Junsuke Tanaka

Pulmonary Collapse and Pneumonia Due to Inhalation of a Waterproofing Aerosol in Female CD-1 Mice

Waterproofing agents consist of mixtures of solvents, repellents and propellants. Because of a fatality and a number of acute respiratory illnesses in humans following the exposure to a waterproofing agent, the aerosol mixtures were tested in mice. Inhalation of the waterproofing agent resulted in pulmonary collapse and pneumonia in mice. By testing fractions of the waterproofing agent it was determined that the fluororesin repellents in the waterproofing agent were responsible for the acute respiratory illness. The water-repelling agent, such as fluororesin, may counteract the surfactant in the alveoli of the lung and cause diffuse pulmonary collapse followed by acute respiratory distress. The recent substitution of less toxic and environmentally more friendly solvents in waterproofing agents may facilitate fluororesin inhalation by increasing the amount of airborne aerosol and changing the diameter of the aerosol particles. This would explain the apparent recent increase of respiratory symptoms following the use of these agents. In this experiment the mice were exposed intermittently to overcome the CNS effects of the solvents.

Cytokine mRNA Expression After Transient and Prolonged Hypotension

The role of cytokines in hemorrhagic shock remains controversial, with some studies showing an elevation of cytokines, whereas others do not. We thus analyzed the changes in tumor necrosis factor (TNF) activity and in mRNA of TNFα, interleukin-1β (IL-1β), and interleukin-6 (IL-6) after transient and prolonged hypotension. In the transient hypotension group (TH group), chronically cannulated rats were bled (20 ml/kg·3min) without fluid resuscitation. They showed transient hypotension, but their blood pressure (BP) quickly stabilized. In the prolonged hypotension group (PH group), the rats were bled and maintained at a mean BP of 40 mmHg for 60 min, and then were resuscitated with the shed, blood and an equal volume of saline over 60 min. The serum TNF activity was measured by cytotoxicity against the L929 tumorigenic murine fibroblast. Messenger RNA of TNFα, IL-1β, and IL-6 in liver was measured semi-quantitatively by high-performance liquid chromatography after reverse transcription and polymerase chain reaction. The increases in the TNF activity were not significant in either of the groups above the prehemorrhage levels, whereas mRNA of TNFα and IL-1β showed a transient elevation in the TH group and a persistent elevation in the TH group. IL-6 mRNA did not increase significantly in the TH group, but did increase in the PH group. These results show that a large hemorrhage induces cytokine mRNA in the liver and also show the differences in the changes of cytokine mRNA after transient and prolonged hypotension.

A Comparative Study of Direct Hemoperfusion and Hemodialysis for the Removal of Glufosinate Ammonium

BASTA is a herbicide containing glufosinate ammonium 18.5% and a surface-active agent. There were six fatalities in 34 cases of glufosinate ammonium poisoning reported by the Japan Poison Information Center. To evaluate efficacy in the removal of glufosinate ammonium from the blood, two bottles were prepared containing 600 mL of heparinized bovine blood with 1 mL or 3 mL of BASTA. Direct hemoperfusion or hemodialysis was performed for two hours at a flow rate of 50 mL/min. The final glufosinate ammonium concentration of the blood bottle containing 1 mL of BASTA decreased to 96.9% of the initial concentration after direct hemoperfusion and to 0.5% after hemodialysis. The final glufosinate ammonium concentration of the bottle containing 3 mL of BASTA decreased to 62.2% after direct hemoperfusion and to 0.9% after hemodialysis. Hemodialysis is more effective than direct hemoperfusion for removal of glufosinate ammonium from blood.

Simple hemorrhage induces tissue factor mRNA in the liver.

Thrombogenic responses are sometimes seen after a large hemorrhage, but the precise mechanisms whereby this phenomenon occurs still remain unknown. We recently showed that plasminogen activator inhibitor-1 rises after a 20-ml/kg hemorrhage in rats and suggested that this change may be one of the contributing factors to the thrombogenic responses after a large hemorrhage. In this study, we set out to detect the changes on the coagulation side, that is, the changes in whole blood clotting time and the mRNA of tissue factor (TF), which is the primary initiator of the clotting cascade. The rats were all bled (20 ml/kg) 3 days after cannulation. The whole blood clotting time was measured by the Lee-White method. Changes in the TF mRNA were detected in the liver by high-performance liquid chromatography after reverse transcription and polynerase chain reaction using glyceraldehyde 3-phosphate dehydrogenase as an external standard. A 20-ml/kg hemorrhage significantly shortened the whole blood clotting time and significantly increased the TF mRNA in the liver at 1, 2, and 4h in comparison to the nonhemorrhage controls. These results indicate that a simple hemorrhage without tissue trauma can induce hypercoagulability and suggest that the induction of TF might be involved in this phenomenon.