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Objectives: We aimed to examine the relationship between the fat-free mass index (FFMI; FFM/height 2 ) and appendicular skeletal muscle mass index (ASMI; ASM/height 2 ), measured using both bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA), and investigate the effects of age and obesity. We also evaluated the suitability of BIA-measured FFMI as a simple surrogate marker of the ASMI and calculated the optimal FFMI cutoff value for low muscle mass screening to diagnose sarcopenia., Design: Cross-sectional study., Setting and Participants: This study included 1313 adults (women, 33.6%) aged 40-87 years (mean age, 55 ± 10 years) from the WASEDA'S Health Study., Methods: Body composition was measured using multifrequency BIA and DXA. Low muscle mass was defined according to the criteria of the Asian Working Group for Sarcopenia 2019., Results: BIA-measured FFMI showed strong positive correlations with both BIA- (r = 0.96) and DXA-measured (r = 0.95) ASMIs. Similarly, in the subgroup analysis according to age and obesity, the FFMI was correlated with the ASMI. The areas under the receiver operating characteristic curve for screening low muscle mass defined by DXA-measured ASMI using BIA-measured FFMI values were 0.95 (95% CI 0.93-0.97) for men and 0.91 (95% CI 0.87-0.94) for women. The optimal BIA-measured FFMI cutoff values for screening low muscle mass defined by DXA-measured ASMI were 17.5 kg/m 2 (sensitivity 89%, specificity 88%) for men and 14.6 kg/m 2 (sensitivity 80%, specificity 86%) for women., Conclusions and Implications: The FFMI showed a strong positive correlation with BIA- and DXA-measured ASMIs, regardless of age and obesity. The FFMI could be a useful simple surrogate marker of the ASMI for low muscle mass screening in sarcopenia in community settings. The suggested FFMI cutoff values for predicting low muscle mass are <18 kg/m 2 in men and <15 kg/m 2 in women., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background & Aims: A limited number of studies have developed simple anthropometric equations that can be implemented for predicting muscle mass in the local community. Several studies have suggested calf circumference as a simple and accurate surrogate maker for muscle mass. We aimed to develop and cross-validate a simple anthropometric equation, which incorporates calf circumference, to predict appendicular skeletal muscle mass (ASM) using dual-energy X-ray absorptiometry (DXA). Furthermore, we conducted a comparative validity assessment of our equation with bioelectrical impedance analysis (BIA) and two previously reported equations using similar variables., Methods: ASM measurements were recorded for 1262 participants (837 men, 425 women) aged 40 years or older. Participants were randomly divided into the development or validation group. Stepwise multiple linear regression was applied to develop the DXA-measured ASM prediction equation. Parameters including age, sex, height, weight, waist circumference, and calf circumference were incorporated as predictor variables. Total error was calculated as the square root of the sum of the square of the difference between DXA-measured and predicted ASMs divided by the total number of individuals., Results: The most optimal ASM prediction equation developed was: ASM (kg) = 2.955 × sex (men = 1, women = 0) + 0.255 × weight (kg) - 0.130 × waist circumference (cm) + 0.308 × calf circumference (cm) + 0.081 × height (cm) - 11.897 (adjusted R 2  = 0.94, standard error of the estimate = 1.2 kg). Our equation had smaller total error and higher intraclass correlation coefficient (ICC) values than those for BIA and two previously reported equations, for both men and women (men, total error = 1.2 kg, ICC = 0.91; women, total error = 1.1 kg, ICC = 0.80). The correlation between DXA-measured ASM and predicted ASM by the present equation was not significantly different from the correlation between DXA-measured ASM and BIA-measured ASM., Conclusions: The equation developed in this study can predict ASM more accurately as compared to equations where calf circumference is used as the sole variable and previously reported equations; it holds potential as a reliable and an effective substitute for estimating ASM., Competing Interests: Conflict of interest All authors declare no conflict of interest., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

This study investigated regulation of autophagy in slow-twitch soleus and fast-twitch plantaris muscles in fasting-related atrophy. Male Fischer-344 rats were subjected to fasting for 1, 2, or 3 days. Greater weight loss was observed in plantaris muscle than in soleus muscle in response to fasting. Western blot analysis demonstrated that LC3-II, a marker protein for macroautophagy, was expressed at a notably higher level in plantaris than in soleus muscle, and that the expression level was fasting duration-dependent. To identify factors related to LC3-II enhancement, autophagy-related signals were examined in both types of muscle. Phosphorylated mTOR was reduced in plantaris but not in soleus muscle. FOXO3a and ER stress signals were unchanged in both muscle types during fasting. These findings suggest that preferential atrophy of fast-twitch muscle is associated with induction of autophagy during fasting and that differences in autophagy regulation are attributable to differential signal regulation in soleus and plantaris muscle., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

We examined the densities of adenosine A(2A) receptors in cardiac and skeletal muscles between untrained and endurance-trained subjects using positron emission tomography (PET) and [7-methyl-11C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([11C]TMSX), a newly developed radioligand for mapping adenosine A(2A) receptors. Five untrained and five endurance-trained subjects participated in this study. The density of adenosine A(2A) receptors was evaluated as the distribution volume of [11C]TMSX in cardiac and triceps brachii muscles in the resting state using PET. The distribution volume of [11C]TMSX in the myocardium was significantly greater than in the triceps brachii muscle in both groups. Further, distribution volumes [11C]TMSX in the trained subjects were significantly grater than those in untrained subjects (myocardium, 3.6+/-0.3 vs. 3.1+/-0.4 ml g(-1); triceps brachii muscle, 1.7+/-0.3 vs. 1.2+/-0.2 ml g(-1), respectively). These results indicate that the densities of adenosine A(2A) receptors in the cardiac and skeletal muscles are greater in the endurance-trained men than in the untrained men.

We examined the potential of [7-methyl-11C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([11C]TMSX) for the assessment of adenosine A2A receptors in muscle. In rodents, specific binding of [11C]TMSX was observed in muscle and heart by blockade with A2A-selective CSC and non-selective theophylline, but not with A1-selective DPCPX. Swimming exercise fluctuated radioligand-receptor binding in these tissues. In a PET study of two subjects, theophylline-infusion slightly deceased the distribution volume of [11C]TMSX in the heart (20% reduction) and muscle (10% reduction), which suggested the specific binding.

Disposition of diprophylline (DPP) and proxyphylline (PXP) and the effect of enoxacin on their disposition were investigated in rats. Concentrations of the two drugs in plasma and urine were measured by HPLC. The pharmacokinetic parameters of the two drugs were estimated by model-independent methods. Although the chemical structures of the two drugs are very similar, remarkable differences in the disposition of the two drugs were observed. Total body clearance (CLT) of DPP was 1.77 L/h/kg, which was sevenfold greater than that of PXP (0.26 L/h/kg). Diprophylline was excreted in an almost completely unchanged form in the urine, but only 50% of PXP was excreted. However, no binding of either drug to proteins in rat plasma was observed. The DPP renal clearance (CLR) was 1.75 L/h/kg, approximately 13-fold the CLR for PXP (0.13 L/h/kg) and sevenfold the rat glomerular filtration rate. This study indicates that in rats, DPP is mainly excreted by active tubular secretion and that renal tubular reabsorption contributes to renal excretion of PXP with glomerular filtration. No significant changes in any pharmacokinetic parameters of the two drugs were observed when they were coadministered with enoxacin, compared with the drug administered alone, suggesting that enoxacin had no effect on the pharmacokinetics of either drug.

The effect of dosage on the pharmacokinetics of the potent bronchodilator enprofylline (3-propylxanthine; PX) and its renal handling were investigated in rats. Enprofylline (PX) was administered iv in dosages of 2.5, 10, 20, and 40 mg/kg, and PX concentration in plasma and urine was determined by HPLC. The pharmacokinetic parameters were estimated by model-independent methods. The disappearance of PX from plasma was delayed as dosage was increased. The corresponding pharmacokinetic parameters also showed dose dependency; increases in the volume of distribution (Vd) and mean residence time (MRT) and a decrease in total body clearance (CLT) were observed as dosage was increased from 2.5 to 40 mg/kg. Approximately 80% of the dose, however, was excreted in urine as unchanged PX. Plasma protein binding studies of PX showed concentration dependency and allowed determination of binding parameters, with an apparent dissociation constant (Kd) of 162.50 microM and a binding capacity (nP) of 565.23 microM. Some pharmacokinetic parameters for unbound PX calculated by total plasma concentration and binding parameters also showed dose-dependent characteristics. However, no significant change in Vd for unbound PX was observed among administered doses, indicating that the distribution of PX into the body tissues is not changed by an increase in dosage. Renal clearance of unbound PX significantly increased as plasma concentration decreased. The maximum transport capacity (Vmax) and the Michaelis-Menten constant (Km) for tubular secretion were 60.53 micrograms/min and 2.27 micrograms/mL, respectively. The aim of the present study is to demonstrate that both saturable tubular secretion and concentration-dependent protein binding are responsible for the dose-dependent pharmacokinetics of PX in rats.