Pooled analysis of two clinical trials comparing the clinical outcomes of topical ciprofloxacin/dexamethasone otic suspension and polymyxin B/neomycin/hydrocortisone otic suspension for the treatment of acute otitis externa in adults and children

Rahman, Ateequr; Rizwan, Shafeequr; Waycaster, Curtis; Wall, G. Michael

doi:10.1016/j.clinthera.2007.09.005

Cited by 24 publications

(8 citation statements)

References 11 publications

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“…These encouraging data thus prompted us to directly test whether post-inoculation administration of Rolipram has any therapeutic effect on treating middle ear inflammation under clinically relevant condition. Ototopical administration works effectively when the eardrum is perforated either pathologically or surgically by tympanostomy tube insertion363738. Thus, we next evaluated whether ototopical administration of Rolipram upregulates CYLD and suppresses inflammation in the middle ear of mice post NTHi infection.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of PDE4B suppresses inflammation by increasing expression of the deubiquitinase CYLD

et al. 2013

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The deubiquitinase CYLD acts as a key negative regulator to tightly control overactive inflammation. Most anti-inflammatory strategies have focused on directly targeting the positive regulator, which often results in significant side effects such as suppression of the host defence response. Here, we show that inhibition of phosphodiesterase 4B (PDE4B) markedly enhances upregulation of CYLD expression in response to bacteria, thereby suggesting that PDE4B acts as a negative regulator for CYLD. Interestingly, in Cyld-deficient mice, inhibition of PDE4B no longer suppresses inflammation. Moreover, PDE4B negatively regulates CYLD via specific activation of JNK2 but not JNK1. Importantly, ototopical post-inoculation administration of a PDE4 inhibitor suppresses inflammation in this animal model, thus demonstrating the therapeutic potential of targeting PDE4. These studies provide insights into how inflammation is tightly regulated via the inhibition of its negative regulator and may also lead to the development of new anti-inflammatory therapeutics that upregulate CYLD expression.

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Section: Resultsmentioning

confidence: 99%

Inhibition of PDE4B suppresses inflammation by increasing expression of the deubiquitinase CYLD

et al. 2013

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“…Our model emulates a dermal infection, which is characterized by a localized lesion, erythema, exudate and oedema, we confirmed that results with conventional histopathological methods, in where we observed inflammatory cells, also there was an increase in the number of peripheral blood neutrophils, specific leukocytes specialized to clear bacterial infections. In order to determine if the model developed is useful for testing anti-inflammatory and antibacterial formulations, we carried out a protocol where we tested the antibacterial effect of ciprofloxacin, antibiotic that has been previously tested as otic formulations [36, 37], and anti-inflammatory effect of hydrocortisone, which has been used as standard of anti-inflammatory effect in skin [4]. Our results showed that the model is useful when the drugs are tested in a curative way as well as preventive way.…”

Section: Discussionmentioning

confidence: 99%

A quantitative model for dermal infection and oedema in BALB/c mice pinna

et al. 2016

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BackgroundPharmaceutical industry demands innovation for developing new molecules to improve effectiveness and safety of therapeutic medicines. Preclinical assays are the first tests performed to evaluate new therapeutic molecules using animal models. Currently, there are several models for evaluation of treatments, for dermal oedema or infection. However, the most common or usual way is to induce the inflammation with chemical substances instead of infectious agents. On the other hand, this kind of models require the implementation of histological techniques and the interpretation of pathologies to verify the effectiveness of the therapy under assessment.This work was focused on developing a quantitative model of infection and oedema in mouse pinna. The infection was achieved with a strain of Streptococcus pyogenes that was inoculated in an injury induced at the auricle of BALB/c mice, the induced oedema was recorded by measuring the ear thickness with a digital micrometer and histopathological analysis was performed to verify the damage. The presence of S. pyogenes at the infection site was determined every day by culture.ResultsOur results showed that S. pyogenes can infect the mouse pinna and that it can be recovered at least for up to 4 days from the infected site; we also found that S. pyogenes can induce a bigger oedema than the PBS-treated control for at least 7 days; our results were validated with an antibacterial and anti-inflammatory formulation made with ciprofloxacin and hydrocortisone.ConclusionsThe model we developed led us to emulate a dermal infection and allowed us to objectively evaluate the increase or decrease of the oedema by measuring the thickness of the ear pinna, and to determine the presence of the pathogen in the infection site. We consider that the model could be useful for assessment of new anti-inflammatory or antibacterial therapies for dermal infections.

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“…CON, adequate protein diet + DW-administered group; PEM, low protein diet + DWadministered group; KBS, low protein diet + KBS-administered group; Arg, low protein diet + Arg-administered group. Giuliano et al, 2012;Rahman et al, 2007;Soheilian et al, 2011). However, Kugelberg et al (2005) reported that Dex eye drops inhibit growth in the newborn rabbit.…”

Section: Discussionmentioning

confidence: 99%

Effect of KH-BaRoKer-SeongJangTang based on traditional medicine theory on longitudinal bone growth

Kim¹,

Jeong²,

Park³

et al. 2014

TANG [HUMANITAS MEDICINE]

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KH-BaRoKer-SeongJangTang (KBS) is a recently developed formulation by using traditional drugs considering traditional medical theory of Oriental books such as ShinNongBonChoGyeong and JuRye, which has been used to improve the growth of child in Korea. Although KBS is usually prescribed to many children who are in retard for their age, its pharmacological effects have not been fully understood in experimental models. The aim of this study was to evaluate the effects of KBS on bone growth. Growth plate thickness and bone parameters such as bone volume/tissue volume (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), connection density (Conn.D), and total porosity were analyzed by means of microcomputed tomography. Serum insulin-like growth factor-I (IGF-I) levels were measured by enzyme-linked immunosorbent assay. Hepatic IGF-I mRNA expression was analyzed by real-time polymerase chain reaction. Phosphorylation of signal transducer and activator of transcription5 (STAT5) was investigated using Western blot analysis and immunohistochemistry. The thickness of growth plate was increased by KBS. BV/TV, Tb.Th, TbN, Conn.D, and total porosity were improved by KBS. Hepatic IGF-I mRNA and serum IGF-I levels were elevated by KBS. Phosphorylation of STAT5 was increased with administration of KBS. These results suggest that KBS would be helpful to children who are in retard for their age through the elevation of IGF-I.

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Pooled analysis of two clinical trials comparing the clinical outcomes of topical ciprofloxacin/dexamethasone otic suspension and polymyxin B/neomycin/hydrocortisone otic suspension for the treatment of acute otitis externa in adults and children

Cited by 24 publications

References 11 publications

Inhibition of PDE4B suppresses inflammation by increasing expression of the deubiquitinase CYLD

Inhibition of PDE4B suppresses inflammation by increasing expression of the deubiquitinase CYLD

A quantitative model for dermal infection and oedema in BALB/c mice pinna

Effect of KH-BaRoKer-SeongJangTang based on traditional medicine theory on longitudinal bone growth

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