Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To summarize, vaccines are regulated in the United States as biologics by CBER and must meet requirements for safety, purity, and potency (efficacy). Although general requirements exist for safety, purity, and potency, specific standards for each vaccine are agreed to by the manufacturer and CBER. The final standards for any vaccine are relevant to the technology used to produce the vaccine. Vaccine efficacy is demonstrated through conducting one or more Phase III trials. A single, definitive, well-controlled, double-blind, placebo-controlled Phase III trial often provides sufficient efficacy data for licensing a vaccine. Pivotal efficacy data may be derived from U.S. or outside the U.S. studies. Bridging studies may be required to link the efficacy data to the intended marketing target population. In the United States, approval for conducting clinical trials is obtained from the FDA through the mechanism of the IND application. Marketing approval is obtained through the mechanism of the PLA and ELA. Postmarketing Phase IV clinical trials are generally requested to develop large-scale field data for safety. Timely communication with the FDA throughout the development and approval process is the most efficient mechanism for meeting all regulatory requirements in the shortest possible time.
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PMID:Regulatory considerations in vaccine design. 755 Dec 50

Earthworm fibrinolytic enzyme II (EFE-II) from Eisenia fetida has a broad hydrolytic specificity for peptide bonds. Our experiments show that EFE-II can hydrolyze the specific chromogenic substrates of thrombin (Chromozym TH), trypsin (Chromozym TRY) and elastase (Chromozym ELA). The Michaelis-Menten constant (K(m)) for Chromozym ELA (approximately 245 microM) is much higher than those for the thrombin (approximately 90 microM) and trypsin (approximately 60 microM) substrates. On the other hand, EFE-II is inhibited most strongly by soybean trypsin inhibitor (SBTI), and weakly inhibited by elastinal, suggesting that EFE-II has a trypsin-like activity. Degradation of plasminogen (PLg) and fibrinogen by EFE-II was investigated after EFE-II had been immobilized onto 1,1'-carboryl-diimidazole (CDI)-activated Sepharose CL-6B. The immobilized EFE-II has 55-60% activity of the native enzyme with a higher thermal and pH resistance. EFE-II cleaves PLg at four hydrolytic sites: Lys(77)-Arg(78), Arg(342)-Met(343), Ala(444)-Ala(445) and Arg(557)-Ile(558). The site Arg(557)-Ile(558) is also recognized and cleaved by tissue plasminogen activator (t-PA) and urokinase (UK), producing active plasmin. Cleaving Ala(444)-Ala(445) released mini-plasmin with secondary activity to hydrolyze fibrin. Immobilized EFE-II degrades not only the Aalpha chain of fibrinogen in the C-terminal region (like human neutrophil elastase, HNE), but also in the N-terminal region at the Val(21)-Glu(22) site.
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PMID:Hydrolysis of fibrinogen and plasminogen by immobilized earthworm fibrinolytic enzyme II from Eisenia fetida. 1295 13