Alpha protease inhibitor

Griese M ci al. Reduced proteolysis of surfactant protein A and changes of the bronchoalveolar lavage fluid proteome by inhaled alpha 1-protease inhibitor in cystic fibrosis. Electrophoresis 2001 22 165-171. 

Alpha-1-Protease Inhibitor (Prolastin) Domase Alfa... 

Alpha-1-Protease Inhibitor (Prolastin) [Respiratory Agent/Alpha Protease Inhibitor Replacement] Uses a,-Antit-rypsin deficiency panacinar emphysema Action Replace human aj-protease inhibitor Dose 60 mg/kg IV once/wk Caution [C, ] Contra Selective IgA deficiencies w/ known IgA antibodies Disp Inj SE Fever, dizziness, flu-like Sxs, allergic Rxns EMS Pt may have chronic lung Dz/damage, monitor resp status OD Not expected to produce life-threatening Sxs... 

Healthy adults Inhalation 1-4 ppm 3 h Decrease in red blood cell membrane acetylcholinesterase activity increase in red blood cell lipids and glucose-6-phosphate dehydrogenase activity, higher concentration resulted in decrease in alpha-1-protease inhibitor activity but not overall enzyme activity in BALF. Mucociliary activity ceased after 45-min exposure to 1.5 and 3.5 ppm for 20 min. Devlin ct al. 1992 Frampton et al. 1992 Rasmusen et al. 1992 Posin et aL 1978 Mohsenin and Gee 1987 Helledayet al. 1995... 

B8. Bata, J., Deviller, P., and Revillard, J. P., Binding of alpha 1 antitrypsin (alpha 1 protease inhibitor) to human lymphocytes. Biochem. Biophys. Res. Commun. 98, 709—716 (1981). 

Dll. Del Mar, E. G., Brodrick, J. W., Geokas, M. C., and Largman, C., Effect of oxidation of methionine in a peptide substrate for human elastases A model for inactivation of alpha 1-protease inhibitor. Biochem. Biophys. Res. Commun. 88,346-350 (1979). 

Stone, P. J., Calore, J. D., McGowan, S. E., Bernardo, J., Snider, G. L., and Franzblau, C., Functional alpha 1-protease inhibitor in the lower respiratory tract of cigarette smokers is not decreased. Science 221, 1187-1189 (1983). 

Mattes, E. et al., Preparahon and properhes of an alpha-1-protease inhibitor concenhate with high specific achvity. Vox Sang., 81, 29-36, 2001. 

K. Nakajima, J. C. Powers, B. M. Ashe, and M. Zimmerman. Mapping the extended substrate binding site of cathepsin G and human leukocyte elastase. Studies with peptide substrates related to the alpha 1-protease inhibitor reactive site. J. Biol. Chem. 254 4027 (1979). 

P19. Pos, O., van der Stelt, M. E., Wolbink, G. J., Nijsten, M. W., van der Tempel, G. L., and van Dijk, W. Changes in the serum concentration and the glycosylation of human alpha 1-acid glycoprotein and alpha 1-protease inhibitor in severely burned persons Relation to interleukin-6 levels. Clin. Exp. Immunol. 82, 579-582 (1990). 

Fletcher, T. S., H. Tsukamoto, and Largman C. 1986. Immunoenzymatic determination of trypsin/alpha 1-protease inhibitor complex in plasma of rats with experimental pancreatitis. Clinical Chemistry 32 1738-1741. 

Nathoo, S.A. and Finlay, T.H., 1987, Fetal-specific forms of alpha 1-protease inhibitors in mouse plasma. Pediatr. Res. 22 1-5. 

Inverse Relationship between Protease Inhibitors and Metastatic Ability. All proteases, apart from possibly CD, appear to be controlled by endogenous inhibitors. In theory, therefore, the ability of malignant cells to produce metastasis could depend not only on the levels of the specific protease, but also on the concentration of relevant endogenous inhibitors. Thus, the presence of high levels of protease inhibitors might inhibit metastasis, while low levels of inhibitors might enhance metastasis. An inverse relationship between a number of specific inhibitors and metastatic potential has now been shown. Some examples of this type of relationship include TIMP-1 in Swiss 3T3 cells (K4), cysteine protease inhibitors in mouse melanoma cells (R6), and an alpha-1-proteinase inhibitor in rat mammary carcinomas (N2). Furthermore, a newly described serine protease inhibitor, known as maspin, was found to be expressed less frequently in advanced human breast cancers compared with early cancers (Z2). 

Patel J, Pal D, Vangal V, Gandhi M, Mitra AL (2002) Transport of HIV-protease inhibitors across 1 alpha,25 di-hydroxy vitamin D3-treated Calu-3 cell monolayers Modulation of P-glycoprotein activity. Pharm Res 19(11) 1696-1703. 

Drugs that may be affected by PDE5 inhibitors include alpha-blockers, amlodipine, angiotensin II receptor blockers, bendroflumethiazide, enalaphl, metoprolol, nifedipine, nitrates, protease inhibitors. 

G7. Gross, V., Scholmerich, J., Leser, H. G., Salm, R., Lausen, M., and Ruckauer, K., Granulocyte elastase in assessment of severity of acute pancreatitis. Comparison with acute-phase proteins C-reactive protein, alpha 1-antitrypsin, and protease inhibitor alpha 2-macroglobulin. Dig. Dis. Sci. 35, 97-105 (1990). 

Mohsenin, V., and J.B.L.Gee. 1987. Acute effect of nitrogen dioxide exposure on the functional activity of alpha-l-protease inhibitor in bronchoalveolar lavage fluid of normal subjects. Am. Rev. Respir. Dis. 136(3) 646—650. 

G22. Gravagna, P., Gianazza, E., Arnaud, P., Neels, M., and Ades, E. W., Modulation of the immune response by plasma protease inhibitors. II. Alpha 2-macroglobulin subunits inhibit natural killer cell cytotoxicity and antibody-dependent cell-mediated cytotoxicity. Scand. J. Immunol. 15, 115-118 (1982). 

ALPHA-BLOCKERS PROTEASE INHIBITORS Possible T alfuzosin levels with ritonavir Uncertain Avoid co-administration... 

Dickinson AM, Shenton BK, Alomran AH, Donnelly PK, Proctor SJ. Inhibition of natural killing and antibody-dependent cell-mediated cytotoxicity by the plasma protease inhibitor alpha 2-macroglobulin (alpha 2M) and alpha 2M protease complexes. Clin Immunol Immunopathol 1985 36 259-5. 

Meyer FJ, Wencker M, Teschler H, Steveling H, Sennekamp J, Costabel U, Konietzko N. Acute allergic reaction and demonstration of specific IgE antibodies against alpha-l-protease inhibitor. Eur Respir J 1998 12(4) 996-7. 

The fecal clearance of alpha-1-antitrypsin (AT) can also be used as a marker of GI protein loss. AT is a glycoprotein (MW 54,000) that is synthesized in the fiver and is normally present in the serum at a concentration of about 1.5 to 2 g/L. It is a protease inhibitor and therefore resistant to degradation by proteolytic enzymes in the GI tract. The fecal clearance of AT correlates with protein loss measured by Cr techniques (r = 0.96). The correlation is not influenced by serum AT concentrations or by fecal weight. AT clearance can be used for both small and large bowel disease and is appficable to the evaluation of enteric protein loss in children or adults.More recent work has confirmed these findings and also confirmed that fecal AT concentration alone does not reliably predict AT clearance (i.e., a timed fecal sample and measurement of serum AT is required). An important observation is that experimentally induced diarrhea in normal subjects leads to an increased AT clear-... 

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