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Context.--Idiopathic pulmonary fibrosis (IPF) is characterized by diffuse interstitial inflammation and fibroblast proliferation with accelerated remodeling of extracellular matrix, which result in irreversible destruction of the lung's architecture. Objective.--To elucidate the production levels, tissue localization, and activation of matrix metalloproteinase 7 (MMP-7) in the lungs of patients with IPF. Design.--Bronchoalveolar lavage analysis was performed in 17 IPF patients and 6 healthy volunteers. Levels of MMP-7 in blood were assayed in 23 IPF patients and 20 controls. Histologic and immunohistochemical analyses were performed on paraffin sections of the lung tissues from patients with IPF, interstitial pneumonia associated with rheumatoid arthritis, or nonspecific interstitial pneumonia. Results.--The proMMP-7 levels in bronchoalveolar lavage fluids from IPF patients were significantly higher than those from healthy controls, although there was no difference in the serum levels between the 2 groups. By immunohistochemistry, proMMP-7 was localized mainly to the hyperplastic alveolar and metaplastic bronchiolar epithelial cells in the lung tissues from IPF patients. Active MMP-7 was immunolocalized on alveolar macrophages and hyperplastic epithelial cells, which were also immunostained with antibody against CD151, a molecule associated with activation of proMMP-7. Immunoblot analysis indicated the overproduction of proMMP-7 together with a small amount of active MMP-7 in bronchoalveolar lavage fluids from IPF patients. The MMP-7 activity was detected in a cross-linked carboxymethylated transferrin film assay. Conclusions.--proMMP-7 is excessively produced by hyperplastic alveolar and metaplastic bronchiolar epithelial cells and activated locally in the lungs of IPF patients, suggesting that MMP-7 may contribute to the pathology of IPF., Idiopathic pulmonary fibrosis (IPF), also called usual interstitial pneumonitis on a pathologic basis, is characterized by diffuse interstitial inflammation, fibroblast proliferation, and accelerated remodeling of extracellular matrix (ECM), which result [...]

Acute respiratory distress syndrome is a serious condition that can arise following direct or indirect lung injury. It is heterogeneous and has a high mortality rate. Supportive care is the mainstay of treatment and there is no definitive pharmacological treatment as yet. Sivelestat is a neutrophil elastase inhibitor approved in Japan and the Republic of Korea for acute lung injury, including acute respiratory distress syndrome in patients with systemic inflammatory response syndrome. The aim of this review is to examine the clinical utility of sivelestat in different disease states, using data from nonclinical and clinical studies. In nonclinical studies, sivelestat appears to show benefit in acute lung injury without inhibiting the host immune defense in cases of infection. Clinical studies do not yet provide a clear consensus. Phase III and IV Japanese studies have shown improvements in pulmonary function, length of intensive care unit stay, and mechanical ventilation, but a non-Japanese multicenter study did not demonstrate sivelestat to have an effect on ventilator-free days or 28-day all-cause mortality. Evidence of improvement in various parameters, including duration of stay in intensive care, mechanical ventilation, the ratio of partial pressure of arterial oxygen and fraction of inspired oxygen (PaO2/FIO2 ratio) ratio, and lung injury scores, has been shown in patients with sepsis or gastric aspiration, and following the surgical treatment of esophageal cancer. To date, there are no particular concerns regarding adverse events, and the available data do not suggest that sivelestat might worsen infections. One study has analyzed cost-effectiveness, finding that sivelestat may reduce costs compared with standard care. The currently available evidence suggests that sivelestat may show some benefit in the treatment of acute lung injury/acute respiratory distress syndrome, although large, randomized controlled trials are needed in specific pathophysiological conditions to explore these potential benefits. [ABSTRACT FROM AUTHOR]

Hypermetabolism is a prominent feature of burn injury, and altered mitochondria function is presumed to contribute to this state. Recently, brown adipose tissue (BAT) was found to be present not only in rodents but also in humans, and its activity is associated with resting metabolic rate. In this report, we elucidate the relationship between burn injury-induced hypermetabolism and BAT activity and the possible role of the mitochondria-targeted peptide SS31 in attenuating burn injury-induced hypermetabolism by using a rat burn injury model. We demonstrate that burn injury induces morphological changes in interscapular BAT (iBAT). Burn injury was associated with iBAT activation, and this effect was positively correlated with increased energy expenditure. BAT activation was associated with augmentation of mitochondria biogenesis, and UCP1 expression in the isolated iBAT mitochondria. In addition, the mitochondria-targeted peptide SS31 attenuated burn injury-induced hypermetabolism, which was accompanied by suppression of UCP1 expression in isolated mitochondria. Our results suggest that BAT plays an important role in burn injury-induced hypermetabolism through its morphological changes and expression of UCP1. [ABSTRACT FROM AUTHOR]

Introduction: Abnormal body temperatures (Tb) are frequently seen in patients with severe sepsis. However, the relationship between Tb abnormalities and the severity of disease is not clear. This study investigated the impact of Tb on disease severity and outcomes in patients with severe sepsis.Methods: We enrolled 624 patients with severe sepsis and grouped them into 6 categories according to their Tb at the time of enrollment. The temperature categories (≤ 35.5 °C, 35.6-36.5 °C, 36.6-37.5 °C, 37.6-38.5 °C, 38.6-39.5 °C, ≥ 39.6 °C) were based on the temperature data of the Acute Physiology and Chronic Health Evaluation II (APACHE II) scoring. We compared patient characteristics, physiological data, and mortality between groups.Results: Patients with Tb of ≤ 36.5 °C had significantly worse sequential organ failure assessment (SOFA) scores when compared with patients with Tb >37.5 °C on the day of enrollment. Scores for APACHE II were also higher in patients with Tb ≤ 35.5 °C when compared with patients with Tb >36.5 °C. The 28-day and hospital mortality was significantly higher in patients with Tb ≤ 36.5 °C. The difference in mortality rate was especially noticeable when patients with Tb ≤ 35.5 °C were compared with patients who had Tb of >36.5 °C. Although mortality did not relate to Tb ranges of ≥ 37.6 °C as compared to reference range of 36.6-37.5 °C, relative risk for 28-day mortality was significantly greater in patients with 35.6-36.5 °C and ≤ 35.5 °C (odds ratio; 2.032, 3.096, respectively). When patients were divided into groups based on the presence (≤ 36.5 °C, n = 160) or absence (>36.5 °C, n = 464) of hypothermia, disseminated intravascular coagulation (DIC) as well as SOFA and APACHE II scores were significantly higher in patients with hypothermia. Patients with hypothermia had significantly higher 28-day and hospital mortality rates than those without hypothermia (38.1% vs. 17.9% and 49.4% vs. 22.6%, respectively). The presence of hypothermia was an independent predictor of 28-day mortality, and the differences between patients with and without hypothermia were observed irrespective of the presence of septic shock.Conclusions: In patients with severe sepsis, hypothermia (Tb ≤ 36.5 °C) was associated with increased mortality and organ failure, irrespective of the presence of septic shock.Trial Registration: UMIN-CTR ID UMIN000008195. [ABSTRACT FROM AUTHOR]

Introduction: To validate the Japanese Association for Acute Medicine (JAAM) disseminated intravascular coagulation (DIC) scoring system in patients with severe sepsis, we conducted a multicenter, prospective study at 15 critical care centers in tertiary care hospitals.Methods: This study included 624 severe sepsis patients. JAAM DIC was scored on the day of diagnosis of severe sepsis (day 1) and day 4. Scores for disease severity and organ dysfunction were also evaluated.Results: The prevalence of JAAM DIC was 46.8% (292/624), and 21% of the DIC patients were scored according to the reduction rate of platelets. The JAAM DIC patients were more seriously ill and exhibited more severe systemic inflammation, a higher prevalence of multiple organ dysfunction syndrome (MODS) and worse outcomes than the non-DIC patients. Disease severity, systemic inflammation, MODS and the mortality rate worsened in accordance with an increased JAAM DIC score on day 1. The Kaplan-Meier curves demonstrated lower 1-year survival in the JAAM DIC patients than in those without DIC (log-rank test P<0.001). The JAAM DIC score on day 1 (odds ratio=1.282, P<0.001) and the Delta JAAM DIC score (odds ratio=0.770, P<0.001) were independent predictors of 28-day death. Dynamic changes in the JAAM DIC score from days 1 to 4 also affected prognoses. The JAAM DIC scoring system included all patients who met the International Society on Thrombosis and Haemostasis overt DIC criteria on day 1. The International Society on Thrombosis and Haemostasis scoring system missed a large number of nonsurvivors recognized by the JAAM scoring system.Conclusions: The JAAM DIC scoring system exhibits good prognostic value in predicting MODS and poor prognosis in patients with severe sepsis and can detect more patients requiring treatment. Conducting repeated daily JAAM scoring increases the ability to predict the patient's prognosis. [ABSTRACT FROM AUTHOR]

In this study, we investigated the correlations between biochemical and hematological test results obtained using microliter-scale fingertip blood samples collected with a newly developed blood collection device and those obtained using conventional venous blood. Eighty volunteer subjects were enrolled in this study. Blood samples were drawn from the fingertip of the ring finger by a single puncture, and 60-µL samples were promptly and accurately aspirated into a blood collection chip. Then the chip was tightly sealed in a chip container and was shaken to mix the contents without dispersion. For biochemical tests other than that for HbA1c, blood was collected without anticoagulant and centrifuged to obtain 15 µL of serum which was then diluted with 190 µL of physiological saline for the assay. For hematological tests and the test for HbA1c, the sample was assayed with blood collected using EDTA-2 K. Good correlations were obtained between the test results of the assay using fingertip blood and that using venous blood. The correlation coefficients were ≥0.97 for TG, T-CHO, HDL-C, LDL-C, GLU, ALT, γ-GTP, UA, BUN, and HbA1c and ≥0.95 for WBC, RBC, Hgb, and Hct. These results suggest that our microliter-scale blood testing system is comparable to assays using venous blood and may be useful as a rapid and simple test to determine basic clinical parameters that are close to the reference intervals.