Integrative role of the histaminergic system in feeding and taste perception

Feeding behavior is regulated by a complex interplay of many endogenous substances, such as peptides and neurotransmitters in the central nervous system. Histamine is a neurotransmitter which expresses an anorectic effect on food intake via histamine H1 receptors. The histaminergic system exists downstream of leptin, a satiety factor secreted from white adipose tissue. Because direct stimulation of the histaminergic system by histamine H3-inverse agonists or antagonists can normalize the obese phenotype in which animal models with exogenous leptin resistance, which resembles human obesity, the potential roles of histamine H3 receptors as a therapeutic target now draw attention. Histaminergic activity is enhanced during feeding, and an oral somatic sensation is thought to affect histaminergic activity while blood glucose levels do not. In addition, gustatory information can modulate histaminergic activity by two mechanisms: by physiological excitation of the chorda tympani nerve, one of the taste nerves and by emotions elicited by taste perception, i.e., taste palatability. Particularly, aversive and hazardous taste stimuli tonically facilitate histaminergic activity, suggesting that the histaminergic system is involved in the response to harmful stimuli. Together with recent findings, it is postulated that the histaminergic system responds to both mechanical and chemical sensory input from the oral cavity during feeding and is exerted as a part of the danger response system

Efficacy and Safety of a Traditional Herbal Medicine, Hochu-ekki-to in the Long-term Management of Kikyo (Delicate Constitution) Patients with Atopic Dermatitis: A 6-month, Multicenter, Double-blind, Randomized, Placebo-controlled Study

Hochu-ekki-to is a traditional herbal (Kampo) medicine that has been shown to be effective for patients with Kikyo (delicate, easily fatigable, or hypersensitive) constitution. Previous case reports have suggested that this herbal drug was effective for a certain subgroup of patients with atopic dermatitis (AD). We aimed to evaluate the efficacy and safety of Hochu-ekki-to in the long-term management of Kikyo patients with AD. In this multicenter, double blind, randomized, placebo-controlled study, 91 Kikyo patients with AD were enrolled. Kikyo condition was evaluated by a questionnaire scoring system. All patients continued their ordinary treatments (topical steroids, topical tacrolimus, emollients or oral antihistamines) before and after their protocol entry. Hochu-ekki-to or placebo was orally administered twice daily for 24 weeks. The skin severity scores, total equivalent amount (TEA) of topical agents used for AD treatment, prominent efficacy (cases with skin severity score = 0 at the end of the study) rate and aggravated rate (more than 50% increase of TEA of topical agents from the beginning of the study) were monitored and evaluated. Seventy-seven out of 91 enrolled patients completed the 24-week treatment course (Hochu-ekki-to: n = 37, placebo: n = 40). The TEA of topical agents (steroids and/or tacrolimus) was significantly (P < 0.05) lower in the Hochu-ekki-to group than in the placebo group, although the overall skin severity scores were not statistically different. The prominent efficacy rate was 19% (7 of 37) in the Hochu-ekki-to group and 5% (2 of 40) in the placebo group (P = 0.06). The aggravated rate was significantly (P < 0.05) lower in the Hochu-ekki-to group (3%; 1 of 37) than in the placebo group (18%; 7 of 39). Only mild adverse events such as nausea and diarrhea were noted in both groups without statistical difference. This placebo-controlled study demonstrates that Hochu-ekki-to is a useful adjunct to conventional treatments for AD patients with Kikyo constitution. Use of Hochu-ekki-to significantly reduces the dose of topical steroids and/or tacrolimus used for AD treatment without aggravating AD

Involvement of leukotriene pathway in the development of sevoflurane-induced pica in rats

We previously reported that sevoflurane-induced pica, kaolin ingestion behavior, in rats has the potential to reflect post-operative nausea and vomiting (PONV) in humans. It is well-known that corticosteroids, which inhibit both prostaglandin and leukotriene syntheses due to phospholipase A2 inhibition, are effective for reducing PONV; however, the precise mechanisms remain unclear. We investigated the involvement of the prostaglandin or leukotriene pathway in the development of sevoflurane-induced pica. We found that sevoflurane-induced pica was effectively inhibited by pretreatment with a leukotriene receptor antagonist (montelukast) or an inhibitor of 5-lipoxygenase (zileuton), rather than an inhibitor of cyclooxygenase (flurbiprofen). Furthermore, we observed that sevoflurane significantly increased urinary leukotriene excretion and 5-lipoxygenase mRNA expression in the spleen, but not hypothalamus. These results suggest that the production of leukotriene may lead to the development of sevoflurane-induced pica in rats, and that inhibition of the leukotriene pathway could be potentially useful for the treatment of PONV.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author