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A high fiber diet (HFD) and dietary supplementation with acetate have been reported to have beneficial effects in a variety of diseases. We investigated the effects of a HFD and acetate supplementation on the gut microbiota and hyperoxia-induced acute lung injury (HALI) in mice. Mice were fed a control diet, HFD, or acetate supplementation for three weeks, and their gut microbiome composition, lung tissues, and bronchoalveolar lavage fluid (BALF) were examined after exposure to ambient air or hyperoxia. Both the HFD and acetate supplementation modified the gut microbiota community and increased the proportion of acetate-producing bacteria in mice exposed to hyperoxia. The HFD and acetate supplementation also increased the abundance of Bacteroides acidifaciens and reduced gut dysbiosis according to the ratio of Firmicutes to Bacteroidetes. Compared with hyperoxia-exposed mice fed a control diet, both the HFD and acetate supplementation significantly increased the survival time while reducing the severity of pulmonary edema and the concentrations of protein and inflammatory mediators in BALF. Moreover, the HFD and acetate supplementation reduced the production of free radicals, attenuated NF-κB signaling activation, and decreased apoptosis in the lung tissues. Overall, this study indicates that a HFD or acetate supplementation reduces the severity of HALI through alterations in the gut microbiota to exert anti-inflammatory effects.

Yu-Hsiang Chiu,1,2 Chen-Chih Chu,1 Chun-Chi Lu,1 Feng-Cheng Liu,1 Shin-En Tang,3 Shi-Jye Chu,1 San-Yuan Kuo,1 Hsiang-Cheng Chen1 1Division of Rheumatology/Immunology/Allergies, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 2Department of Rheumatology and Clinical Immunology, University Medical Centre Utrecht, Utrecht, the Netherlands; 3Division of Thoracic Medicine, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, TaiwanCorrespondence: Hsiang-Cheng Chen, Division of Rheumatology/Immunology/Allergy, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, No. 325, Sec, 2, Cheng-Gong Road, Neihu 114, Taipei, Taiwan, R.O.C, Tel +886 2 87927135, Fax +886 2 87927136, Email hccheng@mail.ndmctsgh.edu.twObjective: Krebs von den Lungen-6 (KL-6) is expressed on regenerating type II pneumocytes and has been recognized as biomarkers in interstitial lung disease (ILD). We aim to identify the role of the serum KL-6 level in patients with newly diagnosed Sjögren syndrome (SS), as well as the correlation between the immunoassays.Methods: Patients with newly diagnosed SS and receiving HRCT for clinical reason during follow-up were included. Baseline KL-6 level was measured via enzyme-linked immunosorbent assay (ELISA) and latex particle-enhanced turbidimetric immunoassay (LETIA).Results: Of the 39 patients, 21 (53.85%) developed interstitial lung disease (ILD) by the conclusion of the follow-up period. The median time to diagnosis of ILD was 2.24 years (IQR 1.15– 4.34) in the ILD group. The median serum KL-6 level, measured using ELISA, was 1232 U/mL (IQR 937– 2242) and 764.5 U/mL (IQR 503.25– 1035.75) in the ILD group and the non-ILD group, respectively (p = 0.001). The median LETIA for serum KL-6 was 329 U/mL (IQR 235– 619) and 245 U/mL (IQR 215.25– 291) in the ILD group and the non-ILD group, respectively (p = 0.074).Conclusion: Serum KL-6 levels were higher in newly diagnosed SS patients with ILD diagnosis during follow-up. Thus, the serum KL-6 level can serve as a valuable biomarker to identify hidden ILD in patients with newly diagnosed SS patients. However, the immunoassay procedure may influence the efficacy of the prediction and its clinical association.Keywords: Sjögren syndrome, interstitial lung disease, KL-6

Background: Patients who have symptoms of sicca, such as dry eyes and mouth, may have Sjögren’s syndrome (SS). However, the conservative culture makes patients hesitate to undergo an invasive biopsy, which contributes to the difficulty of confirming a diagnosis. We aimed to identify the characteristics of patients with sicca symptoms to develop a better predictive value for each item included in the three different diagnostic criteria for SS and clarify the best diagnostic tools for the local population. Methods: This is a single-center retrospective case-control study from January 2016 to December 2017. Patients who underwent sialoscintigraphy because of clinical symptoms of xerostomia and xerophthalmia at one medical center were reviewed via the patients’ electronic medical records. Results: Of 515 patients enrolled, the severity of results for sialoscintigraphy and Schirmer’s test was correlated with a diagnosis of SS and generated receiver operator characteristic curve. The area under curve (AUC) was 0.603 for positive Schirmer’s test, 0.687 for positive anti-Ro/La results, 0.893 for a positive salivary gland biopsy. The AUC was 0.626 and 0.602 for Schirmer’s test which is redefined as

Diabetes is a common comorbidity in patients hospitalized for acute heart failure (AHF), but the relationship between admission glucose level, glycemic gap, and in-hospital mortality in patients with both conditions has not been investigated thoroughly. Clinical data for admission glucose, glycemic gap and in-hospital death in 425 diabetic patients hospitalized because of AHF were collected retrospectively. Glycemic gap was calculated as the A1c-derived average glucose subtracted from the admission plasma glucose level. Receiver operating characteristic (ROC) curves were used to determine the optimal cutoff value for glycemic gap to predict all-cause mortality. Patients with glycemic gap levels >43 mg/dL had higher rates of all-cause death (adjusted hazard ratio, 7.225, 95% confidence interval, 1.355–38.520) than those with glycemic gap levels ≤43 mg/dL. The B-type natriuretic peptide levels incorporated with glycemic gap could increase the predictive capacity for in-hospital mortality and increase the area under the ROC from 0.764 to 0.805 (net reclassification improvement = 9.9%, p

Recent data suggest that short-chain fatty acids (SCFAs), the major fermentation product from gut microbial degradation of dietary fiber, have protective effects against renal ischemia-reperfusion (IR) injury, colitis, and allergic asthma. However, the effect of SCFAs on acute lung injury (ALI) caused by IR is still unclear. In this study, we examine whether SCFAs have protective effects against IR-induced ALI and explore possible protective mechanisms. IR-induced ALI was established by 40 min ischemia followed by 60 min reperfusion in isolated perfused rat lungs. Rats were randomly assigned to one of six groups: control, control + acetate (400 mg/kg), IR, and IR + acetate at one of three dosages (100, 200, 400 mg/kg). Bronchoalveolar lavage fluids (BALF) and lung tissues were obtained and analyzed at the end of the experiment. In vitro, mouse lung epithelial cells (MLE-12) subjected to hypoxia-reoxygenation (HR) were pretreated with acetate (25 mmol/L) and GPR41 or GPR43 siRNA. Acetate decreased lung weight gain, lung weight/body weight ratios, wet/dry weight ratios, pulmonary artery pressure, and protein concentration of the BALF in a dose-dependent manner for IR-induced ALI. Acetate also significantly inhibited the production of TNF-α, IL-6 and CINC-1 in the BALF. Moreover, acetate treatment restored suppressed IκB-α levels and reduced nuclear NF-κB p65 levels in lung tissues. In addition, acetate mitigated IR-induced apoptosis and tight junction disruption in injured lung tissue. In vitro analyses showed that acetate attenuated NF-κB activation and KC/CXCL-1 levels in MLE-12 cells exposed to HR. The protective effects of acetate in vitro were significantly abrogated by GPR41 or GPR43 siRNA. Acetate ameliorates IR-induced acute lung inflammation and its protective mechanism appears to be via the GPR41/43 signaling pathway. Based on our findings, acetate may provide a novel adjuvant therapeutic approach for IR-induced lung injury.

Background Nonradiographic axial spondyloarthropathies (nr-axSpA) are diagnosed by the absence of radiographic sacroiliitis and the presence of bone marrow edema (BME) on magnetic resonance imaging (MRI). According to the classification criteria of the international Assessment of Spondyloarthritis Society (ASAS), structural changes to sacroiliac joints (SIJs) on MRI cannot be used as criteria in the absence of BME. However, less than half the Asian patients with clinically active axSpA show BME. The incidence of human leukocyte antigen (HLA)-B27 is low in Asian populations, which makes it more difficult to identify nr-axSpA. We used MRI to evaluate the structural damage to SIJs in patients with nr-axSpA with and without BME with the aim of identifying the best methodology for accurate diagnosis, especially in populations with less common BME and HLA-B27. Methods One hundred three patients with inflammatory back pain were included in this prospective study. No patient’s radiograph met the definition of positive modified New York criteria. BME and structural damage to SIJ including sclerosis and erosion were assessed independently on coronal and axial short-tau inversion recovery and T1-weighted spin echo MRI scans by two well-trained musculoskeletal radiologists using the Spondyloarthritis Research Consortium of Canada (SPARCC) score. Demographics of patients were collected. Disease characteristics and structural damage were analyzed in patients with and without BME on SIJ MRI. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic performance of structural damage. Results All individuals in the cohort had at least one abnormal finding on SIJ MRI, including BME or structural damage; 36 of 103 patients had BME. We identified a significant positive correlation between SPARCC scores and severe erosion assessed by focal joint space widening (fJSW) (p = 0.001) in these 36 patients. Fifty-eight of the 103 enrolled patients fulfilled the ASAS criteria for nr-axSpA in the either absence or presence of BME. Of these 58 patients, 57 and 19 had erosions or fJSW, respectively, and the presence of BME was significantly correlated with fJSW (phi score of 0.319 and p = 0.015). We demonstrated a significant positive correlation between fJSW and either the presence or the severity of BME in patients with nr-axSpA who met the ASAS definition. There was a positive correlation between BME and fJSW across the whole study cohort (phi score of 0.389; p p p = 0.018 and 0.003, respectively) and SPARCC scores were higher in patients with fJSW (p p = 0.005). We also identified a positive correlation between fJSW and BME in patients with nr-axSpA and normal serum levels of C-reactive protein (phi score of 0.362 and p = 0.001). Conclusion Structural damage detected on SIJ MRI, sclerosis, erosions and fJSW may be present in patients without detectable inflammation on SIJ MRI. However, fJSW is significantly correlated with the severity of inflammation seen on SIJ MRI, which contributes to the accurate diagnosis of nr-axSpA, and it could be used as an alternative diagnostic test for nr-axSpA in the general population, especially for those who do not carry the HLA-B27 gene, Asian patients without BME, or patients with normal serum inflammatory biomarkers.

Previous studies demonstrated that triptolide (PG490) has many anti-inflammatory and immunosuppressive effects. However, little is known about the effect of PG490-88 (a water-soluble derivative of triptolide) on ischemia/reperfusion (I/R)-induced acute lung injury. We assessed the effects of PG490-88 on I/R-induced acute lung injury in rats and on hypoxia/reoxygenation (H/R) in a line of murine epithelial cells. Isolated perfused rat lungs were subjected to 40 min of ischemia, followed by 60 min of reperfusion to induce I/R injury. Induction of I/R led to lung edema, elevated pulmonary arterial pressure, histological evidence of lung inflammation, oxidative stress, and increased levels of TNF-α and CINC-1 in bronchoalveolar lavage fluid. PG490-88 significantly suppressed all of these responses. Additionally, induction of I/R reduced the expression of claudin-4, occludin, and ZO-1, and increased apoptosis in lung tissue. PG490-88 also significantly suppressed these effects. I/R reduced the levels of IκB-α and MKP-1, and increased the levels of nuclear NF-κB and mitogen-activated protein kinase in lung tissue, and PG490-88 suppressed these effects. In vitro studies using mouse lung alveolar epithelial cells indicated that H/R increased the levels of phosphorylated p65 and MIP-2, but decreased the level of IκB-α. PG490-88 also suppressed these effects. In I/R damaged lungs, PG490-88 suppresses the inflammatory response, disruption of tight junction structure, and apoptosis. PG490-88 has the potential as a prophylactic agent to prevent I/R-induced lung injury.

Current treatments for ischemia-reperfusion (IR)-induced acute lung injury are limited. Mesenchymal stem cell-conditioned medium (CM) has been reported to attenuate lung injury. Neural crest stem cells (NCSCs), a type of multipotent stem cells, are more easily obtained than mesenchymal stem cells. We hypothesize that NCSC-CM has anti-inflammatory properties that could protect against IR-induced lung injury in rats. In this study, NCSC-CM was derived from rat NCSCs. Typical acute lung injury was induced by 30-min ischemia followed by 90-min reperfusion in adult male Sprague-Dawley rats. Bronchoalveolar lavage fluid (BALF) and lung tissues were collected to analyze the degree of lung injury after the experiment. NCSC-CM was administered before ischemia and after reperfusion. NCSC-CM treatment significantly attenuated IR-induced lung edema, as indicated by decreases in pulmonary vascular permeability, lung weight gain, wet to dry weight ratio, lung weight to body weight ratio, pulmonary arterial pressure, and protein level in BALF. The levels of tumor necrosis factor-α and interleukin-6 in the BALF were also significantly decreased. Additionally, NCSC-CM improved lung pathology and neutrophil infiltration in the lung tissue, and significantly suppressed nuclear factor (NF)-κB activity and IκB-α degradation in the lung. However, heating NCSC-CM eliminated these protective effects. Our experiment demonstrates that NCSC-CM treatment decreases IR-induced acute lung injury and that the protective mechanism may be attributable to the inhibition of NF-κB activation and the inflammatory response. Therefore, NCSC-CM may be a novel approach for treating IR-induced lung injury.

Various animal studies have shown beneficial effects of hypercapnia in lung injury. However, in patients with acute respiratory distress syndrome (ARDS), there is controversial information regarding the effect of hypercapnia on outcomes. The duration of carbon dioxide inhalation may be the key to the protective effect of hypercapnia. We investigated the effect of pre-treatment with inhaled carbon dioxide on lipopolysaccharide (LPS)-induced lung injury in mice. C57BL/6 mice were randomly divided into a control group or an LPS group. Each LPS group received intratracheal LPS (2 mg/kg), the LPS groups were exposed to hypercapnia (5% carbon dioxide) for 10 min or 60 min before LPS. Bronchoalveolar lavage fluid (BALF) and lung tissues were collected to evaluate the degree of lung injury. LPS significantly increased the ratio of lung weight to body weight, concentrations of BALF protein, tumor necrosis factor-&alpha, and CXCL2, protein carbonyls, neutrophil infiltration, and lung injury score. LPS induced the degradation of the inhibitor of nuclear factor-&kappa, B-&alpha, (I&kappa, ) and nuclear translocation of NF-&kappa, B. LPS increased the surface protein expression of toll-like receptor 4 (TLR4). Pre-treatment with inhaled carbon dioxide for 10 min, but not for 60 min, inhibited LPS-induced pulmonary edema, inflammation, oxidative stress, lung injury, and TLR4 surface expression, and, accordingly, reduced NF-&kappa, B signaling. In summary, our data demonstrated that pre-treatment with 10-min carbon dioxide inhalation can ameliorate LPS-induced lung injury. The protective effect may be associated with down-regulation of the surface expression of TLR4 in the lungs.

Background Sjogren syndrome (SS) is an autoimmune disease presented with exocrine gland inflammation and extra-glandular involvement. The prevalence of pulmonary involvement, including interstitial lung disease (ILD), in patients with primary SS widely varies from 8% to 20%.1, 2Patients with SS with ILD have high morbidity and a fourfold increase in mortality.3 Objectives Krebs von den Lungen-6 (KL-6) is a mucin-like, high-molecular-weight glycoprotein; it is expressed in regenerating type II pneumocytes. Serum KL-6 is highly associated with the activity of ILD in patients with radiation pneumonitis, idiopathic pulmonary fibrosis, hypersensitivity pneumonitis, sarcoidosis, rheumatoid arthritis, polymyositis, dermatomyositis and systemic sclerosis.4-8 The increase in serum KL-6 level might reflect the increase in the number of regenerating type II pneumocytes secondary to pulmonary damage.8 We hypothesise that an early pulmonary damage occurs before clinical or radiological evidence of ILD in patients with SS. Methods In this retrospective case-control study, patients who were diagnosed with primary SS and fulfilled the American-European Consensus Group Criteria for Sjogren’s Syndrome were included. Clinical information, laboratory results on inclusion, images and pulmonary functions test results were recorded via electronic medical records review. Pulmonary radiography including chest X-ray and chest computed tomography was reviewed by a chest physician. Results Of the 39 patients with SS, 21 (53.85%) developed ILD at the end of follow-up. The follow-up period was 2.65 ± 1.88 years. The time to diagnosis of ILD was 2.72 ± 1.74 years in the ILD group. The serum KL-6 level was 1920.10 ± 1974.26 U/ml in the ILD group and 894.11 ± 788.53 U/ml in the non-ILD group (p = 0.001). The diffusing capacity of the lungs for carbon monoxide was 70.76 ± 19.63 mmHg and 91.88 ± 12.02 mmHg in the ILD group and non-ILD group, respectively (p Conclusion Serum KL-6 level is significantly higher in patients with primary SS with developing ILD and may represent an early non-radiographic pulmonary damage. Serum KL-6 can be a valuable biomarker in predicting the development of ILD in patients with primary SS. References [1] Roca F, Dominique S, Schmidt J, et al. Interstitial lung disease in primary Sjogren’s syndrome. Autoimmunity reviews. 2017; 16: 48-54. [2] Kreider M and Highland K. Pulmonary involvement in Sjogren syndrome. Seminars in respiratory and critical care medicine. 2014; 35: 255-64. [3] Palm O, Garen T, Berge Enger T, et al. Clinical pulmonary involvement in primary Sjogren’s syndrome: prevalence, quality of life and mortality-a retrospective study based on registry data. Rheumatology (Oxford, England). 2013; 52: 173-9. [4] Hamada H, Kohno N, Akiyama M and Hiwada K. Monitoring of serum KL-6 antigen in a patient with radiation pneumonia. Chest. 1992; 101: 858-60. [5] Kobayashi J and Kitamura S. Serum KL-6 for the evaluation of active pneumonitis in pulmonary sarcoidosis. Chest. 1996; 109: 1276-82. [6] Oyama T, Kohno N, Yokoyama A, et al. Detection of interstitial pneumonitis in patients with rheumatoid arthritis by measuring circulating levels of KL-6, a human MUC1 mucin. Lung. 1997; 175: 379-85. [7] Takanashi S, Nishina N, Nakazawa M, Kaneko Y and Takeuchi T. Usefulness of serum Krebs von den Lungen-6 for the management of myositis-associated interstitial lung disease. Rheumatology (Oxford, England). 2019. [8] Elhai M, Hoffmann-Vold AM, Avouac J, et al. Performance of candidate serum biomarkers for systemic sclerosis-interstitial lung disease. Arthritis & rheumatology (Hoboken, NJ). 2019. Disclosure of Interests None declared

Background Diabetes is the most common comorbidity of necrotizing fasciitis (NF), but the effect of stress-induced hyperglycemia (SIH) on diabetic patients with NF has never been investigated. The aim of this study was to assess whether SIH, as determined by the glycemic gap between admission glucose levels and A1C-derived average glucose levels, predicts adverse outcomes in diabetic patients hospitalized with NF. Methods We retrospectively reviewed the glycemic gap and clinical outcomes in 252 diabetic patients hospitalized due to NF from 2011 to 2018 in a single medical center in Taiwan. A receiver operating characteristic (ROC) curve was used to analyze the optimal cutoff values for predicting adverse outcomes. Univariate and multivariate logistic regression analyses were employed to identify significant predictors of adverse outcomes. Results In total, 194 diabetic NF patients were enrolled. Compared with patients without adverse outcomes, patients with adverse outcomes had significantly higher glycemic gaps, Acute Physiology and Chronic Health Evaluation (APACHE) II scores and C-reactive protein (CRP) levels; lower albumin and hemoglobin levels; greater incidence of limb loss; and longer hospital and intensive care unit stays. The glycemic gap positively correlates with the laboratory risk indicator for NF scores, APACHE II scores and CRP levels. A glycemic gap of 146 mg/dL was the optimal cutoff value for predicting adverse outcomes using the ROC curve. Compared with patients with glycemic gaps ≤146 mg/dL, those with glycemic gaps >146 mg/dL had higher APACHE II scores and incidence rates of adverse outcomes, especially bacteremia and acute kidney injury. Multivariate analysis revealed that a glycemic gap >146 mg/dL and APACHE II score >15 were independent predictors of adverse outcomes, while the presence of hyperglycemia at admission was not. Conclusions An elevated glycemic gap was significantly independently associated with adverse outcomes in diabetic NF patients. Further prospective studies are warranted to validate the role of the glycemic gap in NF patients with diabetes.

Background:Krebs von den Lungen-6 (KL-6) was recently found to be a serum biomarker for various disease associated interstitial lung disease (ILD) including primary Sjögren syndrome (pSS).1KL-6 is a high-molecular-weight glycoprotein in the Mucin 1 protein group and is majorly expressed by regenerating type II pneumocytes; hence, serum KL-6 levels may reflect the severity of pulmonary damage with regeneration.2Human KL-6 also promotes the proliferation and survival of pulmonary fibroblasts and the differentiation of myofibroblasts, which enhance fibrosis.3, 4Objectives:To evaluate the agreement between the latex particle-enhanced turbidimetric immunoassay with enzyme-linked immunosorbent assay (ELISA) and association with clinical phenotypes.Methods:This retrospective case-control study included 39 patients with pSS, of whom 21 (53.85%) patients developed ILD at the end of follow-up. The serum KL-6 level was compared between latex particle-enhanced turbidimetric immunoassay (Nanopia) and ELISA (MBS2601395; MyBioSource, CA, USA). Electronic medical records were reviewed, including clinical information, images, pulmonary function test, and laboratory results on inclusion, and a chest physician reviewed the results of pulmonary radiography.Results:The two serum KL-6 immunoassays revealed a moderate correlation with a Pearson product-moment correlation coefficient of 0.427. Serum KL-6 levels, measured using ELISA, were 1920.10 ± 1974.26 U/mL and 894.11 ± 788.53 U/mL in the ILD and non-ILD groups, respectively (p = 0.001). The latex particle-enhanced turbidimetric immunoassay for serum KL-6 was 459.62 ± 331.41 U/mL and 265.33 ± 105.37 U/mL in the ILD and non-ILD group, respectively (p = 0.074). The predictive values of serum KL-6 in the area under the receiver-operating characteristic curve were 0.810 and 0.669 in ELISA and latex particle-enhanced turbidimetric immunoassay, respectively.Conclusion:Serum KL-6 is a predicting biomarker in pSS patients who may develop ILD. However, the methodology of immunoassay may influence the efficacy of the prediction and clinical association.References:[1]Chiu Y-H, Lu C-C, Liu F-C, et al. FRI0228 KL-6 AS A BIOMARKER OF DEVELOPING INTERSTITIAL LUNG DISEASE IN PATIENTS WITH SJÖGREN SYNDROME.Ann Rheum Dis. 2019; 78: 793.[2]Yousefi M, Dehghani S, Nosrati R, et al. Aptasensors as a new sensing technology developed for the detection of MUC1 mucin: A review.Biosensors & bioelectronics. 2019; 130: 1-19.[3]Xu L, Yan DR, Zhu SL, et al. KL-6 regulated the expression of HGF, collagen and myofibroblast differentiation.Eur Rev Med Pharmacol Sci. 2013; 17: 3073-7.[4]Ohshimo S, Yokoyama A, Hattori N, Ishikawa N, Hirasawa Y and Kohno N. KL-6, a human MUC1 mucin, promotes proliferation and survival of lung fibroblasts.Biochem Biophys Res Commun. 2005; 338: 1845-52.Acknowledgments:This work was supported by National Defense Medical Center and Tri-Service General Hospital (TSGH-D-109183). The authors thank Kuo’s Yuan In Enterprise co., LTD for supporting Nanopia KL-6 Kit.Disclosure of Interests:None declared

ObjectiveThe aim of this study was to explore whether patients with Sjögren’s syndrome (SS) were susceptible to bisphosphonate (BP)-related osteonecrosis of the jaw (BRONJ) after tooth extraction in the entire population of Taiwan.DesignA nationwide population-based retrospective cohort study.SettingData were extracted from Taiwan’s National Health Insurance Research Database (NHIRD).MethodologyMedical conditions for both the study and control group were categorised using the International Classification of Diseases, 9th Revision. ORs and 95% CIs for associations between SS and osteonecrosis of the jaw (ONJ) were estimated using Cox regression.ResultsOverall, 13 398 patients diagnosed with SS were identified from the NHIRD. An additional 53 592 matched patients formed the control group. At the 3-year follow-up, patients with SS started to exhibit a significantly increased cumulative risk of developing BRONJ compared with that of patients without SS (log rank test ConclusionPatients with SS exhibit an increased risk of developing BRONJ after tooth extraction. BPs should be used with caution in patients with SS.

ObjectivesSjögren’s syndrome (SS) is a systemic autoimmune disorder. Several molecular pathways and the activation of matrix metalloproteinases associated with the pathogenesis of SS participate in the initiation and progression of aortic aneurysm (AA) and aortic dissection (AD). In this study, we aimed to evaluate whether patients with SS exhibit an increased risk of AA or AD.MethodsWe conducted a retrospective cohort study using a database extracted from Taiwan’s National Health Insurance Research Database. All medical conditions for each case and control were categorised using the International Classification of Diseases, Ninth Revision. HRs and 95% CIs for associations between SS and AA/AD were estimated using Cox regression and adjusted for comorbidities.ResultsOur analyses included 10 941 SS cases and 43 764 propensity score-matched controls. Compared with the controls, the patients with SS exhibited a significantly increased risk of developing an AA or AD (adjusted HR=3.642, pConclusionPatients with SS exhibit increased risks of developing AA or AD, and healthcare professionals should be aware of this risk when treating patients with SS. Increased aortic surveillance may be required for patients with SS.

Annexin A1 (AnxA1) is an endogenous protein that modulates anti-inflammatory processes, and its therapeutic potential has been reported in a range of inflammatory diseases. The effect of AnxA1 on ischemia-reperfusion (IR)-induced lung injury has not been examined. In this study, isolated, perfused rat lungs were subjected to IR lung injury induced by ischemia for 40 min, followed by reperfusion for 60 min. The rat lungs were randomly treated with vehicle (phosphate-buffered saline), and Ac2-26 (an active N-terminal peptide of AnxA1) with or without an

Background Valproic acid (VPA) has shown potent anti-inflammatory effect and attenuates acute lung injury. Aim To determine whether the use of VPA is associated with a decreased risk of acute respiratory failure (ARF) in patients with subarachnoid hemorrhage (SAH). Design The Taiwan National Health Insurance Research Database was used to analyse all patients newly diagnosed with SAH from 2000 to 2010. The VPA users were matched for age, gender and index date in 1:2 ratios with randomly selected non-VPA users as a comparison group. Methods Multivariate Cox regression was used to identify the predictors of ARF and to compare the incidence rates of ARF among SAH patients using and not using VPA. Results The study cohort included 16 228 newly diagnosed SAH patients, from which 521 VPA users and 1042 matched non-VPA-exposed individuals were selected. In the VPA-treated cohort and the non-VPA-treated cohort, 117 and 289 patients developed ARF, respectively. Any use of VPA was associated with a 16% decreased risk of ARF requiring mechanical ventilation in 30-day tracking of the SAH patients (adjusted hazard ratio [HR], 0.840, 95% confidence interval [CI], 0.676-0.945). Age, sepsis and pneumonia were identified as independent predictors of ARF in patients with SAH. After stratification, VPA users showed a lower risk of ARF among SAH patients complicated with pneumonia compared with non-users of VPA (adjusted HR, 0.816, 95% CI, 0.652-0.921). Conclusions Any use of VPA was associated with a reduced risk of ARF in patients with SAH. VPA may be beneficial for decreasing the risk of pneumonia-induced ARF in patients with SAH.

Background Chest compression (CC) quality is associated with rescuer posture and body weight. We designed a Kinect module-based real-time audiovisual feedback (AVF) device to investigate the relationship between rescuer posture, body weight, and CC quality. Methods A total of 100 healthcare professionals were enrolled as participants in this randomized trial. A Kinect-based sensor system was used to monitor the depth and rate of CC and provide further real-time feedback. All participants were asked to perform continuous CC on a manikin with and without feedback for 2 min individually in either a kneeling or standing position. Results A kneeling posture can provide higher rate of CC than a standing posture can (111.4 ± 22.6 per minute vs. 99.1 ± 18.9 per minute, p value = 0.005). Real-time AVF feedback can provide a better compression depth, rate, and effective compression ratio (6.16 ± 1.88 cm vs. 5.54 ± 1.89 cm, p value = 0.02; 103.2 ± 21.0/min vs. 96.7 ± 25.8/min, p value = 0.03; 62.6 ± 28.0% vs. 51.0 ± 33.2%, p value = 0.004). Regardless of the effect of real-time feedback, the CC depth correlated to the rescuers' body weight. Rescuers who weighed below 71 kg benefited from the Kinect module-based real-time AVF device in terms of improved CC quality. Conclusion The Kinect-based AVF device can significantly improve CC quality in manikin training in rescuers with their body weight

Stanniocalcin-1 (STC1) is an endogenous glycoprotein whose anti-inflammatory effects occur through induction of uncoupling proteins to reduce oxidative stress. In this study, we tested the hypothesis that exogenous recombinant human STC1 (rhSTC1) protects against lipopolysaccharide (LPS)-induced acute lung injury in mice. Anesthetized C57BL/6 mice underwent intratracheal spraying of LPS (20 µg/10 g body wt), and lung injury was assessed 24h later by analyzing pulmonary edema, bronchoalveolar lavage fluid, and lung histopathology. Lung inflammation, oxidative stress, and expression of STC1 and its downstream uncoupling protein 2 (UCP2) were analyzed at specific time points. Expression of UCP2 was suppressed initially but was subsequently upregulated after STC1 elevation in response to intratracheal administration of LPS. Intratracheal rhSTC1 treatment 1h before or after LPS spraying significantly attenuated pulmonary inflammation, oxidative stress, cell apoptosis, and acute lung injury. Pretreatment with STC1 short interfering RNA 48 h before LPS spraying inhibited the expression of STC1 and UCP2 and significantly increased the extent of lung injury. These findings suggest that STC1 is an endogenous stress protein that may counteract LPS-induced lung injury by inhibiting the inflammatory cascade and inducing antioxidant and antiapoptotic mechanisms. However, the potential clinical application of STC1 and the direct linkage between UCP2 and LPS-induced lung injury remain to be further investigated.

Systemic administration of perfluorocarbons (PFCs) reportedly attenuates acute lung injury induced by acid aspiration and phorbol myristate acetate. However, the effects of PFCs on ischemia–reperfusion (IR)-induced lung injury have not been investigated. Typical acute lung injury was induced in rats by 60 min of ischemia and 60 min of reperfusion in isolated and perfused rat lung model. Rat lungs were randomly assigned to receive PBS (control), 1 % FC-77, IR only, or IR with different doses of FC-77 (0.1 %, 0.5 %, or 1 %). Subsequently, bronchoalveolar lavage fluid (BALF), perfusate, and lung tissues were collected to evaluate the degree of lung injury. IR caused a significant increase in the following parameters: pulmonary arterial pressure, capillary filtration coefficient, lung weight gain, lung weight/body weight ratio, wet/dry lung weight ratio, and protein concentration in BALF. TNF-α and cytokine-induced neutrophil chemoattractant-1 concentrations in perfusate samples and MDA concentration and MPO activities in lung tissues were also significantly increased. Histopathology showed increased septal thickness and neutrophil infiltration in the lung tissues. Furthermore, NF-κB activity was significantly increased in the lungs. However, pretreatment with 1 % FC-77 prior to IR significantly attenuated the increases in these parameters. In conclusion, our results suggest that systemic FC-77 administration had a protective effect on IR-induced acute lung injury. These protective mechanisms may have been mediated by the inhibition of NF-κB activation and attenuation of subsequent inflammatory response.

Background Emerging evidence reveals that nicotinamide phosphoribosyltransferase (NAMPT) has a significant role in the pathophysiology of the inflammatory process. NAMPT inhibition has a beneficial effect in the treatment of a variety of inflammatory diseases. However, it remains unclear whether NAMPT inhibition has an impact on ischemia-reperfusion (I/R)-induced acute lung injury. In this study, we examined whether NAMPT inhibition provided protection against I/R lung injury in rats. Methods Isolated perfused rat lungs were subjected to 40 min of ischemia followed by 60 min of reperfusion. The rats were randomly allotted to the control, control + FK866 (NAMPT inhibitor, 10 mg/kg), I/R, or I/R + FK866 groups (n = 6 per group). The effects of FK866 on human alveolar epithelial cells exposed to hypoxia-reoxygenation (H/R) were also investigated. Results Treatment with FK866 significantly attenuated the increases in lung edema, pulmonary arterial pressure, lung injury scores, and TNF-α, CINC-1, and IL-6 concentrations in bronchoalveolar lavage fluid in the I/R group. Malondialdehyde levels, carbonyl contents and MPO-positive cells in lung tissue were also significantly reduced by FK866. Additionally, FK866 mitigated I/R-stimulated degradation of IκB-α, nuclear translocation of NF-κB, Akt phosphorylation, activation of mitogen-activated protein kinase, and downregulated MKP-1 activity in the injured lung tissue. Furthermore, FK866 increased Bcl-2 and decreased caspase-3 activity in the I/R rat lungs. Comparably, the in vitro experiments showed that FK866 also inhibited IL-8 production and NF-κB activation in human alveolar epithelial cells exposed to H/R. Conclusions Our findings suggest that NAMPT inhibition may be a novel therapeutic approach for I/R-induced lung injury. The protective effects involve the suppression of multiple signal pathways.

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.

Purpose Severe hypoglycemia can result in neural damage, impaired cognitive function, coma, seizures, or death. The decision to admit diabetic patients after initial treatment in the emergency department remains unclear. Our purpose is to identify risk factors for developing recurrent hypoglycemia in diabetic patients admitted for severe hypoglycemia. Materials and methods We reviewed the records of 233 subjects (92 males, 141 females; mean age, 74.1 +/- 9.8 years) with type 2 diabetes treated at a tertiary care teaching hospital and hospitalized for severe hypoglycemia. Results Seventy-four (31.8%) patients were categorized with recurrent hypoglycemia and 159 (68.2%) with non-recurrent. Multivariate logistic regression analysis revealed that patients with loss of a recent meal, coronary artery disease, infection, and poor renal function (lower estimated glomerular filtration rate) were at risk for recurrent hypoglycemia. The use of calcium-channel blockers appeared to be a protective factor for the development of recurrent hypoglycemia. Conclusion There may be a subset of patients with severe hypoglycemia and certain risk factors for recurrent hypoglycemia that should be admitted.

1. Glutamine is an amino acid that is used to treat various diseases. Glutamine has been reported to have protective effects in human pulmonary epithelia-like cells exposed to hyperoxia. However, the effects of glutamine in hyperoxia-induced lung injury have not been investigated in vivo. 2. Mice treated with saline or glutamine [(750 mg/kg) intravenously] were randomly exposed to hyperoxia for 48 or 72 h. Control mice treated with saline or glutamine were exposed to room air. Cytokine levels in bronchoalveolar lavage fluid (BALF), heat shock protein (HSP) 70, the wet/dry (W/D) weight ratio, malondialdehyde (MDA) levels, myeloperoxidase (MPO) activity and pathoglogical findings in lung tissue were evaluated to determine the effects of glutamine on acute lung injury. In addition, survival was monitored. 3. Lung expression of HSP70 was significantly enhanced in both the control (room air) and 48 and 72 h hyperoxic glutamine-treated mice. The W/D ratio, BALF concentrations of tumour necrosis factor-alpha and interleukin-6, MDA levels, MPO activity, neutrophil infiltration and interstitial oedema in lung tissue were significantly lower at 48 and 72 h of hyperoxia in glutamine-treated mice compared with saline-treated mice. 4. In a separate series of experiments evaluating survival, after 96 h continuous exposure to hyperoxia, all saline-treated mice died. In contrast, all glutamine-treated mice died after 108 h exposure to hyperoxia. 5. The data suggest that glutamine administered to mice during hyperoxia has a protective effect against hyperoxia-induced acute lung injury and improves survival.

ObjectiveTo characterize the course of therapy in a large cohort of Chinese patients with thyrotoxic periodic paralysis (TPP), a reversible electrolyte emergency fraught with therapeutic challenges.Design and methodsIn this prospective interventional study, 78 patients with TPP (75 males and three females with an age range of 16–48 years) were consecutively enrolled over a 6-year period. Intravenous KCl at a rate of 10 mmol/h was administered until muscle strength recovered. Serum potassium (K+) and phosphorus concentrations were measured hourly during the paralytic attack and for 6 h after recovery.ResultsThe serum potassium (K+) on attack was 2.1±0.2 mmol/l. The dose of KCl administered to restore muscle strength was 63±32 mmol, and peak serum K+ concentration after recovery was 5.3±0.5 mmol/l. A paradoxical fall in serum K+ concentration >0.1 mmol/l difference between presentation and treatment nadir was observed in approximately one-fourth of TPP patients (n=20). These patients had significantly higher serum-free thyroxine concentration, systolic blood pressure, and heart rate on presentation, as well as serum phosphate concentration on recovery. They not only needed much more KCl supplementation (104±34 vs 48±19 mmol, PP+ (Δ K+) (r=0.68, PConclusionsTPP patients who do not develop paradoxical hypokalemia need a smaller KCl dose to achieve recovery, whereas those who develop paradoxical hypokalemia have more severe hyperthyroidism and hyperadrenergic activity and may require blockage of intracellular K+ shift to prevent rebound hyperkalemia.

Background and purpose: Baicalin has been reported to have anti-inflammatory effects and protect against various tissue injuries. However, the effect of baicalin on air embolism-induced acute lung injury has not been tested yet. Experimental approach: Acute lung injury was induced by infusion of air at a rate of 0.25 mL·min−1 for 1 min into the pulmonary artery of rat isolated lungs. At the end of the experiment, samples were collected for assessment of lung injury, biochemical analysis and histology. Different doses of baicalin (1, 2 and 4 mg·kg−1) were given into the perfusate before air infusion. Key results: Air embolism elicited a significant increase in microvascular permeability (Kf), lung weight gain, wet/dry weight ratio, pulmonary artery pressure and protein concentration in the bronchoalveolar lavage fluid. Levels of the cytokines, tumour necrosis factor α and cytokine-induced neutrophil chemoattractant-1 in perfusate, and malondialdehyde levels and myeloperoxidase activities in lung tissue were also significantly increased. In addition, histological examination showed increased neutrophil infiltration in lung tissues. Furthermore, nuclear factor-κB activity and degradation of IκB-α were significantly increased in lungs. Pretreatment of the lungs with baicalin (4 mg·kg−1) showed a statistically significant difference in all of the assessed parameters, except for alteration in the pulmonary artery pressure. Conclusions and implications: Our study suggests that baicalin attenuated air embolism-induced acute lung injury and may be considered a useful adjunct drug therapy in this clinical condition.

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.

Background Diabetes mellitus (DM) is associated with adverse events or complications in various gastrointestinal diseases. In this study, we examined whether diabetic patients had higher risk for the development of complicated acute appendicitis than nondiabetic patients. The relevant risk factors also were determined. Methods A retrospective study enrolling diabetic and nondiabetic patients who acquired acute appendicitis was conducted at a single institution over a 5-year period. Results We identified 1,184 patients with a primary discharge diagnosis of acute appendicitis. Seventy-one patients were found to have DM. Diabetic patients were older, had a higher risk of developing complicated acute appendicitis (CAA), and had a more prolonged hospital stay compared with nondiabetic patients. On further examination by multivariate logistic regression analysis, DM was an independent risk factor for CAA after adjusting for age and sex. Of the 71 diabetic patients, 46 patients (64.8%) were found to have CAA. The mean age of diabetic patients with uncomplicated acute appendicitis (DM/UAA) and CAA (DM/CAA) had no significant difference. The duration from the onset of symptoms to diagnosis was significantly longer in the DM/CAA than in the DM/UAA group. The mean length of hospital stay also was significantly longer in the DM/CAA than in the DM/UAA group. DM/CAA patients were found to have a higher rate of history of diabetic nephropathy as well as a higher serum creatinine level and a lower estimated glomerular filtration rate than DM/UAA patients. There was no statistical significance regarding patients older or younger than 60 years. Conclusions Our study showed that diabetic patients had a higher risk for the development of CAA and a subsequently longer hospital stay than nondiabetic patients. Age was not an independent risk factor for the development of CAA in diabetic patients in our study. Delayed diagnosis, and probably a history of diabetic nephropathy, as well as poorer renal function were risk factors for the development of CAA in diabetic patients. The single most important risk factor was the duration from the onset of symptoms to diagnosis. Once CAA developed, the length of hospital stay was prolonged significantly.

We assess the prognostic role of initial glucose levels in patients with a first acute myocardial infarction in the emergency department (ED).We conducted a 3-year retrospective cohort study. Patients with a first acute myocardial infarction were recruited from the ED of a tertiary hospital from January 1, 2001, to December 31, 2003. Initial glucose levels in the ED were stratified into 3 levels (normal140 mg/dL; intermediate 140 to 200 mg/dL; and highor = 200 mg/dL). Logistic and Cox regression models were applied to estimate the 1-month short-term and 1-year long-term adverse prognoses, respectively.A total of 198 eligible subjects (159 men and 39 women; mean age 63.1+/-14.2 years) were recruited. The estimated survival curves among the 3 initial glucose levels were significantly different (P=.0002). After adjustment for sex, age, diabetic status, reperfusion therapy, and infarct subtype, the adjusted odds ratio for short-term prognosis progressed with higher levels when compared with the normal level (intermediate level: odds ratio 3.87; 95% confidence interval [CI] 1.71 to 8.78; high level: odds ratio 5.16; 95% CI 1.97 to 13.51). High initial glucose level was an important risk factor for long-term adverse prognosis (hazard ratio 3.08; 95% CI 1.59 to 5.98).A high initial glucose level in the ED is an important and independent predictor of short- and long-term adverse prognoses in patients with first acute myocardial infarction.

Objective: Pulmonary air embolism, causing vessel obstruction and primary or secondary reactions of blood, can lead to acute lung injury. In addition, nitric oxide has been known to play a key role in various causes of lung injury. In this study we employed the isolated rat lung model to investigate the effects of L-arginine on air embolism-induced lung injury. Design: Randomized, controlled study. Setting: Animal-care facility procedure room. Subjects: Forty-two adult male Sprague-Dawley rats each weighing 250-350 g. Interventions: Infusion of air at the rate of 0.25 mL/min for 1 min into the pulmonary artery in isolated and perfused rat lung resulted in pulmonary hypertension and lung edema. Air embolism elicited a significant increase in microvascular permeability as measured by the capillary filtration coefficient, lung weight gain, lung weight-to-body weight ratio, pulmonary arterial pressure, and protein concentration of bronchoalveolar lavage fluid. Measurements and Main Results: Pretreatment with L-arginine (4 mmol/L) significantly attenuated the acute lung injury induced by air embolism as shown by a significant decrease in all of the assessed variables but did not alter the pulmonary arterial pressure (p

To study the effects of dehydroepiandrosterone (prasterone, DHEA) 200 mg/day on cytokine profiles in adult women with active systemic lupus erythematosus (SLE).In a double blind, randomised, placebo controlled study conducted as part of a larger multicentre study, 30 adult women with active SLE received oral DHEA 200 mg/day or placebo for 24 weeks. Baseline prednisone (10 mg/day) and other concomitant SLE medications were to remain constant. The levels of cytokines including interleukin (IL) 1, IL2, interferon gamma, IL4, and IL10 were determined by ELISA. The mean change from baseline to 24 weeks of therapy was analysed.The two groups (DHEA n = 15; placebo n = 15) were well balanced for baseline characteristics. Only IL1beta and IL10 could be detected in the serum of lupus patients; however, there was no significant mean (SD) difference in serum IL1beta before and after treatment (9.94 (8.92) v 9.20 (6.49) pg/ml). IL10 demonstrated a greater and significant reduction from baseline (9.21 (9.66) to 1.89 (1.47) pg/ml in the DHEA treatment group).In a 24 week study of adult Chinese women with mild to moderate SLE, treatment with DHEA 200 mg once daily resulted in significant reduction of serum levels of IL10. This finding may suggest why DHEA could significantly reduce lupus flares.

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.

Oxygen therapy remains the main component of the ventilation strategy for treatment of patients with acute lung injury. Hyperbaric oxygen therapy (HBO(2)) is the intermittent administration of 100% oxygen at pressure greater than sea level and has been applied widely to alleviate a variety of hypoxia-related tissue injuries. The purpose of this study was to evaluate the effect of hyperbaric oxygen on acute lung injury induced by intratracheal spraying of lipopolysaccharide (LPS) in rats. Male Sprague-Dawley rats underwent implantation of a carotid artery catheter under general anesthesia. Aerosolized LPS was delivered twice into the lungs via intratracheal puncture. Animals were either breathing room air (n = 27) or subjected to hyperbaric oxygen (HBO(2)) exposure (n = 27) 1 h after LPS spraying. Acute lung injury was evaluated 5 h and 24 h later. Compared with the control group, intratracheal spraying of LPS caused profound hypoxemia, greater wet/dry weight ratio (W/D) of the lung (5.67 +/- 0.22 vs. 4.98 +/- 0.19), and higher protein concentration (1706 +/- 168 vs. 200 +/- 90 mg/L) and LDH activity (129 +/- 30 vs. 46 +/- 15, mAbs/min) in bronchoalveolar lavage (BAL) fluid. Intratracheal spraying of LPS also caused significant WBC sequestration in the lung tissue. HBO2 treatment significantly reverted hypoxemia, reduced lung injury measures evaluated at 5 and 24 h, and enhanced 24-h animal survival rate (chi = 5.08, P = 0.024). The malondialdehyde (MDA) concentrations in lung tissue and serum were both increased after LPS spraying. Neither single HBO(2) therapy nor five sequential daily treatments enhanced MDA production in lung tissue or serum. Our results suggested that hyperbaric oxygen might reduce acute lung injury caused by intratracheal spraying of LPS in rats. This treatment modality is not associated with enhancement of oxidative stress to the lung.