Simple and robust LC-MS/MS method for quantification of colistin methanesulfonate and colistin in human plasma for therapeutic drug monitoring.

A rapid, simple, and robust LC-MS/MS method was developed and validated for the quantitation of colistin and colistin methanesulfonate (CMS) in human plasma. The method also prevented overestimation of colistin concentration by establishing the stability of CMS under sample preparation conditions, including blood and plasma storage conditions. Polymyxin B1 was used as an internal standard, and positive-ion electrospray ionization in multiple reaction monitoring mode was used for quantification.

Effect of Reduction Sequence during Rolling on Deformed Texture and Anisotropy of Ferritic Stainless Steel.

This investigation studied the effect of reduction sequence during rolling of ferritic stainless steel on texture and anisotropy. A series of thermomechanical processes were performed on the present samples utilizing rolling deformation, with a total height reduction of 83% but with different reduction sequences, 67% + 50% (route A) and 50% + 67% (route B). Microstructural analysis showed that no significant difference was found in terms of the grain morphology between route A and route B.

Staphylococcal Enterotoxin-Specific IgE Sensitization: A Potential Predictor of Fixed Airflow Obstruction in Elderly Asthma.

Purpose: enterotoxin-specific immunoglobulin E (SE-sIgE) sensitization tends to increase with age and is known to be associated with asthma and severity in older adults. However, the long-term impact of SE-sIgE in the elderly remains unknown. This study aimed to examine the relationships between SE-sIgE and fixed airflow obstruction (FAO) in a cohort of elderly asthmatics.

Management of Elderly Asthma: Key Questions and Tentative Answers.

The aging lung undergoes structural changes, immunosenescence, and inflammation, rendering the elderly more susceptible to developing obstructive airway disease. Thus, asthma in those of chronological age ≥ 65 years is not rare. Elderly asthma (EA) imposes considerable burdens in terms of mortality and morbidity, and expenditure.

Clinical predictors of treatment response to tiotropium add-on therapy in adult asthmatic patients: From multicenter real-world cohort data in Korea.

Background: Tiotropium, a long-acting muscarinic antagonist, is recommended for add-on therapy to inhaled corticosteroids (ICS)-long-acting beta 2 agonists (LABA) for severe asthma. However, real-world studies on the predictors of response to tiotropium are limited. We investigated the real-world use of tiotropium in asthmatic adult patients in Korea and we identified predictors of positive response to tiotropium add-on.

Intravenous Mesenchymal Stem Cell Administration Modulates Monocytes/Macrophages and Ameliorates Asthmatic Airway Inflammation in a Murine Asthma Model.

Although asthma is a common chronic airway disease that responds well to anti-inflammatory agents, some patients with asthma are unresponsive to conventional treatment. Mesenchymal stem cells (MSCs) have therapeutic potential for the treatment of inflammatory diseases owing to their immunomodulatory properties. However, the target cells of MSCs are not yet clearly known.

Association between small dense LDL levels and hepatic fibrosis in patients with nonalcoholic fatty liver disease.

While patients with nonalcoholic fatty liver disease (NAFLD) continue to increase worldwide, few hematological biomarkers are helpful. This study examined the potential of small dense low density lipoprotein (sdLDL) as a noninvasive biomarker for NAFLD and investigated the relevance of liver fibrosis. One hundred seventy two patients were enrolled: 121 NAFLD patients and 51 healthy controls.

Peripheral blood transcriptomic clusters uncovered immune phenotypes of asthma.

Background: Transcriptomic analysis has been used to elucidate the complex pathogenesis of heterogeneous disease and may also contribute to identify potential therapeutic targets by delineating the hub genes. This study aimed to investigate whether blood transcriptomic clustering can distinguish clinical and immune phenotypes of asthmatics, and microbiome in asthmatics.

Methods: Transcriptomic expression of peripheral blood mononuclear cells (PBMCs) from 47 asthmatics and 21 non-asthmatics was measured using RNA sequencing.

Intratracheal administration of mesenchymal stem cells modulates lung macrophage polarization and exerts anti-asthmatic effects.

Mesenchymal stem cells (MSCs) possess immunomodulatory properties that have therapeutic potential for the treatment of inflammatory diseases. This study investigates the effects of direct MSC administration on asthmatic airways. Umbilical cord MSCs (ucMSCs) were intratracheally administered to six-week-old female BALB/c mice sensitized and challenged with ovalbumin; airway hyperresponsiveness (AHR), analyses of airway inflammatory cells, lung histology, flow cytometry, and quantitative real-time PCR were performed.

Cigarette smoke aggravates asthma by inducing memory-like type 3 innate lymphoid cells.

Although cigarette smoking is known to exacerbate asthma, only a few clinical asthma studies have been conducted involving smokers. Here we show, by comparing paired sputum and blood samples from smoking and non-smoking patients with asthma, that smoking associates with significantly higher frequencies of pro-inflammatory, natural-cytotoxicity-receptor-non-expressing type 3 innate lymphoid cells (ILC3) in the sputum and memory-like, CD45RO-expressing ILC3s in the blood. These ILC3 frequencies positively correlate with circulating neutrophil counts and M1 alveolar macrophage frequencies, which are known to increase in uncontrolled severe asthma, yet do not correlate with circulating eosinophil frequencies that characterize allergic asthma.

Cytokine Inductions and Intracellular Signal Profiles by Stimulation of dsRNA and SEB in the Macrophages and Epithelial Cells.

Foreign molecules, including viruses and bacteria-derived toxins, can also induce airway inflammation. However, to the best of our knowledge, the roles of these molecules in the development of airway inflammation have not been fully elucidated. Herein, we investigated the precise role and synergistic effect of virus-mimicking double-stranded RNA (dsRNA) and staphylococcal enterotoxin B (SEB) in macrophages and epithelial cells.

Clusters of Severe Eosinophilic Asthma in a Korean Asthma Cohort.

Background: Targeted therapies have broadened the available treatment options for patients with severe eosinophilic asthma (SEA). However, differences in the magnitude of treatment responses among patients indicate the presence of various underlying pathophysiological processes and patient subgroups.

Objectives: We aimed to describe the characteristics of SEA and identify its patient subgroups.

Effect of Acinetobacter lwoffii on the modulation of macrophage activation and asthmatic inflammation.

Background: Although lung macrophages are directly exposed to external stimuli, their exact immunologic roles in asthma are still largely unknown. The aim of this study was to investigate the anti-asthmatic effect of Acinetobacter lwoffii in terms of lung macrophage modulation.

Methods: Six-week-old female BALB/c mice were sensitized and challenged with ovalbumin (OVA) with or without intranasal administration of A.

Transglutaminase 2 mediates lung inflammation and remodeling by transforming growth factor beta 1 alveolar macrophage modulation.

Transforming growth factor beta 1 (TGF-β1) induces pulmonary fibrosis by enhancing epithelial apoptosis and affects the enzymatic activity of transglutaminase 2 (TG2). The aim of this study was to determine the role of TG2 in TGF-β1-induced lung remodeling and alveolar macrophage modulation. We characterized the o effects of TGF-β1 and TG2 on lung inflammation, fibrosis, and macrophage activity using transgenic C57BL/6 mice with wild and null TG2 loci.

A unique population of neutrophils generated by air pollutant-induced lung damage exacerbates airway inflammation.

Background: Diesel exhaust particles (DEPs) are the main component of traffic-related air pollution and have been implicated in the pathogenesis and exacerbation of asthma. However, the mechanism by which DEP exposure aggravates asthma symptoms remains unclear.

Objective: This study aimed to identify a key cellular player of air pollutant-induced asthma exacerbation and development.

Interactions between NCRILC3s and the Microbiome in the Airways Shape Asthma Severity.

Asthma is a heterogeneous disease whose development is shaped by a variety of environmental and genetic factors. While several recent studies suggest that microbial dysbiosis in the gut may promote asthma, little is known about the relationship between the recently discovered lung microbiome and asthma. Innate lymphoid cells (ILCs) have also been shown recently to participate in asthma.