Estimation of Muscle Mass Using Creatinine/Cystatin C Ratio in Japanese Community-Dwelling Older People.

OBJECTIVES: Sarcopenia is defined as a combination of low skeletal muscle mass index (SMI), weak muscle strength, and reduced physical function. Recently, many studies have reported that the creatinine/cystatin C ratio (Cr/CysC) is useful for evaluating muscle mass. We designed a cross-sectional study with separate model development and validation groups to develop a prediction equation to estimate bioimpedance analysis (BIA)-measured SMI with Cr/CysC. DESIGN: The current study was a retrospective cross-sectional study. SETTING AND PARTICIPANTS: The model development group included 908 subjects (288 men and 620 women) from the Frail Elderly in the Sasayama-Tamba Area (FESTA) study, and the validation group included 263 subjects (112 men and 151 women) from participants in the medical checkup program at the Anti-Aging Center in Ehime Prefecture. MEASURES: Multivariate regression analysis indicated that age, hemoglobin (Hb), body weight (BW), and Cr/CysC were independently associated with SMI in both men and women. The SMI prediction equation was developed as follows: Men:4.17-0.012×Age+1.24×(Cr/CysC)-0.0513×Hb+0.0598×BW Women:3.55-0.00765×Age+0.852×(Cr/CysC)-0.0627×Hb+0.0614×BW RESULTS: The SMI prediction equation was applied to the validation group and strong correlations were observed between the BIA-measured and predicted SMI (pSMI) in men and women. According to the receiver operator characteristic (ROC) analysis, the areas under the curve were 0.93 (specificity 89.0%, sensitivity 87.2%) among men and 0.88 (specificity 83.6%, sensitivity 79.6%) among women for using pSMI to identify low SMI in the model development group. The pSMI also indicated high accuracy in ROC analysis for low SMI in the validation group. The Bland-Altman plot regression showed good agreement between BIA-measured and pSMI. CONCLUSIONS AND IMPLICATIONS: Our new prediction equation to estimate SMI is easy to calculate in daily clinical practice and would be useful for diagnosing sarcopenia.

Relationships between cystatin C- and creatinine-based eGFR in Japanese rural community- dwelling older adults with sarcopenia.

BACKGROUND: Sarcopenia is prevalent in patients with chronic kidney disease (CKD). The indices of physical function, such as grip power and gait speed, decreased according to the decline in the estimated glomerular filtration rate (eGFR). METHODS: We examined the relationships between cystatin C-based GFR (eGFRcys), creatinine-based GFR (eGFRcre), their ratio (eGFRcys/eGFRcre) and sarcopenia in community-dwelling older adults in Japan. This cross-sectional study included 302 men aged 73.9 ± 6.2 years and 647 women aged 72.9 ± 5.8 years from a rural area in Hyogo Prefecture, Japan. eGFRcys and eGFRcre were simultaneously measured, and sarcopenia based on the Asia Working Group for Sarcopenia (AWGS) 2019 criteria was evaluated. RESULTS: eGFRcys and the eGFRcys/eGFRcre ratio were significantly correlated with grip power and gait speed (p < 0.001). The eGFRcys/eGFRcre ratio was also correlated with skeletal muscle mass index (SMI) (p < 0.01). Univariate logistic regression analysis showed eGFRcys and eGFRcys/eGFRcre ratio but not eGFRcre were associated with sarcopenia (p < 0.01). The presence of low eGFRcys (CKDcys) and low eGFRcys/eGFRcre ratio (< 1.0) but not that of low eGFRcre (CKDcre) were associated with sarcopenia (p < 0.01). In the multivariate logistic regression analysis, when the eGFRcys/eGFRcre ratio was added as a covariate to the basic model, it was significantly associated with sarcopenia in women (p < 0.05). Moreover, low eGFRcys/eGFRcre ratio (< 1.0) was associated with a higher risk of sarcopenia in men (p < 0.01). CONCLUSION: In conclusion, CKDcys but not CKDcre is associated with sarcopenia. A lower eGFRcys/eGFRcre ratio may be a practical screening marker of sarcopenia in community-dwelling older adults.

The Relationship between Dietary Habits and Frailty in Rural Japanese Community-Dwelling Older Adults: Cross-Sectional Observation Study Using a Brief Self-Administered Dietary History Questionnaire.

To develop effective nutritional interventions for preventing frailty, the specific problems associated with the dietary habits of individuals based on sex differences must be identified. The purpose of this study was to evaluate the association between dietary habits and frailty in rural Japanese community-dwelling older adults. We recruited 800 participants, aged 65 and older, who underwent a comprehensive health examination between November 2015 and December 2017. Dietary habits were assessed by a brief self-administered dietary history questionnaire. Frailty was determined using either the Kihon Checklist (KCL) or the Japanese version of the Cardiovascular Health Study (J-CHS). The percentage of frail older adults was 8.4% according to KCL and 4.0% according to J-CHS. Various kinds of nutrient intakes, including three major nutrients, minerals, and vitamins in frail men, according to KCL, were the lowest. By contrast, there were no differences in nutrient intake between the robust, prefrail, and frail female groups according to KCL. We found significant associations of the intakes of soluble dietary fiber, potassium, folate, and vitamin C with a frail status in men (p = 0.035, 0.023. 0.012, and 0.007, respectively), and an association of the intake of vitamin C with a frail status in women (p = 0.027) according to J-CHS. Attention should be paid to the diagnostic criteria of frailty and to sex differences, when nutritional interventions for the prevention of frailty are planned.

A Naphthalimide-Based Cd(2+) Fluorescent Probe with Carbamoylmethyl Groups Working as Chelators and PET-Promoters under Neutral Conditions.

We have developed a novel naphthalimide-based Cd(2+) fluorescent probe (1), featuring almost no background response, high sensitivity and selectivity toward Cd(2+) through its high association constant [K=(2.10±0.423)×10(6) ], and a practical working pH range. Membrane-permeability was conferred on 1 by replacing the imide and amide substituents with n-butyl groups, and hence the derivative (4) has found practical utility on fluorescent imaging of Cd(2+) in HeLa cells. Comparison of fluorescent properties between various compounds derived from 1 has demonstrated that the carbamoylmethyl groups in 1 function not only as Cd(2+) chelators but also as promoters for photoinduced electron transfer (PET) by lowering the basicity of the two tertiary amino groups. As a result, 1 and 4 exhibited highly practical performance as Cd(2+) probes under neutral conditions.

[Establishment of background color to discriminate among tablets: sharper and more feasible with color-weak simulation as access to safe medication].

Color-weak persons, who in Japan represent approximately 5% of male and 0.2% of female population, may not be able to discriminate among colors of tablets. Thus using color-weak simulation by Variantor™ we evaluated the effects of background colors (light, medium, and dark gray, purple, blue, and blue green) on discrimination among yellow, yellow red, red, and mixed group tablets by our established method. In addition, the influence of white 10-mm ruled squares on background sheets was examined, and the change in color of the tablets and background sheets through the simulation measured. Variance analysis of the data obtained from 42 volunteers demonstrated that with color-weak vision, the best discrimination among yellow, yellow red, or mixed group tablets was achieved on a dark gray background sheet, and a blue background sheet was useful to discriminate among each tablet group in all colors including red. These results were compared with those previously obtained with healthy and cataractous vision, suggesting that gap in color hue and chroma as well as value between background sheets and tablets affects discrimination with color-weak vision. The observed positive effects of white ruled squares, in contrast to those observed on healthy and cataractous vision, demonstrate that a background sheet arranged by two colors allows color-weak persons to discriminate among all sets of tablets in a sharp and feasible manner.

[Establishment of the background color to make discrimination of domestic ethical tablets sharper and more feasible based on the analysis of their color distribution].

In Japan, pharmacists as well as patients often have problems distinguishing one ethical tablet from another because they can be very similar in color. In an attempt to solve this problem, we hypothesized using a background sheet of dark gray identified by N3.5 on the Munsell color system (Munsell CS). The colors of 369 and 656 ethical tablets in Japan and the USA, respectively, were measured. On the Munsell CS, the Japanese tablets were localized mostly in the range of hues between 10R∼10Y with values ≧ 8 and chroma ≦ 4, while the colors of the American tablets were scattered over the hue spectrum with a variety of values and chroma. Based on these findings, we examined the effects of background colors on discrimination between 5 tablets classified into yellow, yellow red, red, or mixed groups that represented typical domestic Japanese tablets. Background colors of light, medium, and dark gray, purple, blue, and blue green were selected based on a general concept on color discrimination. The influence of white 10 mm-ruled squares on background sheets was examined as well. Under JIS Z8723 conditions, 42 volunteers used a 4-point scale to evaluate how clearly they could discriminate between each set of tablets on each of the background sheets. Variance analysis of the obtained data with SPSS demonstrated that with healthy vision, use of a dark gray background sheet with or without ruled squares enabled the sharpest and most feasible discrimination between all sets of tablets. A similar test with dark gray and white clearly demonstrated that the former works as a practical background color for discrimination among different domestic Japanese tablets.

A coumarin-based fluorescent probe for Hg2+ and Ag+ with an N'-acetylthioureido group as a fluorescence switch.

For detection of Hg(2+) and Ag(+), we have developed a coumarin-based probe with an N'-acetylthioureido group as a novel fluorescence switch, in which the hydrogen bond formation between the N-hydrogen and the acetyl O atom markedly increases the susceptibility of the probe toward desulfurization by Hg(2+) and Ag(+).

Synthesis of fused and linked bicyclic nitrogen heterocycles by palladium-catalyzed domino cyclization of propargyl bromides.

The palladium(0)-catalyzed direct construction of bicyclic heterocycles is described. Treatment of propargyl bromides that have nucleophilic functional groups connected by two or three carbon atoms with catalytic [Pd(PPh(3))(4)] affords bis-cyclization products in good yields. The desired bicyclic heterocycles can be obtained selectively when using substrates with appropriate nucleophilic groups. We also describe the reaction of a 2-alkynylazetidine derivative with a catalytic amount of [Pd(PPh(3))(4)] under base-free conditions, which affords the same fused heterocycles as the corresponding propargyl bromides.

Molecular display technology using yeast--arming technology.

A technology to display proteins or peptides on living organisms has been developed over the last two decades. So-called "Molecular display (Arming) technology" or "Cell surface engineering" has been one of the important tools for analyzing and understanding protein function, or for screening of novel clones from libraries. In addition, it endows cells with novel abilities that cannot be added by conventional genetic recombination. In particular, the yeast Saccharomyces cerevisiae has a lot of advantages in molecular display technology. Normal yeast cells can be transformed into a wide variety of "arming yeasts" that have catalytic functions, affinity binding to valuable ligands, bioremediation properties, bio-monitoring properties, etc. This review describes the background, applications, and representative achievements of molecular display technology of yeast.

Which are you watching, an individual reactive oxygen species or total oxidative stress?

The fluorometric measurement of an individual reactive oxygen species (ROS) provides useful biological and biochemical information on ROS as important mediators for the pathological conditions of various diseases and yet requires a highly specific probe toward the target ROS. To design such a specific ROS probe, this report proposes a new strategy based on protection-deprotection chemistry between fluoresceins and their derivatives protected with benzenesulfonyl groups. The strategy has allowed developing new fluorescent probes toward extra- and intracellular hydrogen peroxide or superoxide. Herein, I outline the strategy used for the design of these ROS probes and their probe performance with high selectivity toward hydrogen peroxide and superoxide, which could not be achieved until a simple deprotection, namely, a nonredox reaction, was used as a fluorescing process.

Direct construction of bicyclic heterocycles by palladium-catalyzed domino cyclization of propargyl bromides.

The palladium-catalyzed domino cyclization of propargyl bromides having two nucleophilic functional groups is described. Treatment of 1,7-diamino-5-bromohept-3-yne derivatives with catalytic Pd(PPh3)4 in the presence of NaH in MeOH gives the 2,7-diazabicyclo[4.3.0]non-5-enes in good yields. Interestingly, the regioselectivity of the reaction is completely controlled by the relative reactivity of the amine functional groups, irrespective of the position of the nucleophiles. The malonate derivative also undergoes domino cyclization to produce a hexahydroindole derivative.

Design of a practical fluorescent probe for superoxide based on protection-deprotection chemistry of fluoresceins with benzenesulfonyl protecting groups.

A strategy for designing probes based on protection-deprotection chemistry involving fluoresceins and their benzenesulfonyl (BES) derivatives has led to the development of a much more practical superoxide (O(2) (-.)) probe than the previously reported bis(2,4-dinitro-BES) tetrafluorofluorescein (6 a). Examination of various BES derivatives, developed from the starting point of the prototype probe 6 a, yielded 4,5-dimethoxy-2-nitro-BES tetrafluorofluorescein (BESSo; 7 j) as the optimal reagent. A microtiter plate assay with BESSo showed a tenfold improved detection limit for O(2) (-.) compared with such an assay based on 6 a. BESSo showed markedly better specificity for O(2) (-.) than for GSH or other reactive oxygen species, and this specificity was significantly higher than that of Fe(2+) and some reducing enzymes. These features have resulted in the development of an assay based on BESSo that is capable of providing more unambiguous results for O(2) (-.) release from neutrophils, with or without stimulation by phorbol myristate acetate, as compared with an assay based on 6 a. Intracellular generation of O(2) (-.) in human Jurkat T cells stimulated by butyric acid has been measured by using flow cytometry and fluorescence microscopy utilizing the acetoxymethyl derivative of BESSo.

Important role of the 3-mercaptopropionamide moiety in glutathione: promoting effect on decomposition of the adduct of glutathione with the oxoammonium ion of TEMPO.

Cyclic voltammetry of TEMPO in aqueous 0.1 M NaOH in the presence of glutathione (GSH) or cysteine (Cys) indicated the following points: (i) Both of the thiols rapidly formed adducts 3 with oxoammonium ion 1 anodically generated from TEMPO. (ii) 3 generated from GSH entered a succeeding reaction that generated N-oxide anion 2- (the reduced TEMPO). (iii) 3 produced from Cys remained intact over the time scale of voltammetry. A structural feature of GSH was considered to contribute to the observed behavior of this tripeptide. Possible structural features were evaluated by screening various thiols on the basis of whether they provided GSH-like voltammetric results. The 3-mercaptopropionamide group with an amide hydrogen in GSH was determined to be responsible for the observed difference between GSH and Cys. The likely function is to transform 3 from GSH into a 5-imino-1,2-oxathiolane intermediate, thereby releasing 2-. Product analysis for reactions of model thiols representing GSH and Cys with 1 provided support for this argument and suggested that the reaction of GSH or Cys with 1 would produce the corresponding disulfides, regardless of whether a five-membered ring intermediate was formed. The proposed function of the 3-mercaptopropionamide moiety of GSH may provide useful insight for the molecular design of exogenous thiol compounds as novel drugs for the treatment of GSH-depletion-related disorders.

High performance liquid chromatography equipped with a cathodic detector and column-switching device as a high-throughput method for a phosphatase assay with p-nitrophenyl phosphate.

LC coupled to an electrochemical detector (LC-EC) operating in cathodic mode with a column-switching system realizes a high-throughput detection of p-nitrophenol (NP). The measurement-time for each NP sample was shortened to 20 s, and the successive analyses of 39 samples was completed within 13 min. In the present system, the limits of detection and quantification were 0.15 and 0.20 microM, respectively, and further, up to 25 microM, a linear calibration curve was afforded. Relative standard deviations for standard solutions of 0.20, 1.0, and 25 microM NP were 4.3, 2.0, and 1.1% (n = 5), respectively. Between-run precisions of the analysis of 5.0 and 25 microM NP over 6 days were 4.8 and 1.3%, respectively. A comparison with the commonly used Bessey-Lowry-Brock method indicates that the present LC-EC is useful for the high-throughput assay of acid and alkaline phosphatases in urine and blood samples with a p-nitrophenyl phosphate substrate.

A design of fluorescent probes for superoxide based on a nonredox mechanism.

Fluorometric detection of O2-* is performed based on desulfonylation of 3 to the corresponding fluoresceins 4 through nucleophilic substitution, and this fluorescing process is quite specific toward O2-* over H2O2, t-BuOOH, NaOCl, 1O2, HO*, NO*, and ONOO-. Furthermore, effects of glutathione, cytochrome P450 reductase/NADPH, and diaphorase/NADH are relatively small on the fluorescing process of probe 3 with X = Y = F, which is useful to detect O2-* released from neutrophils stimulated by phorbol myristate acetate with satisfactory sensitivity.

High performance liquid chromatography with an electrochemical detector in the cathodic mode as a tool for the determination of p-nitrophenol and assay of acid phosphatase in urine samples.

Utilizing a commercially available helium-purging device and PEEK tubes for all tubing, especially for connection between the mobile phase and pump, high performance liquid chromatography with an electrochemical detector (ECD/HPLC) at the cathodic mode is a simple and precise method for the determination of p-nitrophenol (NP). Studies with cyclic and hydrodynamic voltammetry indicated that 25% aqueous MeOH containing 0.1% (v/v) CF(3)CO(2)H and -0.8 V vs. Ag/AgCl are the best mobile phase and detection potential for cathodic ECD/HPLC. With the present system, the limits of detection and determination were 0.2 and 0.25 microM, respectively, and up to 50 microM, a linear calibration curve was afforded. Within-day precisions for the analysis of 5 and 50 microM NP were 0.8 and 0.7% (n=6), respectively, and between-day precisions (n=6) for these samples were 3.5 and 2.2%, respectively. Compared with the commonly used Bessey-Lowry-Brock method, cathodic ECD/HPLC was useful for the assay of acid phosphatase in urine samples with p-nitrophenyl phosphate disodium salt as a substrate.