Mesothelioma in Situ of the Spermatic Cord Arising from a Patent Processus Vaginalis: A Case Report.

Mesothelioma is an aggressive tumor originating from mesothelial cells. Mesothelioma of the spermatic cord is a very rare disease, and the most common presentation of this disease is that of aggressive mesothelioma with no description of mesothelioma in situ. We report an extremely rare case of mesothelioma in situ of the spermatic cord arising from a patent processus vaginalis. To our best knowledge, this is the first report of this finding. The identification of a patent processus vaginalis and investigation of single-layered atypical mesothelial cells led to the final diagnosis.

Changes in forced expiratory volume in 1 second over time in patients with controlled asthma at baseline.

BACKGROUND: A predominant feature of asthma is an accelerated rate of decline in forced expiratory volume in 1 s (FEV1), but data on the variability and factors associated with this change in patients with controlled asthma are largely unknown. METHODS: 140 patients with controlled asthma were enrolled based on the Global Initiative for Asthma guidelines. We examined the data of a prospective analysis of the association between asthma control and change in FEV1 over time. RESULTS: A 3-year follow-up assessment was completed in 128 patients. The mean rate of change in FEV1 was a decline of 22.2 mL yr(-1), with significant variation in the levels of change. The between patient standard deviation for the rate of decline was 34.1 mL yr(-1). We next classified the subjects of less than the 25th percentile as rapid decliners, and greater than the 25th percentile as non-rapid decliners. The decrease in the Asthma Control Test score over a 3-year period was higher for rapid decliners than that for non-rapid decliners (p < 0.001). The rapid decliner was more likely to be older, to have higher levels of FeNO, and to have had severe exacerbations during the study. Patients with severe exacerbations had a greater annual decline in FEV1 compared to patients with no exacerbations (-13.6 vs. -53.2 mL yr(-1), p < 0.0001). CONCLUSIONS: Among patients with controlled asthma at baseline, the rate of change in FEV1 is highly variable. Severe exacerbations are strongly associated with a rapid loss of lung function.

TLR3 activation augments matrix metalloproteinase production through reactive nitrogen species generation in human lung fibroblasts.

Viral infection often triggers asthma exacerbation and contributes to airway remodeling. Cell signaling in viral infection is mainly mediated through TLR3. Many mediators are involved in airway remodeling, but matrix metalloproteinases (MMPs) are key players in this process in asthma. However, the role of TLR3 activation in production of MMPs is unknown. In this study, we examined the effects of polyinosinic-polycytidylic acid [poly(I:C)], a ligand for TLR3, on production of MMPs in human lung fibroblasts, with a focus on nitrosative stress in TLR3 modulation of MMP production. After lung fibroblasts were treated with poly(I:C), production of MMP-1, -2, and -9 and inducible NO synthase (iNOS) was assessed. The roles of NF-κB and IFN regulatory factor-3 (IRF-3) in the poly(I:C)-mediated production of MMPs and the responsiveness to poly(I:C) of normal lung fibroblasts and asthmatic lung fibroblasts were also investigated. Poly(I:C) augmented production of MMPs and iNOS in fibroblasts, and an iNOS inhibitor diminished this production of MMPs. Poly(I:C) stimulated translocation of NF-κB and IRF-3 into the nucleus in fibroblasts and inhibition of NF-κB or IRF-3 abrogated the poly(I:C)-induced increase in both iNOS expression and release of MMPs. Poly(I:C)-induced production of iNOS and MMPs was greater in asthmatic fibroblasts than in normal fibroblasts. We conclude that viral infection may induce nitrosative stress and subsequent MMP production via NF-κB- and IRF-3-dependent pathways, thus potentiating viral-induced airway remodeling in asthmatic airways.

Ongoing allergic rhinitis impairs asthma control by enhancing the lower airway inflammation.

BACKGROUND: The relationship between allergic rhinitis and asthma is well accepted; however, little is known about the mechanism that underlies the interactions between the upper and lower airways. OBJECTIVE: To investigate the symptomatic and inflammatory linkages between allergic rhinitis and asthma in patients with atopy. METHODS: We enrolled 520 patients with asthma who were taking inhaled corticosteroids, and examined them by using the Asthma Control Questionnaire, spirometry, exhaled nitric oxide fraction (FENO), visual analog scale for nasal symptoms, allergic rhinitis questionnaire, and serum specific IgE (study 1). The symptomatic and inflammatory marker responses to nasal corticosteroids in patients with incompletely controlled asthma (Asthma Control Questionnaire > 0.75) and moderate-to-severe persistent allergic rhinitis were also observed (study 2). RESULTS: A total of 348 patients (66.9%) had atopy and allergic rhinitis. There was a striking difference in the proportion of patients with incomplete asthma control, depending on the presence as well as the activity of rhinitis (no rhinitis, 11.0%; mild intermittent, 20.4%; moderate-to-severe intermittent, 44.6%; mild persistent, 53.1%; moderate-to-severe persistent, 65.7%). The FENO levels were increased with the activity of rhinitis, and the nasal visual analog scale was positively correlated with the FENO levels (r = 0.31; P < .0001). The additive treatment with nasal corticosteroids improved the nasal visual analog scale, Asthma Control Questionnaire, and FENO levels, and the changes in these variables were correlated with each other in all parameters (all P < .001). CONCLUSION: This observational study of patients with atopy indicates that the ongoing allergic rhinitis is related to worsening of asthma by enhancing the lower airway inflammation.

25-hydroxycholesterol promotes fibroblast-mediated tissue remodeling through NF-κB dependent pathway.

Abnormal structural alterations termed remodeling, including fibrosis and alveolar wall destruction, are important features of the pathophysiology of chronic airway diseases such as chronic obstructive pulmonary disease (COPD) and asthma. 25-hydroxycholesterol (25-HC) is enzymatically produced by cholesterol 25-hydorxylase (CH25H) in macrophages and is reported to be involved in the formation of arteriosclerosis. We previously demonstrated that the expression of CH25H and production of 25HC were increased in the lungs of COPD. However, the role of 25-HC in lung tissue remodeling is unknown. In this study, we investigated the effect of 25-HC on fibroblast-mediated tissue remodeling using human fetal lung fibroblasts (HFL-1) in vitro. 25-HC significantly augmented α-smooth muscle actin (SMA) (P<0.001) and collagen I (P<0.001) expression in HFL-1. 25-HC also significantly enhanced the release and activation of matrix metallaoproteinase (MMP)-2 (P<0.001) and MMP-9 (P<0.001) without any significant effect on the production of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2. 25-HC stimulated transforming growth factor (TGF)-ß1 production (P<0.01) and a neutralizing anti-TGF-ß antibody restored these 25-HC-augmented pro-fibrotic responses. 25-HC significantly promoted the translocation of nuclear factor (NF)-κB p65 into the nuclei (P<0.01), but not phospholylated-c-jun, a complex of activator protein-1. Pharmacological inhibition of NF-κB restored the 25-HC-augmented pro-fibrotic responses and TGF-ß1 release. These results suggest that 25-HC could contribute to fibroblast-mediated lung tissue remodeling by promoting myofibroblast differentiation and the excessive release of extracellular matrix protein and MMPs via an NF-κB-TGF-ß dependent pathway.