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Heatstroke can cause acute kidney injury (AKI), which reportedly progresses to chronic kidney disease. Kidney macrophages may be involved in such injury. Although heat acclimation (HA) provides thermal resilience, its renoprotective effect and mechanism remain unclear. To investigate heat stress-induced kidney injuries in mice and the mitigating effect of HA on them, male C57/BL6J mice were exposed to heat stress (40°C, 1 h) with or without 5-day HA (38°C, 3 h/day) prior to heat stress. Heat stress damaged kidney proximal tubules with an elevation of urinary kidney injury molecule-1. Kidney fibrosis was observed on

We evaluated whether Amagasaki health counseling programs led by public health nurses (PHNs) are contribute to improving cardiovascular disease (CVD) risk factors and CVD mortality among adult residents.This cross-sectional study used a before-and-after comparative design. We evaluated data from health checkups and mortality before and after Amagasaki health promotion programs.Population levels of CVD risk factors body mass index (BMI), waist circumference, systolic and diastolic blood pressure, fasting blood glucose, hemoglobin A1c, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, Triglyceride, aspartate aminotransferase (AST), alanine aminotransferase (ALT), uric acid, γ-glut amyl trans peptidase (γ-GTP), serum creatinine, estimated glomerular filtration rate (eGFR) were compared between 2008 and 2012 when the intervention with the Amagasaki health counseling program started from 2008. In addition, standardized mortality ratio (SMR) of acute myocardial infarction (AMI) were compared between 2003-2007 and 2008-2012.Mean value of most CVD risk factors improved and the SMR for AMI declined, which could be attributable in part to the effort of intensive health education and counseling.

We previously demonstrated that prehabilitation by running on a treadmill leads to improved survival after gut ischemia reperfusion (I/R) in mice. The purpose of this research was to examine whether prehabilitation attenuates inflammatory responses after gut I/R in mice.Male C57BL/6J mice (n = 92) were assigned to the sedentary (n = 46) or the exercise (n = 46) group. The exercise group ran on a treadmill for 4 wk, while the sedentary mice did not exercise. After the 4-week pretreatment, all mice underwent gut I/R and the blood, urine, small intestine, lung, liver, and gastrocnemius were harvested prior to ischemia or at 0, 3, 6, or 24 h after reperfusion. Histologically demonstrated organ damage, cytokine levels in the blood, gut and gastrocnemius, myeloperoxidase activity in the gut, 8-hydroxy-2'-deoxyguanosine levels in urine and the gut, and adenosine triphosphate (ATP) and ATP + ADP + adenosine monophosphate levels in the gut and gastrocnemius were evaluated.The treadmill exercise reduced gut and lung injuries at 3 h and liver injury at 6 h after reperfusion. Running on the treadmill also decreased proinflammatory cytokine levels in the blood at 6 h, gut at 3 h and gastrocnemius at 6 h after reperfusion, myeloperoxidase activity in the gut prior to ischemia, and 6 h after reperfusion and the urinary 8-hydroxy-2'-deoxyguanosine level at 24 h after reperfusion, while ATP levels in exercised mice prior to ischemia and 3 h after reperfusion were increased in the intestine as compared to the levels in sedentary mice.Prehabilitation with treadmill exercise reduces inflammatory responses after gut I/R and may exert protective actions against gut I/R.

Background It is uncertain whether health counselling after community-based health checkups for high-risk individuals of lifestyle-related disease enhances their referral to physicians. Methods We performed a clustered randomized controlled trial of untreated high-risk individuals aged 40 to 74 years who were screened from the annual health checkup in 2014 and 2015 under the national health insurance in 43 municipalities around Japan, assigning 21 intervention and 22 usual care municipalities. The high-risk conditions were severe forms of hypertension, diabetes, dyslipidemia (for men), and proteinuria. For the intervention group, the theory-based health counselling was performed to enhance referrals to physicians, while each municipality performed its own standard counselling for the usual care group. Data on clinical visits and risk factors were collected systematically and anonymously from the databases of health insurance qualification, health insurance claims, and annual health checkups. Hypotheses are that the cumulative proportion of seeing physicians (clinical visits) is higher in the intervention than the usual care groups, and that those in the intervention group have lower cumulative incidence of composite outcomes associated with lifestyle-related diseases. Results The numbers of subjects for the analyses were 8,977 in the intervention group and 6,733 in the usual care group. Among them, 6,758 had hypertension, 2,147 had diabetes, 2,861 had dyslipidemia, and 1,221 had proteinuria in the intervention group, with corresponding numbers of 4,833, 1,517, 2,262, and 845, respectively, in the usual care group. There were no material differences in mean levels and proportions of major cardiovascular risk factors between the two groups. Conclusions We expect to provide scientific evidence on the effectiveness of health counselling.

Although parenteral nutrition (PN) is the only option for providing adequate nutrition to patients who cannot tolerate oral ingestion, it severely impairs intestinal barrier function in terms of morphology and immunity. While addition of either soybean oil (SO) or fish oil (FO) to PN partially reverses these defects, the effects of the oil composition (FO/SO ratio) on morphology and gut-associated lymphoid tissues (GALT) have yet to be elucidated. We focused on the effects of the FO/SO ratio in PN on the number of lymphocytes in Peyer's patches, immunoglobulin A levels, and intestinal structures.Male ICR mice (n = 61) were randomized into five groups; oral nutrition (Chow, n = 14) and four groups receiving PN without oral nutrition. PN solutions contained fat emulsions with the following FO:SO ratios: 0:1 (SO, n = 12), 1:11.5 (11.5FSO, n = 17),1:2 (1:2FSO, n = 13) and 1:0 (FO, n = 5). All mice underwent jugular vein catheter insertion. The PN groups were given isocaloric and isonitrogenous nutritional support with 20% of total calories from fat emulsions with equivalent fat delivery in 11.9 g/kg/d. After 5 d of each feeding, Peyer's patches lymphocytes were isolated from the small intestine, counted and analyzed with flowcytometry for determination of their phenotypes (αβTCR+, γδTCR+, CD4+, CD8+ and B cells). Villus height and crypt depth of the jejunum and ileum were evaluated with hematoxylin-eosin staining. Immunoglobulin A levels in the intestinal washings were also determined.Numbers of total lymphocytes and B lymphocytes in PP were increased in the 1:2 FSO-PN but neither in the 1:11.5 FSO nor the FO group, as compared to the SO group. There were no marked differences among the groups in numbers neither of total T cells nor in any of T cell phenotypes determined. The 1:2 FSO group showed significantly greater villus height and crypt depth than the SO group. IgA levels did not differ significantly among the four PN groups.The PN with 1:2 FSO (FO:SO = 1:2) maintained lymphocyte numbers in PP and intestinal villus morphology at levels nearly the same as those obtained with chow feeding. An appropriate ratio of FO to SO in PN is expected to prevent immunological impairment and morphological atrophy of the gut associated with lack of oral nutrition.

this study explored whether the modification of selected lifestyles is likely to increase life expectancy from middle age onwards, regardless of the presence of major comorbidities.we examined a prospective cohort of 20,373 men and 26,247 women aged 40-80 years. Eight modifiable lifestyle factors were assessed: consumption of fruit, fish and milk, walking and/or sports participation, body-mass index, smoking status, alcohol consumption and sleep duration. Modifiable healthy lifestyle factors scored one point each, for a maximum of eight points. The impact of modifiable healthy lifestyle adoption on lifetime gain during the ages of 40-102 years was analysed.during the median 21 years of follow-up, 8,966 individuals (3,683 men and 5,283 women) died. Life expectancy at 40 years (95% confidence intervals) for 7-8 health lifestyle points was 46.8 (45.6-48.1) and 51.3 (50.0-52.6) years for men and women, respectively. The potential impact of modifiable healthy lifestyle adoption on lifetime gain persisted over the age of 80 years or more, in individuals with ≥5 factors (P 0.001), particularly older men. The benefits were more pronounced among patients with major comorbidities, such as cardiovascular disease, cancer, hypertension, diabetes, kidney disease and those with multimorbidity throughout all age categories.adopting modifiable healthy lifestyles was associated with lifetime gain, even in individuals aged 80 years or more, regardless of the presence of any major comorbidities in each life stage since middle age. The findings imply the importance of improving the one's lifestyle for an increased lifespan, even among older patients and/or those with multimorbidity.

Previous reports suggested that low subcutaneous adiposity increases the risk of cardiovascular events and diabetes. Mechanisms of depot-specific differences are still unknown. During studying tissue-specific roles of ERK2 (MAPK1), we observed Fabp4Cre mediated adipocyte-specific ERK2 knockout mice (AE2KO) with HFHS diet showed diminished the size of adipocytes in an only subcutaneous depot and increased ectopic fat depot and fibrotic steatohepatitis. The male AE2KO was created by crossing the C57BL/6 background Fabp4-Cre with ERK2flox/flox mouse. ERK2flox/flox Cre- mouse was used as a control. ERK2KO was observed only in white adipose tissues. With a normal diet, AE2KO mice showed no phenotype. HFHS diet started at age 6 weeks for 18 weeks. AE2KO exhibited 18% increase in body weight (n=8 each, p Disclosure Y. Ishinoda: None. T. Adachi: None. H. Kumagai: None. Y. Ido: None. M. Noguchi: None. Y. Yumita: None. K. Kagami: None. A. Osaki: None. Y. Satoh: None. S. Endo: None. A. Kasuga: None.

Background Surgical patients with gastrointestinal malignancies are at increased risk for malnutrition. However, the mechanism by which dietary restriction (DR), one form of malnutrition, impairs hepatic immunity remains to be clarified. The present study was designed to examine the influence of DR on hepatic mononuclear cell (MNC) numbers, subpopulations, and cytokine productions (tumor necrosis factor α [TNF-α], interferon gamma [IFN-γ], and interleukin 10 [IL-10]) in response to lipopolysaccharide (LPS) in mice. Immunoglobulin (Ig) A levels in the gallbladder and histopathologic changes in the liver were also assessed. Material and methods Male Institute of Cancer Research mice were randomly assigned to three dietary groups: ad libitum (AD), mild restriction (MR), and severe restriction (SR). The AD, MR, and SR groups received daily mouse chow in amounts of 190, 133, and 76 g/kg, respectively, for 7 d. After the mice had been fed for 7 d, hepatic MNCs were isolated. Total hepatic MNCs were counted and subpopulations were determined by flow cytometry. Cytokine productions (TNF-α, IFN-γ, and IL-10) by hepatic MNCs in response to LPS were measured. Blood samples were analyzed for hepatobiliary biochemical parameters. IgA levels in gallbladder bile were measured with enzyme-linked immunosorbent assay. In addition, liver histologies were examined. Results Hepatic MNC numbers were significantly lower in the MR and SR groups than in the AD group, with no significant difference between the MR and SR groups. The percentage of B cells was significantly lower in the SR group than in the MR and AD groups, whereas the T-cell percentage was higher in the SR group than in the MR and AD groups. The percentage of Kupffer cells was significantly lower in the SR group than in the AD group, whereas that in the MR group was midway between those in the SR and AD groups. TNF-α and IL-10 levels in hepatic MNC culture supernatants were increased LPS-dose dependently in the AD group. However, the increase was slight in the MR group and absent in the SR group. The IgA levels in gallbladder bile were significantly lower in the SR and MR groups than in the AD group. On the basis of hematoxylin and eosin staining of hepatic sections, livers from the SR group showed atrophic hepatocytes and sinusoidal dilatation, whereas these changes were absent in the AD group. Conclusions DR decreases hepatic MNC number with subpopulation changes, reduces IgA levels in gallbladder bile, blunts cytokine production by hepatic MNCs, and induces pathologic damage in the liver, which may be an important mechanism underlying the impaired host defense associated with malnutrition.

The current study investigated the association of post-load insulin levels with glucose tolerance in a Japanese population. A total of 1450 Japanese employees who underwent a 75-g oral glucose tolerance test (OGTT) were included. Glucose tolerance was assessed by 120-min glucose levels during a 75-g OGTT. A penalized cubic regression spline model analysis revealed that the 60- and 120-min insulin levels, but not 0- or 30-min insulin levels, had an inverse U-shaped relationship to the 120-min glucose level. Furthermore, peak insulin level followed an inverse U shape in relation to the 120-min glucose level, whereas the peak of insulin appeared at a later point in time as the 120-min glucose level increased. These associations were similarly observed in both obese and non-obese subgroups, although obesity was associated with higher insulin levels. Peak insulin levels also demonstrated an inverse U shape in association with 0-min glucose levels and indices of β cell function, assessed by the disposition index and the β-cell function index. In conclusion, peak insulin levels followed an inverse U shape in relation to glucose intolerance in a Japanese population, whereas the impairment of glucose tolerance was associated with a delay in the time to reach peak insulin levels.

Background Parenteral nutrition (PN) is indispensable for meeting the caloric and substrate needs of patients who cannot receive adequate amounts of enteral nutrition. However, PN decreases hepatic mononuclear cell (MNC) numbers and impairs their functions. We examined the effects of various ratios of ω-3 to ω-6 polyunsaturated fatty acids on hepatic MNC number and function in a murine model. We focused on serum liver enzymes, lipid metabolism, cytokine production, histopathology, and the outcomes of an intraportal bacterial challenge. Material and methods In experiment 1, male Institute of Cancer Research mice were randomized to CHOW, 67%, 33%, 16%, 8%, 4%, and 0% fish oil (FO)-PN groups. After receiving their respective diets for 5 days, 1.0 × 10 7 Pseudomonas aeruginosa were delivered by intraportal injection. Survival was observed ≤7 days after injection. Liver histologies after intraportal bacterial challenge were examined in the CHOW, 33%, 8%, and 0% FO-PN groups. In experiment 2, the mice were divided into 4 groups: CHOW, 33%, 8%, and 0% FO-PN. After the mice had been fed for 5 days, MNC were isolated. Hepatic MNC were counted and cytokine productions (tumor necrosis factor [TNF]-α and interleukin [IL]-10) by MNC in response to lipopolysaccharide (LPS) were measured. Blood samples were analyzed for lipid metabolism and hepatobiliary biochemical parameters. Liver histologies were also examined. Results In experiment 1, survival times were significantly shorter in the 4% and 0% FO-PN groups than in the CHOW group. Survival rates at 168 hours were 100%, 64%, 86%, 73%, 67%, 11%, and 13% in the CHOW, 67%, 33%, 16%, 8%, 4%, and 0% FO-PN groups, respectively. At 72 hours after intraportal bacterial challenge, the 0% FO-PN group showed severe tissue damage, whereas such damage was reduced in the 8% and 33% FO-PN groups. In experiment 2, the CHOW, 33%, 8%, and 0% FO-PN groups showed LPS dose-dependent increases in TNF-α levels. IL-10 levels were also LPS dose-dependently increased in the CHOW and 33% FO-PN groups. However, no marked changes were observed in response to LPS stimulation in either the 8% or the 0% FO-PN group. There were no differences in serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, or total bilirubin among these 4 groups. In the 0% FO-PN group, serum total cholesterol levels were greater than those in the 8% and 33% FO-PN groups. Without bacterial challenge, livers from the 0% FO-PN group showed steatosis, but these changes were attenuated in the 8% and 33% FO-PN groups. Conclusion The 30–40% ratio of FO to soybean oil with 20% of total calories supplied by lipid seems to be the best PN for preservation of hepatic MNC number and function.

Aim The aim of the current study was to develop a predictive model of insulin resistance using general health checkup data in Japanese employees with one or more metabolic risk factors. Methods We used a database of 846 Japanese employees with one or more metabolic risk factors who underwent general health checkup and a 75-g oral glucose tolerance test (OGTT). Logistic regression models were developed to predict existing insulin resistance evaluated using the Matsuda index. The predictive performance of these models was assessed using the C statistic. Results The C statistics of body mass index (BMI), waist circumference and their combined use were 0.743, 0.732 and 0.749, with no significant differences. The multivariate backward selection model, in which BMI, the levels of plasma glucose, high-density lipoprotein (HDL) cholesterol, log-transformed triglycerides and log-transformed alanine aminotransferase and hypertension under treatment remained, had a C statistic of 0.816, with a significant difference compared to the combined use of BMI and waist circumference (p＜0.01). The C statistic was not significantly reduced when the levels of log-transformed triglycerides and log-transformed alanine aminotransferase and hypertension under treatment were simultaneously excluded from the multivariate model (p=0.14). On the other hand, further exclusion of any of the remaining three variables significantly reduced the C statistic (all p＜0.01). Conclusions When predicting the presence of insulin resistance using general health checkup data in Japanese employees with metabolic risk factors, it is important to take into consideration the BMI and fasting plasma glucose and HDL cholesterol levels.

Aims/Introduction The aim of the present study was to determine whether weight reduction is associated with improvement of glycemic control in non‐obese and obese subjects with or without visceral fat accumulation, whose hemoglobin A1c (A1C) is 5.6–6.4%. Materials and Methods A total of 798 male subjects whose A1C levels were between 5.6% and 6.4% were divided into subgroups based on body mass index (BMI) and/or estimated visceral fat area (eVFA), and were analyzed with respect to the relationships between 1‐year changes in BMI (ΔBMI) and A1C (ΔA1C). Results In both the BMI ≥25 and BMI 100 cm2 (n = 293, r = 0.256, P

Background Blast lung injuries (BLI) caused by blast waves are extremely critical in the prehospital setting, and hypotension is thought to be the main cause of death in such cases. The present study aimed to elucidate the pathophysiology of severe BLI using laser-induced shock wave (LISW) and identify the initial treatment. Methods The current investigation comprised two parts. For the validation study, mice were randomly allocated to groups that received a single shot of 1.2, 1.3, or 1.4 J/cm2 LISW to both lungs. The survival rates, systolic blood pressure (sBP), heart rate (HR), peripheral oxyhemoglobin saturation (SpO2), and shock index were monitored for 60 min, and lung tissues were analyzed histopathologically. The study evaluated the effects of catecholamines as follows. Randomly assigned mice received 1.4 J/cm2 LISW followed by the immediate intraperitoneal administration of dobutamine, noradrenalin, or normal saline. The primary outcome was the survival rate. Additionally, sBP, HR, SpO2, and the shock index were measured before and 5 and 10 min after LISW, and the cardiac output, left ventricular ejection fraction, and systemic vascular resistance (SVR) were determined before and 1 min after LISW. Results The triad of BLI (hypotension, bradycardia, and hypoxemia) was evident immediately after LISW. The survival rates worsened with increasing doses of LISW (100 % in 1.2 J/cm2 vs. 60 % in 1.3 J/cm2, 10 % in 1.4 J/cm2). The histopathological findings were compatible with those of human BLI. The survival rate in LISW high group (1.4 J/cm2) was highest in the group that received noradrenalin (100 %), with significantly elevated SVR values (from 565 to 1451 dyn s/min5). In contrast, the survival rates in the dobutamine and normal saline groups were 40 and 10 %, respectively, and the SVR values did not change significantly after LISW in either group. Conclusions The main cause of death during the initial phase of severe BLI is hypotension due to the absence of peripheral vasoconstriction. Therefore, the immediate administration of noradrenalin may be an effective treatment during the initial phase of severe BLI.

Parenteral nutrition (PN) causes intestinal mucosal atrophy, gut-associated lymphoid tissue (GALT) atrophy and dysfunction, leading to impaired mucosal immunity and increased susceptibility to infectious complications. Therefore, new PN formulations are needed to maintain mucosal immunity. Short-chain fatty acids have been demonstrated to exert beneficial effects on the intestinal mucosa. We examined the effects of adding butyric acid to PN on GALT lymphocyte numbers, phenotypes, mucosal immunoglobulin A (IgA) levels, and intestinal morphology in mice.Male Institute of Cancer Research mice (n = 103) were randomized to receive either standard PN (S-PN), butyric acid-supplemented PN (Bu-PN), or ad libitum chow (control) groups. The mice were fed these respective diets for 5 days. In experiment 1, cells were isolated from Peyer's patches (PPs) to determine lymphocyte numbers and phenotypes (αβTCR(+), γδTCR(+), CD4(+), CD8(+), B220(+) cells). IgA levels in small intestinal washings were also measured. In experiment 2, IgA levels in respiratory tract (bronchoalveolar and nasal) washings were measured. In experiment 3, small intestinal morphology was evaluated.Lymphocyte yields from PPs and small intestinal, bronchoalveolar, and nasal washing IgA levels were all significantly lower in the S-PN group than in the control group. Bu-PN moderately, but significantly, restored PP lymphocyte numbers, as well as intestinal and bronchoalveolar IgA levels, as compared with S-PN. Villous height and crypt depth in the small intestine were significantly decreased in the S-PN group vs the control group, however Bu-PN restored intestinal morphology.A new PN formula containing butyric acid is feasible and would ameliorate PN-induced impairment of mucosal immunity.

Aims/Introduction: The aim of the present study was to determine the predictors of deterioration of glucose tolerance in individuals with normal glucose tolerance (NGT) and abdominal obesity, and whether a lifestyle intervention to reduce visceral fat is effective in these individuals. Materials and Methods: The study subjects were 251 individuals who had abdominal obesity with certain risk factors (hypertension, high fasting plasma glucose (FPG), elevated hemoglobin A1c (HbA1c), dyslipidemia and hyperuricemia) and underwent oral glucose tolerance test (OGTT) in 2004 and 2005. Results: Using the area under the receiver operating characteristic curve, we found that PG at 0 min, 60 min, and area under the curve (AUC) of glucose from 0 to 120 min (AUC [glucose0–120]) in OGTT were significant predictors of deterioration of glucose tolerance, with optimal cut-off values of 95 mg/dL, 158 mg/dL and 271 mg h/dL, respectively. Although the rate of deterioration of glucose tolerance didn’t decrease with reductions in visceral fat area (VFA) over the 1-year period in subjects with NGT, the rate tended to decrease with reductions in VFA in high-risk NGT subjects (PG at 0 min > 95 or at 60 min > 158, or AUC [glucose0–120] > 271). Conclusions: These results suggest that reduction of visceral fat over 1 year might not be beneficial in all subjects with NGT, but is beneficial in high-risk NGT. We propose that individuals with values of the aforementioned predictors higher than the cut-off levels, even those with NGT, should receive a lifestyle intervention program aimed at reducing visceral fat to prevent deterioration of glucose tolerance. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00080.x, 2011)

Parenteral nutrition (PN) reduces the number of hepatic mononuclear cell (MNCs) and impairs their function, resulting in poor survival after intraportal bacterial challenge in mice. Our recent animal study demonstrated resumption of enteral nutrition after PN to rapidly restore hepatic MNC numbers (in 12 hours) and lipopolysaccharide (LPS) receptor expression on Kupffer cells (in 48 hours). The present study examined the time courses of hepatic MNC number reductions and LPS receptor expression changes in mice receiving PN.Male mice (n = 49) from the Institute of Cancer Research were divided into chow (n = 8), PN0.5 (n = 8), PN1 (n = 8), PN2 (n = 9), PN3 (n = 9), and PN5 (n = 7) groups. The chow group was given chow with an intravenous saline infusion. The PN groups were fed parenterally for 0.5, 1, 2, 3, or 5 days following the chow-feeding courses. After 7 days of nutrition support, hepatic MNCs were isolated and counted. The expression of LPS receptors on Kupffer cells was analyzed by flow cytometry.Hepatic MNC numbers rapidly reached their lowest level in the PN0.5 and PN1 groups but were somewhat restored thereafter and remained stable after the third day, without significant differences between any 2 of the PN groups. CD14 and Toll-like receptor 4/MD-2 expressions both showed significant reductions in the PN1 group compared with the chow group and gradually decreased to their lowest levels in the PN5 group.PN administration rapidly reduces hepatic MNC numbers and LPS receptor expression on Kupffer cells.

Lectin microarray is an emerging technique, which will accelerate glycan profiling and discovery of glycan-related biomarkers. One of the most important stages in realizing the potential of the technique is to achieve sufficiently high sensitivity to detect even the low concentrations of some target glycoproteins which occur in sera or tissues. Previously, we developed a lectin microarray based on an evanescent-field fluorescence-assisted detection principle that allows rapid profiling of glycoproteins. Here, we report optimization of procedures for lectin spotting and immobilization to improve the sensitivity and reproducibility of the lectin microarray. The improved microarray allows high-sensitivity detection of even monovalent oligosaccharides that generally have a low affinity with lectins (K(d)>10(-6) M). The LOD observed for RCA120, a representative plant lectin, with asialofetuin, and an asialo-biantennary N-glycan probe were determined to be 100 pg/mL and 100 pM, respectively. With the improved lectin microarray system, closely related structural isomers, i.e., Le(a) and Le(x), were clearly differentiated by the difference in signal patterns on relevant multiple lectins, even though specific lectins to detect these glycan structures were not available. The result proved a previously proposed concept of lectin-based glycan profiling.

The use of the bisfluorous chain-type propanoyl (Bfp) group as a fluorous protective group made it possible to rapidly synthesize the Gb2 and Gb3 oligosaccharide derivatives by a simple fluorous-organic extraction purification. Furthermore, the fluorescence-labeled Gb2 and Gb3 oligosaccharides were prepared as a potential Vero Toxins detecting reagent.

We investigated the cut‐off point of the Matsuda Index in Japanese according to the guideline from the Clinical and Laboratory Standards Institute. A total of 1,596 subjects free from medications for diabetes mellitus, dyslipidemia and/or hypertension, and without cardiovascular diseases or chronic renal failure underwent a health check‐up and oral glucose tolerance test (OGTT). We recruited 204 healthy reference individuals with normal glucose tolerance without obesity, any component of metabolic syndrome or elevated alanine aminotransferase. The Matsuda Index was calculated with 0‐ and 120‐min data during OGTT. As the index was not normally distributed (P

Glycosyl amino acids having natural glycan were useful for the interaction assay of oligosaccharides. A glycochip containing the whole structure of an oligosaccharide was easily prepared by the immobilization of the glycosyl amino acid. Furthermore, fluorescence probes were introduced into the glycosyl amino acid while maintaining the whole structure of oligosaccharide. By using these labeled oligosaccharides, fluorescence polarization (FP) and fluorescence correlation spectroscopy (FCS) analyzed the carbohydrate-lectin interaction in a solution assay system.

AIMS/INTRODUCTION: Weight reduction improves glycemic control in obese men with glycated hemoglobin (HbA1c) of 5.6-6.4%, suggesting that it can prevent the development of diabetes in these patients. The aim of the present study was to quantify the amount of weight reduction necessary for minimization of diabetes risk in Japanese men with visceral fat accumulation. MATERIALS AND METHODS: The study participants were 482 men with an estimated visceral fat area of ≥100 cm(2), HbA1c of 5.6-6.4%, fasting plasma glucose (FPG) of

Aim The clustering of metabolic abnormalities occurs not only due to abdominal obesity but also other etiologies. We investigated the contribution of visceral fat accumulation and the circulating adiponectin level to the clustering of metabolic abnormalities in a Japanese population. Methods We used the data for 1,989 Japanese employees to perform a structural equation modeling analysis. According to the concept of metabolic syndrome, we developed a multiple indicator multiple cause (MIMIC) model and investigated to what extent measurements of the visceral fat area (VFA) and circulating adiponectin levels explain the morbidity of clustering of metabolic abnormalities, represented as a latent variable termed "risk clustering." The following clinically measurable parameters were set as the phenotypes of the risk clustering: systolic blood pressure and glucose, high-density lipoprotein cholesterol, triglyceride, uric acid and alanine aminotransferase levels. Results The mean age of the subjects was 46±11 years, and 72% of the participants were men. A VFA of ≥100 cm(2) was observed in 32% of the subjects. The squared multiple correlation R(2) of the risk clustering was as high as 0.73, indicating that the measurements of the VFA and adiponectin levels explained 73% of the variance in the risk clustering. The R(2) between the risk clustering and metabolic parameters ranged from 0.14 to 0.54, thus indicating that these metabolic parameters reflected the development of morbidity of the risk clustering in the body within a range of 14% to 54%. Conclusions The measurements of the VFA and adiponectin level makes a considerable contribution to the risk clustering.

The screening of dysglycemia in the non-fasting state is a challenging issue in healthcare practice. We investigated whether the additional measurement of circulating adiponectin levels could improve screening performance. We used a database of 1190 Japanese employees with metabolic risk factors, who underwent a 75-g oral glucose tolerance test (OGTT), following non-fasting health check-ups. Dysglycemia was defined as fasting glucose levels >= 6.1 mmol/L or 2-hr glucose levels >= 7.8 mmol/L during the OGTT. Logistic regression analysis revealed that decreased adiponectin levels were associated with dysglycemia, independently of postprandial glucose (PG) and hemoglobin A1c (HbA1c) levels, as well as other health check-up data (p

Aim Some employees have difficulty undergoing health checkups in the workplace in a fasting state. However, hypertriglyceridemia is usually diagnosed based on fasting triglyceride (TG) measurements. The current study investigated the performance of non-fasting health checkup data for predicting hypertriglyceridemia in a Japanese population. Methods We recruited a total of 1,959 Japanese employees who had their fasting TG levels reexamined after undergoing initial health checkups under either a fasting (the fasting population; n= 856) or non-fasting state (the non-fasting population; n= 1103). Hypertriglyceridemia was defined as a fasting TG level of ≥ 1.7 mmol/l. Results The area under the receiver operating characteristic (ROC) curve of the initial TG measurements for reexamination-detected hypertriglyceridemia was 0.85 in the fasting population and 0.83 in the non-fasting population. The area under the ROC curve of the initial TG measurements in the non-fasting population was not inferior to that of the multivariate model where other non-fasting health checkup data were added. The optimal non-fasting TG cutoff point was 2.0 mmol/l. The cutoff point was further lowered when the population was limited to patients undergoing health checkups four or more hours after their last meal and when the prevalence of hypertriglyceridemia in the population was simulated to be reduced. Conclusions The non-fasting workplace TG measurements by themselves exhibited a tolerable performance for predicting hypertriglyceridemia. The optimal cutoff point in Japanese employees appears to be lower than 2.3 mmol/l, the recently proposed Western cutoff point.

The aim of the current study was to investigate whether obese subjects have different insulin secretory capacity compared to lean subjects with the same glucose tolerance in a Japanese population. We included a total of 1749 Japanese employees who underwent 75-g oral glucose tolerance test (OGTT). The study population was divided into deciles of 120-min glucose levels and the indices of insulin secretion and insulin sensitivity in each decile were compared between the subjects with and without obesity (body mass index ≥ 25 kg/m2). The indices used in the current study were Matsuda index, insulinogenic index, and disposition index. Obese subjects had significantly lower values of Matsuda index and significantly higher value of insulinogenic index than non-obese subjects in every decile (all p0.05). On the other hand, disposition index was not significantly different between non-obese and obese subjects in any decile of 120-min glucose level (all p0.05). Similar findings were observed when the study population was classified by waist circumference. In conclusion, disposition index derived from the data of 75-g OGTT was similarly decreased in obese Japanese subjects compared to non-obese Japanese subjects with the same post-load glucose levels. Future studies will be needed to confirm whether the development of glucose intolerance in obese Japanese subjects is accompanied by the same degree of pancreatic beta cell dysfunction as non-obese Japanese subjects.

We found that the recombinant endo -β- N -acetylglucosaminidase of Mucor hiemalis (Endo-M) expressed in Candida boidinii had the transglycosylation activity of transferring a bisecting hybrid-type oligosaccharide from an ovalbumin glycopeptide to the acceptor ( p -nitrophenyl 2-acetamido-2-deoxy-β- d -glucopyranoside) in a good yield of 43%.

AIM The use of ethnic-specific cutoff values of waist circumference (WC) has been recently recommended, but they were originally developed on different statistical grounds. We investigated whether different statistical procedures and clinical settings generate different WC cutoff values in one ethnic population. METHODS We recruited 3810 Japanese subjects and performed the following three statistical analyses: 1) search for WC cutoff points associated with the risk of clustering metabolic abnormalities, 2) calculation of WC associated with certain body mass index (BMI) levels, 3) evaluation with receiver operating characteristic (ROC) curves for the risk. We also simulated population models to evaluate whether WC cutoff values depend on the clinical settings of the study population. RESULTS First, in risk analysis, males and females had the same risk when females had 10 cm larger WC than males, although the risk increased almost linearly, without any clear threshold. Second, WC corresponding to BMI of 25 kg/m(2) was 87 cm in males and 85 cm in females, with a slight sex difference. Third, ROC curves showed that the male optimal cutoff value was 85 cm, larger than the female one (79 cm). However, simulated population models with various WC distributions gave different ROC curves and different WC cutoff values. Furthermore, WC cutoff values varied by age in any of the three statistical procedures. CONCLUSIONS Different statistical grounds could generate different WC cutoff values. If one plans to establish a unified trans-ethnic diagnostic tool of metabolic syndrome, ethnic-specific WC cutoff values should be primarily provided based on a unified statistical ground.

Objective The aim of this study was to evaluate the effects of health checkup and the health education "Hokenshido" program based on the concept that visceral fat accumulation causes metabolic syndrome (MetS), leading to cardiovascular disease (CVD). Methods and Subjects Based on the Japanese definition of metabolic syndrome, in the annual health checkup for general subjects, the measurement of waist circumference and use of "Where am I?" chart on the way to develop atherosclerosis were introduced. The study group comprised 3,174 Japanese employees [2,440 males (46±11 years, mean ± SD), 734 females (43±10 years)], who underwent annual health checkup in 2003, 2004, and 2005. The medical staff provided "Hokenshido" for subjects assessed as having MetS and/or at high risk for CVD. Results The prevalence of the MetS in 2003, 2004 and 2005 decreased in males (20.8%, 17.2%, 14.4%, p

Aim: The accumulation of Visceral fat is known to precede metabolic disorders and atherosclerosis. This study aimed to determine the relationships between body mass index (BMI), waist circumference (WC), estimated visceral fat area (eVFA) measured by bioelectrical impedance analysis (BIA), and obesity-related cardiovascular risk factors. Methods: The study population was 2,870 middle-aged Japanese employees (males/females=2,322/ 548), who had undergone a health check-up. Results: In the receiver operating characteristic (ROC) curve, the cutoff levels yielding maximal sensitivity plus specificity for predicting the prevalence of ≥ 2 risks were, 24.5 kg/m 2 for BMI, 84.6 cm for WC, and 111 cm 2 for eVFA in males, and 23.6 kg/m 2 , 81.5 cm, and 67 cm 2 in females. The average number of risk factors was over 1.0 in those with a BMI ≥ 25 kg/m 2 and with a WC ≥ 85 cm for males, ≥ 28 kg/m 2 and ≥ 95 cm respectively for females, and those with an eVFA ≥ 100 cm 2 for both males and females. In males, it was around 1.0 with cutoff levels of BMI, WC, and eVFA from the ROC curve. However, in females, it was around 0.6, because the prevalence of subjects with obesity and multiple risks was very low. Conclusions: These results suggested that the cutoff level for visceral fat reduction should be set based on an absolute value of risk factors, rather than a calculated value. In regular health check-up, it may be useful to set an absolute cutoff value for eVFA at 100 cm 2 as criteria to screen for multiple obesity-related cardiovascular risk factors. J Atheroscler Thromb, 2010; 17:1237-1245.

Summary Background & aims Total parenteral nutrition (TPN) impairs host immunocompetence, a mechanism possibly underlying the high morbidity of infectious complications in critically ill patients. Our recent study demonstrated TPN to reduce the number and function of hepatic mononuclear cells (MNCs) and to worsen survival after intraportal Pseudomonas challenge in mice. The present study examined the duration of enteral nutrition (EN) needed to reverse TPN-induced changes in hepatic MNCs in a murine model. Methods Male ICR mice (6 weeks) received 5 days of TPN followed by 0 (TPN), 12 (EN12), 24 (EN24), 48 (EN48) or 72 (EN72)h of chow feeding. Control mice (Control) were given chow with intravenous saline infusions for 5 days. After nutritional support, hepatic MNCs were isolated and counted. Lipopolysaccharide (LPS) receptor expressions (CD14 and TLR4/MD2) on Kupffer cells were analyzed by flowcytometry. In addition, TPN, EN12, EN48 and control mice were given intraportal Pseudomonas challenge and survival was monitored. Results The TPN group was significantly lower in hepatic MNC number and LPS receptor expressions than the Control group. However, EN quickly reversed TPN-induced hepatic impairments in MNC loss within 12h, CD14 expression within 48h and TLR4/MD2 expression within 24h. Survival of the EN48 group was significantly improved as compared with the TPN and EN12 groups. Conclusions EN rapidly reverses TPN-induced impairment of hepatic immunity along with increased hepatic MNC numbers and LPS receptor expressions on Kupffer cells.

Visceral fat accumulation is associated with the development of metabolic disorders such as glucose intolerance, dyslipidemia, hypertension, and atherosclerotic cardiovascular diseases (1–8). However, the relationship between reduction of visceral fat and decrease in the number of metabolic risk factors has not been defined in the general population. Recently, we developed a new technique, the abdominal bioelectrical impedance analysis (BIA), to evaluate visceral fat area (VFA) (9). The aim of this study was to investigate whether reduction of visceral fat, estimated by the BIA, is associated with a decrease in the number of metabolic risk factors. The study group comprised 2,336 Japanese men (aged mean ± SD 48.0 ± 10.5 years, BMI 24.2 ± 2.9 kg/m2), who were employees of Amagasaki City Office, an urban area, and had undergone annual health check-ups in both 2004 and 2005. After the health check-up, the medical staff provided risk factor–oriented, rather than obesity-oriented, health promotion programs to select individuals with visceral fat accumulation and multiple risk factors, with the aim of encouraging a scientific understanding of the spectrum of metabolic syndrome from visceral fat accumulation to atherosclerotic cardiovascular diseases. In this study, we used VFA estimated by the BIA, which was shown to correlate significantly with VFA determined by computed tomography (9). The measurement of VFA by BIA complied with the Guidelines of the Ethical Committees of …

Microalbuminuria has been recognized recently as a risk factor for cardiovascular diseases as well as renal failure and is often found in subjects with metabolic syndrome. The relationship between visceral fat accumulation and microalbuminuria, urinary albumin-to-creatinine ratio (UACR), has not been fully clarified. Our cross-sectional study demonstrated that visceral fat accumulation is associated with increases in UACR. However, the accompanying obesity-related risk factors, especially hemoglobin A1c (HbA1c) and elevated blood pressure, strongly increased the risk of UACR (1). We have reported that reductions in both body weight and estimated visceral fat area (eVFA) measured by the bioelectrical impedance analysis method (2) were accompanied by reductions in the number of obesity-related cardiovascular risk factors (3) and increases in serum levels of adiponectin (4) in our longitudinal Amagasaki Visceral Fat Study, in which intensive risk factor–oriented health promotion programs were …

Adiponectin was identified as an adipocytokine in the human adipose tissue cDNA library. It has antiatherosclerotic and antidiabetic properties in experimental studies, and its blood levels are low in obesity, diabetes, cardiovascular diseases, and metabolic syndrome. Several studies have reported that weight reduction in massively obese subjects is associated with a rise in serum adiponectin (APN) concentration (1–3). However, the relationship between changes in APN and BMI, waist circumference (WC), and visceral fat accumulation (VFA) in general population has not been reported. The present study investigated 1-year change in APN (ΔAPN) in relation to changes in BMI (ΔBMI), WC …

Objective Visceral fat accumulation is an underlying component of the metabolic syndrome (MetS). Hypoadiponectinemia is one of the key molecules of the MetS. In the present study, we investigated the relationship between the serum uric acid level, visceral fat accumulation and serum adiponectin concentration in Japanese men. Patients and Methods The study group comprised 1,520 Japanese employed men (mean age: 45.6±10.4 years, ± SD), who had undergone an annual health check-up both in 2004 and 2005. In addition to parameters measured in the annual health check-up, visceral fat area (VFA) and serum adiponectin concentration were measured by the bioelectrical impedance analysis method and a sandwich enzyme-linked immunosorbent assay (ELISA) system, respectively. Results Visceral fat accumulation was identified in 56.1% of the subjects with hyperuricemia. There was significant positive correlation between visceral fat area and serum uric acid levels (r=0.223, p

Background Circulating thiobarbituric acid-reacting substance (TBARS) levels, a marker of systemic oxidative stress, are predictive of cardiovascular events. However, they has not been evaluated in Japanese, especially with regard to the factors that contribute to the changes in circulating TBARS levels. We investigated the cross-sectional and longitudinal relationships between circulating TBARS levels and various clinicobiochemical parameters in middle-aged men. Methods In this population-based study (The Amagasaki Visceral Fat Study), 1,178 Japanese male urban workers who had undergone health check-ups in 2006, 2007 and 2008 and were not on medications for metabolic disorders during the follow-up period, were enrolled. Serum TBARS levels were measured by the method of Yagi. The estimated visceral fat area (eVFA) by bioelectrical impedance was measured annually. After health check-ups, subjects received health education with lifestyle modification by medical personnel. Results The number of cardiovascular risk factors (hypertension, hyperglycemia, low HDL-C, hypertriglyceridemia, hyperuricemia, hyper-LDL-C and impaired renal function) augmented with the increases in log-eVFA (p < 0.0001) and log-TBARS (p < 0.0001). The combination of TBARS and eVFA had a multiplicative effect on risk factor accumulation (F value = 79.1, p = 0.0065). Stepwise multiple regression analysis identified log-eVFA, as well as age, log-body mass index (BMI), LDL-C, log-adiponectin, γ-glutamyl transpeptidase (γ-GTP) and uric acid as significant determinants of log-TBARS. Stepwise multiple regression analysis identified one-year changes in eVFA as well as BMI, γ-GTP and estimated glomerular filtration rate (eGFR) as significant determinants of one-year change in TBARS, and biennial changes in eVFA as well as BMI and γ-GTP, eGFR as significant determinants of biennial change in TBARS. Conclusions The present study showed a significant cross-sectional and longitudinal correlation between TBARS and eVFA, as well as BMI and γ- GTP, eGFR. Visceral fat reduction may independently associate with the improvement in systemic ROS in middle-aged Japanese men. Trial Registration The Amagasaki Visceral Fat Study UMIN000002391.

The physical damage inflicted by blast waves is called primary blast injury, and lungs are vulnerable to blast waves [1]. Blast lung injuries (BLI) can be extremely critical during the super-acute phase, and hypotension is supposed to be the main cause of death (1) , but its etiology has not been elucidated. Recent studies have demonstrated that hypotension is mediated by the absence of vasoconstriction [2]. However, research investigated the effectiveness of catecholamine for BLI during the super-acute phase was not identified.