Development of a mouse model mimicking key aspects of a viral asthma exacerbation

2013 ◽  
Vol 126 (8) ◽  
pp. 567-580 ◽  
Author(s):  
Deborah L. Clarke ◽  
Nicola H. E. Davis ◽  
Jayesh B. Majithiya ◽  
Sian C. Piper ◽  
Arthur Lewis ◽  
...  
Keyword(s):  
Mouse Model ◽  
Asthma Exacerbation ◽  
Resistant Mouse ◽  
Disease Mechanisms ◽  
Asthma Exacerbations ◽  
Key Aspects ◽  
Novel Therapeutic

The present study describes a corticosteroid-resistant mouse model mimicking key aspects of viral asthma exacerbation which may provide better understanding of disease mechanisms and could be used to build early confidence in novel therapeutic axes targeting viral asthma exacerbations in asthmatics.

scholarly journals Membandingkan Kejadian Gangguan Gastrointestinal Penggunaan Aminofilin dan Salbutamol pada Pasien Eksaserbasi Asma di Surabaya

2019 ◽  
Vol 1 (1) ◽  
pp. 1-10
Author(s):  
Amelia Lorensia ◽  
Zullies Ikawati ◽  
Tri Murti Andayani ◽  
Daniel Maranatha ◽  
Rizki Amalia
Keyword(s):  
Asthma Exacerbation ◽  
Acute Asthma ◽  
Shortness Of Breath ◽  
Drug Reactions ◽  
Asthma Exacerbations ◽  
Gastrointestinal Problems ◽  
Asthma Patients ◽  
Quasi Experimental ◽  
Expiratory Air ◽  
Over Time

Abstract—Asthma is a heterogeneous disease, which is characterized by inflammation of the respiratory tract with respiratory classification such as wheezing, shortness of breath, distress in the chest and coughing over time and intensity with variations in expiratory air flow. In Indonesia the prevalence of asthma is uncertain, it is not estimated that 2-5% of Indonesia's population has asthma. The main objective of this study is to study gastrointestinal-related cases of the use of aminophylline and salbutamol in asthma exacerbation patients in hospitals in Surabaya and also to discuss gastrointestinal problems related to ADRs (Bad Drug Reactions) using the use of aminophylline and salbutamol on Naranjo scale. In this study using the Quasi Experimental method. This research was conducted in October 2014 to February 2015. The results of the study of 7 samples obtained 14.29% using ADR from the use of aminophylline and from 13 patients in the use of salbutamol was not found ADR can be used in accordance with the existing salbutamol in patients with asthma exacerbations at hospitals in Surabaya. The general benefits of this study are useful in monitoring the treatment of acute asthma patients who need salbutamol and theophylline therapy so as to reduce the incidence of ADR. Abstrak—Asma merupakan penyakit heterogen, yang ditandai dengan peradangan saluran napas kronis dengan disertai riwayat gejala pernapasan seperti mengi, sesak napas, rasa tertekan di dada dan batuk dari waktu ke waktu dan intensitas dengan variasi keterbatasan aliran udara ekspirasi. Di Indonesia prevalensi asma belum diketahui secara pasti, namun diperkirakan 2-5 % penduduk Indonesia menderita asma. Tujuan utama penelitian ini adalah untuk mengetahui perbedaan kejadian gangguan gastrointestinal pada penggunaan aminofilin dan salbutamol pada pasien eksaserbasi asma di Rumah Sakit di Surabaya serta mengetahui kejadian gangguan gastrointestinal terkait ADRs (Adverse Drug Reaction) akibat penggunaan aminofilin dan salbutamol berdasarkan penilaian Naranjo scale. Pada penelitian ini menggunakan metode Quasi Eksperimental. Penelitian ini dilakukan pada bulan Oktober 2014 sampai Februari 2015. Hasil penelitian dari 7 sampel diperoleh 14,29% mengalami ADR dari penggunaan aminofilin dan dari 13 pasien pada pengguanaan salbutamol tidak ditemukan ADR sehingga dapat disimpulkan bahwa tidak ada perbedaan kejadian gangguan gastrointestinal pada penggunaan aminofilin dan salbutamol pada pasien eksaserbasi asma di Rumah Sakit di Surabaya. Manfaat umum dari penelitian ini adalah berguna dalam monitoring pengobatan pasien asma akut terutama yang mendapat terapi salbutamol dan teofilin sehingga dapat mengurangi angka kejadian ADR.

scholarly journals The upper-airway microbiota and loss of asthma control among asthmatic children

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Yanjiao Zhou ◽  
Daniel Jackson ◽  
Leonard B. Bacharier ◽  
David Mauger ◽  
Homer Boushey ◽  
...  
Keyword(s):  
Asthma Control ◽  
Asthma Exacerbation ◽  
Upper Airway ◽  
Severe Exacerbation ◽  
Asthmatic Children ◽  
Time Points ◽  
Asthma Exacerbations ◽  
Severe Asthma Exacerbation ◽  
Airway Microbiome ◽  
One Year

AbstractThe airway microbiome has an important role in asthma pathophysiology. However, little is known on the relationships between the airway microbiome of asthmatic children, loss of asthma control, and severe exacerbations. Here we report that the microbiota’s dynamic patterns and compositions are related to asthma exacerbations. We collected nasal blow samples (n = 319) longitudinally during a clinical trial at 2 time-points within one year: randomization when asthma is under control, and at time of early loss of asthma control (yellow zone (YZ)). We report that participants whose microbiota was dominated by the commensal Corynebacterium + Dolosigranulum cluster at RD experience the lowest rates of YZs (p = 0.005) and have longer time to develop at least 2 episodes of YZ (p = 0.03). The airway microbiota have changed from randomization to YZ. A switch from the Corynebacterium + Dolosigranulum cluster at randomization to the Moraxella- cluster at YZ poses the highest risk of severe asthma exacerbation (p = 0.04). Corynebacterium’s relative abundance at YZ is inversely associated with severe exacerbation (p = 0.002).

scholarly journals Generality of Post-Antimicrobial Treatment Persistence of Borrelia burgdorferi Strains N40 and B31 in Genetically Susceptible and Resistant Mouse Strains

2019 ◽  
Vol 87 (10) ◽  
Author(s):  
Emir Hodzic ◽  
Denise M. Imai ◽  
Edlin Escobar
Keyword(s):  
Mouse Model ◽  
Borrelia Burgdorferi ◽  
Clinical Relevance ◽  
Antimicrobial Agents ◽  
Basic Feature ◽  
Antimicrobial Treatment ◽  
Mouse Strains ◽  
Resistant Mouse ◽  
Content Type ◽  
Disease Resistant

ABSTRACT A basic feature of infection caused by Borrelia burgdorferi, the etiological agent of Lyme borreliosis, is that persistent infection is the rule in its many hosts. The ability to persist and evade host immune clearance poses a challenge to effective antimicrobial treatment. A link between therapy failure and the presence of persister cells has started to emerge. There is growing experimental evidence that viable but noncultivable spirochetes persist following treatment with several different antimicrobial agents. The current study utilized the mouse model to evaluate if persistence occurs following antimicrobial treatment in disease-susceptible (C3H/HeJ [C3H]) and disease-resistant (C57BL/6 [B6]) mouse strains infected with B. burgdorferi strains N40 and B31 and to confirm the generality of this phenomenon, as well as to assess the persisters’ clinical relevance. The status of infection was evaluated at 12 and 18 months after treatment. The results demonstrated that persistent spirochetes remain viable for up to 18 months following treatment, as well as being noncultivable. The phenomenon of persistence in disease-susceptible C3H mice is equally evident in disease-resistant B6 mice and not unique to any particular B. burgdorferi strain. The results also demonstrate that, following antimicrobial treatment, both strains of B. burgdorferi, N40 and B31, lose one or more plasmids. The study demonstrated that noncultivable spirochetes can persist in a host following antimicrobial treatment for a long time but did not demonstrate their clinical relevance in a mouse model of chronic infection. The clinical relevance of persistent spirochetes beyond 18 months following antimicrobial treatment requires further studies in other animal models.

Abstract 4392: Vaccination targeting IGF-IR sensitizes tumors to tamoxifen therapy in an anti-estrogen resistant mouse model

2012 ◽  
Author(s):  
Denise L. Cecil ◽  
Kyong Hwa Park ◽  
Ekram Gad ◽  
Lauren Rastetter ◽  
Mary L. Disis
Keyword(s):  
Mouse Model ◽  
Tamoxifen Therapy ◽  
Resistant Mouse

Double-stranded RNA evokes exacerbation in a mouse model of corticosteroid refractory asthma

2015 ◽  
Vol 129 (11) ◽  
pp. 973-987 ◽  
Author(s):  
Jorge De Alba ◽  
Raquel Otal ◽  
Elena Calama ◽  
Anna Domenech ◽  
Neus Prats ◽  
...  
Keyword(s):  
Mouse Model ◽  
Asthma Exacerbation ◽  
Airway Hyperreactivity ◽  
Asthma Phenotype ◽  
Double Stranded Rna ◽  
Cytokines And Chemokines ◽  
Set Up ◽  
Refractory Asthma ◽  
Viral Exacerbation ◽  
Pro Inflammatory Cytokines

We have set up a new murine model mimicking aspects of viral exacerbation in a corticosteroid-refractory asthma phenotype. Our model shows an exacerbation of airway hyperreactivity, enhanced inflammation and elevated pro-inflammatory cytokines and chemokines associated with human asthma exacerbation.

In Silico Prediction of Novel Drug Combinations to Combat Bortezomib-Resistant Multiple Myeloma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1344-1344
Author(s):  
Holly A. F. Stessman ◽  
Tian Xia ◽  
Aatif Mansoor ◽  
Raamesh Deshpande ◽  
Linda B. Baughn ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Myeloma ◽  
Cell Lines ◽  
In Silico ◽  
Research Funding ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Mouse Cell ◽  
Resistant Mouse ◽  
Novel Therapeutic

Abstract Abstract 1344 Bortezomib/VELCADE® (Bz) is a proteasome inhibitor that has been used successfully in the treatment of multiple myeloma (MM) patients. However, acquired resistance to Bz is an emerging problem. Thus, there is a need for novel therapeutic combinations that enhance Bz sensitivity or re-sensitize Bz resistant MM cells to Bz. The Connectivity Map (CMAP; Broad Institute) database contains treatment-induced transcriptional signatures from 1,309 bioactive compounds in 4 human cancer cell lines. An input signature can be used to query the database for correlated drug signatures, a technique that has been used previously to identify drugs that combat chemoresistance in cancer (Wei, et al. Cancer Cell (2006) 10:331). In this study we used in silico bioinformatic screening of gene expression profiles from isogenic pairs of Bz sensitive and resistant mouse cell lines derived from the iMycCα/Bcl-xL mouse model of plasma cell malignancy to identify compounds that combat Bz resistance. We established Bz-induced kinetic gene expression profiles (GEPs) in 3 pairs of Bz sensitive and resistant mouse cell lines over the course of 24 hours. GEPs were collected in the absence of large-scale cell death. The 16 and 24 hour time points were averaged and compared between each Bz sensitive and resistant pair. Genes in the sensitive cell line with a fold change greater than 2, relative to the resistant line, were given the binary distinction of “up” or “down” depending on the direction of change. Genes that met these criteria were assembled into signatures, and then used as inputs for CMAP queries to identify compounds that induce similar transcriptional responses. In all pairs, treatment of the Bz sensitive line correlated with GEPs of drugs that target the proteasome, NF-κB, HSP90 and microtubules, as indicated by positive connectivity scores. However eight compounds, all classified as Topoisomerase (Topo) I and/or II inhibitors, were negatively correlated to our input signature. A negative connectivity score could have two interpretations: (1) this could indicate simply that Topos are upregulated by Bz treatment in Bz sensitive lines, which has been previously reported (Congdan, et al. Biochem. Pharmacol. (2008) 74: 883); or (2) this score could be interpreted as Topos are inhibited in Bz resistant cells upon Bz treatment. This led us to ask whether Topo inhibitors could target Bz resistant MM cells and re-sensitize them to Bz. Indeed, we found that multiple Topo inhibitors were significantly more active against Bz resistant cells as single agents and restored sensitivity to Bz when combined with Bz as a cocktail regimen. This work demonstrates the potential of this in silico bioinformatic approach for identifying novel therapeutic combinations that overcome Bz resistance in MM. Furthermore, it identifies Topo inhibitors – drugs that are already approved for clinical use – as agents that may have utility in combating Bz resistance in refractory MM patients. Disclosures: Stessman: Millennium: The Takeda Oncology Company: Research Funding. Van Ness:Millennium: The Takeda Oncology Company: Research Funding.

IL-10 leads to a higher parasite persistence in a resistant mouse model of Leishmania major infection

2002 ◽  
Vol 51 (4) ◽  
pp. 367-379 ◽  
Author(s):  
Alexandra Viana da Costa ◽  
Michel Huerre ◽  
Myriam Delacre ◽  
Claude Auriault ◽  
José Manuel Correia Costa ◽  
...  
Keyword(s):  
Mouse Model ◽  
Leishmania Major ◽  
Resistant Mouse ◽  
Major Infection
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