Significant decrease in delirium referrals after changing hypnotic from benzodiazepine to suvorexant.

BACKGROUND: The use of benzodiazepines (BZDs) causes delirium, especially in elderly people. For this reason, suvorexant has been recommended as the first-line hypnotic in elderly patients. The aim of this study was to determine whether the first-line use of suvorexant, instead of BZDs, decreases referrals for delirium in elderly patients. METHODS: Since May 2016 at Nagoya Ekisaikai Hospital, suvorexant has been recommended as the first-line hypnotic instead of BZDs. In May 2017, suvorexant was adopted as the first-line hypnotic. The number of delirium cases referred to psychiatry was compared among three consecutive periods: period A (May 2015-April 2016), during which BZDs were mainly used for insomnia; period B (May 2016-April 2017), during which the use of suvorexant was recommended instead of BZDs; and period C (May 2017-April 2018), during which suvorexant was principally adopted as the first-line hypnotic for insomnia. Potential confounding factors that may affect the development of delirium were also examined during the three periods. RESULTS: The number of delirium referral cases in elderly patients in each period decreased, from 133 in period A to 86 in period B and 53 in period C. The rate of delirium referral cases decreased significantly every year (P = 9.02 × 10-10 ). Almost no significant confounding factors other than hypnotics were detected during the three periods. CONCLUSION: The referrals for delirium in elderly patients decreased significantly after the hypnotic was changed from BZDs to suvorexant.

Intramolecular Aminolactonization for Synthesis of Furoindolin-2-One.

Propellanes are polycyclic compounds in which tricyclic systems share one carbon-carbon single bond. Propellane frameworks that consist of larger sized rings are found in a variety of natural products. As an approach to the stereoselective synthesis of the propellane framework, one of the efficient methods is forming several rings in a single operation. Lapidilectine B (1) is composed of a propellane framework and was synthesized through the oxidative cyclization of trisubstituted alkenes. When the alkene with an ester moiety was treated with N-iodosuccinimide (NIS), iodocyclization proceeded to give the cyclic carbamate. On the other hand, when PhI(OAc)2 was allowed to react in the carboxyl form, a furoindolin-2-one structure corresponding to the A-B-C ring of lapidilectine B (1) was produced. Furthermore, when Pd(OAc)2 catalyst was used for cyclization under oxidative conditions, the product yield was improved.

Effects of Miconazole Oral Gel on Blood Concentrations of Tacrolimus and Cyclosporine: A Retrospective Observational Study.

BACKGROUND: Although azole antifungal agents have been shown to affect the pharmacokinetics of calcineurin inhibitors such as tacrolimus (TAC) and cyclosporine (CyA) by inhibiting drug metabolism, there are few clinical reports on drug interactions between miconazole (MCZ) oral gel and calcineurin inhibitors. In this study, the effects of MCZ oral gel on the blood concentrations of TAC and CyA were investigated. METHODS: In this retrospective study, 18 patients concomitantly administered MCZ oral gel and TAC (9 for dermatomyositis, 3 for myasthenia gravis, 2 for systemic lupus erythematosus, 2 for rheumatoid arthritis, 1 for polymyositis, 1 for prevention of graft-versus-host disease after bone marrow transplantation), and 15 patients concomitantly administered MCZ oral gel and CyA (11 for interstitial pneumonia, 2 for pemphigus, 1 for eosinophilic granulomatosis with polyangiitis, 1 for systemic lupus erythematosus) were evaluated. The dose-adjusted blood concentrations of TAC or CyA were compared before and after the initiation of MCZ oral gel. RESULTS: The trough blood concentration/dose (C/D) ratios of TAC and CyA increased significantly with the administration of MCZ oral gel. The median C/D ratios of TAC and CyA increased by 108% (range: -44% to 216%) and 44% (range: -34% to 195%), respectively. CONCLUSIONS: These results suggest that MCZ oral gel affects the pharmacokinetics of TAC and CyA. Detailed monitoring of the blood concentrations of these drugs, followed by dose adjustments, is needed for each patient because of the difficulties associated with accurately predicting the degree of the effects of MCZ oral gel.

Cyclopiazonic acid discharges intracellular Ca2+ stores and stimulates Ca2+ influx in cultured human gingival fibroblasts.

The effect of cyclopiazonic acid (CPA) on changes in the intracellular free Ca2+ concentration ([Ca2+]i) evoked by bradykinin (BK), histamine (HIST) and thapsigargin (TG) was investigated in human gingival fibroblasts. CPA itself dose-dependently stimulated [Ca2+]i responses in both the absence and presence of extracellular Ca2+. Pretreatment with CPA (< 5 microM) enhanced the [Ca2+]i responses evoked by 5 nM BK and 1 mM HIST. However, CPA-pretreatment depressed the [Ca2+]i response evoked by 1 microM TG in a dose-dependent manner. Moreover, CPA accelerated the Ca2+ influx caused by 5 nM BK and 1mM HIST, but did not alter that caused by 1 microM TG. These results indicate that CPA discharges intracellular Ca2+ stores, resulting in their depletion, and enhances Ca2+ influx across the plasma membrane.

Behavior of HO-1-N-1, buccal mucosa carcinoma derived cells, on [Ca2+]i responses to stimulants.

Buccal mucosa carcinoma-derived cell line, HO-1-N-1, epithelial-like cells, was obtained in order to investigate the characteristics of oral cancer cells and examine the [Ca2+]i responses to stimulants, such as bradykinin (BK), histamine (HIST), thapsigargin (TG), epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha ). Intracellular Ca2+ influx was observed by all stimulants that enhanced the [Ca2+]i response. However, intracellular Ca2+ release was not observed in response to growth factors. The [Ca2+]i response of BK (100 nM) was inhibited by 10 micro M of the BKB2 antagonist, D-Arg-[Hyp3, Thi5,8, D-Phe7]-BK, and HIST (1 mM) was completely inhibited by 100 nM of the H1 antagonist, (+)-chlorpheniramine, in the presence and absence of extracellular Ca2+ (1.5 mM).