Long-term macrolide antibiotics in asthma therapy

Macrolide antibiotics drew worldwide attention when their use was dramatically successful in the treatment of diffuse panbronchiolitis in 1980s. The success was attributed to their immunomodulatory effects, rather than their antimicrobial properties. Since then, studies have shown that macrolides exert their immunomodulatory effects through several mechanisms, including suppression of proinflammatory cytokines, promoting apoptosis of inflammatory cells, improving phagocytic function, ameliorating airway hypersecretion, and inhibiting production of reactive oxygen species. Macrolides have also been studied in the treatment of asthma. This review highlights the role of macrolides in the treatment of asthma, presenting an overview of the main clinical trials. Despite favourable preclinical data and reports of anecdotal successes, the results of clinical trials are conflicting. This may be due to the heterogeneous nature of asthma. Further studies are needed to identify particular subgroup of asthma that will respond to macrolides

demerge

DESHIMA merge code for observed datasetsIf you use this software, please cite it as below

demerge

Merge DESHIMA datasets observed with ASTEIf you use this software, please cite it as below

demerge

Merge DESHIMA datasets observed with ASTEIf you use this software, please cite it as below

demerge

Merge DESHIMA datasets observed with ASTEIf you use this software, please cite it as below

Epipericardial fat necrosis: A case report

Epipericardial fat necrosis is a rare cause of acute pleuritic chest pain and is a benign and self-limiting condition. It is important to distinguish epipericardial fat necrosis from other diseases that cause acute chest pain, such as acute myocardial infarction, pulmonary embolism, and acute pericarditis, because conservative treatment is recommended for epipericardial fat necrosis. This report presents the case of a 25-year-old man with severe pleuritic chest pain located on the left anterior side that was associated with dyspnea. Electrocardiogram and laboratory data were normal, except for a slight elevation of C-reactive protein level. Contrast-enhanced chest computed tomography revealed a fatty ovoid lesion surrounded by a thick rim on the left side of the pericardial fat. Fat stranding was observed both inside and adjacent to the fatty ovoid lesion. A slight contrast enhancement of the thick rim and a slight linear enhancement inside the lesion were observed. Furthermore, a small amount of left pleural effusion was observed. The patient was diagnosed with epipericardial fat necrosis and treated with analgesics, and the symptoms improved 1 week after the emergency department visit. Radiologists should be familiar with epipericardial fat necrosis to prevent overlooking and misdiagnosing the condition

Involvement of Parkin‐mediated mitophagy in the pathogenesis of chronic obstructive pulmonary disease‐related sarcopenia

BackgroundSarcopenia is characterized by the loss of skeletal muscle mass and strength and is associated with poor prognosis in patients with chronic obstructive pulmonary disease (COPD). Cigarette smoke (CS) exposure, a major cause for COPD, induces mitochondrial damage, which has been implicated in sarcopenia pathogenesis. The current study sought to examine the involvement of insufficient Parkin-mediated mitophagy, a mitochondrion-selective autophagy, in the mechanisms by which dysfunctional mitochondria accumulate with excessive reactive oxygen species (ROS) production in the development of COPD-related sarcopenia.MethodsThe involvement of Parkin-mediated mitophagy was examined using in vitro models of myotube formation, in vivo CS-exposure model using Parkin-/- mice, and human muscle samples from patients with COPD-related sarcopenia.ResultsCigarette smoke extract (CSE) induced myotube atrophy with concomitant 30% reduction in Parkin expression levels (P < 0.05). Parkin-mediated mitophagy regulated myotube atrophy by modulating mitochondrial damage and mitochondrial ROS production. Increased mitochondrial ROS was responsible for myotube atrophy by activating Muscle Ring Finger 1 (MuRF-1)-mediated myosin heavy chain (MHC) degradation. Parkin-/- mice with prolonged CS exposure showed enhanced limb muscle atrophy with a 31.7% reduction in limb muscle weights (P < 0.01) and 2.3 times greater MuRF-1 expression (P < 0.01) compared with wild-type mice with concomitant accumulation of damaged mitochondria and oxidative modifications in 4HNE expression. Patients with COPD-related sarcopenia exhibited significantly reduced Parkin but increased MuRF-1 protein levels (35% lower and 2.5 times greater protein levels compared with control patients, P < 0.01 and P < 0.05, respectively) and damaged mitochondria accumulation demonstrated in muscles. Electric pulse stimulation-induced muscle contraction prevented CSE-induced MHC reduction by maintaining Parkin levels in myotubes.ConclusionsTaken together, COPD-related sarcopenia can be attributed to insufficient Parkin-mediated mitophagy and increased mitochondrial ROS causing enhanced muscle atrophy through MuRF-1 activation, which may be at least partly preventable through optimal physical exercise