Characterization of a hypoallergenic wheat line lacking ω-5 gliadin.

BACKGROUND: There is no curative treatment for wheat-dependent exercise-induced anaphylaxis (WDEIA). ω-5 Gliadin is one of the dominant allergens affecting WDEIA patients. The use of ω-5 gliadin-free wheat flour in the regular diet is considered one of the prophylactic approaches against the elicitation of allergic symptoms and sensitization to ω-5 gliadin. We sought to find hypoallergenic bread wheat (or common wheat) that lacked the genes encoding ω-5 gliadin and to evaluate its in vitro allergenicity. We also aimed to evaluate the sensitization ability of one of the selected hypoallergenic wheat lines by using a possible animal model of wheat allergy. METHODS: We screened the deletion lines of bread wheat by western blotting to ascertain common wheat lines lacking the ω-5 gliadin locus. The deletion lines we used have partial deficiency of chromosome 1B (Endo and Gill, 1996). To assess sensitization ability of gluten from the selected deletion line, guinea pigs were fed with either the gluten from the selected deletion line or commercially available gluten, and allergic score was evaluated after challenging the same gluten preparations. RESULTS: We found that a deletion line 1BS-18 had the least deficiency of chromosome 1B among the deletion stocks lacking the ω-5 gliadin locus. The challenge test using the guinea pigs revealed that the symptoms induced by application of the 1BS-18 gluten were much less than that of commercially available gluten. CONCLUSIONS: The deletion line 1BS-18, which lacked the ω-5 gliadin locus, is likely to have a low sensitization capacity in the guinea pig. The use of the wheat products of the 1BS-18 line in daily life may provide a feasible solution for the onset of wheat allergy.

Depression, stroke and gender: evidence of a stronger association in men.

BACKGROUND/AIMS: Depression is associated with an increased risk for stroke. The aim of this study was to examine whether demographic and socioeconomic factors modify this association. METHODS: This follow-up study comprised 137 305 men and 188 924 women aged ≥30 years from a nationwide sample of primary healthcare centres in Sweden. We identified 4718 first-ever stroke cases (2217 men and 2501 women) during the follow-up period (2005-2007). Multilevel logistic regression models were used to calculate ORs and examine interactions in order to determine whether the association between depression and stroke differs by demographic or socioeconomic factors. RESULTS: Depression was associated with significantly greater odds of stroke after adjustment for potential confounding factors (OR=1.22, 95% CI 1.08 to 1.38). Interaction tests showed that the effect of depression on stroke was higher in men compared with women (the difference in OR between men and women was 1.30, 95% CI 1.01 to 1.68), that is, the association between depression and stroke was modified by gender. CONCLUSIONS: Our findings suggest that the depression-stroke association is modified by gender. Further studies are required to examine the underlying mechanisms in men and women.

Relationship between physical activity and chronic musculoskeletal pain among community-dwelling Japanese adults.

BACKGROUND: Both little and excessive physical activity (PA) may relate to chronic musculoskeletal pain. The primary objective of this study was to characterize the relationship of PA levels with chronic low back pain (CLBP) and chronic knee pain (CKP). METHODS: We evaluated 4559 adults aged 40-79 years in a community-based cross-sectional survey conducted in 2009 in Shimane, Japan. We used self-administered questionnaires to assess sociodemographics and health status: PA was assessed by the International Physical Activity Questionnaire, and CLBP and CKP were assessed by a modified version of the Knee Pain Screening Tool. We examined relationships of PA with prevalence of CLBP and CKP using Poisson regression, controlling for potential confounders. RESULTS: CLBP and CKP were both prevalent (14.1% and 10.7%, respectively) and associated with history of injury, medication use, and consultation with physicians. PA was not significantly related to CLBP or CKP (P > 0.05) before or after adjustment for potential confounders. For example, compared with adults reporting moderate PA (8.25-23.0 MET-hours/week), prevalence ratios for CKP adjusted for sex, age, education years, self-rated health, depressive symptom, smoking, chronic disease history, and body-mass index were 1.12 (95% confidential interval [CI] 0.84-1.50) among those with the lowest PA and 1.26 (95% CI 0.93-1.70) among those with the highest PA (P quadratic = 0.08). The prevalence ratios were further attenuated toward the null after additional adjustment for history of injury, medication use, and consultation (P quadratic = 0.17). CONCLUSIONS: This cross-sectional study showed that there were no significant linear or quadratic relationships of self-reported PA with CLBP and CKP. Future longitudinal study with objective measurements is needed.

MC4R rs17782313 gene polymorphism was associated with glycated hemoglobin independently of its effect on BMI in Japanese: the Shimane COHRE study.

BACKGROUND: Type 2 diabetes (T2D) is among the leading public health problems in Japan, and glycated hemoglobin (HbA1c) can be used to screen the population for T2D. Gene polymorphisms, known to be associated with obesity, may predispose individuals to T2D. Rs17782313 the melanocortin 4 receptor (MC4R) has shown one of the strongest associations with body mass index (BMI). We conducted a study to investigate whether rs17782313 (TT versus TC + CC) was associated with HbA1c. METHOD: We conducted a cross-sectional study including 1142 Japanese adults (446 men: 64.9 ± 14.4 years and 696 women: 66.7 ± 12.3 years). MC4R rs17782313 was genotyped using fast real-time polymerase chain reaction. RESULTS: TC + CC genotype group showed significantly greater BMI (p = 0.039) and HbA1c (p = 0.001) than TT genotype group after adjustment for gender, age and, for HbA1c, BMI. Further analysis using linear regression analysis confirmed that the effect of MC4R rs17782313 on HbA1c (ß = 0.08; p = 0.003) was independent of the effect age, gender, BMI, low density lipoprotein cholesterol, homeostasis model assessment of insulin resistance and of beta cell function. This significant independent association was similarly noticed in non-obese (ß = 2.82; p = 0.005) subgroups. CONCLUSION: MC4R rs17782313 was associated with obesity and could confer a certain susceptibility to T2D that could be independent of its pro-obesity effect.

A community-wide campaign to promote physical activity in middle-aged and elderly people: a cluster randomized controlled trial.

BACKGROUND: We aimed to evaluate the effectiveness of a community-wide campaign (CWC) for promoting physical activity in middle-aged and elderly people. METHODS: A cluster randomized controlled trial (RCT) with a community as the unit of randomization was performed using a population-based random-sampled evaluation by self-administered questionnaires in the city of Unnan, Shimane Prefecture, Japan. The evaluation sample included 6000 residents aged 40 to 79 years. We randomly allocated nine communities to the intervention group and three to the control group. The intervention was a CWC from 2009 to 2010 to promote physical activity, and it comprised information, education, and support delivery. The primary outcome was a change in engaging in regular aerobic, flexibility, and/or muscle-strengthening activities evaluated at the individual level. RESULTS: In total, 4414 residents aged 40-79 years responded to a self-administered questionnaire (73.6% response rate). Awareness of the CWC was 79% in the intervention group. Awareness and knowledge were significantly different between the intervention and control groups, although there were no significant differences in belief and intention. The 1-year CWC did not significantly promote the recommended level of physical activity (adjusted odds ratio: 0.97; 95% confidence interval: 0.84-1.14). CONCLUSIONS: This cluster RCT showed that the CWC did not promote physical activity in 1 year. Significant differences were observed in awareness and knowledge between intervention and control groups as short-term impacts of the campaign. TRIAL REGISTRATION: UMIN-CTR UMIN000002683.

Prevalence of wheat allergy in Japanese adults.

BACKGROUND: Wheat is one of the most common causes of food allergies. The exact prevalence of wheat allergy has not been well delineated in Japanese adults. METHODS: We enrolled 935 adults in a cohort study established by Shimane University in order to examine the determinants of lifestyle-related diseases. A screening was conducted by a questionnaire-based examination and a detection of serum omega-5 gliadin-specific IgE. Subjects who tested positive in the questionnaire-based examination and/or the serum omega-5 gliadin-specific IgE test were further examined by detailed interviews and skin prick tests. RESULTS: A total of 22 subjects were picked up by the screening process, and 17 of these were further examined by secondary testing. Only two subjects were conclusively identified as having wheat allergy. CONCLUSIONS: The prevalence of wheat allergy in Japanese adults was found to be 0.21% by using a combination of questionnaire-based examination, skin prick test and serum omega-5 gliadin-specific IgE test.

Antiobesity effect of polyphenolic compounds from molokheiya (Corchorus olitorius L.) leaves in LDL receptor-deficient mice.

BACKGROUND: Dietary supplementation with polyphenolic compounds is associated with reduced diet-induced obesity and metabolic disorders in humans. The antioxidative properties of polyphenolic compounds contribute to their antiobesity effect in animal experiments and human studies. AIM: The aim of the study was to investigate the antiobesity effect of polyphenolic compounds from molokheiya leaves in LDLR-/- mice fed high-fat diet and to elucidate the mechanism of this effect. METHODS: Three groups of LDLR-/- mice were fed with a high-fat diet, supplemented with 0% (control), 1 or 3% molokheiya leaf powder (MLP). Gene expression in the liver associated with lipid and glucose metabolism was analyzed, and physical parameters and blood biochemistry were determined. RESULTS: Compared to controls, mice body weight gain (P = 0.003), liver weight (P = 0.001) and liver triglyceride levels (P = 0.005) were significantly lower in the two MLP groups. Epididymal adipose tissue weight (P = 0.003) was reduced in the 3% MLP group. Liver tissue gene expression of gp91phox (NOX2), involved in oxidative stress, was significantly down-regulated (P = 0.005), and PPARα and CPT1A, related to the activation of ß-oxidation, were significantly up-regulated (P = 0.025 and 0.006, respectively) in the 3% MLP group compared to the control group. CONCLUSIONS: Our results demonstrate an antiobesity effect of polyphenolic compounds from molokheiya leaves and that this effect is associated with reduction in oxidative stress and enhancement of ß-oxidation in the liver. Consumption of molokheiya leaves may be beneficial for preventing diet-induced obesity.

Association between a hilly neighborhood environment and falls among rural older adults: a cross-sectional study.

Objective: Falls in older adults are a major public health issue, and it is unclear whether the neighborhood environment is associated with falls among this group. This cross-sectional study investigated whether hilly neighborhood environmental factors were associated with fall status (falls or fear of falling) in rural Japanese older adults. Materials and Methods: Data obtained from 965 participants aged 65 years and older living in Unnan City, Shimane Prefecture, Japan, in 2017 were analyzed. Fall status was assessed based on the 1-year fall incidence (yes/no) for the past year and fear of falling (yes/no) using a self-report questionnaire. For hilly neighborhood environmental factors, the mean elevation and land slope were assessed using a geographic information system. The logistic regression model examined the odds ratios (OR) and 95% confidence intervals (CIs) of fall status in quartiles for elevation and land slope, respectively, and was adjusted for confounders. Results: Falls and fear of falling were observed in 16.8% and 43.2% of participants, respectively. Falls were associated with elevation (OR 1.99, 95% CI 1.17-3.37 for Q2 vs. Q1; OR 2.02, 95% CI 1.19-3.44 for Q3 vs. Q1) and land slope (OR 1.74, 95% CI 1.04-2.93 for Q3 vs. Q1; OR 1.74, 95% CI 1.04-2.93 for Q4 vs. Q1). Fear of falling was associated with elevation (OR 1.78, 95% CI 1.19-2.65 for Q3 vs. Q1) and land slope (OR 1.51, 95% CI 1.01-2.25 for Q4 vs. Q1). Conclusion: Our study found that elevation and land slope as hilly neighborhood environment factors were positively associated with falls or fear of falling among older adults living in rural Japan. Prospective observational studies that investigate the effects of region-specific environmental factors on falls among older adults should be conducted.

Effect of flavonol glycoside in mulberry (Morus alba L.) leaf on glucose metabolism and oxidative stress in liver in diet-induced obese mice.

BACKGROUND: Mulberry therapies on type 2 diabetic patients or streptozotocin-induced diabetic rats have been reported to improve fasting blood glucose levels. We investigated the effects of dietary consumption of mulberry-leaf powder and purified quercetin 3-(6-malonylglucoside), the quantitatively major flavonol glycoside in mulberry leaves, on glucose and lipid metabolism in high-fat diet-induced obese mice. Male C57BL/6J mice aged 8 weeks were assigned to three groups (control, mulberry leaf powder (MLP), and quercetin 3-(6-malonylglucoside) (Q3MG)) and treated with their respective diets for 8 weeks. RESULTS: We found that dietary supplementation of 10 g MLP kg(-1) or 1 g Q3MG kg(-1) in high-fat diet effectively suppressed blood glucose levels. We also noted increased expression of glycolysis-related genes and suppression of thiobarbituric acid reactive substances concentrations in the liver of Q3MG group compared to control mice. CONCLUSION: Dietary consumption of Q3MG, the quantitatively major flavonol glycoside in mulberry leaves, improved hyperglycemia in obese mice and reduced oxidative stress in the liver.

Prevalence of lifestyle-related chronic diseases among agricultural and non-agricultural workers in ruralareas of Japan: the Shimane CoHRE study.

Objective: Engaging in agriculture greatly affects workers' lifestyles, particularly related to physical activity. This study aimed to clarify the prevalence of lifestyle-related chronic diseases among workers engaging and not engaging in agriculture in rural areas of Japan. Methods: A total of 4,666 consecutive participants aged ≥40 years (1,929 men and 2,737 women) were recruited during health examinations conducted from 2006 to 2014. For analysis, the participants were divided by sex and age into those engaging in agriculture and those not engaging in agriculture. Results: Engaging in agriculture may be contributing with a low prevalence of dyslipidemia, a constitutive factor of metabolic syndrome, in both sexes between the ages of 40 and 64 years. In the elderly aged ≥65 years, engaging in agriculture may influence the low prevalence of hypertension in men. Hypertension, a strong risk factor for stroke and cardiovascular disease, is very frequent among the Japanese elderly and, therefore, engaging in agriculture may have a significant impact on its prevention and control. Conclusion: In rural areas of Japan, engaging in agriculture may contribute to the control of lipid metabolism in middle-aged individuals and blood pressure in the elderly.

Environmental correlates of physical activity in driving and non-driving rural Japanese women.

OBJECTIVE: This study examined the relationship between physical activity and the environment among rural Japanese women, and whether that relationship varied with driving status. METHODS: 434 women aged 40-64 years in Unnan City, rural Japan, were surveyed in 2006 about physical activity and their neighborhood environments. The proximity and frequency of public transport were measured using geographic information systems software. RESULTS: Perceived good access to public transport and recreational facilities, presence of bike lanes, and good aesthetics were among factors positively associated with being physically active. The interaction between the convenience of bus service and driving status was statistically significant (P=0.023). Non-drivers residing in areas where bus service was moderately convenient were more likely to be active than those who were without it. CONCLUSION: These findings suggested that driving status is a potential modifier of the relationship between physical activity and the convenience of bus service and that convenient bus service is important for promoting physical activity especially in non-drivers.

J-curve association between alcohol intake and varicose veins in Japan: The Shimane CoHRE Study.

The effect of alcohol intake on varicose veins (VV) has not been determined by its consumption level. The aim of this study was to investigate the association between alcohol intake and VV in an elderly general population. Using a cross-sectional approach, the Shimane CoHRE Study data, comprising a total of 1060 participants, were analyzed. By multivariate regression analysis adjusted with basic characteristics, past work history, lifestyle-related factors and medical history, compared with non-drinkers, mild drinkers (<20.0 g/day) showed a significantly lower adjusted odds ratio (aOR) of VV (aOR = 0.64, P = 0.036). In a similar way, regular drinkers (1-5 days/week) showed a significantly lower aOR of VV when compared with occasional drinkers (aOR = 0.57, P = 0.032). VV and alcohol intake showed J-curve relationships. In a stratified analysis by alcohol consumption levels, the association of smoking and VV were also observed in moderate to heavy drinkers and habitual drinkers. These findings can provide better understanding of pathophysiological mechanism and be used for evidence-based patient education.

Variation of interleukin 8 -251 A>T polymorphism in worldwide populations and intra-ethnic differences in Japanese populations.

BACKGROUND: Interleukin-8 (IL8) is a member of the family of chemokines. The IL8 gene has polymorphic variations, and the genotype of IL8 -251 A>T is associated with smoking behavior and cancer progression. METHOD: IL8 -251 A>T polymorphism were investigated in Japanese, from 5 different areas, in Ovambo, Turkish, Mongolian and Korean populations by PCR with confronting 2-pair primers (PCR-CTPP) analysis. RESULTS: A subpopulation analysis of Japan revealed a north-to-south increase in the frequency of the IL8 -251 T allele. Among the 5 groups, the Japanese showed the highest frequency of mutant allele followed by the Turks. The distribution pattern in the Japanese was different from those of Mongolians and Koreans. In the Ovambo population, no mutant allele homozygote subject was found and the frequency of mutant alleles was the lowest, similar to that in Gambians. CONCLUSION: The present study is the first to demonstrate the Japan population inter-prefecture differences in IL8 -251 A>T polymorphism as well as a certain genetic heterogeneity in the worldwide distribution of IL8 -251 A>T polymorphism. The distribution results may help define the true significance of IL8 -251 A>T polymorphism as a marker for smoking behavior in populations worldwide.

High frequency of cardiovascular risk factors in overweight adult Japanese subjects.

BACKGROUND: It has been suggested that Japanese subjects categorized as having normal weight (body mass index [BMI]<25.0) as defined by WHO (2000) have a tendency toward increased incidence of dyslipidemia and diabetes. Our objective was to assess the suitability for Japanese subjects of the Regional Office for the Western Pacific Region of WHO criteria pertaining to obesity (WPRO criteria, 2000) by analyzing cardiovascular risk factors relative to gender and age in overweight Japanese with BMI of 23.0-24.9. METHODS: There were 3,608 subjects (2,387 men: 42.3+/-0.2 years and 1,221 women: 41.6+/-0.3 years) who participated in a community setting and cross-sectional study and were not using any prescription drugs for obesity-related diseases. BMI and cardiovascular risk factors (blood pressure, plasma levels of total cholesterol, LDL-cholesterol, HDL-cholesterol, triglyceride, Lp(a), glucose, HbA1C, uric acid, white blood cell count, AST, ALT and gamma-GTP) were compared by BMI classes and by gender and age group. RESULTS: The subjects were categorized as 21% "overweight" (23.0-24.9 BMI), 17% "obese I" (25.0-29.9 BMI) and 2% "obese II" (over 30.0 BMI), all based on WPRO criteria. Graded increases in BMI classes based on these WPRO criteria were positively associated with frequency and values of cardiovascular risk factors, and the "overweight" had a significantly higher risk of cardiovascular disease than did the "normal" subjects. CONCLUSION: While a relationship between BMI and cardiovascular risk factors is gender and age specific, our investigation, highlighting the increasing risks of "overweight" with a BMI of 23.0-24.9, suggests that WPRO criteria are more relevant and therefore suitable for Japanese subjects.

Plasma n-3 polyunsaturated fatty acid and cardiovascular disease risk factors in Japanese, Korean and Mongolian workers.

The favorable role of n-3 polyunsaturated fatty acid (PUFA) in cardiovascular disease (CVD) has been demonstrated in animal experiments and in humans in Western countries, but its effect remains controversial in Asian populations. An observational study of Japanese, Koreans and Mongolians with extended histories of remarkably different frequencies of fish intake was conducted to examine whether differences in plasma n-3 PUFA affects CVD risk factors. We conducted a cross-sectional study in workplace settings and determined body mass index (BMI), blood pressure, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglyceride (TG), glucose, insulin, homeostasis model assessment-insulin resistance (HOMA-IR) and fatty acid composition in plasma. A total of 411 Japanese, 418 Korean and 252 Mongolian workers aged 30-60 yr participated in this study. The Japanese ate fish more frequently and had remarkably higher values of eicosapentaenoic acid, docosahexaenoic acid and n-3 PUFA, and lower values of BMI and HOMA-IR, followed by the Koreans, and then the Mongolians. In age groups, the Japanese and Koreans showed a similar tendency of increase in n-3 PUFA with increasing age. General linear measurement multivariate analysis after adjustment for gender, age, smoking, drinking, exercise habits and BMI showed n-3 PUFA was associated with HDL-C and TG in the Japanese, while it was associated with systolic blood pressure in the Koreans, and TG in the Mongolians. In conclusion, an increase in n-3 PUFA was associated with HDL-C and TG in the Japanese and Mongolians, but these beneficial effects were not constant across the three Asian ethnic groups.

[HOMA-IR and related clinical parameters].

Metabolic syndrome (MS) is based on visceral obesity and insulin resistance (IR) and, shows abnormalities in fat and glucose metabolism as well as hypertension. We investigated the relationship between IR and various risk factors for atherosclerosis in 378 male subjects (averaged age: 63.8 +/- 15.2 years) and 509 female subjects (averaged age: 67.1 +/- 13.5 years) recruited from a health check examination. Homeostasis model assessment (HOMA-IR) was used as an indicator of IR. Body mass index (BMI), triglyceride (TG), remnant-like particle cholesterol (RLP-C) and C-reactive protein (CRP) showed a good correlation (r > 0.2) with HOMA-IR. LDL cholesterol(LDL-C), small dense LDL(sdLDL) and HbA1c showed less stringent (r < 0.2) but still significant correlation with HOMA-IR. In contrast, oxidized LDL (oxLDL) and systolic blood pressure did not show any correlation. A multiple regression analysis indicated that BMI, RLP-C, HDL-C, HbA1c and CRP were independently correlated with HOMA-IR. These observations suggested that, among the three new lipid parameters (i.e., RLP-C, sdLDL and oxLDL), RLP-C was the most closely related to the IR status.

Association between knee pain and gait speed decline in rural Japanese community-dwelling older adults: 1-year prospective cohort study.

AIM: The present study examined whether knee pain was associated with decline in maximum gait speed (MGS) in a rural mountainous region. METHODS: This was a population-based 1-year prospective cohort study. A total of 658 men and women aged 60 years and older participated in the baseline survey in 2006, and 400 individuals participated in the follow-up survey in 2007. We compared the incidence of meaningful decline in gait speed (≥0.1 m/s) in older adults with different knee pain levels (none, mild, severe), estimating incidence rate ratio (IRR) by multivariable-adjusted Poisson regression model. RESULTS: Meaningful decline in MGS presented in 24.3% of participants, especially in men (30.3%). Baseline knee pain level was significantly related to meaningful decline in MGS after adjustment of potential confounders (IRR 1.79 for mild pain, 1.84 for severe pain; P for trend <0.01). In sensitivity analyses with change in MGS as the continuous variable, the association was not significant, but a similar negative association with knee pain was confirmed (mild pain ß = -0.040, severe pain ß = -0.088; P for trend = 0.104). In addition, older adults with knee pain at both baseline and follow up had a higher risk of meaningful decline in MGS (IRR 2.33, 95% CI 1.59-3.40) compared with those who had no pain at baseline or follow up. CONCLUSIONS: Knee pain was associated with a decline in gait speed at 1-year follow up. Prevention and treatment of knee pain might be important for suppression of decline in physical function in older adults.

Effect of salt intake on blood pressure in patients receiving antihypertensive therapy: Shimane CoHRE Study.

BACKGROUND: Salt intake is recognized as an important risk factor for hypertension in the general population. On the other hand, the availability of various classes of antihypertensive drugs means that it is generally not considered crucial to control the salt intake of hypertensive patients. In this study, we evaluated whether blood pressure (BP) was correlated with 24-hour salt intake in patients receiving antihypertensive therapy. METHODS: A total of 1496 consecutive participants undergoing health screening examinations were recruited. Subjects were divided into two groups according to their antihypertensive medications checked on prescriptions: 1005 subjects without antihypertensive therapy (untreated subjects) and 491 subjects with antihypertensive therapy (treated subjects). The 24-hour urinary sodium excretion (24h-uNa), a surrogate marker for daily salt intake, was estimated with the formula proposed by Tanaka et al. in 2002. RESULTS: Univariate analysis indicated that 24h-uNa was positively correlated with the systolic BP of both untreated and treated subjects. This was confirmed by multiple linear regression analysis after adjustment for confounding factors (untreated subjects: partial regression coefficient ß=1.45 ± 0.26, p<0.001; treated subjects: ß=0.75 ± 0.27, p=0.01). Salt intake was also correlated with the pulse pressure in both treated subjects (ß=0.55 ± 0.24, p=0.02) and untreated subjects (ß=0.93 ± 0.19, p<0.001). CONCLUSION: These results suggest the importance of reducing salt intake in hypertensive patients on pharmacotherapy, as well as in the general population. Further studies of hypertensive patients employing 24-h urine collection are warranted to confirm the present findings.