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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.

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.

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.

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.

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.

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

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.