Objectives: To determine whether oral capsaicin troche supplementation with every meal upregulates the impairment of upper respiratory protective reflexes such as the swallowing reflex and the cough ...reflex.
Design: Randomized, controlled study with recruitment through nursing homes.
Setting: Sendai, Japan, from September 2002 through December 2003.
Participants: Sixty‐four participants in nursing homes with a mean age±standard deviation of 81.9±1.0 with stable physical status.
Intervention: Participants were randomly assigned to the program for the supplementation of capsaicin trochisci or placebo trochisci before every meal for 4 weeks.
Measurements: Assessment of individual latency time of the swallowing reflex (LTSR) and cough reflex sensitivity.
Results: Before the commencement of this study, there were no significant baseline differences in multiple parameters between the intervention group and control group. LTSR in participants in the intervention group was significantly shorter than in the control group (P<.05). The odds ratio (OR) of the shortening of the LTSR of more than 1 minute in the intervention group was 3.4 (95% confidence interval (CI)=1.1−10.4), compared with the control group (P=.03). In particular, daily capsaicin supplementation significantly increased the ratio of LTSR reduction at 4 weeks after the study to baseline LTSR in the high‐risk group (baseline LTSR >6.0 seconds) compared with the low‐risk group (baseline LTSR <3.0 seconds) and the intermediate group (3.0 seconds <baseline LTSR <6.0 seconds) (P<.005). Seventeen (52.1%) participants in the intervention group and seven (21.9%) in the control group showed improvement in cough reflex sensitivity (OR=4.1, 95% CI=1.4−12.2; P<.01).
Conclusion: Daily capsaicin supplementation resulted in a significant improvement in upper protective respiratory reflexes, particularly in older people with a high risk for aspiration.
Numerous phenomenological parallels have been drawn between f - and d - electron systems in an attempt to understand their display of unconventional superconductivity. The microscopics of how ...electrons evolve from participation in large moment antiferromagnetism to superconductivity in these systems, however, remains a mystery. Knowing the origin of Cooper paired electrons in momentum space is a crucial prerequisite for understanding the pairing mechanism. Of special interest are pressure-induced superconductors CeIn 3 and CeRhIn 5 in which disparate magnetic and superconducting orders apparently coexist—arising from within the same f -electron degrees of freedom. Here, we present ambient pressure quantum oscillation measurements on CeIn 3 that crucially identify the electronic structure—potentially similar to high-temperature superconductors. Heavy hole pockets of f -character are revealed in CeIn 3 , undergoing an unexpected effective mass divergence well before the antiferromagnetic critical field. We thus uncover the softening of a branch of quasiparticle excitations located away from the traditional spin fluctuation-dominated antiferromagnetic quantum critical point. The observed Fermi surface of dispersive f -electrons in CeIn 3 could potentially explain the emergence of Cooper pairs from within a strong moment antiferromagnet.
We measured temperature dependence of electrical resistivity and the specific heat as a function of magnetic field up to 8 T in CeAl2. At the metamagnetic transition around 6 T, the coefficient A (ρ ...∞ AT2) and Sommerfeld coefficient reduce by 25 %. Such non drastic reduction implies magnetically insensitive phonon could enhance the A and γ in CeAl2 even in low temperature.
The pharmacokinetics of TAK-475 (lapaquistat acetate), a squalene synthase inhibitor, was investigated in rats and dogs. After oral administration of (14)C-labeled TAK-475 ((14)CTAK-475) to rats and ...dogs at a dose of 10 mg/kg, the bioavailability (BA) was relatively low at 3.5 and 8.2%, respectively. The main component of the radioactivity in the plasma was M-I, which has a comparable pharmacological activity to TAK-475 in vitro. The radioactivity in the portal plasma after intraduodenal administration of (14)CTAK-475 to portal vein-cannulated rat was also mainly M-I, suggesting that most of the TAK-475 was hydrolyzed to M-I during the permeable process in the intestine. The concentrations of M-I in the liver, the main organ of cholesterol biosynthesis, were much higher than those in the plasma after oral administration of (14)CTAK-475 to rats. The main elimination route of the radioactivity was fecal excretion after oral administration of (14)CTAK-475 to rats and dogs, and the absorbed radioactivity was mainly excreted via the bile as M-I in rats. M-I excreted into the bile was partially subjected to enterohepatic circulation. These results suggest that although the BA values of TAK-475 are low, M-I can exert compensatory pharmacological effects in the animals. These pharmacokinetic characteristics in animals were also confirmed in the clinical studies. The evaluation of M-I disposition is important for the pharmacokinetics, pharmacodynamics and toxicity of TAK-475 in animals and humans.
Monocyte-derived dendritic cells (mDCs) and NK cells are reciprocally activate via cytokines and cell–cell contact. Although seven human NKG2D ligands (NKG2DLs), UL16-binding proteins (ULBP) 1, 2, 3 ...and 4, retinoic acid early transcript 1G (RAET1G) and MHC class I-related chains A and B, have been reported, the differential distribution and roles of these ligands in the maturation of human mDCs have not been elucidated. In the present study, we produced polyclonal antibodies (pAbs) directed against human ULBP1, 2 and 3. All these ULBPs were detected on human mDCs when probed by the pAbs, although their expression profiles were different. We next investigated what kinds of Toll-like receptor agonists and RNA viruses influenza virus, human respiratory syncytial virus (RSV), measles virus and hepatitis C virus (HCV) induced the expression of NKG2DLs on mDCs. ULBP1 was up-regulated on mDCs in response to LPS or infection with RSV. The expression of ULBP2 was induced by LPS and poly I:C, indicating that the TIR-containing adapter molecule-1 (TIR domain-containing adaptor-inducing IFN) pathway is associated with ULBP2 induction. Although infection with HCV did not cause up-regulation of NKG2DLs, other RNA virus infections and poly I:C promoted expression of ULBP2 and RAET1G in an IFN-α/β-independent manner. Finally, the over-expression of ULBP1 and 2 on mDCs facilitated NK cell proliferation and IFN-γ production through a mDC–NK cell interaction in the presence of IL-2. Hence, the results reflect the important role of NKG2DLs on human mDCs in mDC-mediated NK cell activation.
TAK-475 (lapaquistat acetate) is a squalene synthase inhibitor and M-I is a pharmacologically active metabolite of TAK-475. Preclinical pharmacokinetic studies have demonstrated that most of the ...dosed TAK-475 was hydrolyzed to M-I during the absorption process and the concentrations of M-I in the liver, the main organ of cholesterol biosynthesis, were much higher than those in the plasma after oral administration to rats. In the present study, the mechanism of the hepatic uptake of M-I was investigated.The uptake studies of (14)C-labeled M-I into rat and human hepatocytes indicated that the uptakes of M-I were concentrative, temperature-dependent and saturable in both species with Km values of 4.7 and 2.8 μmol/L, respectively. M-I uptake was also inhibited by cyclosporin A, an inhibitor for hepatic uptake transporters including organic anion transporting polypeptide (OATP). In the human hepatocytes, M-I uptake was hardly inhibited by estrone 3-sulfate as an inhibitor for OATP1B1, and most of the M-I uptake was Na(+)-independent. Uptake studies using human transporter-expressing cells revealed the saturable uptake of M-I for OATP1B3 with a Km of 2.13 μmol/L. No obvious uptake of M-I was observed in the OATP1B1-expressing cells.These results indicated that M-I was taken up into hepatocytes via transporters in both rats and humans. OATP1B3 would be mainly involved in the hepatic uptake of M-I in humans. These findings suggested that hepatic uptake transporters might contribute to the liver-selective inhibition of cholesterol synthesis by TAK-475. This is the first to clarify a carrier-mediated hepatic uptake mechanism for squalene synthase inhibitors.
High Field Specific Heat in CeCu2Ge2 Dong, Chao; Imajo, Shusaku; Kohama, Yoshimitsu ...
Meeting Abstracts of the Physical Society of Japan,
2019
Journal Article
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