Preclinical evaluation of alpha-1-proteinase inhibitor

Fournel, Michael A.; Newgren, James O.; Betancourt, Carmen M.; Irwin, Russell G.

doi:10.1016/0002-9343(88)90157-x

Cited by 7 publications

(4 citation statements)

References 8 publications

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“…The study design originally required subjects receiving AAT augmentation therapy to discontinue that therapy 28 days before vector administration, on the basis of published data indicating that the elimination half-life of infused AAT is 2 to 3 days (20,21). Although this resulted in total AAT levels that were well within the expected range for PI*ZZ subjects at day Ϫ1, substantial residual levels of M-type AAT were detected in these subjects, and the ''washout'' period was extended to 56 days for subjects enrolled in cohorts 2 and 3.…”

Section: Discussionmentioning

confidence: 99%

Sustained transgene expression despite T lymphocyte responses in a clinical trial of rAAV1-AAT gene therapy

Brantly

Chulay

Wang

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

286

239

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Fig. 2.Transformants releasing E␤C suffered less damage than control lines when EPNs were present. (A) Root damage measured on plants that had received neither WCR eggs nor nematodes was minimal, and there was no difference between transformed and nontransformed plants (n ϭ 5, P ϭ 0.87). (B) Root damage on plants that received only WCR eggs, but no nematodes, was substantial. Again, no significant difference was found between the transformed and nontransformed plants (n ϭ 5, P ϭ 0.18). (C) In plots that received WCR eggs and H. megidis, roots from transformed plants (pooled) had significantly less damage than roots from control lines (n ϭ 30, P ϭ 0.007). Approximately one-quarter of the transformed plants were found not to emit E␤C. Removing these plants from the statistical analysis did not significantly affect the results. The letters above the bars indicate significant differences within a graph. Error bars indicate standard errors.

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Section: Discussionmentioning

confidence: 99%

Sustained transgene expression despite T lymphocyte responses in a clinical trial of rAAV1-AAT gene therapy

Brantly

Chulay

Wang

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

286

239

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“…A1PI has been prepared from pooled human plasma and used as replacement therapy for adults affected by emphysema due to an inherited deficiency of A1AT. A weekly intravenous dose of 60 mg/kg consistently maintains functional and antigenic concentrations of A1PI in the serum and epithelial lining fluid of the lungs above threshold concentrations [1], with a half-life of approximately 110 h [2].…”

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confidence: 98%

Functional and Antigenic Concentrations of Alpha-1-Proteinase Inhibitor after Administration for the Prevention of Chronic Lung Disease of Prematurity

et al. 1999

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Objective and Methods: Alpha-1-proteinase inhibitor (A1PI) supplementation has been used in adults with inherited alpha-1-antitrypsin (A1AT) deficiency to impede the development of emphysema. A1PI supplementation may also be useful for protecting premature neonates who receive mechanical ventilation from the development of chronic lung disease (CLD). However, the pharmacokinetics of exogenous A1PI in this population are unknown. We attempted to determine the disposition of A1PI in premature infants with birth weight 600–1,250 g who received 60 mg/kg on days 0, 4, 7 and 14 in a randomized, placebo-controlled, double-blind trial. Functional and antigenic plasma concentrations of A1PI were measured at specified time points. Results: On both functional and antigenic assays, concentrations began in the normal adult range and rose from day 0 to 10 then fell slightly, but remained above initial values. The concentrations were not significantly different between the treatment and placebo groups. Conclusions: The results of this study indicate that neonatal pharmacokinetics of A1PI differ markedly from those of the adult. Total plasma clearance of exogenous A1PI seems high in the ventilated premature neonate. Higher or more frequent doses may be necessary to maintain A1PI plasma concentrations above baseline.

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“…Plasma serpins are involved in the regulation of multiple proteolytic events, and serious pathologic developments are caused by a wide range of serine proteinases (Travis and Salvesen, 1983;Carrell and Boswell, 1986;Carrell et al, 1987;Patterson, 1991). They have therefore often served biotechnologically as bioindicators in health and hazard assessments of animals that are suffering from pathologic or environmental stress (Fournel et al, 1988;Smith and Roberts, 1994;Carrell and Lomas, 1997).…”

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confidence: 99%

Purification and Characterization of Serum Serpin from Carp (Cyprinus carpio)

Aranishi

1999

Mar. Biotechnol.

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: A serine proteinase inhibitor, termed serpin62, was purified to homogeneity from carp serum with an increase in specific inhibitory activity of 6.2-fold and a 3% recovery rate after separation from alpha1-antitrypsin. Specific inhibitory activity of serpin62 against bovine pancreatic trypsin was less than half of the specific antitryptic activity of alpha1-antitrypsin. Under both reducing and nonreducing conditions, serpin62 was estimated to have a molecular weight (62,000) apparently larger than that of alpha1-antitrypsin (55,000). They both consist of single polypeptide chains, but serpin62 differs from serine proteinase inhibitors from muscles of carp and white croaker in molecular weight and structure. Antibody raised against serpin62 immunologically crossreacted with serpin62 and had no crossreactivity with fish serum alpha1-antitrypsin and muscular analogues. The antibody was susceptible to both serpin62 and its derivatives, which were widely distributed in carp tissues. Serpin62 is most likely distinct from other fish serine proteinase inhibitors expressing antitryptic activity physicochemically and immunologically.

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Preclinical evaluation of alpha-1-proteinase inhibitor

Cited by 7 publications

References 8 publications

Sustained transgene expression despite T lymphocyte responses in a clinical trial of rAAV1-AAT gene therapy

Sustained transgene expression despite T lymphocyte responses in a clinical trial of rAAV1-AAT gene therapy

Functional and Antigenic Concentrations of Alpha-1-Proteinase Inhibitor after Administration for the Prevention of Chronic Lung Disease of Prematurity

Purification and Characterization of Serum Serpin from Carp (Cyprinus carpio)

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