3-Fluoroazetidinecarboxylic Acids and trans,trans-3,4-Difluoroproline as Peptide Scaffolds: Inhibition of Pancreatic Cancer Cell Growth by a Fluoroazetidine Iminosugar.

Reverse aldol opening renders amides of 3-hydroxyazetidinecarboxylic acids (3-OH-Aze) unstable above pH 8. Aze, found in sugar beet, is mis-incorporated for proline in peptides in humans and is associated with multiple sclerosis and teratogenesis. Aze-containing peptides may be oxygenated by prolyl hydroxylases resulting in potential damage of the protein by a reverse aldol of the hydroxyazetidine; this, rather than changes in conformation, may account for the deleterious effects of Aze. This paper describes the synthesis of 3-fluoro-Aze amino acids as hydroxy-Aze analogues which are not susceptible to aldol cleavage. 4-(Azidomethyl)-3-fluoro-Aze and 3,4-difluoroproline are new peptide building blocks. trans,trans-2,4-Dihydroxy-3-fluoroazetidine, an iminosugar, inhibits the growth of pancreatic cancer cells to a similar degree as gemcitabine.

Negative attitudes of healthy older adults toward unhealthy older adults: Focus on the subjective health.

Negative attitudes toward older adults, especially those with declining physical function and/or advanced dementia (i.e., unhealthy older adults), are serious. It is important to identify psychological factors associated with such negative attitudes toward unhealthy older adults. In this study, we focused on subjective health (subjective perception of one's own health status). We tested the hypothesis that healthy older adults with lower subjective health have more negative attitudes toward unhealthy older adults. We also examined whether this association is still pronounced after controlling for the participants' physical health status and demographics. In this study, an online survey was conducted among Japanese older adults who were not certified as needing long-term care (N = 1,082, aged 65-88). To control for the participants' physical health status, we focus on frailty. We conducted a factor analysis and multiple regression analysis on negative attitudes toward unhealthy older adults. As a result, healthy older participants with lower subjective health perceived unhealthy older adults negatively, and this association was still pronounced even after controlling for the participants' frailty score and demographics. Based on our findings, it is suggested that increasing the subjective health of older adults may help them view each other more positively. Therefore, it is important to devise gerontological and psychological interventions to improve older adults' subjective health. This study has limitations, such as the fact that we conducted only an online survey. Previous studies on how older adults perceive the social group of older adults are scarce, and further studies are expected.

The relationship between frailty and social participation: focus on subjective health.

OBJECTIVE: Active participation of the older adults in the society is crucial; however, frailty prevents social participation. Meanwhile, many older adults participate daily in social activities, even with frailty. This study aims to examine whether older adults with frailty have lower social participation than those without frailty in Japan. We also investigated whether older adults with frailty and higher subjective health participate in society to the same extent as the general older population. This study included 1,082 Japanese individuals aged 65 years and older participating in the online survey. Participants answered questions on social participation, frailty, subjective health, and demographics. RESULTS: Participants in the robust group had higher social participation rates than those in the frailty and pre-frailty groups. Meanwhile, frail older participants with higher subjective health had similar social participation as the robust participants. Many older adults acquire frailty despite their individual effort. Meanwhile, improving subjective health may be effective, even with frailty. The relationship between subjective health, frailty, and social participation is primitive and further studies are needed.

Cytotoxic evaluation of cubic boron nitride in human origin cultured cells.

The aim of this study was to evaluate the cytotoxicity of cubic boron nitride (cBN), a component of surgical cutting tools. The small quantities of cBN that typically remain on implants as a result of the manufacturing process may act as abrasives, injuring tissues surrounding the implant. To determine how cBN affects cells, we treated human neuroblastoma cells (NB-1) and human articular chondrocytes (nHAC-kn) with different concentrations of cBN powder and assessed cell growth and cell survival using the methyl-thiazol-tetrazolium (MTT) assay and a fluorescence probe assay. We also assessed the effects of tungsten carbide (WC) and cobalt (Co), two common components of joint implants, on cell growth and cell survival. Both cBN and WC moderately inhibited NB-1 and nHAC-kn cell growth. However, cBN and WC did not affect cell survival, even at high concentrations (40 microg/ml). By contrast, Co affected cell survival, inducing cell death in both cell types at increasing concentrations. These results suggest that cBN may be less toxic than WC alloys containing Co.