Anti-inflammatory effects of low-dose oral theophylline in atopic asthma

Sullivan, Paul; Jaffar, ZH; Page, Clive; Costello, John; Bekir, Sümeyye Alparslan; Jeffery, Peter K.

doi:10.1016/s0140-6736(94)90127-9

Cited by 377 publications

(197 citation statements)

References 14 publications

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“…This effect was comparable to previous reports on the ability of chronic treatment with low dose theophylline to inhibit allergen-induced late phase reactions [22]. However, clinical efficacy of the PDE4-inhibitors cilomilast and roflumilast has mainly been studied in COPD.…”

Section: Early Clinical Trials With Pde4-inhibitorssupporting

confidence: 87%

PDE4-inhibitors: A novel, targeted therapy for obstructive airways disease

Diamant

Spina

2011

Pulmonary Pharmacology & Therapeutics

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SummaryRoflumilast is a selective once daily, oral phosphodiesterase-4 inhibitor that has recently been registered in all European Union countries as novel targeted therapy for COPD, while FDA approval for the USA market is expected in 2011. In several phase III trials in patients with moderate to (very) severe COPD and in patients with symptoms of chronic bronchitis and recurrent exacerbations, roflumilast showed sustained clinical efficacy by improving lung function and by reducing exacerbation rates. These beneficial effects have also been demonstrated when added to long-acting bronchodilators (both LABA and LAMA), underscoring the anti-inflammatory activity of roflumilast in COPD. Pooled data analysis showed overall mild to moderate, mostly self-limiting adverse events, mainly consisting of nausea, diarrhea and weight loss. In this review we discuss the results of the 4 registration studies showing promising effects of roflumilast in COPD and provide an overview of the topics that still need to be addressed. keywords: PDE4-inhibitor, roflumilast, clinical trials, chronic obstructive airways disease 3

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Section: Early Clinical Trials With Pde4-inhibitorssupporting

confidence: 87%

PDE4-inhibitors: A novel, targeted therapy for obstructive airways disease

Diamant

Spina

2011

Pulmonary Pharmacology & Therapeutics

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“…Aminophylline, a nonselective PDE inhibitor, has been traditionally used for the treatment of asthma. It has been shown that aminophylline has numerous antiinflammatory effects, including the inhibition of inflammatory mediators and activation of NF-κB (22)(23)(24)(25). Previously, other groups have reported that a PDE5 inhibitor restores mdx mouse muscle to normal (20,21,26).…”

Section: Discussionmentioning

confidence: 99%

Drug screening in a zebrafish model of Duchenne muscular dystrophy

Kawahara

Karpf

Myers

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

159

176

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Two known zebrafish dystrophin mutants, sapje and sapje-like (sap c/100 ), represent excellent small-animal models of human muscular dystrophy. Using these dystrophin-null zebrafish, we have screened the Prestwick chemical library for small molecules that modulate the muscle phenotype in these fish. With a quick and easy birefringence assay, we have identified seven small molecules that influence muscle pathology in dystrophin-null zebrafish without restoration of dystrophin expression. Three of seven candidate chemicals restored normal birefringence and increased survival of dystrophin-null fish. One chemical, aminophylline, which is known to be a nonselective phosphodiesterase (PDE) inhibitor, had the greatest ability to restore normal muscle structure and up-regulate the cAMP-dependent PKA pathway in treated dystrophin-deficient fish. Moreover, other PDE inhibitors also reduced the percentage of affected sapje fish. The identification of compounds, especially PDE inhibitors, that moderate the muscle phenotype in these dystrophin-null zebrafish validates the screening protocol described here and may lead to candidate molecules to be used as therapeutic interventions in human muscular dystrophy.phosphodiesterase inhibitor | chemical treatment M uscular dystrophy is a disease in which the muscle forms normally at first but then degenerates faster than it can be repaired. The most common form of muscular dystrophy is Duchenne muscular dystrophy (DMD), representing more than 90% of the diagnosed cases. Mutations in the dystrophin gene were found to be the cause of both DMD and Becker muscular dystrophy (1, 2). Currently, prednisone is the only treatment option available for muscular dystrophy patients in the United States, although there are currently other options through approved clinical trials. Other treatments currently being tested or considered for treating muscular dystrophy include the small molecule PTC124, which promotes read-through of nonsense mutations (3), encouraging muscle development by myostatin down-regulation (4, 5), and the use of oligonucleotides to promote exon skipping to restore dystrophin expression (6).Recently, a number of chemical and drug screens have been published using zebrafish embryos (7-11). It is possible to quickly produce large numbers of mutant offspring that can then be assayed in multiwell plates and treated with different chemicals to determine if disease progression is modulated. Many of these screens have been highly successful in disease modeling (7) and drug screening (8-10), making the zebrafish ideal for highthroughput whole-organism screening of candidate compounds. Chemical compounds of relatively small molecular weight can bind to specific proteins and alter their function, resulting in nonheritable phenotype changes.In addition to their suitability for chemical screens, zebrafish also represent a good model to investigate genes involved in muscle development and degeneration, including human muscular dystrophy (12-18). The orthologs of many dystrophin-glycoprot...

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“…Previous studies reported that diabetics may show hypertrophy of the adrenal cortex concomitant with an increase in the adrenal steroid production (Kraus Schleimer 1990). In a variety of species, treatment with glucocorticoid effectively prevented infiltration of eosinophils into local tissue sites after antigen stimulation (Sanjar et al 1990, Sullivan et al 1994. We have recently reported that rats with alloxan diabetes show a reduction in the pleural mast cell population and also a suppression of the antigen-induced pleural eosinophilia, phenomena clearly sensitive to insulin treatment (Diaz et al 1996).…”

Section: Previous Studies Have Evidenced For the Existence Of Interacmentioning

confidence: 99%