Correlation between postprandial bile acids and body fat mass in healthy normal-weight subjects

Background

Bile acids (BAs) play important roles in glucose regulation and energy homeostasis via G protein-coupled receptors, such as enteroendocrine L cell TGR5. The aim of the present study was to investigate the relationship between postprandial BA levels and body composition after ingestion of a standard test meal.

Methods

Eleven healthy subjects of normal weight (body-mass index, 22.0 ± 1.6 kg/m² [mean ± SD]), ingested a 400-kcal test meal, and blood samples were obtained from them before ingestion and every 30 min for 120 min after ingestion. The BA fractions were measured with high-performance liquid chromatography. To evaluate body composition, body impedance analysis was performed 1 h before ingestion of the test meal.

Results

Concentrations of both total BA and total glycine-conjugated BA (GCBA) at 30, 60, 90, and 120 min after test-meal ingestion were significantly higher than those at baseline. The body-mass index was correlated with total GCBA at baseline. Moreover, body fat mass was correlated with total GCBA at 30 min (r = – 0.688, P = 0.019) and 60 min (r = – 0.642, P = 0.033) and with total BA at 30 min (r = – 0.688, P = 0.019) and 60 min (r = – 0.642, P = 0.033).

Conclusion

The postprandial BA response is inversely related with body fat mass in healthy subjects of normal weight.     

成年人身高与去脂组织重的关系

目的研究成年人去脂组织重(fat-free mass,FFM)与身高之间的关系,并建立预测FFM的简单方程.方法对955名健康成年人进行人体测量和生物电阻抗测量,按BMI分为肥胖组和非肥胖组,按年龄分别45岁以下组和45岁以上组,分析FFM与年龄和肥胖的关系.根据FFM是身高的异速生长指数的模型关系,进行非线性回归,建立指数曲线回归方程.结果18～45岁健康成年人的身高为(1.65±0.07)m,体质量为(62.03±10.69)kg,体脂质量(11.28±6.75)kg,体脂含量(17.91±8.67)%,去脂组织含量(82.02±8.87)%,BMI(22.85±2.99)kg/m2,而46～74岁健康成年人的相应指标为(1.62±0.08)m,体质量为(66.08±10.21)kg,体脂质量(14.56±6.44)kg,体脂含量(22.09±9.23)%,去脂组织含量(77.58±10.07)%,BMI(25.19±2.95)kg/m2,差异有显著性意义(P＜0.05);18～45岁与46～74岁的健康人的FFM分别为(50.93±10.23),(51.53±10.07)kg,差异无显著性意义(P＞0.05);健康成年人的FFM并不随年龄增加;非肥胖组与肥胖组的FFM也是相对不变的.预测男性FFM的适宜方程为FFM(kg)=24.98×身高1.68,预测女性FFM的适宜方程为FFM(kg)=22.84×身高1.42.结论以身高为变量能估计出正常成年人FFM的近似值.     

The relation between potassium in body fluids and total body potassium in healthy and diabetic subjects.

1. The concentration of potassium in the erythrocytes and the plasma of forty-one normal subjects and twenty-five diabetic patients was measured and the results were used to calculate the total amount of potassium in the erythrocyte mass and the total amount of potassium in the plasma. The total body potassium was measured in a whole-body monitor. 2. In normal subjects a close correlation was found between total erythrocyte potassium and total body potassium and also between total plasma potassium and total body potassium. 3. The regression relation between total body potassium and total erythrocyte potassium in normal subjects was used to predict the total body potassium in diabetic patients. There was reasonable agreement between the measured and predicted total body potassium but there was poor agreement between the measured total body potassium and that predicted from the patient's height and age or height and age or height, weight and age.     

Relationship between electrocardiographic RR and QT interval variabilities and indices of ventricular function in healthy subjects

To date there has been no simultaneous characterization of the influence of physical exercise on cardiac ventricular function and cardiac electrical variability. Consequently, little is known about the relationship between the ventricular function and either heart rate (RR) or repolarization (QT) variability. In particular, the relationship between the QT variability index (QTVI) and ventricular function would be of clinical interest. Eight males of similar age (20.7 +/- 0.4 years (mean +/- SD)), mass (78.4 +/- 7.7 kg) and aerobic fitness (50.7 +/- 4.9 ml kg(-1) min(-1)) undertook progressive bicycle exercise. A three-lead Holter ECG was recorded continuously during pre-exercise, exercise and recovery, and mean values of RR and QT, their variabilities (RMSSD and SDNN) and their relative variability (QTVI) were determined. Traditional indices of ventricular function were determined beat to beat via impedance cardiography, and beat-to-beat blood pressure was recorded via photoplethysmography. Multiple linear regression analysis using the stepwise method resulted in significant models for each of the dependent variables (RR, QT, RR and QT variabilities, QTVI), using indices of the ventricular function as predictor variables. Notably, the QTVI reflected both the stroke volume index (SVI) and the acceleration index (ACI), which are measures of cardiac 'output' per contraction and the force of contraction, respectively. This relationship was largely unperturbed by physical exercise, in contrast with the results for all other dependent variables. We conclude that the QTVI is a reasonably consistent measure of the cardiac ventricular function, and as such is a more useful index than other parameters based on RR or QT interval alone.     

Reproducibility indices applied to cervical pressure pain threshold measurements in healthy subjects

OBJECTIVES: To apply various statistical indices for reproducibility analysis of pressure pain threshold measurements and to derive a preferred pressure pain threshold measurement protocol based on these indices. METHODS: The pressure pain threshold of 3 pairs of right and left homologous cervical region sites were measured in 20 healthy subjects (10 women, 10 men) using a hand-held pressure algometer. Measurements took place on 2 occasions (test 1 and test 2) separated by a mean interval of 1 week. On each testing session, the site-related pressure pain thresholds were measured 3 times each according to 2 different protocols. Protocol A consisted of a repetitive order, namely 3 consecutive measurements at each site before proceeding to the next, whereas protocol B consisted of an alternate order in which 3 consecutive rounds of all individually tested sites took place. For test 1, protocol A was followed by protocol B with an hour interval. For test 2, the reverse order took place. RESULTS: The findings revealed no significant differences between the two protocols and indicated a significant rise (P < 0.0001) in the absolute scores from test 1 to test 2 in both protocols. Absolute values (mean +/-SD) derived from the entire sample of pressure pain threshold sites ranged from 140 +/- 60 to 198.7 +/- 95 kPa (1.60 +/- 0.6 to 1.99 +/- 0.95 kg/cm, respectively). No significant gender or side differences were noted. Pearson r as well as the intraclass correlation coefficient revealed good to excellent reproducibility for both protocols and for all sites measured: r = 0.79-0.94 and intraclass correlation coefficient(3,3) = 0.85-0.96, respectively. To define site-specific cutoff values indicating change at the 95% confidence level, 1.96*SEM was calculated, and its values ranged from 31.6 to 58.2 kPa, which correspond to 16.8% to 32.8% of the absolute mean values. In addition, the limits of agreement, which depict the individual test-retest differences relative to their mean, indicated a heteroscedastic trend. DISCUSSION: The two protocols yielded very similar results. However, on the grounds of patient's comfort and compliance as well as facility of application, protocol B stands out as the more preferred between the two.     

Association between insulin resistance, body mass and neopterin concentrations.

Obesity is frequently associated with insulin resistance. Recently an important role of the cytokine tumor necrosis factor-alpha in mediating insulin resistance of obesity through its overexpression in fat tissue has been reported. In order to examine the relation of insulin resistance to obesity and to serum neopterin, as a parameter of immune activation, we studied 1234 otherwise healthy outpatients, who visited the physician's office for a medical health check-up. 7% showed elevated glucose concentrations, 34% elevated body mass indices. There were significant correlations between glucose concentrations and body mass indices and of the latter with serum neopterin concentrations. Neopterin concentrations were significantly higher in patients with elevated body mass indices (Mann-Whitney test, U = 131 358, p = 0.0003) and elevated glucose concentrations (Mann-Whitney test, U = 35 350 p =0.02). The data may indicate that moderate immune stimulation plays a role in the development of insulin resistance, and an influence of tumor necrosis factor-alpha seems to be probable.     

Association between body mass index and functional independence measure in patients with deconditioning

OBJECTIVE: To assess the association of body mass index (BMI) with functional independence measure (FIM) score in patients with deconditioning. We also examined whether the association was different for motor and cognitive subscales of the FIM instrument. DESIGN: A retrospective study of 1077 inpatients admitted to the general medicine service for deconditioning at an acute rehabilitation hospital. Patients were classified into underweight (BMI < 18.5), normal range (BMI = 18.5-24.9), overweight (BMI = 25.0-29.9), obese class I (BMI = 30.0-34.9), obese class II (BMI = 35.0-39.9), and obese class III (BMI > or = 40). RESULTS: Median gain in FIM scores from admission to discharge was highest in obese class I patients (27 points), followed by obese class II patients (26 points). The most gain in FIM scores was accounted for by the motor subscale. Adjusting for age, gender, and length of in-hospital stay, obese class I patients had a 5.8-point (95% confidence limits = 1.2, 7.0) higher gain in FIM score compared with patients with BMI in the normal range. CONCLUSIONS: In an acute rehabilitation setting, obese patients had higher gains in FIM scores as compared with normal-range-BMI patients. Most of the improvements in FIM scores were accounted for by the motor subscale, with little or no improvement on the cognitive scale.     

Association between homocysteine and neopterin in healthy subjects measured by a simple HPLC-fluorometric method.

OBJECTIVES: Neopterin and homocysteine promote vascular smooth muscle cell proliferation through the activation of nuclear factor(kappa) B. The aim of this study was to investigate the relation between these two compounds in healthy subjects by a rapid HPLC-fluorometric method which simplifies sample pretreatment for the measurement of neopterin in serum. DESIGN AND METHODS: In 40 healthy subjects (45.9 +/- 2.1 yr, mean +/- SEM, 10 males, 30 females) serum neopterin concentrations were measured by HPLC-fluorometry and enzyme-linked immunusorbant assay-ELISA and the results were compared. Urinary neopterin and plasma total homocysteine concentrations were assayed by HPLC-fluorometry. RESULTS: Serum neopterin concentrations measured by HPLC and ELISA were 7.5 +/- 0.4 and 7.4 +/- 0.3 nmol/L, respectively, r = 0.92, p < 0.01. Urinary neopterin level was 163.9 +/- 11.0 nmol/mmol creatinine and plasma total homocysteine 7.6 +/- 0.4 micromol/L. A significant positive correlation was observed between serum neopterin and plasma total homocysteine (r = 0.59, p < 0.01). CONCLUSIONS: A simple and rapid sample pretreatment for the measurement of neopterin in serum has been introduced. The significant positive correlation between neopterin and homocysteine implies that, interference with leukocyte function might be a new possible mechanism for the deleterious effects of homocysteine on vascular function.     

Association between reduced low density lipoprotein oxidation and inhibition of monocyte chemoattractant protein-1 production in statin-treated subjects

Monocyte chemoattractant protein-1 (MCP-1) is essential in atherogenesis. Oxidized lipids regulate MCP-1 expression and release from mononuclear cells. In this study we investigated (1) whether statin therapy reduces lipopolysaccharide (LPS)-stimulated MCP-1 production in human whole-blood samples and (2) the relationships between in vitro low-density lipoprotein (LDL) oxidation and MCP-1 production. Fasting blood samples were obtained from 55 healthy nonsmoking adults with moderate hypercholesterolemia who were participating in a randomized double-blind 8-week trial comparing the effects of statin therapy with those of placebo on cytokine production. Samples were analyzed for resistance to copper-mediated LDL oxidation (lag time in minutes), as well as MCP-1- and interleukin-8 (IL-8)-stimulated production. Statin therapy reduced MCP-1 production (mean +/- SD) -161 +/- 399 pg/mL/mm 3 white cells) compared with 267 +/- 985 pg/mL/mm 3 in the placebo group, but changes were not different between active and placebo groups ( P = .13). Statin therapy also increased lag times (median [interquartile range]; 20.5 [7.0-51.2] minutes vs -17.0 [-5.3-16.5] minutes; P = .067 for group difference). Inhibition of MCP-1 production correlated with prolongation of lag time ( r = .46, P = .0056) in statin-treated subjects. Statin therapy reduced MCP-1 production in the whole blood of human subjects and these changes were correlated with improvement in LDL oxidative resistance.     

Correlation between body mass index and striatal dopamine transporter availability in healthy volunteers--a SPECT study

Recent lines of research suggest that, in addition to hypothalamic sites, the striatum dopaminergic system may be a target for regulating homeostasis that may be represented by the body mass index (BMI). Although it has been reported that the striatal dopamine receptor (DRD2) availability of very obese individuals was reduced in proportion to their BMI, the correlation between the striatal dopamine system and the BMI in healthy individuals remains unclear. To investigate this relationship, the striatal dopamine transporter (DAT) availability of 50 healthy volunteers was measured using single position emission computational topography (SPECT) and [99mTc]-TRODAT-1. The serum levels of sugar, C-peptide, insulin, glycosylated hemoglobin and leptin were measured. Our results showed that age and the BMI are significantly negatively associated with the striatal DAT availability. Moreover, BMI was the only significant predictor for striatal DAT availability. These results suggest that the striatal dopamine system may be involved in body mass index regulation. Thus, molecular imaging studies measuring the striatal DAT availability should consider the BMI, rather than age, as a covariant.     

Influence of C4B null genes on cytomegalovirus antibody titers in healthy blood donors

C4B null genes (C4B*Q0) have been found with increased frequency in persons with viral diseases, including hepatitis and human immunodeficiency virus infection. Whether a relationship might exist between the presence of C4B*Q0 and antibodies to cytomegalovirus (CMV) was investigated. Fifty blood donors who were seropositive for CMV antibodies and 101 healthy nondonors were C4-allotyped with electrophoresis immunofixation. CMV-seropositive sera were titrated for CMV IgG-specific antibody by enzyme-linked immunosorbent assay, and serum IgG levels were assayed by rate nephelometry. C4B*Q0 was higher in the CMV antibody-positive group than in nondonors (p = 0.05), but the increase was most significant (p = 0.028) in donors with the highest titers of CMV antibodies. There was poor correlation (r = 0.015) between CMV titers and plasma IgG levels. Serum C4B levels were lower in CMV antibody-positive donors with one C4B null gene than in matched nondonors or nondonors not having any null genes.     

Interpretations of SARS-CoV-2 IgM and IgG antibody titers in the seroepidemiological study of asymptomatic healthy volunteers

IntroductionThe usefulness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody tests in asymptomatic individuals has not been well validated, although they have satisfied sensitivity and specificity in symptomatic patients. In this study, we investigated the significance of IgM and IgG antibody titers against SARS-CoV-2 in the serum of asymptomatic healthy subjects.MethodsFrom June 2020, we recruited 10,039 participants to the project named the University of Tokyo COVID-19 Antibody Titer Survey (UT-CATS), and measured iFlash-SARS-CoV-2 IgM and IgG (YHLO IgM and IgG) titers in the collected serum. For the samples with increased IgM or IgG titers, we performed additional measurements using Elecsys Anti-SARS-CoV-2 Ig (Roche total Ig) and Architect SARS-CoV-2 IgG (Abbott IgG) and investigated the reactivity to N, S1, and receptor binding domain (RBD) proteins.ResultsAfter setting the cutoff value at 5 AU/mL, 61 (0.61%) were positive for YHLO IgM and 104 (1.04%) for YHLO IgG. Few samples with elevated YHLO IgM showed reactivity to S1 or RBD proteins, and IgG titers did not increase during the follow-up in any samples. The samples with elevated YHLO IgG consisted of two groups: one reacted to S1 or RBD proteins and the other did not, which was reflected in the results of Roche total Ig.ConclusionsIn SARS-CoV-2 seroepidemiological studies of asymptomatic participants, sufficient attention should be given to the interpretation of the results of YHLO IgM and IgG, and the combined use of YHLO IgG and Roche total Ig might be more reliable.     

Effect of body position on foot and ankle volume in healthy subjects

Physical therapy treatments for and evaluation of lower limb swelling are usually performed in supine lying position. However, the limb is usually treated or assessed in the dependent position, i.e. sitting or standing. The purpose of this study was to determine the possible confounding effect of subject positioning on foot and ankle volume. Sixty healthy individuals were randomly positioned into motionless standing, sitting or supine lying for 30 min. Volumetric measurements of the dominant leg were taken with a foot and ankle volumeter before and after 30 min of positioning. A significant difference between the three groups for foot and ankle volume change (F(2,53) = 35.41, P<0.001) was found. A post-hoc Tukey HSD test revealed that the difference was statistically significant between sitting and standing as well as supine lying and standing (P<0.001). No statistical significance was found between sitting and supine lying (P = 0.90). Standing caused the greatest increase in foot and ankle volume followed by sitting then supine lying. The results indicate that treating or assessing a limb with the subject in a sitting position would not be significantly different from a subject who is positioned in supine lying. However, it is not known whether the height and the distance from the heart to the feet were comparable between the groups, and so it is recommended that, where possible, treatment and assessment of lower leg swelling should be undertaken with the leg in a non-dependent position and definitely not in standing.     

Pharmacokinetic interaction between fosamprenavir-ritonavir and rifabutin in healthy subjects

Rifabutin (RFB) is administered for treatment of tuberculosis and Mycobacterium avium complex infection, including use for patients coinfected with human immunodeficiency virus (HIV). Increased systemic exposure to RFB and its equipotent active metabolite, 25-O-desacetyl-RFB (dAc-RFB), has been reported during concomitant administration of CYP3A4 inhibitors, including ritonavir (RTV), lopinavir, and amprenavir (APV); therefore, a reduction in the RFB dosage is recommended when it is coadministered with these protease inhibitors. Fosamprenavir (FPV), the phosphate ester prodrug of the HIV type 1 protease inhibitor APV, is administered either with or without RTV. A randomized, open-label, two-period, two-sequence, balanced, crossover drug interaction study was conducted with 22 healthy adult subjects to compare steady-state plasma RFB pharmacokinetic parameters during concomitant administration of FPV-RTV (700/100 mg twice a day [BID]) with a 75%-reduced RFB dose (150 mg every other day [QOD]) to the standard RFB regimen (300 mg once per day [QD]) by geometric least-squares mean ratios. Relative to results with RFB (300 mg QD), coadministration of dose-adjusted RFB with FPV-RTV resulted in an unchanged RFB area under the concentration-time curve for 0 to 48 h (AUC(0-48)) and a 14% decrease in the maximum concentration of drug in plasma (C(max)), whereas the AUC(0-48) and C(max) of dAc-RFB were increased by 11- and 6-fold, respectively, resulting in a 64% increase in the total antimycobacterial AUC(0-48). Relative to historical controls, the plasma APV AUC from 0 h to the end of the dosing interval (AUC(0-tau)) and C(max) were increased approximately 35%, and the concentration at the end of the dosing interval at steady state was unchanged following coadministration of RFB with FPV-RTV. The safety profile of the combination of RFB and FPV-RTV was consistent with previously described events with RFB or FPV-RTV alone. Based on the results of this study, a reduction in the RFB dose by > or =75% (to 150 mg QOD or three times per week) is recommended when it is coadministered with FPV-RTV (700/100 mg BID).     

Interaction between warfarin and propafenone in healthy volunteer subjects

The effect of propafenone on the pharmacokinetics and pharmacologic effects of warfarin was studied in healthy normal male volunteer subjects. Each drug was administered alone for 1 week followed by a combined administration for 1 additional week. Blood samples were analyzed for propafenone and warfarin concentrations and the effect of each treatment on the prothrombin time was assessed. The concurrent administration of warfarin did not produce any changes in the absorption or disposition kinetics of propafenone. Concurrent propafenone administration did lead to a reduction in the clearance of warfarin, resulting in an average increase of 38% in the mean steady-state plasma warfarin concentration. During the combined therapy phase, the prothrombin time increased significantly (P less than 0.01) from the "warfarin alone" phase. We conclude from this study that the concomitant administration of propafenone and warfarin may lead to an enhanced anticoagulant effect that may require a reduction in the warfarin dose.     

云南红河地区哈尼族体质量、体质量指数与跟骨超声速度

背景：国外学者报道人群骨量20%归于环境因素,80%归于遗传因素,骨密度的种族及民族差异是很明显的.目的：调查云南红河地区哈尼族跟骨定量超声测量,分析其与体质量及体质量指数之间关系.方法：采取随机整群抽样和调查者入户调查的方式对云南省红河地区哈尼族人群300名进行抽样调查,其中男109名,女性191名.现场访谈填写调查表并测量血压、身高、腰围、体质量等,同时均用Achil es Express跟骨定量超声测量仪测量被调查者的右侧跟骨超声速度,并进行相关性分析.结果与结论：被调查的人群体质量平均为（46.39±8.44） kg,体质量指数平均为（21.07±3.21） kg/m2跟骨定量超声传导速度值为（1512.38±36.77） m/s.相关分析显示,右跟骨定量传导速度值与跟骨密度T值相关性高,可以预测跟骨骨密度.跟骨定量超声传导速度值除与年龄呈负相关,与体质量及体质量指数均呈正相关,并均有显著性意义.提示云南省红河地区哈尼族中老年人的跟骨骨密度与体质量及体质量指数有显著的相关关系.     

Association between irisin and homocysteine in euglycemic and diabetic subjects

ObjectivesThe aim of study was to explore whether a relationship exists between homocysteine and irisin in type 2 diabetes (T2D) patients—a population with a high risk of developing cardiovascular disease—and euglycemic controls.Design and methods69 T2D patients and 75 control subjects (adjusted by body mass index (BMI)) were included in the study. Irisin and homocysteine concentrations and anthropometric and biochemical variables were determined.ResultsLevels of homocysteine were significantly higher (11.0 ± 3.0 vs 12.4 ± 4.2 μmol/l) and levels of irisin were lower (279 ± 58 vs 263 ± 38 ng/ml) in T2D patients. When both T2D and controls were considered, irisin was found to correlate only with homocysteine (r = − 0.215; p = 0.011). Moreover, a decreasing trend in irisin levels was observed according to homocysteine tertile (p = 0.034).ConclusionsOur results provide evidence of an association between irisin and homocysteine, which may be due to nicotinamide metabolism. The clinical significance of this relationship is unclear, but our findings may prompt further mechanistic research to investigate the role played by irisin in vascular disorders.