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Towards a practical clinical use of fractioned exhaled nitric oxide levels in chronic cough
No full textMetformin reverts the secretion of CXCL8 induced by TNF-α in primary cultures of human thyroid cells: An additional indirect anti-tumor effect of the drug
No full textCONTEXT:
Metformin displays both direct and indirect anti-tumor effects. CXCL8 is a crucial downstream mediator of Nuclear-Factor-κB signaling related to the growth and progression of thyroid cancers. Targeting CXCL8 results in prolonged survival and reduced metastatic spread in in-vivo animal models of thyroid tumors.
OBJECTIVE:
This study aimed to evaluate whether metformin inhibits the secretion of CXCL8 induced by Tumor-Necrosis-Factor-α (TNF-α) in primary cultures of normal and tumor human thyroid cells as well as in thyroid cancer cell lines.
METHODS:
Normal human thyrocytes, papillary thyroid cancer cells, and thyroid cancer cell lines (TPC-1 and BCPAP) were stimulated with TNF-α (10 ng/mL) alone or in combination with metformin (0.01, 0.1, 1, 2.5, 5, and 10mM). CXCL8 levels were measured in the cell supernatants after 24 hours.
RESULTS:
Metformin significantly and dose-dependently inhibited the TNF-α-induced CXCL8 secretion in both normal thyrocytes (ANOVA: F = 42.04; P < .0001) and papillary thyroid cancer cells (ANOVA: F = 21.691; P < .0001) but not in TPC-1 and BCPAP cell lines.
CONCLUSION:
Metformin inhibits the TNF-α-induced CXCL8 secretion in primary cultures of normal thyroid cells and differentiated thyroid cancer cells at least of the most frequent poorly aggressive phenotype. The recruitment of neutrophils within the thyroid gland is a crucial metastasis-promoting factor, and it depends on the amount of CXCL8 produced by both tumor cells and by the more abundant normal thyroid cells exposed to TNF-α. Thus, the here-reported inhibiting effect of metformin on TNF-α-induced CXCL8 secretion could be considered as a further indirect anticancer property of the drug
Espettorato indotto e patologie dell'apparato respiratorio
No full textInduced sputum is a nonivasive technique useful to assess airway inflammation. Sputum is induced through the inhalation of ultrasonic nebulized hypertonic saline solution and pre-treatment of the subject with b2 agonist is recommended to avoid bronchoconstriction. After the inhalation period the subject is invited to cough and to produce sputum. The sample is sent to the laboratory within 2 hours where it is solubilised in order to evaluate total cells and differential inflammatory cell count. Sputum of a healthy subject is mainly constituted by macrophages and neutrophils while eosinophils, lymphocytes and epithelial cells are only rarely present. Most asthmatic subjects have an increase of eosinophils in their sputum samples but neutrophilic or paucigranular patterns are also found in asthmatics' airways. Sputum eosinophils are usually predictors of a good response to inhaled or systemic corticosteroid therapy, whereas the presence of neutrophils in induced sputum, suggests a different therapeutic choice since neutrophils are not responsive to steroids. Furthermore, neutrophils are the most represented inflammatory cells in the sputum samples of subjects with chronic obstructive pulmonary disease (COPD). Total cells and sputum neutrophils increase during disease exacerbation. In the sputum of COPD subjects, the presence of eosinophils can precede an exacerbation and envisages a favourable response to steroids. Soluble mediators can be measured in the supernatant of processed induced sputum samples, particularly many cytokines, chemokines and other markers of inflammation and oxidative stress, but none of them seems to be particularly useful for the diagnosis or for the follow-up of patients with respiratory diseases. The majority of studies on induced sputum are conducted on asthmatic and COPD subjects but the scarce invasiveness of the procedure also allows its application in other pulmonary diseases such as eosinophilic bronchitis, cystic fibrosis, interstitial lung diseases
How Do Inflammatory Mediators, Immune Response and Air Pollution Contribute to COVID-19 Disease Severity? A Lesson to Learn
Full text linkInflammatory and immune processes are defensive mechanisms that aim to remove harmful agents. As a response to infections, inflammation and immune response contribute to the pathophysiological mechanisms of diseases. Coronavirus disease 2019 (COVID-19), whose underlying mechanisms remain not fully elucidated, has posed new challenges for the knowledge of pathophysiology. Chiefly, the inflammatory process and immune response appear to be unique features of COVID-19 that result in developing a hyper-inflammatory syndrome, and air pollution, the world's largest health risk factor, may partly explain the behaviour and fate of COVID-19. Understanding the mechanisms involved in the progression of COVID-19 is of fundamental importance in order to avoid the late stage of the disease, associated with a poor prognosis. Here, the role of the inflammatory and immune mediators in COVID-19 pathophysiology is discussed
Is bronchodilator the correct treatment for COPD subjects before EBUS?
Full text linkEndobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) is a reliable and commonly established technique, enabling real-time guidance of transbronchial needle aspiration of mediastinal and hilar structures and parabronchial lung masses. As EBUS-TBNA became more available and adopted by clinicians, questions emerged about the optimal performance of the procedure. Although EBUS is considered safe, there are few complications that could occur during the test, correlated with both the procedure itself and the patient's characteristics. Moreover, this technique is often addressed to patients with overlapping airways diseases, which might have higher risk of complications during the procedure. Chronic obstructive pulmonary disease (COPD) patients could experience EBUS-TBNA with a relative high frequency due to their risk of developing lung cancer. The irreversible bronchial constriction characteristic of the disease raises some questions on premedication before bronchoscopic procedures. It is mandatory to optimize every aspect of the procedure in order to minimize the risk of complications, especially for fragile patients. Whether the use of inhaled bronchodilators before the procedure could improve the outcome of the procedure in COPD patients is reviewed in this article. No clear indication emerged from the literature suggesting the need of more studies in order to clarify this point
Lung Involvement in Patients with Ulcerative Colitis: Relationship between Exhaled Nitric Oxide and Lung Function
No full textUlcerative colitis (UC) is characterized by immune system dysregulation with frequent extraintestinal manifestations, including airway involvement. A reduction in CO diffusing capacity and functional alterations in small airways have been described. An extended analysis of fractional exhaled nitric oxide (FeNO) may distinguish the sites of production, and the presence of small airway inflammation may be a useful, non-invasive marker for patient follow-up. The aim of our study was to compare the PFTs as well as FeNO and CANO values of UC patients with different clinical disease activities and healthy subjects to reveal lung function abnormalities and the presence of subclinical airway inflammation. We enrolled 42 adult outpatients at different clinical activity stages of UC (39 ± 13 years) and a healthy control group of 41 subjects (29 ± 3 years). C-reactive protein (CRP) and FeNO values at different flows (50,100, and 200 mL/s) were collected. All patients performed pulmonary function tests (PFTs) with static volumes and diffusing capacity (DLCO). FeNO and CANO values were significantly increased in UC patients when compared with controls (p = 0.0008 and p < 0.0001, respectively) and were proportional to disease activity (FeNO class 3: 28.1 ppb vs. classes 1–2: 7.7 ppb; CANO values class 3: 8.6 ppb vs. classes 1–2: 2.7 ppb (p < 0.0001)). TLC and DLCO were significantly reduced in severe (Mayo 3) UC patients (p = 0.010 and p = 0.003, respectively). The results of this study show significant lung functional abnormalities in UC patients and suggest the presence of airway inflammation directly correlated with disease activity, suggesting the need for an integrated approach in routine assessment
Normal human thyroid cells, BCPAP, and TPC-1 thyroid tumor cell lines display different profile in both basal and TNF-α-induced CXCL8 secretion
No full textCXCL8 is secreted by both normal human thyrocytes (NHT) and thyroid cancer cell lines. CXCL8 displays several tumor-promoting effects and recent evidences indicate that its concentrations within the tumor microenvironment can impact the clinical course of the malignancy. Aim of this study was to compare the basal secretion of CXCL8 among NHT and thyroid cancer cell lines (TPC-1 and BCPAP), and to assess the specific cell response to TNF-α in terms of CXCL8 secretion. NHT primary cultures, TPC-1 and BCPAP cell lines were cultured with or without TNF-α (0, 0.1, 1, 10, and 100 ng/ml). CXCL8 levels were measured in the cell supernatants after 24 h. In basal condition, significant differences in the mean levels of CXCL8 were observed among the three cell types: NHT (110.5 ± 56.2 pg/ml), TPC1 (467.4 ± 43.2 pg/ml), and BCPAP (1731.8 ± 493.3 pg/ml), (F = 35.06; p < 0.0001). TNF-α significantly and in a dose-response manner induced CXCL8 secretion in NHT (F = 25.53; p < 0.00001), TPC-1 (F = 13.38; p < 0.0001), and BCPAP (F = 9.88; p < 0.001) cells. The magnitude of the TNF-α effect (fold-increase vs. basal level of CXCL8) differed significantly among the three cell types (F = 10.47; p < 0.0001). BCPAP were identified as the cells showing the highest basal secretion of CXCL8 and the less responsive to TNF-α. NHT, TPC-1, and BCPAP display significant differences in the secretion of both basal and TNF-α-induced CXCL8 secretion. These results indicate that the mechanisms regulating the secretion of CXCL8 differ in tumor cells harboring different genetic alterations suggesting that specific strategies aimed at inhibiting CXCL8 secretion will be required
[Fractional exhaled nitric oxide measurement during specific inhalation challenge tests]
No full textThe aim of the work is to evaluate the usefulness of the evaluation of the fractional exhaled nitric oxide (FeNO) in patients with suspected occupational asthma (OA) during the specific inhalation challenge (SIC). We evaluated 5 subjects with OA confirmed by SIC and 7 subjects with negative SIC result. In subjects with confirmed OA, but not in SIC negative subjects, a significant increase in FeNO values has been reported. In conclusion, FeNO measurement may be considered a useful tollfor the evaluation of bronchial inflammation during the SIC
Inhaled beclometasone dipropionate/formoterol fumarate extrafine fixed combination for the treatment of asthma
No full textInhaled therapy is often considered the cornerstone of asthma management and international guidelines recommend combination therapy of inhaled corticosteroids (ICS) and long-acting-beta2-agonists (LABA) in a large proportion of asthmatic patients. The effectiveness of ICS/LABA is dependent on the correct choice of device and proper inhalation technique, this influences drug delivery and distribution along the bronchial tree, including the most peripheral airways. The fixed combination of beclometasone dipropionate/formoterol fumarate (BDP/FF) is the only extrafine formulation available in pressurized metered dose inhaler (pMDI) and in dry powder inhaler (DPI). Here, we focus on the recent significant advances regarding BDP/FF fixed combination for the treatment of asthma
Analysis of Patients with Asthma and Mixed Granulocytic Inflammatory Pattern in Sputum
No full textBackground: Patients with asthma usually present airway inflammation classified as eosinophilic, neutrophilic, mixed granulocytic, and paucigranulocytic pattern according to sputum inflammatory cells. Objective: The aim of the study was to analyze clinical and biological characteristics of patients with asthma and mixed granulocytic pattern in comparison with the other groups. Methods: Induced sputum was used to assess airway inflammation; lung function was evaluated as well as blood leukocytes and disease control. History of comorbidities was collected. Results: We retrospectively analyzed 231 subjects with asthma; patients with mixed granulocytic pattern were more frequently male compared with paucigranulocytic subjects, older than eosinophilic and paucigranulocytic patients with increased number and vitality of sputum cells compared to eosinophilic and paucigranulocytic patients and higher cumulative illness rating score, related to increased age. Smoking history, age of disease onset, and ICS treatment were not associated with higher mixed granulocytic pattern occurrence. Subjects with neutrophilic inflammation (mixed granulocytic and neutrophilic patterns considered altogether) were more frequently obese. In subjects under 67 years of age (median of the enrolled subjects), arterial hypertension was the only comorbidity more frequent in mixed granulocytic than in the other groups. 137/231 subjects were re-valuated during follow-up. Lung function of patients with mixed granulocytic, neutrophilic, and paucigranulocytic patterns improved less than that of eosinophilic patients. Conclusion: Aging and presence of comorbidities, in particular obesity and hypertension, are characteristics of patients with asthma and mixed granulocytic pattern. They could respond less well to treatment than eosinophilic patients
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