In order to clarify the effect of constituent ions on an electroacoustic phenomenon in an aqueous solution of ionic surfactant, we measured the total vibration current (TVI) as a function of the molarity of aqueous solution of several ionic surfactants at 298.15 K under atmospheric pressure. The different counterion caused the remarkable change in TVI, while the difference in alkyl chain length of surfactant ion hardly affected TVI. This suggests that the size and/or aggregation number of micelle is not a crucial factor contributing to TVI. Employing the fluorocarbon surfactant, on the other hand, there appeared a fairly large change compared to the hydrocarbon surfactant. This implies that the density contrast between medium and micelle is significant for TVI.

抄録全体を表示

Docosahexaenoic acid (DHA) regulates the lipid metabolism and inflammation that is closely associated with oxidative stress. The present study investigated the effects of DHA on the development of nonalcoholic steatohepatitis (NASH). To induce fatty liver, rats were fed choline-deficient high-fat diets (CDHF). The rats were then divided into 4 groups treated over the subsequent 6 weeks as follows: control, CDHF, CDHF+oxidative stress (NASH), and NASH+DHA (1.0 g/kg, p.o.). Rats of the control group were fed MF chow diet only. NASH rats showed severe steatohepatitis and liver fibrosis. Treatment with DHA significantly decreased the n-6/n-3 ratio in the livers and increased plasma SOD like activity compared with NASH rats. In addition, DHA attenuated the liver fibrosis during NASH development. Therefore, a higher DHA ratio in the liver of NASH rats might regulate the inflammatory response through a low n-6 ratio and diminished oxidative stress, effectively inhibiting liver fibrosis during NASH progression. These results suggested that DHA is a novel functional food for the prevention of NASH.

抄録全体を表示

The monoterpene D-limonene and its metabolites have been shown to exert chemopreventive and chemotherapeutic effects against different tumours in animal models and clinical trials. However, it is unknown whether these compounds modulate the inflammatory response in RAW 264.7 macrophage cells. The present study was therefore designed to elucidate the pharmacological and biological effects of D-limonene on the production of pro-inflammatory cytokines and inflammatory mediators in macrophages. The results indicate that D-limonene is an effective inhibitor of lipopolysaccharide (LPS)-induced NO and prostaglandin E₂ production in RAW 264.7 cells. These inhibitory effects of D-limonene included dose-dependent decreases in the expression of iNOS and COX-2 proteins. To evaluate the inhibitory effects of D-limonene on other cytokines, we also measured TNF-α, IL-1β, and IL-6 levels in the cell supernatants of LPS-stimulated RAW 264.7 macrophages by enzyme-linked immunosorbent assay. In these assays, D-limonene decreased the expression of TNF-α, IL-1β, and IL-6 in a dose-dependent manner. To assess the suitability of D-limonene for cosmetic applications, we also performed 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assays on HaCaT keratinocytes. D-limonene did not display any cytotoxicity in these assays. From these results, we suggest that D-limonene may be considered a potential anti-inflammatory candidate.

抄録全体を表示

To evaluate the pharmacological properties of cilostazol (CLZ), we examined its intraocular pressure (IOP) -lowering effect. CLZ is an inhibitor of Type III phosphodiesterase that increases intracellular cyclic AMP levels by restraining platelet aggregation, and has a potential protective effect against atherosclerosis. We attempted to apply it for use as an anti-glaucoma agent; however, the application of CLZ in the ophthalmic field is limited due to its poor water solubility. We attempted to enhance CLZ solubility using 2-hydroxypropyl-β-cyclodextrin (HPβCD). The solubility of CLZ increased with increasing HPβCD concentrations, and 0.05% CLZ was dissolved in 10% HPβCD. Moreover, fine particle suspension of 0.5% CLZ in 5% HPβCD (soluble CLZ: ca. 0.027%) were prepared using a Microfluidizer, an impact-type emulsifying comminution device. In an in vitro transcorneal penetration experiment through the rabbit cornea, the CLZ penetration rate was dependent on the CLZ content of the solutions and suspensions. When a 0.05% CLZ ophthalmic solution was instilled into a rabbit eye, the absorption rate constant for CLZ into an aqueous humor was 0.0059±0.001 min^–1, and the elimination rate constant was 0.048±0.024 min^–1. Also CLZ ophthalmic solutions and fine particle suspension were examined to for their ability to reduce enhanced intraocular pressure (IOP) of rabbits in a darkroom. The instillation of 0.05% CLZ ophthalmic solutions and 0.5% CLZ fine particle suspensions into rabbit eyes reduced the enhanced IOP. These results demonstrate that the instillation of CLZ ophthalmic solutions and fine particle suspensions may represent an effective anti-glaucoma formulation.

抄録全体を表示

Desmosine (DES) and isodesmosine (IDES) are both pyridinium amino acid isomers that serve as cross-linking molecules binding the polymeric chains of amino acids into elastin. Found in urine, they are markers for the degradation of elastin which occurs in chronic obstructive pulmonary disease (COPD). In this study, a robust method using ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) with selected reaction monitoring (SRM) mode was developed for the analysis of DES and IDES in human urine. Pyridylethyl-cysteine (PE-Cys) as internal standard (I.S.) was employed for the quantification of DES and IDES. The analytes and I.S. were extracted by solid-phase extraction with Oasis MCX cartridges and separated on an AccQ-Tag™ Ultra column. The assay was accurate (-6.8% to 14.5%) and precise (2.8% to 13.8%) within the concentration range of 1 to 250 pmol/mL. Moreover, the recovery and stability (working/ I.S. solution, urine samples with added elastin, and pretreated sample) was investigated, and these parameters were found acceptable. The UPLC-MS/MS method was validated and had good reproducibility and stability for the quantification of DES and IDES, which requires only 100 mL of human urine. This assay will be a useful means for measuring DES and IDES levels in urine with robustness and characterizing patients with COPD.

抄録全体を表示

Diabetic keratopathy is a well-known ocular complication secondary to type 2 diabetes mellitus. In this study, we performed a kinetic analysis of corneal wound healing in Long-Evans rats (normal rat) and Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of type 2 diabetes mellitus. Corneal wound healing in 7-week-old normal rats was mostly complete 24 h after corneal epithelial abrasion, and the process of corneal wound healing took place according to an equation with a first-order rate constant. The rate of corneal wound healing in normal rats decreased with aging. The process of corneal wound healing in 38- and 60-week-old normal and OLETF rats occurred in two phases with rate constants for the first and second phases represented as α and β, respectively. The α and β values in 38- and 60-week-old OLETF rats were lower than those in normal rats of the corresponding age. Furthermore, a close relationship was observed between the corneal wound healing rate constant and plasma glucose levels in OLETF rats. The present studies suggest the sequence of events that occur following damage to the corneal surface in OLETF rats as a model animal for a human type 2 diabetes mellitus.

抄録全体を表示

Mannosylerythritol lipids (MELs), the extracellular glycolipids produced from feedstock by yeasts belonging to the genus Pseudozyma, are the most promising biosurfactants known due to its versatile interfacial and biochemical actions. In order to broaden the application in cosmetics, the cell activating property of MELs was investigated using cultured fibroblast and papilla cells, and a three-dimensional cultured human skin model. The di-acetylated MEL (MEL-A) produced from soybean oil significantly increased the viability of the fibroblast cells over 150% compared with that of control cells. On the other hand, no cell activation was observed by the treatment with MEL-A produced from olive oil. The mono-acetylated MEL (MEL-B) hardly increased the cell viability. The viability of the fibroblast cells decreased with the addition of more than 1 μg/L of MELs, whereas the cultured human skin cells showed high viability with 5 μg/L of MELs. Interestingly, the papilla cells were dramatically activated with 0.001 μg/L of MEL-A produced from soybean oil: the cell viability reached at 150% compared with that of control cells. Consequently, the present MEL-A produced from soybean oil should have a potential as a new hair growth agent stimulating the papilla cells.

抄録全体を表示