Direct exposure of human alpha-1-proteinase inhibitor to the gas-phase smoke from one cigarette results in an initial rapid loss of elastase inhibitory capacity, the amount of which is dependent upon the age of the smoke. This short-term inactivation is not seen when the protein is exposed to aqueous extracts of cigarette smoke (as had been done in the past). Both exposure regimens result in a slow inactivation occurring over several days. We suggest that the short-term inactivation may be due to a peroxynitrate (or a similar reactive species) that is formed from radicals in the gas phase but is unstable in aqueous solution.
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http://dx.doi.org/10.1016/s0006-291x(84)80086-8 | DOI Listing |
Heliyon
June 2024
Ross Pierce MD, LLC, 1330 West Avenue Unit 506, Miami Beach, FL 33139, USA.
Clinical benefit of Alpha-Proteinase Inhibitor (Human) (A-PI) products for Alpha-antitrypsin deficiency (AATD) is uncertain, based on a systematic review of observational studies and randomized controlled trials (RCTs) in AATD of Alpha-Proteinase Inhibitor (Human) (A-PI) products. At the recommended dose, A-PI products raise its serum concentration but do not normalize levels. Observational studies suggest A-PI might modestly slow progression of airflow limitation in patients with intermediate airflow obstruction, a finding not confirmed by three placebo-controlled RCTs of limited power, which showed non-significant rates of forced expiratory volume in 1Â s (FEV) change favoring placebo.
View Article and Find Full Text PDFFront Pharmacol
November 2023
Hospital Pharmacy Department, Hospital Universitario Costa del Sol, Marbella, Spain.
Intravenous augmentation therapy with human alpha-1 proteinase inhibitor for the management of respiratory disease is recommended for people with alpha-1 antitrypsin deficiency (AATD) who are nonsmokers or former smokers. Augmentation therapy usually requires weekly administration at the hospital or clinic and poses an additional burden for patients due to interference with daily life, including work and social activities. Self-administration is a useful alternative to overcome this limitation, but there is a lack of published information on clinical outcomes.
View Article and Find Full Text PDFPulm Pharmacol Ther
December 2023
Takeda Development Center Americas, Inc., Cambridge, MA, United States.
Introduction: The recommended standard dose for α-proteinase inhibitor (A1PI) augmentation therapy is 60 mg/kg once-weekly (QW) intravenous (IV) infusions that aim to maintain systemic A1PI levels >11 μM, the biochemical efficacy threshold, in patients with α-antitrypsin deficiency (AATD). However, this standard dose may not be optimal for all patients. Body weight-based dosing, alternative dosing regimens, and treatment interruption periods were evaluated using population pharmacokinetic (PopPK) modeling and simulations.
View Article and Find Full Text PDFThe universal proteinase inhibitor α2-macroglobulin (α₂-MG) exhibiting antiviral and immunomodulatory activities, is considered as an important participant in the infectious process. The activity of α₂-MG in the new coronavirus infection and post-covid syndrome (long COVID) has not been studied yet. We examined 85 patients diagnosed with community-acquired bilateral polysegmental pneumonia developed under conditions of a new coronavirus infection SARS-CoV-2.
View Article and Find Full Text PDFAm J Respir Crit Care Med
November 2023
Department of Medicine, Irish Center for Genetic Lung Disease, Royal College of Surgeons in Ireland, Dublin, Ireland.
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