Irreversible enzyme inhibitors. CLIII. Proteolytic enzymes. 11. Inhibition of guinea pig complement by substituted phenoxyacetamides

1969 ◽  
Vol 12 (3) ◽  
pp. 415-419 ◽  
Author(s):  
Bernard Randall Baker ◽  
Jeffrey A. Hurlbut
Keyword(s):  
Guinea Pig ◽  
Enzyme Inhibitors ◽  
Proteolytic Enzymes

scholarly journals STUDIES ON THE PATHOGENESIS OF FEVER

1962 ◽  
Vol 115 (1) ◽  
pp. 37-47 ◽  
Author(s):  
Hans Klaus Kaiser ◽  
W. Barry Wood
Keyword(s):  
Salt Solution ◽  
Enzyme Inhibitors ◽  
Proteolytic Enzymes ◽  
Chemical Characteristics ◽  
Polymorphonuclear Leucocytes ◽  
Endogenous Pyrogen ◽  
Diisopropyl Fluorophosphate ◽  
Sufficient Concentration

The production of endogenous pyrogen by intact granulocytes obtained from acute peritoneal exudates is blocked by arsenite, iodoacetate, p-chloromercuribenzoate, and N-ethylmaleimide in concentrations of 2 x 10–4 M. When the concentration of these sulfhydryl-reactive enzyme inhibitors is increased to 2 x 10–2 M, only the iodoacetate inactivates the pyrogen molecule, whereas the arsenite, the p-chloromercuribenzoate, and the N-ethylmaleimide have no gross effect upon its thermogenic activity. Both diisopropyl fluorophosphate and dinitrofluorobenzene are even more potent inactivators of the pyrogen molecule than iodoacetate, although the action of the DFP cannot be blocked or reversed by known antagonists such as 2-pyridine aldoxime methiodide and hydroxylamine. Proteolytic enzymes, potentially capable of degrading leucocytic pyrogen, are released from polymorphonuclear leucocytes, along with the pyrogen, when the cells are incubated in normal salt solution. These enzymes are readily activated by a sufficient concentration of glutathione (2 x 10–2 M). They are not present in preparations of partially purified leucocytic pyrogen from which much of the non-pyrogenic protein has been removed. Glutathione by itself, even at concentrations as high as 2 x 10–1 M, does not affect in the gross the thermogenic activity of the purified pyrogen. The implications of these findings in relation to both the production and the chemical characteristics of leucocytic pyrogen are discussed.

scholarly journals Review of recently used techniques and materials to improve the efficiency of orally administered proteins/peptides

2019 ◽  
Vol 28 (1) ◽  
pp. 403-416 ◽  
Author(s):  
Yousif H-E. Y. Ibrahim ◽  
Géza Regdon ◽  
Elnazeer I. Hamedelniel ◽  
Tamás Sovány
Keyword(s):  
Enzyme Inhibitors ◽  
Proteolytic Enzymes ◽  
Absorption Enhancement ◽  
Polymeric Nanocarriers ◽  
Mucoadhesive Polymers ◽  
Macromolecular Drugs ◽  
Regulatory Aspect ◽  
Routes Of Drug Administration ◽  
Stability Issues ◽  
Near Future

Abstract Objectives The main objective of present review is to explore and evaluate the effectiveness of recently developed methods to improve the bioavailability of orally administered biopharmaceutical drugs. Methods A systematic search of sciencedirect, tandfonline and Google Scholar databases based on various sets of keywords was performed. All results were evaluated based on their abstracts, and irrelevant studies were neglected during further evaluation. Results At present, biopharmaceuticals are used as injectable therapies as they are not absorbed adequately from the different routes of drug administration, particularly the oral one. Their insufficient absorption is attributed to their high molecular weight, degradation by proteolytic enzymes, high hydrophilicity and rigidity of the absorptive tissues. From industrial aspect incorporation of enzyme inhibitors (EIs) and permeation enhancers (PEs) and mucoadhesive polymers into conventional dosage forms may be the easiest way of formulation of orally administered macromolecular drugs, but the effectiveness of protection and absorption enhancement here is the most questionable. Conjugation may be problematic from regulatory aspect. Encapsulation into lipid-based vesicles sufficiently protects the incorporated macromolecule and improves intestinal uptake but have considerable stability issues. In contrast, polymeric nanocarriers may provide good stability but provides lower internalization efficacy in comparison with the lipid-based carriers. Conclusion It can be concluded that the combination of the advantages of mucoadhesive polymeric and lid-based carriers in hybrid lipid/polymer nanoparticles may result in improved absorption and might represent a potential means for the oral administration of therapeutic proteins in the near future.

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