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PubMed2003

Plasma platelet activating factor-acetylhydrolase (PAF-AH).

The platelet-activating factor-acetylhydrolase (PAF-AH) is an enzyme which catalyzes the hydrolysis of acetyl ester at the sn-2 position of PAF. The family of PAF-AHs consists of two intracellular isoforms (Ib and II), and one secreted isoform (plasma). These PAF-AHs show different biochemical characteristics and molecular structures. Plasma PAF-AH and intracellular isoform, II degrade not only PAF but also oxidatively fragmented phospholipids with potent biological activities. Among these PAF-AHs, plasma PAF-AH has been the target of many clinical studies in inflammatory diseases, such as asthma, sepsis, and vascular diseases, because the plasma PAF-AH activity in the patients with these diseases is altered when compared with normal individuals. Finding a genetic deficiency in the plasma PAF-AH opened the gate in elucidating the protecting role of this enzyme in inflammatory diseases. The most common loss-of-function mutation, V279F, is found in more than 30% of Japanese subjects (4% homozygous, 27% heterozygous). This single nucleotide polymorphism in plasma PAF-AH and the resulting enzymatic deficiency is thought to be a genetic risk factor in various inflammatory diseases in Japanese subjects. Administration of recombinant plasma PAF-AH or transfer of the plasma PAF-AH gene improves pathology in animal models. Therefore, substitution of plasma PAF-AH would be an effective in the treatment of the patients with the inflammatory diseases and a novel clinical approach. In addition, the detection of polymorphisms in the plasma PAF-AH gene and abnormalities in enzyme activity would be beneficial in the diagnosis of the inflammatory diseases.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMedDate not supplied

Bleeding and thrombosis in children with acute lymphoblastic leukaemia, treated according to the ALL-BFM-90 protocol.

A multi-center retrospective survey was conducted to evaluate the incidence and types of hemostatic complications occurring in children with acute lymphoblastic leukemia (ALL) during treatment according to the ALL-BFM-90 treatment protocol. All of the BFM-treatment centers (n = 77) were approached and a 95% response rate with information on 1100 patients was obtained. Thrombotic or bleeding episodes occurred in 31 patients (2.8%), 19 of whom had thrombosis and 12 bleeding complications, involving the central nervous system (42%), the subclavian vein (29%), the gastro-intestinal tract, skin, lower extremities or pelvis (29%). Recovery was noted in 28 of 31 patients, while 3 died as a result of hemostatic complications. Bleeding or thrombosis occurred in patients receiving prophylactic substitution with plasma or plasma-derived concentrates (n = 16) as well as in those without substitution (n = 13). The majority of hemostatic complications (90%) occurred during the induction therapy of the treatment protocol, in particular during the period which included simultaneous administration of glucocorticoids and E. coli L-asparaginase. The concurrent administration of E. coli L-asparaginase and glucocorticoids may be an additional risk factor for thromboembolic events during therapy according to the ALL-BFM-90 protocol.

Adolescent↗
PubMed1998

Virus inactivation by solvent/detergent treatment and the manufacture of SD-plasma.

Solvent/Detergent (SD) is an extraordinarily effective means for eliminating enveloped viruses from plasma and plasma products. The safety margin suggested by the rapid and complete kill of enveloped viruses observed in the laboratory has been confirmed repeatedly by groups worldwide and by thirteen years of routine clinical use encompassing an estimated 35 million doses of a wide variety of products. Throughout this time, there has not been a single documented case of enveloped virus transmission by an SD-treated product. This record of safety spawned the development of SD-treated plasma as a substitute for fresh frozen plasma (FFP) and has encouraged the adoption of SD for the treatment of non-blood products such as monoclonal antibodies and those derived from recombinant DNA procedures. This review summarizes the use of SD treatment, including its use in combination with other viral elimination procedures, and also summarizes Vitex's initial experience in the manufacture of SD-Plasma, recently licensed by the U.S. FDA.

Blood-Borne Pathogens↗