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To compare the sensitivity, specificity, and total accuracy of an HbA1c ofor =6.5% in the detection of hyperglycemia (PPHG) relative to those of a fasting blood glucose (FBG) ofor =7.0 mmol/L.A total of 6,010 subjects (2,987 men and 3,023 women) living or working in Kasugai, Japan, underwent a medical checkup at Kasugai City Medical Care Center between April 2001 and March 2002. For the 91 subjects who had either a FBG ofor =7.0 mmol/L or an HbA1c ofor =6.5%, a 75-g oral glucose tolerance test was performed to confirm or exclude PPHG. We calculated the true- and false-positive odds ratios to evaluate the sensitivity and specificity of HbA1c relative to FBG, and compared the overall accuracy by calculating the conditional relative odds ratio (CROR).Among the 91 subjects, the true- and false-positive odds ratios were 0.43 (95% CI 0.26-0.69) and 0.40 (0.13-1.27) (Fisher's exact test, P.090), respectively; the CROR was 1.07 (95% CI 0.30-3.75).Although the HbA1c test was marginally more specific but less sensitive than the FBG test, at the given cutoff points the accuracies of two tests were equivalent.

The discriminating abilities of fasting plasma glucose (FPG) and HbA1c were compared on screening tests for impaired glucose tolerance (IGT) and IGT plus diabetes mellitus by the receiver operating characteristic (ROC) curve analysis. Furthermore, effects of sex, age and BMI were examined on sensitivity and specificity of the optimal cutoff points. This study included 997 subjects who were recruited for 75 g OGTT after the first screening of the Japan Diabetes Prevention Program. According to the 1997 criteria of the American Diabetes Association (ADA), 140 subjects were classified as diabetic and 256 as IGT. The areas under the ROC curves of FPG were significantly larger than those of HbA1c. The optimal cutoff points of FPG were 102 mg/dl for IGT and 105 mg/dl for IGT plus diabetes mellitus. Those of HbA1c were both 5.3%. In screening with FPG, females had significantly lower sensitivity and higher specificity than males, and the specificity for IGT plus diabetes mellitus was the lowest in the obese group. In screening with HbA1c, the specificity was low in the older and the obese groups. We concluded that FPG was superior to HbA1c for screening of IGT and IGT plus diabetes mellitus and the optimal cutoff point of FPG would be 102 mg/dl or greater.

Little is known about the regulatory effects of steroid hormones on the intestinal H(+)/oligopeptide transporter PEPT1. In the present study, we investigated the effects of progesterone and its related compounds on the uptake of cephalexin, a typical PEPT1 substrate, using the human intestinal cell line Caco-2. Caco-2 cell monolayers were cultured on plastic cell culture plates coated with rat tail collagen type I. The determination of cephalexin uptake was performed with HPLC. To investigate the effect of progesterone treatment on cephalexin uptake, the monolayers were incubated with cephalexin after progesterone treatment. Progesterone decreased cephalexin uptake in a concentration-dependent manner, and the IC(50) value was calculated to be 2.3 microM. A significant decrease in cephalexin uptake was observed after progesterone treatment for 12 h, and the decrease was maximal when the monolayers were treated for 24-72 h. Cephalexin uptake was significantly inhibited by treatments with 17alpha-hydroxyprogesterone, norethisterone, and chlormadinone. By contrast, treatment with dehydroepiandrosterone, pregnenolone, estradiol, testosterone, hydrocortisone, and dexamethasone did not affect cephalexin uptake. The effects of progesterone and norethisterone treatment on the kinetic parameters of cephalexin uptake were investigated. The saturable component of cephalexin uptake was markedly inhibited by progesterone and norethisterone treatments. The J(max) of cephalexin uptake with progesterone and norethisterone treatments was significantly decreased compared with the control, whereas K(m) and K(d) values were not affected. Therefore the quantitative decrease in PEPT1 density is considered to be one cause of the decrease in cephalexin uptake with progesterone and norethisterone treatments.

The aim of this study was to investigate whether the concomitant administration of the substrates or inhibitors of PEPT1, OCTN1, OCTN2, and P-glycoprotein affects the intestinal absorption of sulpiride in rats. The absorption of sulpiride from rat intestine was decreased by the substrates or inhibitors of PEPT1, OCTN1, and OCTN2. On the other hand, the absorption was increased by the substrates of P-glycoprotein. The effects of these concomitantly administered drugs on the pharmacokinetic behavior of sulpiride after oral administration in rats were investigated. Peak concentration (C(max)) and area under the plasma concentration-time curve (AUC(0-8 h)) of sulpiride were decreased by the concomitant administration of the substrates or inhibitors of PEPT1, OCTN1, and OCTN2. However, the same parameters were significantly increased by the concomitant administration of the substrates of P-glycoprotein. The present results suggest the possibility of drug-drug interaction during the absorption process in the small intestine due to the coadministration of sulpiride and these agents. These findings provide important information for preventing adverse effects and for ensuring the effectiveness of sulpiride and concomitantly administered drugs.

We investigated whether cephalexin transport in Caco-2 cells is regulated by insulin. After the insulin pretreatment, cephalexin uptake, and transport as well as PEPT1 mRNA and protein expression in the cells were measured. Cephalexin uptake was significantly increased by the insulin pretreatment. Insulin significantly increased cephalexin saturable uptake, but had no significant effect on the non-saturable one. PEPT1 protein expression on the apical membrane, but not PEPT1 mRNA expression, was increased by the insulin pretreatment. The enhancement of cephalexin uptake by the insulin pretreatment was inhibited by genistein, a tyrosine kinase inhibitor, and colchicine, an agent that disrupts protein translocation. Apical-to-basolateral transport of cephalexin has increased by the insulin pretreatment at the apical side and long-term insulin pretreatment at the basolateral side. It is considered that insulin mainly binds to its receptor on the apical and basolateral membranes, thereby promoting PEPT1 translocation from the intracellular pool to the apical membrane surface; consequently, PEPT1 protein expression on the apical membrane is increased.

KV-2920 is a novel acyl-CoA: cholesterol acyltransferase (ACAT) inhibitor. To confirm the efficacy of KV-2920-low density lipoprotein (LDL) complex (KV-LDL complex) as a drug-carrier complex on experimental atherosclerosis, we examined its inhibitory effects in vitro and in vivo. LDL was isolated from human plasma and the KV-LDL complex was prepared by incubation in the presence of Celite 545. The complex contained about 800 mol KV-2920 in 1 mol LDL. The cholesterol levels in the serum and aorta of atherogenic mice after 14 weeks of feeding were significantly higher than those of nonatherogenic mice. With the intravenous injection of KV-LDL complex, although the cholesterol levels in the serum were not influenced, the level of cholesterol ester in the aorta of atherogenic mice was significantly reduced. The concentration of cholesterol ester in the macrophages derived from ICR mice was predominantly increased by incubation with LDL for 48 h, this increase was significantly inhibited by incubation with KV-LDL complex. Moreover, the complex also inhibited the increase of cholesterol ester in macrophages following incubation with oxidized LDL. These findings suggest that KV-LDL complex inhibits the foam cell formation of macrophages though action of KV-2920 as an ACAT inhibitor, and prevents the accumulation of cholesterol ester in the aorta of atherogenic mice. Therefore, KV-LDL complex may be useful as a drug-carrier complex in antiatherosclerotic therapy.

To evaluate the physical strength, cerebral function, and mental health conditions in elderly persons, and to examine the correlation between these functions. The subjects were 151 independent-living elderly Japanese women, mean age 70 +/-5 years (+/-SD; range, 60 to 80 years), with normal abilities in daily life. The health check-up was conducted from April to May 1997. Physical strength was estimated by measuring seven activities. Cerebral functions were assessed by six sub-tests of the General Aptitude Test Battery (GATB). Their mental health status was measured by four sub-scales of the General Health Questionnaire (GHQ)-28. The physical strenght and almost all of the cerebral functions decreased with age. Social dysfunction and severe depression on the GHQ sub-scales also worsened with age. Physical strength was strongly correlated with cerebral functions after adjusting for the confounding effect of aging. There were also interrelations between physical strength and mental health. This study provided important information on the correlation between physical and mental status in elderly women. Future longitudinal studies with the intervention of physical training are required to determine whether a causal relationship exists between these factors.

Objective: To clarify the influences of age on dietary intakes and plasma concentrations of fatty acids (FAs) in Japanese female dietitians. Subjects and methods: In autumn 1996, we estimated dietary FA intakes based on 7 day weighed diet records and analyzed plasma FA concentrations in 79 healthy Japanese female dietitians, and investigated their relationships with age, dividing into three age groups (young (32–42 y), middle-aged (43–50 y) and elderly (51–66 y)). Results: Dietary intakes of total FA, saturated FAs, monounsaturated FAs, n-3 polyunsaturated FAs (PUFAs) and α-linolenic acid (18:3n-3) were significantly highest in the middle-aged group, and lowest in the elderly. Similar trends were observed for dietary intakes of n-6 PUFAs and linoleic acid (18:2n-6), but there were no differences with regard to eicosapentaenoic acid (EPA; 20:5n-3), docosahexaenoic acid (DHA; 22:6n-3) and n-3 highly unsaturated FAs (HUFAs=EPA+22:5n-3+DHA). On the other hand, plasma concentrations of all FAs except for arachidonic acid (20:4n-6) demonstrated positive correlations with age. Moreover, plasma concentrations of EPA in all age groups, DHA in the elderly and n-3 HUFAs in the middle-aged and the elderly were all positively correlated with dietary intakes. Conclusions: We should take into account the influence of age on dietary habit and lipid metabolism when interpreting associations between dietary FA intakes and plasma FA concentrations. Sponsorship: This study was supported in part by a grant-in-aid from the Ministry of Education, Science, Sports, Culture and Technology, Japan (06454242).

We investigated whether the uptake of a specific antipsychotic agent, sulpiride, in Caco-2 cells is mediated by a carrier-mediated system. Caco-2 cell monolayers were cultured in plastic culture dishes and uptake and efflux studies were conducted. The determination of sulpiride was performed by HPLC. At 37 degrees C, sulpiride uptake in pH 6.0 was twice as much as in pH 7.4. At 4 degrees C, however, no significant difference was observed between pH 6.0 and 7.4. The uptake at 4 degrees C was markedly lower than that obtained at 37 degrees C. The subtraction of the uptake at 4 degrees C from the uptake at 37 degrees C indicated a saturable process, and the result of the Eadie-Hofstee plot analysis indicated that the uptake consists of two or more saturable components. The uptake was significantly inhibited by uncoupler, protonophore, amino acid modifying agent and proteinase. Sulpiride efflux was temperature-dependent and was significantly inhibited by uncoupler and amino acid modifying agent. These findings indicate that sulpiride uptake and efflux in Caco-2 cells are carrier-mediated. Furthermore, the uptake was significantly decreased by some substrates and inhibitors of peptide transporter, PEPT1, and organic cation transporters, OCTN1 and OCTN2, and was significantly increased by preloading with them. The uptake was also significantly increased by a typical substrate of P-glycoprotein. From these findings, we presumed that peptide transporter PEPT1 and organic cation transporters OCTN1 and OCTN2 are involved with this uptake. P-glycoprotein may also contribute to the efflux of sulpiride.

Objective: To assess the relative validity of a semi-quantitative food frequency questionnaire (SQFFQ) against 28 day weighed diet records (WDRs). Subjects and methods: The SQFFQ was administered to 106 (21 male and 85 female) Japanese dietitians in Aichi Prefecture in autumn, 1996 and four-season consecutive 7 day WDRs were carried out during 1996–1997. We evaluated validity of intakes of 15 foods and 31 macro- and micro-nutrients based on the SQFFQ against those according to 28 day WDRs among 79 Japanese female dietitians. Results: Mean daily intakes of selected foods and nutrients determined by the SQFFQ were generally equivalent to those measured by 28 day WDRs. Pearson's de-attenuated correlation coefficients (CCs) with log-transformation and energy-adjustment between intakes of selected foods and nutrients quantified by the SQFFQ and 28 day WDRs (minimum–median–maximum) ranged from 0.17 (beverages)–0.52 to 0.74 (rice), and Spearman's rank CCs with energy-adjustment ranged from 0.28 (confectionery)–0.42 to 0.68 (rice). Respective Pearson's CCs for intakes of nutrients were 0.28 (PUFAs)–0.51 to 0.73 (magnesium), and Spearman's rank CCs ranged from 0.23 (n-3 PUFAs)–0.45 to 0.71 (magnesium). Favorably higher agreement for intakes of foods/nutrients was achieved along with lower disagreement. Conclusions: Satisfactorily higher relative validity was attained in Japanese female dietitians with the SQFFQ. This calibrated questionnaire seems therefore appropriate for administration to Japanese dietitians to clarify associations between diet and health/disease. Sponsorship: A grant-in-aid from the Ministry of Education, Science, Sports and Culture (06454242). European Journal of Clinical Nutrition (2001) 55, 735–742

The branched-chain alpha-ketoacid dehydrogenase (BCKDH) complex is the rate-limiting enzyme in the catabolism of branched-chain amino acids. In the present study, we examined the effects of exercise training on the activity and enzyme expression of the hepatic BCKDH complex in diabetic rats. The rats were prepared by intravenous injections of streptozotocin (50 mg/kg BW), and exercise training was accomplished by treadmill running for 45 min/d for 4 wk. The total and actual activities of hepatic BCKDH complex were significantly increased to approximately 160% by 4 wk of diabetes. On the other hand, diabetic rats in the trained group had the same level of activities as those in the normal rats, indicating that exercise training inhibited the diabetes-induced increase in the enzyme activities. The activity state (% active form) of the enzyme complex was about 100% in all groups and was not affected by diabetes or training. The protein amounts of the enzyme subunits (E1alpha and E2) and the abundance of mRNA for the E2 subunit, but not for the other subunits, in the liver had the same trend as the activities. These results suggest that the capacity for branched-chain amino acid catabolism in streptozotocin-induced diabetic rats is reduced by exercise training and that this modification is associated with the suppression of diabetes-induced BCKDH complex expression in the liver.

Covalent modification of the pyruvate dehydrogenase complex provides an important regulatory mechanism for controlling the disposal of glucose and other compounds metabolized to pyruvate. Regulation of the complex by this mechanism is achieved in part by tissue-specific expression of the genes encoding isoenzymes of pyruvate dehydrogenase kinase (PDK). Starvation is known from our previous work to increase PDK activity of heart and skeletal muscle by increasing the amount of PDK isoenzyme 4 (PDK4) present in these tissues. This study demonstrates that increased expression of both PDK4 and PDK2 occurs in rat liver, kidney, and lactating mammary gland in response to starvation. PDK4 and PDK2 message levels were also increased by starvation in the two tissues examined (liver and kidney), suggesting enhancement of gene transcription. Changes in PDK2 message and protein were of similar magnitude, but changes in PDK4 message were greater than those in PDK4 protein, suggesting regulation at the level of translation. In contrast to these tissues, starvation had little or no effect on PDK2 and PDK4 protein in brain, white adipose tissue, and brown adipose tissue. Nevertheless, PDK4 message levels were significantly increased in brain and white adipose tissue by starvation. The findings of this study indicate that increased expression of PDK isoenzymes is an important mechanism for bringing about inactivation of the pyruvate dehydrogenase complex during starvation in many but not all tissues of the body. The absence of this mechanism preserves the capacity of neuronal tissue to utilize glucose for energy during starvation.

The effects of dexamethasone palmitate incorporated into lipid emulsion(D-lipo) on foam cell formation and atherosclerosis model mice were examined. The cholesterol ester(CE) concentration in derived macrophages from mouse peritoneal cavity was increased markedly by oxidized LDL. The CE increment was associated with conversion of macrophages to foam cell. D-lipo significantly inhibited the CE increment on macrophages induced by oxidized LDL. The inhibition effect of D-lipo on foam cell formation was similar with that of dexamethasone phosphate as control. The atherogenic mouse was induced by the maintaining with an atherogenic diet for 14 weeks. D-lipo or dexamethasone phosphate was intravenously administered to mouse once a week from 8 to 14 weeks. The cholesterol concentration in serum and aortic CE deposition on the atherogenic mouse were significantly increased as compared to those of the control mouse. Although the increment of cholesterol concentration in serum was not changed, CE accumulation in the aorta of atherogenic mouse was inhibited by D-lipo(150 and 750 nmol/kg). Dexamethasone phosphate(750 nmol/kg) did not affect to cholesterol concentration in serum and CE accumulation in the aorta of atherogenic mouse. These findings suggest that D-lipo is useful as an anti-atherosclerosis.

Post-exercise hyperketonemia in poorly-controlled diabetic patients is a well recognized phenomenon, but because studies concerning changes in ketone body metabolism in muscle during and/or after exercise are scarce, we measured the intramuscular 3-hydroxybutyrate (3-OHBA) and lactate concentrations in 12 diabetic (streptozotocin-induced; 60 mg/kg, ip) and 13 non-diabetic control rats before and after a 1-h muscle contraction. One thigh tetanic contraction was elicited at a tetanic frequency of 60 tetani/min and the other thigh was kept resting. We used a microdialysis technique in both quadriceps muscles, vastus lateralis, and the right jugular vein. Blood flow in both femoral muscles was also monitored before and after contraction. Dialysate 3-OHBA and lactate levels in contracting and non-contracting muscles and in blood showed a significant increase after contraction (P0.05) in diabetic rats. In control rats there was no significant change in dialysate 3-OHBA or the lactate concentration in contracting and non-contracting muscles or in blood before and after contraction. A significant increase in contracting muscle blood flow was observed only for the first 5 min after contraction in diabetic and control rats. These results suggest that 3-OHBA uptake in contracting muscle is reduced, and that this phenomenon may play a role in post-exercise ketosis in diabetes.

This study investigated whether conditions known to alter the activity and phosphorylation state of the pyruvate dehydrogenase complex have specific effects on the levels of isoenzymes of pyruvate dehydrogenase kinase (PDK) in rat heart. Immunoblot analysis revealed a remarkable increase in the amount of PDK4 in the hearts of rats that had been starved or rendered diabetic with streptozotocin. Re-feeding of starved rats and insulin treatment of diabetic rats very effectively reversed the increase in PDK4 protein and restored PDK enzyme activity to levels of chow-fed control rats. Starvation and diabetes also markedly increased the abundance of PDK4 mRNA, and re-feeding and insulin treatment reduced levels of the message to that of controls. In contrast with the findings for PDK4, little or no changes in the amounts of PDK1 and PDK2 protein and the abundance of their messages occurred in response to starvation and diabetes. The observed shift in the relative abundance of PDK isoenzymes probably explains previous studies of the effects of starvation and diabetes on heart PDK activity. The results indicate that control of the amount of PDK4 is important in long-term regulation of the activity of the pyruvate dehydrogenase complex in rat heart.

Five mitochondrial protein kinases, all members of a new family of protein kinases, have now been identified, cloned, expressed as recombinant proteins, and partially characterized with respect to catalytic and regulatory properties. Four members of this unique family of eukaryotic protein kinases correspond to pyruvate dehydrogenase kinase isozymes which regulate the activity of the pyruvate dehydrogenase complex, an important regulatory enzyme at the interface between glycolysis and the citric acid cycle. The fifth member of this family corresponds to the branched-chain alpha-ketoacid dehydrogenase kinase, an enzyme responsible for phosphorylation and inactivation of the branched-chain alpha-ketoacid dehydrogenase complex, the most important regulatory enzyme in the pathway for the disposal of branched-chain amino acids. At least three long-term control mechanisms have evolved to conserve branched chain amino acids for protein synthesis during periods of dietary protein insufficiency. Increased expression of the branched-chain alpha-ketoacid dehydrogenase kinase is perhaps the most important because this leads to phosphorylation and nearly complete inactivation of the liver branched-chain alpha-ketoacid dehydrogenase complex. Decreased amounts of the liver branched-chain alpha-ketoacid dehydrogenase complex secondary to a decrease in liver mitochondria also decrease the liver's capacity for branched-chain keto acid oxidation. Finally, the number of E1 subunits of the branched-chain alpha-ketoacid dehydrogenase complex is reduced to less than a full complement of 12 heterotetramers per complex in the liver of protein-starved rats. Since the E1 component is rate-limiting for activity and also the component of the complex inhibited by phosphorylation, this decrease in number further limits overall enzyme activity and makes the complex more sensitive to regulation by phosphorylation in this nutritional state. The branched-chain alpha-ketoacid dehydrogenase kinase phosphorylates serine 293 of the E1 alpha subunit of the branched-chain alpha-ketoacid dehydrogenase complex. Site-directed mutagenesis of amino acid residues surrounding serine 293 reveals that arginine 288, histidine 292 and aspartate 296 are critical to dehydrogenase activity, that histidine 292 is critical to binding the coenzyme thiamine pyrophosphate, and that serine 293 exists at or in close proximity to the active site of the dehydrogenase. Alanine scanning mutagenesis of residues in the immediate vicinity of the phosphorylation site (serine 293) indicates that only arginine 288 is required for recognition of serine 293 as a phosphorylation site by the branched-chain alpha-ketoacid dehydrogenase kinase. Phosphorylation appears to inhibit dehydrogenase activity by introducing a negative charge directly into the active site pocket of the E1 dehydrogenase component of the branched-chain alpha-ketoacid dehydrogenase complex. A model based on the X-ray crystal structure of transketolase is being used to predict residues involved in thiamine pyrophosphate binding and to help visualize how phosphorylation within the channel leading to the reactive carbon of thiamine pyrophosphate inhibits catalytic activity. The isoenzymes of pyruvate dehydrogenase kinase differ greatly in terms of their specific activities, kinetic parameters and regulatory properties. Chemically-induced diabetes in the rat induces significant changes in the pyruvate dehydrogenase kinase isoenzyme 2 in liver. Preliminary findings suggest hormonal control of the activity state of the pyruvate dehydrogenase complex may involves tissue specific induced changes in expression of the pyruvate dehydrogenase kinase isoenzymes.

A micro method for the determination of pilsicainide hydrochloride, an antiarrhythmic agent, in human serum was developed. In this method, serum containing the drug was extracted with benzene under alkaline conditions and then the extract was analyzed by high-performance liquid chromatography using a 5 mm Shim-pack HRC-CN column (150 mm×4.6 mm I.D.) at 40°C.The mobile phase was 65 mM sodium perchlorate-acetonitrile (85: 15). The flow-rate was kept at 1.2 ml/min and the column effluent was monitored at 200 nm. Lidocaine hydrochloride or disopiramide phosphate was used as an internal standard. The method is accurate and reproducible for routine monitoring of serum pilsicainide hydrochloride.The serum levels of pilsicainide hydrochloride in 30 patients monitored at 1.2 to 15.5 hrs after the last dose prior to blood sampling varied from 0.18 to 1.52μg/ml. Relatively large interindividual differences were observed in the apparent total body clearances and elimination half-lives estimated using a computer program (PEDA). We recommend that the serum levels of pilsicainide hydrochloride be monitored in patients receiving this drug therapy.

Background Lifestyle modifications are considered the most effective means of delaying or preventing the development of type 2 diabetes (T2DM). To contain the growing population of T2DM, it is critical to clarify effective and efficient settings for intervention and modalities for intervention delivery with a wide population reach. The Japan Diabetes Outcome Intervention Trial-1 (J-DOIT1) is a cluster randomized controlled trial to test whether goal-focused lifestyle coaching delivered by telephone can prevent the development of T2DM in high-risk individuals in a real-world setting. This paper describes the study design and recruitment of the study subjects. Methods For the recruitment of study subjects and their follow-up annually over 3 years, we employed health checkups conducted annually at communities and worksites. Health care divisions recruited from communities and companies across Japan formed groups as a cluster randomization unit. Candidates for the study, aged 20-65 years with fasting plasma glucose (FPG) of 5.6-6.9 mmol/l, were recruited from each group using health checkups results in 2006. Goal-focused lifestyle support is delivered by healthcare providers via telephone over a one-year period. Study subjects will be followed-up for three years by annual health checkups. Primary outcome is the development of diabetes defined as FPG≥7.0 mmol/l on annual health checkup or based on self-report, which is confirmed by referring to medical cards. Results Forty-three groups (clusters), formed from 17 health care divisions, were randomly assigned to an intervention arm (22 groups) or control arm (21 clusters) between March 2007 and February 2008. A total of 2840 participants, 1336 from the intervention and 1504 from the control arm, were recruited. Consent rate was about 20%, with no difference between the intervention and control arms. There were no differences in cluster size and characteristics of cluster between the groups. There were no differences in individual characteristics between the study arms. Conclusion We have launched J-DOIT1, a nation-wide trial to prevent the development of T2DM in high-risk individuals using telephone-delivered intervention. This trial is expected to contribute to evidence-based real-world preventive practices. Trial registration UMIN000000662.

The Koryu gold-silver mine is located approximately at 141°19' of east longitude and 42°51' of north latitude in southwestern Hokkaido. The ore deposits are of epithermal gold-silver-quartz vein type, and they are composed of the No. 1-No. 7 veins hosted by the Miocene black mudstone. In this study, we have determined homogenization and ice melting temperatures of fluid inclusions in quartz, and chemical compositions of some ore minerals by microprobe analyses for the interpretation of mechanism of gold-silver deposition in the two veins (No. 1 and No. 3). Three stages of mineralization are discriminated on the basis of brecciation and cross-cutting relations in the vein, and gold-silver deposition occurred predominantly during the middle stage. The ores ordinarily exhibit banded structure composed of quartz, ±adularia, ±clay minerals, ±carbonates, and gold-silver and other metallic minerals (ginguro). The ore minerals are electrum (44-74 atom.%Ag), aguilarite (Se/(S+Se) atomic ratio : 0.25-0.51), pyrargyrite-proustite, pearceite-polybasite, miargyrite, Ag-bearing tetrahedrite (22-24 wt.%Ag) , galena, sphalerite (0.6-1.2 mole% FeS), chalcopyrite and pyrite etc. Ag content of electrum tends to decrease slightly toward the upper levels in the No. 3 vein, whereas FeS content of sphalerite is invariable between the upper and lower levels. Fluid inclusions observed in quartz of the middle stage are two phase and liquidrich type. Homogenization temperatures for the No. 1 vein are mainly 220°-270°C with high frequency in the range 250°-260°C. The temperatures for the No. 3 vein are about the same as those for the No. 1 vein, but show higher values (250°-280°C) at 30 mL. Ice melting temperatures of inclusion fluids for the No. 1 and No. 3 veins are from −0.4°C to −1.3°C, and from −0.5°C to −1.4°C, respectively. Spatial variations of these homogenization and ice melting temperatures, together with the data previously reported, would indicate that the relatively CO2-rich ore fluids had boiled on the way to form ore shoots.

The Ezuri Kuroko deposits are located approximately at 140°36'of east longitude and 40°15' of north latitude in the Hokuroku district of Akita Prefecture. The ore deposits are hosted by basaltic tuff and dacitic rocks of the Miocene age, and they are composed mainly of stratiform black ores. In this paper, the features of Au- and Ag-bearing ores and minerals are described, and the environment of the mineralization is estimated from the FeS content of sphalerite and the data of fluid inclusions in sphalerite. Gold- and/or silver-bearing minerals identified by microscopic examination and electron microprobe analysis are electrum, stromeyerite, pearceite, mckinstryite, argyrodite and fahlore (up to 7.8 atomic % Ag). These minerals are particularly found in fine-grained massive black ore. Most of electrum contains 30-40 atomic % Ag, and Ag distribution of an individual grain is comparatively homogeneous. Silver content of black ore (20-1, 260 ppm) is dependent on the amount of fahlore as well as of other silver minerals. The ranges of homogenization temperatures of fluid inclusions in sphalerite are 236°-283°C (breccia-like black ore), 210°-279°C (massive black ore) and 165°-230°C (coarse-grained sphalerite filling cavities in massive black ore), respectively. The FeS content of sphalerite coexisting with electrum is less than 0.2 mole%. Taking account of the effect of pressure, it is deduced from these data that Au- and Ag-bearing ores were formed in a range of ca. 240°-290°C under the condition of a high activity of sulfur. Furthermore, it appears that gold was precipitated from Au(HS)2− complex mainly owing to cooling and a decrease in H2S concentration of ore-forming fluids caused by mixing with seawater and/or by precipitation of metal sulfides.

The present study was conducted to examine alterations in the concentrations of plasma free amino acids, glucose, insulin, free fatty acids (FFAs), and urea nitrogen induced by branched-chain amino acid (BCAA) supplementation in young men. Overnight-fasted subjects ingested drinks containing 1 or 5 g of a BCAA mixture (weight ratio of 1 : 2.3 : 1.2 for isoleucine : leucine : valine), and blood was intermittently collected for 3 h after ingestion. Ingestion of the BCAA mixture resulted in significant increases in the plasma concentrations of individual BCAAs, corresponding to the amounts of amino acids ingested. On the other hand, plasma concentrations of methionine and aromatic amino acids tended to decrease in the trial with 5 g BCAAs, suggesting that BCAA ingestion affects the metabolism of these amino acids. The ingestion of BCAAs temporarily increased plasma insulin levels and affected plasma concentrations of FFAs, but had almost no effect on glucose or urea nitrogen.

Background A randomized control trial was performed to test whether a lifestyle intervention program, carried out in a primary healthcare setting using existing resources, can reduce the incidence of type 2 diabetes in Japanese with impaired glucose tolerance (IGT). The results of 3 years' intervention are summarized. Methods Through health checkups in communities and workplaces, 304 middle-aged IGT subjects with a mean body mass index (BMI) of 24.5 kg/m2 were recruited and randomized to the intervention group or control group. The lifestyle intervention was carried out for 3 years by public health nurses using the curriculum and educational materials provided by the study group. Results After 1 year, the intervention had significantly improved body weight (-1.5 ± 0.7 vs. -0.7 ± 2.5 kg in the control; p = 0.023) and daily non-exercise leisure time energy expenditure (25 ± 113 vs. -3 ± 98 kcal; p = 0.045). Insulin sensitivity assessed by the Matsuda index was improved by the intervention during the 3 years. The 3-year cumulative incidence tended to be lower in the intervention group (14.8% vs.8.2%, log-rank test: p = 0.097). In a sub-analysis for the subjects with a BMI > 22.5 kg/m2, a significant reduction in the cumulative incidence was found (p = 0.027). Conclusions The present lifestyle intervention program using existing healthcare resources is beneficial in preventing diabetes in Japanese with IGT. This has important implications for primary healthcare-based diabetes prevention. Trial registration number UMIN000003136

The authors examined the effect of branched-chain amino acid (BCAA) supplementation on squat-exercise-induced delayed-onset muscle soreness (DOMS) using 12 young, healthy, untrained female participants. The experiment was conducted with a crossover double-blind design. In the morning on the exercise-session day, the participants ingested either BCAA (isoleucine:leucine:valine = 1:2.3:1.2) or dextrin at 100 mg/kg body weight before the squat exercise, which consisted of 7 sets of 20 squats/set with 3-min intervals between sets. DOMS showed a peak on Days 2 and 3 in both trials, but the level of soreness was significantly lower in the BCAA trial than in the placebo. Leg-muscle force during maximal voluntary isometric contractions was measured 2 d after exercise (Day 3), and the BCAA supplementation suppressed the muscle-force decrease (to ~80% of the value recorded under the control conditions) observed in the placebo trial. Plasma BCAA concentrations, which decreased after exercise in the placebo trial, were markedly elevated during the 2 hr postexercise in the BCAA trial. Serum myoglobin concentration was increased by exercise in the placebo but not in the BCAA trial. The concentration of plasma elastase as an index of neutrophil activation appeared to increase after the squat exercise in both trials, but the change in the elastase level was significant only in the placebo trial. These results suggest that muscle damage may be suppressed by BCAA supplementation.

Goshajinkigan (GJG), an aqueous extract of a combination of 10 herbal medicines, is widely used for the treatment of diabetic neuropathy in Japan. In this study, the effect of GJG on insulin-induced glucose disposal in normal and streptozotocin (STZ) diabetic rats was analyzed using the euglycemic clamp technique. Male Wistar rats, aged 9 weeks, were randomly assigned to six groups: group NS, normal rats receiving saline; group NG, normal rats receiving GJG (800 mg x kg(-1) x day(-1), p.o.); group NGL, normal rats receiving GJG + N(G)-monomethyl-L-arginine (L-NMMA, 1 mg x kg(-1) x min(-1), i.v.); group DS, diabetic rats receiving saline; group DG, diabetic rats receiving GJG; group DGL, diabetic rats receiving GJG + L-NMMA. After daily oral administrations of saline or GJG for one week, euglycemic clamp experiments were performed. The metabolic clearance rates of glucose (MCR) in the DS, DG, and DGL groups (8.7 +/- 2.9, 18.2 +/- 2.5, and 8.1 +/- 1.8 ml x kg(-1) x min(-1), respectively) were significantly lower than those in the NS, NG, and NGL groups (24.1 +/- 4.5, 24.5 +/- 3.1, and 22.2 +/- 2.1 ml x kg(-1) x min(-1), respectively). In addition, the MCR in the DG group was significantly higher than that in the DS and DGL groups, while no significant difference was detected among the NS, NG, and NGL groups. Furthermore, the amelioration of insulin resistance by GJG in diabetic rats was hampered by L-NMMA infusion. These results suggest that daily GJG administrations ameliorate insulin resistance in STZ-diabetic rats, and that the nitric oxide pathway may mediate the effect of GJG.

Metabolic syndrome (MetS) is an established concept. However, it is characterized by a number of different definitions as well as different cut-off points (COPs) for waist circumference (WC) and different modes for incorporating WC into the diagnostic criteria. Abdominal ultrasonography was performed in 2,333 subjects who also underwent comprehensive medical examinations between April and July 2006. The odds ratios for the number of MetS components were calculated by taking central obesity status into account and considering concurrent fatty liver as an independent variable. We compared the areas under the receiver operating characteristic (ROC) curves for fatty liver and MetS using several MetS criteria. Regardless of the WC criterion selected, we observed a strong linear trend for an association (trend P

The present study was conducted to examine alterations in plasma free amino acid concentrations induced by squat exercise and branched-chain amino acid (BCAA) supplementation in young, untrained female subjects. In the morning on the exercise session day, participants ingested drinks containing either BCAA (isoleucine:leucine:valine=1:2.3:1.2) or dextrin (placebo) at 0.1 g/kg body weight 15 min before a squat exercise session, which consisted of 7 sets of 20 squats, with 3 min intervals between sets. In the placebo trial, plasma BCAA concentrations were decreased subsequent to exercise, whereas they were significantly increased in the BCAA trial until 2 h after exercise. Marked changes in other free amino acids in response to squat exercise and BCAA supplementation were observed. In particular, plasma concentrations of methionine and aromatic amino acids were temporarily decreased in the BCAA trial, being significantly lower than those in the placebo trial. These results suggest that BCAA intake before exercise affects methionine and aromatic amino acid metabolism.

To clarify sex and seasonal variations of plasma antioxidant concentrations among middle-aged Japanese.We investigated sex and seasonal variations of plasma antioxidant concentrations, including retinol, alpha-tocopherol, and carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein and lycopene), in 55 middle-aged dietitians (46 women and 9 men) in Aichi Prefecture, Central Japan, who took no supplements from autumn 1996 to summer 1997. Reversed-phase high performance liquid chromatography was used to measure plasma antioxidant concentrations in overnight-fasting blood samples.Plasma levels of alpha-tocopherol, alpha-/beta-carotene, b-cryptoxanthin and lutein were significantly influenced by sex, being significantly higher for women than men in each corresponding season; retinol and lycopene, however, showed no such difference. For women, winter values of alpha-tocopherol, alpha-/beta-carotene, lutein and lycopene were significantly lower than corresponding summer values, and had reached their annual lowest. Retinol failed to show any significant seasonal variation, whereas the winter value of beta-cryptoxanthin had reached its annual highest. For men, beta-cryptoxanthin exhibited significant seasonal changes and was also highest in winter. Winter values of alpha-tocopherol, alpha-/beta-carotene and lycopene were lower compared with other seasons, but not statistically significant, probably due to the small sample size.The findings indicate that sex and seasonal variations of plasma antioxidant concentrations should be taken into account in nutritional epidemiologic studies.

Despite the lack of evidence for efficacy, an annual health examination has been advocated for the general population by the Japanese government. We conducted a cross-sectional survey to understand the attitudes of Japanese physicians toward the annual examinations.In October 2003, a questionnaire was mailed to 1971 physicians registered with Aichi Prefecture Medical Association as internists. The survey was designed to determine their opinions about the effectiveness of the periodic health examination and each of its components.The response rate was 37%. Eighty-five percent believed that a periodic health examination was effective. Nearly 80% believed that height and weight should be measured, and more than 90% supported blood pressure measurements. Nearly 70% supported a physical examination of chest and abdomen. About half believed that vision and hearing tests should be performed for all ages. More than 90% considered performing a variety of laboratory tests valuable. Three-quarters supported hepatitis B surface antigen and hepatitis C antibody determinations. Seventy to eighty percent valued the screening tests for lung, stomach, colon, breast and cervical cancer.Most Japanese primary care physicians believe that a comprehensive annual health examination as currently endorsed by public health authorities is effective.

Objectives To examine the effects of telephone-delivered lifestyle coaching on preventing the development of type 2 diabetes mellitus (T2DM) in participants with impaired fasting glucose (IFG). Design Cluster randomised trial. Setting 40 groups from 17 healthcare divisions in Japan: companies (31), communities (6) and mixed settings (3). Participants Participants aged 20–65 years with fasting plasma glucose (FPG) of 5.6–6.9 mmol/L were invited from the 17 healthcare divisions. Randomisation The groups were then randomly assigned to an intervention or a control arm by independent statisticians according to a computer-generated list. Intervention The intervention arm received a 1-year telephone-delivered intervention provided by three private lifestyle support centres (at different frequencies: low-frequency (3 times), middle-frequency (6 times) and high-frequency (10 times) support calls). The intervention and control arms both received self-help devices such as a weight scale and pedometer. Outcomes Participants were followed up using data from annual health check-ups and a questionnaire regarding lifestyle. The primary outcome was the development of T2DM defined as FPG ≥7.0 mmol/L, the diagnosis of diabetes, or use of an antidiabetic drug, confirmed by referring to medical cards. Results Of 14 473 screened individuals, participants were enrolled in either the intervention (n=1240) arm or control (n=1367) arm. Overall, the HR for the development of T2DM in the intervention arm during 5.5 years was 1.00 (95% CI 0.74 to 1.34). In the subanalysis, the HR was 0.59 (95% CI 0.42 to 0.83) in the subgroup that received phone calls the most frequently, compared with the control arm. A limitation of the study includes a lack of blinding. Conclusions High-frequency telephone-delivered lifestyle support could effectively prevent T2DM in participants with IFG in a primary healthcare setting, although low-frequency and middle-frequency phone calls did not. Trial registration number This trial has been registered with the University Hospital Medical Information Network (UMIN000000662).

We conducted a human study to examine the effects of BCAA supplementation on DOMS and muscle fatigue induced by exercise. 12 healthy female students (21-24 years old, BMI: 19.4 ± 0.5), who did not ...

BCAA catabolism in skeletal muscle is regulated by the branched-chain alpha-keto acid dehydrogenase (BCKDH) complex, located at the second step in the BCAA catabolic pathway. The activity of the BCKDH complex is regulated by a phosphorylation/dephosphorylation cycle. Almost all of BCKDH complex in skeletal muscle under normal and resting conditions is in an inactive/phosphorylated state, which may contribute to muscle protein synthesis and muscle growth. Exercise activates the muscle BCKDH complex, resulting in enhanced BCAA catabolism. Therefore, exercise may increase the BCAA requirement. It has been reported that BCAA supplementation before exercise attenuates the breakdown of muscle proteins during exercise in humans and that leucine strongly promotes protein synthesis in skeletal muscle in humans and rats, suggesting that a BCAA supplement may attenuate muscle damage induced by exercise and promote recovery from the damage. We have examined the effects of BCAA supplementation on delayed-onset muscle soreness (DOMS) and muscle fatigue induced by squat exercise in humans. The results obtained showed that BCAA supplementation prior to squat exercise decreased DOMS and muscle fatigue occurring for a few days after exercise. These findings suggest that BCAAs may be useful for muscle recovery following exercise.

We investigated the effects of progesterone and norethisterone on the apical-to-basolateral and basolateral-to-apical transports of cephalexin, a typical peptide transporter PEPT1 substrate, and the PEPT1 mRNA and protein expression levels, using the human intestinal cell line, Caco-2. Caco-2 cell monolayers (passages 50 to 60) were cultured on permeable membrane, plastic culture dish and culture tube. The Caco-2 cell monolayers were pretreated with progesterone and norethisterone (3, 10, 30 microM) for 24 h. After the pretreatment, the apical-to-basolateral and basolateral-to-apical transports of cephalexin were measured, and the densities of PEPT1 mRNA and protein expression levels were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot, respectively. The apical-to-basolateral transport of cephalexin was significantly decreased by the progesterone and norethisterone (30 microM each) pretreatments. By contrast, the basolateral-to-apical transport of cephalexin was not altered by the same pretreatments. The densities of PEPT1 mRNA and protein expressions were significantly decreased by progesterone and norethisterone (each at 3 and 10 microM) pretreatments compared with those of the non-treated Caco-2 cells. The results suggest that the transcription of the PEPT1 gene is downregulated by the progesterone and norethisterone pretreatments. Further studies are needed to clarify whether the inhibition of the PEPT1 gene transcription by progesterone pretreatment proceeds via sigma1-receptor or progesterone receptor.

We examined the effects of ingesting a non-sugar chocolate containing polydextrose and lactitol in place of sucrose and lactose on the concentrations of plasma glucose and serum insulin and triglyceride in humans. A regular chocolate was used as the control. A crossover study was employed, and the subjects each ingested 46 g of the control or non-sugar chocolate in the experiments. Alterations in the blood components were monitored for a period of 150 min after ingestion. The control chocolate elevated the concentrations of plasma glucose and serum insulin, with the peak occurring 30 min after ingestion, but the non-sugar chocolate had a very minor effect. The serum triglyceride concentration gradually increased after ingesting the control chocolate, but was only slightly elevated 150 min after ingesting the non-sugar chocolate. An animal study also showed an attenuated response of serum triglyceride to the administration of a fat emulsion containing polydextrose and lactitol, suggesting that the triglyceride transit through the gut was promoted by these compounds. These results suggest that, compared to regular chocolate, fat absorption in the gut was less after ingesting the non-sugar chocolate, presumably resulting in less effect on body fat deposition.

A cross-sectional study was conducted to clarify the associations of lifestyle factors (habitual exercise, alcohol intake and smoking habit) and plasma fatty acid (FA) concentrations as biomarkers of dietary FA intakes. We collected 7-d weighed diet records, lifestyle information and blood samples from 15 male and 79 female Japanese dietitians, and estimated dietary FA intakes and analyzed plasma FA concentrations. Plasma concentrations of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and (n-3) highly unsaturated FA (HUFA) derived from marine foods, but not linoleic and alpha-linolenic acid from plant origins, demonstrated positive correlations with dietary intakes (r = 0.303-0.602, P < 0.05) in both genders. Multiple linear regression analyses adjusted for age, BMI, total energy intake, fat (or respective FA) consumption and lifestyle factors showed that dietary intakes of EPA, DHA and (n-3) HUFA were positively associated with age in men (P < 0.05) and negatively associated with BMI in women [P < 0.01 for DHA and (n-3) HUFA]. The plasma concentrations of EPA, DHA and (n-3) HUFA in women were found to be positively associated with age and marine oil (or respective FA) intake (P < 0.01), and negatively associated with total energy intake [P < 0.05 for EPA and (n-3) HUFA]. Lifestyle factors were not associated with dietary FA intakes and plasma FA concentrations. These findings suggest that the plasma concentrations of EPA, DHA and (n-3) HUFA might be useful biomarkers for the assessment of relative FA intakes without considering associations with habitual exercise, alcohol intake and smoking habit.

Objective: To study seasonal variation in intake and plasma concentrations of fatty acids (FAs) in Japanese female dietitians. Subjects and methods: We assessed consumption of FAs based on four season 7 consecutive day weighed diet records from 71 Japanese female dietitians in 1996–1997. Using overnight fasting venous blood, plasma concentrations of FAs were analyzed by gas chromatography. Seasonal variation in consumption and plasma concentrations was examined by ANOVA for repeated values, followed by Tukey's multiple t-test. We calculated Spearman's partial rank correlation coefficients (CCs) between intake and plasma concentrations of FAs. Furthermore, we computed inter-seasonal Spearman's partial rank CCs for consumption and plasma concentrations of FAs. Results: Statistically significant seasonal differences were observed in consumption for most FAs, except for myristic acid, monounsaturated FAs, oleic acid, n-6 polyunsaturated FAs (PUFAs), linoleic acid, γ-linolenic acid, α-linolenic acid, PUFAs/saturated FAs, and n-6 PUFAs/n-3 PUFAs, and for most plasma concentrations, except for stearic acid, γ-linolenic acid, n-3 PUFAs, α-linolenic acid, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and n-3 highly unsaturated FAs (HUFAs). However, statistically significant Spearman's partial rank CCs between intake and plasma concentrations were observed for EPA, DHA, n-3 HUFAs, n-6 PUFAs/n-3 PUFAs and n-6 PUFAs/n-3 HUFAs for almost all seasons. Conclusions: Seasonal variation exists in consumption and plasma concentrations of FAs, so that this should be taken into account in epidemiological analyses, including case–control and cohort studies.

To identify the serious emotional impacts as socio-psychological problems encountered by patients with late adolescent onset type 1 diabetes since their disease onset.Thirteen patients (aged 21-35 years) with type 1 diabetes, onset age from 17 to 28, were interviewed. To extract their disturbing experiences from the content of the interviews, a qualitative analysis was carried out. We categorized their experiences as socio-psychological problems.Twenty-two items of socio-psychological problems which posed obstacles to the control of diabetes were found. Problems with particularly strong impacts included a fulminant crisis prior to hospitalization; surprise and shock of patients themselves and family members upon diagnosis; unacceptable feelings against insulin injections and diabetes; difficulty and anxiety over frequent and unexpected occurrences of hypoglycemia; noncompliance with diet therapy; stress of disclosing the disease to fiancés and their parents; no understanding of or knowledge about diabetes on the part of people around them; restricted range in occupation selection, travel and daily life; existence of stigma; no place for performing insulin injections; resistant or negative feelings against disclosing to others that they had diabetes; acceptance of the disease using various emotional coping behaviors.These results suggest that for patients with such problems we should seek a more effective sort of intervention to improve their quality of life (QOL).

We investigated the intestinal absorption and pharmacokinetics of cephalexin, as well as the intestinal H + /oligopeptide transporter PEPT1 mRNA and protein levels in type 1 and type 2 diabetic rats. Cephalexin disappearance from the duodenum loop was significantly lower in streptozotocin-induced type 1 diabetic rats and higher in hyperinsulinemic type 2 diabetic GK and Zucker-fa/fa (Zucker) rats, than in control rats. These results were speculated to be due to the enhancement of intestinal absorption of cephalexin in GK and Zucker rats. Intestinal PEPT1 mRNA levels were not significantly different between control and diabetic rats; however, the brush-border membrane vesicle PEPT1 protein levels were increased in GK and Zucker rats. After oral administration of cephalexin, plasma cephalexin concentrations and pharmacokinetic parameters, area under the concentration versus time curve from 0 to infinity, AUC 0→∞ , and maximum plasma concentration, C max , in GK and Zucker rats were markedly higher than in control rats. From these findings, it is considered that intestinal absorption of drugs mediated by PEPT1 may be enhanced in hyperinsulinemic type 2 diabetes mellitus rats.

Objective:To study daily, weekly, seasonal, within and between-individual variance in intake of selected nutrients and minimal days necessary for assessing true intake with a specified degree of error based on four season consecutive 7 day weighed diet records (WDRs).Subjects and Methods:We evaluated consumption of energy and 30 nutrients based on four season consecutive 7 day WDRs from 80 Japanese female dietitians in 1996-1997.We examined daily, weekly, seasonal, within- and between-individual variation in nutrient intake, relative contributions of their variances to total variance, and minimal days required to estimate a person's nutrient intake within 10% and 20% of their true mean with 95% confidence intervals.Results:The relative contributions of variation for all nutrients by person were larger than those by day, week and season.Within-individual variances were greater than the between-individual variances.The ratios of within- vs.between-individual variances thus ranged from 1.3 - 26.9.Minimal days necessary for estimating nutrient consumption per person within 10% (20%) of the true mean with 95% confidence intervals ranged from 10-35 (3-9) days for energy and major nutrients and 15-640 (4-160) days for micro-nutrients.Conclusions:The relative contributions of variability by person were largest for all nutrients, followed by those due to sequence of days, season and day of week.Within-individual variation was greater than between-individual variation.Minimal days necessary for ascertaining major nutrients were in general fewer than micro-nutrients. J Epidemiol, 2002;12:85-92

Objective: To examine reproducibility of assessed intake of foods and nutrients according to a semi-quantitative food frequency questionnaire (SQFFQ) in Japanese female dietitians. Subjects and Methods: An SQFFQ was self-administered to 106 (21 male and 85 female) Japanese dietitians in Aichi prefecture in autumn 1996 and the same questionnaire was repeated in autumn 1997. Reproducibility was evaluated in terms of consumption of 15 foods and energy and 30 macro- and micro-nutrients based on the SQFFQ from 84 Japanese female dietitians. Results: For intake of foods, Pearson's correlation coefficients (CCs) with log-transformation and energy adjustment (minimum - median - maximum) ranged from 0.35 (beverages) - 0.61 - 0.71 (dairy products). ANOVA intraclass correlation coefficients (ICCs) with log-transformation and energy adjustment ranged from 0.49 (beverages) - 0.74 - 0.82 (dairy products). Spearman's rank CCs with energy adjustment ranged from 0.43 (confectionery) - 0.57 - 0.76 (dairy products). Weighted kappa statistics with energy adjustment ranged from 0.34 (confectionery) - 0.49 - 0.71 (dairy products). For consumption of nutrients, Pearson's CCs with log-transformation and energy adjustment ranged from 0.23 (zinc) - 0.55 - 0.74 (insoluble dietary fiber). ANOVA ICCs with log-transformation and energy adjustment ranged from 0.37 (zinc) - 0.70 - 0.84 (insoluble dietary fiber). Spearman's rank CCs with energy adjustment ranged from 0.25 (zinc) - 0.56 - 0.74 (magnesium). Weighted kappa statistics with energy adjustment ranged from 0.25 (zinc) - 0.50 -0.68 (insoluble dietary fiber). Conclusions: Substantially high reproducibility of consumption of foods and nutrients was attained from an SQFFQ self-administered to Japanese female dietitians.

Objectives To determine the effects of a lifestyle intervention on the development of type 2 diabetes mellitus (T2DM) among participants with impaired glucose tolerance (IGT), in particular in the subgroup with baseline glycated hemoglobin (HbA1c) levels ≥5.7%, in primary healthcare settings. Design Randomized controlled trial. Setting 32 healthcare centers in Japan. Participants Participants with IGT, aged 30–60 years, were randomly assigned to either an intensive lifestyle intervention group (ILG) or a usual care group (UCG). Interventions During the initial 6 months, participants in the ILG received four group sessions on healthy lifestyles by public health providers. An individual session was further conducted biannually during the 3 years. Participants in the UCG received usual care such as one group session on healthy lifestyles. Outcome measures The primary endpoint was the development of T2DM based on an oral glucose tolerance test. Results The mean follow-up period was 2.3 years. The annual incidence of T2DM were 2.7 and 5.1/100 person-years of follow-up in the ILG (n=145) and UCG (n=149), respectively. The cumulative incidence of T2DM was significantly lower in the ILG than in the UCG among participants with HbA1c levels ≥5.7% (log-rank=3.52, p=0.06; Breslow=4.05, p=0.04; Tarone-Ware=3.79, p=0.05), while this was not found among participants with HbA1c levels Conclusions Intensive lifestyle intervention in primary healthcare setting is effective in preventing the development of T2DM in IGT participants with HbA1c levels ≥5.7%, relative to those with HbA1c levels Trial registration number UMIN000003136.

In order to confirm the efficacy of dexamethasone palmitate (DP)-low density lipoprotein (LDL) complex on experimental atherosclerosis in vivo, we examined whether DP-LDL complex could be effective for cholesterol ester accumulation in the aorta of atherogenic mice. Nonatherogenic and atherogenic mice were fed with normal and atherogenic diet for 14 weeks, respectively. Dexamethasone (DEX), lipid emulsion containing DP (DP-LE), or DP-LDL complex was intravenously injected once a week from 8 to 14 weeks. Cholesterol levels in serum and aorta in the atherogenic mice were significantly higher than those of nonatherogenic mice. Injection of DP-LDL complex significantly reduced cholesterol ester (CE) accumulation in the aorta of atherogenic mice. The reduction of CE accumulation in aorta treated with DP-LDL complexes was 10 and 100 times more potent than that with DP-LE and DEX, respectively. The radioactivity in the aorta of atherogenic mice treated with 3H-DP-LDL complex was significantly higher than that with 3H-DP-LE and 3H-DEX at 24 h after injection. Even 7 d after injection, a significant amount of radioactivity was present only in the aorta of atherogenic mice treated with DP-LDL complex. This result suggests that DP-LDL complex is selectively delivered to the atherogenic lesions in the aorta of atherogenic mice, and then DP released from the complex inhibits CE accumulation in the aortic intima. Therefore, DP-LDL complex may be a good drug-carrier in drug delivery system for atherosclerosis.

We used low density lipoprotein (LDL) as a carrier of site-specific delivery of drugs to atherosclerotic lesions, prepared a dexamethasone palmitate (DP)-LDL complex, and examined the effect of the DP-LDL complex on foam cell formation of macrophages in vitro. LDL was isolated from human plasma and the DP-LDL complex was prepared by incubation in the presence of Celite 545. The complex contained about 50 mol of DP in 1 mol of LDL. When macrophages were incubated with LDL for 48 h, cholesterol ester was accumulated in the macrophages, indicating foam cell formation. This accumulation of cholesterol ester was significantly inhibited by incubation with the DP-LDL complex. The potency of the DP-LDL complex was similar to that of dexamethasone alone. The DP-LDL complex also significantly attenuated the accumulation of cholesterol ester induced by incubation with LDL prior to the incubation with the DP-LDL complex. These findings indicated that the DP-LDL complex showed similar characteristics to LDL, and the DP-LDL complex inhibited the foam cell formation of macrophages in in vitro experiments. This DP-LDL complex has a possibility as a drug-carrier complex for use in atherosclerosis.