肺高血圧症に対するトロンボキサン合成阻害作用をもった新規長期作用型プロスタサイクリンアゴニストの経口投与

BACKGROUND: Continuous administration of prostacyclin has improved the survival of patients with pulmonary arterial hypertension (PAH). However, this treatment has some problems, including its short duration of activity and difficult delivery. Therefore, we developed ONO-1301, an orally active, long-acting prostacyclin agonist with thromboxane synthase inhibitory activity. METHODS AND RESULTS: We investigated whether oral administration of ONO-1301 can both prevent and reverse monocrotaline (MCT)-induced PAH in rats. Rats were randomly assigned to receive repeated oral administration of ONO-1301 twice daily beginning either 1 or 8 days after subcutaneous injection of MCT. A control group received oral saline, and a sham group received a subcutaneous injection of saline instead of MCT. MCT-treated controls developed significant pulmonary hypertension. Treatment with ONO-1301 from day 1 or 8 significantly attenuated the increases in right ventricular systolic pressure and the increase in medial wall thickness of pulmonary arterioles. Kaplan-Meier survival curves demonstrated that the effect of ONO-1301 was equivalent to that of an endothelin receptor antagonist and a phosphodiesterase-5 inhibitor. A single oral dose of ONO-1301 increased plasma cAMP levels for up to 6h. Treatment with ONO-1301 significantly decreased urinary 11-dehydro-thromboxane B2 and increased the plasma hepatocyte growth factor concentration. CONCLUSIONS: Oral administration of ONO-1301 ameliorated PAH in rats, an effect that may occur through cAMP and hepatocyte growth factor.博士（医学）・乙1326号・平成26年3月17日日本循環器学会の許諾を得て登録（2014年6月6日付）ジャーナル公式サイト（日本循環器学会HP内）：https://www.j-circ.or.jp/journal/公開サイト（J-STAGE）：https://www.jstage.jst.go.jp/browse/circj

Serum markers in interstitial pneumonia with and without Pneumocystis jirovecii colonization: a prospective study

<p>Abstract</p> <p>Background</p> <p>In patients with chronic respiratory disease, <it>Pneumocystis jirovecii (P. jirovecii) </it>colonization is observed, and may influence disease progression and systemic inflammation. <it>Pneumocystis </it>pneumonia causes interstitial changes, so making a diagnosis of PCP in patients who have interstitial pneumonia (IP) with <it>P. jirovecii </it>colonization is sometimes difficult based on radiography.</p> <p>Methods</p> <p>This study investigated the prevalence of <it>P. jirovecii </it>colonization in IP patients and assessed pulmonary injury due to <it>P. jirovecii </it>colonization by measurement of serum markers (KL-6, SP-A, SP-D, and (1→3) β-D-glucan (β-D-glucan)) and the peripheral lymphocyte counts, prospectively. A total of 75 patients with idiopathic pulmonary fibrosis (n = 29), collagen vascular-related interstitial pneumonia (n = 19), chronic bronchitis or pneumonia (n = 20), and <it>Pneumocystis </it>pneumonia (n = 7) were enrolled in this prospective study. <it>P. jirovecii </it>DNA was detected in sputum samples, while serum markers and the lymphocyte count were measured in the peripheral blood.</p> <p>Results</p> <p>IP patients (idiopathic pulmonary fibrosis and collagen vascular-related IP) who received oral corticosteroids had a high prevalence of <it>P. jirovecii </it>colonization (23.3%). In IP patients, oral corticosteroid therapy was a significant risk factor for <it>P. jirovecii </it>colonization (<it>P </it>< 0.05). Serum markers did not show differences between IP patients with and without <it>P. jirovecii </it>colonization. The β-D-glucan level and lymphocyte count differed between patients with <it>Pneumocystis </it>pneumonia or <it>P. jirovecii </it>colonization.</p> <p>Conclusion</p> <p>Serum levels of KL-6, SP-A, SP-D, and β-D-glucan were not useful for detecting <it>P. jirovecii </it>colonization in IP patients. However, the serum β-D-glucan level and lymphocyte count were useful for distinguishing <it>P. jirovecii </it>colonization from <it>pneumocystis </it>pneumonia in IP patients.</p