our work indicates that IDO1 is increased in TICs and that mitocans suppress the protein.

• MeSH
• alfa-tokoferol farmakologie   MeSH
• antigeny CD98 genetika   metabolismus   MeSH
• fytogenní protinádorové látky farmakologie   MeSH
• indolamin-2,3,-dioxygenasa genetika   metabolismus   MeSH
• kynurenin metabolismus   MeSH
• lidé MeSH
• metabolické sítě a dráhy účinky léků   genetika   MeSH
• mitochondrie účinky léků   metabolismus   MeSH
• nádorové buněčné linie MeSH
• nádorové kmenové buňky účinky léků   metabolismus   patologie   MeSH
• přenašeč velkých neutrálních aminokyselin 1 genetika   metabolismus   MeSH
• regulace genové exprese u nádorů * MeSH
• respirační komplex II genetika   metabolismus   MeSH
• signální transdukce MeSH
• tryptofan metabolismus   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

INTRODUCTION: Crohn's disease (CD) is a disabling chronic enteropathy sustained by a harmful T-cell response toward antigens of the gut microbiota in genetically susceptible subjects. Growing evidence highlights the safety and possible efficacy of mesenchymal stem cells (MSCs) as a new therapeutic tool for this condition. Therefore, we aimed to investigate the effects of bone marrow-derived MSCs on pathogenic T cells with a view to clinical application. METHODS: T-cell lines from both inflamed and non-inflamed colonic mucosal specimens of CD patients and from healthy mucosa of control subjects were grown with the antigen muramyl-dipeptide in the absence or presence of donors' MSCs. The MSC effects were evaluated in terms of T-cell viability, apoptotic rate, proliferative response, immunophenotype, and cytokine profile. The role of the indoleamine 2,3-dioxygenase (IDO) was established by adding a specific inhibitor, the 1-methyl-DL-tryptophan, and by using MSCs transfected with the small interfering RNA (siRNA) targeting IDO. The relevance of cell-cell contact was evaluated by applying transwell membranes. RESULTS: A significant reduction in both cell viability and proliferative response to muramyl-dipeptide, with simultaneous increase in the apoptotic rate, was found in T cells from both inflamed and non-inflamed CD mucosa when co-cultured with MSCs and was reverted by inhibiting IDO activity and expression. A reduction of the activated CD4(+)CD25(+) subset and increase of the CD3(+)CD69(+) population were also observed when T-cell lines from CD mucosa were co-cultured with MSCs. In parallel, an inhibitory effect was evident on the expression of the pro-inflammatory cytokines tumor necrosis factor-α, interferon-γ, interleukin-17A and -21, whereas that of the transforming growth factor-β and interleukin-6 were increased, and production of the tolerogenic molecule soluble HLA-G was high. These latter effects were almost completely eliminated by blocking the IDO, whose activity was upregulated in MSCs co-cultured with CD T cells. The use of a semipermeable membrane partially inhibited the MSC immunosuppressive effects. Finally, hardly any effects of MSCs were observed when T cells obtained from control subjects were used. CONCLUSION: MSCs exert potent immunomodulant effects on antigen-specific T cells in CD through a complex paracrine and cell-cell contact-mediated action, which may be exploited for widespread therapeutic use.

• MeSH
• acetylmuramyl-alanyl-isoglutamin farmakologie   MeSH
• antigeny povrchové metabolismus   MeSH
• apoptóza účinky léků   MeSH
• buňky kostní dřeně cytologie   MeSH
• časosběrné zobrazování MeSH
• Crohnova nemoc patologie   MeSH
• cytokiny metabolismus   MeSH
• dospělí MeSH
• HLA-G antigeny metabolismus   MeSH
• imunofenotypizace MeSH
• indolamin-2,3,-dioxygenasa antagonisté a inhibitory   genetika   metabolismus   MeSH
• kokultivační techniky MeSH
• kultivované buňky MeSH
• lidé středního věku MeSH
• lidé MeSH
• malá interferující RNA metabolismus   MeSH
• mezenchymální kmenové buňky cytologie   metabolismus   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• proliferace buněk účinky léků   MeSH
• RNA interference MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• střevní sliznice cytologie   MeSH
• T-lymfocyty cytologie   účinky léků   imunologie   MeSH
• tryptofan analogy a deriváty   farmakologie   MeSH
• viabilita buněk MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Maternal immune activation during pregnancy is a risk factor for offspring neuropsychiatric disorders. Among the mechanistic pathways by which maternal inflammation can affect fetal brain development and programming, those involving tryptophan (TRP) metabolism have drawn attention because various TRP metabolites have neuroactive properties. This study evaluates the effect of bacterial (lipopolysaccharides/LPS) and viral (polyinosinic:polycytidylic acid/poly I:C) placental infection on TRP metabolism using an ex vivo model. Human placenta explants were exposed to LPS or poly I:C, and the release of TRP metabolites was analyzed together with the expression of related genes and proteins and the functional activity of key enzymes in TRP metabolism. The rate-limiting enzyme in the serotonin pathway, tryptophan hydroxylase, showed reduced expression and functional activity in explants exposed to LPS or poly I:C. Conversely, the rate-limiting enzyme in the kynurenine pathway, indoleamine dioxygenase, exhibited increased activity, gene, and protein expression, suggesting that placental infection mainly promotes TRP metabolism via the kynurenine (KYN) pathway. Furthermore, we observed that treatment with LPS or poly I:C increased activity in the kynurenine monooxygenase branch of the KYN pathway. We conclude that placental infection impairs TRP homeostasis, resulting in decreased production of serotonin and an imbalance in the ratio between quinolinic acid and kynurenic acid. This disrupted homeostasis may eventually expose the fetus to suboptimal/toxic levels of neuroactive molecules and impair fetal brain development.

• MeSH
• indolamin-2,3,-dioxygenasa metabolismus   MeSH
• kynurenin * metabolismus   MeSH
• lidé MeSH
• lipopolysacharidy toxicita   MeSH
• placenta * metabolismus   MeSH
• poly I metabolismus   MeSH
• serotonin metabolismus   MeSH
• těhotenství MeSH
• tryptofan metabolismus   MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Dosažení patologické kompletní odpovědi po neoadjuvantní chemoterapii je ukazatelem dlouhodobé kontroly onemocnění. V předchozím projektu byla patologická kompletní odpověď pozorována významně častěji u nemocných s nádory expresí HER-2 a bez exprese HER-2 i hormonálních receptorů. Cílem předkládaného projektu je studovat biologickou odpověď na neoadjuvantní chemoterapii. Použity budou standardní režimy chemoterapie používané v jednotlivých centrech a volbu léčby projekt neovlivní. V retrospektivní studii na materiálu nemocných z 2 center budou vyhodnoceny rozdíly tumor infiltrujících lymfocytů u nemocných s různým fenotypem nádoru, bude také studován vliv exprese indoleamin 2,3-dioxygenázy na přítomnost tumor infiltrujících lymfocytů a bude provedeno imunohistochemické zhodnocení fenotypu nádoru. Budou rovněž sledovány změny metabolismu železa a citrulin, ukazatel toxicity léčby.; Pathologic complete response is an indicator of long-term disease control after neoadjuvant chemotherapy in breast carcinoma. In our earlier study, patologic complete response was observed significantly more often in patients with tumors expressing HER-2 or triple negative tumors. The aim of the present study is to study biologic response to neoadjuvant chemotherapy in patients treated with standard regimens that will not be affected by the project. In a retrospective study on material from patients in 2 centers difference in tumor infiltrating lymphocytes in patients with different tumor phenotype as well as the association between indoleamine 2,3-dioxygenase expression and the presence of tumor infiltrating lymphocytes will be evaluated together with tumor phenotype using immunohistochemistry. Alterations of iron metabolism and citrulline, an indicator of intestinal toxicity, will also be assessed.

• MeSH
• alfa-tokoferol MeSH
• citrulin analýza   MeSH
• fenotyp MeSH
• imunohistochemie MeSH
• imunologické faktory MeSH
• indolamin-2,3,-dioxygenasa MeSH
• karcinom prsu in situ MeSH
• kynurenin MeSH
• lymfocyty účinky léků   MeSH
• nádory prsu MeSH
• neoadjuvantní terapie MeSH
• neopterin MeSH
• poruchy metabolismu železa MeSH
• prognóza MeSH
• receptor erbB-2 MeSH
• retrospektivní studie MeSH
• triple-negativní karcinom prsu MeSH
• vitamin A MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• onkologie
• gynekologie a porodnictví
• NLK Publikační typ
• závěrečné zprávy o řešení grantu IGA MZ ČR

V posledních letech se věnuje vzrůstající pozornost enzymu indolamin 2,3-dioxygenáze (IDO), která rozkládá tryptofan. Rychle totiž přibývá poznatků o tom, že kynurenin a další metabolity tryptofanu hrají významnou roli v patogenezi zhoubných nádorů a některých nervových a psychiatrických onemocnění. Postupné poznávání mechanismů, které se při jejich vzniku a průběhu uplatňují, umožňuje bližší poznání etiologických faktorů a tvoří předpoklady pro zlepšení jejich diagnostiky a léčby. V onkologii se nejvíce úsilí soustřeďuje na vývoj a prověrku substancí, které inhibují IDO. Očekává se, že některé z nich se významně uplatní v imunoterapii nádorů. V oblasti duševních poruch, především pak schizofrenie a depresivní poruchy, je role IDO spojována s imunitní dysregulací. IDO u těchto onemocnění přestavuje možný mediátor mezi imunitními změnami a poruchou funkce mozku. Změna aktivity IDO rovněž může zprostředkovat interakci mezi genetickou dispozicí a faktory prostředí v patofyziologii těchto onemocnění.

In the last years an attention has been paid to the indoleamine 2,3-dioxygenase (IDO), an enzyme catabolising L-tryptophan to kynurenine. Growing evidence has been accumulated that kynurenine and other metabolites of tryptophan play an important role in the pathogenesis of malignant tumours and some neurological and psychiatric disorders. The gradual recognition of mechanisms operative in their development may help to identify etiological factors involved and becomes prerequisite for the progress in their diagnostics and therapy. In oncology, great effort is directed to the development and testing of substances inhibiting IDO activity. It is expected that some of them will be utilized in the immunotherapy of cancer. In the field of psychiatric disorders, namely in schizophrenia and depression, the role of IDO is linked to immune dysregulation. In those diseases, IDO represents a potential mediator between immunological reactivity and alterations of the brain function. Changes in the IDO activity may also mediate interaction between the genetic predisposition and environmental factors.

• MeSH
• deprese imunologie   MeSH
• dioxygenasy * fyziologie   metabolismus   MeSH
• duševní poruchy metabolismus   patofyziologie   MeSH
• genetická predispozice k nemoci MeSH
• imunoterapie MeSH
• lidé MeSH
• nádory imunologie   metabolismus   MeSH
• oxygenasy * fyziologie   metabolismus   MeSH
• schizofrenie imunologie   MeSH
• Th1 buňky imunologie   MeSH
• Th2 buňky imunologie   MeSH
• toxoplazmóza imunologie   MeSH
• tryptofan-2,3-dioxygenasa * fyziologie   metabolismus   MeSH
• tryptofan imunologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

The immunoregulatory properties of mesenchymal stem cells (MSCs) have been well documented in various models in vitro and in vivo. Furthermore, a population of regulatory B cells (Bregs) that produce relatively high concentrations of IL-10 has been recently described. To study the relationship between MSCs and Bregs, we analyzed the effects of MSCs on IL-10 production by lipopolysaccharide (LPS)-activated mouse B cells. The production of IL-10 by B cells remained preserved in the presence of MSCs and was even significantly enhanced by IFN-γ. However, the production of IL-10 was strongly suppressed in cultures containing MSCs and IFN-γ. Preincubation of MSCs, but not of B cells, with IFN-γ induced the suppression of IL-10 secretion in cultures containing MSCs and B cells. The supernatants from IFN-γ-treated MSCs had no inhibitory effect, and the suppression of IL-10 production was abrogated if the MSCs and B cells were separated in a transwell system. Analysis of the gene expression of IFN-γ- or IFN-γ and LPS-treated MSCs revealed a strong upregulation of genes for indoleamine-2,3-dioxygenase (IDO), cyclooxygenase-2 (Cox-2) and programmed cell death-ligand 1 (PD-L1). While the inhibition of IDO activity or the inclusion of the neutralization monoclonal antibody anti-PD-L1 did not abrogate the suppression, indomethacin, an inhibitor of Cox-2, completely inhibited the MSC-mediated suppression of IL-10 production. Accordingly, the production of IL-10 by B cells was inhibited by exogenous prostaglandin E2. The results thus suggest that IFN-γ-treated MSCs strongly inhibit IL-10 production by activated B cells by a mechanism requiring cell contact and involving the Cox-2 pathway.

• MeSH
• aktivace lymfocytů účinky léků   MeSH
• antigeny CD274 antagonisté a inhibitory   genetika   imunologie   MeSH
• B-lymfocyty cytologie   účinky léků   imunologie   MeSH
• cyklooxygenasa 2 genetika   imunologie   MeSH
• difuzní komory kultivační MeSH
• dinoproston farmakologie   MeSH
• indolamin-2,3,-dioxygenasa genetika   imunologie   MeSH
• indomethacin farmakologie   MeSH
• inhibitory cyklooxygenasy farmakologie   MeSH
• interferon gama farmakologie   MeSH
• interleukin-10 antagonisté a inhibitory   genetika   imunologie   MeSH
• kokultivační techniky MeSH
• kultivační média speciální farmakologie   MeSH
• lipopolysacharidy farmakologie   MeSH
• mezenchymální kmenové buňky cytologie   účinky léků   imunologie   MeSH
• mezibuněčná komunikace imunologie   MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• neutralizující protilátky farmakologie   MeSH
• primární buněčná kultura MeSH
• regulace genové exprese MeSH
• signální transdukce MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Esenciální aminokyselina tryptofan slouží jako substrát pro tvorbu řady bioaktivních sloučenin. V anabolických procesech je využívána jen malá část tryptofanu, zatímco velká většina je metabolizována kynureninovou cestou. Degradace tryptofanu na kynurenin je v současné době chápána jako klíčový regulátor vrozené a adaptivní imunity. Hlavním kontrolním enzymem této dráhy je indolamin 2,3-dioxygenáza (IDO). Jedná se o enzym, který katalyzuje počáteční krok při jeho přeměně na kynurenin. Jednou z fyziologických rolí tohoto enzymu je regulovat zánětlivý proces a mírnit jeho případné nežádoucí účinky. Deplece tryptofanu a přítomnost kynureninů vede k anergii efektorových T lymfocytů, aktivaci T regulačních buněk a může stimulovat dendritické buňky k diferenciaci na imunosupresivní fenotyp. Zvýšená degradace tryptofanu je pozorována u nemocí a poruch provázených buněčnou imunitní aktivací, např. infekčních a autoimunitních onemocnění, alergických stavů a nádorových onemocnění. Stanovení hladiny tryptofanu nebo jeho metabolitů by mohlo být přínosné z hlediska monitorování některých imunopatologických stavů. Problémem však zůstává technická dostupnost laboratorního stanovení tohoto parametru. Aktivitu IDO lze stanovit i nepřímo poměrem kynureninu a tryptofanu, což je spolehlivý index degradace tryptofanu.

The essential amino acid tryptophan is a substrate for the generation of several bioactive compounds with important physiological roles. Only a small fraction of ingested tryptophan is used in anabolic processes, whereas the large majority is metabolized along the kynurenine pathway of tryptophan degradation. This pathway generates a range of metabolites, collectively known as kynurenines, involved in inflammation and immune response. The kynurenine pathway is highly regulated in the immune system, where it promotes immunosuppression in response to inflammation or infection. Kynurenine reduces the activity of natural killer cells, dendritic cells, or proliferating T cells. Indoleamine 2,3-dioxygenase is a rate-limiting enzyme for tryptophan metabolism. Increased tryptophan degradation is observed in diseases and disorders accompanied by cellular immune activation, such as infectious and autoimmune diseases, allergic conditions and cancer. Determination of the level of tryptophan or its metabolites could be beneficial in terms of monitoring certain immunopathological conditions. Actually, indoleamine 2,3-dioxygenase activity could be indirectly measured by the kynurenin to tryptophan ratio, a reliable index of tryptophan breakdown

• MeSH
• aktivní imunita fyziologie   imunologie   MeSH
• alergie enzymologie   imunologie   MeSH
• autoimunitní nemoci epidemiologie   imunologie   metabolismus   MeSH
• imunologická tolerance imunologie   MeSH
• indolamin-2,3,-dioxygenasa fyziologie   imunologie   MeSH
• kynurenin metabolismus   MeSH
• lidé MeSH
• nádory metabolismus   MeSH
• střevní mikroflóra imunologie   MeSH
• tryptofan * analýza   imunologie   metabolismus   MeSH
• vysokoúčinná kapalinová chromatografie metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Mesenchymal stem cells (MSCs) represent a population of cells which have the ability to regulate reactivity of T and B lymphocytes by multiple mechanisms. The immunoregulatory activities of MSCs are strictly influenced by the cytokine environment. Here we show that two functionally distinct cytokines, interleukin-4 (IL-4) and interferon-γ (IFN-γ), significantly potentiate the ability of MSCs to inhibit IL-10 production by activated regulatory B cells (Bregs). However, MSCs in the presence of IL-4 or IFN-γ inhibit the IL-10 production by different mechanisms. Preincubation of MSCs with IFN-γ led to the suppression, but pretreatment with IL-4 of neither MSCs nor B cells resulted in the suppression of IL-10 production. The search for candidate regulatory molecules expressed in cytokine-treated MSCs revealed different patterns of the gene expression. Pretreatment of MSCs with IFN-γ, but not with IL-4, induced expression of indoleamine-2,3-dioxygenase, cyclooxygenase-2 and programmed cell death-ligand 1. To identify the molecule(s) responsible for the suppression of IL-10 production, we used specific inhibitors of the putative regulatory molecules. We found that indomethacine, an inhibitor of cyclooxygenase-2 (Cox-2) activity, completely abrogated the inhibition of IL-10 production in cultures containing MSCs and IFN-γ, but had no effect on the suppression in cell cultures containing MSCs and IL-4. The results show that MSCs can inhibit the response of B cells to one stimulus by different mechanisms in dependence on the cytokine environment and thus support the idea of the complexity of immunoregulatory action of MSCs.

• MeSH
• aktivace lymfocytů účinky léků   imunologie   MeSH
• antigeny CD279 genetika   imunologie   metabolismus   MeSH
• buněčné mikroprostředí účinky léků   imunologie   MeSH
• cyklooxygenasa 2 genetika   imunologie   metabolismus   MeSH
• cytokiny imunologie   metabolismus   farmakologie   MeSH
• ELISA MeSH
• exprese genu účinky léků   genetika   imunologie   MeSH
• indolamin-2,3,-dioxygenasa genetika   imunologie   metabolismus   MeSH
• interferon gama farmakologie   MeSH
• interleukin-10 imunologie   metabolismus   MeSH
• interleukin-4 farmakologie   MeSH
• interleukin-6 genetika   imunologie   metabolismus   MeSH
• kokultivační techniky MeSH
• kultivované buňky MeSH
• mezenchymální kmenové buňky účinky léků   imunologie   metabolismus   MeSH
• myši MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• regulační B-lymfocyty účinky léků   imunologie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Tryptophan is an essential amino acid whose metabolites play key roles in diverse physiological processes. Due to low reserves in the body, especially under various catabolic conditions, tryptophan deficiency manifests itself rapidly, and both the serotonin and kynurenine pathways of metabolism are clinically significant in critically ill patients. In this review, we highlight these pathways as sources of serotonin and melatonin, which then regulate neurotransmission, influence circadian rhythm, cognitive functions, and the development of delirium. Kynurenines serve important signaling functions in inter-organ communication and modulate endogenous inflammation. Increased plasma kynurenine levels and kynurenine-tryptophan ratios are early indicators for the development of sepsis. They also influence the regulation of skeletal muscle mass and thereby the development of polyneuromyopathy in critically ill patients. The modulation of tryptophan metabolism could help prevent and treat age-related disease with low grade chronic inflammation as well as post intensive care syndrome in all its varied manifestations: cognitive decline (including delirium or dementia), physical impairment (catabolism, protein breakdown, loss of muscle mass and tone), and mental impairment (depression, anxiety or post-traumatic stress disorder).

• MeSH
• delirium etiologie   MeSH
• deprese etiologie   MeSH
• indolamin-2,3,-dioxygenasa metabolismus   MeSH
• kosterní svaly metabolismus   MeSH
• kritický stav * MeSH
• kynurenin metabolismus   MeSH
• lidé MeSH
• melatonin biosyntéza   MeSH
• sepse metabolismus   MeSH
• serotonin biosyntéza   MeSH
• tryptofan nedostatek   MeSH
• zánět metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH