Dexamethasone and RU24858 induce survival and growth factor receptor bound protein 2, leukotriene B4 receptor 1 and annexin-1 expression in primary human neutrophils

Glucocorticoids are widely used anti-inflammatory medication in diseases like asthma and chronic obstructive pulmonary disease. Glucocorticoids can either activate (transactivation) or inhibit (transrepression) transcription. RU24858 was introduced as a dissociated glucocorticoid and it has been reported to transrepress but not to transactivate. The aim of this study was to compare the effects of RU24858 and dexamethasone in human neutrophils. RU24858 delayed spontaneous neutrophil apoptosis and further enhanced GM-CSF- induced neutrophil survival to a similar extent as dexamethasone. Like dexamethasone RU24858 also reduced CXCL8 and MIP-1α. Unexpectedly however, RU24858 increased the expression of the glucocorticoid-inducible genes BLT-1, Annexin-1 and Grb-2 in neutrophils to a similar level as seen with dexamethasone. We have shown here that dexamethasone and RU24858 both increase Grb-2, BLT1 and Annexin-1 expression and inhibit CXCL8 and MIP-1α production. This suggests that RU24858 was not able to dissociate between transactivation and transrepression in human neutrophils but enhanced neutrophil survival. © the author(s), publisher and licensee Libertas Academica Ltd

Epithermal Neutron Beam Interference with Cardiac Pacemakers

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Health-related quality of life, anxiety, depression, beliefs of medication, and self-efficacy in individuals with severe asthma : a population-based study

Objective: Individuals with severe asthma often report poor Health-related quality of life (HRQoL) and more research is essential to increase understanding of how they may be helped to improve HRQoL. The main aim of the current paper is to evaluate HRQoL, and possible factors influencing HRQoL, in individuals with severe asthma. The aim is also to explore associations among anxiety, depression, beliefs of medication, self-efficacy, and HRQoL among individuals with severe and other asthma as well as those with no asthma. Methods: Participants with severe asthma (n = 59), other asthma (n = 526), and no asthma (n = 902) were recruited from West Sweden Asthma Study, a population-based study, which includes both questionnaire surveys and clinical examinations. Results: Individuals with severe asthma had worse physical HRQoL (measured with SF-8) than those with other and no asthma (median 48.4, 51.9, and 54.3, respectively). They also had worse mental HRQoL (median 46.7) and reported higher anxiety and depression scores (measured using HADS, median 5.0 and 3.5, respectively) compared to no asthma (median 4.0 and 2.0, respectively). HRQoL was particularly affected among women with severe asthma. Individuals with severe asthma believed that their asthma medication was more necessary than those with other asthma, but they reported more concern for the medication. Asthma control and packyears predicted physical HRQoL and anxiety predicted mental HRQoL among individuals with severe asthma. Conclusions: Efforts to improve asthma control and to reduce anxiety may improve HRQoL in individuals with severe asthma. Especially, women with severe asthma seem to need support to improve their HRQoL. Reducing concerns with asthma medication is most likely essential as high concerns may lead to poor adherence, which in turn may negatively affect asthma control and HRQoL.Peer reviewe

Histone deacetylase inhibitors induce apoptosis in human eosinophils and neutrophils

BACKGROUND: Granulocytes are important in the pathogenesis of several inflammatory diseases. Apoptosis is pivotal in the resolution of inflammation. Apoptosis in malignant cells is induced by histone deacetylase (HDAC) inhibitors, whereas HDAC inhibitors do not usually induce apoptosis in non-malignant cells. The aim of the present study was to explore the effects of HDAC inhibitors on apoptosis in human eosinophils and neutrophils. METHODS: Apoptosis was assessed by relative DNA fragmentation assay, annexin-V binding, and morphologic analysis. HDAC activity in nuclear extracts was measured with a nonisotopic assay. HDAC expression was measured by real-time PCR. RESULTS: A HDAC inhibitor Trichostatin A (TSA) induced apoptosis in the presence of survival-prolonging cytokines interleukin-5 and granulocyte-macrophage colony stimulating factor (GM-CSF) in eosinophils and neutrophils. TSA enhanced constitutive eosinophil and neutrophil apoptosis. Similar effects were seen with a structurally dissimilar HDAC inhibitor apicidin. TSA showed additive effect on the glucocorticoid-induced eosinophil apoptosis, but antagonized glucocorticoid-induced neutrophil survival. Eosinophils and neutrophils expressed all HDACs at the mRNA level except that HDAC5 and HDAC11 mRNA expression was very low in both cell types, HDAC8 mRNA was very low in neutrophils and HDAC9 mRNA low in eosinophils. TSA reduced eosinophil and neutrophil nuclear HDAC activities by ~50-60%, suggesting a non-histone target. However, TSA did not increase the acetylation of a non-histone target NF-κB p65. c-jun-N-terminal kinase and caspases 3 and 6 may be involved in the mechanism of TSA-induced apoptosis, whereas PI3-kinase and caspase 8 are not. CONCLUSIONS: HDAC inhibitors enhance apoptosis in human eosinophils and neutrophils in the absence and presence of survival-prolonging cytokines and glucocorticoids

Diagnosis and Pharmacotherapy of Stable Chronic Obstructive Pulmonary Disease : The Finnish Guidelines

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The Future of Business Discourse Teaching

This chapter will:; ; ; Explore ways in which new media and digital technologies are shaping business communication and highlight the importance of digital communicative competence for learners and teachers;; ; ; Discuss ways in which the digital workplace can be brought into the business discourse classroom;; ; ; Discuss the role of Business English and other business languages in international business and what this means for business discourse teaching;; ; ; Consider how the multicultural workplace can inform business discourse teaching;; ; ; Provide a case study that illustrates some of the above developments, together with a set of tasks appropriate for the business discourse classroom, and a set of further readings

Re-evaluation of diagnostic parameters is crucial for obtaining accurate data on idiopathic pulmonary fibrosis

Background: The FinnishIPF registry is a prospective, longitudinal national registry study on the epidemiology of idiopathic pulmonary fibrosis (IPF). It was designed to describe the characteristics, management and prognosis of prevalent and incident IPF patients. The study was initiated in 2012. Methods: We present here results limited to five university hospitals. Patients with IPF were screened from hospital registries using ICD-10 diagnosis codes J84.1 and J84.9. All patients who gave informed consent were included and evaluated using novel diagnostic criteria. Point prevalence on the 31st of December in 2012 was calculated using the reported population in each university hospital city as the denominator. Results: Patients with ICD-10 codes J84.1 and J84.9 yielded a heterogeneous group - on the basis of patient records assessed by pulmonologists only 20-30 % of the cases were IPF. After clinical, radiological and histological re-evaluation 111 of 123 (90 %) of patients fulfilled the clinical criteria of IPF. The estimated prevalence of IPF was 8.6 cases/100 000. 60.4 % were men. Forty four percent of the patients were never-smokers. At diagnosis, the patients' mean age was 73.5 years and mean FVC was 80.4 % and DLCO 57.3 % of predicted. Conclusions: Our results suggest that hospital registries are inaccurate for epidemiological studies unless patients are carefully re-evaluated. IPF is diagnosed in Finland at a stage when lung function is still quite well preserved. Smoking in patients with IPF was less common than in previous reports.Peer reviewe