scholarly journals Ebselen prevents cigarette smoke-induced gastrointestinal dysfunction in mice

2020 ◽  
Vol 134 (22) ◽  
pp. 2943-2957
Author(s):  
Gayathri K. Balasuriya ◽  
Mitra Mohsenipour ◽  
Kurt Brassington ◽  
Aleksandar Dobric ◽  
Simone N. De Luca ◽  
...  
Keyword(s):  
Mouse Model ◽  
Ex Vivo ◽  
Imaging Techniques ◽  
Chronic Obstructive ◽  
Enteric Neuron ◽  
Gastrointestinal Dysfunction ◽  
Obstructive Pulmonary Disease ◽  
Beneficial Effects ◽  
Frequency Changes ◽  
Underlying Mechanisms

Abstract Gastrointestinal (GI) dysfunction is a common comorbidity of chronic obstructive pulmonary disease (COPD) for which a major cause is cigarette smoking (CS). The underlying mechanisms and precise effects of CS on gut contractility, however, are not fully characterised. Therefore, the aim of the present study was to investigate whether CS impacts GI function and structure in a mouse model of CS-induced COPD. We also aimed to investigate GI function in the presence of ebselen, an antioxidant that has shown beneficial effects on lung inflammation resulting from CS exposure. Mice were exposed to CS for 2 or 6 months. GI structure was analysed by histology and immunofluorescence. After 2 months of CS exposure, ex vivo gut motility was analysed using video-imaging techniques to examine changes in colonic migrating motor complexes (CMMCs). CS decreased colon length in mice. Mice exposed to CS for 2 months had a higher frequency of CMMCs and a reduced resting colonic diameter but no change in enteric neuron numbers. Ten days cessation after 2 months CS reversed CMMC frequency changes but not the reduced colonic diameter phenotype. Ebselen treatment reversed the CS-induced reduction in colonic diameter. After 6 months CS, the number of myenteric nitric-oxide producing neurons was significantly reduced. This is the first evidence of colonic dysmotility in a mouse model of CS-induced COPD. Dysmotility after 2 months CS is not due to altered neuron numbers; however, prolonged CS-exposure significantly reduced enteric neuron numbers in mice. Further research is needed to assess potential therapeutic applications of ebselen in GI dysfunction in COPD.

scholarly journals Mepenzolate bromide displays beneficial effects in a mouse model of chronic obstructive pulmonary disease

2013 ◽  
Vol 4 (1) ◽  
Author(s):  
Ken-Ichiro Tanaka ◽  
Tomoaki Ishihara ◽  
Toshifumi Sugizaki ◽  
Daisuke Kobayashi ◽  
Yasunobu Yamashita ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Mouse Model ◽  
Pulmonary Disease ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Beneficial Effects

scholarly journals Common and Novel Markers for Measuring Inflammation and Oxidative Stress Ex Vivo in Research and Clinical Practice—Which to Use Regarding Disease Outcomes?

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 414
Author(s):  
Alain Menzel ◽  
Hanen Samouda ◽  
Francois Dohet ◽  
Suva Loap ◽  
Mohammed S. Ellulu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Clinical Practice ◽  
Acute Phase Proteins ◽  
Ex Vivo ◽  
Chronic Obstructive ◽  
Low Grade ◽  
Obstructive Pulmonary Disease ◽  
Amyloid A ◽  
Non Invasive ◽  
Markers Of Inflammation

Many chronic conditions such as cancer, chronic obstructive pulmonary disease, type-2 diabetes, obesity, peripheral/coronary artery disease and auto-immune diseases are associated with low-grade inflammation. Closely related to inflammation is oxidative stress (OS), which can be either causal or secondary to inflammation. While a low level of OS is physiological, chronically increased OS is deleterious. Therefore, valid biomarkers of these signalling pathways may enable detection and following progression of OS/inflammation as well as to evaluate treatment efficacy. Such biomarkers should be stable and obtainable through non-invasive methods and their determination should be affordable and easy. The most frequently used inflammatory markers include acute-phase proteins, essentially CRP, serum amyloid A, fibrinogen and procalcitonin, and cytokines, predominantly TNFα, interleukins 1β, 6, 8, 10 and 12 and their receptors and IFNγ. Some cytokines appear to be disease-specific. Conversely, OS—being ubiquitous—and its biomarkers appear less disease or tissue-specific. These include lipid peroxidation products, e.g., F2-isoprostanes and malondialdehyde, DNA breakdown products (e.g., 8-OH-dG), protein adducts (e.g., carbonylated proteins), or antioxidant status. More novel markers include also –omics related ones, as well as non-invasive, questionnaire-based measures, such as the dietary inflammatory-index (DII), but their link to biological responses may be variable. Nevertheless, many of these markers have been clearly related to a number of diseases. However, their use in clinical practice is often limited, due to lacking analytical or clinical validation, or technical challenges. In this review, we strive to highlight frequently employed and useful markers of inflammation-related OS, including novel promising markers.

scholarly journals Present and future utility of computed tomography scanning in the assessment and management of COPD

2016 ◽  
Vol 48 (1) ◽  
pp. 216-228 ◽  
Author(s):  
Kristoffer Ostridge ◽  
Tom M.A. Wilkinson
Keyword(s):  
Computed Tomography ◽  
Clinical Applications ◽  
Wall Thickening ◽  
Chronic Obstructive ◽  
Clinical Tool ◽  
Obstructive Pulmonary Disease ◽  
Lung Structure ◽  
Computed Tomography Scanning ◽  
Underlying Mechanisms ◽  
Future Utility

Computed tomography (CT) is the modality of choice for imaging the thorax and lung structure. In chronic obstructive pulmonary disease (COPD), it used to recognise the key morphological features of emphysema, bronchial wall thickening and gas trapping. Despite this, its place in the investigation and management of COPD is yet to be determined, and it is not routinely recommended. However, lung CT already has important clinical applications where it can be used to diagnose concomitant pathology and determine which patients with severe emphysema are appropriate for lung volume reduction procedures. Furthermore, novel quantitative analysis techniques permit objective measurements of pulmonary and extrapulmonary manifestations of the disease. These techniques can give important insights into COPD, and help explore the heterogeneity and underlying mechanisms of the condition. In time, it is hoped that these techniques can be used in clinical trials to help develop disease-specific therapy and, ultimately, as a clinical tool in identifying patients who would benefit most from new and existing treatments. This review discusses the current clinical applications for CT imaging in COPD and quantification techniques, and its potential future role in stratifying disease for optimal outcome.

In vivo characterization of the transitional bronchioles by aerosol-derived airway morphometry

1999 ◽  
Vol 87 (3) ◽  
pp. 920-927 ◽  
Author(s):  
Kirby L. Zeman ◽  
Gerhard Scheuch ◽  
Knut Sommerer ◽  
James S. Brown ◽  
William D. Bennett
Keyword(s):  
Ex Vivo ◽  
Normal Subjects ◽  
Characteristic Line ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Lung Capacity ◽  
Single Breath ◽  
In Vivo Characterization

Effective airway dimensions (EADs) were determined in vivo by aerosol-derived airway morphometry as a function of volumetric lung depth (VLD) to identify and characterize, noninvasively, the caliber of the transitional bronchiole region of the human lung and to compare the EADs by age, gender, and disease. By logarithmically plotting EAD vs. VLD, two distinct regions of the lung emerged that were identified by characteristic line slopes. The intersection of proximal and distal segments was defined as VLDtransand associated EADtrans. In our normal subjects ( n = 20), VLDtrans [345 ± 83 (SD) ml] correlated significantly with anatomic dead space (224 ± 34 ml) and end of phase II of single-breath nitrogen washout (360 ± 53 ml). The corresponding EADtranswas 0.42 ± 0.07 mm, in agreement with other ex vivo measurements of the transitional bronchioles. VLDtrans was smaller (216 ± 64 ml) and EADtrans was larger (0.83 ± 0.04 mm) in our patients with chronic obstructive pulmonary disease ( n = 13). VLDtrans increased with age for children (age 8–18 yr; P = 0.006, n = 26) and with total lung capacity for age 8–81 yr ( P < 0.001, n = 61). This study extends the usefulness of aerosol-derived airway morphometry to in vivo measurements of the transitional bronchioles.

scholarly journals Eosinophil-derived IL-13 promotes emphysema

2019 ◽  
Vol 53 (5) ◽  
pp. 1801291 ◽  
Author(s):  
Alfred D. Doyle ◽  
Manali Mukherjee ◽  
William E. LeSuer ◽  
Tyler B. Bittner ◽  
Saif M. Pasha ◽  
...  
Keyword(s):  
Mouse Model ◽  
Inflammatory Responses ◽  
Pulmonary Inflammation ◽  
Forced Expiratory Volume ◽  
Chronic Obstructive ◽  
Chronic Type ◽  
Obstructive Pulmonary Disease ◽  
Lung Eosinophilia

The inflammatory responses in chronic airway diseases leading to emphysema are not fully defined. We hypothesised that lung eosinophilia contributes to airspace enlargement in a mouse model and to emphysema in patients with chronic obstructive pulmonary disease (COPD).A transgenic mouse model of chronic type 2 pulmonary inflammation (I5/hE2) was used to examine eosinophil-dependent mechanisms leading to airspace enlargement. Human sputum samples were collected for translational studies examining eosinophilia and matrix metalloprotease (MMP)-12 levels in patients with chronic airways disease.Airspace enlargement was identified in I5/hE2 mice and was dependent on eosinophils. Examination of I5/hE2 bronchoalveolar lavage identified elevated MMP-12, a mediator of emphysema. We showed, in vitro, that eosinophil-derived interleukin (IL)-13 promoted alveolar macrophage MMP-12 production. Airspace enlargement in I5/hE2 mice was dependent on MMP-12 and eosinophil-derived IL-4/13. Consistent with this, MMP-12 was elevated in patients with sputum eosinophilia and computed tomography evidence of emphysema, and also negatively correlated with forced expiratory volume in 1 s.A mouse model of chronic type 2 pulmonary inflammation exhibited airspace enlargement dependent on MMP-12 and eosinophil-derived IL-4/13. In chronic airways disease patients, lung eosinophilia was associated with elevated MMP-12 levels, which was a predictor of emphysema. These findings suggest an underappreciated mechanism by which eosinophils contribute to the pathologies associated with asthma and COPD.

scholarly journals IL-22 and its receptors are increased in human and experimental COPD and contribute to pathogenesis

2019 ◽  
Vol 54 (1) ◽  
pp. 1800174 ◽  
Author(s):  
Malcolm R. Starkey ◽  
Maximilian W. Plank ◽  
Paolo Casolari ◽  
Alberto Papi ◽  
Stelios Pavlidis ◽  
...  
Keyword(s):  
T Cells ◽  
Γδ T Cells ◽  
Lymphoid Cells ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Protein Levels ◽  
Copd Patients ◽  
Cellular Source ◽  
Group 3 ◽  
Underlying Mechanisms

Chronic obstructive pulmonary disease (COPD) is the third leading cause of morbidity and death globally. The lack of effective treatments results from an incomplete understanding of the underlying mechanisms driving COPD pathogenesis.Interleukin (IL)-22 has been implicated in airway inflammation and is increased in COPD patients. However, its roles in the pathogenesis of COPD is poorly understood. Here, we investigated the role of IL-22 in human COPD and in cigarette smoke (CS)-induced experimental COPD.IL-22 and IL-22 receptor mRNA expression and protein levels were increased in COPD patients compared to healthy smoking or non-smoking controls. IL-22 and IL-22 receptor levels were increased in the lungs of mice with experimental COPD compared to controls and the cellular source of IL-22 included CD4+ T-helper cells, γδ T-cells, natural killer T-cells and group 3 innate lymphoid cells. CS-induced pulmonary neutrophils were reduced in IL-22-deficient (Il22−/−) mice. CS-induced airway remodelling and emphysema-like alveolar enlargement did not occur in Il22−/− mice. Il22−/− mice had improved lung function in terms of airway resistance, total lung capacity, inspiratory capacity, forced vital capacity and compliance.These data highlight important roles for IL-22 and its receptors in human COPD and CS-induced experimental COPD.

scholarly journals Chronic Cigarette Smoke Exposure Primes NK Cell Activation in a Mouse Model of Chronic Obstructive Pulmonary Disease

2010 ◽  
Vol 184 (8) ◽  
pp. 4460-4469 ◽  
Author(s):  
Gregory T. Motz ◽  
Bryan L. Eppert ◽  
Brian W. Wortham ◽  
Robyn M. Amos-Kroohs ◽  
Jennifer L. Flury ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Mouse Model ◽  
Pulmonary Disease ◽  
Cigarette Smoke ◽  
Cell Activation ◽  
Nk Cell ◽  
Smoke Exposure ◽  
Cigarette Smoke Exposure ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease

scholarly journals Herbal Formula, PM014, Attenuates Lung Inflammation in a Murine Model of Chronic Obstructive Pulmonary Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Hyojung Lee ◽  
Youngeun Kim ◽  
Hye Jin Kim ◽  
Soojin Park ◽  
Young Pyo Jang ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Murine Model ◽  
Lung Inflammation ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Chronic Obstructive ◽  
Herbal Formula ◽  
Obstructive Pulmonary Disease ◽  
Beneficial Effects

Chronic obstructive pulmonary disease (COPD), which is characterized by airway obstruction, leads to, as the two major forms of COPD, chronic bronchitis and emphysema. This study was conducted to evaluate the effects of herbal formula, PM014, in a murine model of COPD. Balb/c mice were treated once with each herb extract in PM014 or PM014 mixture via an oral injection. Lipopolysaccharide (LPS) or elastase/LPS were administrated to the mice to induce a disease that resembles COPD. PM014 treatment significantly attenuated the increased accumulation of immune cells in bronchoalveolar lavage fluid (BALF) compared to control mice. In addition, the TNF-αand IL-6 levels in BALF were decreased in the PM014 mice. Furthermore, histological analysis demonstrated that PM014 attenuated the hazardous effects of lung inflammation. These data suggest that PM014 exerts beneficial effects against forms of COPD such as lung inflammation.

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