Intralesional Hyaluronic Acid Injection for Chondrodermatitis Nodularis Helicis: A Novel Treatment for Rapid Relief of Pain and Healing of Ulcerations.

BACKGROUND: Chondrodermatitis nodularis helicis (CNH) is a common chronic condition characterized by a tender nodule on the helix or antihelix of the ear which may or may not have accompanying crusting, scaling, or ulceration and that is often difficult to treat. OBJECTIVE: Develop an easy, effective, and durable treatment to reduce the pain and clinical signs including ulcerations associated with CNH using injectable hyaluronic acid (HA). MATERIALS AND METHODS: Twenty-four patients were injected and followed up in 2 to 4 weeks intervals using 0.2 to 0.3 mL of various HA with a high G-Prime. RESULTS: Injectable HA significantly improved the symptoms and also the clinical appearance of all patients treated after 1 or 2 injections except 1 patient. Extrusion of the material through a preexisting ulcer usually required a second follow-up injection 2 weeks later. No adverse events were noted with the injections other than the intentional visible bulging of the injected region with HA. CONCLUSION: Injectable HA provides almost immediate relief from the discomfort of CNH in most cases in less than 1 or 2 weeks, significantly improves the clinical appearance over time and resolves accompanying ulcerations.

Efficient In Vitro and In Vivo Anti-Inflammatory Activity of a Diamine-PEGylated Oleanolic Acid Derivative.

Recent evidence has shown that inflammation can contribute to all tumorigenic states. We have investigated the anti-inflammatory effects of a diamine-PEGylated derivative of oleanolic acid (OADP), in vitro and in vivo with inflammation models. In addition, we have determined the sub-cytotoxic concentrations for anti-inflammatory assays of OADP in RAW 264.7 cells. The inflammatory process began with incubation with lipopolysaccharide (LPS). Nitric oxide production levels were also determined, exceeding 75% inhibition of NO for a concentration of 1 µg/mL of OADP. Cell-cycle analysis showed a reversal of the arrest in the G0/G1 phase in LPS-stimulated RAW 264.7 cells. Furthermore, through Western blot analysis, we have determined the probable molecular mechanism activated by OADP; the inhibition of the expression of cytokines such as TNF-α, IL-1ß, iNOS, and COX-2; and the blocking of p-IκBα production in LPS-stimulated RAW 264.7 cells. Finally, we have analyzed the anti-inflammatory action of OADP in a mouse acute ear edema, in male BL/6J mice treated with OADP and tetradecanoyl phorbol acetate (TPA). Treatment with OADP induced greater suppression of edema and decreased the ear thickness 14% more than diclofenac. The development of new derivatives such as OADP with powerful anti-inflammatory effects could represent an effective therapeutic strategy against inflammation and tumorigenic processes.

Screening Anti-Inflammatory Effects of Flavanones Solutions.

There are a large number of remedies in traditional medicine focused on relieving pain and inflammation. Flavanones have been a potential source in the search for leading compounds and biologically active components, and they have been the focus of much research and development in recent years. Eysenhardtia platycarpa is used in traditional medicine for the treatment of kidney diseases, bladder infections, and diabetes mellitus. Many compounds have been isolated from this plant, such as flavones, flavanones, phenolic compounds, triterpenoid acids, chalcones, sugars, and fatty acids, among others. In this paper, natural flavanone 1 (extracted from Eysenhardtia platycarpa) as lead compound and flavanones 1a-1d as its structural analogues were screened for anti-inflammatory activity using Molinspiration® and PASS Online in a computational study. The hydro alcoholic solutions (FS) of flavanones 1, 1a-1d (FS1, FS1a-FS1d) were also assayed to investigate their in vivo anti-inflammatory cutaneous effect using two experimental models, a rat ear edema induced by arachidonic acid (AA) and a mouse ear edema induced by 12-O-tetradecanoylphorbol acetate (TPA). Histological studies and analysis of pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6 were also assessed in AA-inflamed rat ear tissue. The results showed that the flavanone hydro alcoholic solutions (FS) caused edema inhibition in both evaluated models. This study suggests that the evaluated flavanones will be effective when used in the future in skin pathologies with inflammation, with the results showing 1b and 1d to be the best.

Production and Characterization of Chitooligosaccharides: Evaluation of Acute Toxicity, Healing, and Anti-Inflammatory Actions.

The search for promising biomolecules such as chitooligosaccharides (COS) has increased due to the need for healing products that act efficiently, avoiding complications resulting from exacerbated inflammation. Therefore, this study aimed to produce COS in two stages of hydrolysis using chitosanases derived from Bacillus toyonensis. Additionally, this study aimed to structurally characterize the COS via mass spectrometry, to analyze their biocompatibility in acute toxicity models in vivo, to evaluate their healing action in a cell migration model in vitro, to analyze the anti-inflammatory activity in in vivo models of xylol-induced ear edema and zymosan-induced air pouch, and to assess the wound repair action in vivo. The structural characterization process pointed out the presence of hexamers. The in vitro and in vivo biocompatibility of COS was reaffirmed. The COS stimulated the fibroblast migration. In the in vivo inflammatory assays, COS showed an antiedematogenic response and significant reductions in leukocyte migration, cytokine release, and protein exudate. The COS healing effect in vivo was confirmed by the significant wound reduction after seven days of the experiment. These results indicated that the presence of hexamers influences the COS biological properties, which have potential uses in the pharmaceutical field due to their healing and anti-inflammatory action.

Sarcoidosis of the ear, nose and throat: A review of the literature.

OBJECTIVES: Sarcoidosis is a multisystemic inflammatory disease with extrathoracic manifestations, most commonly affecting the young and middle-aged, female and Black populations. Diagnosis usually requires evidence of non-caseating granulomata and, when treated, prognosis is usually favourable. We aim to establish the incidence, clinical features and optimal treatment of ENT manifestations of this disease. DESIGN: We performed a PubMed literature review to determine the evidence base supporting this. RESULTS: ENT manifestations are present in 5%-15% of patients with sarcoidosis, often as a presenting feature, and require vigilance for swift recognition and coordinated additional treatment specific to the organ. Laryngeal sarcoidosis presents with difficulty in breathing, dysphonia and cough, and may be treated by speech and language therapy (SLT) or intralesional injection, dilatation or tissue reduction. Nasal disease presents with crusting, rhinitis, nasal obstruction and anosmia, usually without sinus involvement. It is treated by topical nasal or intralesional treatments but may also require endoscopic sinus surgery, laser treatment or even nasal reconstruction. Otological disease is uncommon but includes audiovestibular symptoms, both sensorineural and conductive hearing loss, and skin lesions. CONCLUSIONS: The consequences of ENT manifestations of sarcoidosis can be uncomfortable, disabling and even life-threatening. Effective management strategies require good diagnostic skills and use of specific therapies combined with established treatments such as corticosteroids. Comparisons of treatment outcomes are needed to establish best practice in this area.

[Modern aspects of inflammatory external ear diseases treatment]. / Sovremennye aspekty lecheniya vospalitel'nykh zabolevanii naruzhnogo ukha.

The article deals with the problem of inflammatory diseases of the external ear. A review of pruritic dermatoses of the external auditory canal was carried out. It has been shown that in chronic dermatoses, the contamination of the skin with bacterial and fungal pathogens significantly increases, which leads to a high risk of developing secondary infectious pathological processes. Treatment of dermatological inflammatory ear diseases includes careful daily hygiene of the external auditory canal and pharmacotherapy, a key aspect of which is the use of topical etiotropic, anti-inflammatory, and symptomatic drugs. The advantage of the combined drug candiderm is described, which, thanks to the unique combination of beclomethasone, gentamicin and clotrimazole in the composition, effectively relieves the symptoms of external ear dermatoses.

6-Deoxy- and 11-Hydroxytolypodiols: Meroterpenoids from the Cyanobacterium HT-58-2.

Chemical investigation of cyanobacterial strain HT-58-2, which most closely aligns with the genus Brasilomena, has led to the isolation of two compounds related to tolypodiol. The structures and absolute configuration of 6-deoxytolypodiol (1) and 11-hydroxytolypodiol (2) were elucidated by spectroscopic and spectrometric analysis. While tolypodiol previously showed anti-inflammatory activity in a mouse ear edema assay, only 2 reduced in vitro thromboxane B2 and superoxide anion (O2-) generation from Escherichia coli lipopolysaccharide-activated rat neonatal microglia to any appreciable degree.

Successful treatment of erythematous-squamous disorders of the external auditory canal with tacrolimus and clotrimazole in otic oil: Our experience in 25 patients.

The external auditory canal (EAC) comprises a special area where erythematous-scaly diseases are located. Among the main dermatoses that can affect EAC seborrheic dermatitis, psoriasis, irritant or allergic contact dermatitis, chronic external otitis (atrial eczematoid dermatitis) and cutaneous lupus should be considered. In this study, 25 consecutive patients were recruited on our dermatological outpatient clinic, 9 men and 16 women, with a clinical diagnosis of localized erythematous-squamous dermatoses in EAC. The mean age was 48.8 years (16-83). The mean time of evolution of the dermatoses was 11.44 months (2-36). Regarding the diagnosis, 14 patients were diagnosed with seborrheic dermatitis (56%), 9 patients with psoriasis (36%), 1 patient with subacute cutaneous lupus (4%), and 1 patient with allergic contact dermatitis to corticosteroids (4%). The indicated treatment was tacrolimus 0.1% and clotrimazole 1% in otic oil, twice a day, for 1 month. The EAC had to be cleaned initially with saline solution impregnated on a swab from the ears. The IGA score and pruritus showed a high results, with important improvement of almost all patients. The satisfaction of the patients obtained with the TSQM-9 questionnaire was 95.2. Retreatment showed an equal efficacy observed during the first treatment period. The efficacy and the absence of side effects with the treatment make this magistral formula an adequate therapeutic option for these dermatoses.

Design, Synthesis and Evaluation of 3-Substituted Coumarin Derivatives as Anti-inflammatory Agents.

Coumarin moiety has garnered momentous attention especially in the design of compounds with significant biological activities. In this work, a series of 3-substituted coumarin derivatives 6a-6l were synthesized and fully characterized. Most of the compounds could obviously inhibit the activity of cyclooxygenase-1 (COX-1) at the concentration of 10 µM. Besides, 6h and 6l exhibited highest inhibitory effects against COX-2 with inhibition rates of 33.48 and 35.71%, respectively. Detailed structure-activity relationships (SARs) were also discussed. In vivo studies, 6b, 6i and 6l could remarkably repress the xylene-induced ear swelling in mice at the dose of 20 mg/kg. Especially, 6l seemed to be the most effective compound at the dose of 10 mg/kg, displaying favorable anti-inflammatory activity comparable to indomethacin. All of these findings suggested that 6l might be utilized as a candidate for the treatment of inflammatory diseases.

Effect of Terpenoids and Flavonoids Isolated from Baccharis conferta Kunth on TPA-Induced Ear Edema in Mice.

In this study, we isolated from the aerial parts of Baccharis conferta Kunth (i) a new neoclerodane, denominated "bacchofertone"; (ii) four known terpenes: schensianol A, bacchofertin, kingidiol and oleanolic acid; and (iii) two flavonoids: cirsimaritin and hispidulin. All structures were identified by an exhaustive analysis of nuclear magnetic resonance (NMR) and mass spectroscopy (MS). Extracts from aerial parts were screened for anti-inflammatory activity in the mice ear edema model of 12-O-tetradecanoylforbol-13-acetate mice. Dichloromethane extract (BcD) exhibited 78.5 ± 0.72% inhibition of edema, followed by the BcD2 and BcD3 fractions of 71.4% and 82.9% respectively, at a dose of 1 mg/ear. Kingidiol and cirsimaritin were the most potent compounds identified, with a median effective dose of 0.12 and 0.16 mg/ear, respectively. A histological analysis showed that the topical application of TPA promoted intense cell infiltration, and this inflammatory parameter was reduced with the topical application of isolated compounds.

Computational and Biological Comparisons of Plant Steroids as Modulators of Inflammation through Interacting with Glucocorticoid Receptor.

Despite the usefulness of glucocorticoids, they may cause hazardous side effects that limit their use. Searching for compounds that are as equally efficient as glucocorticoids, but with less side effects, the current study compared plant steroids, namely, glycyrrhetinic acid, guggulsterone, boswellic acid, withaferin A, and diosgenin with the classical glucocorticoid, fluticasone. This was approached both in silico using molecular docking against glucocorticoid receptor (GR) and in vivo in two different animal models. All tested compounds interacted with GR, but only boswellic acid and withaferin A showed docking results comparable to fluticasone, as well as similar in vivo anti-inflammatory effects, by significantly decreasing serum levels of interleukin-6 and tumor necrosis factor-α in cotton pellet-induced granuloma in rats. In addition, both compounds significantly decreased the percent of change in ear weight in croton oil-induced ear edema in mice and the granuloma weight in cotton pellet-induced granuloma in rats, to levels comparable to that of fluticasone. Both boswellic acid and withaferin A had no effect on adrenal index, but only withaferin A significantly increased the thymus index. In conclusion, boswellic acid may have comparable anti-inflammatory effects to fluticasone with fewer side effects.

Otic drug delivery systems: formulation principles and recent developments.

Disorders of the ear severely impact the quality of life of millions of people, but the treatment of these disorders is an ongoing, but often overlooked challenge particularly in terms of formulation design and product development. The prevalence of ear disorders has spurred significant efforts to develop new therapeutic agents, but perhaps less innovation has been applied to new drug delivery systems to improve the efficacy of ear disease treatments. This review provides a brief overview of physiology, major diseases, and current therapies used via the otic route of administration. The primary focuses are on the various administration routes and their formulation principles. The article also presents recent advances in otic drug deliveries as well as potential limitations. Otic drug delivery technology will likely evolve in the next decade and more efficient or specific treatments for ear disease will arise from the development of less invasive drug delivery methods, safe and highly controlled drug delivery systems, and biotechnology targeting therapies.

[Opportunistic mycoses of ENT organs. Part 1]. / Opportunisticheskie mikozy LOR-organov. Soobshchenie 1.

The present literature review summarizes information about the diseases of the upper respiratory tract and the ears caused by opportunistic fungi. The factors responsible for the increased frequency of opportunistic infections, among which mycosis is the leading one, are given. The exogenous and endogenous risk factors are described. The main pathogens of opportunistic mycotic infections of the ENT-organs are listed. Special attention is given to the mechanism underlying the development of anti-colonial immunity of the upper respiratory tract and the ears and the formation of the antifungal immunity of the macroorganism as a whole. The data on the pathogenetic factors of mycelial and yeast-like micromycetes are presented. The main variants of the pathogenetic mechanisms, such as adhesion, invasive growth, and penetration, behind the formation of the mycotic lesions are considered. These biological properties of the fungi contribute to their ability to cause a wide range of pathological changes - from the superficial lesions of the skin and mucous membranes of the ENT organs to the deep invasive processes. The protective cellular and humoral immune reactions of a macroorganism that develop in response to the introduction of a pathogenic fungus are described. The review lists the main nosological forms of mycosis known to affect the ENT-organs with special reference to the leading role of the yeast-like fungi belonging to the genus Candida in the development of mycotic lesions of these biotopes (64.65%). The most pathogenic species, Candida albicans, prevails in the structure of the yeast-like fungi biome whereas the leading role in the development of mycosis of the ENT organs by micromycetes of mold belongs to the species Aspergillus niger.

Evaluation of Biological Activity and Computer-Aided Design of New Soft Glucocorticoids.

Soft glucocorticoids are compounds that are biotransformed to inactive and non-toxic metabolites and have fewer side effects than traditional glucocorticoids. A new class of 17ß-carboxamide steroids has been recently introduced by our group. In this study, local anti-inflammatory activity of these derivatives was evaluated by use of the croton oil-induced ear edema test. Glucocorticoids with the highest maximal edema inhibition (MEI) were pointed out, and the systemic side effects of those with the lowest EC50 values were significantly lower in comparison to dexamethasone. A 3D-QSAR model was created and employed for the design of 27 compounds. By use of the sequential combination of ligand-based and structure-based virtual screening, three compounds were selected from the ChEMBL library and used as a starting point for the design of 15 derivatives. Molecular docking analysis of the designed derivatives with the highest predicted MEI and relative glucocorticoid receptor binding affinity (20, 22, 24-1, 25-1, 27, VS7, VS13, and VS14) confirmed the presence of interactions with the glucocorticoid receptor that are important for the activity.

Sonographic diagnosis of acute mastoiditis and subsequent retroauricular abscess in a pediatric cochlear implant recipient: A case report.

When acute mastoiditis occurs in cochlear implant recipients, it can progress to subsequent retroauricular abscess due to the absence of the external mastoid cortex resulting from mastoidectomy performed for cochlear implantation. The management goal is to control infection while preserving the implanted device. A 2-year-old boy with cochlear implants developed acute mastoiditis and a subsequent retroauricular abscess. The patient underwent a surgical intervention based on the diagnosis made utilizing gray-scale and power Doppler sonography. This case illustrates the diagnostic usefulness of sonography in this rare situation. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 45:515-519, 2017.

Use of oral fluralaner for the treatment of Psoroptes cuniculi in 15 naturally infested rabbits.

BACKGROUND: Psoroptes cuniculi, a nonburrowing ear mite, is a common ectoparasite of rabbits. Constant irritation of the auditory canal by the presence of this mite can lead to otitis externa or otoacariasis. OBJECTIVE: The goal of this study was to evaluate the effect of fluralaner on rabbits naturally infested with P. cuniculi and exhibiting clinical signs. ANIMALS: Fifteen female New Zealand domestic rabbits with otitis due to naturally occurring infestation with P. cuniculi. METHODS: The external ears and ear canals of each individual were examined; samples of otic exudate were extracted with cotton swabs and examined microscopically for identification of the ectoparasite. Each animal was treated with a single 25 mg/kg oral dose of fluralaner. The amount of otic exudate/cerumen was assessed and samples were obtained from the ears to evaluate for presence or absence of mites at 4, 8, 12, 16, 20, 40 and 90 days after receiving treatment. RESULTS: Post-treatment, the amount of otic exudate decreased rapidly in all animals; by Day 12 and until the end of the study all rabbits were judged to have low amount of exudate with normally visible canals. The percentage of ears positive for P. cuniculi decreased to 13.3% of ears sampled by Day 4, and by Day 12 all rabbits were negative for the parasite. CONCLUSION: Administration of a single oral dose of fluralaner was effective for the treatment of naturally occurring P. cuniculi infestation in rabbits during a 90 day period.

Self-Nanoemulsifying Drug Delivery Systems Containing Plantago lanceolata-An Assessment of Their Antioxidant and Antiinflammatory Effects.

The most important components of Plantago lanceolata L. leaves are catalpol, aucubin, and acteoside (=verbascoside). These bioactive compounds possess different pharmacological effects: anti-inflammatory, antioxidant, antineoplastic, and hepatoprotective. The aim of this study was to protect Plantago lanceolata extract from hydrolysis and to improve its antioxidant effect using self-nano-emulsifying drug delivery systems (SNEDDS). Eight SNEDDS compositions were prepared, and their physical properties, in vitro cytotoxicity, and in vivo AST/ALT values were investigated. MTT cell viability assay was performed on Caco-2 cells. The well-diluted samples (200 to 1000-fold dilutions) proved to be non-cytotoxic. The acute administration of PL-SNEDDS compositions resulted in minor changes in hepatic markers (AST, ALT), except for compositions 4 and 8 due to their high Transcutol contents (80%). The non-toxic compositions showed a significant increase in free radical scavenger activity measured by the DPPH test compared to the blank SNEDDS. An indirect dissolution test was performed, based on the result of the DPPH antioxidant assay; the dissolution profiles of Plantago lancolata extract were statistically different from each SNEDDS. The anti-inflammatory effect of PL-SNEDDS compositions was confirmed by the ear inflammation test. For the complete examination period, all compositions decreased ear edema as compared to the positive (untreated) control. It can be concluded that PL-SNEDDS compositions could be used to deliver active natural compounds in a stable, efficient, and safe manner.

Evidence-based veterinary dermatology: a review of published studies of treatments for Otodectes cynotis (ear mite) infestation in cats.

BACKGROUND: Otodectes cynotis (ear mite) accounts for 50-80% of cases of otitis externa in cats. Various treatment options exist but evidence-based reviews on treatments for this parasite have not been conducted. HYPOTHESIS/OBJECTIVES: The purpose of this study was to systematically review the efficacy of treatments for Otodectes cynotis infestation in cats, to provide recommendations for their use and to suggest methodologies for future clinical trials and research. METHODS: Electronic searches were carried out using the PubMed, CAB Direct and Thomson Reuters Web of Science; relevant topics were hand searched. The review was restricted to peer reviewed articles without limitation of language and publication date; only in vivo studies were included. The data were extracted and tabulated, then compared with regard to study design. With only a few randomized and controlled trials (RCTs) available, it was not possible to perform a meta-analysis of the pooled data. RESULTS: A total of 27 trials published between 1978 and 2015 fulfilled the selection criteria; 17 different pharmacological interventions were identified. There were two blinded RCTs and 25 open uncontrolled trials. CONCLUSIONS AND CLINICAL IMPORTANCE: There is fair evidence for recommending spot-on 10% imidacloprid +1% moxidectin or selamectin, once or twice 30 days apart, while there is insufficient evidence for or against recommending all other medications due to the quality of study designs in spite of their high efficacies. Future blinded RCTs, using placebo or appropriate active drugs, are required; outcome measurements on both clinical and microbiological and parasitological improvement, and proper follow-up periods are recommended.

Imiquimod treatment for Equus caballus papillomavirus infection in equine aural plaques.

BACKGROUND: Aural plaques are a dermatopathy associated with Equus caballus papillomavirus (EcPV). This disease affects horses of all ages, genders and breeds, and causes sensitivity of the ears. HYPOTHESIS/OBJECTIVES: The aim of this study was to evaluate the clinical efficacy of 5% imiquimod cream for the treatment of aural plaques and to compare the PCR detection of EcPV 3, 4, 5 and 6 before and after treatment. ANIMALS: Eight horses diagnosed with aural plaques (14 ears) were used. Three mares with unilateral aural plaques were used as untreated controls. METHODS: Imiquimod cream was applied every 48 h until complete resolution of the aural plaques was observed. Animals were evaluated clinically for 180 days after the end of treatment. PCR for detecting EcPV 3, 4, 5 and 6 was performed using aural plaque biopsies collected before and at 90 days after the end of treatment. RESULTS: Clinical resolution was observed in 93% of the treated ears. Imiquimod treatment promoted the clearance of EcPV in 71.4% of the treated ears. Clinical remission of the aural plaques and changes in EcPV DNA positivity between the first and second biopsies were not observed in the control group. In 75% of horses, sedation was required in order to carry out pretreatment cleaning. CONCLUSIONS: The results of this study support the hypothesis that 5% imiquimod cream may be used as an effective treatment for aural plaques in horses.

The Usefulness of 0.2% Topical Nitroglycerin for Chondrodermatitis Nodularis Helicis.

BACKGROUND AND OBJECTIVE: Chondrodermatitis nodularis helicis (CNH) is a painful idiopathic degenerative condition involving the skin and cartilage of the helix or antihelix of the ear. Topical nitroglycerin 2% is a relatively recent treatment option for CNH that has produced good results, although with adverse effects (17% of cases). The use of a lower concentration would probably achieve similar results with fewer adverse effects. The aim of this study was to evaluate the effectiveness and safety of topical nitroglycerin 0.2% in the treatment of CNH. MATERIAL AND METHODS: We performed a retrospective observational study of patients treated in 2 Spanish hospitals between 2012 and 2014. The effectiveness of treatment was determined by clinical photography and assessment of symptoms using a verbal numerical rating scale. RESULTS: Of the 29 patients treated, 93% showed clinical improvement. In the group of responders, mean treatment duration was 1.8 months and mean follow-up was 5.9 months. Overall tolerance was good in all cases. CONCLUSION: Topical nitroglycerin 0.2% is an effective and well-tolerated conservative treatment option that improves the appearance of lesions and provides symptomatic relief in the majority of patients with CNH.