| Lack of effect of oral 4-phenylbutyrate on serum alpha-1-antitrypsin in patients with alpha-1-antitrypsin deficiency: a preliminary study. | |
| | |
MedLine Citation:
|
PMID: 15187777 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
OBJECTIVE: In homozygotes with ZZ genotype alpha-1-antitrypsin (alpha1AT) deficiency, mutant alpha1ATZ protein (alpha1ATZ) accumulates in hepatocytes, rather than being secreted into the blood. Homozygous individuals experience emphysema as a result of reduced levels of circulating alpha1AT in the lung with which to inhibit connective tissue breakdown. Homozygotes may also experience liver disease from the accumulation of alpha1ATZ within hepatocytes, which causes liver damage. A previous study indicated that the compound 4-phenylbutyrate (4-PBA) mediated a significant increase in release of alpha1ATZ from cells in tissue culture and in a mouse model of alpha1AT deficiency. The authors hypothesized that 4-PBA could be used to treat both the liver and lung disease of humans with alpha1AT deficiency. METHODS: In this preliminary, open label study the authors evaluated the effect of 14 days of oral 4-PBA therapy on alpha1AT blood levels in 10 patients with alpha1AT deficiency. RESULTS: There was no significant increase in alpha1AT blood level associated with 4-PBA administration. Symptomatic and metabolic side effects were significant. CONCLUSION: 4-PBA did not increase alpha1AT blood levels in humans with alpha1AT deficiency in this preliminary trial. |
| | |
Authors:
|
Jeffrey H Teckman |
Related Documents
:
|
3051117 - Acute allograft rejection in liver transplant recipients: lack of correlation with loss... 1041797 - The terminal hepatic microcirculation in the rat. 425797 - Injury of liver in experimental salmonellosis of rabbits infected by salmonella agona. 7378257 - Roles of hepatic blood flow and enzyme activity in the kinetics of propranolol and sota... 16414297 - Airway blood flow reactivity in smokers. 9046847 - Comparison of three methods for analysis of urinary sediments. |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
|
Title: Journal of pediatric gastroenterology and nutrition Volume: 39 ISSN: 0277-2116 ISO Abbreviation: J. Pediatr. Gastroenterol. Nutr. Publication Date: 2004 Jul |
Date Detail:
|
Created Date: 2004-06-09 Completed Date: 2005-01-13 Revised Date: 2007-11-14 |
Medline Journal Info:
|
Nlm Unique ID: 8211545 Medline TA: J Pediatr Gastroenterol Nutr Country: United States |
Other Details:
|
Languages: eng Pagination: 34-7 Citation Subset: IM |
Affiliation:
|
Department of Pediatrics, Washington University School of Medicine, St. Louis Children's Hospital, St. Louis, Missouri, USA. teckman@wustl.edu |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Administration, Oral Adolescent Adult Child Child, Preschool Dose-Response Relationship, Drug Female Humans Liver Diseases / drug therapy*, etiology Lung Diseases / drug therapy*, etiology Male Middle Aged Phenylbutyrates / administration & dosage*, adverse effects, therapeutic use alpha 1-Antitrypsin / drug effects, metabolism* alpha 1-Antitrypsin Deficiency / complications*, drug therapy, genetics |
| Grant Support | |
ID/Acronym/Agency:
|
M01RR00036/RR/NCRR NIH HHS; R03DK56154/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Phenylbutyrates; 0/alpha 1-Antitrypsin; 1821-12-1/4-phenylbutyric acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Effects of protein deprivation on growth and small intestine morphology are not improved by glutamin...
Next Document: Dietary nucleotides and intestinal blood flow velocity in term infants.