Small intestinal injury caused by non-steroidal anti-inflammatory drugs (NSAIDs) or aspirin is an epoch making topic in clinical field with the aid of new devices, capsule endoscopy and double balloon enteroscopy to look at small intestine directly. However, the injury has been reported in animals since more than 40 years ago. Proposed mechanisms are impairment of mucosal defense through inhibition of cyclooxygenase (COX) resulting in deficiency of prostaglandins, and mitochondrial disorder. Possible aggressive factors are NSAIDs/aspirin themselves, bile, and enterobacteria. Translocation of enterobacteria through the mucosa impaired integrity may be the first step of the injury. Bacterial lipopolysaccharides stimulate toll-like receptor-4 in macrophages, which increases proinflammatory cytokines through MyD88 signaling pathway. Finally neutrophils are activated and the small intestinal mucosa is injured with the attacks of NSAIDs/aspirin themselves, bile, and proteolytic enzymes and active oxygen species released by neutrophils. Candidates of treatment tools are prostaglandin derivatives, mucoprotective drugs, probiotics, and mitochondrial protective drugs such as metronidazole and cyclosporin A. Further clinical studies are needed to elucidate the effect in humans.
This study deals with the development and performance evaluation of a positive reference material for hemolysis testing, which is used for evaluating the biological safety of medical devices. Genapol X-080, a nonionic detergent, was selected as a candidate hemolytic substance in a survey of 23 chemical compounds; it showed significant hemolytic activity against rabbit defibrinated blood at concentrations more than 20 µg/mL. A polyvinyl chloride (PVC) sheet spiked with 0.6% (w/w) of the compound exhibited weak hemolytic activity in direct contact and/or extract-based assays after 4 h incubation at 37°C. A PVC sheet containing 5.8% (w/w) Genapol X-080 induced complete hemolysis in both assays. The amount of Genapol X-080 eluted from each PVC sheet during hemolysis testing using the direct contact method increased time-dependently and reached 25.6 (former sheet) or 1154 (later sheet) µg/mL after 4 h incubation, which was similar to or much higher than the critical micelle concentration, respectively. Similar elution behavior was observed using the extract-based method, and the Genapol X-080 content in test solutions prepared by autoclave extraction of both sheets was 22.5 and 358 µg/mL, respectively, indicating a clear relationship between the degree of hemolytic activity and the eluted amount of Genapol X-080. Thus, a PVC sheet spiked with a compound exhibiting different hemolytic activity depending on its concentration may be useful as a positive reference material to validate the hemolysis tests.
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