松田 安史

Objectives. 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2), which requires oxidized nicotinamide adenine dinucleotide as a cofactor, metabolizes endogenous glucocorticoids. Since 11beta-HSD2 has been detected in lung epithelial cells, we examined whether carbenoxolone, a potent inhibitor of 11beta-HSD, would enhance endogenous glucocorticoid action on lung fluid balance and inflammation. Design. Controlled laboratory study. Setting., University research laboratory. Subjects. Adult Sprague-Dawley rats (n = 66). Interventions., Rats were intraperitoneally injected with carbenoxolone (2 x 10 mg(.)kg(-1.)day(-1) for 3 days) and allowed free access to water and food. Rats were further challenged with endotoxin instillation (1 mg/kg). Measurements and Main Results: We discovered that carbenoxolone significantly increased messenger RNA expression of all three epithelial sodium channel subunits in distal lung tissues (two-fold increase of alpha-subunit, four-fold increase of beta-subunit, and two-fold increase of gamma-subunit) as well as in trachea. Carbenoxolone increased the amiloride-sensitive alveolar fluid clearance significantly. When rats were further challenged by endotoxin instillation (1 mg/kg), pretreatment with carbenoxolone significantly inhibited endotoxin-induced increase in lung neutrophils as well as tumor necrosis factor-a and cytokine-induced neutrophil chemoattractant-1 concentrations in serum and bronchoalveolar lavage fluid. Conclusions: These beneficial effects of carbenoxolone on lung fluid balance and inflammation are very similar to those expected when glucocorticoids are introduced exogenously. We conclude that carbenoxolone increased the actions of endogenous bioactive glucocorticoids on lung cells by reducing local steroid breakdown.

Background. Cold preservation is the most practical method to maintain the viability of isolated lungs. However, rapid cooling may affect pulmonary endothelial function. We examined the effects of microtubule stabilization with paclitaxel on pulmonary endothelial barrier integrity under cold temperature. Methods. Human pulmonary arterial endothelial cells were incubated at VC for 2 hr in the presence or absence of paclitaxel (2.5 mumol/L). Microtubules was visualized using immunocytochemical techniques. Ultrasonic attenuation was measured with scanning acoustic microscopy. Endothelial barrier integrity was measured as transendothelial electric resistance. In addition, we examined graft function in a rat lung transplantation model, in which the donor lung had been preserved in the presence of paclitaxel (2.5 mumol/L) at 4degreesC for 12 hr. Results. Low temperature caused a reversible microtubule disassembly, but the structure of microtubules was preserved by paclitaxel. Paclitaxel prevented the cooling-induced decrease in ultrasonic attenuation and transendothelial electric resistance. In a rat transplantation model, we found that preservation with paclitaxel successfully improved the oxygenation performance of the donor lung, which demonstrated only mild congestion and less significant interstitial edema without fluid accumulation in the alveolar spaces. Conclusions. Our results indicate that microtubule stabilization with paclitaxel maybe beneficial to prevent the loss of the endothelial barrier during cold preservation. We conclude that the use of paclitaxel in organ preservation solutions is useful in protecting pulmonary endothelial barrier integrity during cold preservation, thereby reducing the occurrence of early graft failure.

A case of primary mucinous cystadenocarcinoma of the lung is presented. The patient was a 42-year-old woman with a 5-cm left lung mass. Left lower lobectomy was performed and analysis of a frozen section revealed mucinous cystadenocarcinoma. The tumor was a fibrous, walled cyst containing abundant mucinous material. Sparse groups of malignant cells were microscopically observed in pools of mucin; thus, the tumor resembled mucinous cystadenocarcinoma that occurs in the ovary, appendix, or pancreas. The tumor we found is a very rare intrapulmonary neoplasm that is differentiated from a metastatic lesion and mucinous bronchoalveolar carcinoma by its very different clinical course and prognosis. (C) 2003 by The Society of Thoracic Surgeons.