Effects of CHF6297, a potent and selective p38{alpha} MAPK inhibitor, in murine models of steroid resistant lung inflammation

We report here the effect of CHF6297, a potent and selective inhaled p38MAPK inhibitor, in three murine models of steroid-resistant lung inflammation. In mice exposed to tobacco smoke (TS), CHF6297, administered intranasally (i.n.) b.i.d. for 4 days at 0.03 or 0.3mg/kg, dose-dependently inhibited the corticosteroid-resistant TS-induced neutrophil influx in bronchoalveolar lavage (BAL) reaching a % of inhibition of 29.7±15.3 (n.s.) and 62±8.4 (p
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Airway Pharmacology and Treatment Source Type: research

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E-cigarette users are 29 per cent more likely to suffer emphysema and asthma than smokers, a new study reveals. Their risk of lung disease is 3.3 times more likely than smokers at 2.5.
Source: the Mail online | Health - Category: Consumer Health News Source Type: news
Publication date: January 2020Source: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, Volume 129, Issue 1Author(s): Kevin MaObjectivesSjögren syndrome (SS) is an autoimmune disease with oral manifestations. SS may result in hormonal imbalance and immune dysfunction, and its occurrence could be related to comorbidities, including endometriosis. The prevalence rate of endometriosis in women with chronic pelvic pain is greater than 33%, and in SS patients, the prevalence rate is 6.3%. Given the limited number of available studies, we sought to determine whether patients with endometriosis have a higher ri...
Source: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology - Category: ENT & OMF Source Type: research
ConclusionsAdjunctive procedures that can facilitate a decrease in the cumulative dosages of corticosteroids and immunosuppressants have great value in the management of PV. CO2 laser vaporization is a safe procedure with minimal morbidity and no long-term side effects and should be considered as an adjunctive treatment option for management of recalcitrant lesions in patients with oral PV.
Source: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology - Category: ENT & OMF Source Type: research
Plasma cell cheilitis (PCC) is an unusual benign plasma cell proliferative disease of an unknown etiology that clinically presents as erythematous-violaceous plaques, ulcerations, or eruptions often affecting the lower lip. PCC is known to respond poorly to corticosteroid treatment. A 43-year-old male presented with multiple painful hemorrhagic crusts on the lower lip that had developed over 1 month. An incisional biopsy was performed and microscopy showed a bandlike inflammatory cell infiltration composed mainly of plasma cells in the connective tissue.
Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics - Category: ENT & OMF Authors: Source Type: research
A white 47-year-old woman complained about a lesion in gingiva present for 2 months. Her medical history included systemic erythematosus lupus with previous use of corticosteroids. The intraoral examination revealed an irregularly shaped gingival ulcer in the upper posterior region. Radiographic examination showed no significant abnormalities. According to clinical and radiographic features, malignant or infectious lesions were hypothesized. After an incisional biopsy, microscopic evaluation revealed an intense mixed inflammatory infiltrate with the presence of Reed-Sternberg –like cells of Hodgkin lymphoma.
Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics - Category: ENT & OMF Authors: Source Type: research
Vascular injuries in the oral cavity cause anesthetic and functional problems, and a high risk of severe hemorrhages in simple surgical treatments; therapy with copper wires and corticosteroids generates local coagulation and fibrosis and are effective for an uncomplicated resection. Through a series of cases, clinical and anatomopathologic characteristics of the combined sclerotherapy effects are described, as an alternative for the treatment of vascular malformations performed on 7 patients, using intralesional corticoid (0.2 mL/cm2) for 2 or 3 weeks, followed by a cerclage with copper wires, for 1 week, until color chan...
Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics - Category: ENT & OMF Authors: Source Type: research
Conclusions: In this cohort of elderly patients, those with cardiac failure and COPD or asthma were more prone to being submitted to NIV or IMV. RSV infection was associated with higher mortality independently of significant co-morbidities.
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Respiratory infections Source Type: research
We report here the pharmacological characterization of the tool compound CHD39359, a PI3K selective inhibitor, and, in particular, its activity in a murine model of asthma exacerbation induced by IAV. CHD39359 inhibited PI3K enzyme and Akt phosphorylation in THP-1 monocytes with nanomolar potency (IC50=0.79nM and IC50=0.50nM, respectively) and showed>500-fold selectivity against PI3K, PI3Kβ and PI3Kα. CHD39359 inhibited mouse neutrophil chemotaxis with IC50=0.32nM and reduced oxidative burst with IC50=4.2nM in neutrophils obtained from COPD patients. In a corticosteroid-insensitive model of exacerbation induc...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Airway Cell Biology and Immunopathology Source Type: research
Steroids are a mainstay of treatment for chronic respiratory diseases, such as asthma and COPD. Intriguingly, data emerging from the 2009 flu pandemic suggests that corticosteroid may have explained the association of asthma with less severe outcomes in patients hospitalised with influenza1. Since macrophages are a major target of influenza infection, the aim of the present study was to analyse the effect of corticosteroids on macrophage infection by influenza.Human monocyte-derived macrophages (MDM) were exposed to H3N2 X31 influenza virus or UV-irradiated virus (UVX31) for 24 h in the presence or absence of 10–7 M ...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: 10.1 Respiratory Infections Source Type: research
Conclusion: Our data suggest that carbocisteine might protect against FluA replication in vivo.
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: 5.1 Airway Pharmacology and Treatment Source Type: research
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