Inflammation & Allergy - Drug Targets

(Formerly 'Current Drug Targets - Inflammation & Allergy')

ISSN: 1871-5281

Upcoming Articles


Metal Allergens of Growing Significance: Epidemiology, Immunotoxicology, Strategies for Testing and Prevention
Giovanni Forte, Francesco Petrucci and Beatrice Bocca
[Abstract]


Non-IgE Mediated Food Allergy
Harumi Jyonouchi
[Abstract]


Lead Compounds for Anti-inflammatory Drugs Isolated from the Plants of the Traditional Oriental Medicine in Korea
JangJa Hong, Kuk Hyun Shin, Soon Sung Lim, Jong Hwan Kwak, OkPyo Zee, Kenji Ishihara, Noriyasu Hirasawa, Toshio Seyama and Kazuo Ohuchi>
[Abstract]


Pulmonary Arterial Hypertension: Need to Treat
Dimosthenis Lykouras, Fotis Sampsonas, Alex Kaparianos, Georgios Efremidis, Kiriakos Karkoulias, George Tsoukalas and Kostas Spiropoulos
[Abstract]




Abstracts

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Metal Allergens of Growing Significance: Epidemiology, Immunotoxicology, Strategies for Testing and Prevention
Giovanni Forte, Francesco Petrucci and Beatrice Bocca

Metal-induced allergic contact dermatitis (ACD) is expressed in a wide range of cutaneous reactions following dermal and systemic exposure to products such as cosmetics and tattoos, detergents, jewellery and piercing, leather tanning, articular prostheses and dental implants. Apart from the well known significance of nickel in developing ACD, other metals such as aluminium, beryllium, chromium, cobalt, copper, gold, iridium, mercury, palladium, platinum, rhodium and titanium represented emerging causes of skin hypersensitivity. Despite the European Union directives that limit the total nickel content in jewellery alloys, the water soluble chromium (VI) in cement, and metals banned in cosmetics, the diffusion of metal-induced ACD remained quite high. On this basis, a review on the epidemiology of metal allergens, the types of exposure, the skin penetration, the immune response, and the protein interaction is motivated. Moreover, in vivo and in vitro tests for the identification and potency of skin-sensitizing metals are here reviewed in a risk assessment framework for the protection of consumer’s health. Avenues for ACD prevention and therapy such as observance of maximum allowable metal levels, optimization of metallurgic characteristics, efficacy of chelating agents and personal protection are also discussed.


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Non-IgE Mediated Food Allergy
Harumi Jyonouchi

Adverse reactions to dietary proteins (DPs) can impose a significant impact on one’s daily life and can even affect the ‘life style’ of an entire family. Adverse reactions to DPs may or may not be immune-mediated. The immune-mediated adverse reaction to food is defined as food allergy (FA) which is roughly divided into IgE mediated or non-IgE mediated FA (NFA). As opposed to IgE mediated FA, NFA primarily affects the GI mucosa. In addition, there is far less of an understanding of NFA than IgE-mediated FA and its clinical relevance is likely under-estimated in most cases. This is partly due to delayed onset of symptoms and subsequent difficulty in making the clinical association between offending food and clinical symptoms. The lack of easily accessible diagnostic measures also contributes to the problem.

The gut mucosal barrier is thought to have developed to execute an immensely difficult task; digestion and absorption of nutrients without provoking immune responses and cohabiting with commensal flora in a mutual beneficial relationship, while maintaining an immune defense against pathogenic microbes. The gut mucosal immune system accomplishes this task partly by establishing tolerance to macronutrients with potent immunogenecity. Immune tolerance to macronutrients (DPs) is maintained in part by active suppressive mechanisms involving antigen (Ag)-specific regulatory T (Treg) cells. This active immune tolerance state appears to be affected by various environmental factors such as change in commensal flora.

In the first few years of life, humans gradually develop an intricate balance between tolerance and immune reactivity in the gut mucosa along with a tremendous expansion of gut associated lymphoid tissue (GALT). Not surprisingly, both IgE and non-IgE mediated food allergy (FA) is frequently seen during this period. The most common causative DPs for NFA are those contained in infant formulas (cow’s milk and soy proteins). Unlike IgE mediated FA, NFA is rarely life-threatening. However, NFA to DPs can cause significant morbidity in rapidly growing infants and young children. A better understanding of pathogenesis of NFA is crucial for timely management of NFA in this vulnerable population.

This review discusses the gut mucosal immune system in the first few years of life including genetic/environmental factors affecting the development of mucosal immune system and pathogenesis of NFA in association with clinical/laboratory findings.


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Lead Compounds for Anti-inflammatory Drugs Isolated from the Plants of the Traditional Oriental Medicine in Korea
JangJa Hong, Kuk Hyun Shin, Soon Sung Lim, Jong Hwan Kwak, OkPyo Zee, Kenji Ishihara, Noriyasu Hirasawa, Toshio Seyama and Kazuo Ohuchi

Effects of compounds isolated from medicinal plants in Korea on prostaglandin E₂  (PGE₂) production in rat peritoneal macrophages were examined, and mechanism of action of the active constituents was analyzed. The active constituents were as follows; tectorigenin and tectoridin isolated from the rhizomes of Belamcanda chinensis, platycodin D isolated from the roots of Platycodon grandiflorum, imperatorin isolated from the roots of Angelica dahurica, and hyperin isolated from the roots of Acanthopanax chiisanensis. These compounds inhibit the induction of cyclooxygenase-2 (COX-2), thus inhibiting PGE₂ production. The chemically synthesized chalcone derivative, 2’-hydroxy-4’-methoxychalcone, also inhibits PGE₂ production by suppressing COX-2 induction. In contrast, taiwanin C isolated from the roots of Acanthopanax chiisanensis inhibited PGE₂ production by direct inhibition of COX-1 and COX-2.


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Pulmonary Arterial Hypertension: Need to Treat
Dimosthenis Lykouras, Fotis Sampsonas, Alex Kaparianos, Georgios Efremidis, Kiriakos Karkoulias, George Tsoukalas and Kostas Spiropoulos

Pulmonary Arterial Hypertension (PAH) is defined by a persistent elevation in pulmonary artery pressure with normal left-sided pressures. It is characterized by increased pulmonary vascular resistance due to increased vascular tone and structural remodeling of pulmonary vessels. PAH is a quite rare condition, thus considering the rarity, subtle presentation, and diagnostic dilemma commonly posed by this disease, underdiagnosis and underreporting are probably widespread. In order to reach a diagnosis the use of echocardiography, right-heart catheterization and the six-minute walk test is essential.

As far as therapy is concerned, the patient should be supported by oxygen, diuretics, anticoagulants, digoxin and suggest life-style changes. After diagnosing the condition ca-blockers should be administered to those who respond positively in acute vasodilation test. Other agents used, target the endothelin pathway (ET-1 blockers such as bosentan), the NO pathway (sildenafil, inhaled NO, L-arginine) and the prostacyclin pathway (prostacyclin analogues). In some cases surgical treatment is essential (atrial septestomy, pulmonary endarterectomy, lung and heart transplantation). Finally, future therapies include administration of VIP and SSRIs. The goals of evaluating pulmonary hypertension are detection, definition of severity and the nature of the hemodynamic lesion and its consequences, diagnosis of causal or associated conditions, and determination of optimal therapy.