Ear inflammation

Vertex also put in clinical trial VX-765, another caspase-1 -specific, YVAD-derived peptidomimetic that is in vitro slightly more potent then pralnacasan (IC50 0.8 nM). Evaluation of VX-765 in a mouse model of oxazolone-induced dermatitis showed a dose-dependent (10-100 mg/kg) inhibition of ear inflammation. Consequently, VX-765 was enrolled in a 4-week phase Ila safety and pharmacokinetic study for psoriasis. However, Vertex has not communicated any results yet. 

One of the conspicuous resorcinols is HU-308 (362), which is a CB2-specific agonist this compound does not bind to CBi (if > 10 uM), but has a significant affinity for CB2 ( i = 22.7 nM) [226]. HU-308 elicited analgesic activity in a formalin-induced peripheral pain model and an anti-infiam-matory effect on arachidonic acid-induced ear inflammation, though it showed no activity in a tetrad of behavioural tests, which are linked to CNS activity (Table 6.34). 

Anti-edema activity. Methanol extract of the rhizome, applied topically to mice at a dose of 2 mg/ear, was active vs 12-0-tetradecanoyl-13-acetate-induced ear inflammation. The inhibition ratio was nine " . 

In order to avoid even the minimal systemic side effects seen with currently available corticosteroids, scientists at Glaxo synthesized a series of androstane 17/ -car-boxylates and carbothiolates. It was found that halomethyl carbothiolates showed the highest topical activity as assessed by the inhibition of croton oil-induced ear inflammation in mice. The highest activity was found in the fluoromethyl car-bo thiolate-17-propionate (fluticasone propionate) synthesized from flumethasone [49-51],... 

Development of new drugs and devices to treat diseases of the external ear requires an understanding of pathophysiology and knowledge about the most common organisms responsible for ear inflammation and infections. 

Alkaloids isolated from an unidentified colonial zoanthid have also exhibited interesting biological activities. Zoanthamine (5), zoanthenamine (6), zoanthamide (7), and 28-deoxyzoanthenamine (8) possess inhibitory activity in the phorbol myristate acetate (PMA)-induced mouse ear inflammation assay, as well as analgesic activity (22). Zoanthamine (5) also exhibited strong nematicidal activity against the root-knot nematode (Meloidogyne javanica) and antibacterial activity (41). 

Gary, J. R, Liu, Y., Laskin, J. D., Heck, D. E., Ho, C.-T., and Huang, M. T. 2006. Inhibitory effects of epigallocatechin-3-gallate, theaflavins and caffeine on 12-O-tetra-decanoylphorbol-13-acetate induced mouse ear inflammation and expression of inflammatory cytokines. Proc. AACR 47 66. 

Effect of theaflavin mixture on TPA-induced ear inflammation and levels of inflammatory mediators in female CD-I mice... 

Table II. Inhibitory Activity of Curcuminoids (0.6 imoi) on TP A (2 ng)-lnduced Mouse Ear Inflammation...

The activation of mast cells by allergen initiates the asthma symptoms within minutes after allergen contact, the early allergic response (EAR), within horns the late allergic response (LAR), and within years and after rqDeated asthma episodes, chronic airway inflammation, airway remodeling, and airway hyperresponsiveness. 

Frequently, the EAR is followed by a late phase response 4-6 h later and it is caused by the pulmonary sequestration of eosinophils, neutrophils, mast cells, and T-lymphocytes. This leukocyte recruitment depends on mast cell-derived mediators such as TNFa and various chemokines, as well as on the expression of adhesion molecules on leukocytes (e.g. VLA-4, CD11/18) and vascular endothelial cells (e.g. VCAM-1, ICAM-1, E-selectin). Products of these leukocytes have several functions First, they cause the second phase of bron-choconstriction, mucus secretion, and airway swelling second, they cause tissue destruction third, they launch and entertain the chronic inflammation. 

Asthma is a chronic inflammatory disease. Therefore steroids represent the most important and most frequently used medication. Already after the fust treatment, steroids reduce cellular infiltration, inflammation, and the LAR, whereas changes in the EAR require prolonged treatment to lower the existent IgE levels. The mechanisms of steroid actions are complex and only incompletely understood. Besides their general antiinflammatory properties (see chapter glucocorticoids), the reduction of IL-4 and IL-5 production from T-lymphocytes is particularly important for asthma therapy. The introduction of inhaled steroids, which have dramatically limited side effects of steroids, is considered one of the most important advancements in asthma therapy. Inhaled steroids (beclomethasone, budesonide, fluticasone, triamcinolone, momethasone) are used in mild, moderate, and partially also in severe asthma oral steroids are used only in severe asthma and the treatment of status asthmaticus. Minor side effects of most inhaled steroids are hoarseness and candidasis, which are avoided by the prodrug steroid ciclesonide. 

Otic preparations are instilled in the external auditory canal and may be used to relieve pain, treat infection and inflammation, and aid in the removal of earwax. When the patient has an inner ear infection, systemic antibiotic therapy is indicated. 

The nurse assesses the patient s response to therapy. For example a decrease in pain or inflammation should occur. The nurse examines the outer ear and ear canal for any local redness or irritation that may indicate sensitivity to die drug. 

Rabbit Ear Bioassay for Acnegenic Activity. Acnegenic activity of 2-7-DCDD, 1,2,3,4-TCDD, 2,3,7,8-TCDD, HCDD, and OCDD was tested by applying 0.1 ml of either a solvent solution or the supernatant of a solvent suspension of each compound to the inner surface of the rabbit s ears five days a week for four weeks. The ears were examined weekly for signs of chloracne, inflammation, and hyperkeratosis. The responses were divided into five categories (1) none, (2) very slight, (3) slight, (4) moderate, and (5) severe. 

Otitis media, or inflammation of the middle ear, is the most common reason for prescribing antibiotics in children. It usually occurs after a viral infection of the nasopharynx and can be subclassified as acute otitis media or otitis media with... 

Multiple factors play a role in the development of AOM. Viral infection of the nasopharynx impairs eustachian tube function and causes mucosal inflammation, impairing mucociliary clearance and promoting bacterial proliferation and infection. Children are predisposed to AOM because their eustachian tubes are shorter, more flaccid, and more horizontal than adults, which make them less functional for drainage and protection of the middle ear from bacterial entry. Clinical signs and symptoms of AOM are the result of host immune response and damage to cells caused by inflammatory mediators such as tumor necrosis factor and interleukins that are released from bacteria.4... 

Acute otitis media Inflammation of the middle ear accompanied by fluid in the middle ear space and signs or symptoms of an acute ear infection. 

Otitis media is an inflammation of the middle ear. Acute otitis media involves the rapid onset of signs and symptoms of inflammation in the middle ear that manifests clinically as one or more of the following otalgia (denoted by pulling of the ear in some infants), hearing loss, fever, or irritability. Otitis media with effusion (accumulation of liquid in the middle ear cavity) differs from acute otitis media in that signs and symptoms of an acute infection are absent. 

Direct application of phenol to the inner ear of rats has resulted in external otitis, inner ear damage, and decreased brain-stem auditory response (Schmidt et al. 1990), and inflammation of the tympanic membrane (Schmidt and Hellstrom 1993). These studies were conducted because phenol has been used as a topical anesthetic in infected ears. 

NDGA also inhibits 5-LO in a variety of systems [65-68]. In vivo, antiinflammatory activity has been reported in lipopolysaccharide (LPS)-in-duced knee inflammation in rats [69] and in AAE and croton oil induced ear oedema [70,71]. However, in a 14-day clinical trial in psoriasis, no efficacy was seen following topical application of NDGA [72]. Although this compound has been used as an archetypal 5-LO inhibitor in many studies, the general antioxidant properties of this compound require caution in these interpretations. 

Otitis media is inflammation or infection of the middle ear and is not usually associated with back pain. Osteoporosis is a condition occurring mostly in postmenopausal women and is characterised by brittle bones caused by reduced bone mass. It is presented with pain. If it occurs in the vertebral structure the condition may be associated with chronic back pain. Pregnancy may be associated with back pain because of an increase in weight and the increased strain. 

Otitis externa inflammation or infection of the external ear Otitis interna labyrinthitis, inflammation or infection of the inner ear... 

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