132 research outputs found

    Management Reality of Female Patients with COPD: A Multicenter Cross-Sectional CAP Study in Japan

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    Tasuku Yamamoto,1,2 Keiji Oishi,1 Syuichiro Ohata,1 Yoriyuki Murata,1 Yoshikazu Yamaji,1 Maki Asami-Noyama,1 Nobutaka Edakuni,1 Tomoyuki Kakugawa,3 Tsunahiko Hirano,1 Kazuto Matsunaga1 1Department of Respiratory Medicine and Infectious Disease, Graduate School of Medicine, Yamaguchi University, Ube, Yamaguchi, Japan; 2Department of Respiratory Medicine, National Hospital Organization Yamaguchi-Ube Medical Center, Ube, Yamaguchi, Japan; 3Department of Pulmonology and Gerontology, Graduate School of Medicine, Yamaguchi University, Ube, Yamaguchi, JapanCorrespondence: Keiji Oishi, Department of Respiratory Medicine and Infectious Disease, Graduate School of Medicine, Yamaguchi University, 1-1-1 Minami-kogushi, Ube, Yamaguchi, 755-8505, Japan, Tel +81 836 85 3123, Fax +81 836 85 3124, Email [email protected]: Reports from Europe and North America suggest that female chronic obstructive pulmonary disease (COPD) patients have a higher symptom burden and mortality than male patients. However, little is known about the management reality of female patients with COPD in Japan.Patients and Methods: We compared the clinical characteristics of female COPD patients with those of male using the cohort of the COPD Assessment in Practice study, which is a cross-sectional multicenter observational study.Results: Of the 1168 patients, 133 (11.4%) were female. A history of never smoking was higher in females than males (p< 0.01). Although there was no difference in age or forced expiratory volume in one second (FEV1) % predicted between the groups, modified medical research council dyspnea scale (mMRC) and number of frequent exacerbators were higher in females (mMRC≥ 2: p< 0.01; number of exacerbations≥ 2: p=0.011). The mean forced vital capacity and FEV1 values in females were lower than those in males (p< 0.0001 and p< 0.0001, respectively). Females were more likely to use long-term oxygen therapy and inhaled corticosteroids than males (p=0.016 and p< 0.01, respectively). The prevalence of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) groups B, C, D (ABCD GOLD 2017 classification), and E (ABE GOLD 2023 classification) was higher in females than in males.Conclusion: The disease burden of female patients with COPD is higher than that of male patients in Japan, suggesting the importance of interventions considering female-dominant features such as lower absolute FVC and FEV1, respiratory failure, and asthma-like conditions.Keywords: chronic obstructive pulmonary disease, exacerbation, subjective symptoms, gender difference, observational stud

    Differential effects of human neutrophil peptide-1 on growth factor and interleukin-8 production by human lung fibroblasts and epithelial cells.

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    alpha-Defensins, antimicrobial peptides produced mainly by neutrophils, have been reported to be associated with a wide variety of lung diseases, including idiopathic pulmonary fibrosis (IPF), cystic fibrosis (CF), and diffuse panbronchiolitis (DPB). In each disease, alpha-defensins are located in different areas, such as around the alveolar septa in IPF and around the airways in CF and DPB, suggesting that alpha-defensins play different roles. Meanwhile, growth factors are known to contribute to IPF, CF, and DPB. alpha-Defensins are known to induce interleukin (IL)-8 in airway epithelial cells, but the effects of alpha-defensins on the release of growth factors from various components in the lung have not been sufficiently investigated. In the present study, the in vitro effects of human neutrophil peptide (HNP)-1 (a subtype of alpha-defensin) on the expressions of IL-8 and growth factors in lung fibroblasts, bronchial epithelial cells, and alveolar epithelial cells were examined. HNP-1 mainly enhanced the expression of IL-8 in epithelial cells, whereas it enhanced transforming growth factor-beta and vascular endothelial growth factor expressions in lung fibroblasts. These results suggest that alpha-defensins play different roles in the pathogenesis of IPF, CF, and DPB according to the location in the lung where the alpha-defensins are mainly produced

    Continuous Regional Arterial Infusion with Fluorouracil and Octreotide Attenuates Severe Acute Pancreatitis in a Canine Model

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    Aim: To investigate the therapeutic effects of fluorouracil (5-Fu) and octreotide (Oct) continuous regional arterial infusion (CRAI,) alone or in combination, was administered in a canine model of severe acute pancreatitis (SAP). Materials and Methods: The animals were divided into five groups; group A (Sham), group B (SAP), group C (SAP and 5-Fu), group D (SAP and Oct), and group E (SAP and 5-Fu + Oct). Levels of amylase, alpha-tumor necrosis factor (TNF-alpha), blood urea nitrogen (BUN), creatinine, thromboxane B2 and 6-keto-prostaglandin F1 alpha were measured both before and after the induction of SAP. Pathologic examination of the pancreas and kidneys was performed after termination of the study. Results: Pathologic changes noted in the pancreas in SAP significantly improved following CRAI with either single or combined administration of 5-Fu and Oct, where combination therapy demonstrated the lowest injury score. All treatment groups had significantly lower levels of serum TNF-alpha and amylase activity (P<0.05), though only groups D and E had a lower BUN level as compared to group B. The plasma thromboxane B-2 level increased in SAP, but the ratio of thromboxane B-2/6-keto-prostaglandin F-1 alpha decreased in the treatment groups, with the combination therapy (group E) demonstrating the lowest ratio as compared to the other 3 experimental groups (P<0.05). Conclusions: The findings in the present study demonstrate an attenuation of SAP in a canine model following CRAI administration with 5-Fu or Oct, alone or in combination

    Evaluation of 18F-2-deoxy-2-fluoro-glucose positron emission tomography for gastric cancer screening in asymptomatic individuals undergoing endoscopy

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    18F-2-deoxy-2-fluoro-glucose Positron Emission Tomography (FDG-PET) has been recently proposed as a promising cancer-screening test. However, the validity of FDG-PET in cancer screening has not been evaluated. We investigated the sensitivity of FDG-PET compared with upper gastric endoscopy in gastric cancer screening for asymptomatic individuals. A total of 2861 consecutive subjects (1600 men and 1261 women) who were asymptomatic and who underwent both FDG-PET and upper gastrointestinal endoscopy between 1 February 2004 and 31 January 2005 were included in this study. Both endoscopists and a radiologist were unaware of the results of the other diagnostic tests. The FDG-PET images were examined using criteria determined by the pattern of FDG accumulation. Sensitivity and specificity of FDG-PET were calculated compared with endoscopic diagnosis as the gold standard. Among 2861 subjects enrolled in the study, there were 20 subjects with gastric cancer, of whom 18 were T1 in depth of cancer invasion. Positive FDG-PET results were obtained only in 2 of the 20 cancer subjects. The calculated sensitivity and specificity for overall gastric cancers were 10.0% (95% confidence interval (CI): 1.2–31.7%) and 99.2% (95% CI: 98.8–99.5%), respectively. 18F-2-deoxy-2-fluoro-glucose Positron Emission Tomography was poorly sensitive for detection of gastric cancer in the early stages

    Characterization of Oseltamivir-Resistant 2009 H1N1 Pandemic Influenza A Viruses

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    Influenza viruses resistant to antiviral drugs emerge frequently. Not surprisingly, the widespread treatment in many countries of patients infected with 2009 pandemic influenza A (H1N1) viruses with the neuraminidase (NA) inhibitors oseltamivir and zanamivir has led to the emergence of pandemic strains resistant to these drugs. Sporadic cases of pandemic influenza have been associated with mutant viruses possessing a histidine-to-tyrosine substitution at position 274 (H274Y) in the NA, a mutation known to be responsible for oseltamivir resistance. Here, we characterized in vitro and in vivo properties of two pairs of oseltaimivir-sensitive and -resistant (possessing the NA H274Y substitution) 2009 H1N1 pandemic viruses isolated in different parts of the world. An in vitro NA inhibition assay confirmed that the NA H274Y substitution confers oseltamivir resistance to 2009 H1N1 pandemic viruses. In mouse lungs, we found no significant difference in replication between oseltamivir-sensitive and -resistant viruses. In the lungs of mice treated with oseltamivir or even zanamivir, 2009 H1N1 pandemic viruses with the NA H274Y substitution replicated efficiently. Pathological analysis revealed that the pathogenicities of the oseltamivir-resistant viruses were comparable to those of their oseltamivir-sensitive counterparts in ferrets. Further, the oseltamivir-resistant viruses transmitted between ferrets as efficiently as their oseltamivir-sensitive counterparts. Collectively, these data indicate that oseltamivir-resistant 2009 H1N1 pandemic viruses with the NA H274Y substitution were comparable to their oseltamivir-sensitive counterparts in their pathogenicity and transmissibility in animal models. Our findings highlight the possibility that NA H274Y-possessing oseltamivir-resistant 2009 H1N1 pandemic viruses could supersede oseltamivir-sensitive viruses, as occurred with seasonal H1N1 viruses

    In Vitro Effects of Pirfenidone on Cardiac Fibroblasts: Proliferation, Myofibroblast Differentiation, Migration and Cytokine Secretion

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    Cardiac fibroblasts (CFs) are the primary cell type responsible for cardiac fibrosis during pathological myocardial remodeling. Several studies have illustrated that pirfenidone (5-methyl-1-phenyl-2-[1H]-pyridone) attenuates cardiac fibrosis in different animal models. However, the effects of pirfenidone on cardiac fibroblast behavior have not been examined. In this study, we investigated whether pirfenidone directly modulates cardiac fibroblast behavior that is important in myocardial remodeling such as proliferation, myofibroblast differentiation, migration and cytokine secretion. Fibroblasts were isolated from neonatal rat hearts and bioassays were performed to determine the effects of pirfenidone on fibroblast function. We demonstrated that treatment of CFs with pirfenidone resulted in decreased proliferation, and attenuated fibroblast α-smooth muscle actin expression and collagen contractility. Boyden chamber assay illustrated that pirfenidone inhibited fibroblast migration ability, probably by decreasing the ratio of matrix metalloproteinase-9 to tissue inhibitor of metalloproteinase-1. Furthermore, pirfenidone attenuated the synthesis and secretion of transforming growth factor-β1 but elevated that of interleukin-10. These direct and pleiotropic effects of pirfenidone on cardiac fibroblasts point to its potential use in the treatment of adverse myocardial remodeling

    Carboxylic ester hydrolases from hyperthermophiles

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    Carboxylic ester hydrolyzing enzymes constitute a large group of enzymes that are able to catalyze the hydrolysis, synthesis or transesterification of an ester bond. They can be found in all three domains of life, including the group of hyperthermophilic bacteria and archaea. Esterases from the latter group often exhibit a high intrinsic stability, which makes them of interest them for various biotechnological applications. In this review, we aim to give an overview of all characterized carboxylic ester hydrolases from hyperthermophilic microorganisms and provide details on their substrate specificity, kinetics, optimal catalytic conditions, and stability. Approaches for the discovery of new carboxylic ester hydrolases are described. Special attention is given to the currently characterized hyperthermophilic enzymes with respect to their biochemical properties, 3D structure, and classification
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