The role of antihistamines in the new millennium.

Histamine, a pivotal mediator of inflammation, has been the target of therapeutic intervention in allergic disorders for the better part of the past century. During this time, the benefit-to-risk profiles of H1-receptor antagonists have improved. This review explores the pharmacologic properties of these agents, their roles in treating allergic disorders, their safety, and the avenues of future inquiry that might further define their therapeutic possibilities.

Induction of IgE responses using a recombinant mosquito salivary allergen rAed a 2 without adjuvant in mice.

Background: Reactions to mosquito bites are a global problem. Several salivary proteins from Aedes (Ae.) aegypti, the most common mosquito species, have been cloned and expressed.

Production and characterization of monoclonal antibodies to two new mosquito Aedes aegypti salivary proteins.

Mosquito salivary proteins, which are fundamental to the process of blood feeding, also facilitate disease transmission and cause allergic reactions. The identification and characterisation of these proteins have been hampered by the difficulty of obtaining them in purified form. In this report, we describe the production of mouse monoclonal antibodies (mAbs) against mosquito salivary proteins.

Allergic rhinobronchitis: the asthma-allergic rhinitis link.

Allergic rhinitis and asthma are linked by epidemiologic, histologic, physiologic, and immunopathologic characteristics and by a common therapeutic approach. Epidemiologically, the disorders often coexist. Histologically, the upper and lower airways are lined, and linked, by the respiratory epithelium.

Prospective, long-term safety evaluation of the H1-receptor antagonist cetirizine in very young children with atopic dermatitis. ETAC Study Group. Early Treatment of the Atopic Child.

Background: In very young children, H(1 )-receptor antagonists have not been adequately studied, although they are widely used and assumed to be safe.

Objective: Our objective was to test the hypothesis that cetirizine would be as safe as placebo for long-term use in this population.

Methods: In the prospective, double-blind, parallel-group, 18-month-long Early Treatment of the Atopic Child (ETAC) study, 817 children with atopic dermatitis who were 12 to 24 months old at study entry were randomized to receive either cetirizine 0.

Non-cardiac adverse effects of antihistamines (H1-receptor antagonists).

Antihistamines, available without prescription in many countries, are generally considered to be safe medications; however, the old first-generation H1 antagonists commonly cause adverse central nervous system (CNS) effects, even when administered in usual doses. Patients may not be aware of these effects and do not necessarily develop tolerance to them. In contrast, the new, second-generation H1 antagonists are relatively free from adverse effects in the CNS, primarily because they do not cross the blood-brain barrier and block the important neurotransmitter function of histamine.

Is antihistamine (H1-receptor antagonist) therapy useful in clinical asthma?

Airway hyperresponsiveness to histamine is a hallmark of asthma, and histamine inhalation reproduces asthma symptoms. Plasma histamine concentrations are elevated during the early and late responses to inhaled allergens, and may also increase during spontaneous acute asthma episodes. Ordinary doses of currently available antihistamines (H1-receptor antagonists) have minimal bronchodilator and bronchoprotective activity.

Clinical pharmacology of new histamine H1 receptor antagonists.

The recently introduced H1 receptor antagonists ebastine, fexofenadine and mizolastine, and the relatively new H1 antagonists acrivastine, astemizole, azelastine, cetirizine, levocabastine and loratadine, are diverse in terms of chemical structure and clinical pharmacology, although they have similar efficacy in the treatment of patients with allergic disorders. Acrivastine is characterised by a short terminal elimination half-life (t1/2 beta) [1.7 hours] and an 8-hour duration of action.

Common health problems in HIV-infected travelers to the (sub)tropics.

Background: A study was conducted to estimate the incidence of health problems in HIV-infected travelers with various degrees of immunodeficiency to the (sub)tropics.

Methods: A retrospective questionnaire-based study among HIV-infected patients attending the outpatient department of a university hospital during three months in 1996 with a history of travel to (sub)tropical destinations in the proceeding 12 months. The outcome measures were incidences of and medical consultation rates for common travel-associated illnesses.

Inhaled glucocorticoids in children: A favourable therapeutic index.

In children with persistent asthma, inhaled glucocorticoids decrease symptoms and exacerbations, decrease the need for rescue bronchodilator medications, improve airway patency and reduce airway hyperresponsiveness. When administered in the lowest doses that prevent symptoms and eliminate the need for supplemental courses of oral glucocorticoids, they are unlikely to cause clinically important systemic adverse events. Inhaled glucocorticoids have a favourable risk to benefit ratio in this population.

IP-10 mediated reinforcement of human type 1 cytokine synthesis to environmental allergens among non-atopic subjects.

Background: Non-atopic subjects do not differ from those with allergic rhinitis or asthma in their ability to respond to environmental antigens, but in the nature of their response. IP-10, a CXC (alpha) chemokine, is produced by a wide variety of cell types, and differs from most chemokines in its specificity for activated lymphocytes. Here, we examine its potential role in the maintenance of putatively protective, type-1-dominated cytokine responses among non-atopic individuals.

Mizolastine: antihistaminic activity from preclinical data to clinical evaluation.

Mizolastine, a new H1-receptor antagonist, is highly selective for histamine H1 receptors and has no anticholinergic, antiadrenergic, or antiserotonin activity. It is rapidly absorbed after oral ingestion, with peak plasma concentrations occurring at 1.5 h.

Central nervous system effects of H1-receptor antagonists in the elderly.

Background: The potential adverse central nervous system effects of H1-receptor antagonists have not been optimally studied in the elderly.

Objective: We hypothesized that newer H1-receptor antagonists such as cetirizine and loratadine would cause less central nervous system dysfunction than the older H1-receptor antagonists diphenhydramine and chlorpheniramine in this population, as they do in younger subjects.

Methods: We performed a randomized, double-blind, single-dose, placebo-controlled, 5-way crossover study in 15 healthy elderly subjects (mean age 71 +/- SD 5 years).

The clinical pharmacology of brompheniramine in children.

Background: Brompheniramine has been widely used in the treatment of allergic rhinitis and other disorders during the past 4 decades. There are no published studies of its clinical pharmacology in children.

Objectives: This study was performed to test the hypothesis that brompheniramine would have a prompt onset of action and a 24-hour duration of action in children.

Environmental antigen-induced IL-13 responses are elevated among subjects with allergic rhinitis, are independent of IL-4, and are inhibited by endogenous IFN-gamma synthesis.

Human immediate hypersensitivity diseases represent the most common example of chronic excessive Th2-like activation in developed nations. While IL-13 shares many functional properties with IL-4, the intensity and regulation of environmental Ag-stimulated IL-13 synthesis by allergic vs nonallergic individuals remain ill defined. Here, we examine the intensity of polyclonally and Ag-stimulated IL-13 production by PBMC of 20 subjects with seasonal allergic rhinitis and 20 healthy controls.

Benefits and risks of inhaled glucocorticoids in children with persistent asthma.

In children, an inhaled glucocorticoid is currently the medication of choice for the long-term control of persistent asthma. Inhaled glucocorticoids are significantly more effective than nonsteroidal medications on all outcome measures of asthma treatment. They reduce the frequency of symptoms and of acute asthma exacerbations, decrease the need for "rescue" medications, improve airway patency, and reduce airway hyperresponsiveness.

A mouse model of mosquito allergy for study of antigen-specific IgE and IgG subclass responses, lymphocyte proliferation, and IL-4 and IFN-gamma production.

To date, there are no ideal animal models for study of natural sensitization leading to IgE- and lymphocyte-mediated hypersensitivities. We established such a model in which four BALB/c mice were each sensitized by exposure to at least 16 mosquito Aedes aegypti bites, twice a week for 4 weeks. Four non-exposed control mice were also studied.

Human IP-10 selectively promotes dominance of polyclonally activated and environmental antigen-driven IFN-gamma over IL-4 responses.

Human interferon-inducible protein 10 (IP-10) differs from most chemokines in its apparent specificity for activated T lymphocytes. We hypothesized that IP-10 was relevant not only for recruiting T cells to inflammatory sites, but also for regulating cytokine synthesis patterns. We examined the effect of recombinant human IP-10 (rhIP-10) on human interferon gamma (IFN-gamma) and interleukin 4 (IL-4) production by fresh peripheral blood mononuclear cells.

Immunoblot analysis of salivary allergens in 10 mosquito species with worldwide distribution and the human IgE responses to these allergens.

Background: Most people develop skin reactions to mosquito bites, however, little is known about mosquito salivary allergens and the IgE responses to them.

Objectives: We sought to identify these allergens and the specific IgE responses they elicit.

Methods: Saliva or salivary gland extracts were prepared from 10 mosquito species, including seven species with worldwide distribution: Aedes (Ae.

Highly sensitive and specific ELISA with monoclonal antibody capture to measure Dermatophagoides farinae 1-specific IgE.

Background: Dermatophagoides farinae (Der f) is a major allergen in Der f extract. Measurement of Der f I-specific IgE has not been commonly used, because of the difficulty in obtaining large amounts of purified Der f 1.

Objectives: To improve the diagnosis of dust mite allergy, we wanted to develop an ELISA to measure Der f 1-specific IgE in which purified Der f 1 is not required.

Expression and rapid purification of an Aedes aegypti salivary allergen by a baculovirus system.

Mosquito salivary proteins cause allergic reactions in humans. Recombinant salivary allergens will facilitate both the diagnosis and immunotherapy of mosquito allergy. The Aed a 1, a 68-kD apyrase in the saliva of Aedes aegypti, has been demonstrated to be an allergen which binds to the IgE of mosquito-allergic subjects.