The purpose of the present study was to compare the effects of risedronate (RIS) and alfacalcidol (ALF) on the cortical and cancellous bone mass and mechanical properties in ovariectomized rats in a head-to-head fashion. Forty female Sprague-Dawley rats, 7 mo of age, were randomized into six groups: the sham-operated control (Sham) group, and five ovariectomized groups: treated with vehicle, RIS (0.1, 1.0, or 2.5 mg/kg, p.o., daily), and ALF (0.5 μg/kg, p.o., daily). At the end of the 8-wk experimental period, bone histomorphometric analyses of the cancellous bone of the proximal tibial metaphysis and cortical bone of the tibial disphysis was performed, and the mechanical properties of the bone were evaluated at the femoral distal metaphysis (FDM) and femoral diaphysis (FD). RIS prevented the decrease in the cancellous bone volume/total tissue volume (BV/TV) noted in ovariectomized rats in a dose-dependent manner, by suppressing increases in cancellous bone formation and resorption, without any apparent effect on the Ct Ar or maximum load of the FDM or FD. On the other hand, ALF increased the cancellous BV/TV, Ct Ar, and maximum load of the FDM or FD, by mildly decreasing cancellous bone formation and resorption, increasing periosteal and endocortical bone formation, and preventing an increase in endocortical bone resorption. Thus, the present study clearly showed that RIS and ALF had differential effects on the cortical and cancellous bone mass and mechanical properties in ovariectomized rats.

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In the previous analysis of our human mineral balance studies, we demonstrated positive correlations between the balances of calcium (Ca) and magnesium (Mg) and sodium (Na) intake in the range of 3.06 and 4.06 g/d or 43.71 and 96.40 mg/kg body weight (BW)/d, but there was no correlation between Na intake and Na balance. This suggested that the balances of Ca and Mg are affected by Na intake. Therefore, in the current study, we recalculated equilibrium intakes for Ca and Mg when balances of their intakes and outputs were equal to zero within the above Na range to reduce the effects of Na intake. From 1986 to 2000, 90 volunteers (10 male, 80 female; age 18 to 28 y) took part in 9 mineral balance studies. The balance periods ranged from 8 to 12 d, with adaptation periods of 2 to 4 d. The dietary intakes of Ca and Mg ranged from 294 to 719 and 154 to 334 mg/d, or from 4.83 to 15.07 and 2.44 to 6.42 mg/kg BW/d, respectively. Intake of Ca significantly correlated with Ca balance (r²=0.268; p<0.0001). When the balance was equal to zero, the mean value and upper limit of the 95% confidence interval for the regression equation between intake vs. balance were 10.072 and 10.660 mg/kg BW/d, respectively. Mg intake correlated significantly with Mg balance (r²=0.141, p=0.003). When the balance was equal to zero, the mean value and upper limit of the 95% confidence interval for the regression equation between intake and balance were 4.078 and 4.287 mg/kg BW/d, respectively.

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Although the effects of nutrition and immune status on disease development have been investigated, little attention has been given to changes in immune function in the elderly vulnerable to coronary artery disease (CAD). Our objective was to evaluate the association between immune variables and CAD risk factors, and nutritional factors related to immune and lipid profiles in elderly Koreans (n=90). The subjects were divided into three groups based on serum low-density lipoprotein cholesterol (LDL-cholesterol) level: risk (≥160 mg/dL), borderline (130-160 mg/dL), and control groups (<130 mg/dL). Concanavalin A-induced lymphocyte proliferation rate and interleukin (IL)-2 secretion were significantly lower in the risk group than the control group. The subjects in the risk group showed the highest serum concentrations of proinflammatory mediators such as complement 3 (C3), IL-1β, and IL-1 receptor antagonist (IL-1RA). The nutrient intake status of the subjects was generally satisfactory without differences among groups. IL-1RA concentration was negatively associated with intake of vitamin E and C3 was positively related to intake of Ca and Fe in the subjects with LDL-cholesterol ≥130 mg/dL. This study suggests that elderly individuals with high serum LDL-cholesterol are in a mild chronic inflammation state and micronutrient status such as vitamin E, Ca, and Fe may relate to this state.

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To evaluate the long-term effect of mild-early maternal protein malnutrition on weight gain, hematological parameters and macrophage function in rats at adult age, we compared rats whose dams were fed diets containing either 9.5% (low protein—LPD) or 23% protein (normal—NPD) for the first 12 d of lactation. At 80 d of age, the functions of spreading, phagocytosis and killing Candida albicans were determined in resident peritoneal macrophages, whereas leukocytes and red blood cells were counted in peripheral blood. The number of resident peritoneal macrophages from LPD was the same as from NPD, but the ability of spreading and phagocytosing opsonised yeast was impaired. Besides, they were not able to block the germ tube formation or kill C. albicans to the same extent as in the control group. The low protein diet produced a significant reduction in the pups' growth and in hematological parameters although no difference was found in leukocyte counts. Taken together the data suggest that protein malnutrition during early lactation induces permanent alterations in macrophage function, body composition and hematological status, which are not restored completely even after a normal protein diet is supplied.

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We investigated the effects of dietary supplementation of zinc (Zn) with or without vitamin A (Vit. A), to elucidate any cross activity between the two micronutrients, on memory and nerve growth factor (NGF) production in ddY male mice depleted for the two elements. After 3 mo-feeding with a Zn and Vit. A deficient (VAD) diet, mice were divided into three groups and replenished with normal Zn with VAD diet (NZ-VAD), high Zn with VAD diet (HZ-VAD) or normal Zn+normal Vit. A (NZ-NVA) for additional 2 mo. One more group was made and given the normal diet for the same period (Control group). Levels of NGF were measured from extracts of hippocampus, cerebellum and cortex at the end of the 3rd and 5th month. In addition, a radial arm maze task was performed at the end of the 5th month. The two Zn supplemented groups (NZ-VAD and HZ-VAD) tended to show high NGF concentration but memory was not improved. However, improved memory was observed in the NZ-NVA group. From these results we concluded that Zn may increase NGF; however, memory was improved only when Vit. A was sufficient.

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Many studies have suggested that the intake of soy products may protect against the occurrence of breast cancer because of the considerable amount of isoflavones they contain. To review the results of the observational studies, we performed this meta-analysis of the relevant literature. We searched Medline for reports that examined the association between soyfood consumption (or isoflavone intake) and breast cancer risk from January 1966 to April 2006. The random-effects model was used to estimate the pooled relative risk (RR). Twenty-one independent studies (14 case-control studies and 7 cohort studies) were included in the final analysis. The pooled RR of breast cancer for soyfood intake was 0.75 with a 95% CI of 0.59-0.95. As the main types of soyfood in Japan and China, tofu and miso showed clear protective effects. Isoflavone intake resulted in a 20% decrease in risk (RR=0.81, 95% CI 0.67-0.99). The pooled RR varied little according to study stratification. When the studies published in Japanese and Chinese were added, the inverse associations between soyfood, tofu and breast cancer risk became slightly stronger. The weak association of miso was possibly due to the high concentration of salt in miso soup. In the present analysis, we did not find strong evidence for publication bias in the combination of the studies. This meta-analysis supported the hypotheses that soyfood intake may be associated with a decreased risk of breast cancer due to the isoflavones. Further epidemiological studies need to be conducted with more comprehensive information about the soyfood, and more accurate assessment of the isoflavones.

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The antioxidative effect and protective potential against diabetes of the broccoli flower were investigated both in vitro and in a diabetic rat model. Among fractions of MeOH, CH₂Cl₂, BuOH, and H₂O, the BuOH fraction exerted the strongest inhibitory activities on 1,1-diphenyl-2-picrylhydrazyl radical, radical-induced protein oxidation, and nitric oxide generation by sodium nitroprusside. The in vitro results suggest that the BuOH fraction from the broccoli flower has a protective potential against oxidative stress. The rat model with diabetes induced by streptozotocin was employed to evaluate the protective effect of the BuOH fraction in vivo. Diabetic rats showed reduced body weight gain and heavier kidney and liver weights than normal rats, while oral administration of the BuOH fraction at an oral dose of 100 or 200 mg/kg body weight/d for 20 d attenuated the physiological changes induced by diabetes. In addition, oral administration of the BuOH fraction to diabetic rats led to significant decreases in serum glucose and glycosylated protein, while it resulted in the increase of serum albumin, implying that the BuOH fraction improves the abnormal metabolism of glucose and protein that leads to oxidative stress. Moreover, it significantly reduced thiobarbituric acid-reactive substance levels in serum, hepatic and renal mitochondria. This suggests that the BuOH fraction would alleviate the oxidative stress associated with diabetes through the inhibition of lipid peroxidation. The present study demonstrates that the BuOH fraction has an antioxidative effect in vitro and it protects against oxidative stress induced by diabetes in an in vivo model.

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In our previous study, we demonstrated that retrograded starch, a kind of resistant starch, of beans reduced serum lipid levels in rats. In this study, we examined whether retrograded starch in potato pulps could reduce serum lipid concentrations. Rats were given diets containing 15 g of retrograded starch in potato pulps from the Benimaru potato (BM) or Hokkaikogane potato (HK) in a 100 g diet for 4 wk. At the 4th week, the total cholesterol level in the serum in the BM group and serum triglyceride (TG) level in the HK group were significantly lower than those in the control group. In the BM group, the contents of fecal bile acids were significantly higher than those in the control group. On the other hand, in the HK group, the hepatic mRNA level of fatty acid synthase (FAS) was significantly lower than that in the control group. The FAS mRNA level correlated with the mRNA level of sterol regulatory element-binding protein-1c (SREBP-1c), a regulator of expression of FAS, positively. These results suggested that BM pulp promoted the excretion of bile acids, which resulted in a low concentration of serum cholesterol. On the other hand, HK pulp inhibited the synthesis of fatty acids at the mRNA levels of FAS and SREBP-1c, which might lead to a reduction of the serum TG level.

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Male mice (11 mo old) were fed 5% lard, fish oil, or Kazunoko (salted fish roe product) lipids for 4 mo to investigate their effects on maze behavior. The time required and distance traveled to reach the maze exit, and number of times that a mouse strayed into blind alleys in the maze, and the fatty acid compositions of brain lipids after the maze-behavior experiment were measured. The Kazunoko lipid group showed a significant improvement in all three parameters compared with the lard diet group, but the fish oil group showed only a significant decrease in the number of times that a mouse strayed into blind alleys compared with the lard diet group. The mice in the fish oil and Kazunoko lipid groups had significantly lower levels of arachidonic acid and higher percentages of docosahexaenoic acid in brain lipids compared with animals in the lard group. The mice in the Kazunoko lipid group had significantly lower levels of arachidonic acid in brain lipids than those in the fish oil group but the percentages of docosahexaenoic acid were not significantly different between these two diet groups. Our results suggest that an intake of Kazunoko lipids may suppress the percentage of n-6 fatty acids in brain lipids and this diet can be even more effective than fish oil as a supplement to improve learning capacity in mice.

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Effects of Chlorella regularis (dried cell powder)—cultured axenically under heterotrophic conditions, and provided as a dietary supplement—and its fractions on the blood pressure, cerebral stroke lesions, and life-span of stroke-prone spontaneously hypertensive rats (SHRSP/Izm) were investigated. When SHRSP were fed on diets with supplemented Chlorella to a commercial diet (Funabashi SP), elevation of blood pressure was significantly lower in the Chlorella groups than in the control group. At 21 wk of feeding, serum total cholesterol was significantly lower in the Chlorella groups than in the control group. Histopathological examination revealed cerebral vascular accidents in the brains of the control group, but those of Chlorella groups showed apparently low incidence compared to the control group. The average life-span of the Chlorella groups were significantly longer than that of the control group (p<0.001). Chlorella powder was fractionated into three fractions, lipid-soluble, hot water-soluble, and residual fractions. The diets supplemented with lipid or residual fractions equivalent to 10% Chlorella significantly suppressed elevation of blood pressure in SHRSP, and then decreased the incidence rate of cerebral vessel lesions compared to the control group. Chemical analysis revealed that the lipid fraction contained large quantities of antioxidants, including carotenoids (especially lutein) and others, and phospholipids involved in aorta collagen and elastin metabolism; the residual fraction contained high concentrations of arginine, enhancing the function of blood vessels. The control diet contained only a little these substances. These experimental results suggest that the beneficial effect of Chlorella on SHRSP is caused by the synergistic action of several ingredients of Chlorella, which play a role in sustention of a vascular function of rats.

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Rice seed endosperm has two types of protein bodies (PB). Type I protein body (PB-I) accumulates prolamin and is hard to digest, while type II protein body (PB-II) mainly consists of glutelin, an easily digestible protein. A simple method to process rice protein and improve its digestibility was tested from the viewpoint of its application to food manufacturing. Rice protein prepared by alkaline extraction followed by neutralization sedimentation (AE-RP) was compared with that prepared by starch degradation by α-amylase (SD-RP). The crude protein content of AE-RP and SD-RP was 84.7% and 78.2%, respectively. There were no major differences in protein composition among AE-RP, SD-RP and rice flour by SDS-PAGE, except 16 kDa polypeptide. With respect to amino acids, all the groups showed quite similar compositions, although cysteine and methionine were lower in AE-RP. In an in vitro digestion study with pepsin and pancreatin, both the SDS-PAGE analysis of protein pattern and the crude protein content of undigested residue clearly demonstrated that AE-RP has a higher digestibility than SD-RP. To find the cause of the difference in digestibility, the structural property of protein bodies by two production methods was compared using electron microscopy. PB-II of AE-RP was transformed into small, amorphous granules, while that of SD-RP was still kept partial protein body structures. PB-I of AE-RP kept its protein body structure, but produced double layers. From the finding that glutelin-gold was detected by immunochemistry not only in small, amorphous granules but also in PB-I, mainly the cortex layer, in AE-RP, it became clear that PB-I was swollen and fragile as a result of alkali treatment. These results strongly indicate that the improvement in digestibility of AE-RP is a result of the structural change of PB-I and -II caused by alkaline extraction.

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Tocotrienols are a class of vitamin E reported to be potent antioxidants, besides having the ability to inhibit the HMG-CoA reductase enzyme. This study assessed the effects of 3 doses of tocotrienol-rich vitamin E (TRE) on plasma tocotrienol isomer concentration, arterial compliance, plasma total antioxidant status (TAS), aortic systolic blood pressure (ASBP), serum total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) in healthy males. Methodology: This randomised, blinded end-point, placebo-controlled clinical trial with a parallel design involved 36 healthy male subjects who took either an oral placebo or TRE at doses of 80, 160 or 320 mg daily for 2 mo. Baseline and end-of-treatment measurements of vitamin E concentration, arterial compliance [assessed by aortic femoral pulse wave velocity (PWV) and augmentation index (AI)], ASBP, plasma TAS, serum TC and LDL-C were taken. Results: Baseline tocotrienol isomer concentrations were low and not detectable in some subjects. Upon supplementation, all TRE-treated groups showed significant difference from placebo for their change in α, γ and δ tocotrienol concentrations from baseline to end of treatment. There was a linear dose and blood level relationship for all the isomers. There was no significant difference between groups for their change in PWV, AI, plasma TAS, ASBP, TC or LDL-C from baseline to end of treatment. Groups 160 mg (p=0.024) and 320 mg (p=0.049) showed significant reductions in their ASBP. Group 320 mg showed a significant 9.2% improvement in TAS. Conclusion: TRE at doses up to 320 mg daily were well tolerated. Treatment significantly increased α, δ, and γ tocotrienol concentrations but did not significantly affect arterial compliance, plasma TAS, serum TC or LDL-C levels in normal subjects.

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The objective of this study was to examine how transient high plasma homocysteine (Hcy) levels affect the metabolism of Hcy, the activity and expression of S-adenosylhomocysteine (SAH) hydrolase which catalyzes both SAH hydrolysis and SAH synthesis. Wistar ST rats (males) were cannulated in the right jugular vein for intravenous infusion of physiological saline or DL-Hcy solutions (15 and 30 mg/mL) for 1 h at 1.1 mL/h/rat. The content of S-adenosylmethionine (SAM), SAH-synthetic activity of SAH hydrolase and the expression of SAH hydrolase mRNA in liver extracts showed no significant difference in the Hcy infused groups as compared to the Control group. On the other hand, the contents of hepatic SAH in the Hcy infused groups were dose-dependent and significantly higher than that of the Control group. Thus, this study showed that hepatic SAH increased without any increase in the SAH-synthetic activity and the expression of SAH hydrolase mRNA under transient high plasma Hcy levels after intravenous infusion of Hcy.

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