scholarly journals Novel Mouse Models of Fungal Asthma

Author(s):  
Michael Daines ◽  
Rhea Pereira ◽  
Aubrey Cunningham ◽  
Barry Pryor ◽  
David G. Besselsen ◽  
...  

Alternaria alternata is a ubiquitous fungus and a major allergen associated with the development of asthma. Inhalation of intact spores is the primary cause of human exposure to fungal allergen. However, allergen-rich cultured fungal filtrates are oftentimes used in the current models of fungal sensitization that do not fully reflect real-life exposures. Thus, establishing novel spore exposure models is imperative. In this study, we established novel fungal exposure models of both adult and neonate to live spores. We examined pathophysiological changes in the spore models as compared to the non-exposure controls and also to the conventional filtrate models. While both Alternaria filtrate- and spore-exposed adult BALB/c mice developed elevated airway hyperresponsiveness (AHR), filtrates induced a greater IgE mediated response and higher broncholavage eosinophils than spores. In contrast, the mice exposed to Alternaria spores had higher numbers of neutrophils. Both exposures induced comparable levels of lung tissue inflammation and mucous cell metaplasia (MCM). In the neonatal model, exposure to Alternaria spores resulted in a significant increase of AHR in both adult and neonatal mice. Increased levels of IgE in both neonatal and adult mice exposed to spores was associated with increased eosinophilia in the treatment groups. Adult demonstrated increased numbers of lymphocytes that was paralleled by increased IgG1 production. Both adults and neonates demonstrated similarly increased eosinophilia, IgE, tissue inflammation and MCM.

Diagnostics ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 83
Author(s):  
Shih-Lung Cheng

Despite the expansion of the understanding in asthma pathophysiology and the continual advances in disease management, a small subgroup of patients remains partially controlled or refractory to standard treatments. Upon the identification of immunoglobulin E (IgE) and other inflammatory mediators, investigations and developments of targeted agents have thrived. Omalizumab is a humanized monoclonal antibody that specifically targets the circulating IgE, which in turn impedes and reduces subsequent releases of the proinflammatory mediators. In the past decade, omalizumab has been proven to be efficacious and well-tolerated in the treatment of moderate-to-severe asthma in both trials and real-life studies, most notably in reducing exacerbation rates and corticosteroid use. While growing evidence has demonstrated that omalizumab may be potentially beneficial in treating other allergic diseases, its indication remains confined to treating severe allergic asthma and chronic idiopathic urticaria. Future efforts may be bestowed on determining the optimal length of omalizumab treatment, seeking biomarkers that could better predict treatment response and as well as extending its indications.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1485.3-1485
Author(s):  
F. Carubbi ◽  
A. Alunno ◽  
P. Cipriani ◽  
V. Pavlych ◽  
C. DI Muzio ◽  
...  

Background:Over the last 2 decades rituximab (RTX) has been widely used, albeit off-label, in primary Sjögren’s syndrome (pSS). Several studies reported that B-lymphocyte depletion with RTX is effective in this disease not only by reducing disease activity but also by affecting the inflammation and the lymphoid organization that occur in target tissues. With the recent release of several RTX biosimilars (bRTX) on the market, the demonstration of their interchangeability with RTX originator (oRTX) is required.Objectives:To compare efficacy and safety of oRTX and bRTX in pSS patients in a real-life setting.Methods:Clinical records of pSS patients referring to a tertiary rheumatology clinic were retrospectively evaluated. Patients having received at least 2 courses of either oRTX or bRTX (1000 mg IV infusion, repeated after 2 weeks -1 course- and the course repeated after 24 weeks) with complete data at baseline and after 3, 6, 9 and 12 months of treatment were enrolled. Disease activity was assessed with the EULAR SS disease activity index (ESSDAI) and its clinical version without the biological domain (ClinESSDAI). Patient-reported symptoms were assessed with the EULAR SS Patient Reported Index (ESSPRI).Results:Seven patients that received oRTX and 7 patients that received bRTX were enrolled. Baseline clinical features, including ESSDAI and ESSPRI were similar in the 2 treatment groups. Both compounds significantly reduced ESSDAI and ESSPRI as early as 3 months and no difference between the groups was observed at any time point (Figure 1). Of interest, ESSDAI slowly decreased until month 6 when the most pronounced reduction was observed. Conversely, ESSPRI dropped to its lowest values already at month 3. With regard to safety, at 12 months of follow-up no adverse event was observed in any of the treatment groups.Conclusion:At 12 months of follow-up, oRTX and bRTX display similar efficacy and safety profiles. The improvement of patient reported outcomes is faster than the improvement of disease activity with both compounds. Our data support interchangeability of oRTX and bRTX in pSS.References:[1]Carubbi F et al. Arthritis Res Ther. 2013;15(5):R172[2]Carubbi F et al. Lupus. 2014;23(13):1337-49Figure 1 ESSDAI and ESSPRI values at every time point in the 2 treatment groups. Asterisks indicate p values <0.05 compared to the other treatment group at the same time pointDisclosure of Interests:Francesco Carubbi Speakers bureau: Francesco Carubbi received speaker honoraria from Abbvie and Celgene outside this work., Alessia Alunno: None declared, Paola Cipriani Grant/research support from: Actelion, Pfizer, Speakers bureau: Actelion, Pfizer, Viktoriya Pavlych: None declared, claudia di muzio: None declared, Roberto Gerli: None declared, Roberto Giacomelli Grant/research support from: Actelion, Pfizer, Speakers bureau: Abbvie, Roche, Actelion, BMS, MSD, Ely Lilly, SOBI, Pfizer


1992 ◽  
Vol 71 (3_suppl) ◽  
pp. 811-813 ◽  
Author(s):  
F. Schäfer ◽  
S.J. Raven ◽  
T.A. Parr

A major criterion for assessing the value of any experimental model in scientific research is the degree of correspondence between its results and data from the real-life process it is designed to model. Intra-oral models aimed at predicting the anti-caries efficacy of toothpastes or other topical treatments should therefore be calibrated against treatments proven to be effective in a caries clinical trial. For this to be achieved, it is necessary that a model with high sensitivity be designed, while at the same time retaining relevance to the process to be modeled. This means that the effects of the various experimental conditions and parameters of the model on its performance must be understood. The purpose of this paper was to assess the influence of two specific factors on the performance of an in situ enamel remineralization model, which is based on human enamel slabs attached to partial dentures. The two factors are initial lesion severity and origin of enamel sample. The results indicated that initial lesion size affected whether net remineralization or net demineralization occurred during in situ treatment. Samples with an initial range of from 1500 to 2500 (ΔZ) tended more toward demineralization than did samples with ΔZ > 3500. This means that treatment groups must be well-balanced with respect to initial lesion size. Differences in initial demineralization severity between different tooth locations must also be considered so that systematic treatment bias can be avoided. The solution used in the model discussed here is based on a balanced experimental design, which allows this effect to be taken into account in the data analysis.


2016 ◽  
Vol 16 (12) ◽  
Author(s):  
Zhonghua Zhang ◽  
Tiina Reponen ◽  
Gurjit K. Khurana Hershey
Keyword(s):  

Chemotherapy ◽  
2019 ◽  
Vol 64 (1) ◽  
pp. 8-16 ◽  
Author(s):  
Vittorio Magri ◽  
Gianpaolo Perletti ◽  
Tommaso Cai ◽  
Konstantinos Stamatiou ◽  
Alberto Trinchieri ◽  
...  

Background: Mounting worldwide resistance trends make the use of fluoroquinolone (FQ) antibacterial agents increasingly difficult. This is felt more acutely in the case of urogenital infections, which are mainly caused by Gram-negative pathogens. For years, levofloxacin and other FQs have been the first-line drugs for treating National Institutes of Health (NIH) category II chronic bacteria prostatitis (CBP). Eradication rates achieved by levofloxacin in the frame of randomized trials vary greatly, ranging between 71 and 86%. Objectives: This was a retrospective observational study to investigate the efficacy of levofloxacin against CBP in a real-life setting (urological outpatient wards). Methods: A database including the clinical records of >2,500 CBP patients was reviewed. Patients were selected based on strict inclusion criteria. They were treated for 4 weeks with 500 mg levofloxacin per day, alone or combined with other antibacterials. Besides standard urological procedures including the 4-glass test for pathogen isolation, international symptom questionnaires (the NIH Chronic Prostatitis Symptom Index [NIH-CPSI] and International Prostate Symptom Score [IPSS]) were administered. Results: Pathogen eradication was achieved in 79% of the cases treated with levofloxacin as a single agent and 87.8% of patients who received a combination of levofloxacin and azithromycin. The 11% increase in the eradication rate in the latter group is statistically significant. In addition, the levofloxacin-azithromycin combination caused a significant decrease in prostate volume and significantly increased the bladder-voided volume. IPSS and NIH-CPSI values and the urinary peak flow rate decreased to a similar extent in both treatment groups. No adverse effects were reported by patients belonging to either treatment group. Conclusion: Levofloxacin retained its therapeutic efficacy in patients assessed in a real-life setting, and high eradication rates were attained when it was administered as a single agent. A combination of an FQ with azithromycin induced a significant improvement of eradication rates. This strategy may be an interesting option in both first-referral and relapsing cases, although caution should be exercised when patients are at risk of developing arrhythmias, tendinitis, or other adverse effects.


2016 ◽  
Vol 8 (5) ◽  
pp. 438 ◽  
Author(s):  
Chang-Ching Yeh ◽  
Hsiao-Yun Tai ◽  
Hong Chou ◽  
Keh-Gong Wu ◽  
Horng-Der Shen

Allergy ◽  
2002 ◽  
Vol 57 (2) ◽  
pp. 98-106 ◽  
Author(s):  
G. Pasini ◽  
B. Simonato ◽  
A. Curioni ◽  
S. Vincenzi ◽  
A. Cristaudo ◽  
...  

2019 ◽  
Vol 3 (2) ◽  
pp. 86-95
Author(s):  
Esti Novi Andyarini ◽  
Nova Lusiana ◽  
Ika Mustika ◽  
Estri Kusumawati ◽  
Sri Hidayati ◽  
...  

Aspartame is safe for consumption according to the prescribed ADI, but this artificial sweetener is not nutritious or does not contain calories so it is not recommended to be consumed during pregnancy. This study was to analyze cariometric effect of aspartame doses in the development of fetal mice (Mus muculus L.). The type of research used was experimental laboratory research on 24 adult mice with 4 treatment groups, control, aspartame dose 13 mg / Kg BB, 39 mg / Kg BB and 78 mg / Kg BB. Data was analyzed using SPSS 16 with one way ANOVA. Based on the results of the study there were changes in the number and weight of the fetus due to aspartame doses, there was no change in fetal length due  of aspartame dose variations. Consumption of aspartame during pregnancy should be avoided because it can cause teratogenic effects. For further research, it is necessary to observe the morphology and histology of the fetus which is expressed by aspartame to determine the types of congenital abnormalities.


2019 ◽  
Vol 12 ◽  
pp. 1179173X1987843 ◽  
Author(s):  
Pasquale Caponnetto ◽  
Jennifer DiPiazza ◽  
Giorgio Carlo Cappello ◽  
Shirin Demma ◽  
Marilena Maglia ◽  
...  

Background: Tobacco use is a global pandemic, affecting an estimated 1.2 billion people and resulting in substantial health burdens and associated costs. Objectives: The aim of this study was to estimate the efficacy of several treatments for smoking cessation in a real-life setting and to evaluate predictors of smoking abstinence. Methods: This research was designed with a sample of 593 cases recorded over the period between 2015 and 2016. Six treatment groups were included: (1) bupropion and motivational interviewing (MI); (2) bupropion, nicotine replacement therapy (NRT), and MI; (3) NRT and MI; (4) varenicline and MI; (5) personal vaporizer electronic cigarette and MI; and (6) electronic cigarette, cigarette like “cigalike,” and MI. Results: Results support the efficacy of all treatment groups when used in a real-life setting. The predictors of smoking abstinence were sex, partner smoking status, previous quit attempts, daily consumption, self-efficacy, and level of nicotine dependence. Conclusions: The use of different therapeutic strategies in clinical practice, including pharmacotherapy and nonstandard electronic nicotine delivery systems, such as an electronic cigarette, ensures a greater chance of cessation success and the possibility of tailoring interventions according to patients’ resources.


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