Platelet aggregation factor preparation

The studies mentioned above indicate that bromelain has a certain cytotoxic potential. It remains an open question whether the observed antineoplastic effects of bromelain preparations reside in the proteolytic enzyme or in some or more other components of the mixture. Before the work of Maurer et al. [104] and of Batkin et al. [105], the antitumor activity of bromelain was explained primarily by its fibrinolytic and platelet aggregation inhibitory activity, which is believed to interfere with the fibrin and coagulation features of tumor cells [2], More recently, Desser and Rehberger [107] demonstrated that bromelain stimulates the production of alpha tumor necrosis factor in human peripheral blood mononuclear cell cultures in a time-dependent manner. Immunomodulation, especially the release of cytokines, is believed to be responsible for the possible therapeutic potential of bromelain. However, further experimental evidence is necessary, first, to prove the antineoplastic action of the proteolytic enzyme, and second, to demonstrate that bromelain in vivo is a valuable therapeutic agent in humans. 

The preparation and the assay of the components of fibrinolysis and thrombolysis have been reviewed." The amino-acid sequences at the NH2-terminus, molecular weights, and amino-acid compositions of human prothrombin, factors IX and X, and a new plasma protein have been compared." Desialylation of human plasma factor VIII decreased its ristocetin-induced platelet-aggregation activity and facilitated its clearance by hepatocytes, but its procoagulant activity was not affected." " Experiments in vivo have confirmed the view that the inhibi-... 

The receptors for Factor Vlll/von Willebrand factor that are present on human platelets are directly proportional to the extent of ristocetin-induced platelet aggregating activity. Factor Vlll-related protein aggregates are multimers of pairs of basic sub-unit chains. Further studies support the hypothesis that the underlying defect in von Willebrand type II disease may be incomplete assembly of Factor Vlll/von Willebrand factor monomer molecules into oligomers at the quaternary level of molecular organization. In von Willebrand Type I disease reduced synthesis of the Factor Vlll/von Willebrand factor sub-unit or of primary polymers (mol. wt. 1.0 x 10 ) may be the defect. When prepared from lipid-poor plasma the size heterogeneity ranges from 6.0 x 10 to 2.0 x 10 . ... 

In 1979, the chemical structure of PAF was identified as l-alkyl-2-acetyl-sn-gIycero-3-phosphocholine (Fig. 2) (D.J. Hanahan, 1979 M.L. Blank, 1979 J. Benveniste, 1979). The semi-synthetic preparation tested in these initial experiments aggregated platelets at concentrations as low as 10 " M and induced an anti-hypertensive response when as little as 60 ng were administered intravenously to hypertensive or normotensive rats. Threshold concentrations vary by cell type and organism, but PAF can activate human inflammatory cells at concentrations as low as 10 M. PAF induces diverse biological responses (Table 1) and has been implicated as a contributing factor in the pathogenesis of such diverse disease processes as asthma, hypertension, allergies, inflammation, and anaphylaxis. 

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