Specific inflammation
Dotaz
Zobrazit nápovědu
BACKGROUND: About every fourth patient with major depressive disorder (MDD) shows evidence of systemic inflammation. Previous studies have shown inflammation-depression associations of multiple serum inflammatory markers and multiple specific depressive symptoms. It remains unclear, however, if these associations extend to genetic/lifetime predisposition to higher inflammatory marker levels and what role metabolic factors such as Body Mass Index (BMI) play. It is also unclear whether inflammation-symptom associations reflect direct or indirect associations, which can be disentangled using network analysis. METHODS: This study examined associations of polygenic risk scores (PRSs) for immuno-metabolic markers (C-reactive protein [CRP], interleukin [IL]-6, IL-10, tumour necrosis factor [TNF]-α, BMI) with seven depressive symptoms in one general population sample, the UK Biobank study (n = 110,010), and two patient samples, the Munich Antidepressant Response Signature (MARS, n = 1058) and Sequenced Treatment Alternatives to Relieve Depression (STAR*D, n = 1143) studies. Network analysis was applied jointly for these samples using fused graphical least absolute shrinkage and selection operator (FGL) estimation as primary analysis and, individually, using unregularized model search estimation. Stability of results was assessed using bootstrapping and three consistency criteria were defined to appraise robustness and replicability of results across estimation methods, network bootstrapping, and samples. RESULTS: Network analysis results displayed to-be-expected PRS-PRS and symptom-symptom associations (termed edges), respectively, that were mostly positive. Using FGL estimation, results further suggested 28, 29, and six PRS-symptom edges in MARS, STAR*D, and UK Biobank samples, respectively. Unregularized model search estimation suggested three PRS-symptom edges in the UK Biobank sample. Applying our consistency criteria to these associations indicated that only the association of higher CRP PRS with greater changes in appetite fulfilled all three criteria. Four additional associations fulfilled at least two consistency criteria; specifically, higher CRP PRS was associated with greater fatigue and reduced anhedonia, higher TNF-α PRS was associated with greater fatigue, and higher BMI PRS with greater changes in appetite and anhedonia. Associations of the BMI PRS with anhedonia, however, showed an inconsistent valence across estimation methods. CONCLUSIONS: Genetic predisposition to higher systemic inflammatory markers are primarily associated with somatic/neurovegetative symptoms of depression such as changes in appetite and fatigue, consistent with previous studies based on circulating levels of inflammatory markers. We extend these findings by providing evidence that associations are direct (using network analysis) and extend to genetic predisposition to immuno-metabolic markers (using PRSs). Our findings can inform selection of patients with inflammation-related symptoms into clinical trials of immune-modulating drugs for MDD.
- MeSH
- antidepresiva terapeutické užití MeSH
- C-reaktivní protein analýza MeSH
- deprese * genetika MeSH
- depresivní porucha unipolární * farmakoterapie genetika MeSH
- lidé MeSH
- multifaktoriální dědičnost MeSH
- zánět farmakoterapie genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Research Support, N.I.H., Extramural MeSH
Diferenciální diagnostika infekční a neinfekční etiologie zánětu je v mnoha klinických situacích těžko řešitelným problémem. V 90. letech se v této oblasti významně uplatnil nový parametr-Prokalcitonin. Ačkoli jeho fyziologická role a regulace mechanismů jeho produkce jsou dosud nedostatečně objasněny, významnost jeho stanovení, jako senzitivního a specifického parametru pro těžkou bakteriální infekci se systémovými projevy, byla již dostatečně prokázána. V současné době je považován za specifičtější markerzávažnosti sepse než interleukin-hnebo C-reaktivní protein. Jeho stanovení zásadním způsobem ovlivňuje diagnostiku pacientů v kritických stavech, stejně jako vedení antibiotické terapie u těchto nemocných.
The differential diagnosis of infectious and noninfectious ethiology of an injlammation is difficult problem in many clinical situations. In the nineties new important marker - procalcitonin - appears. Although its physiological role and regulation of its production is not sufficiently explained, procalcitonin has been shown to be important, sensitive and specific marker of the bacterial infection triggering a systemicinjlammatory reaction in the body. Nowadays procalcitonin is believed to be more specific marker of the severity of sepsis than interleukin-h or C-reactive protein. The determination of procalcitonin concentration is of important value for the diagnostic algorithm in critically ill patienxs and for antibiotic therapy.
- MeSH
- bakteriální infekce diagnóza MeSH
- kalcitonin analogy a deriváty diagnostické užití fyziologie MeSH
- lidé MeSH
- mediátory zánětu diagnostické užití fyziologie MeSH
- sepse diagnóza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Zánět je komplexní reakce organizmu, která se vyvíjí jako odpověď na invazi infekčního agens nebojako odpověď na poškození buněk a tkání. Přesná a včasná lokalizace infekčního nebo zánětlivéholožiska umožní rychlé odstranění příčiny jeho vzniku. V průběhu posledních 30 let byla vyvinutacelá řada radiofarmak více či méně použitelných pro scintigrafickou detekci zánětlivých a infekčníchonemocnění. Snahou je, aby nově vyvíjené látky nebyly toxické, nevyvolávaly imunitní reakce,absorbovaná radiační dávka byla co nejnižší, dále aby se tyto látky významně kumulovaly v cílenétkáni (tj. v zánětu) a akumulace v ostatních tkáních byla minimální, popřípadě aby docházelok rychlému odstraňování radiofarmaka z necílených tkání. Snahou je, aby tyto látky byly i snadnodostupné a cenově nenákladné. Cílem je také vyvinout takové látky, které by vykazovaly nejendostatečnou citlivost, ale i specifitu vůči určitým typům zánětů nebo infekcí. Hlavní indikace,u kterých jsou k detekci používána radiofarmaka, jsou zánětlivé choroby střev, sepse měkkýchtkání, převážně v břišní oblasti, muskuloskeletární infekce a horečka neznámého původu 11, 15) .
Inflammation is a complex reaction of the organism which develops as a response to invasion of aninfectious subject or as a response to injury to cells or tissues. Correct and early localization ofinfection or an inflammatory lesion allows removing the inflammatory cause quickly. Over the recentthirty years, a wide range of radiopharmaceuticals, more or less applicable in scintigraphic imagingof inflammatory and infectious diseases, have been developed. The aim has been to develop newsubstances that are non-toxic, do not provoke immune reactions, and produce a minimal absorbedradioactive dose. Furthermore, these substances should accumulate significantly in the target tissue(i.e. in inflammation), while the accumulation in non-target tissues should be minimal or theelimination of radiopharmaceuticals from non-target tissues must be quick. The goal is that thesesubstances may also be easily available and inexpensive. Another purpose is to develop suchsubstances that could possess not only sufficient sensitivity but also specificity in relation to certaintypes of inflammation and infection. The main indications for radionuclide imaging are as follows:inflammatory bowel disease, soft tissue sepsis, predominantly abdominal sepsis, musculoskeletalinfection, and fever of unknown origin.
Progress in inflammation research
1st ed. xiii, 201 s.
This volume is a comprehensive review of the structure/function and biology of molecules belonging to the TGF-ß superfamily. Because molecules in this family have very diverse biological roles, the editors have chosen to focus on the parts they play in the specific areas of inflammation and wound/fracture healing. While molecules in the TGF-ß superfamily have been extensively studied, there are few, if any, publications which have taken a broad perspective on this family, most having chosen to focus on just one very small area. This book is therefore unusual in that it offers a comprehensive overview of the current state of the field, providing both in-depth and essential background material suitable for both clinicians and scientists alike.
- Konspekt
- Patologie. Klinická medicína
- NLK Obory
- vnitřní lékařství
- MeSH
- absces chirurgie patologie MeSH
- chirurgie operační MeSH
- dospělí MeSH
- farmakoterapie MeSH
- krk MeSH
- lidé středního věku MeSH
- lidé MeSH
- mortalita MeSH
- otorinolaryngologické nemoci komplikace mortalita terapie MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Článek podává přehled fyziologických imunitních reakcí, které se účastní při serózních zánětech centrálního nervového systému. Je zdůrazněna lokální imunitní reakce v mozkové tkáni, migrace lymfocytů přes hematoencefalickou bariéru, nespecifické a specifické imunitní reakce s přihlédnutím k mechanizmům likvidace infekčního agens.
The article summarises physiologic immune reacfions, which participate in serous central nervous system inflammations. There is accented a local immune reacfion in the brain fissue, a lymphocyte migration across the haematoencephalic barrier, non-specific and specific immune reactions which are in connection with mechanisms of infections agent destruction.
- MeSH
- bakteriální infekce centrálního nervového systému imunologie mikrobiologie MeSH
- hematoencefalická bariéra fyziologie MeSH
- imunita genetika MeSH
- lidé MeSH
- T-lymfocyty fyziologie MeSH
- virové nemoci CNS imunologie virologie MeSH
- zánět imunologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Začiatočné rozpoznanie mikróbov, ktoré vniknú do organizmu, sa zakladá na ich geneticky zakódovaných molekulových vzoroch patogénnosti (PAMPs), ktoré umožňujú odpovedať na mikróbnu inváziu ihneď, čiže ešte pred vznikom aktívnej špecifickej imunity. Táto odpoveď hostiteľa na infekciu a poranenie sa realizuje prostredníctvom neustále sa rozširujúcej skupiny receptorov patriacich do veľkorodiny receptorov pre interleukín-1 (IL-1Rs) a receptorov podobných Toll (TLRs). Členovia obidvoch týchto rodín obsahujú v cytoplamových častiach ich molekúl doménu TIR (Toll/IL-1R). Doteraz sa zistilo desať IL-1Rs (vrátane IL-1RI a IL-18R) a desať TLRs (TLR1 až TLR10). Exprimujú sa najmä na bunkách, ktoré sa nachádzajú na tkanivách prichádzajúcich do kontaktu s vonkajším prostredím. Aktivácia TLRs má za následok aktiváciu priamych antimikróbnych mechanizmov, ako súčasti prirodzenej imunity, expresiu kostimulačných molekúl a uvoľnenie cytokínov, ktoré regulujú adaptívnu imunitnú odpoveď. Prenos signálov cez tieto receptory môže zodpovedať aj za stimuláciu dozrievania imunitného systému a môže sa preto zúčastňovať na patogenéze alergických chorôb. Využitie poznatkov o TLRs sa pravdepodobne v budúcnosti bude dať preto využiť pri nových účinných postupoch liečby osobitne atopických chorôb. Genetické a vývojové variácie v expresii TLRs môžu ovplyvňovať individuálnu predispozíciu na infekcie v detskom veku a prispievať k zvýšenej citlivosti nielen na alergie, ale aj na zápalové a autoimunitné choroby.
Initial recognition of microbes, as they enter the body, is based on germ line-encoded pathogen-associated molecular patterns (PAMPs) to respond immediately to the microbial invasion before the development of active specific immunity. This host response to infection and injury is performed through an expanding group of receptors belonging to the superfamily of interleukin-1 receptors (IL-1Rs) and Toll-like receptors (TLRs). They both contain the Toll-IL-1 receptor (TIR) domain which occurs in the cytosolic region. So far, ten IL-1Rs (including IL-1RI and IL-18R) and ten TLRs (TLR1 to TLR10) have been revealed. They are predominatly expressed on cells at the interface of the body with the environment. The activation of TLRs leads to direct antimicrobial pathways, as a part of innate immunity, to the expression of co-stimulatory molecules and to the release of cytokines that instruct the adaptive immune response. Signalling via these receptors may be also responsible for driving the maturation of the adult immune system and therefore it may participate in the pathogenesis of allergic diseases. Exploitation of the TLR signalling will probably lead to novel effective therapies for these diseases. Genetic and developmental variations in the expression of TLRs may affect the individual predisposition to infections in childhood and may contribute to the increased susceptibility not only to allergies but to inflammatory and autoimmune diseases as well.
INTRODUCTION: Production of endothelial nitric oxide declines with advancing age. On the other hand, ageing itself is associated with a mild degree of chronic inflammation. Besides, asymptomatic infectious and non-infectious inflammation is frequent in old age. All this may lead to an increased formation of nitric oxide via inducible nitric oxide synthase. The plasma levels of nitric oxide metabolites in older age groups are not known. The aim of our study was to determine the plasma levels of metabolites of nitric oxide (nitrite and nitrate) and to correlate them with the levels of inflammation markers in clinically healthy individuals aged over 80. METHODS: The plasma levels of nitrite/nitrate as well as erythrocyte sedimentation rate, and the levels of C-reactive protein and tumor necrosis factor alpha were determined in a group of 30 clinically healthy individuals aged over 80 years. Results were compared with those obtained in a control group. RESULTS: Nitrate levels were increased and the levels of inflammation markers were significantly higher compared with those in a control group. CONCLUSIONS: The levels of nitric oxide metabolites in elderly, clinically healthy individuals may be increased due to inflammation (Tab. 2, Fig. 1, Ref. 32). F
The initiation of human parturition is not fully understood to date. The data from animal experiments demonstrate that the primary impulse for the initiation of physiological labor arises from the fetal hypothalamo-pituitary-adrenal axis (HPA). HPA is responsible for the stimulation of steroid synthesis and prostaglandin production and, in turn, the cervical dilation and the beginning of myometrial contractions. Animal experiments, however, are only partly suitable for understanding the mechanism of human labor due to substantial species-specificity. In human, the changing levels of placental CRH control the production of fetal and placental steroids. The fundamental pathogenic manifestation of spontaneous preterm labor is inflammation and similar processes also underlie the full term one. While in full term labor it is not yet precisely known what starts this process, in the preterm one, several factors have been discussed like infection, uteroplacental ischemia, and hormonal abnormalities (progesterone- or CRH-related). Inflammatory processes affect both the mother and the fetus. Fetal inflammatory response (FIRS), which can be expected for children born preterm, is frequently associated with long-term complications, in particular neurological and pulmonary. Research in this field is therefore aimed at predicting preterm labor, and on predicting the fetal inflammatory response. The role of progesterone and its receptors in the pathophysiology of preterm labor are likewise intensively studied. Clinical results on the use of additive doses of progesterone in secondary prevention of preterm labor and current experimental studies point to progesterone and its receptors playing a key role in the pathophysiology of preterm labor. This article is part of a Special Issue entitled 'Pregnancy and Steroids'.
- MeSH
- lidé MeSH
- mediátory zánětu fyziologie MeSH
- předčasná porodní činnost imunologie metabolismus MeSH
- progesteron fyziologie MeSH
- těhotenství MeSH
- zánět metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH