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A better understanding of farmers’ investment strategies associated with climate and weather is crucial to protecting farming and other climate-exposed sectors from extreme hydrometeorological events. Accordingly, this study employed a field experiment to investigate the investment decisions under risk and uncertainty by 213 farmers from four regions of Taiwan. Each was asked 30 questions that paired “no investment,” “investment with crop insurance,” “investment with subsidized crop insurance,” and “investment” as possible responses. By providing imperfect information and various probabilities of certain states occurring, the experimental scenarios mimicked various types of weather-forecasting services. As well as their socioeconomic characteristics, the background information we collected about the participants included their experiences of natural disasters and what actions they take to protect their crops from weather damage. The sampled farmers became more conservative in their decision-making as the weather forecasts they received became more precise, except when increases in risk were associated with high returns. The provision of insurance subsidies also had a conservatizing effect. However, considerable variation in investment preferences was observed according to the farmers’ crop types. For those seeking to create comprehensive policies aimed at helping the agricultural sector deal with the costs of damage from extreme events, this study has important implications. This approach could be extended to research on the perceptions of decision-makers in other climate-exposed sectors such as the construction industry.

Chiung-Zuei Chen,1 Chau-Chyun Sheu,2 Shih-Lung Cheng,3,4 Hao-Chien Wang,5 Meng-Chih Lin,6 Wu-Huei Hsu,7 Kang-Yun Lee,8 Diahn-Warng Perng,9 Hen-I Lin,10 Ming-Shian Lin,11 Sheng-Hao Lin,12 Jong-Rung Tsai,13 Chin-Chou Wang,6 Cheng-Yi Wang,10 Tsung-Ming Yang,14 Ching-Lung Liu,15 Tsai-Yu Wang,16 Ching-Hsiung Lin12,17,18 1Division of Pulmonary Medicine, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 2Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, 807, Taiwan; 3Department of Internal Medicine, Far Eastern Memorial Hospital, Taipei, 220, Taiwan; 4Department of Chemical Engineering and Materials Science, Yuan Ze University, Zhongli, Taoyuan, 320, Taiwan; 5Department of Internal Medicine, National Taiwan University Hospital, Taipei, 100, Taiwan; 6Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, 404, Taiwan; 7Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, 833, Taiwan; 8Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, 110, Taiwan; 9Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, 112, Taiwan; 10Department of Internal Medicine, Cardinal Tien Hospital, Fu-Jen Catholic University, Taipei, 242, Taiwan; 11Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, 600, Taiwan; 12Division of Chest Medicine, Changhua Christian Hospital, Changhua, 500, Taiwan; 13Division of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan; 14Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Taoyuan City, Taiwan; 15Division of Chest Medicine, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, 104, Taiwan; 16Pulmonary Disease Research Centre, Department of Thoracic Medicine, Chang Gung Memorial Hospital, Chang Gung University, School of Medicine, Taipei, Taiwan; 17Institute of Genomics and Bioinformatics, National Chung Hsing University, Taichung, 402, Taiwan; 18Department of Recreation and Holistic Wellness, MingDao University, Changhua, 523, TaiwanCorrespondence: Ching-Hsiung LinDivision of Chest Medicine, Department of Internal Medicine, Changhua Christian Hospital, 135 Nanhsiao Street, Changhua, 50006, TaiwanTel +886-4-7238595Fax +886-4-7232942Email 47822@cch.org.twBackground and Aim: Chronic obstructive pulmonary disease (COPD) is frequently underdiagnosed because of the unavailability of spirometers, especially in resource-limited outpatient settings. This study provides real-world evidence to identify optimal approaches for COPD case finding in outpatient settings.Methods: This retrospective study enrolled individuals who were at risk of COPD (age ≥ 40 years, ≥ 10 pack-years, and ≥ 1 respiratory symptom). Eligible participants were examined using various COPD case-finding tools, namely the COPD Population Screener (COPD-PS) questionnaire, a COPD prediction (PCOPD) model, and a microspirometer, Spirobank Smart; subsequently, the participants underwent confirmatory spirometry. The definition and confirmation of COPD were based on conventional spirometry. Receiver operating characteristic curve (ROC), area under the curve (AUC), and decision curve analyses were conducted, and a clinical impact curve was constructed.Results: In total, 385 participants took part in the study [284 without COPD (73.77%) and 101 with COPD (26.23%)]. The microspirometer exhibited a higher AUC value than did the COPD-PS questionnaire and the PCOPD model. The AUC for microspirometry was 0.908 (95% confidence interval [CI] = 0.87– 0.95), that for the PCOPD model was 0.788 (95% CI = 0.74– 0.84), and that for the COPD-PS questionnaire was 0.726 (95% CI = 0.67– 0.78). Decision and clinical impact curve analyses revealed that a microspirometry-derived FEV1/FVC ratio of < 74% had superior clinical utility to the other measurement tools.Conclusion: The PCOPD model and COPD-PS questionnaire were useful for identifying symptomatic patients likely to have COPD, but microspirometry was more accurate and had higher clinical utility. This study provides real-world evidence to identify optimal practices for COPD case finding; such practices ensure that physicians have convenient access to up-to-date evidence when they encounter a symptomatic patient likely to have COPD.Keywords: COPD, COPD case-finding, PCOPD model, COPD-PS questionnaire, microspirometry, spirometry

The main purpose of this research was to evaluate and analyze the economic value of the meteorological information services (MIS) provided by the Central Weather Bureau (CWB) when applied to aquaculture in Taiwan. In this research, a contingent valuation method (CVM) was used to inquire about the subjective rating given to the CWB’s meteorological information services based on the responses to a national level questionnaire distributed among aquaculture farmers. The subjective rating revealed how the aquaculture farmers rated the accuracy of the MIS provided by the CWB and how they recognized the impact of the MIS on their aquaculture output. On this basis, this research determined the economic value brought about by the application of the meteorological information services. In order to understand the main factors affecting the respondents’ willingness-to-pay (WTP) for the MIS, this research also conducted an empirical estimation of the bid function. The results indicated that the main factors affecting the WTP were found to include the respondents’ subjective rating of the meteorological information services (including the accuracy rating and the effect rating), traditional social and economic background variables such as income and education level, as well as fish species. In addition, through testing the estimation of the bid function, it was also found that the survey sample used in this research had a significant starting point bias effect, which needed to be corrected using econometric methods. According to the empirical results, the median willingness-to-pay (WTP) of aquaculture farmers in Taiwan was 3544 New Taiwan Dollars (NTD)/person/year and the total economic value at the national level ranged from 157 million to 209 million NTD per year. Since the MIS service users have often lacked sufficient knowledge and ability to interpret the weather forecasts, how to strengthen the capabilities of service users in using MIS through the promotion of training programs and improve the value of the MIS may be an important policy insight.

Chronic obstructive pulmonary disease (COPD) is preventable and treatable. However, many patients remain undiagnosed and untreated due to the underutilization or unavailability of spirometers. Accordingly, we used Spirobank Smart, an app-based spirometer, for facilitating the early detection of COPD in outpatient clinics. This prospective study recruited individuals who were at risk of COPD (i.e., with age of ≥40 years, ≥10 pack-years of smoking, and at least one respiratory symptoms) but had no previous COPD diagnosis. Eligible participants were examined with Spirobank Smart and then underwent confirmatory spirometry (performed using a diagnostic spirometer), regardless of their Spirobank Smart test results. COPD was defined and confirmed using the postbronchodilator forced expiratory volume in 1 s/forced vital capacity values of &lt, 0.70 as measured by confirmatory spirometry. A total of 767 participants were enrolled and examined using Spirobank Smart, 370 participants (94.3% men, mean age of 60.9 years and mean 42.6 pack-years of smoking) underwent confirmatory spirometry. Confirmatory spirometry identified COPD in 103 participants (27.8%). At the optimal cutoff point of 0.74 that was determined using Spirobank Smart for COPD diagnosis, the area under the receiver operating characteristic was 0.903 (95% confidence interval (CI) = 0.860–0.947). Multivariate logistic regression revealed that participants who have an FEV1/FVC ratio of &lt, 74% that was determined using Spirobank Smart (odds ratio (OR) = 58.58, 95% CI = 27.29–125.75) and old age (OR = 3.23, 95% CI = 1.04–10.07 for 60 ≤ age &lt, 65, OR = 5.82, 95% CI = 2.22–15.27 for age ≥ 65) had a higher risk of COPD. The Spirobank Smart is a simple and adequate tool for early COPD detection in outpatient clinics. Early diagnosis and appropriate therapy based on GOLD guidelines can positively influence respiratory symptoms and quality of life.

This review briefly summarizes the situation regarding food security in East and Southeast Asia. In accordance with the World Food Summit definition and 2009 Declaration of the World Summit on Food Security, the four pillars of food security—food availability, access to food, the stability of food supplies, and food utilization—are closely scrutinized along with the characteristics of food security at the sub-regional level. Historical trends for the agricultural economy and the food trade, such as food imports and exports, production and consumption, and the food price index in the sub-region, are presented and statistically analysed. Additionally, because agricultural industry in this region is vulnerable to climate change, issues about how climate change affects food security in food production systems, agricultural livelihoods, nutrition, and food policy making, which can be linked to the four pillars in different ways, are also discussed.

Acute lung injury (ALI) is the clinical disorder of acute hypoxemic respiratory deficiency and it is associated with a high mortality rate. Increased lung permeability, infiltration of inflammatory cells, secretion of inflammatory cytokines, and pulmonary edema are hallmarks of ALI. Currently, there is no effective pharmacological agent approved for ALI, and the treatment regimens available are mostly supportive. Mesenchymal stem cells (MSCs) are multipotent stromal cells with immunomodulating potential, which therefore hold great promise for the treatment of ALI. We established an LPS-induced ALI mouse model by intratracheal injection of lipopolysaccharide (LPS). Human umbilical cord-derived MSCs (hUC-MSCs) were delivered through the tail vein to assess the effects of MSCs on relieving LPS-induced ALI. Intratracheal injection of LPS increased the infiltration of neutrophils and enhanced the expression of pro-inflammatory cytokines, such as IL-6, IL-1β and TNF-α. Administration of hUC-MSCs decreased pathological signs of inflammation, as well as reduced ALI scores. The levels of IL-6, IL-1β and TNF-α were also dose-dependently inhibited in the bronchoalveolar lavage fluids from damaged lung tissues. Moreover, MPO and BAX levels were decreased by the hUC-MSC treatment, suggesting hUC-MSCs may play the role in inhibiting ROS production and apoptotic death in ALI repair. These results highlight the potential of hUC-MSCs to alleviate bacterial endotoxin-induced inflammation, and may represent an effective modality for the treatment of ALI in clinical settings.

This research uses the contingent valuation method to evaluate the economic benefits of the meteorological information services provided by the Central Weather Bureau for livestock farming in Taiwan. The results show that the subjective rating of the accuracy of information services dominates the willingness to pay. After correcting the possible bias, the annual total economic value of meteorological information services of livestock farmers in Taiwan is about 120.75 million NTD~135.97 million NTD.

β-elemonic acid, a known triterpene, exhibits anti-inflammatory effects, yet research on the pharmacological effects of β-elemonic acid is rare. We investigated the anticancer effects and the related molecular mechanisms of β-elemonic acid on human non-small cell lung cancer (NSCLC) A549 cells. The effects of β-elemonic acid on the growth of A549 cells were studied using a 3-(4,5)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was detected using Annexin V staining. The effect of β-elemonic acid on the cell cycle of A549 cells was assessed using the propidium iodide method. The change in reactive oxygen species (ROS) was detected using a dichlorodihydrofluorescein diacetate (DCFH-DA) assay with microscopic examination. The expression levels of Bcl-2 family proteins, mitogen-activated protein kinase (MAPK) family proteins and cyclooxygenase 2 (COX-2) were detected using western blot analysis. Our data revealed that β-elemonic acid strongly induced human A549 lung cancer cell death in a dose- and time-dependent manner as determined by the MTT assay. β-elemonic acid-induced cell death was considered to be apoptotic when the phosphatidylserine exposure was observed using Annexin V staining. The death of human A549 lung cancer cells was caused by apoptosis induced by activation of ROS activity, increase in the sub-G1 proportion, downregulation of Bcl-2 expression, upregulation of Bax expression and inhibition of the MAPK signaling pathways. These results clearly demonstrated that β-elemonic acid inhibits proliferation by inducing hypoploid cells and cell apoptosis. Moreover, the anticancer effects of β-elemonic acid were related to the MAPK signaling pathway, ROS activation and glutathione depletion in human A549 lung cancer cells.

Some patients with nonsmall-cell lung cancer (NSCLC) without epidermal growth factor receptor (EGFR) mutations still respond to gefitinib and erlotinib, suggesting that there may be a mechanism(s) other than the EGFR pathway that mediates the tumoricidal effects. In the current study, we tested the efficacy of TD-19, a novel compound chemically modified from erlotinib, which has more potent apoptotic effects than erlotinib in EGFR wild-type NSCLC cell lines. TD-19 induced significant cell death and apoptosis in H358, H441, H460, and A549 cells, as evidenced by increased caspase-3 activity and cleavage of procaspase-9 and poly (ADP-ribose) polymerase. The apoptotic effect of TD-19 in H460 cells, which were resistant to erlotinib, was associated with downregulation of cancerous inhibitor of protein phosphatase 2A (CIP2A), increased protein phosphatase 2A (PP2A) activity, and decreased AKT phosphorylation, but minimal effects on EGFR phosphorylation. Overexpression of CIP2A partially protected the H460 cells from TD-19-induced apoptosis. Okadaic acid, a known PP2A inhibitor, significantly reduced TD-19-induced apoptosis, while forskolin, which increased PP2A activity, increased the apoptotic effect of TD-19. TD-19 inhibited the growth of H460 xenograft tumors by ∼80%. We conclude that TD-19 exerted tumoricidal effects on NSCLC cells. TD-19 provides proof that the CIP2A pathway may be a novel target for the treatment of EGFR wild-type NSCLC.

Most meteorological information services in Taiwan are currently provided by the Central Weather Bureau, Ministry of Transportation and Communications. As agricultural production activities are sensitive to weather and climate conditions, meteorological information services are more important for agricultural decision-makers than those in other sectors. This study uses the contingent valuation method to estimate the economic value of meteorological information services in Taiwan for agricultural producers. We assess the agricultural producers&rsquo, willingness to pay (WTP) for the meteorological information services, conducting a national face-to-face survey of 400 registered farmers in 20 municipalities in Taiwan in 2013. The results show the adjusted WTP for every agricultural household each year with a 95% confidence interval which ranges from 56.06 US dollars to 90.92 US dollars. The inferred annual economic value of meteorological information services for agricultural producers in Taiwan is between 28.06 million US dollars and 45.51 million US dollars. Moreover, the agricultural producers&rsquo, subjective assessment of weather forecast accuracy, farm size, and first bid price significantly affect the amount agricultural producers are willing to pay for meteorological information services.

OBJECTIVE: Most of the existing findings on the association between diabetes mellitus and colorectal cancer were generated from studies in Western societies. However, significant differences in cancer incidence and cancer-prone lifestyles are apparent between Asian and Western countries. This study aims to estimate the risks of colorectal cancer in the diabetic population in Taiwan by conducting a large-scale, controlled cohort study. METHODS: From Taiwan's Longitudinal Health Insurance Database 2005 (LHID2005), a total of 37 001 diabetic patients were identified. We also obtained data for four controls per patient, matched for sex, age and year of first entry into the LHID2005. All patients were followed up from the date of entry into the LHID2005 until they developed colorectal cancer or to the end of 2006, whichever was earlier. We used Cox's regression models to assess the risk of developing colorectal cancer, with adjustment for sex, age, comorbid disorders, and socioeconomic characteristics. RESULTS: We identified 37 001 diabetic patients and 148 004 controls. The adjusted hazard ratio for colorectal cancer in diabetes mellitus patients was 2.1 (95% confidence interval, 1.82-2.42) compared with controls. The risk was significant to both men and women. The adjusted hazard ratios for colorectal cancer were 2.03 (95% confidence interval, 1.68-2.47) in male diabetes mellitus patients and 2.17 (95% confidence interval, 1.77-2.67) in female diabetes mellitus patients. CONCLUSIONS: Our findings based on a large population-based cohort study provide evidence that diabetes mellitus may increase the risk of colorectal cancer in Asians.

Beauvericin (BEA) is a cyclic hexadepsipeptide that derives from Codyceps cicadae. Our previous study results indicated that the cytotoxic effects of BEA on human A549 lung cancer cells BEA occur through an apoptotic pathway, which involves the up-regulation of cytochrome c release from mitochondria, upregulation of caspase 3 activity, and cellular and morphological changes. In this study, we identified that the mitogen-activated protein kinase (MAPK) inhibitor U0126 inhibits the cytotoxic effects of BEA on A549 cells. After exposing human A549 cells to 10 μM BEA, we observed a significant and dose-dependent increase in the percentage of hypoploid (sub-G1) phase cells in the A549 population. Following the pretreatment of the A549 cells with 25 μM U0126, the distribution of A549 cells in the sub-G1 phase decreased significantly. The BEA treatment resulted in a significant increase apoptosis in A549 cells by in situ terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Moreover, the MEK1/2 (mitogen-activated protein kinase kinase)-ERK42/44 (extracellular signal-regulated kinases)-90RSK (ribosomal s6 kinase) signaling pathway was activated in BEA-induced apoptotic A549 cells. Furthermore, treatment with MEK1/2 inhibitor U0126 was capable to attenuate the BEA induced typical apoptotic morphological change, apoptotic cells, and MEK1/2-ERK42/44-90RSK signaling pathway. These results suggested that MEK1/2-ERK42/44-90RSK signaling pathway may play a important role in BEA-induced apoptosis in human NSCLC A549 cancer cells.

BACKGROUND: The effectiveness of noninvasive ventilation (NIV) after extubation in preventing post-extubation respiratory failure is still controversial. METHODS: We conducted a prospective, multicenter randomized controlled study involving patients on mechanical ventilation for > 48 hours who tolerated a 2-hour spontaneous breathing trial and were subsequently extubated. The patients were randomized to NIV or standard medical therapy. Re-intubation rate within 72 hours was the primary outcome measure. Multivariable logistic regression analysis was used to determine predictors for extubation failure. RESULTS: We randomized 406 patients to either NIV (no. = 202) or standard medical therapy (no. = 204). The 2 groups had similar baseline clinical characteristics. There were no differences in extubation failure (13.2% in control and 14.9% in NIV), intensive care unit or hospital mortality. Cardiac failure was a more common cause of extubation failure in control than in NIV. There was no difference in rapid shallow breathing index (RSBI) in extubation failure patients between control (80) and NIV (73). When using data from all patients, we found Acute Physiology and Chronic Health Evaluation (APACHE II) scores (odds ratio [OR] 1.13, 95% CI 1.07–1.20, P < .001), maximal inspiratory pressure (OR 1.04, 95% CI 1.00–1.08, P = .03), and RSBI (OR 1.03, 95% CI 1.02–1.05, P < .001) to be predictors of extubation failure. Abundant secretions were the most common reason (35.1%) for extubation failure identified by attending physicians. CONCLUSIONS: Preventive use of NIV after extubation in patients who passed spontaneous breathing trial did not show benefits in decreasing extubation failure rate or the mortality rate.

The aim of this study was to evaluate the diagnostic performance of an enzyme-linked immunospot (ELISPOT) assay for interferon-γ in patients with suspected genitourinary tuberculosis (TB). A total of 30 patients with suspected genitourinary TB at the National Taiwan University Hospital, Taipei, Taiwan, were prospectively enrolled from January 2007 to December 2009, and 12 of whom had positive urine culture for Mycobacterium tuberculosis . Frequency and dysuria were the most common symptoms noted in 6 (50.0%) and 4 (33.3%) patients, respectively. Pyuria was the most common finding of urinalysis noted in 11 (91.7%) patients. Six (50.0%) patients had positive acid-fast stain in urine. Among the 30 patients, 13 patients had positive ELISPOT assay. Eleven patients with positive ELISPOT assay had culture-confirmed TB, and the remaining 2 patients without evidence of active TB had positive ELISPOT assay. The overall sensitivity, specificity, positive predictive value, and negative predictive value for genitourinary TB diagnosis by the ELISPOT assay were 91.7% (95% confidence interval [CI], 59.8–99.6%), 88.9% (95% CI, 63.9–98.1%), 84.6% (95% CI, 53.7–97.3%), and 94.1% (95% CI, 69.2–96.7%), respectively. In conclusion, ELISPOT assay can provide useful support in diagnosing genitourinary TB.

The interferon-γ enzyme-linked immunospot assay (ELISPOT) has been demonstrated to be useful in the diagnosis of active tuberculosis (TB). In this study we aimed to evaluate the diagnostic performance of the ELISPOT assay in cancer patients with suspected pulmonary TB. Eighty-one cancer patients with suspected pulmonary TB were prospectively enrolled from April 2007 to December 2008, to investigate the diagnostic sensitivity and specificity of the ELISPOT assay. Of the 38 patients with TB, 33 (86.8%) had positive ELISPOT results. Of the 43 patients without TB, the results of the ELISPOT assay were negative in 35 (81.3%) patients. The overall sensitivity was 86.8%, specificity 81.3%, positive predictive value 80.5% and negative predictive value 87.5%. No significant difference was noted for the diagnostic performance of the ELISPOT assay for diagnosing TB between solid cancer and haematological cancer patients. In addition, a quantitative study did not show that TB patients with solid cancers have a better response than haematological cancer patients as measured by spot-forming cells per 10(6) peripheral blood mononuclear cells after exposure to early secretory antigenic target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10). In conclusion, the ELISPOT assay could be a useful supplementary tool for the diagnosis of pulmonary TB among cancer patients, irrespective of cancer type.

Background Mild hypothermia has become an important treatment for ischemic brain injury. However, the role of mild hypothermia in air embolism-induced lung injury has not been explored. In this study, we investigated whether treatment with mild hypothermia before and synchronous with air infusion can attenuate acute lung injury induced by air embolism. Methods In this rat model study (Sprague-Dawley rats), pulmonary air embolism was induced by venous infusion of air at a rate of 25 microL/min for 40 minutes. Control animals received no air infusion. The rats were randomly assigned to 2 control groups of normothermia (37 degrees C) and mild hypothermia (34 degrees C) and 3 air embolism groups of mild hypothermia induced before air infusion, normothermia with air infusion, and mild hypothermia induced synchronous with air infusion. At the end of the experiment, the variables of lung injury were assessed. Results Air infusion elicited a significant increase in lung wet/dry weight ratio and protein, lactate dehydrogenase, and tumor necrosis factor-alpha concentration of the bronchoalveolar lavage fluid. Myeloperoxidase activity, neutrophil infiltration, and interstitial edema in lung tissue were also significantly increased. In addition, nuclear factor-kappaB activity was significantly increased in the lungs. Treatment with mild hypothermia before air infusion reduced increases in these variables, whereas mild hypothermia synchronous with air infusion had no significant effect on them. Conclusions Our study suggests that mild hypothermia before air infusion decreases air embolism-induced acute lung injury. The protective mechanism seems to be the inhibition of inflammation.

OBJECTIVES: To evaluate the diagnostic performance of procalcitonin (PCT) in elderly patients with bacterial infection in the emergency department (ED). DESIGN: Prospective. SETTING: ED of a tertiary care hospital. PARTICIPANTS: Elderly patients with systemic inflammatory response syndrome (SIRS) enrolled from September 2004 through August 2005. MEASUREMENTS: A serum sample for the measurement of PCT, two sets of blood cultures, and other cultures of relevant specimens from infection sites were collected in the ED. Two independent experts blinded to the PCT results classified the patients into bacterial infection and nonbacterial infection groups. RESULTS: Of the 262 patients with SIRS enrolled, 204 were classified as having bacterial infection and 48 as having bacteremia. PCT levels were significantly higher in patients with bacteremia than in those without. The area under the receiver operating characteristic curve for identification of bacteremia according to PCT was 0.817 for the old-old group (≥75), significantly higher than 0.639 for the young-old group (65–74); P=.02). The diagnostic sensitivity, specificity, positive predictive value, and negative predictive value of PCT for bacteremia in patients aged 75 and older were 96.0%, 68.3%, 33.8%, and 98.8%, respectively, with a PCT cutoff value of 0.38 ng/mL. CONCLUSION: PCT is sensitive for diagnosing bacteremia in elderly patients with SIRS at ED admission but is helpful in excluding bacteremia only in those aged 75 and older. PCT is not an independent predictor of local infections in these patients.

Acid aspiration or intrapulmonary instillation of gastric particles causes lung inflammation leading to acute lung injury (ALI). Hypercapnia exerts different effects on ALI caused by various insults. The effects of hypercapnia on lung inflammation and injury due to acid aspiration are yet to be determined. The present study was designed to investigate the involvement of inducible nitric oxide synthase (iNOS) and other mediators in acid-aspiration-induced ALI. We also sought to evaluate the effects of hypercapnia on the lung and associated changes induced by acid aspiration. We used Spague-Dawley rats anesthetized with intraperitioneal pentobarbital (40 mg/kg). Gastric acid particles were prepared from the stomach contents of rats at necropsy. The rats were randomly assigned to receive intratracheal instillation of physiological saline solution (PSS) at pH 7.24 (Control group), PSS at pH 1.25 (Low pH, LPH group), gastric particles (GP group), and GP with low pH PSS (GPLPH group). There were 10 rats in each group. The animals were observed for 6 hrs. To evaluate the effects of hypercapnia, we carried out two series of experiments: one under normocapnia and the other under hypercapnia with alteration of CO2 fraction in inspired air. Arterial pressure (AP) was monitored from the femoral arterial catheter. Heart rate was obtained from AP traicing. We determined the blood gases and acid-base status. Lung weight to body weight (LW/BW) ratio, LW gain (LWG), protein concentration in bronchoalveolar lavage (PCBAL) and leakage of Evans blue dye tracer were measured. Plasma nitrate/nitrite, methyl guanidine (MG), myeloperoxidase (MPO), phospholipase A2 (PLA2), proinflammatory cytokines were assessed. Histopathological examination of the lung tissue was performed. We employed reverse-transcriptase polymerase chain reaction to detect the expression of iNOS mRNA. GP and GPLPH caused hypotension, decreases in PaO2, pH and SaO2, and an increase in PaCO2. The insults also elevated LW/BW, LWG, PCBAL and dye leakage, plasma nitrate/nitrite, MG, MPO, PLA2, tumor necrosis factor(alpha), interleukin-beta and interleukin-6. The lung pathology was characterized by alveolar edema and hemorrhage with inflammatory cells infiltration. Assessment of lung injury score revealed that GP and GPLPH caused ALI. Furthermore, hypercapnia significantly enhanced ALI and associated changes following LPH, GP and GPLPH. Intratracheal instillation of GP in normal or low pH PSS causes ALI accompanied with biochemical changes. The release of nitric oxide via iNOS isoform is detrimental to the lung. Hypercapnia tended to enhance ALI and associated changes induced by gastric acid instillation.

Hyperglycemia and hypoxia synergistically retard diabetic wound healing. We investigated the direct effect of hyperbaric and normobaric hyperoxia on skin fibroblasts cultured in a high-glucose medium. Detroit 551 human dermal fibroblasts cultured in Dulbecco's modified Eagle's medium containing d-glucose had reduced cell survival compared with cells grown in normal glucose medium; survival was 27.5+/-3.8% lower in 25 mM glucose and 30.6+/-3.7% lower in 50 mM glucose. Cell survival decreased because of inhibition of cell proliferation and enhanced cell death. Daily hyperbaric oxygen therapy at 2.5 atmosphere absolute for 90 minutes on 3 consecutive days reduced cell proliferation and increased cell death in normal cultured fibroblasts. Hyperbaric oxygen therapy and high-glucose medium had a synergistic effect and reduced survival by 37.6+/-4.4% (25 mM glucose) and 39.6+/-5.1% (50 mM glucose). The effects of hyperbaric oxygen and high-glucose medium were associated with overproduction of reactive oxygen species. Our results suggest that direct exposure of skin fibroblasts to hyperbaric oxygen affects cell growth and superimposes the toxic effect of high glucose. This cytotoxicity may be related to the production of reactive oxygen species in the fibroblasts.

A horizontal surveillance study was conducted to identify common bacteria and mycobacteria from 611 respiratory aspirates and 165 urinary samples from 611 patients hospitalised at 17 respiratory care wards (RCWs) in Taiwan. Some major resistance phenotypes, including methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis, and multidrug-resistant Pseudomonas aeruginosa (MDR-PA) and Acinetobacter baumannii (MDR-AB), were identified. Pulsotypes of ESBL-producing P. mirabilis isolates were determined by pulsed-field gel electrophoresis. The prevalences of MRSA, ESBL-producing E. coli (K. pneumoniae and P. mirabilis), carbapenem-resistant (resistant to imipenem and meropenem) P. aeruginosa, MDR-PA, carbapenem-resistant A. baumannii and MDR-AB were, respectively, 86.7%, 20.0% (50.7% and 24.1%), 18.4%, 1.2%, 32.1% and 8.9% for respiratory aspirates and 100%, 25.4% (27.3% and 25.0%), 48.3%, 10.3%, 50.0% and 21.4% for catheterised urinary samples. Among the 44 respiratory isolates of P. mirabilis with an ESBL phenotype, 22 different pulsotypes (80% identity) were identified. Among 103 isolates of mycobacteria, 90 (87.4%) belonged to rapidly growing mycobacteria and 4 (4%) were Mycobacterium tuberculosis. Among the 404 patients with available clinical information, true infections were found in 28.0%, the most prevalent of which were urinary tract infection (20.5%) and ventilator-associated pneumonia (10.9%). High prevalences of various multidrug-resistant bacteria among the respiratory and urinary tracts of patients present a clinical difficulty in choosing empirical antibiotic treatment in RCWs.

The purpose of this study was to develop a case management program for patients with chronic obstructive pulmonary disease (COPD) and to test the effects of the developed program on patient length of stay in the hospital, medical costs, disease knowledge and level of satisfaction with nursing care received. This quasi-experimental study focused on a group of 50 COPD patients (24 in the control group and 26 in the experimental one), all treated in one hospital medical ward in northern Taiwan. The control group received routine care, while those in the experimental group received a COPD case management protocol. Data for the control group was collected between September of 2003 and January 2004. Data for the experimental group was collected between April and December 2004. Data collection instruments included medical records, the COPD Knowledge Measurement scale, and the Patient Satisfaction with Nursing Care Questionnaire. Descriptive and inferential statistical analyses were applied to describe demographics, length of stay, medical cost, patient disease-related knowledge, and patient satisfaction with nursing care. Results indicated that, while the study found no significant difference in length of stay and medical cost between the two groups, the use of case management procedures improved patient disease-related knowledge and satisfaction with nursing care. This conclusion supports the premise that case management improves patient care in these two dimensions and is, thus, an effective approach in the management of patients diagnosed with secondary COPD infections.

1. Acute lung injury (ALI) or acute respiratory distress syndrome is a serious clinical problem with high mortality. N-Acetylcysteine (NAC) is an anti-oxidant and a free radical scavenger. It has been reported recently that NAC ameliorates organ damage induced by endotoxin (lipopolysaccharide; LPS) in conscious rats. The present study was designed to evaluate the effects of NAC on LPS-induced ALI and other changes in anaesthetized rats. 2. Sprague-Dawley rats were anaesthetized with pentobarbital (40 mg/kg, i.p.). Endotracheal intubation was performed to provide artificial ventilation. Arterial pressure and heart rate were monitored. The extent of ALI was evaluated with the lung weight (LW)/bodyweight ratio, LW gain, exhaled nitric oxide (NO) and protein concentration in bronchoalveolar lavage (PCBAL). Haematocrit, white blood cells, plasma nitrate/nitrite, methyl guanidine (MG), tumour necrosis factor (TNF)-alpha and interleukin (IL)-1b were measured. Pathological changes in the lung were examined and evaluated. 3. Endotoxaemia was produced by injection of 10 mg/kg, i.v., LPS (Escherichia coli). Animals were randomly divided into three groups. In the vehicle group, rats received an i.v. drip of physiological saline solution (PSS) at a rate of 0.3 mL/h. The LPS group received an i.v. drip of PSS for 1 h, followed by LPS (10 mg/kg by slow blous injection, i.v., over 1-2 min). Rats in the LPS + NAC group received NAC by i.v. drip at a rate of 150 mg/kg per h (0.3 mL/h) for 60 min starting 10 min before LPS administration (10 mg/kg by slow blous injection, i.v., over 1-2 min). Each group was observed for a period of 6 h. 4. N-Acetylcysteine treatment improved the LPS-induced hypotension and leukocytopenia. It also reduced the extent of ALI, as evidenced by reductions in LW changes, exhaled NO, PCBAL and lung pathology. In addition, NAC diminished the LPS-induced increases in nitrate/nitrite, MG, TNF-a and IL-1b. 5. In another series of experiments, LPS increased the mortality rate compared with the vehicle group (i.v. drip of PSS at a rate of 0.3 mL/h) during a 6 h observation period. N-Acetylcysteine, given 10 min prior to LPS, significantly increased the survival rate. 6. The results of the present study suggest that NAC exerts a protective effect on the LPS-induced ALI. The mechanisms of action may be mediated through the reduction of the production of NO, free radicals and pro-inflammatory cytokines.

Beauvericin (BEA), a cyclic hexadepsipeptide from Codyceps cicadae , possesses anti-convulsion, anti-arrhythmia, sedation, and anti-tumor activities. It has been reported that BEA induces apoptosis in several cancer cell lines. However, the molecular mechanism underlying the BEA-induced apoptotic process is not yet clearly understood. In the present study, the intracellular signaling pathways of BEA-induced apoptosis in human non-small cell lung cancer (NSCLC) A549 cells were investigated using morphological analysis and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) technique. In this study, BEA-induced apoptosis in human NSCLC A549 cells demonstrated a BEA concentration- and treatment time-dependent manner. This BEA-induced apoptosis in human NSCLC A549 cells was also accompanied by the up-regulation of Bax, Bak, and p-Bad and down-regulation of p-Bcl-2, but no effect on the levels of Bcl-X L or Bad proteins. Moreover, the BEA treatment resulted in a significant reduction of mitochondrial membrane potential, increase in the release of mitochondrial cytochrome c (cyt c ), and activation of caspase 3. Furthermore, treatment with caspase 3 inhibitor (z-DEVD-fmk) was capable to prevent the BEA-induced caspase 3 activity and cell death. These results clearly demonstrate that the induction of apoptosis by BEA involves multiple cellular/molecular pathways and strongly suggest that pro- and anti-apoptotic Bcl-2 family proteins, mitochondrial membrane potential, mitochondrial cyt c , and caspase 3, they all participate in BEA-induced apoptotic process in human NSCLC A549 cells.

The lung alveolar epithelium consists of type I and type II pneumocytes. In vivo, the type II cell is the progenitor cell from which the type I cell originates. When freshly-isolated type II cells are cultured under conventional conditions they rapidly lose their phenotypic properties and attain characteristics of type I cells. Taking advantage of this transdifferentiation, we sought to identify genes that are differentially expressed during culture of rat type II cells. Using suppression subtractive hybridization (SSH), a vacuolar-type H+-ATPase (V-ATPase) C2 subunit gene (Atp6v1c2) was found to be enriched in freshly isolated rat type II cells compared to those cultured for 4 days. Northern blotting and reverse-transcription polymerase chain reaction (RT-PCR) confirmed the differential expression of Atp6v1c2 during in vitro culture of isolated type II cells. Expression ofAtp6v1c2 was significantly reduced early during in vitro culture: almost 90% reduction was observed after 24 h of incubation as determined by real-time PCR. In situ hybridization showed that Atp6v1c2 is expressed in both bronchiolar and alveolar lung epithelial cells, an expression pattern similar to that of surfactant protein B (SP-B). Multi-tissue Northern blotting revealed a unique tissue distribution with Atp6v1c2 expression limited to lung, kidney and testis. The presence and expression of Atp6v1c2 gene transcript isoforms, resulting from alternative splicing, were also investigated. Elucidation of differential expression of Atp6v1c2 in type II cells and further studies of its regulation may provide information useful in understanding the molecular mechanism underlying phenotypic and functional changes during transdifferentiation of alveolar epithelial cells.

SUMMARY 1. The present study was designed to determine whether U74500A could ameliorate acute lung injury (ALI) induced by phorbol myristate acetate (PMA) in our rat isolated lung model compared with any amelioration induced by dimethylthiourea (DMTU), superoxide dismutase (SOD) and catalase. 2. Acute lung injury was induced successfully by PMA during 60 min of observation. At 2 µg/kg, PMA elicited a significant increase in microvascular permeability (measured using the capillary filtration coefficient Kfc), lung weight gain, the lung weight/bodyweight ratio, pulmonary arterial pressure and protein concentration of the bronchoalveolar lavage fluid. 3. Pretreatment with 1.5 mg/kg U74500A significantly attenuated ALI; there was no significant increase in any parameters measured, except for pulmonary arterial pressure. The protective effect of U74500A was approximately the same as that of 600 mg/kg DMTU. However, 6000 U/kg SOD, 50 000 U/kg catalase and 6000 U/kg SOD + 50 000 U/kg catalase had no protective effect. 4. These experimental data suggest that U74500A significantly ameliorates ALI induced by PMA in rats.

In this study, we determined the effect of inhaled nitric oxide (NO) on the acute lung injury induced by phorbol myristate acetate (PMA) in isolated rat lung. Typical acute lung injury was induced successfully by PMA during 60 min of observation. PMA (2 microg/kg) elicited a significant increase in microvascular permeability, (measured using the capillary filtration coefficient Kfc), lung weight gain, lung weight/body weight ratio, pulmonary arterial pressure (PAP) and protein concentration of the bronchoalveolar lavage fluid. Pretreatment with inhaled NO (30 ppm) significantly exacerbated acute lung injury. All of the parameters reflective of lung injury increased significantly except PAP (P0.05). Coadministration of Nomega-nitro-L-arginine methyl ester (L-NAME) (5 mM) attenuated the detrimental effect of inhaled NO in PMA-induced lung injury, except for PAP. In addition, L-NAME (5 mM) significantly attenuated PMA-induced acute lung injury except for PAP. These experimental data suggest that inhaled NO significantly exacerbated acute lung injury induced by PMA in rats. L-NAME attenuated the detrimental effect of inhaled NO.

Summary 1. In the present study, we determined whether the endogenous nitric oxide (NO) synthase (NOS) inhibitor Nω-nitro-l-arginine methyl ester (l-NAME) could ameliorate the acute lung injury (ALI) induced by phorbol myristate acetate (PMA) in rat isolated lung. 2. Typical ALI was induced successfully by PMA during 60 min of observation. At 2 µg/kg, PMA elicited a significant increase in microvascular permeability (measured using the capillary filtration coefficient Kfc), lung weight gain, lung weight/bodyweight ratio, pulmonary arterial pressure (PAP) and protein concentration of bronchoalveolar lavage fluid. 3. Pretreatment with the NOS inhibitor l-NAME (5 mmol/L) significantly attenuated ALI. None of the parameters reflective of lung injury showed significant increase, except for PAP (P

Background Epidermal growth factor receptor ( EGFR ) inhibitors show favorable clinical response in some patients with non-small cell lung cancer (NSCLC) who have no EGFR mutation, indicating alternative mechanisms for their tumoricidal effects. We previously showed erlotinib, a selective EGFR antagonist, inhibited the growth of sensitive hepatocellular carcinoma cells by inhibiting the cancerous inhibitor of protein phosphatase 2A ( CIP2A ) pathway. The aim of this study was to determine if erlotinib can also inhibit the growth of NSCLC cells by inactivating the CIP2A -dependent signaling pathway. Methods Four NSCLC cell lines (H358 H441 H460 and A549) were treated with erlotinib to determine their sensitivity to erlotinib-induced cell death and apoptosis. Expression of CIP2A and the downstream AKT were analyzed. The effects of CIP2A on erlotinib-induced apoptosis were confirmed by overexpression of CIP2A and knockdown of CIP2A gene expression in the sensitive cells and resistant cells, respectively. In vivo efficacy of erlotinib against H358 xenograft tumor was also determined in nude mice. Results Erlotinib induced significant cell death and apoptosis in H358 and H441 cells, as evidenced by increased caspase 3 activity and cleavage of pro - caspase 9 and PARP , but not in H460 or A549 cells. The apoptotic effect of erlotinib in the sensitive H358 cells was associated with downregulation of CIP2A , increase in PP2A activity and decrease in AKT phosphorylation. Overexpression of CIP2A and AKT protected the sensitive H358 cells from erlotinib-induced apoptosis. Knockdown of CIP2A gene expression by siRNA enhanced the erlotinib-induced apoptotic in the resistant H460 cells that resembled the sensitive H358 cells. Erlotinib also inhibited the growth of H358 tumors in nude mice. Conclusions The CIP2A -dependent pathway mediates the tumoricidal effects of erlotinib on NSCLC cells without EGFR mutations in vitro and in vivo . CIP2A may be a novel molecular target against NSCLC for future drug development.

Adaptive support ventilation (ASV) is a new mode of mechanical ventilation that seeks an optimal breathing pattern based on the minimum work of breathing (WOB) principle. The operator's manual for the ventilators that provide ASV recommends that the %MinVol setting be started at 100% (the 100%MinVol setting), but it is unclear whether that setting reduces WOB in patients with respiratory failure.We studied 22 hemodynamically stable patients with respiratory failure who were on pressure-support ventilation. We switched the ventilation mode to ASV and started at the 100%MinVol setting. We then increased the %MinVol setting by 10% every 5 min until 1-3 mandatory breaths per min appeared, and called that setting the ASV target point. We then tested 2 additional %MinVol settings: 20% below the ASV target point (target-point-20%), and 20% above the ASV target point (target-point+20%). We tested each %MinVol setting for 10 min. At the end of each 10-min period we measured respiratory variables, pressure-time product (PTP), and airway occlusion pressure at 0.1 s after the onset of inspiratory flow (P(0.1)).In 18 patients (82%), at the 100%MinVol setting, the actual minute volume (V(E)) was greater than the target V(E). At the ASV target point the mean +/- SD %MinVol setting was 165 +/- 54% and was associated with a 40% decrease in PTP and P(0.1), but V(E) did not change. At target-point+20%, V(E) increased slightly, primarily due to a small increase in tidal volume, and PTP and P(0.1) further decreased. At target-point-20%, PTP and P(0.1) were similar to those at the 100%MinVol setting. At the ASV target point the 6 patients with chronic obstructive pulmonary disease had a lower mean %MinVol setting (125 +/- 23%) than the 16 patients who did not have chronic obstructive pulmonary disease (180 +/- 55%).The 100%MinVol setting was frequently not associated with lower WOB in patients with respiratory failure. The %MinVol setting that significantly reduced WOB could be detected by increasing the %MinVol setting until a few mandatory breaths began to appear, and was on average 165% of the MinVol setting.

To evaluate the diagnostic performance of procalcitonin (PCT) in elderly patients with bacterial infection in the emergency department (ED).Prospective.ED of a tertiary care hospital.Elderly patients with systemic inflammatory response syndrome (SIRS) enrolled from September 2004 through August 2005.A serum sample for the measurement of PCT, two sets of blood cultures, and other cultures of relevant specimens from infection sites were collected in the ED. Two independent experts blinded to the PCT results classified the patients into bacterial infection and nonbacterial infection groups.Of the 262 patients with SIRS enrolled, 204 were classified as having bacterial infection and 48 as having bacteremia. PCT levels were significantly higher in patients with bacteremia than in those without. The area under the receiver operating characteristic curve for identification of bacteremia according to PCT was 0.817 for the old-old group (or=75), significantly higher than 0.639 for the young-old group (65-74); P=.02). The diagnostic sensitivity, specificity, positive predictive value, and negative predictive value of PCT for bacteremia in patients aged 75 and older were 96.0%, 68.3%, 33.8%, and 98.8%, respectively, with a PCT cutoff value of 0.38 ng/mL.PCT is sensitive for diagnosing bacteremia in elderly patients with SIRS at ED admission but is helpful in excluding bacteremia only in those aged 75 and older. PCT is not an independent predictor of local infections in these patients.

Objective Our aim was to study the expression of inducible nitric oxide synthase (iNOS) in 2 experimental models: (1) ischemia/reperfusion (I/R) of the lung tissues and (2) oleic acid infusion. The protective effect of an iNOS inhibitor, aminoguanidine, was evaluated in these 2 injury models. Materials and Methods Real-time polymerase chain reactions and Western blots were used to assess the mRNA and protein expressions of iNOS in lung tissues after applying 2 injury models. In the I/R model, ischemia was induced by clamping one branch of the pulmonary artery for 60 minutes and then reperfusing for 120 minutes. In the bone fracture model, lung injury was induced by intravenous (IV) infusion of oleic acid (0.1 mL/kg); analysis was performed 6 hours after injury. Blood samples were collected for the assay of 3 inflammatory parameters: tumor necrosis factor α, hydroxyl radicals, and nitric oxide (NO). The wet/dry lung weight ratio was used as a parameter reflecting the lung injury level. Results mRNA and protein expressions of iNOS were significantly increased in these 2 lung injury models compared with the controls. Blood concentrations of TNFα, hydroxyl radicals, NO, and wet/dry lung weight ratio were also significantly higher in the 2 experimental groups than in the sham-treated group. The iNOS inhibitor aminoguanidine (20 mg/kg) significantly attenuated the lung injury induced by these challenges. Conclusions Reperfusion of the ischemic lung tissues or IV infusion of oleic acid can both induce lung injury by activating systemic inflammatory responses and inducing iNOS expression. Administration of aminoguanidine can significantly attenuate the injury, suggesting that iNOS expression may play a critical role in the lung injury induced in these 2 models.

Our aim was to study the expressions of matrix metalloprotease 9 (MMP9) and the effects of the MMP inhibitor Ilomastat in both ischemia/reperfusion (I/R)- and oleic acid (OA)-induced lung injury models.Real-time polymerase chain reactions and Western blots were used to assess mRNA and protein expressions of MMP9 in lung tissues after I/R or OA lung injury. Ischemia was induced by clamping one branch of the pulmonary artery for 60 minutes and then reperfusing for 120 minutes. In the OA model, lung injury was induced by intravenous infusion of OA (0.1 mL/kg) for 20 minutes and then observation for 6 hours. Lavage leukocyte concentration and wet/dry lung weight ratio were used to assess lung inflammation and injury. Blood samples were collected for assays of hydroxyl radicals and nitric oxide. The MMP inhibitor Ilomastat (100 microg/kg) was administered before I/R and OA infusion.mRNA and protein expressions of MMP9 were significantly increased in both lung injury models. Ilomastat decreased MMP9 mRNA and protein expressions but did not reach statistical significance. Blood concentrations of hydroxyl radicals and nitric oxide, wet/dry lung weight ratios, and lavage leukocyte concentrations were significantly higher in both experimental groups compared with the sham group (P.001). Ilomastat significantly attenuated the extent of lung inflammation and injury induced by both I/R and OA.MMP may play a critical role in the lung injury induced by I/R and OA infusion.

Purpose: Ventilator-induced lung injury (VILI) is a recognized complication of mechanical ventilation. Although the specific mechanism by which mechanical ventilation causes lung injury remains an active area of study, both alveolar overdistension and cyclical airway collapse and recruitment have been suggested as contributing causes. We hypothesized that mechanical ventilation in the absence of positive end-expiratory pressure (PEEP) causes VILI to be more severe and regionally variable as compared with PEEP = 8 cm H 2 O. Materials and Methods: To test this hypothesis, anesthetized, supine rabbits were mechanically ventilated with an end-inspiratory pressure of 28 cm H 2 O and either 0 or 8 cm H 2 O PEEP for 4 hours. Regional lung injury was determined by histologic scoring. Results: In the absence of PEEP, lung injury was regionally variable and greatest in the dorsal-caudal lung. This regional injury heterogeneity was abolished by the addition of PEEP = 8 cm H 2 O. Conclusions: These results suggest that VILI is regionally heterogeneous and spatially correlates with regions in which cyclical airway collapse and recruitment is most likely to occur.

Objectives To evaluate pancreatic juice translocation after ischemia and reperfusion (I/R) of the superior mesenteric artery (SMA). Methods Ischemia was induced by clamping the rat SMA for 40 minutes, after which flow was restored and the SMA reperfused for 300 minutes. The blood levels of amylase and lipase were measured to reflect the dislocation of pancreatic juice. Organ injury parameters, such as the blood concentrations of alanine aminotransferase, creatinine kinase, and creatinine and the lung weight/body weight ratio were measured as well as inflammatory parameters such as tumor necrosis factor, hydroxyl radical, and nitric oxide levels. Results Organ injury and inflammatory parameters all increased significantly after I/R. Reperfusion of the intestine also induced a significant increase in the levels of pancreatic juice in the blood. After administration of the enzyme inhibitor, gabexate mesilate (FOY; 10 mg/kg), by injection into the duodenum, organ injury was significantly attenuated. Conclusions These findings suggested that I/R of the SMA induced multiple organ injuries that appeared to be dependent on the translocation of pancreatic enzymes.

Antioxidants have been shown to be effective in attenuating acute lung injury. In this study, we determine the effects of various antioxidants by different mechanisms on the lipopolysaccharide (LPS)-induced changes. LPS was administered intravenously at a dose of 10 mg/kg to anesthetized rats. LPS induced a significant decrease in blood pressure (P0.01) and increased exhaled nitric oxide (NO) from 3.60+/-0.18 to 35.53+/-3.23 ppb (P0.01) during an observation period of 4 h. Plasma nitrate concentrations also increased from 0.61+/-0.06 to 1.54+/-0.22 micromol/l (P0.05). LPS-induced oxygen radical release from white blood cells isolated from rat peripheral blood also increased significantly (P0.001). After the experiment, the lung weight was obtained and lung tissues were taken for the determination of mRNA expression of inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta) and manganese superoxide dismutase (MnSOD). Histological examination of the lungs was also performed. In the control group injected with saline solution, mRNA expressions of iNOS, IL-1beta, TNF-alpha and MnSOD were absent. Four hours after LPS administration, mRNA expressions of iNOS, IL-1beta, and MnSOD were significantly enhanced, but TNF-alpha was not discernibly expressed. LPS also caused a twofold increase in lung weight. Pathological examination revealed endothelial cell damage and interstitial edema. Various antioxidants were given 1 h after LPS administration. These agents include SOD, catalase (CAT), SOD + CAT or vitamin C (ascorbic acid). These antioxidants effectively reversed the systemic hypotension, reduced the quantity of exhaled NO and plasma nitrate concentration, and prevented acute lung injury. Administration of various antioxidants also significantly attenuated LPS-induced oxygen radical release by rat white blood cells. LPS induced mRNA expressions of MnSOD and iNOS were significantly depressed by these antioxidants. However, only SOD + CAT and vitamin C inhibited the mRNA expression of IL-1beta. These results suggest that oxygen radicals are responsible for LPS-induced lung injury. Antioxidants can attenuate the lung injury by inhibiting mRNA expressions of iNOS and IL-1beta.

The aim of this study was to investigate the role of nitric oxide (NO) in hepatic ischemia-reperfusion (I/R) injury in rats. Immunohistochemistry was used to examine the protein expression of endothelial and inducible nitric oxide synthases (eNOS, iNOS) and nitrotyrosine after I/R challenges to the liver, and blood levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactic dehydrogenase (LDH), hydroxyl radical and NO were measured before ischemia and after reperfusion. Ischemia was induced by occlusion of the common hepatic artery and portal vein for 40 min, followed by reperfusion for 90 min. Reperfusion of the liver induced a significant increase in the blood concentrations of AST, ALT, LDH (n = 8; P0.001), hydroxyl radical (n = 8; P0.001) and NO (n = 8; P0.01). The eNOS, iNOS, nitrotyrosine, SOD1 and SOD2 protein expression was also found to increase significantly after reperfusion (n = 3). Administration of the NOS inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) (n = 8) had a protective effect on the I/R-related injury, but the NO donor L-arginine (L-Arg) (n = 8) potentiated the damage caused by I/R. These results suggest that reperfusion of the liver induces expression of NOS, which is related to the elevation of blood NO. The increase in hydroxyl radical concentration was accompanied by an increase in antioxidant enzyme expression (SOD1 and SOD2), and an increase in nitrotyrosine expression was also observed, reflecting the increased production of NO and oxygen radicals. We concluded from the protective effect of L-NAME and the potentiation by L-Arg that NOS expression and increases in NO and hydroxyl radical production have deleterious effects on the response to I/R in the liver.

The quantity and duration of production of tumor necrosis factor (TNF) is tightly controlled due to its potential to cause serious harm. For example, TNF release in response to overwhelming bacterial infection has been implicated as the first step in potentially lethal septic shock. Prostaglandins and leukotrienes are thought to play opposing roles in regulating TNF production by monocytes and macrophages. We investigated the effects of 5 drugs on the production of TNF by cells of the murine macrophage line RAW264 after stimulation with bacterial lipopolysaccharide endotoxin (LPS). These drugs were of the following 3 classes: cyclooxygenase inhibitors indomethacin (indo) and ibuprofen (ibu); 5-lipoxygenase inhibitors VZ 65 and AA-861; and methylxanthine pentoxyfilline (PTX). While indo and ibu treatment resulted in increased TNF production, PTX, VZ 65, and AA-861 significantly inhibited TNF production, whether administered simultaneously with LPS or 30 min after LPS treatment. VZ 65 and AA-861 also inhibited prostaglandin E2 (PGE2) production, coupled with an absence of any rise in intracellular cAMP. Leukotriene B4 (LTB4) levels peaked at 15 min and approached background level at 30 min after LPS treatment. Taken together, these data suggest that VZ 65 and AA-861 may inhibit TNF production through mechanism(s) independent of LTB4 production. VZ 65, AA-861, and PTX all diminished the rate of TNF mRNA transcription, yet VZ 65 and AA-861 appeared to enhance message stability. We conclude that while PTX reduced TNF protein levels by inhibiting TNF mRNA transcription, both VZ 65 and AA-861 exerted opposing effects on TNF transcription and increased mRNA stability.