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This study sought to evaluate the effects of two vaccine doses and the extent of SARS-CoV-2 infection among healthcare workers. We measured immunoglobulin G antibody titers against SARS-CoV-2 nucleocapsid and spike protein among healthcare workers at Gunma University Hospital. In March 2021, prior to BNT-162b2 vaccination, two of 771 participants were seropositive for nucleocapsid and spike protein, whereas 768 were seronegative. The remaining one participant was seropositive for nucleocapsid protein but seronegative for spike protein. A total of 769 participants were seropositive for spike protein after two vaccination doses. The two seropositive participants prior to vaccination showed the highest antibody titers after the second vaccination. They were probably infected with SARS-CoV-2 without clinical symptoms before March 2021. Four weeks after the second vaccination, a younger age was associated with higher antibody titers against SARS-CoV-2 spike protein. Thirty-two weeks after the second vaccination, blood samples were collected from 342 of 769 participants. Antibody titers at 32 weeks after the second vaccination significantly decreased compared with those at 4 weeks after the second vaccination among all age groups. The rate of decrease in antibody titers between 4 and 32 weeks after the second vaccination was greater in the female participants. No sex differences were observed in the antibody titers within each age group. BNT-162b2 vaccination thus induced seroconversion in an age-dependent manner. Serological screening could further establish the likelihood of subclinical SARS-CoV-2 infection.

Background: Insulin resistance is a well-known predictor and risk factor for Type 2 Diabetes Mellitus (T2DM). Higher hematocrit induced by higher insulin resistance affects blood rheology. Objective: This study intended to reveal the association between indices of insulin resistance and hemorheological parameters during a 75 g oral glucose tolerance test (75-g OGTT). Methods: A total of 575 healthy young Japanese participants took 75-g OGTT. We then analyzed the association between insulin resistance indices and hematological parameters. Results: The Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was significantly correlated with hematocrit (Ht), hemoglobin (Hb), Red Blood Cell (RBC), White Blood Cell (WBC), platelet count, lipid parameters, and Body Mass Index (BMI). The Matsuda index was negatively correlated with RBC count, WBC count, platelet count, Total Cholesterol (TC), Low-Density Lipoprotein-Cholesterol (LDL-C), triglyceride (TG), and positively correlated with High-Density Lipoprotein-Cholesterol (HDL-C). The disposition index was negatively correlated with Hb, RBC count, LDL-C, and BMI, while remaining positively correlated with HDL-C. The Homeostasis Model Assessment of beta cell (HOMA- IR ) was positively correlated with WBC count, platelet count, TC, LDL-C, and TG. The insulinogenic index was positively correlated with WBC count, platelet count, and TC. Multiple regression analysis revealed that HOMA-IR was independently associated with TG, and the Matsuda index was independently associated with TG, WBC count, and platelet count. The insulinogenic index was independently associated with WBC count. Conclusion: Cardinal rheological parameters reflected insulin resistance and were released even in the young, healthy Japanese individuals within the physiological range of glycemic control.

In this study, our aim was to validate whether the automated measurement of salivary testosterone and cortisol concentrations and the testosterone-to-cortisol (T/C) ratio considering their individual circadian rhythms can be used to assess the stress response of male athletes to different exercise intensities accurately and effectively. We measured the salivary testosterone and cortisol concentrations and their respective serum concentrations that were collected from 20 male long-distance runners via passive drooling in the morning and evening for two consecutive days involving different exercise intensities. An electrochemiluminescence immunoassay was performed to evaluate the salivary testosterone and cortisol concentrations. The results showed a positive correlation between the salivary testosterone and cortisol concentrations and their respective serum concentrations. The participants were divided into high-intensity and low-intensity exercise groups. The high-intensity exercise group showed a significantly higher rate of change in the salivary cortisol concentration and significantly lower rate of change in the T/C ratio in the evening of day 1. Our results indicated that the automated assessment of salivary cortisol concentrations and the T/C ratio could distinguish between exercises at different intensities, which may be beneficial for detecting differences in stress responses among athletes.

To elucidate the age-related sex difference in glucose tolerance, we conducted 75 g oral glucose tolerance tests in 1156 participants. Participants were divided into four groups, namely, young (22–29) males, young females, middle-aged (>50) males, and middle-aged females. According to the Japanese Clinical Practice Guideline for Diabetes 2019, the prevalence of normal glucose tolerance (NGT) was significantly lower in middle-aged than in young participants. The prevalence of high-normal fasting plasma glucose (FPG) was higher, and NGT was lower in young males (high-normal FPG 15.2%, NGT 82.0%) than young females (high-FPG 3.9%, NGT 94.3%). Combined glucose intolerance (CGI) was higher and NGT was lower in middle-aged males (CGI 10.2%, NGT 25.2%) than in middle-aged females (CGI 3.3%, NGT 39.8%). FPG and body mass index (BMI) were the lowest and Homeostatic model assessment beta cell function (HOMA-β) was the highest in young females, followed by young males, middle-aged females, and middle-aged males. Multiple linear regression analysis revealed that BMI weakly correlated with HOMA-β and Matsuda index in all subjects except young females. The superior glucose tolerance in females was apparent in young, but attenuated in middle-aged females. The differences are due to the higher insulin secretion potential and lower BMI in young females.

There are currently no established cutoff levels for thyrotropin (TSH) within the reference intervals associated with carotid atherosclerosis to prevent the onset of cardiovascular diseases. The present study aimed to determine the TSH cutoff level associated with carotid maximum intima-media thickness (max IMT) in euthyroid premenopausal, perimenopausal and postmenopausal women.We conducted a cross-sectional study of 468 euthyroid women who had not been treated for or diagnosed with cardiovascular diseases and/or metabolic disorders among 1221 Japanese women who participated in a comprehensive medical examination at the Hidaka Hospital, Japan. Participants' weight, blood pressure, plasma glucose, serum lipoprotein, free thyroxine and TSH were measured and an interview about menstruation was conducted. Carotid ultrasonography was performed to determine max IMT.Max IMT significantly increased stepwise as menopausal status progressed (p0.001). Serum TSH levels were significantly higher in participants with carotid plaques, defined as max IMT ≥1.1 mm (p = 0.038), and were independently associated with the presence of carotid plaque using multivariate logistic regression analysis (β =1.218, p = 0.036). In postmenopausal women, significantly higher carotid max IMT values were observed in women with serum TSH ≥2.5 μIU/mL compared with women with concentrations2.5 μIU/mL (p = 0.018) without elevated total cholesterol and low-density lipoprotein cholesterol concentrations. These differences were not observed in premenopausal women.Laboratory finding of serum TSH concentration ≥2.5 μIU/mL may be useful to assess risk of atherosclerosis, especially in postmenopausal women.

Objective: Given the association between diabetes suppression and inhibition of diet-induced elevation in glucose and insulin, we investigated the effects of adding glucomannan to rice gruel on pre- and postprandial glucose and insulin concentrations. Methods: A total of 25 Japanese subjects without a history of diabetes or gastrointestinal disease (all males; aged 37–60 years; body mass index 20.4–31.6) participated in this study. Subjects received a 75-g oral glucose tolerance test (75gOGTT) and rice gruel containing 0, 0.4, or 0.8% of glucomannan. Blood samples were then obtained at preload and at 30, 60, and 120 min after receiving 75 g of glucose or rice gruel with or without glucomannan. Results: After the 75gOGTT, 8 subjects had normal glucose tolerance (NGT), whereas 17 showed a borderline pattern. Moreover, our data showed that greater amounts of glucomannan promoted lesser 30-min postload plasma glucose and insulin levels, with differences being larger in the borderline group than in the NGT group. Conclusions: Glucomannan dose-dependently inhibited the rice gruel-induced increase in 30-min postprandial plasma glucose and insulin levels. Furthermore, greater inhibitory effects on glucose and insulin elevation were observed in the borderline group than in the NGT group.

Background Two important regulators for circulating lipid metabolisms are lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL). In relation to this, glycosylphosphatidylinositol anchored high-density lipoprotein binding protein 1 (GPIHBP1) has been shown to have a vital role in LPL lipolytic processing. However, the relationships between skeletal muscle mass and lipid metabolism, including LPL, GPIHBP1, and HTGL, remain to be elucidated. Demonstration of these relationships may lead to clarification of the metabolic dysfunctions caused by sarcopenia. In this study, these relationships were investigated in young Japanese men who had no age-related factors; participants included wrestling athletes with abundant skeletal muscle. Methods A total of 111 young Japanese men who were not taking medications were enrolled; 70 wrestling athletes and 41 control students were included. The participants’ body compositions, serum concentrations of lipoprotein, LPL, GPIHBP1 and HTGL and thyroid function test results were determined under conditions of no extreme dietary restrictions and exercises. Results Compared with the control participants, wrestling athletes had significantly higher skeletal muscle index (SMI) (p

Objective Several studies have demonstrated that the secreted glycoprotein and integrin ligand milk fat globule-associated protein with epidermal growth factor- and factor VIII-like domains (MFG-E8) negatively regulates fibrosis in the liver, lungs, and respiratory tract. However, the mechanisms and roles of MFG-E8 in skin fibrosis in systemic sclerosis (SSc) have not been characterized. We undertook this study to elucidate the role of MFG-E8 in skin fibrosis in SSc. Methods We assessed expression of MFG-E8 in the skin and serum in SSc patients. We examined the effect of recombinant MFG-E8 (rMFG-E8) on latent transforming growth factor β (TGFβ)-induced gene/protein expression in SSc fibroblasts. We examined the effects of deficiency or administration of MFG-E8 on fibrosis mouse models. Results We demonstrated that MFG-E8 expression around dermal blood vessels and the serum MFG-E8 level in SSc patients (n = 7 and n = 44, respectively) were lower than those in healthy individuals (n = 6 and n = 28, respectively). Treatment with rMFG-E8 significantly inhibited latent TGFβ-induced expression of type I collagen, α-smooth muscle actin, and CCN2 in SSc fibroblasts (n = 3-8), which suggested that MFG-E8 inhibited activation of latent TGFβ as well as TGFβ signaling via binding to αv integrin. In a mouse model of bleomycin-induced fibrosis (n = 5-8) and in a TSK mouse model (a genetic model of SSc) (n = 5-10), deficient expression of MFG-E8 significantly enhanced both pulmonary and skin fibrosis, and administration of rMFG-E8 significantly inhibited bleomycin-induced dermal fibrosis. Conclusion These results suggest that vasculopathy-induced dysfunction of pericytes and endothelial cells, the main cells secreting MFG-E8, may be associated with the decreased expression of MFG-E8 in SSc and that the deficient inhibitory regulation of latent TGFβ-induced skin fibrosis by MFG-E8 may be involved in the pathogenesis of SSc and may be a therapeutic target for fibrosis in SSc patients.

Background: There are conflicting reports with regard to the superiority of cortisol as a stress marker in high-altitude training due to the influence of the circadian rhythm. This study aimed to determine if the automated measurement of salivary cortisol concentration via sequential sampling could detect the differences in acclimatization and exercise stress between two altitude camps. Methods: A total of 12 elite female long-distance runners living near sea levels were enrolled in this study. For the first camp simulating higher altitude, the runners lived at 1800 m and trained at 1700 m for 7 days. For the second camp simulating lower altitude, they lived at 1550 m and trained at 1300 m for 7 days. Their saliva was sequentially collected on the last 2 days during each camp involving different intensity exercise in the morning and afternoon. The salivary cortisol concentrations were measured using electrochemiluminescence immunoassay. Results: The sequential saliva collection and automated measurement were able to detect the basal levels and exercise-induced changes in the salivary cortisol within the runners' circadian rhythms in each altitude camp. Before dinner, the basal salivary cortisol concentrations were significantly higher in the higher-altitude camp. The rate of change in the salivary cortisol concentration after the afternoon exercise on day 2 of the higher-altitude camp with higher exercise intensity was significantly higher than that in the lower-altitude camp (p = 0.003). The rate of change in the salivary cortisol concentration during the morning exercise on day 2 was significantly higher in the higher-altitude camp than in lower-altitude camp (p = 0.028) despite the same exercise programs and intensities. Conclusions: Measurement of the salivary cortisol levels during the circadian rhythms could detect the differences in acclimatization and exercise stress between two altitude camps. Automated measurements of salivary cortisol concentrations via sequential saliva sampling may be useful for assessing adaptation disorders and excessive exercise stress and also help develop adequate high-altitude training programs for athletes.

Background: Exercise stress promoted cortisol and testosterone secretions that have their own circadian rhythms. It is necessary that the testosterone, cortisol and testosterone/cortisol ratio (T/C ratio) are measured through their rhythms for use in monitoring exercise-induced stress in athletes. Automated measurement has not been applied to salivary testosterone, which requires passive drooling difficult to collect sufficient saliva rapidly. This study aimed to verify whether automated measurements of the testosterone and cortisol concentrations and T/C ratio using saliva collected sequentially can effectively assess exercise intensity differences within circadian rhythms in male athletes.Methods: We investigated the correlations of testosterone and cortisol concentrations measured by electrochemiluminescence immunoassay (ECLIA) between saliva and sera collected from 20 male long-distance runners. We collected the runners' saliva sequentially by passive drooling on two consecutive days involving different intensity trainings in the morning and evening; salivary testosterone and cortisol concentrations were measured by ECLIA. Each exercise intensity was measured by running distances, velocities, Borg scale score and maximum pulse rate during exercise.Results: The salivary testosterone and cortisol concentrations were positively correlated with the respective total serum hormone concentrations. The runners were divided into low-intensity exercise group (n = 8) and high-intensity exercise group (n = 7), in which five runners were excluded because measurable saliva samples could not be obtained due to low volume and high-viscosity. Sequential saliva collection and automated measurements detected the runners' circadian rhythms of testosterone, cortisol and T/C ratio. The rate of change in the salivary cortisol concentrations were significantly higher and that in the T/C ratio was significantly lower in the evening interval training on day 1 in the high-intensity exercise group which had significantly higher running velocity, Borg scale score, and maximum pulse rate values; this relationship was not shown for salivary testosterone.Conclusions: Automated measurements of the salivary cortisol concentration and the T/C ratio reflected different exercise intensities may be useful for creating appropriate exercise programs for athletes. Conversely, the automated measurements of salivary testosterone and T/C ratio, which require passive drooling to collect saliva, may be less suitable for practical use with athletes than the salivary cortisol-only measurement

Background: Recently, we showed that konjac glucomannan (KGM) inhibited rice gruel-induced postprandial elevation of plasma glucose and insulin. To extend that research, we investigated the effects of adding KGM to rice gruel on pre- and postprandial circulating lipoprotein lipase (LPL), glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1), and triglyceride concentrations. Methods: Twenty-four Japanese male subjects without diabetes or gastrointestinal diseases (aged 46–56 years) were included. Subjects received rice gruel containing 0% or 0.8% of KGM (0%G and 0.8%G, respectively). Blood samples were obtained at preload and 30, 60, and 120 min after receiving rice gruel with or without 0.8% KGM. LPL, GPIHBP1, and triglyceride concentrations in these samples were measured. Results: Circulating triglycerides were significantly reduced at 30 min and then returned to the fasting value in the subjects who received 0%G, whereas lower triglyceride levels were sustained in those who received 0.8%G. Although circulating levels of LPL and GPIHBP1 were significantly reduced for 0%G, they were increased for 0.8%G. We found a significant negative correlation between circulating levels of fasting LPL and triglycerides and a significant positive correlation between circulating levels of fasting LPL and GPIHBP1. A significant negative correlation between circulating levels of triglycerides at 120 min and fasting LPL was shown in the 0.8%G group, but not in the 0%G group. A significant positive correlation between circulating levels of LPL at 0 min and 120 min was shown in the 0%G and 0.8%G groups.Conclusions: The results demonstrated a novel pleiotropic effect of KGM. Supplementation of KGM powder in rice gruel sustained lower levels of triglycerides accompanying elevation of LPL and GPIHBP1, which attenuated lipid metabolism. Additionally, fasting LPL is a predictor of postprandial circulating levels of LPL.Trial registration: UMIN registration number: UMIN000025950; registered at February 1st. 2017; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000029247

This paper describes the simultaneous capillary electrophoresis (CE) of anions and cations using an anion exchange-modified capillary, which was prepared by chemical coating with a cationic silylating reagent, and its application to saliva analysis. The CE method provides high-throughput (5 min for a single sample injection) analysis by generating a high-velocity electroosmotic flow at pH 3.0–3.5. The detection limits at a signal-to-noise ratio of 3 ranged from 1.2 to 18 μM for anions and 1.0 to 2.7 μM for cations. The relative standard deviations for the migration times and peak areas of analytes (n = 4) ranged from 0.05% to 0.40% and 0.94% to 4.7%, respectively. The CE system was used to analyze 11 common ions in saliva samples collected from long-distance runners and sedentary university students before and after running for a set distance or a set time. Interestingly, the SCN− concentrations decreased in the saliva samples of all 14 athletes and 16 sedentary students after running. Furthermore, when the concentrations of the analyzed ions were compared with that of cortisol as a typical stress marker by multiple regression analysis, SCN− and NO3− in saliva samples from the two subject groups strongly correlated with cortisol levels, as determined by an electrochemiluminescence immunoassay. This study improves our knowledge of both the analytical methodology for CE and statistical methods for identifying common ions that could be used as physical stress markers.

Background Few nutritional markers reflect the hypermetabolic state of athletes with high levels of skeletal muscle. Although branched-chain amino acids (BCAA) play crucial roles in protein metabolism in skeletal muscle, the relation between circulating BCAA concentration and skeletal muscle mass has not been fully understood. The aim of this study is to evaluate the association between skeletal muscle mass and serum BCAA to tyrosine ratio (BTR), a convenient indicator of circulating BCAA, in young Japanese men including wrestling athletes with high skeletal muscle mass. Methods The study enrolled 111 young Japanese men: 70 wrestling athletes and 41 controls. None were taking medications or undergoing extreme dietary restriction or an intense exercise regimen. Each participant’s body composition, serum concentrations of albumin and rapid turnover proteins, BTR, and thyroid function were assessed. Results Compared to the controls, the athletes had significantly higher weight-adjusted skeletal muscle mass (SMM) ( p < 0.001) and skeletal muscle index (SMI) ( p < 0.001), and lower serum albumin concentration ( p < 0.001) and BTR ( p < 0.001). Kruskal–Wallis tests with Bonferroni multiple comparison tests showed that serum albumin concentration and BTR were significantly lower in the participants with higher SMM and SMI. Spearman's correlation analyses showed that SMM and SMI were inversely correlated with serum albumin concentration (SMM, ρ = −0.315, p = 0.001; SMI, ρ = −0.511, p < 0.001) and BTR (SMM, ρ = −0.424, p < 0.001; SMI, ρ = −0.511, p < 0.001). Serum albumin concentration was positively correlated with BTR (ρ = 0.438, p < 0.001), transthyretin (ρ = 0.281, p = 0.003) and transferrin (ρ = 0.299, p = 0.001), but BTR was not correlated with other nutritional indicators. Serum concentration of free 3,5,3′-triiodothyronine was inversely correlated with BTR (ρ = −0.308, p = 0.001), but not with serum albumin or skeletal muscle mass. Conclusions These results suggest that the consumption of circulating BCAAs increases with increased skeletal muscle mass and is facilitated by thyroid hormones independent of skeletal muscle mass. Serum BTR may be a useful biomarker to assess the hypermetabolic state of athletes.

Background Overtraining syndrome, caused by prolonged excessive stress, results in reduced performance and cortisol responsiveness in athletes. It is necessary to collect saliva samples sequentially within circadian rhythm for assessing exercise stress by measuring cortisol concentrations, and automated cortisol measurements using electrochemiluminescence immunoassay (ECLIA) may be useful for measuring a large number of saliva samples. In this study, we evaluated the appropriate use of cortisol-based exercise stress assessment within the circadian rhythm, which may diagnose and prevent overtraining syndrome in athletes. Methods We collected saliva and sera from 54 healthy participants and analyzed the correlation between salivary cortisol concentrations measured by ECLIA and enzyme-linked immunosorbent assay (ELISA) or serum cortisol analysis. We also collected saliva continuously from 12 female long-distance runners on 2 consecutive days involving different intensities and types of exercise early in the morning and in the afternoon and measured salivary cortisol concentrations using ECLIA. Each exercise intensity of runners was measured by running velocities, Borg Scale score, and rate of change in the pulse rate by exercise. Results ECLIA-based salivary cortisol concentrations correlated positively with those detected by ELISA (ρ = 0.924, p < 0.001) and serum cortisol (ρ = 0.591, p = 0.001). In long-distance runners, circadian rhythm of salivary cortisol, including the peak after waking and the decrease promptly thereafter, were detected on both days by continuous saliva sampling. The rates of change in salivary cortisol concentrations were significantly lower after an early morning exercise than after an afternoon exercise on both days (day 1, p = 0.002, and day 2, p = 0.003). In the early morning exercise, the rate of change in salivary cortisol concentration was significantly higher on day 1 than on day 2 (p = 0.034), similar to a significant difference in running velocities (p = 0.001). Conclusions Our results suggest that automated ECLIA-based salivary cortisol measurements are able to detect the athletes’ circadian rhythm and compare the exercise stress intensities at the same times on different days, even in the early morning, possibly leading to the prevention of overtraining syndrome.

Aims This study aims to assess insulin secretion and resistance through oral glucose tolerance test (OGTT) among young Japanese individuals. Subjects and methods We enrolled 595 young healthy Japanese individuals aged 22‐29 years. They underwent an OGTT, and their results were divided into 4 groups (I‐IV), according to the time at which their plasma glucose concentration declined below the fasting glucose concentration (30, 60 or 120 minutes or never as groups I, II, III and IV, respectively). Results We classified 575 normal glucose‐tolerant subjects into 4 groups (I‐IV) with I: 28 (4.9%), II: 120 (20.9%), III: 143 (24.9%) and IV: 284 (49.4%) individuals. The Matsuda, insulinogenic and disposition indices were decreased from groups I to IV. ROC curves of disposition index reflecting the composition of insulin secretion and sensitivity classified the prolonged glucose elevation group (group III + IV) from the rapid glucose lowering group (group II; AUC = 0.847). Conclusions Even in a young and healthy Japanese individual within the physiological range of glycaemic control, there is a sequential decrease in insulin sensitivity and secretion., ROC curves of indices between groups identifying the high‐risk group from the low‐risk group. Good AUCs were obtained in disposition index (AUC = 0.847) better than the insulinogenic index and Matsuda index (AUC = 0.786, 0.616, respectively).

In 2014, for the protection of medical workers against measles and rubella infection, the Japanese Society for Infection Prevention and Control (JSIPC) recommended either maintaining antibody titers of seroprotective range or two-dose vaccination. JSIPC defined antibody titers into 3 ranges: seroprotective as expected prevention of infection, seronegative as under detection levels, and seropositive as antibody titers ranged between seronegative and seroprotective. This study aimed to explore the association between the number of vaccine doses received and the antibody titers against measles and rubella among Japanese college students majoring in childcare. A total of 841 female students with no history of measles or rubella were serologically screened at the time of college admission between 2015 and 2018. All 841 students had been vaccinated against measles; 738 (87.8%) received two doses of the measles vaccine and 103 (12.2%) received one dose. Likewise, 839 students, except for two, had been vaccinated against rubella; 719 (85.7%) received two doses of the rubella vaccine and 120 (14.3%) received one dose. We thus found that 107 students (12.7%) were seropositive for measles-specific IgG and 731 (86.9%) attained seroprotective titers. By contrast, in case of rubella-specific IgG, only 462 students (55.1%) attained seroprotective titers, and 371 students (44.1%) were seropositive. The two students without receiving rubella vaccination were classified as seronegative. In conclusion, despite that > 85% of students surveyed had received two doses of measles and rubella vaccines, a substantial number of students remain susceptible to measles and especially rubella at the time of college admission.

In a recent study, we showed that konjac glucomannan (KGM) inhibits rice gruel-induced postprandial increases in plasma glucose and insulin levels. To extend this research, we investigated the effects of KGM addition to rice gruel on pre- and postprandial concentrations of circulating lipoprotein lipase (LPL), glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1), hepatic triglyceride lipase (HTGL), free fatty acids (FFA), and triglycerides (TG). A total of 13 Japanese men, without diabetes, dyslipidemia, or gastrointestinal diseases, interchangeably ingested rice gruel containing no KGM (0%G), rice gruel supplemented with 0.4% KGM (0.4%G), and rice gruel supplemented with 0.8% KGM (0.8%G), every Sunday for 3 weeks. Blood samples were obtained at baseline and at 30, 60, and 120 min after ingestion to measure the abovementioned lipid parameters. Lipid parameters showed small, but significant, changes. Significant reductions were found in circulating FFA levels among all participants. Circulating TG levels significantly declined at 30 min and then remained nearly constant in the 0.8%G group but exhibited no significant difference in the 0%G and 0.4%G groups. Although circulating levels of LPL and GPIHBP1 significantly decreased in the 0%G and 0.4%G groups, they increased at 120 min in the 0.8%G group. Participants in the 0%G and 0.4%G groups showed significant decreases in circulating HTGL levels, which was not observed in the 0.8%G group. Our results demonstrate the novel pleiotropic effects of KGM. Supplementation of rice gruel with KGM powder led to TG reduction accompanied by LPL and GPIHBP1 elevation and HTGL stabilization, thereby attenuating TG metabolism.

Objectives To evaluate fasting serum insulin levels and insulin resistance, and their association with blood rheology, in Japanese young adults without diabetes. Methods Blood samples were analysed and blood rheology was estimated using haematological parameters. Whole blood passage time was measured using a Hitachi MC-FAN© microchannel array flow analyser. Results Out of 151 subjects (mean age, 24.1 ± 1.5 years), fasting serum insulin levels and insulin resistance (using homeostasis model assessment-estimated insulin resistance [HOMA-IR]), were positively correlated with longer whole blood passage times and higher values for haematocrit (Hct), haemoglobin (Hb), fibrinogen, body weight, body mass index (BMI), triglycerides, and low-density lipoprotein cholesterol (LDL-C)/high-density lipoprotein cholesterol (HDL-C) ratio, and were negatively correlated with HDL-C. Whole blood passage time correlated with body weight, BMI, LDL-C/HDL-C ratio, Hct, Hb, white blood cell (WBC) count, platelet count, fibrinogen, fasting serum insulin levels, and HOMA-IR. Multiple regression analysis revealed that whole blood passage time was independently associated with Hct, fibrinogen levels, and WBC count. Conclusions Fasting serum insulin levels and insulin resistance were associated with blood rheology, and may influence blood rheology by modulating haematological parameters and lipid parameters in young adults without diabetes.

Background:Apolipoprotein M (ApoM) is bound to high-density lipoprotein (HDL) in plasma, and HDL hasanticoagulation effects. However, the association between ApoM and biomarkers of coagulation was unclear.Therefore, we investigated relationships between ApoM and biomarkers of coagulation.Methods: Serum samples from 233 Japanese participants including with diabetes mellitus, hypertension,dyslipidemia, or healthy controls were analyzed. Serum ApoM levels were measured using Enzyme-LinkedImmuno-Sorbent Assay(ELISA).Results:Analysis of all 233 participants showed that ApoM levels were positively correlated with age (r＝0.284,p＜0.001), total cholesterol (TC;r＝0.477, p＜0.001), HDL-cholesterol (HDL-C;r＝0.234, p＜0.001) and lowdensitylipoprotein cholesterol (LDL-C;r＝0.331, p＜0.001). Higher ApoM levels were correlated with shorteractivated partial thromboplastin time(APTT;r＝－0.226,p＝0.001) and prothrombin time(PT,％;r＝0.326,p＜0.001). Separate analysis of the 115 healthy controls showed that ApoM levels were positively correlated with age,TC, HDL-C and LDL-C, and higher ApoM levels were correlated with shorter PT.Conclusion:Serum levels of ApoM may influence biomarkers of coagulation.

Deiodinase 2 (DIO2) plays an important role in thyroid hormone metabolism and its regulation. However, molecular mechanism that regulates DIO2 activity remains unclear; only mutaions in selenocysteine insertion sequence binding protein 2 and selenocysteine tranfer RNA (tRNA[Ser]Sec) are reported to result in decreased DIO2 activity. Two patients with clinical evidence of abnormal thyroid hormone metabolism were identified and found to have TSHR mutations as well as DIO2 T92A single nucleotide polymorphism (SNP). Primary-cultured fibroblasts from one patient present a high level of basal DIO2 enzymatic activity, possibly due to compensation by augmented DIO2 expression. However, this high enzymatic active state yet fails to respond to accelerating TSH. Consequently, TSHR mutations along with DIO2 T92A SNP (“double hit”) may lead to a significant reduction in DIO2 activity stimulated by TSH, and thereby may have clinical relevance in a select population of hypothyroidism patients who might benefit from a T3/T4 combination therapy.

Thyroid hormones (THs) exert a number of physiological effects on the cardiovascular system. Some of the nongenomic actions of T3 are achieved by cross coupling the TH receptor (TR) with the phosphatidylinositol 3-kinase (PI3K)/protein kinase Akt (Akt) pathway. We observed that both T3 and T4 rapidly stimulated Akt phosphorylation and Ras-related C3 botulinum toxin substrate 1 (Rac1) activation, which resulted in cell migration, in a PI3K-dependent manner in human umbilical vein endothelial cells (HUVECs). We identified the expression of type 2 iodothyronine deiodinase (D2), which converts T4 to T3, and TRα1 in HUVECs. D2 activity was significantly stimulated by (Bu)2cAMP in HUVECs. The blockade of D2 activity through transfection of small interfering RNA (siRNA) specific to D2 as well as by addition of iopanoic acid, a potent D2 inhibitor, abolished Akt phosphorylation, Rac activation, and cell migration induced by T4 but not by T3. The inhibition of TRα1 expression by the transfection of siRNA for TRα1 canceled Akt phosphorylation, Rac activation, and cell migration induced by T3 and T4. These findings suggest that conversion of T4 to T3 by D2 is required for TRα1/PI3K-mediated nongenomic actions of T4 in HUVECs, including stimulation of Akt phosphorylation and Rac activation, which result in cell migration.

Oxidative stress is a crucial factor in the pathogenesis and development of cardiovascular disease. Recently, simplified methods for the detection of reactive oxygen species (ROS) using the derivatives of reactive oxygen metabolites (d-ROMs) test as an index of ROS products and the biological antioxidant potential (BAP) test as an index of antioxidant potential have been utilized. These methods are easy to perform, quick, inexpensive since they use small equipment, and provide reliable results compared with established oxidative stress and antioxidant markers. Because oxidative stress has been shown to represent the balance of production of ROS and antioxidant capacity, it is more appropriate to evaluate ROS and antioxidant capacity simultaneously. However, no study has examined the associations among d-ROMs, BAP values, and carotid artery intima-media thickness (IMT) concurrently. Therefore, we studied the associations among d-ROMs, BAP values, and the carotid artery IMT. Carotid artery IMT, blood pressure (BP), fasting circulating d-ROMs, BAP, glucose metabolism, lipid, and C-reactive protein levels were measured in 95 subjects (age: 49.5 ± 13.8 years; men: 41; women: 54), including 42 healthy subjects and 53 patients with hypertension, dyslipidemia, and diabetes mellitus who were not on medication. The results of multiple regression analysis revealed that dependent carotid artery IMT determinants remained significantly associated with age, systolic BP, total cholesterol, and BAP, whereas dependent BAP determinants remained significantly associated with body mass index and carotid artery IMT. BAP was strongly correlated with carotid artery IMT in our cohort. Our results suggest that BAP may be a useful risk marker for carotid atherosclerosis.