Long-term omalizumab use in the treatment of exercise-induced anaphylaxis.

Reported is a case of a 39-year-old male who was diagnosed with exercise-induced anaphylaxis (EIA). He was initially treated prophylactically with fexofenadine, montelukast, and ranitidine. He also used an epinephrine autoinjector as needed. He was refractory to these medications and continued to have episodes of EIA. He was then started on a trial of omalizumab, an immunoglobulin E monoclonal antibody, and had resolution of the EIA episodes. After discontinuation of the omalizumab, the EIA episodes returned. He was restarted on omalizumab and since that time, has had 5 years free of EIA episodes and can now exercise without any symptoms. To our knowledge, this is only the third case in the literature of successful treatment of EIA by using omalizumab. This case was unique because it provided successful long-term use of omalizumab for EIA. Further studies are recommended for the use of omalizumab in the treatment of EIA.

Allergic Stomatitis From Orthodontic Adhesives.

We report a case of a type IV hypersensitivity reaction causing oral stomatitis, presumed to be the result of common dental adhesives. The case was diagnosed using patch testing to the dental adhesives that were used in the patient. Both of the adhesives tested contained a form of acrylate that is being seen more frequently in the literature as a cause of type IV hypersensitivity reactions. Metals can cause allergic reactions; however, other contact items need to be considered as a cause of oral allergic reactions. Cases of allergic stomatitis are rising and there is question if all-in-one adhesives may be contributing to this rise.

Two interacting binding sites for quinacrine derivatives in the active site of trypanothione reductase: a template for drug design.

Trypanothione reductase is a key enzyme in the trypanothione-based redox metabolism of pathogenic trypanosomes. Because this system is absent in humans, being replaced with glutathione and glutathione reductase, it offers a target for selective inhibition. The rational design of potent inhibitors requires accurate structures of enzyme-inhibitor complexes, but this is lacking for trypanothione reductase. We therefore used quinacrine mustard, an alkylating derivative of the competitive inhibitor quinacrine, to probe the active site of this dimeric flavoprotein. Quinacrine mustard irreversibly inactivates Trypanosoma cruzi trypanothione reductase, but not human glutathione reductase, in a time-dependent manner with a stoichiometry of two inhibitors bound per monomer. The rate of inactivation is dependent upon the oxidation state of trypanothione reductase, with the NADPH-reduced form being inactivated significantly faster than the oxidized form. Inactivation is slowed by clomipramine and a melarsen oxide-trypanothione adduct (both are competitive inhibitors) but accelerated by quinacrine. The structure of the trypanothione reductase-quinacrine mustard adduct was determined to 2.7 A, revealing two molecules of inhibitor bound in the trypanothione-binding site. The acridine moieties interact with each other through pi-stacking effects, and one acridine interacts in a similar fashion with a tryptophan residue. These interactions provide a molecular explanation for the differing effects of clomipramine and quinacrine on inactivation by quinacrine mustard. Synergism with quinacrine occurs as a result of these planar acridines being able to stack together in the active site cleft, thereby gaining an increased number of binding interactions, whereas antagonism occurs with nonplanar molecules, such as clomipramine, where stacking is not possible.