Effects of an Amphoteric Antiallergic Agent, HSR-609, on Antigen-Induced Late Phase Nasal Eosinophilia in Brown Norway Rats

Musoh, Keiichi; Nakamura, Nobuaki; Nagai, Hiroichi

doi:10.1159/000028406

Cited by 2 publications

(2 citation statements)

References 45 publications

(54 reference statements)

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“…All major laboratory rat strains have been used to establish allergic conjunctivitis models. Next to Brown-Norway rats (60,61), which are also the preferred strain for the induction of allergic airway inflammation (45,46) IgE-mediated models. IgE-mediated models of rat conjunctivitis used either direct or indirect sensitization and a large number of questions were answered with this species.…”

Section: Ratsmentioning

confidence: 99%

Animal models of allergic and inflammatory conjunctivitis

Groneberg

Bielory

Fischer

et al. 2003

Allergy

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Numerous recent reports have demonstrated an increase in the prevalence and incidence of allergic conditions during the past years which affect approximately 25% of the general population (1) and about US$ 6 billion alone are estimated as direct costs of allergic rhinoconjunctivitis (2). Whereas a large amount of studies have focused on the pathophysiology of allergic rhinitis and asthma over the past years, ocular allergies are less well studied. However, allergic diseases affecting the eye are very common (3) and pediatric studies have shown that within distinct cohorts, up to 32% of allergic children have an ocular allergy as the primary manifestation of allergy (4). Allergic eye diseases such as allergic conjunctivitis commonly present with the symptoms of itchy, watery, red, sore and swollen eyes, but not pain (5).In contrast to the large amount of experimental studies on allergic asthma and the detailed knowledge that exists on mediators of allergic airway inflammation (6-8), there are few experimental studies using models of allergic eye diseases. Detailed reviews to assess the pathophysiology and immunology of ocular allergies have been limited. This review hopefully fills this void to provide the clinical and translational researcher in the area of ocular allergy. Pathophysiology of ocular allergiesBefore characterizing the different animal models of ocular allergy which have been established so far, it is crucial to reflect that within the area of ocular allergies, different disease entities exist and that only some of them may be mimicked by animal models. Formally, conjunctivitis may be divided into allergic and nonallergic conjunctivitis and the allergic form may also be subdivided into IgE-mediated and non-IgE-mediated allergic conjunctivitis ( Fig. 1) (9). Clinically, the spectrum of conjunctivitis types can be subdivided into allergic conjunctivitis, atopic keratoconjunctivitis, vernal keratoconjunctivitis and giant papillary conjunctivitis.In contrast to the other forms of conjunctivitis, allergic conjunctivitis is commonly based on an IgEmediated hypersensitivity reaction. Furthermore, allergic Allergic eye diseases are complex inflammatory conditions of the conjunctiva with an increasing prevalence and incidence. The diseases are often concomitant with other allergic diseases such as allergic rhinitis, atopic dermatitis and allergic asthma. Despite the disabling and prominent symptoms of ocular allergies, they are less well studied and further insights into the molecular basics are still required. To establish new therapeutic approaches and assess immunological mechanisms, animal models of ocular allergies have been developed in the past years. The major forms of allergic ocular diseases, seasonal and perennial allergic conjunctivitis, vernal and atopic keratoconjunctivitis and giant papillary conjunctivitis, each have different pathophysiological and immunological components. In contrast to these distinct entities, the current animal models are based on the sensitization against a small numbe...

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Section: Ratsmentioning

confidence: 99%

Animal models of allergic and inflammatory conjunctivitis

Groneberg

Bielory

Fischer

et al. 2003

Allergy

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“…In two rodent models of antigen-induced inflammation, HSR-609 significantly reduced eosinophil infiltration into the upper and lower airways during the LP reaction [92,93]. Concomitant reduction of IL-5 concentrations and inhibition of bronchial hyper-reactivity suggests that the anti-allergic effects of HSR-609 are linked to multiple anti-inflammatory mechanisms aside from H 1 antagonism.…”

Section: Anti-inflammatory Activitymentioning

confidence: 99%

Antihistamines in late-phase clinical development for allergic disease

Salmun

2002

Expert Opinion on Investigational Drugs

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Allergic rhinitis (AR) is a global health concern and shares a high comorbidity with asthma. Recent research suggests that different allergic diseases, such as AR, asthma, allergic conjunctivitis and chronic idiopathic urticaria (CIU), are evoked by common pathological mechanisms characterised by the release of histamine and other inflammatory mediators. Although H(1) receptor antagonists are the mainstay of therapy for allergic disease, the unacceptably high incidence of anticholinergic and CNS-related side effects of first-generation H(1) antagonists led to the search for improved second-generation H(1) antagonists. While many of these agents were largely devoid of CNS side effects, their tendency for drug-drug interactions (e.g., terfenadine and astemizole) resulted in an increased incidence of cardiotoxicity. Furthermore, second-generation H(1) antagonists exhibited weak anti-inflammatory properties and had no effect on nasal congestion. These observations emphasised the need for newer anti-allergic agents with a broader spectrum of activity and an improved safety profile. Among the newer H(1) antagonists currently in clinical development, desloratadine and mizolastine are the most widely studied. Both have a rapid onset of action, and desloratadine has demonstrated clinical efficacy in AR, CIU and seasonal asthma. Desloratadine has several advantages over other H(1) antagonists in that it has proven decongestant activity, a sparing effect on the use of bronchodilators (beta(2)-agonists) and a low potential for drug interactions. The broad anti-inflammatory properties of desloratadine and mizolastine, which distinguish these agents from other H(1) antagonists in clinical development (e.g., norastemizole and levocetirizine), suggest they may have a more profound impact on the underlying disease in patients suffering from different forms of allergy. The lack of clinical efficacy and safety data on rupatadine and HSR-609, both novel H(1) antagonists, precludes an accurate assessment of their potential for treating allergic disease. Epinastine and efletirizine are being developed exclusively for topical application and are unlikely to play a significant role in the management of allergic diseases as a whole.

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Effects of an Amphoteric Antiallergic Agent, HSR-609, on Antigen-Induced Late Phase Nasal Eosinophilia in Brown Norway Rats

Cited by 2 publications

References 45 publications

Animal models of allergic and inflammatory conjunctivitis

Animal models of allergic and inflammatory conjunctivitis

Antihistamines in late-phase clinical development for allergic disease

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