Reactive Oxygen Species and Antioxidative Defense in Chronic Obstructive Pulmonary Disease

The respiratory system is continuously exposed to endogenous and exogenous oxidants. Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation of the airways, leading to the destruction of lung parenchyma (emphysema) and declining pulmonary function. It is increasingly obvious that reactive oxygen species (ROS) and reactive nitrogen species (RNS) contribute to the progression and amplification of the inflammatory responses related to this disease. First, we described the association between cigarette smoking, the most representative exogenous oxidant, and COPD and then presented the multiple pathophysiological aspects of ROS and antioxidative defense systems in the development and progression of COPD. Second, the relationship between nitric oxide system (endothelial) dysfunction and oxidative stress has been discussed. Third, we have provided data on the use of these biomarkers in the pathogenetic mechanisms involved in COPD and its progression and presented an overview of oxidative stress biomarkers having clinical applications in respiratory medicine, including those in exhaled breath, as per recent observations. Finally, we explained the findings of recent clinical and experimental studies evaluating the efficacy of antioxidative interventions for COPD. Future breakthroughs in antioxidative therapy may provide a promising therapeutic strategy for the prevention and treatment of COPD.</p

A case of axillary lymphadenitis caused by Mycobacterium intracellulare in an immunocompetent patient

Axillary lymphadenitis caused by non-tuberculous mycobacteria is rare and has been reported in immunocompromised hosts. Herein, we report the case of a 67-year-old man without immunodeficiency who developed right axillary lymphadenitis caused by Mycobacterium intracellulare and showed a small nodular shadow in the left pulmonary apex. Biopsy of the right axillary lymph node revealed several epithelioid granulomas, and the culture of the lymph node aspirate yielded Mycobacterium intracellulare. The lymph node lesion and left lung apex shadow resolved spontaneously after careful outpatient monitoring. This case suggests that axillary lymphadenitis could be caused by Mycobacterium intracellulare in an immunocompetent patient

Acute respiratory distress syndrome following infection of influenza A (H1N1) virus

A 28-year-old man with a history of mental retardation was admitted to our hospital because of dyspnea, cough and high fever. His SpO(2) level at room-environmental conditions was in the eighties, and his chest radiograph showed diffuse infiltrates in both lungs. He was diagnosed as suffering from influenza A by a rapid influenza virus antigen test. The echocardiogram showed no evidence of left cardiac failure; therefore, his symptoms were consistent with acute respiratory distress syndrome (ARDS). Oseltamivir was started, and antibiotics were also given because of the possibility of secondary bacterial infection. Due to respiratory failure and low blood pressure, which suggested septic shock, intensive treatments including mechanical ventilation were performed. Corticosteroid therapy was started for ARDS and sepsis, and these therapies improved his respiratory condition. Polymerase chain reaction of his pharyngeal swab revealed that he had influenza A (H1N1). This is the first case of ARDS following infection by influenza A (H1N1) virus in Japan

Protective Effects of Bisoprolol against Acute Exacerbation in Moderate-to-Severe Chronic Obstructive Pulmonary Disease

Although recent retrospective studies suggested that the use of β-blockers appears to help improve the mortality rate and decrease the rate of exacerbation in chronic obstructive pulmonary disease (COPD) patients with heart failure, the effects of β-blockers on COPD patients without heart failure have not been established. Based on previous reports, we have launched a multicenter, prospective, single-arm phase II study to evaluate the preventive effect of the cardioselective β-blocker bisoprolol in COPD exacerbation, in Japanese individuals with moderate-to-severe COPD who do not have heart failure but do have hypertension requiring the use of medication. The primary endpoint is the rate of mild-to-severe COPD exacerbation. The results of this study will clarify whether bisoprolol can prevent exacerbation in COPD patients without heart failure

The effects of inhaling hydrogen gas on macrophage polarization, fibrosis, and lung function in mice with bleomycin-induced lung injury

Background : Acute respiratory distress syndrome, which is caused by acute lung injury, is a destructive respiratory disorder caused by a systemic inflammatory response. Persistent inflammation results in irreversible alveolar fibrosis. Because hydrogen gas possesses anti-inflammatory properties, we hypothesized that daily repeated inhalation of hydrogen gas could suppress persistent lung inflammation by inducing functional changes in macrophages, and consequently inhibit lung fibrosis during late-phase lung injury. Methods : To test this hypothesis, lung injury was induced in mice by intratracheal administration of bleomycin (1.0 mg/kg). Mice were exposed to control gas (air) or hydrogen (3.2% in air) for 6 h every day for 7 or 21 days. Respiratory physiology, tissue pathology, markers of inflammation, and macrophage phenotypes were examined. Results : Mice with bleomycin-induced lung injury that received daily hydrogen therapy for 21 days (BH group) exhibited higher static compliance (0.056 mL/cmH(2)O, 95% CI 0.047-0.064) than mice with bleomycin-induced lung injury exposed only to air (BA group; 0.042 mL/cmH(2)O, 95% CI 0.031-0.053, p = 0.02) and lower static elastance (BH 18.8 cmH(2)O/mL, [95% CI 15.4-22.2] vs. BA 26.7 cmH(2)O/mL [95% CI 19.6-33.8], p = 0.02). When the mRNA levels of pro-inflammatory cytokines were examined 7 days after bleomycin administration, interleukin (IL)-6, IL-4 and IL-13 were significantly lower in the BH group than in the BA group. There were significantly fewer M2-biased macrophages in the alveolar interstitium of the BH group than in the BA group (3.1% [95% CI 1.6-4.5%] vs. 1.1% [95% CI 0.3-1.8%], p = 0.008). Conclusions The results suggest that hydrogen inhalation inhibits the deterioration of respiratory physiological function and alveolar fibrosis in this model of lung injury

Heerfordt’s Syndrome Associated with a High Fever and Elevation of TNF-α

Heerfordtʼs syndrome is a rare manifestation of sarcoidosis and is defined as a combination of facial palsy, parotid swelling, and uveitis, associated with a low-grade fever. We report a case of Heerfordtʼs syndrome presenting with a high fever and increased serum tumor necrosis factor alpha (TNF-α) levels. The patient had facial palsy, parotid swelling, uveitis, and swelling of the right supraclavicular and hilar lymph nodes. Corticosteroid therapy was initiated, and her symptoms soon resolved completely, in tandem with a decrease in TNF-α serum levels

Case report: Severe respiratory failure caused by licorice

Licorice, one of the most commonly used herbs, can cause hypokalemia, metabolic alkalosis, and apparent mineralocorticoid excess, also known as pseudoaldosteronism. Herein, we present a case of diaphragmatic dysfunction caused by licorice administration. An 80-year-old woman who had been taking dietary supplements and following a restricted diet for approximately 6 months was brought to the emergency department with impaired consciousness. Chronic respiratory acidosis was observed, and hypertension and hypokalemia became more prominent during hospitalization. History revealed that she was taking herbal medicines containing licorice. Based on the results of hormone tests, the patient was diagnosed with pseudoaldosteronism. Chest radiography and pulmonary function tests confirmed the clinical diagnosis of diaphragmatic dysfunction. The metabolic alkalosis resulting from licorice administration may have contributed to the impairment of the respiratory muscles. This case suggests that caution should be exercised when using licorice in patients with preexisting health or medical issues such as advanced age, malnutrition, and electrolyte imbalance

公共交通車内における協力行動と規範に関する国際比較

本研究では、我が国において、公共交通車内における「弱者に席を譲る」「騒ぐ自分の子どもを注意する（抑止する）」という二つの協力行動を促すための有効な方策を明らかにすることを目的とし、欧州と東アジアの6か国における協力行動と規範の関係性に着目した。協力行動と規範の主観的評価については国際アンケート調査から、「マナーに関するアナウンスや掲示物」等、協力行動に影響を及ぼすと考えられる環境要因については鉄道会社のWebサイトや現地調査から把握し、分析を行った。その結果、「優先席」で席を譲る行動を促すアナウンスは、優先席以外で席を譲る行動を阻害している可能性がある事、また「騒ぐ自分の子供を注意する」行動を促すためには、周囲の協力行動に対する認知「記述的規範」を高める事が効果的である可能性が示された。This study examine the effective measures to encourage cooperative behavior of the "yield one\u27s seat to the elderly or pregnant women" and "scold noisy one\u27s children" in the public transportation.In order to its purpose, we focused on relationship between cooperative behavior and norm in Europe and East Asia of six countries. We conducted international survey that measured subjective evaluation of cooperative behavior and norms, and obtain data about environmental factors (such as announcement and bulletin) that are considered to affect the cooperative behavior from the field survey and the web site of railway company. Analysis results showed that announcement for urging to "yield your seat" at priority seat interrupt its behavior at seat other than priority seat ,and that it is effective to raise descriptive norm (awareness of the surrounding behavior) for encouraging to "scold noisy one\u27s children"

Hemorrhage from varices in hepaticojejunostomy in the fifth and tenth year after surgery for hepatic hilar bile duct cancer: a case report

We report a case of a 64-year-old female patient who underwent a right lobectomy of the liver (including total resection of the caudate lobe), dissection of the group 2 lymph nodes, left hepaticojejunostomy (Roux-en-Y fashion), and reconstruction of the portal vein (end-to-end anastomosis between the main portal vein and the left portal branch) for treatment of hepatic hilar bile duct cancer in 1996. In 2001, the anastomotic site of the hepaticojejunostomy was dissected and re-anastomosed due to gastrointestinal bleeding caused by variceal rupture in the jejunal loop. In 2006, splenectomy was performed for recurrence of gastrointestinal bleeding due to another variceal rupture in the jejunal loop. Portal venography performed perioperatively showed a decrease in portal blood flow into the liver via the jejunal varices and an increase in portal blood flow into the liver via the left gastric vein. She had two jejunal variceal ruptures at five-year intervals after extrahepatic portal obstruction and underwent successful treatments

Loss of IL-33 enhances elastase-induced and cigarette smoke extract-induced emphysema in mice

Background IL-33, which is known to induce type 2 immune responses via group 2 innate lymphoid cells, has been reported to contribute to neutrophilic airway inflammation in chronic obstructive pulmonary disease. However, its role in the pathogenesis of emphysema remains unclear. Methods We determined the role of interleukin (IL)-33 in the development of emphysema using porcine pancreas elastase (PPE) and cigarette smoke extract (CSE) in mice. First, IL-33(-/-) mice and wild-type (WT) mice were given PPE intratracheally. The numbers of inflammatory cells, and the levels of cytokines and chemokines in the bronchoalveolar lavage (BAL) fluid and lung homogenates, were analyzed; quantitative morphometry of lung sections was also performed. Second, mice received CSE by intratracheal instillation. Quantitative morphometry of lung sections was then performed again. Results Intratracheal instillation of PPE induced emphysematous changes and increased IL-33 levels in the lungs. Compared to WT mice, IL-33(-/-) mice showed significantly greater PPE-induced emphysematous changes. No differences were observed between IL-33(-/-) and WT mice in the numbers of macrophages or neutrophils in BAL fluid. The levels of hepatocyte growth factor were lower in the BAL fluid of PPE-treated IL-33(-/-) mice than WT mice. IL-33(-/-) mice also showed significantly greater emphysematous changes in the lungs, compared to WT mice, following intratracheal instillation of CSE. Conclusion These observations suggest that loss of IL-33 promotes the development of emphysema and may be potentially harmful to patients with COPD