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inhibitor GPD-1116 markedly attenuates the development of cigarette smoke-induced emphysema in senescence-accelerated mice P1 strain. Am J Physiol Lung Cell Mol Physiol 294: L196-L204, 2008. First published November 9, 2007 doi:10.1152/ajplung.00173.2007.-Phosphodiesterase 4 (PDE4) is an intracellular enzyme specifically degrading cAMP, a second messenger exerting inhibitory effects on many inflammatory cells. To investigate whether GPD-1116 (a PDE4 inhibitor) prevents murine lungs from developing cigarette smoke-induced emphysema, the senescence-accelerated mouse (SAM) P1 strain was exposed to either fresh air or cigarette smoke for 8 wk with or without oral administration of GPD-1116. We confirmed the development of smoke-induced emphysema in SAMP1 [air vs. smoke (means Ϯ SE); the mean linear intercepts (MLI), 52.9 Ϯ 0.8 vs. 68.4 Ϯ 4.2 m, P Ͻ 0.05, and destructive index (DI), 4.5% Ϯ 1.3% vs. 16.0% Ϯ 0.4%, P Ͻ 0.01]. Emphysema was markedly attenuated by GPD-1116 (MLI ϭ 57.0 Ϯ 1.4 m, P Ͻ 0.05; DI ϭ 8.2% Ϯ 0.6%, P Ͻ 0.01) compared with smoke-exposed SAMP1 without GPD-1116. Smokeinduced apoptosis of lung cells were also reduced by administration of GPD-1116. Matrix metalloproteinase (MMP)-12 activity in bronchoalveolar lavage fluid (BALF) was increased by smoke exposure (air vs. smoke, 4.1 Ϯ 1.1 vs. 40.5 Ϯ 16.2 area/g protein; P Ͻ 0.05), but GPD-1116 significantly decreased MMP-12 activity in smokeexposed mice (5.3 Ϯ 2.1 area/g protein). However, VEGF content in lung tissues and BALF decreased after smoke exposure, and the decrease was not markedly restored by oral administration of GPD-1116. Our study suggests that GPD-1116 attenuates smoke-induced emphysema by inhibiting the increase of smoke-induced MMP-12 activity and protecting lung cells from apoptosis, but is not likely to alleviate cigarette smoke-induced decrease of VEGF in SAMP1 lungs.protease; aging; apoptosis; oxidative stress; vascular endothelial growth factor CHRONIC OBSTRUCTIVE PULMONARY disease (COPD) is a disease state characterized by airflow limitation and is a global health problem in terms of morbidity, mortality, and economic burden (16). Chronic cigarette smoke exposure is the most important risk factor and induces chronic inflammation of the airways and lung parenchyma by recruiting and activating inflammatory cells to release proteinases, particularity elastase from neutrophils and various metalloproteinases from alveolar macrophages. Accordingly, drugs that control the underlying inflammatory and destructive processes are required for the treatment of COPD.Phosphodiesterases (PDEs) are intracellular enzymes that degrade cyclic nucleotides. Among many isozymes, phosphodiesterase 4 (PDE4) specifically degrades cAMP, a second messenger exerting inhibitory effects on many inflammatory cells. PDE4 is ubiquitously expressed among inflammatory and immune cells including neutrophils, CD8ϩ T cells, macrophages, mast cells, eosinophils, and airway epithelial cells (1,17,30). PDE4 inhibitors show suppressive effects on various in vitro responses, ...

PURPOSEThe complexity of lung cancer treatment is rapidly increasing, necessitating the use of multidisciplinary approaches for improving outcomes. Although it is common for institutions to have their own tumor boards, tumor boards connecting several general hospitals, and therefore allowing for more diverse opinions, are not prevalent.MATERIALS AND METHODSA tumor board connecting eight hospitals was formed to discuss patients for whom formulating a treatment strategy was difficult. Physicians and hospital staff accessed a high-security communication line via LiveOn ( Japan Media Systems Corporation, Tokyo, Japan), which is completely isolated from the Internet and password protected, that enables each hospital to share the electronic medical records and images of relevant patients at other hospitals on desktop computers in real time. The lung cancer tumor board began in April 2017 and has since been held every Tuesday evening for 1 hour. Preparatory records containing the age, sex, histology, TNM classification, background, and discussion points for each patient are created before each tumor board meeting. After the tumor board discussion, all conclusions and related articles used in the board are added to the minutes, which are finalized as Microsoft Word files, consolidated, and archived. These files can be retrieved later using key words.RESULTSFrom April 2017 to June 2018, 202 patients were discussed. Although TNM classification was not changed for any patient, diverse opinions led to a change in the proposed strategy for 49 of 202 patients.CONCLUSIONThe multidisciplinary tumor board was useful in obtaining various opinions from the perspectives of different experts. This should be evaluated in a prospective study.

Abstract

The aim of this study was to measure nicotine concentrations in inspired and expired air so as to learn more about respiratory (nasopharyngeal cavity and lung) nicotine absorption from inspired air and to estimate the nicotine intake during passive smoking. A total of 17 young non-smoking women were exposed to experimental passive smoking. Inspired and expired air was sucked at a constant rate into samplers filled with acid-treated diatomite (Uniport-S) to absorb nicotine in the air. Absorbed nicotine was assayed by gas chromatography. The range of nicotine concentration in the inspired air was 40-200 micrograms/m3. In this setting, 47 samples obtained from the 17 subjects were assayed. Nicotine absorption, which was calculated as [(nicotine concentration in inspired air-nicotine concentration in expired air)/nicotine concentration in inspired air] x 100, remained at 60%-80% (mean +/- SD, 71.3% +/- 10.2%) without being affected by the nicotine concentration in the inspired air. From this result, it was estimated that the average intake of nicotine was 0.026 mg/h in a group of non-smokers exposed in a room containing a nicotine concentration of 100 micrograms/m3, which is equivalent to fairly severe involuntary tobacco smoking. This is the first report on the estimation of respiratory nicotine absorption and nicotine intake during passive smoking based on the direct measurement of nicotine concentrations in both inspired and expired air.