- MeSH
- cystická fibróza * MeSH
- individualizovaná medicína MeSH
- kolforsin farmakologie MeSH
- lidé MeSH
- mutace MeSH
- protein CFTR genetika MeSH
- střevní sliznice MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- dopisy MeSH
BACKGROUND: In primary ciliary dyskinesia (PCD) there is no single diagnostic test. Different predictive tools have been proposed to guide referral of high-risk patients for further diagnostic workup. We aimed to test clinical index (CI) on a large unselected cohort and compare its characteristics with other widely used tools-PICADAR and NA-CDCF. METHODS: CI, PICADAR, and NA-CDCF scores were calculated in 1401 patients with suspected PCD referred to our center. Their predictive characteristics were analyzed using receiver operating characteristics (ROC) curves and compared to each other. Nasal nitric oxide (nNO) was measured in 569 patients older than 3 years. RESULTS: PCD was diagnosed in 67 (4.8%) patients. CI, PICADAR, and NA-CDCF scores were higher in PCD than in nonPCD group (all p < 0.001). The area under the ROC curve (AUC) for CI was larger than for NA-CDCF (p = 0.005); AUCPICADAR and AUCNA-CDCF did not differ (p = 0.093). An overlap in signs and symptoms among tools was identified. PICADAR could not be assessed in 86 (6.1%) patients without chronic wet cough. For CI laterality or congenital heart defects assessment was not necessary. nNO further improved predictive power of all three tools. CONCLUSION: CI is a feasible predictive tool for PCD that may outperform PICADAR and NA-CFCD.
- Publikační typ
- časopisecké články MeSH
Primární ciliární dyskineze (PCD) je vzácné, geneticky podmíněné onemocnění dané poruchou funkce pohyblivých řasinek, které hrají důležitou roli v mechanickém očišťování dýchacích cest. Ciliární dysfunkce způsobuje stagnaci hlenu a rekurentní infekce horních i dolních cest dýchacích. PCD je geneticky velmi heterogenní nemoc (dosud byly identifikovány mutace v nejméně 50 genech), to se projevuje i ve variabilitě klinického obrazu a závažnosti postižení. U části pacientů se onemocnění manifestuje již v novorozeneckém věku, u většiny nemocných je však diagnóza stanovena až v průběhu staršího dětského věku, nebo v dospělosti. Příčinou poddiagnostikovanosti PCD je kombinace více faktorů: nízká informovanost odborné i laické veřejnosti, genotypově-fenotypová variabilita nemoci i náročná diagnostika. Včasné stanovení diagnózy PCD je důležité pro včasné zahájení adekvátní terapie, ovlivnění prognózy pacientů a také ke snížení psychické zátěže i nastavení optimální adherence k léčbě.
Cíl studie: posouzení využitelnosti sérového kalprotektinu jako biomarkeru bakteriální infekce v rutinní praxi. Typ studie: prospektivní, observační studie. Název a sídlo pracoviště: Ústřední vojenská nemocnice – Vojenská fakultní nemocnice Praha Materiál a metody: do studie byli zařazeni všichni pacienti přijatí na Kliniku infekčních nemocí v období leden až březen 2020. Sérový kalprotektin byl stanoven pomocí systému EVOLIS™ Microplate a komerčně dostupné enzymoimunoeseje firmy Biovendor. Výsledky: celkem byla vyhodnocena data 36 nemocných (24 mužů a 12 žen s průměrným věkem 63,9 let), u kterých byla potvrzena diagnóza virové nebo bakteriální infekce. Nejčastějším zdrojem bakteriální infekce byly dýchací cesty (33,3 %), následované měkkými tkáněmi (25 %) a infekcemi urogenitálního a gastrointestinálního traktu (shodně 16,7 %). Virovou infekci nejčastěji představovala chřipka A (66,6 %). Medián sérové koncentrace kalprotektinu u bakteriální infekce byl 4,12 mg/L oproti 2,03 mg/L při infekci virové. U 12 nemocných s bakteriální infekcí a zvýšeným C-reaktivním proteinem (CRP), u kterých nebyl zvýšen prokalcitonin (PCT), byla zjištěna zvýšená hodnota sérového kalprotektinu. Naopak u osmi nemocných s potvrzenou bakteriální infekcí nebyl kalprotektin zvýšen, čtyři z těchto pacientů měli současně s CRP zvýšený i PCT a čtyři nemocní měli zvýšené pouze CRP. V souboru byl rovněž případ bakteriální infekce se zvýšeným kalprotektinem a negativním CRP i PCT. Závěr: výsledky naší studie naznačily význam sérového kalprotektinu jako doplňkového parametru pro diagnostiku bakteriální infekce.
Objective: evaluation of clinical use of serum calprotectin as biomarker of bacterial infection Design: prospective, observational study Settings: Military University Hospital Prague Material and Methods: all patients admitted to the Department of infectious Diseases during the period between January and March 2020 were enrolled to the study. Serum calprotectin was analyzed using EVOLIS™ Microplate system and commercially available assay from the Biovendor company. Results: Altogether, data of 36 enrolled patients with proven bacterial or viral infection (24 males and 12 females with mean age 63.9 years) were evaluated. The most frequent source of bacterial infection was respiratory tract (33.3 %) followed by soft tissue (25 %) and infections of urogenital and gastrointestinal tracts (both 16.7 %). The most common viral infection was flu A (66.6 %). Median of calprotectin serum concentration in bacterial infection was 4.12 mg/L in comparison to 2.03 mg/L in viral infection. In 12 patients with bacterial infection with negative procalcitonin (PCT) levels, both C-reactive protein (CRP) and calprotectin were elevated. On the other hand, eight patients with proven bacterial infection had negative calprotectin serum levels. Four of these patients had elevated CRP and PCT and four CRP only. In addition, in the cohort with bacterial infection, there was one patient with calprotectin elevation only. Conclusion: the results of our study indicated serum calprotectin as additional parameter of bacterial infection.
Primární ciliární dyskineze (PCD) je vzácné geneticky podmíněné onemocnění s pestrou symptomatologií. Na tuto diagnózu je potřeba vždy myslet u dětí i dospělých s rekurentní nebo chronickou nemocností v oblasti horních a dolních dýchacích cest, často ve spojitosti s poruchami sluchu. nemocnění se obvykle projeví již krátce po narození jako dechová tíseň novorozence nebo novorozenecká rýma. Pacienti pak po celý život trpí chronickým vlhkým kašlem a opakovanými záněty dýchacích cest a plic, jež mohou vyústit až v bronchiektázie. Na možnou ciliopatii je nutné pomýšlet při situs viscerum inversus nebo jiných poruchách laterality, častější jsou také poruchy plodnosti. Včasné stanovení diagnózy a zahájení komplexní péče jsou klíčové pro prognózu nemocných, jelikož k regresi plicních funkcí devastaci plicní tkáně dochází u některých fenotypů již v časném věku pacienta.
Primary ciliary dyskinesia (PCD) is a rare genetic diseases with diverse clinical symptoms. Clinicians hould think of PCD in the differential diagnostic process in both children and adults who suffer from recurrent or chronic upper and lower respiratory tract symptoms frequently accompanied by hearing impairment. he first manifestations of PCD often occur very early in life and might present as an acute respiratory istress syndrome of a newborn or neonatal rhinitis. During the whole life the patients suffer from chronic wet cough and recurrent airway and lung inflammations, which can result in bronchiectasis. Situs viscerum inversus, other laterality defects and fertility disorders are other common symptoms in PCD. Early diagnosis and complex therapy play a key role in the prognosis of PCD patients, as deterioration of lung functions andlung tissue destruction may occur at an early age in some phenotypes.
Endocrine disruptors (EDs) are compounds that interfere with the balance of the endocrine system by mimicking or antagonising the effects of endogenous hormones, by altering the synthesis and metabolism of natural hormones, or by modifying hormone receptor levels. The synthetic estrogen 17α-ethinylestradiol (EE2) and the environmental carcinogen benzo[a]pyrene (BaP) are exogenous EDs whereas the estrogenic hormone 17β-estradiol is a natural endogenous ED. Although the biological effects of these individual EDs have partially been studied previously, their toxicity when acting in combination has not yet been investigated. Here we treated Wistar rats with BaP, EE2 and estradiol alone or in combination and studied the influence of EE2 and estradiol on: (i) the expression of cytochrome P450 (CYP) 1A1 and 1B1 in rat liver on the transcriptional and translational levels; (ii) the inducibility of these CYP enzymes by BaP in this rat organ; (iii) the formation of BaP-DNA adducts in rat liver in vivo; and (iv) the generation of BaP-induced DNA adducts after activation of BaP with hepatic microsomes of rats exposed to BaP, EE2 and estradiol and with recombinant rat CYP1A1 in vitro. BaP acted as a strong and moderate inducer of CYP1A1 and 1B1 in rat liver, respectively, whereas EE2 or estradiol alone had no effect on the expression of these enzymes. However, when EE2 was administered to rats together with BaP, it significantly decreased the potency of BaP to induce CYP1A1 and 1B1 gene expression. For EE2, but not estradiol, this also correlated with a reduction of BaP-induced CYP1A1 enzyme activity in rat hepatic microsomes. Further, while EE2 and estradiol did not form covalent adducts with DNA, they affected BaP-derived DNA adduct formations in vivo and in vitro. The observed decrease in BaP-DNA adduct levels in rat liver in vivo resulted from the inhibition of CYP1A1-mediated BaP bioactivation by EE2 and estradiol. Our results indicate that BaP genotoxicity mediated through its activation by CYP1A1 in rats in vivo is modulated by estradiol and its synthetic derivative EE2.
- MeSH
- benzopyren toxicita MeSH
- cytochrom P-450 CYP1A1 biosyntéza genetika MeSH
- endokrinní disruptory toxicita MeSH
- estradiol toxicita MeSH
- ethinylestradiol toxicita MeSH
- jaterní mikrozomy účinky léků enzymologie MeSH
- krysa rodu rattus MeSH
- potkani Wistar MeSH
- regulace genové exprese enzymů * účinky léků MeSH
- synergismus léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
The aim of the study was to compare the adsorption ability of two adsorbent materials, namely diosmectite and activated charcoal towards selected model compounds that are most commonly involved in acute intoxication. Eleven model compounds were selected: acetylsalicylic acid, α-amanitin, amlodipine, digoxin, phenobarbital, ibuprofen, imipramine, carbamazepine, oxazepam, promethazine, and theophylline. Of the tested compounds, promethazine and imipramine were the most effectively adsorbed to diosmectite. Their adsorption to diosmectite (0.356±0.029mg promethazine/mg diosmectite and 0.354±0.019mg imipramine/mg diosmectite, respectively) was significantly higher than their adsorption to activated charcoal. The effect of temperature and pH on the adsorption efficiencies was also evaluated. In the case of experiments with mixture of both adsorbents, they mostly behaved in a solution independently or in a slightly antagonistic way. Using various methods such as N2 adsorption and thermogravimetric analysis, the structure and texture of diosmectite and activated charcoal were attained.
- MeSH
- adsorpce MeSH
- alfa-amanitin chemie MeSH
- amlodipin chemie MeSH
- antidota chemie MeSH
- Aspirin chemie MeSH
- digoxin chemie MeSH
- dřevěné a živočišné uhlí chemie MeSH
- fenobarbital chemie MeSH
- ibuprofen chemie MeSH
- imipramin chemie MeSH
- karbamazepin chemie MeSH
- otrava prevence a kontrola MeSH
- oxazepam chemie MeSH
- promethazin chemie MeSH
- silikáty chemie MeSH
- theofylin chemie MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
OBJECTIVES: The term "endocrine disruptor" (ED) is used for compounds that mimic or antagonize the effects of endogenous hormones. Synthetic estrogen 17α-ethinylestradiol (EE2) and a human carcinogen benzo[a]pyrene (BaP) are assigned as exogenous endocrine disruptors and an estrogenic hormone estradiol is a natural endogenous disruptor. Here, the potency of these three disruptors administered to rats individually and in combination to induce expression of cytochrome P450 (CYP) enzymes involved in their own metabolism (CYP1A1, 2C and 3A) in vivo was investigated. METHODS: Changes in CYP protein expression after exposure of rats to BaP, EE2 or estradiol were analyzed by Western blotting. Using the HPLC method, CYP1A1, 2C and 3A specific activities in hepatic microsomes isolated from exposed rats were analyzed. RESULTS: Whereas exposure to BaP induces expression of CYP1A1 protein and its marker activity (Sudan I oxidation) in liver, kidney and lung of rats, no significant induction of this CYP and its enzyme activity was produced by EE2 and estradiol. Treatment of BaP in combination with EE2 and/or estradiol decreased the BaP-mediated CYP1A1 induction in liver of exposed rats. BaP also induces CYP2C11 protein in rat liver and kidney, but does not increase its enzyme activity measured as testosterone 16α-hydroxylation. The enzyme activity of another enzyme of the 2C subfamily, CYP2C6, diclofenac 4'-hydroxylation, is even decreased by BaP. The CYP2C11 protein expression and/or its activity are also increased in liver of rats treated with EE2 and estradiol, but its expression is significantly decreased in lung. The CYP2C6 activity is also elevated by treatment of rats with EE2 and estradiol administered individually as well as in their combination. Whereas only a slight increase in CYP3A protein expression was found by BaP in rat liver, its enzyme activity, testosterone 6β-hydroxyalation, increased significantly in this organ. In contrast, no effect or even a decrease in CYP3A expression and its enzyme activity was produced by EE2 and estradiol in rats exposed to these compounds.
- MeSH
- benzopyren farmakologie MeSH
- endokrinní disruptory farmakologie MeSH
- estradiol farmakologie MeSH
- estrogeny farmakologie MeSH
- ethinylestradiol farmakologie MeSH
- jaterní mikrozomy metabolismus MeSH
- krysa rodu rattus MeSH
- potkani Wistar MeSH
- systém (enzymů) cytochromů P-450 metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
