N-C Axially Chiral Anilines: Electronic Effect on Barrier to Rotation and A Remote Proton Brake.

N-Aryl-N-methyl-2-tert-butyl-6-methylaniline derivatives exhibit a rotationally stable N-C axially chiral structure and the rotational barriers around an N-C chiral axis increased with the increase in electron-withdrawing character of para-substituent on the aryl group. X-ray crystal structural analysis and the DFT calculation suggested that the considerable change of the rotational barriers by the electron effect of para-substituents is due to the disappearance of resonance stabilization energy caused by the twisting of para-substituted phenyl group in the transition state. This structural property of the N-C axially chiral anilines was employed to reveal a new acid-decelerated molecular rotor caused by the protonation at the remote position (remote proton brake).

Family Caregivers' Needs in Long-Term Care Facilities: A Descriptive Qualitative Study.

PURPOSE: To explore the needs of family caregivers (FCs) and how these are addressed in long-term care facilities (LTCFs). METHOD: A descriptive qualitative study was performed, using semi-structured interviews with 23 FCs from seven LTCFs in Japan. RESULTS: Inductive content analysis revealed three main themes: Coexistent Needs Related to Residents' and FCs' Own Well-Being, Means by Which FCs Promote Residents' and Their Own Well-Being, and Managing Conflicting Needs by Prioritizing and Compromising. FCs recognized that their needs relate to the well-being of residents and themselves, and both needs coexist. To address these multifaceted needs, FCs engaged in various activities while seeking support. However, limited availability of means often made it challenging to meet multiple needs simultaneously, leading FCs to manage these conflicting needs by prioritizing or compromising. CONCLUSION: The current study underscores the significance of comprehensive support that simultaneously addresses FCs' conflicting needs, rather than approaching each need separately. [Research in Gerontological Nursing, xx(x), xx-xx.].

Culture density contributes to hepatic functions of fresh human hepatocytes isolated from chimeric mice with humanized livers: Novel, long-term, functional two-dimensional in vitro tool for developing new drugs.

Chimeric mice with humanized livers are considered a useful animal model for predicting human (h-) drug metabolism and toxicity. In this study, the characteristics of fresh h-hepatocytes (cFHHs, PXB-cells®) isolated from chimeric mice (PXB-mice®) were evaluated in vitro to confirm their utility for drug development. cFHHs cultured at high density (2.13 × 105 cells/cm2) displayed stable production of h-albumin and cytochrome P450 (CYP) 3A activities for at least 21 days. The mRNA expression levels of 10 of 13 CYP, UDP-glucuronosyltransferase (UGT), and transporters were maintained at >10% of the levels of freshly isolated cFHHs after 21 days. From 1 week, many bile canaliculi were observed between cFHHs, and the accumulation of the multidrug resistance-associated protein and bile salt export pump substrates in these bile canaliculi was clearly inhibited by cyclosporin A. Microarray analysis of cFHHs cultured at high density and at low density (0.53 × 105 cells/cm2) revealed that high density culture maintained high expressions of some transcription factors (HNF4α, PXR, and FXR) perhaps involved in the high CYP, UGT and transporter gene expressions of cFHHs. These results strongly suggest that cFHHs could be a novel in vitro tool for drug development studies.

[Simultaneous determination of ochratoxin A, B and citrinin in foods by HPLC-FL and LC/MS/MS].

Methods using high-performance liquid chromatography with fluorescence detection (HPLC-FL) and using liquid chromatography with tandem mass spectrometry (LC/MS/MS) were developed for simultaneous determination of ochratoxin A (OTA), ochratoxin B (OTB) and citrinin (CIT) in cereal, fruit, and coffee products. The samples were extracted with ethyl acetate under an acidic condition, and then cleaned up with liquid-liquid separation. The test solutions were analyzed by reverse-phase HPLC-FL and LC/MS/MS. Mass spectral acquisition was performed in positive ion mode by applying multiple reaction monitoring. The performances of both detectors were almost equivalent. The recoveries of OTA and OTB were 87-111%, and that of CIT were 70-88%. The limits of quantification (S/N> or =10) of OTA, OTB and CIT was 0.1 mug/kg or less. These methods were considered to be useful for the determination of the three mycotoxins at low levels (0.1 microg/kg).

[Investigation of ochratoxin a, B and citrinin contamination in various commercial foods].

Ochratoxin A (OTA), ochratoxin B (OTB) and citrinin (CIT) in commercial foods were simultaneously determined and confirmed with high-performance liquid chromatography (HPLC) and liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS). The samples examined were made up of cereal, fruit, coffee, and cacao products. The limits of quantification (S/N> or =10) of OTA, OTB and CIT were 0.1 microg/kg or less. Aflatoxins (AF), deoxynivalenol (DON) and fumonisins were also surveyed. Of 157 samples examined, 44 were contaminated with OTA at levels of 0.11 to 4.0 microg/kg. At least 2 positive samples were labeled as domestics. In most positive samples, the OTA level was low, less than 1 microg/kg. The highest incidence of OTA was observed in cacao powder (10/12), followed by instant coffee (5/7), cocoa (5/8) and raisin (6/13). OTB was found in fruit and cacao products containing relatively high levels of OTA. Co-occurrence of OTA, CIT and DON was found in cereal products, and co-occurrence of OTA and AF was found in cacao products. Approximately 30% of naturally contaminated OTA in roasted coffee bean moved into the extract solution when brewed with paper filter.

Effects of long-term administration of hesperidin and glucosyl hesperidin to spontaneously hypertensive rats.

Hesperidin (HES) is a flavonoid contained in citrus fruit peel. We investigated the effects of long-term administration of HES and its newly developed water soluble analogue, glucosyl hesperidin (GHES), to spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Animals were fed with diets containing HES or GHES (30 mg/d/kg body weight) for 25 wk. While the daily food intake and the body weight of administered rats were not different from those of the non-administered control rats in both SHR and WKY through the experimental period, the blood pressure and heart rate of SHR administered HES or GHES for longer than 15 wk decreased as compared to the control group. The blood pressure and heart rate of WKY were not changed by the long-term administration of HES or GHES. These results suggest that HES and GHES have anti-hypertensive effects on hypertensive animals.

Glucosyl hesperidin improves serum cholesterol composition and inhibits hypertrophy in vasculature.

Long-term administration of hesperidin (HES) or glucosyl hesperidin (GHES), a water-soluble analogue of HES, brings about an antihypertensive effect on spontaneously hypertensive rats (SHR). In the present study, we investigated the effects of long-term administration of HES and GHES (corresponding to 30 mg/d/kg body weight) on serum lipid concentration and morphology of vasculature. Serum HDL cholesterol increased in both SHR and Wistar-Kyoto rats (WKY) fed a HES- or GHES-containing diet for 25 wk. Simultaneously, GHES administration reduced the vascular diameter and media-intimal cross-sectional area of the abdominal aorta in SHR. These results suggest that HES as well as GHES improves serum cholesterol composition and that GHES inhibits hypertrophy in vasculature as well.