Salivary immunoglobulin A (IgA) concentration increased significantly after subjects viewed a humorous videotape and did not change significantly after they viewed a didactic videotape. Scores on a questionnaire measuring the perceived use of humor as a coping skill were positively related to initial IgA concentration and inversely related to changes in IgA concentration after subjects' viewing of the humorous videotape, which implies a ceiling effect. Enhancement of the immune system may be one link between anecdotal claims of relationships between an individual's being in a positive emotional state and healing.

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Purine-based analogs of SDZ 211-500 (5) were prepared and evaluated as inactivation modifiers of guinea pig or human cardiac sodium (Na) channels expressed in Xenopus oocytes. Substances which remove or slow the Na channel inactivation process in cardiac tissue are anticipated to prolong the effective refractory period and increase inotropy and thus have potential utility as antiarrhythmic agents. Heterocyclic substitution at the 6-position of the purine ring resulted in compounds with increased Na activity and potency, with 5-membered heterocycles being optimal. Only minor modifications to the benzhydrylpiperazine side chain were tolerated. Selected compounds which delayed the inactivation of Na channels were found to increase refractoriness and contractility in a rabbit Langendorff heart model, consistent with the cellular mechanism. Activity in both the oocyte and rabbit heart assays was specific to the S enantiomers. Preliminary in vivo activity has been demonstrated following intravenous infusion. The most promising compound on the basis of in vitro data is the formylpyrrole (S)-74, which is 25-fold more potent than DPI 201-106 (1) in the human heart Na channel assay.

No abstract