Protease inhibitors: a panacea?

With the increasing evidence of protease involvement in several diseases, novel strategies for drug development involve the use of protease inhibitors (PIs). The local balance between protease inhibitors and proteases is an important determinant of the occurrence and progression of a particular disease. Hence, enzymes and their cognate inhibitors are finding their applications as diagnostic and prognostic markers. PIs are widely implicated for their use in host defense against infection, tissue repair and matrix production, blood coagulation, cancer, and they are, therefore, the current focus as therapeutic alternatives for major diseases such as AIDS and Alzheimer's diseases. This review is a brief summary of the varied role of protein protease inhibitors in controlling the activity of aberrant enzymes in several diseases afflicting mankind today.

Intestinal worm burden and serum cholesterol or lipid concentration in a Shipibo population (Peru).

Paired samples of stool and serum of 32 members of the Shipibo tribe resident in the rain forest of the Peruvian lowlands were tested for worm egg count and serum lipid parameters, respectively. 90% of the stool samples tested were found to contain eggs or larvae of several worm species, most commonly 3 or 4 different species. Serum lipid levels were found to be relatively low, most probably due to a low proportion of dietary fat ranging from 16-31%. Statistical analysis showed a significant inverse correlation between worm egg excretion and HDL levels which was true for hookworm, strongyloides and trichuris, but not for ascaris. The mechanisms underlying the observed association between intestinal worm load and HDL reduction are not completely understood and may include reduced HDL synthesis in the gut wall due to inflammatory and/or toxic irritation.

Eosinophil diamine oxidase activity in acute inflammation in humans.

Eosinophil diamine oxidase, histaminase, activity was assayed in acute inflammatory states and correlated to disease activity. Correlation to serum and urine histamine, metabolites of histamine and granulocyte histamine metabolizing enzymes was also studied. Using a radiochromatagraphic assay, diamine oxidase, histaminase, activity was determined in human peripheral blood eosinophils from patients with acute inflammatory states including active asthma, cold-induced urticaria and parasitic infestation; eosinophils from non-active asthmatic patients and normals were used as controls. Eosinophils were purified over a metrizamide discontinuous (16-30%) gradient. Total eosinophils were purified over a metrizamide discontinuous (16-30%) gradient. Total eosinophil histaminase activity was increased two- to three-fold in patients with active disease and returned to lower levels in eosinophils from patients without active disease or with treated disease. Thus, the induction of eosinophil histaminase might be a control mechanism for the inflammation induced by histamine during these acute inflammatory states.