scholarly journals Development of highly potent glucocorticoids for steroid-resistant severe asthma

2019 ◽  
Vol 116 (14) ◽  
pp. 6932-6937 ◽  
Author(s):  
Yuanzheng He ◽  
Jingjing Shi ◽  
Quang Tam Nguyen ◽  
Erli You ◽  
Hongbo Liu ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Unique Property ◽  
Asthma Treatment ◽  
Delivery Method ◽  
Fluticasone Furoate ◽  
Steroid Resistant ◽  
Inhalation Delivery ◽  
Pharmacokinetic Properties ◽  
Inhaled Glucocorticoids ◽  
Insight Into

Clinical application of inhaled glucocorticoids (GCs) has been hampered in the case of steroid-resistant severe asthma. To overcome this limitation, we have developed a series of highly potent GCs, including VSGC12, VSG158, and VSG159 based on the structural insight into the glucocorticoid receptor (GR). Particularly, VSG158 exhibits a maximal repression of lung inflammation and is 10 times more potent than the currently most potent clinical GC, Fluticasone Furoate (FF), in a murine model of asthma. More importantly, VSG158 displays a unique property to reduce neutrophilic inflammation in a steroid-resistant airway inflammation model, which is refractory to clinically available GCs, including dexamethasone and FF. VSG158 and VSG159 are able to deliver effective treatments with reduced off-target and side effects. In addition, these GCs also display pharmacokinetic properties that are suitable for the inhalation delivery method for asthma treatment. Taken together, the excellent therapeutic and side-effect profile of these highly potent GCs holds promise for treating steroid-resistant severe asthma.

scholarly journals Peptide drugs for photopharmacology: how much of a safety advantage can be gained by photocontrol?

2020 ◽  
Vol 2 (1) ◽  
pp. FDD28 ◽  
Author(s):  
Oleg Babii ◽  
Sergii Afonin ◽  
Tim Schober ◽  
Liudmyla V Garmanchuk ◽  
Liudmyla I Ostapchenko ◽  
...  
Keyword(s):  
Chemotherapeutic Agent ◽  
In Vitro Cytotoxicity ◽  
Pharmacokinetic Parameters ◽  
Cancer Model ◽  
Pharmacokinetic Properties ◽  
Insight Into ◽  
Safety Advantage ◽  
Murine Cancer Model

Aim: To verify whether photocontrol of biological activity could augment safety of a chemotherapeutic agent. Materials & methods: LD50 values for gramicidin S and photoisomeric forms of its photoswitchable diarylethene-containing analogs were determined using mice. The results were compared with data obtained from cell viability measurements taken for the same compounds. Absorption, Distribution, Metabolism, and Elimination (ADME) tests using a murine cancer model were conducted to get insight into the underlying reasons for the observed in vivo toxicity. Results: While in vitro cytotoxicity values of the photoisomers differed substantially, the differences in the observed LD50 values were less pronounced due to unfavorable pharmacokinetic parameters. Conclusion: Despite unfavorable pharmacokinetic properties as in the representative case studied here, there is an overall advantage to be gained in the safety profile of a chemotherapeutic agent via photocontrol. Nevertheless, optimization of the pharmacokinetic parameters of photoisomers is an important issue to be addressed during the development of photopharmacological drugs.

New insight into the clinical characteristics of adults vs children with severe asthma

2002 ◽  
Vol 109 (1) ◽  
pp. S353-S353 ◽  
Author(s):  
Henry Avner Jenkins ◽  
Stanley J Szefler ◽  
Ronina A Covar ◽  
Monica Jones ◽  
Eleanor E Brown ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Clinical Characteristics ◽  
Insight Into

Severe asthma treatment: need for characterising patients

The Lancet ◽  
2005 ◽  
Vol 365 (9463) ◽  
pp. 974-976 ◽  
Author(s):  
Liam G Heaney ◽  
Douglas S Robinson
Keyword(s):  
Severe Asthma ◽  
Asthma Treatment ◽  
Treatment Need

scholarly journals 2SPD-012 Cost minimisation study in severe asthma treatment

2020 ◽  
Author(s):  
J Ramos Rodríguez ◽  
S García Gil ◽  
L Cantarelli ◽  
J González García ◽  
C Romero Delgado ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Asthma Treatment ◽  
Cost Minimisation

Steroid-resistant inflammation in a mouse model of severe asthma is not inhibited by the combination of theophylline and budesonide

2018 ◽  
Author(s):  
Vince Russell ◽  
Mariapia Brana ◽  
Daniela Pompilio ◽  
Giulia Ambrosi ◽  
Filippo Andreetta ◽  
...  
Keyword(s):  
Mouse Model ◽  
Severe Asthma ◽  
Steroid Resistant

A Case Study; Extracorporeal Gas Exchange for Severe Asthma Treatment

2007 ◽  
Vol 119 (1) ◽  
pp. S173
Author(s):  
Y. Ogawa ◽  
E.G. Brooks ◽  
L. Williams ◽  
J. Lynch ◽  
J.B. Zwischenberger
Keyword(s):  
Gas Exchange ◽  
Severe Asthma ◽  
Asthma Treatment ◽  
Extracorporeal Gas Exchange

scholarly journals A retrospective analysis of severe asthma treatment with Mepolizumab

2019 ◽  
Vol 5 (1) ◽  
pp. 023-026
Author(s):  
M Serao ◽  
R Vigliarolo ◽  
T Trequattrini ◽  
A Succu ◽  
M Lilli
Keyword(s):  
Retrospective Analysis ◽  
Severe Asthma ◽  
Asthma Treatment
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