Recommendations for the Conduct of Acute Inhalation Limit Tests

This paper reviews the scientific issues related to exposureconcentrations and particle sizes used in acute inhalation limittests. The current United States Environmental Protection Agency(USEPA) recommended exposure concentration for such tests is5 mg/liter, while this level is very high, it is often achievable.On the other hand, its toxicological relevance is questionable.The USEPA recommendation that 25% of the particle distributionbe less than 1 µm is a more difficult issue to address.Physical laws for aerosol particle generation and behavior limitthe minimum size of particles in an exposure atmosphere at aconcentration of 5 mg/liter. Particle size also influences depositionsite in the respiratory tract. Since damage to any region ofthe respiratory tract can produce lethality, and it is not possibleto predict, a priori, the most responsive region of the tractor the most harmful particle size of an untested agent, acutelimit testing should employ particles in a size range that depositsthroughout the entire rodent respiratory tract. Particles between1 and 4 µm mass median aerodynamic diameter (MMAD) arewell suited for such studies. It is, therefore, recommendedthat the limit test concentration should be the highest concentration(up to 5 mg/liter) that can be achieved while still maintaininga particle size distribution having an MMAD between 1 and 4µm.     

中医疲劳术语整理研究

以疲劳术语系列中的“倦类”为代表进行释义并阐述了整理疲劳术语的意义的目的。其意义和目的为：阐明中医疲劳的病因，病机，规范描述疲劳的术语，为探讨中医抗疲劳及调治亚健康的方药提供线索与依据。     

105Changes in Nitric Oxide Levels After Deep Dermal injury in the Female,Red Duroc Pig (FRDP)

Introduction : Hypertrophic scar is a devastating sequel to burns and other tangential skin injuries. It follows deep dermal injuries and does not occur after superficial injuries. Nitric oxide (NO) plays many important roles in wound healing from inflammation to scar remodeling. Studies have shown that expression of nitric oxide synthase and nitric oxide production are decreased in human hypertrophic scar. However little is known about NO involvement in the early stages of hypertrophic scarring, because of the lack of an animal model. It was recently reported that the female red Duroc pig (FRDP) makes thick scar, which is similar to human hypertrophic scar. We hypothesized that NO production in wounds on the female, red Duroc pig is similar to that of human hypertrophic scar and that NO involvement in deep wounds is different from that in superficial wounds. Methods : Superficial (0.015” to 0.030”) and deep (0.045” to 0.060”) wounds were created on the backs of four FRDPs. Biopsies were collected at weeks 1.5, 4, 8 and 21 post wounding including samples of uninjured skin. Nitric oxide levels were measured with the Griess reaction assay and normalized with tissue protein level. Results : Superficial wounds healed with an invisible scar whereas the deep wounds healed with scar resembling mild hypertrophic scar. The thickness of the scars from the deep wounds was significantly greater than uninjured skin and healed superficial wounds (p < 0.01). NO levels were increased at 1.5 weeks in deep wounds compared to superficial wounds and uninjured skin (p < 0.05). At 8 weeks, NO levels in deep wounds had returned to the level of uninjured tissue and superficial wounds. By 21 weeks, NO levels had decreased significantly when compared to superficial wounds (p < 0.01). There were no differences in NO levels between uninjured skin and superficial wounds at any time point (p > 0.05). Conclusions : NO production is similar in late, deep wounds on the female, red Duroc pig to that reported in the literature for human hypertrophic scar further validating this animal model. NO production is quite different after deep wounds as compared to superficial wounds in the FRDP. Early elevation in nitric oxide production might account for excessive inflammation in deep wounds that become thick scars in the FRDP. Nitric oxide regulators and effects at early stages of scar formation should be elucidated further and the FRDP appears to be a useful model.     

Improved outcome of chronic Pseudomonas aeruginosa lung infection is associated with induction of a Th1-dominated cytokine response

Repeated challenge with antigen is involved in the pathogenesis of a variety of pulmonary diseases. Patients with cystic fibrosis (CF) experience recurrent pulmonary colonization with Pseudomonas aeruginosa before establishment of chronic lung infection. To mimic recurrent lung infections in CF patients, the lungs of susceptible BALB/c mice were re-infected with P. aeruginosa 14 days after the initial infection. Singly-infected BALB/c mice, as well as non-infected mice, were used as controls. Decreased mortality and milder lung inflammation in re-infected BALB/c mice, as well as a tendency for improved clearance of bacteria, was observed when compared with singly-infected mice. The improved outcome in re-infected mice correlated with changes in CD4 cell numbers. Surface expression of LFA-1 on pulmonary CD4 cells was increased in re-infected compared with singly-infected mice. Moreover, resistance to re-infection was paralleled by a shift towards a Th1-dominated response and increased IL-12 production. No significant increase in serum IgG was observed in the re-infected mice. In conclusion, these results indicate a protective role for a Th1-dominated response, independent of antibody production, in chronic P. aeruginosa lung infection in CF.