Alpha1-antitrypsin
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Respiratory medicine, ISSN 0954-6111 vol. 94, suppl. C, August 2000
S21 s. : il., tab. ; 28 cm
Chest. 6, ISSN 0012-3692 Supplement Vol. 110
237S-294S s. : il. ; 30 cm
Acta paediatrica ; Vol. 83 Supplement 393
[1st ed.] 36 s. : fot. ; 28 cm
European respiratory journal, ISSN 0904-1850 Supplement Vol. 3. 9
52 s. : obr., bibliogr. přeruš.
Deficit α1-antitrypsinu, nejčastější genetická porucha dospělého věku, nese ve své těžké formě vysoké riziko časného vývoje plicního emfyzému. Je charakterizován rychlým poklesem plicních funkcí a jeho nositelé se často stávají kandidáty transplantace plic. V posledních letech bylo prokázáno, že pravidelné podávání α1 antitrypsinu vede ke zpomalení destrukce plicní tkáně a pravděpodobně modifikuje průběh a prognózu onemocnění.
Alpha1-antitrypsin deficiency, the most common genetic disorder seen in adults, is associated – in its severe form – with a high risk of pulmonary emphysema development. It is characterized by rapid decrease of pulmonary functions, often making the sufferers lung transplant candidates. It the last years, it has been shown that regular administration of α1-antitrypsin slows down the destruction of lung tissue, thus likely modifying the course and prognosis of the illness.
- Klíčová slova
- studie RAPID,
- MeSH
- alfa-1-antitrypsin aplikace a dávkování terapeutické užití MeSH
- chronická obstrukční plicní nemoc * etiologie prevence a kontrola MeSH
- deficit alfa1-antitrypsinu * farmakoterapie komplikace MeSH
- hodnocení výsledků zdravotní péče MeSH
- lidé MeSH
- plicní emfyzém etiologie prevence a kontrola MeSH
- randomizované kontrolované studie jako téma MeSH
- Check Tag
- lidé MeSH
BACKGROUND AND AIMS: Alpha-1 antitrypsin deficiency is an inherited disorder caused by alpha-1 antitrypsin (AAT) mutations. We analysed the association between alcohol intake and liver-related parameters in individuals with the heterozygous/homozygous Pi*Z AAT variant (Pi*MZ/Pi*ZZ genotype) found in the United Kingdom Biobank and the European Alpha1 liver consortium. METHODS: Reported alcohol consumption was evaluated in two cohorts: (i) the community-based United Kingdom Biobank (17 145 Pi*MZ, 141 Pi*ZZ subjects, and 425 002 non-carriers [Pi*MM]); and (ii) the European Alpha1 liver consortium (561 Pi*ZZ individuals). Cohort (ii) included measurements of carbohydrate-deficient transferrin (CDT). RESULTS: In both cohorts, no/low alcohol intake was reported by >80% of individuals, while harmful consumption was rare (~1%). Among Pi*MM and Pi*MZ individuals from cohort (i), moderate alcohol consumption resulted in a <30% increased rate of elevated transaminases and ~50% increase in elevated gamma-glutamyl transferase values, while harmful alcohol intake led to an at least twofold increase in the abnormal levels. In Pi*ZZ individuals from both cohorts, moderate alcohol consumption had no marked impact on serum transaminase levels. Among Pi*ZZ subjects from cohort (ii) who reported no/low alcohol consumption, those with increased CDT levels more often had signs of advanced liver disease. CONCLUSIONS: Pi*MZ/Pi*ZZ genotype does not seem to markedly aggravate the hepatic toxicity of moderate alcohol consumption. CDT values might be helpful to detect alcohol consumption in those with advanced fibrosis. More data are needed to evaluate the impact of harmful alcohol consumption.
- MeSH
- alfa-1-antitrypsin * genetika krev MeSH
- deficit alfa1-antitrypsinu * genetika krev diagnóza komplikace MeSH
- dospělí MeSH
- fenotyp * MeSH
- gama-glutamyltransferasa krev MeSH
- genotyp MeSH
- játra patologie MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- pití alkoholu * škodlivé účinky MeSH
- senioři MeSH
- transferin * analýza metabolismus analogy a deriváty MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Evropa MeSH
- Spojené království MeSH
AIMS: The aim was develop stable human cell line stable over-expressing transcription co-activator peroxisome proliferator-activated receptor gamma co-activator 1α (PGC-1α) with restored hepatospecific functions and increased expression of major xenobiotic metabolizing enzymes. METHODS: Six clones of HepG2-PGC-1α and one control clone HepG2-pcDNA3 were isolated and analyzed for secretion of hepatospecific markers, fibrinogen, albumin and alpha1-antitrypsin. Expression levels of protein and mRNA of hepatocyte nuclear factor (HNF4α), pregnane X receptor (PXR) and aryl hydrocarbon receptor (AhR) were determined. We measured basal and ligand inducible expression of CYP1A1 and CYP3A4. RESULTS: Stably transfected cell line HepG2-PGC-1α derived from HepG2 cells over-expressing PGC-1α displayed increased secretion of fibrinogen, but not albumin or alpha1-antitrypsin compared to parent HepG2 cells. We found increased levels of HNF4α, PXR and AhR proteins but not their mRNAs in HepG2-PGC1 cells. Basal expression of CYP3A4 protein in HepG2-PGC-1α cells was increased but rifampicin-inducible expression of CYP3A4 protein was lowered in comparison with parent HepG2 cells. Induction of CYP3A4 mRNA varied between 1.3 - 1.9 fold in individual clones. Expression of TCDD-inducible CYP1A1 protein was lower in HepG2-PGC-1α cells than in parent HepG2 cells. Induction of CYP1A1 mRNA by TCDD in HepG2-PGC-1α cells was comparable with that in parent HepG2 cells and ranged between 103 - 198 fold. CONCLUSION: Stable expression of PGC-1α in HepG2 cells restores several hepatospecific functions, such as secretion of fibrinogen, expression of HNF4α1 and xenoreceptors PXR and AhR. However, the expression and induction of key drug-metabolizing enzymes (CYP1A1 and CYP3A4) were not improved.
- MeSH
- buňky Hep G2 MeSH
- cytochrom P-450 CYP1A1 metabolismus MeSH
- cytochrom P-450 CYP3A metabolismus MeSH
- fibrinogen sekrece MeSH
- gentamiciny farmakologie MeSH
- hepatocytární jaderný faktor 4 metabolismus MeSH
- hepatocyty metabolismus MeSH
- lidé MeSH
- nádorové biomarkery metabolismus MeSH
- polychlorované dibenzodioxiny farmakologie MeSH
- PPAR gama metabolismus MeSH
- receptory aromatických uhlovodíků metabolismus MeSH
- steroidní receptory metabolismus MeSH
- teratogeny farmakologie MeSH
- transfekce metody MeSH
- transkripční faktory bHLH metabolismus MeSH
- transkripční faktory metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Uvádíme výsledky vyšetifeni sedmi pracovníků exponovaných zinku při bodovém svářeni spodků autobusů, u menz bylo zjištěno zvýšené vylučování zinku močí, svědčící pro zvýšenou expozici zinku. Šest vyšetřovaných bylo léčeno pio aiteriální hypertenzi, v laboratorním nálezu byla zjištěna šestkrát lehce a přechodně zvýšená aktivita ALT a pětkrát zvýšená koncentrace cholesterolu v plazmě. Z imunologických nálezů je nejčastější lehké snížení koncentrace alfa1antitrypsinu, klinicky se tento deficit neprojevil. Všetřované budeme nadále sledovat.
The authors present the results of examinations of seven workers engaged in welding of bottom parts of buses. In these workers elevated urinary zinc excretion was found suggesting increased exposure to zinc. The objective finding comprised most frequently arterial hypertension (six times), the laboratory finding revealed a slihght and transient increase of tiie ALT activity (six times) and elevated cholesterol concentrations (five times). As to immunological findings, a slight reduction ofthe alpha1 antitrypsin (five times) was most frequent, while this defect was not clinically manifest. The subjects will be followed up.
