Elimination of the Causes of Poor Sleep Underlying Delirium is a Basic Strategy to Prevent Delirium.

Delirium is a very common but annoying clinical state that interferes with the treatment of background disease and delays recovery. Delirium is a troublesome condition that exhausts not only the patient but also his/her family and healthcare professionals. Since aging is a risk factor for delirium, how to control delirium is an extremely important issue in an aging society. Phenotype of delirium is so diverse that it is difficult to elucidate the mechanism of individual symptoms, but it is clinically well known that maintaining sleep quality is important in preventing and improving delirium. Drugs and factors that are known to disrupt the sleep-wake cycle also overlap with the risk factors for delirium, indicating the close connection between delirium and sleep. Although the sleep-wake cycle is tightly regulated by many neurotransmitters and hormones, the role of each substance in this cycle is being elucidated in detail. It is well known that acetylcholine is one of the most important neurotransmitters involved in wakefulness, and anticholinergic drugs reduce rapid eye movement sleep. Anticholinergic drugs are also the major drug causing drug-induced delirium. Several clinical studies have reported that melatonin receptor agonists reduce delirium. Some clinical studies have examined the relationship between delirium and environmental factors that interfere with sleep, such as noise and brightness. The purpose of this review is to organize the cause of poor sleep underlying delirium and propose strategies to prevent delirium, based on rich neurological and pharmacological findings of sleep. We consider that elimination of causes of sleep deprivation underlying delirium is one of the most effective prevention strategies for delirium.

Influence of particle size on the in vitro and in vivo anti-inflammatory and anti-allergic activities of a curcumin lipid nanoemulsion.

The polyphenolic compound, curcumin, is a natural yellow pigment component of turmeric. It exerts various biological effects, such as anti-inflammatory effects, and we have previously demonstrated that curcumin is a specific inhibitor of DNA polymerase λ. Curcumin is characterized by poor bioavailability as it is water-insoluble, is poorly absorbed and is systemically eliminated. In order to increase the bioavailability of curcumin, in this study, we produced a curcumin-loaded lipid nanoemulsion of various particle sizes (50, 100 and 200 nm). The curcumin lipid nanoemulsion was prepared by a modified thin-film hydration method followed by sonication. To identify the optimal particle size which exhibits the strongest physiological activity, we investigated the inhibitory effects of the obtained nanoemulsions against inflammatory and allergic activities. In in vitro cell culture experiments, the 100-nm curcumin lipid nanoemulsion showed the most prominent inhibitory effect on the production of tumor necrosis factor-α (TNF-α) induced by lipopolysaccharide (LPS) in RAW264.7 murine macrophages, and on the release of ß-hexosaminidase induced by the calcium ionophore, A23187, in rat basophilic leukemia RBL-2H3 cells. In an in vivo experiment, in which mice were administered the curcumin-loaded lipid nanoemulsion of various particle sizes, the 100-nm curcumin lipid nanoemulsion showed the most prominent anti-inflammatory and anti-allergic effects, inhibiting 12-O-tetradecanoylphorbol-13-acetate-induced inflammatory ear edema and immunoglobulin E (IgE)-induced passive cutaneous anaphylactic (PCA) reaction. The effects of particle size on serum curcumin absorption were also assessed in mice, and the 100-nm lipid nanoemulsion showed the greatest absorption. The results from our study suggest that the physiological activities of curcumin lipid nanoemulsions differ depending on particle size. Our data indicate that the curcumin lipid nanoemulsion with a particle size of 100 nm has potential for use in enhancing the bioavailability and medical value of curcumin.