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Biomedical subjects

J Andrew Grant

Publications and source records attributed to J Andrew Grant.

5 recordsLinked to original sources
PubMed2004

Immunomodulation: the future of allergy and asthma treatment.

PURPOSE OF REVIEW: As the prevalence of asthma and allergic disease increases around the world, it is clear that more effective therapies and disease-modifying agents are needed. Treatment for allergic disease is evolving with an increase in understanding of the etiology. RECENT FINDINGS: The first immunomodulatory treatment was recently approved for use in the United States when the Food and Drug Administration approved the use of a humanized monoclonal anti-IgE antibody in patients with allergic asthma. Another strategy that has proved effective in a murine model is the downregulation of the whole immune system by targeting adhesion molecules, which has been evaluated in a recent human trial. Other strategies for the treatment of allergic diseases concentrate on refocusing the immune system away from an allergic-type response. These include the use of targeted therapies towards specific cytokines, cytokine receptors or chemokine receptors, and the use of specific bacterial DNA sequences (unmethylated cytosine-guanine dinucleotides). Finally, attention is being focused on possible therapies that may tilt the immune response to a non-allergic response by interfering with signaling molecule pathways. SUMMARY: Immunomodulation will play a key role in future therapies for allergic disease. These treatment modalities may not only treat allergic disease, but also be beneficial in reducing the morbidity and mortality for which it is responsible.

Animals↗
PubMed2004

Levocetirizine: the allergist's arsenal grows larger.

Antihistamines are the cornerstone of treatment for many allergic diseases, such as allergic rhinitis and chronic urticaria. Since the discovery of their beneficial effects in the 1940s, scientists have found molecules with greater selectivity to block specific histamine receptors without some of the detrimental side effects that are seen if antihistamines cross the blood-brain barrier. Levocetirizine is the active enantiomer of cetirizine and a selective H(1)-histamine blocker. It exhibits many favourable characteristics of an ideal antihistamine, both pharmacodynamically and pharmacokinetically, including high bioavailability, rapid onset of action, limited distribution and low degree of metabolism. Furthermore, clinical trials indicate that it is safe and effective for the treatment of allergic rhinitis and chronic urticaria with a minimal amount of untoward effects.

Allergy and Immunology↗
PubMed2003

Gaussian docking functions.

A shape-based Gaussian docking function is constructed which uses Gaussian functions to represent the shapes of individual atoms. A set of 20 trypsin ligand-protein complexes are drawn from the Protein Data Bank (PDB), the ligands are separated from the proteins, and then are docked back into the active sites using numerical optimization of this function. It is found that by employing this docking function, quasi-Newton optimization is capable of moving ligands great distances [on average 7 A root mean square distance (RMSD)] to locate the correctly docked structure. It is also found that a ligand drawn from one PDB file can be docked into a trypsin structure drawn from any of the trypsin PDB files. This implies that this scoring function is not limited to more accurate x-ray structures, as is the case for many of the conventional docking methods, but could be extended to homology models.

Binding Sites↗
PubMed2002

A double-blind, randomized, single-dose, crossover comparison of levocetirizine with ebastine, fexofenadine, loratadine, mizolastine, and placebo: suppression of histamine-induced wheal-and-flare response during 24 hours in healthy male subjects.

BACKGROUND: Levocetirizine is the active enantiomer of cetirizine, a potent drug with little metabolism widely used for allergic rhinitis and urticaria. OBJECTIVE: This study compares the potency, consistency, onset, and duration of action of levocetirizine with other popular antihistamines. METHODS: Levocetirizine 5 mg, ebastine 10 mg, fexofenadine 180 mg, loratadine 10 mg, mizolastine 10 mg, or placebo in single doses were given to 18 healthy male volunteers in a double-blind, crossover, randomized fashion. Wheal-and-flare responses to epicutaneous histamine dihydrochloride (100 mg/mL) challenge were measured at 0, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours after each dose. RESULTS: The overall effect of each drug was evaluated by the area under the curve (0 to 24 hours). Levocetirizine was the most potent and consistently effective drug for inhibiting the histamine-induced wheal-and-flare surface areas. Ebastine, fexofenadine, and mizolastine ranked next and had almost identical effects for inhibiting the wheal. Loratadine was the least potent drug. Levocetirizine, fexofenadine, and mizolastine inhibited the wheal-and-flare response after 1 hour and reached their peak for inhibition after 4 hours. Ebastine and loratadine could be distinguished from placebo only after 4 hours. After treatment with levocetirizine, all 18 subjects had >95% inhibition of the wheal response at one timepoint. Fexofenadine, mizolastine, and ebastine were inhibitory in declining order. All treatments were considered safe and well tolerated. CONCLUSIONS: Levocetirizine, the active enantiomer of cetirizine, is more potent and consistent than other popular H1 antihistamines for blocking the cutaneous response to histamine. These findings may predict the efficacy of this drug in treating allergic disorders.

Adult↗