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Objective Ghrelin is a novel gastric peptide identified in 1999 as a ‘hunger hormone’. Plasma ghrelin level is decreased in human obesity. Factors associated with ghrelin have been mainly investigated in western countries where the prevalence of obesity is high. The aim of this study is to examine factors associated with plasma ghrelin in a Japanese general population where obesity is not so common. Methods Fasting ghrelin levels were measured by ELISA in 638 subjects in 2005–2007. We measured body mass index (BMI), waist circumference and blood pressure. Blood was drawn in the morning after a 12-h fast for determinations of ghrelin, lipid, glucose (FPG), insulin, estimated glomerular filtration rate (eGFR) and uric acid levels. Univariate and multiple stepwise regression analyses were performed to find out factors associated with ghrelin. Results In our population, the mean BMI was 23·8 kg/m2, indicating a nonobese population. Results of univariate analysis showed that age (P

Gymnastatins F (1) and Q (2) were successfully synthesized using the tandem Michael and aldol reaction of the corresponding spirodienones with hemiacetal functions. Inspection of the optical purities of the substrates suggested that undesired racemization does not proceed during the tandem reaction. Results of theoretical calculations agreed with the ratio of the reaction outcome.

Ceriporiopsis subvermispora is a selective white-rot fungus that secretes alk(en)ylitaconic acids named ceriporic acids, known as ion redox silencers. In this study, we analysed a series of extracellular lipid-related metabolites produced by the fungus and found that a wide variety of ceriporic acids and fatty acids, including those with odd-numbered and very long-chains, were produced in wood meal cultures. Two new ceriporic acids, (R)-3-[(Z)-tetradec-7-enyl]-itaconic acid (ceriporic acid E) and (R)-3-[(Z)-tetradec-5-enyl]-itaconic acid (ceriporic acid F), were for the first time identified by dimethyl disulfide derivatisation, followed by GC/EI-MS, 1H and homonuclear J-resolved 2D NMR and feeding experiments with [13C-U] glucose coupled with multiple-stage mass spectrometry. In separation by GC and LC, a reversed correlation of elution sequences between a nonpolar GC column and an ODS-LC column for cis and trans isomers of ω7 and ω9 lipids was found, and the elution of new metabolites was in accordance with the prevailing theory. The biosynthetic precursors of ceriporic acid F can be proposed as oxaloacetate and 16:1Δ7-CoA. Because fatty acids biosynthesised from 16:1Δ7-CoA have been reported for only a limited number of organisms, the highly individual structure of ceriporic acid F is highlighted.

Ghrelin is a novel gastric peptide identified in 1999 as a 'hunger hormone'. Plasma ghrelin level is decreased in human obesity. Factors associated with ghrelin have been mainly investigated in western countries where the prevalence of obesity is high. The aim of this study is to examine factors associated with plasma ghrelin in a Japanese general population where obesity is not so common.Fasting ghrelin levels were measured by ELISA in 638 subjects in 2005-2007. We measured body mass index (BMI), waist circumference and blood pressure. Blood was drawn in the morning after a 12-h fast for determinations of ghrelin, lipid, glucose (FPG), insulin, estimated glomerular filtration rate (eGFR) and uric acid levels. Univariate and multiple stepwise regression analyses were performed to find out factors associated with ghrelin.In our population, the mean BMI was 23·8 kg/m(2) , indicating a nonobese population. Results of univariate analysis showed that age (P0·001), BMI (P0·001), waist (P0·001), triglycerides (P0·01), FPG (P0·01), insulin (P0·001) and uric acid (P0·05) were inversely associated with ghrelin. High-density lipoprotein (HDL) cholesterol (P0·001) and eGFR (P0·05) were positively associated with ghrelin. Men had lower ghrelin levels than women (P0·001). Results of the multiple stepwise regression analysis revealed that age (P0·001; inversely), female gender (P0·001), insulin (P0·001; inversely), HDL cholesterol (P=0·005), BMI (P=0·01; inversely) and uric acid (P=0·045; inversely) were significantly and independently associated with ghrelin.The present study demonstrated that age and gender affected plasma ghrelin levels more than BMI. This may well be because of the low prevalence of overweight in our population.

High mobility group box 1 (HMGB1), a nonhistone chromatin-associated protein, is implicated as a mediator of both infectious and non-infectious inflammatory conditions. Clinical research on this protein in humans just has begun; serum HMGB1 was reported to be elevated in a small number of critically ill patients suffering from sepsis. However, the kinetics, distribution and factors associated with circulating HMGB1 are unknown in a general population. In this study, we examined these issues in a large population of healthy subjects. Fasting blood samples were obtained from 626 subjects (237 males and 389 females). HMGB1 levels showed a skewed distribution with a mean of 1.65 ± 0.04 ng/ml. Multiple stepwise regression analyses found that white blood cell (WBC) counts (P = .016) and the soluble form of receptor for advanced glycation end products (sRAGE; P < .001, inversely), which is also known to be a receptor for HMGB1, were independently associated with HMGB1 levels. We demonstrated for the first time that circulating HMGB1 levels were inversely associated with sRAGE levels in a general population. Because RAGE is involved in HMGB1 signaling, our present study suggests that sRAGE may capture and eliminate circulating HMGB1 in humans.

Ceriporic acids are a class of alk(en)ylitaconic acids produced by a selective lignin-degrading fungus, Ceriporiopsis subvermispora. The unique function of alkylitaconic acid is the redox silencing of the Fenton reaction system by inhibiting reduction of Fe3+. Ceriporic acids have an asymmetric centre at carbon-3, but absolute configuration has not been determined. We have isolated a series of ceriporic acids from the cultures of C. subvermispora, and measured their NMR spectra using a chiral shift reagent. In comparison with NMR spectra of (R)-(−)- and (S)-(+)-methylsuccinic acid and those of natural and chemically synthesized racemic mixtures of ceriporic acids, we have determined the absolute configuration of ceriporic acids as (R)-3-tetradecylitaconic acid (ceriporic acid A), (R)-3-hexadecylitaconic acid (ceriporic acid B) and (R,Z)-2-(hexadec-7-enyl)-3-itaconic acid (ceriporic acid C). We herein discuss their stereoselective biosynthetic pathway and the structural diversity of fungal secondary metabolites.

We developed a simple and sensitive assay for the 8-methyl ether of xanthurenic acid in serum by high-performance liquid chromatography with fluorescence detection (excitation at 340 nm, emission at 450 nm). The compound under study in serum samples was extracted with Sep-Pak C18 cartridge and the extract was applied to an octadecylsilane-bonded column (Nucleosil 5C18, 150 x 4 mm I.D.). The mobile phase used was a mixture of 0.05 M sodium acetate buffer (pH 6.0), containing 5 mM sodium 1-octanesulfonate and 0.1 mM Na2EDTA, and acetonitrile (93:7, v/v). The 8-methyl ether of xanthurenic acid from serum samples was sufficiently separated to be clearly distinguishable. The quantification limit was 2 x 10(-14) mol, which was sensitive enough to detect 8-methyl ether of xanthurenic acid in serum from normal subjects. The method was applied to samples from patients with deficiency in tryptophan metabolism, xanthurenic acid/3-hydroxy kynurenineuria and showed a striking elevation in serum 8-methyl ether of xanthurenic acid.

We developed a simple and sensitive assay for the urinary 8-methyl ether of xanthurenic acid (XA-OMe) by high-performance liquid chromatography with fluorescence detection (excitation at 340 nm; emission at 450 nm). Urine samples were diluted with 0.03 M potassium phosphate buffer (pH 6.0) and applied to an octadecylsilane-bonded column (Nucleosil 5C 18 , 150 × 4 mm I.D.). The mobile phase used was a mixture of this same buffer and acetonitrile (1000:140, v/v). Both direct injection of urine and solvent extraction prior to HPLC were tested and showed a good correlation and sensitivity, although the peak of XA-OMe was occasionaly less distinguishable from close peaks in urine from normal controls by the direct injection method. The quantification limit was 5 · 10 −14 mol which was sensitive enough to detect XA-OMe in urine from normal subjects. The method was applied to samples from patients with a deficiency in tryptophan catabolism, xanthurenic acid/3-hydroxykynurenine-uria and showed a striking elevation in urinary XA-OMe excretion.

ratio, 1.9 (95%CI: 1.09 3.33), 2.04 (956%CI:1.01 4.15) and 2.98 (95%CI: 1.36 6.55) respectively. This association of the ECG abnormalities with coronary death was independent of age, body mass index, systolic blood pressure, serum cholesterol level, blood sugar level, smoking and drinking. Conclusion: ST-segment depression, T-wave abnormality and ST-T abnormality in ECG are associated with significantly higher risk for CVD and CHD mortality in women.

Purpose: Cyanotic congenital heart disease (CCHD) induces secondary erythrocytosis and CCHD is thought to be one of the risk factors for cholelithiasis, but the frequency of cholelithiasis and/or gallstones in patients with CCHD is unknown. Materials and Methods: A hundred and two patients with CHD were divided into 4 groups: group A 22 CCHD without reparative surgery or with palliative surgery; group B 35 CCHD after repair who were eliminated cyanosis; group C 17 acyanotic CHD without repair; and group D 28 acyanotic CHD after repair. Gallstones were studied by abdominal ultrasonography or CT in each patient. For analysis of risk factors, patient records regarding cyanotic period, family history and past abdominal surgery were reviewed and blood pressures, lipid profiles, blood sugar and liver enzyme were evaluated. Results: Cholecystectomy due to cholelithiasis was underwent in 7 of 279 CCHD patients (2.5%). In group A, 7 patients (31%) underwent cholecystectomy, and 3 patients (18%) have gallstones. In group B, 11 patients (37%) had gallstones. In group C, nobody had gallstones, and in group D 2 patients (7%) had gallstones. SPO2 was significantly lower and red blood cell, hemoglobin, hematocrit, HbA1C and total bilirubin levels were significantly higher in group A (p 19.8, 95%CI 1.30 300.1). Conclusions: The incidence of cholelithiasis and gallstones is significantly high in CCHD regardless of repair. The most important factor related to gallstones was having CCHD even after desaturation was improved by surgical repair.

cholesterol, triglyceride (TG), and high density lipoprotein (HDL) cholesterol at baseline and four weeks after treatment with the statin. Results: The total cholesterol and LDL levels in both groups were significantly decreased four weeks later, and HDL level was significantly increased in both groups, but not TG level in vytorin group. In addition, the change of LDL cholesterol in vytorin group was significantly higher than it in lipitor (52.4% vs 44.1% respectively p < 0.05). The central PWV (cfPWV) and peripheral PWV (cfPWV) in lipitor group was significantly decreased compared with those in vytorin group (p < 0.05). Conclusions: Although co-administration of simvastatin and ezetimibe might show much more lipid lowering effect compared with atorvastatin, only atorvastatin might show pleiotrophic effect for short-term treatment in hypercholesterolemia.