Yoshichika Sando

Pioglitazone, a Peroxisome Proliferator-Activated Receptor Gamma Ligand, Suppresses Bleomycin-Induced Acute Lung Injury and Fibrosis

Background: Peroxisome proliferator-activated receptor-γ (PPARγ) ligands have been shown to possess potent anti-inflammatory actions. Idiopathic interstitial pneumonia is defined as a specific form of chronic fibrosing lung disease characterized by progressive fibrosis which leads to deterioration and destruction of the lungs. Objective: To investigate whether the PPARγ ligand pioglitazone (PGZ) inhibited bleomycin (BLM)-induced acute lung injury and subsequent fibrosis. Methods: BLM was administered intratracheally to Wistar rats which were then treated with PGZ. Rat alveolar macrophages were stimulated with BLM for 6 h with or without PGZ pretreatment for 18 h. MRC-5 cells (human lung fibroblasts) were treated with PGZ for 18 h. After the treatment, the cells were stimulated with transforming growth factor- β (TGF-β) for 6 h. Results: PGZ inhibited BLM-induced acute lung injury and subsequent lung fibrosis when it was administered from day –7. PGZ treatment suppressed the accumulation of inflammatory cells in lungs and the concentration of tumor necrosis factor-α (TNF-α) in bronchoalveolar lavage fluid on day 3. PGZ also inhibited BLM-induced TNF-α production in alveolar macrophages. Furthermore, PGZ inhibited fibrotic changes and an increase in hydroxyproline content in lungs after instillation of BLM, even when PGZ was administered in the period from day 7 to day 28. Northern blot analyses revealed that PGZ inhibited TGF-β-induced procollagen I and connective tissue growth factor (CTGF) expression in MRC-5 cells. Conclusion: These results suggest that activation of PPARγ ameliorates BLM-induced acute inflammatory responses and fibrotic changes at least partly through suppression of TNF-α, procollagen I and CTGF expression. Beneficial effects of this PPARγ ligand on inflammatory and fibrotic processes open new perspectives for a potential role of PPARγ as a molecular target in fibroproliferative lung diseases.

N Epsilon-(Hexanoyl) Lysine, A New Oxidative Stress Marker, is Increased in Metabolic Syndrome, but not in Obstructive Sleep Apnea

Background:It is well known that oxidative stress is induced by metabolic syndrome (MetS), leading to cardiovascular diseases. On the other hand, obstructive sleep apnea syndrome (OSAS) is frequently complicated with MetS, and OSAS is also considered to induce oxidative stress. Thus, we examined the plasma and urine markers of oxidative stress and antioxidant status in patients with OSAS with or without MetS. Methods:Sixty-nine Japanese men suspected of having OSAS were recruited. We divided all patients into 3 groups: nonobese patients, obese patients without MetS, and patients with MetS. Oxidative stress markers, plasma and urine 8-hydroxydeoxyguanosine (8-OHdG) and plasma N epsilon-(hexanoyl) lysine (HEL), and an antioxidant status marker, plasma total antioxidant status, were measured by enzyme-linked immunosorbent assay. Results:The plasma HEL level was significantly increased in patients with MetS, whereas neither plasma and urine 8-OHdG levels nor plasma total antioxidant status level was different in patients with MetS. Furthermore, the plasma HEL level was significantly and positively correlated with fasting plasma glucose, serum insulin, and homeostasis model assessment-insulin resistance index in all subjects. Conclusions:The oxidative stress is strongly associated with the presence of MetS but not related to the presence or severity of OSAS. Furthermore, we demonstrated that the plasma concentration of HEL is a more sensitive biomarker of oxidative stress in patients with MetS than the plasma and urine levels of 8-OHdG.

Pleural amyloidosis in a patient with intractable pleural effusion and multiple myeloma

Pleural involvement of systemic amyloidosis has been rarely reported. We report a case with multiple myeloma presenting an intractable right pleural effusion, in which pleural amyloidosis was diagnosed through pleural biopsy using a Cope needle. The diagnosis of pleural amyloidosis is important, because its refractory pleural effusion should be treated with pleurodesis. Since closed pleural biopsy using a Cope needle is much less invasive than thoracoscopy, the former should be attempted first whenever pleural amyloidosis is suspected.

Indomethacin induced bulky lymphadenopathy and eosinophilic pneumonia.

Abstract: Indomethacin is one of the most popular non‐steroidal anti‐inflammatory drugs (NSAID). Although NSAID occasionally provoke bronchospasm and hypersensitivity pneumonia, they seldom cause lymphadenopathy. This is the first report in which NSAID induced both eosinophilic pneumonia and bulky intrathoracic lymphadenopathy simultaneously. A 76‐year‐old Japanese man experienced high fever and dyspnoea after using an indomethacin suppository. Computed tomography scan of his chest revealed massive mediastinal and hilar lymphadenopathy along with diffuse infiltration in both lungs. He was diagnosed to have eosinophilic pneumonia because of eosinophilia in his peripheral blood and bronchoalveolar lavage fluid (BALF). Without using glucocorticoids, the pulmonary infiltration and lymphadenopathy subsided spontaneously. As the blastoid transformation test using the lymphocytes in his BALF was positive to indomethacin, we judged that both his eosinophilic pneumonia and mediastinal lymphadenopathy were due to a hypersensitivity reaction to indomethacin. An allergic reaction to NSAID should be considered as a rare cause of mediastinal lymphadenopathy.

Pulmonary nocardiosis during immunosuppressive therapy for idiopathic pulmonary fibrosis

Nocardiosis is a subacute or chronic suppurative infection caused by Nocardia species. Although it is more common in immunocompromised hosts, idiopathic pulmonary fibrosis (IPF) has not been recognized as a predisposing factor for nocardial infection. We report a case of IPF, in which pulmonary nocardiosis developed during treatment with prednisolone and cyclophosphamide. The risk of pulmonary nocardiosis may be increased in cases of IPF on immunosuppressive therapy. Since IPF often accompanies lung carcinoma, it is important to correctly differentiate nocardiosis from carcinoma.

Bilateral Empyema Mimicking Cardiac Tamponade

Accessible online at: www.karger.com/journals/res A 68-year-old lean female was admitted because of severe dyspnea and fainting. On admission, she was pale and sometimes coughed up purulent sputum. Her vital signs were as follows: blood pressure 99/66 mm Hg, pulse 110/min, body temperature 38.2°C. The jugular veins were dilated, but no edema was present. Chest radiograph revealed a markedly enlarged ‘cardiac’ shadow and a patchy infiltration (fig. 1). An electrocardiogram showed sinus tachycardia and flattened T waves in the lateral chest leads. Laboratory investigations revealed leukocytosis, positive inflammatory reactions, mild anemia, elevation of serum transaminases, and mild hypoxemia, but serum autoantibodies including antinuclear antibody, rheumatoid factor, SS-A and SS-B were negative. Ultrasound echographic study disclosed liver congestion and retention of a large amount of fluid around the heart. From these findings, she was initially diagnosed to have cardiac tamponade and pneumonia. Plain computed tomography (CT) of the chest demonstrated plenty of fluid surrounding the heart (fig. 2A). However, after contrast enhancement CT clearly depicted the pericardium inside the effusion, in addition to the anterior conjugation line of pleurae (fig. 2B). The fluid space consisted of bilateral thoracic cavities. The effusion obtained by thoracentesis was chocolate colored, and contained 8,000 cells/mm3, most of which were polymorphonuclear neutrophils. Pseudomonas aeruginosa was cultured from both sputum and left pleural effusion. Another CT after clinical improvement following treatment with intravenous imipenem and chest drainage showed focal pleural thickening and cylindrical bronchiectasis. We proposed that pneumonia had developed from chronic Pseudomonas infection in the bronchiectatic lesions, leading to unilateral empyema, which penetrated into the other pleural cavity through the anterior conjunction. The fluid that localized around the heart compressed the pericardium owing to the pleural adhesion, and induced fainting, hypotension and liver congestion.