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Treatment Resistent Asthma

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https://www.readbyqxmd.com/read/28223414/the-flavonoid-cyanidin-blocks-binding-of-the-cytokine-interleukin-17a-to-the-il-17ra-subunit-to-alleviate-inflammation-in-vivo
#1
Caini Liu, Liang Zhu, Koichi Fukuda, Suidong Ouyang, Xing Chen, Chenhui Wang, Cun-Jin Zhang, Bradley Martin, Chunfang Gu, Luke Qin, Suguna Rachakonda, Mark Aronica, Jun Qin, Xiaoxia Li
Cyanidin, a key flavonoid that is present in red berries and other fruits, attenuates the development of several diseases, including asthma, diabetes, atherosclerosis, and cancer, through its anti-inflammatory effects. We investigated the molecular basis of cyanidin action. Through a structure-based search for small molecules that inhibit signaling by the proinflammatory cytokine interleukin-17A (IL-17A), we found that cyanidin specifically recognizes an IL-17A binding site in the IL-17A receptor subunit (IL-17RA) and inhibits the IL-17A/IL-17RA interaction...
February 21, 2017: Science Signaling
https://www.readbyqxmd.com/read/28223227/mitogen-activated-protein-kinases-as-therapeutic-targets-for-asthma
#2
REVIEW
MirHojjat Khorasanizadeh, Mahsa Eskian, Erwin W Gelfand, Nima Rezaei
Corticosteroid-resistant asthmatics, although comprising only a portion of the asthma population, account for most of the morbidity, mortality and economic burden associated with asthma. Moreover, corticosteroids are not effective inhibitors of airway remodeling changes, and their long-term use is associated with debilitating systemic side effects. Therefore, potent and safe novel therapeutic alternatives, targeting basic pathophysiological mechanisms responsible for the severe asthmatic phenotype are urgently needed...
February 13, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28162182/-therapeutic-effects-of-histone-deacetylase-inhibitor-givinostat-on-air-inflammation-and-high-airway-resistance-in-a-murine-asthma-model
#3
X M Su, Y Ren, L F Kong, J Kang
Objective: To investigate the therapeutic effects of givinostat, a histone deacetylase inhibitor (HDACI), on the development of chronic asthma with airway inflammation, airway remodeling and airway hyperresponsiveness (AHR). Methods: BALB/C mice were randomly divided into control group, asthma group, dexamethasone group and givinostat group (n=12 per group). AHR was assessed. Total cell numbers and differential counts, interleukin-4(IL-4), interleukin-5(IL-5) and interferon-γ (IFNγ) levels in the bronchoalveolar lavage fluid (BALF) were measured in the above 4 groups...
February 1, 2017: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
https://www.readbyqxmd.com/read/28141723/anxiety-associated-with-asthma-exacerbations-and-overuse-of-medication-the-role-of-cultural-competency
#4
Yousuke T Horikawa, Tina Y Udaka, Janet K Crow, John I Takayama, Martin T Stein
Toshi, a 14-year-old Japanese boy, had uncontrolled asthma after relocating from Japan with his family 1 year ago. In Japan, he was diagnosed with moderate, persistent asthma, which was controlled with salmeterol and albuterol on an as needed basis. Since moving to the United States, Toshi complained of frequent dyspnea.Initially, he was seen by a Japanese physician who prescribed 200 mg of fluticasone 3 times a day and albuterol nebulization as needed. When Toshi came to the Pediatric Primary Care Clinic, he reported using his nebulizer up to 25 times daily...
February 2017: Journal of Developmental and Behavioral Pediatrics: JDBP
https://www.readbyqxmd.com/read/28131832/treatment-of-obese-asthma-in-a-mouse-model-by-simvastatin-is-associated-with-improving-dyslipidemia-and-decreasing-leptin-level
#5
Wei Han, Jun Li, Huaping Tang, Lixin Sun
Obesity can cause or worsen asthma. Compared with common asthma, obese asthma is difficult to control. Statins are effective serum cholesterol-lowering agents in clinical practice, and they also have anti-inflammatory properties, which in theory are potentially beneficial in asthma. Many studies have shown that simvastatin has good therapeutic effect in animal models of asthma. However, the therapeutic effect and action mechanism of simvastatin for obese asthma remain unclear. Leptin, a satiety hormone, is in positive correlation with total body fat mass and may also play a significant role in the pathogenesis of asthma...
March 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28112586/genetic-variation-in-the-glucocorticoid-pathway-involved-in-interindividual-differences-in-the-glucocorticoid-treatment
#6
Qian-Qian Song, Wan-Ying Xie, Yong-Jun Tang, Jun Zhang, Jie Liu
Glucocorticoids (GCs) are widely used for treating asthma, rheumatoid arthritis, nephrotic syndrome, acute lymphoblastic leukemia and other autoimmune diseases. However, in a subgroup of patients, failure to respond to GCs is known as GC resistance or GC insensitivity. This represents an important barrier to effective treatment and a clinical problem requiring an urgent solution. Genetic variation in the GC pathway is a significant factor in interindividual differences in GC treatment. This article reviews the pharmacogenetics of GCs in diverse diseases based on the GC pathway...
February 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28106744/oligonucleotide-therapy-for-obstructive-and-restrictive-respiratory-diseases
#7
REVIEW
Wupeng Liao, Jinrui Dong, Hong Yong Peh, Lay Hong Tan, Kah Suan Lim, Li Li, Wai-Shiu Fred Wong
Inhaled oligonucleotide is an emerging therapeutic modality for various common respiratory diseases, including obstructive airway diseases like asthma and chronic obstructive pulmonary disease (COPD) and restrictive airway diseases like idiopathic pulmonary fibrosis (IPF). The advantage of direct accessibility for oligonucleotide molecules to the lung target sites, bypassing systemic administration, makes this therapeutic approach promising with minimized potential systemic side effects. Asthma, COPD, and IPF are common chronic respiratory diseases, characterized by persistent airway inflammation and dysregulated tissue repair and remodeling, although each individual disease has its unique etiology...
January 17, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28101344/evaluation-of-pharmacological-relaxation-effect-of-the-natural-product-naringin-on-in-vitro-cultured-airway-smooth-muscle-cells-and-in-vivo-ovalbumin-induced-asthma-balb-c-mice
#8
Yue Wang, Yun Lu, Mingzhi Luo, Xiaohao Shi, Yan Pan, Huilong Zeng, Linhong Deng
Asthma has become a common chronic respiratory disease worldwide and its prevalence is predicted to continue increasing in the next decade, particularly in developing countries. A key component in asthma therapy is to alleviate the excessive bronchial airway narrowing ultimately due to airway smooth muscle contraction, which is often facilitated by a smooth muscle relaxant, such as the β2-adrenergic agonists. Recently, bitter taste receptor (TAS2R) agonists, including saccharin and chloroquine, have been found to potently relax the airway smooth muscle cells (ASMCs) via intracellular Ca(2+) signaling...
December 2016: Biomedical Reports
https://www.readbyqxmd.com/read/28093362/hypoxia-inducible-factor-1%C3%AE-inhibition-modulates-airway-hyperresponsiveness-and-nitric-oxide-levels-in-a-balb-c-mouse-model-of-asthma
#9
Carola Dewitz, Elisa McEachern, Stephanie Shin, Kathryn Akong, Dale G Nagle, David H Broide, Praveen Akuthota, Laura E Crotty Alexander
: Hypoxia-inducible factor (HIF)-1α is a master regulator of inflammation and is upregulated in alveolar macrophages and lung parenchyma in asthma. HIF-1α regulates select pathways in allergic inflammation, and thus may drive particular asthma phenotypes. This work examines the role of pharmacologic HIF-1α inhibition in allergic inflammatory airway disease (AIAD) pathogenesis in BALB/c mice, which develop an airway hyperresponsiveness (AHR) asthma phenotype. Systemic treatment with HIF-1α antagonist YC-1 suppressed the increase in HIF-1α expression seen in control AIAD mice...
January 14, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28093225/il-4r-suppresses-airway-inflammation-in-bronchial-asthma-by-inhibiting-the-il-4-stat6-pathway
#10
Ying Liu, Hui Zhang, Ran Ni, Wen-Qing Jia, Yuan-Yuan Wang
OBJECTIVE: This study aims to explore the mechanisms of how IL-4R suppresses airway inflammation in bronchial asthma by inhibiting the IL-4/STAT6 pathway. METHODS: A total of 27 BALB/c male mice were selected and divided into control, asthma and IL-4R groups. Ovalbumin-induced mouse asthma model was established. Maximal pulmonary resistance was recorded. Hematoxylin and eosin (HE) and periodic acid Schiff (PAS) staining were conducted to observe the pathological changes in lung tissue...
January 13, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28087617/in-vitro-activity-of-the-antiasthmatic-drug-zafirlukast-against-the-oral-pathogens-porphyromonas-gingivalis-and-streptococcus-mutans
#11
Evelien Gerits, Isolde Van der Massen, Katleen Vandamme, Kaat De Cremer, Katrijn De Brucker, Karin Thevissen, Bruno P A Cammue, Serge Beullens, Maarten Fauvart, Natalie Verstraeten, Jan Michiels
Oral infections are among the most common diseases worldwide. Many protocols for the prevention and treatment of oral infections have been described, yet no golden standard has been developed so far. The antiseptic chlorhexidine and antibiotics are often used in these treatment procedures. However, long-term use of chlorhexidine can lead to side effects and extensive use of antibiotics can promote the development of antibiotic-resistant bacteria, which in turn can compromise the effectiveness of the treatment...
January 12, 2017: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/28077097/what-patients-really-think-about-asthma-guidelines-barriers-to-guideline-implementation-from-the-patients-perspective
#12
H Lingner, B Burger, P Kardos, C P Criée, H Worth, E Hummers-Pradier
BACKGROUND: Treatment of asthma does not always comply with asthma guidelines (AG). This may be rooted in direct or indirect resistance on the doctors' and/or patients' side or be caused by the healthcare system. To assess whether patients' concepts and attitudes are really an implementation barrier for AG, we analysed the patients' perspective of a "good asthma therapy" and contrasted their wishes with current recommendations. METHODS: Using a qualitative exploratory design, topic centred focus group (FG) discussions were performed until theoretical saturation was reached...
January 11, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/28053340/population-screening-and-treatment-of-helicobacter-pylori-infection
#13
REVIEW
Anthony O'Connor, Colm A O'Morain, Alexander C Ford
Helicobacter pylori is an important human pathogen, associated with a substantial burden from both malignant and non-malignant diseases. The bacterium is classed as a human carcinogen, being strongly linked with gastric cancer, the third most common cause of cancer death worldwide and is also associated with common conditions such as dyspepsia and peptic ulcer. Eradication of H. pylori reduces the incidence of gastric cancer and peptic ulcer, as well as the prevalence and costs of managing dyspepsia. Economic analyses suggest that eradication of H...
January 5, 2017: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28045928/altered-epithelial-gene-expression-in-peripheral-airways-of-severe-asthma
#14
Akul Singhania, Hitasha Rupani, Nivenka Jayasekera, Simon Lumb, Paul Hales, Neil Gozzard, Donna E Davies, Christopher H Woelk, Peter H Howarth
Management of severe asthma remains a challenge despite treatment with glucocorticosteroid therapy. The majority of studies investigating disease mechanisms in treatment-resistant severe asthma have previously focused on the large central airways, with very few utilizing transcriptomic approaches. The small peripheral airways, which comprise the majority of the airway surface area, remain an unexplored area in severe asthma and were targeted for global epithelial gene expression profiling in this study. Differences between central and peripheral airways were evaluated using transcriptomic analysis (Affymetrix HG U133 plus 2...
2017: PloS One
https://www.readbyqxmd.com/read/28043871/bcl-2-inhibitors-reduce-steroid-insensitive-airway-inflammation
#15
Bao-Ping Tian, Li-Xia Xia, Zheng-Qiang Bao, Hao Zhang, Zhi-Wei Xu, Yuan-Yuan Mao, Chao Cao, Luan-Qing Che, Jin-Kai Liu, Wen Li, Zhi-Hua Chen, Songmin Ying, Hua-Hao Shen
BACKGROUND: Asthmatic inflammation is dominated by accumulation of either eosinophils, neutrophils, or both in the airways. Disposal of these inflammatory cells is the key to disease control. Eosinophilic airway inflammation is responsive to corticosteroid treatment, whereas neutrophilic inflammation is resistant and increases the burden of global health care. Corticosteroid-resistant neutrophilic asthma remains mechanistically poorly understood and requires novel effective therapeutic strategies...
December 31, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28042341/anti-angiogenic-nanotherapy-inhibits-airway-remodeling-and-hyper-responsiveness-of-dust-mite-triggered-asthma-in-the-brown-norway-rat
#16
Gregory M Lanza, John Jenkins, Anne H Schmieder, Aigul Moldobaeva, Grace Cui, Huiying Zhang, Xiaoxia Yang, Qiong Zhong, Jochen Keupp, Ismail Sergin, Krishna S Paranandi, Lindsey Eldridge, John S Allen, Todd Williams, Michael J Scott, Babak Razani, Elizabeth M Wagner
Although angiogenesis is a hallmark feature of asthmatic inflammatory responses, therapeutic anti-angiogenesis interventions have received little attention. Objective: Assess the effectiveness of anti-angiogenic Sn2 lipase-labile prodrugs delivered via αvβ3-micellar nanotherapy to suppress microvascular expansion, bronchial remodeling, and airway hyper-responsiveness in Brown Norway rats exposed to serial house dust mite (HDM) inhalation challenges. Results: Anti-neovascular effectiveness of αvβ3-mixed micelles incorporating docetaxel-prodrug (Dxtl-PD) or fumagillin-prodrug (Fum-PD) were shown to robustly suppress neovascular expansion (p<0...
2017: Theranostics
https://www.readbyqxmd.com/read/28035367/redistribution-of-adrenomedullary-nicotinic-acetylcholine-receptor-subunits-and-the-effect-on-circulating-epinephrine-levels-in-a-murine-model-of-acute-asthma
#17
Xi Chen, Juntao Feng, Chengping Hu, Qingwu Qin, Yuanyuan Li, Ling Qin
The lack of circulating epinephrine (EPI) in the pathogenesis of asthma has long been attributed to the lack of adrenergic nerves in human airways. However, in this study we considered that EPI levels are regulated by EPI release in addition to synthesis. Nicotinic acetylcholine receptors (nAChRs) have been shown to control EPI release, and we hypothesized that redistribution of nAChR subunits modulates EPI release and circulating EPI levels. Using a mouse model of asthma, circulating EPI levels were measured by enzyme-linked immunosorbent assays...
February 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28025926/clinical-and-economic-burden-of-elevated-blood-eosinophils-in-patients-with-and-without-uncontrolled-asthma
#18
Julian Casciano, Jerry Krishnan, Zenobia Dotiwala, Chenghui Li, Shawn X Sun
BACKGROUND: The European Respiratory Society and American Thoracic Society (ERS/ATS) published guidelines in 2014 for the evaluation and treatment of asthma. These guidelines draw attention to management of patients with asthma that remains uncontrolled despite therapy. One phenotypic characteristic of therapy-resistant asthma is eosinophil elevation. It is important to better understand the burden of care gaps in this patient subgroup in order to support improved treatment strategies in the future...
January 2017: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/27999674/development-and-validation-of-a-novel-bioassay-to-determine-glucocorticoid-sensitivity
#19
Emily L Williams, Madeleine L Stimpson, Peter L Collins, Doyo G Enki, Ashish Sinha, Richard W Lee, Ashwin D Dhanda
BACKGROUND: Glucocorticoids (GCs) remain the first line treatment for almost all non-infectious inflammatory diseases, ranging from acute asthma to rheumatoid arthritis. However, across all conditions, patients have a variable response to GCs with approximately 30% being non-responders. This group of GC resistant patients is typically exposed to high-dose GCs and their side-effects before more appropriate immunotherapy is instituted. Hence, there is a pressing clinical need for a predictive biomarker of GC responsiveness...
2016: Biomarker Research
https://www.readbyqxmd.com/read/27998434/-effect-of-bcyrn1-on-proliferation-and-migration-of-airway-smooth-muscle-cells-in-rat-model-of-asthma
#20
X Y Zhang, L J Ma, Y L Guo, S Gao, L M Zhao, X S Li, X Y Tang, D J Cheng, L X Zhang, Z C Chen
Objective: To detect the effect of brain cytoplasmic RNA 1 (BCYRN1) on the proliferation and migration of airway smooth muscle cells (ASMCs) in rat model of asthma. Methods: Male SD rats were randomly divided into control group and asthma group (n=10 each). The ovalbumin (OVA) model was constructed in asthma group. Real time-qPCR was performed to detect the level of BCYRN1 in the ASMCs separated from the airway tissue of these rats. Then 2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2, 4-disulfophenyl)-2H-tetrazolium (WST-1) assay, roche real-time cell analyzer assay and Transwell cell migration assay were performed to detect the viability/proliferation and migration of ASMCs which were transfected with Ad-BCYRN1...
December 13, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
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