Assessment of the best gait parameter in relation to bone status in community-dwelling young-old and old-old women in Japan

Even if physical exercise contributes to bone health of the elderly, intense activities have the potential to worsen the risk of osteoporosis. This fact and the inevitable decrease of mobility with age increase the likelihood that the mobility parameter that best benefits bone health differs with age. The aim of this study was to objectively assess the gait parameter that most strongly influences bone health of young-old and old-old women. Subjects comprised 200 community-dwelling elderly women (132 young-old, 68 old-old) registered at welfare centers for the aged. Bone status was examined in the right heel by quantitative ultrasound (QUS) and indicated as stiffness index (SI). Gait parameters including usual and maximum walking speed (UWS and MWS, respectively), daily walking steps (DWS), obstacle-negotiating gait, and stair-climbing were examined objectively. Other bone-related physical factors (body components, handgrip strength, and masticatory function) were measured and adjusted while performing assessment. After adjustment for covariates, multiple linear regression analysis showed that MWS had the strongest association with SI in young-old women and DWS had the strongest association with SI in old-old women. To prevent osteoporosis, brisk walking exercise and engaging in movement in everyday life, respectively, should be advocated for young-old women and old-old women in Japan.     

Discovery of Novel Benzo[a]phenoxazine SSJ-183 as a Drug Candidate for Malaria

相似文献   

Blood–brain barrier transport of naloxone does not involve P-glycoprotein-mediated efflux

The blood–brain barrier (BBB) transport of naloxone, a potent and specific opioid antagonist, was investigated in rats using the brain uptake index method and the brain efflux index method. The apparent influx clearance of [³H]naloxone across the BBB was 0.305 mL/min/g brain. [³H]naloxone was eliminated from the brain with an apparent elimination half-life of 15.1 min after microinjection into the parietal cortex area 2 regions of the rat brain. The apparent efflux clearance of [³H]naloxone across the BBB was 0.152 mL/min/g brain, which was calculated from the elimination rate constant (4.79 × 10^?2 min^?1) and the distribution volume in the brain (3.18 mL/g brain). The influx clearance across the BBB was two times greater than the efflux clearance. The elimination of [³H]naloxone from the brain was not inhibited in the presence of the typical P-glycoprotein (P-gp) inhibitors such as quinidine, verapamil, vinblastine, and vincristine, indicating that naloxone is not a P-gp substrate in the rat. In vitro experiments by using human multidrug resistance 1 (MDR1)/P-gp overexpressing HeLa cells showed that the uptake of naloxone by the cells did not change in the presence of the P-gp inhibitors. In conclusion, the present results obtained from in vivo and in vitro studies suggest that P-gp is not involved in the BBB transport of naloxone. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:413–421, 2010     

Masticatory function and cognitive function

Recent studies have suggest that masticatory (chewing) function is useful for maintaining neurocognitive function in the elderly. For example, a reduced ability to masticate, such as that resulting from toothlessness or soft-diet feeding, causes learning and memory deficits in aged animals and pathologic changes in the hippocampus. In addition, occlusal disharmony impairs hippocampal memory processes via chronic stress, and induces similar hippocampal pathology. Chewing, however, rescues stress-induced suppression of long-term potentiation in the hippocampus and the stress-induced impairment of hippocampal-dependent learning. These findings strongly suggest a link between mastication and neurocognitive function.     

TCRzeta mRNA splice variant forms observed in the peripheral blood T cells from systemic lupus erythematosus patients

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease of unknown etiology. Tyrosine phosphorylation and protein expression of the T-cell receptor ζ chain (ζ) have been reported to be significantly decreased in SLE T cells. In addition, ζ mRNA with alternatively spliced 3′ untranslated region (ζmRNA/as-3′UTR) is detected predominantly in SLE T cells, and aberrant ζ mRNA accompanied by the mutations in the open reading frame including ζ mRNA lacking exon7 (ζmRNA/exon7-) is observed in SLE T cells. These ζ mRNA splice variant forms exhibit a reduction in the expression of TCR/CD3 complex and ζ protein on their cell surface due to the instability of ζ mRNA splice variant forms as well as the reduction in interleukin (IL)-2 production after stimulating with anti-CD3 antibody. Data from cDNA microarray showed that 36 genes encoding cytokines and chemokines, including IL-2, IL-15, IL-18, and TGF-β2, were down-regulated in the MA5.8 cells transfected with the ζ mRNA splice variant forms. Another 16 genes were up-regulated and included genes associated with membranous proteins and cell damage granules, including the genes encoding poliovirus-receptor-related 2, syndecan-1, and granzyme A.     

Increased expression of membrane TNF-alpha on activated peripheral CD8+ T cells in systemic lupus erythematosus

Membrane TNF-alpha is a precursor form of soluble TNF-alpha and exerts pro-inflammatory functions in a cell-to-cell contact manner. We showed that membrane TNF-alpha is induced upon activation on the cell surface of CD4+ T cells and CD8+ T cells. In patients with systemic lupus erythematosus (SLE), the percentage of membrane TNF-alpha-bearing CD8+ T cells (41.5+/-12.3%) was significantly higher compared with those of healthy controls (26.7+/-3.9%) (p=0.007) or patients with rheumatoid arthritis (29.8+/-15.4%) (p=0.038). Membrane TNF-alpha-bearing CD8+ T cells from SLE patients displayed cytotoxic activity against L929 cells. It is possible that membrane TNF-alpha may be involved in the increased apoptosis and the generation of autoantigens in SLE.     

Down-regulation of the internal ribosome entry site (IRES)-mediated translation of the hepatitis C virus: critical role of binding of the stem-loop IIId domain of IRES and the viral core protein

In a previous study, we observed that hepatitis C virus (HCV) core protein specifically inhibits translation initiated by an HCV internal ribosome entry site (IRES). To investigate the mechanism by which down-regulation of HCV translation occurs, a series of mutations were introduced into the IRES element, as well as the core protein, and their effect on IRES activity examined in this study. We found that expression of the core protein inhibits HCV translation possibly by binding to a stem-loop IIId domain, particularly a GGG triplet within the hairpin loop structure of the domain, within the IRES. Basic-residue clusters located at the N-terminus of the core protein have an inhibitory effect on HCV translation, and at least one of three known clusters is required for inhibition. We propose a model in which competitive binding of the core protein for the IRES and 40S ribosomal subunit regulates HCV translation.     

Orthography effect on brain activities in the working memory process for phonologically ambiguous syllables: a functional magnetic resonance imaging study using Japanese speakers

English /l/ and /r/ sounds are not distinctive for Japanese speakers and they are loosely associated with corresponding graphemes. The purpose of this study was to investigate the brain activities in the memory process for the graphemes containing 'l' and 'r' in Japanese speakers. Two functional magnetic resonance imaging (at 1.5 T) experiments was conducted using syllable working memory tasks. The task using 'l' and 'r' syllables was coupled with either task using 'b' and 'n' syllables (l/r versus b/n block-designed experiment), or 'd' and 'n' syllables (l/r versus d/n block-designed experiment). The results revealed that the l/r working memory tasks induced augmented activation specifically in the right middle frontal gyrus (BA9, 46) and the right superior parietal lobule (BA7), compared with the b/n or d/n tasks. The results indicate that a visually-biased memory process (i.e. excessive visual rehearsal or monitoring) was executed for phonologically ambiguous syllables. Significant activation in the left inferior frontal gyrus was not observed only in the b/n task, probably because articulatory contrast between /b/ and /n/ sounds was highly clear for Japanese speakers.     

Metabolism of 7‐ethoxycoumarin,safrole, flavanone and hydroxyflavanone by cytochrome P450 2A6 variants

CYP 2A6 is a human enzyme that metabolizes many xenobiotics including coumarin, indole, nicotine and carcinogenic nitrosamines. The gene for CYP2A6 is polymorphic. There are few data available to clarify the relationship between P450 genetic variants and the metabolism of materials in food. The CYP 2A6 wild‐type protein and 13 mutants (CYP2A6.1, CYP2A6.2, CYP2A6.5, CYP2A6.6, CYP2A6.7, CYP2A6.8, CYP2A6.11, CYP2A6.15, CYP2A6.16, CYP2A6.17, CYP2A6.18, CYP2A6.21, CYP2A6.23 and CYP2A6.25) were co‐expressed with NADPH‐cytochrome P450 reductase in E. coli. The hydroxylase activities toward 7‐ethoxycoumarin, coumarin, safrole, flavanone and hydroxyflavanone were examined. Ten types of CYP2A6 variants except for CYP2A6.2, CYP2A6.5 and CYP2A6.6 showed Soret peaks (450 nm) typical of P450 in the reduced CO‐difference spectra and had 7‐ethoxycoumarin O‐deethylase activities. CYP2A6.15 and CYP2A6.18 showed higher activities for safrole 1′‐hydroxylation than CYP2A6.1. CYP2A6.25 and CYP2A6.7 had lower safrole 1′‐hydroxylase activities. CYP2A6.7 had lower flavanone 6‐ and 2′‐hydroxylase activities, whereas CYP2A6.25 had higher 6‐hydroxylase activity and lower 2′‐hydroxylase activity. Hydroxyflavanone was metabolized by CYP2A6.25, but was not metabolized by wild‐type CYP2A6.1. These results indicate that CYP2A6.25 possessed new substrate specificity toward flavonoids. Copyright © 2012 John Wiley & Sons, Ltd.     

P-glycoprotein mediates brain-to-blood efflux transport of buprenorphine across the blood–brain barrier

The involvement of P-glycoprotein (P-gp) in buprenorphine (BNP) transport at the blood–brain barrier (BBB) in rats was investigated in vivo by means of both the brain uptake index technique and the brain efflux index technique. P-gp inhibitors, such as cyclosporin A, quinidine and verapamil, enhanced the apparent brain uptake of [³H]BNP by 1.5-fold. The increment of the BNP uptake by the brain suggests the involvement of a P-gp efflux mechanism of BNP transport at the BBB. [³H]BNP was eliminated with an apparent elimination half-life of 27.5 min after microinjection into the parietal cortex area 2 regions of the rat brain. The apparent efflux clearance of [³H]BNP across the BBB was 0.154 ml/min/g brain, which was calculated from the elimination rate constant (2.52 × 10^{? 2} min^{? 1}) and the distribution volume in the brain (6.11 ml/g brain). The efflux transport of [³H]BNP was inhibited by range from 32 to 64% in the presence of P-gp inhibitors. The present results suggest that BNP is transported from the brain across the BBB via a P-gp-mediated efflux transport system, at least in part.