Search

Preliminary studies have shown that a lithogenic diet (LG), which contains cholesterol and cholic acid, induces gallstones and hepatic lipid accumulation (HLA), and reduction of blood triglyceride in mice. We hypothesized that an LG induces HLA by diminishing hepatic triglyceride excretion; however, there is no clear understanding of the mechanism of LG-induced HLA. This study aimed to investigate transcript expression related to the synthesis, expenditure, and efflux of hepatic triglyceride, in mice fed an LG for 4 weeks. Results showed lower plasma concentrations of triglyceride in the LG group than in the control group, but no symptoms of hepatic injury were observed. Hepatic mRNA expressions of patatin-like phospholipase domain containing 3 (Pnpla3), microsomal triglyceride transfer protein (Mttp), and acyl-CoA oxidase 1 (Acox1) were also reduced in the LG group. Deoxycholic acid and lithocholic acid promoted intracellular lipid accumulation, reduced triglyceride concentration in media, and suppressed expression of PNPLA3 and MTTP in HepG2 human hepatoma cells. These findings suggest that deoxycholic acid and lithocholic acid promote HLA by inhibiting the expression of PNPLA3, ACOX1, and MTTP that are involved in lipid metabolism.

Left atrial (LA) dysfunction is known to be a more sensitive prognostic marker than left ventricular (LV) dysfunction in patients with heart failure (HF). Persistent LA overload increases LA stiffness which impairs LA relaxation. The aim of this study was to investigate whether LA filling time is associated with clinical outcomes in patients with HF. Two-dimensional speckle tracking echocardiography (2DSTE) was performed at discharge, to measure LA and LV strain in 179 HF patients admitted to our hospital. The LA filling time index (LAFTI) was defined as the time from onset of the R wave to the peak LA systolic strain divided by the R-R interval. All patients were prospectively followed with cardiac events including cardiac death and rehospitalization for HF. There were 64 cardiac events during a median follow-up period of 451 days. There were no significant differences in heart rate, severity of HF at discharge, etiology of HF, severity of mitral regurgitation, or LV global longitudinal strain between the cardiac event group and no cardiac event group. Patients with cardiac events had significantly higher levels of brain natriuretic peptide (BNP), ratio of the E wave to e' (E/e'), left atrial volume index (LAVI), and lower LAFTI than those without. Kaplan-Meier analysis showed that patients with lower LAFTI were associated with higher cardiac event rates. Multivariate Cox hazard analysis showed that LAFTI was independently associated with the cardiac events after adjustment for confounding factors. In conclusion, LAFTI is a feasible predictor for cardiac events in patients with HF.

Amenamevir (ASP2151), a herpesvirus helicase-primase inhibitor, is currently used for the treatment of herpes zoster in Japan. Amenamevir is mainly metabolized in the liver, and urinary excretion of amenamevir is approximately 10% in healthy adults. The increase of systemic exposure in non-dialysis patients with severe renal impairment was much less than that associated with nucleoside antiviral agents. The aim of this study was to evaluate the pharmacokinetics and dialyzability of a single oral dose (400 mg) of amenamevir in hemodialysis patients.This was a single-arm, open-label, multicenter clinical pharmacology study. Nine patients aged 20-80 years with end-stage kidney disease and undergoing maintenance hemodialysis three times weekly were enrolled. Pharmacokinetics and dialyzability were investigated by serial collection of blood samples until 48 h post-dose during the study.The maximum plasma concentration and time to reach maximum plasma concentration during 24 h post-dose were 1585 ng/mL and 6.2 h, respectively. The area under the plasma concentration-time curve (AUC) from time zero to 24 h was 23,890 ng h/mL. The median terminal elimination half-life within 24 h before, during, and after hemodialysis was 14.7, 15.2, and 12.4 h, respectively. The AUC in hemodialysis patients was approximately double that in healthy adults. This increase in AUC was much less than that reported in nucleoside antiviral agents. The hemodialysis clearance, elimination fraction percentage, and amount of amenamevir removed were 37.8 mL/min, 28.1%, and 132.0 μg, respectively. The amount of amenamevir removed by hemodialysis was minimal. None of the hemodialysis parameters were associated with serum albumin. This study revealed no clinically relevant safety concerns.There were no clinically relevant safety concerns when 400 mg of amenamevir was administered as a single dose to hemodialysis patients without dose adjustment and/or modification of the dosing schedule.JapicCTI-184242.

Introduction Amenamevir (ASP2151), a herpesvirus helicase-primase inhibitor, is currently used for the treatment of herpes zoster in Japan. Amenamevir is mainly metabolized in the liver, and urinary excretion of amenamevir is approximately 10% in healthy adults. The increase of systemic exposure in non-dialysis patients with severe renal impairment was much less than that associated with nucleoside antiviral agents. The aim of this study was to evaluate the pharmacokinetics and dialyzability of a single oral dose (400 mg) of amenamevir in hemodialysis patients. Methods This was a single-arm, open-label, multicenter clinical pharmacology study. Nine patients aged 20–80 years with end-stage kidney disease and undergoing maintenance hemodialysis three times weekly were enrolled. Pharmacokinetics and dialyzability were investigated by serial collection of blood samples until 48 h post-dose during the study. Results The maximum plasma concentration and time to reach maximum plasma concentration during 24 h post-dose were 1585 ng/mL and 6.2 h, respectively. The area under the plasma concentration–time curve (AUC) from time zero to 24 h was 23,890 ng h/mL. The median terminal elimination half-life within 24 h before, during, and after hemodialysis was 14.7, 15.2, and 12.4 h, respectively. The AUC in hemodialysis patients was approximately double that in healthy adults. This increase in AUC was much less than that reported in nucleoside antiviral agents. The hemodialysis clearance, elimination fraction percentage, and amount of amenamevir removed were 37.8 mL/min, 28.1%, and 132.0 μg, respectively. The amount of amenamevir removed by hemodialysis was minimal. None of the hemodialysis parameters were associated with serum albumin. This study revealed no clinically relevant safety concerns. Conclusion There were no clinically relevant safety concerns when 400 mg of amenamevir was administered as a single dose to hemodialysis patients without dose adjustment and/or modification of the dosing schedule. Trial Registration JapicCTI-184242. Electronic Supplementary Material The online version of this article (10.1007/s12325-020-01375-1) contains supplementary material, which is available to authorized users.

The incidence of acute coronary obstruction during transcatheter aortic valve implantation (TAVI) is low (1.0%); however, it is associated with high mortality. An 83-year-old female with a history of chest pain and syncope was diagnosed with severe aortic stenosis. Computed tomography showed severely calcified aortic leaflets with a low left coronary ostial height of 7.8 mm, which indicates a high risk of coronary obstruction. TAVI was performed using the right femoral artery approach under general anesthesia. To prevent coronary obstruction and minimize coronary flow obstruction, coronary protection of the left main tract (LMT) via the left radial artery was established with a perfusion balloon. We crossed a 23 mm Sapien 3 transcatheter heart valve and settled it at an appropriate position on the aortic valve. After inflation of the perfusion balloon at the LMT, we started rapid ventricular pacing, and deployed the Sapien 3 using the KBI technique. Hemodynamics were stable and aortography showed excellent coronary flow with no stenosis of the LMT ostium. This strategy may serve as a useful method to prevent coronary obstruction and minimize coronary ischemia.

The lycopene content of tomatoes is important because of its effects on vital physiological functions such as improvement of glucose tolerance and non-alcoholic fatty liver disease. To investigate the influence of the lycopene content of tomatoes on glucose tolerance and hepatic lipid content, homogenates of lycopene-rich (LR) or lycopene-free negative control (NC) tomato varieties were administrated to normal rats for 4 weeks. At the end of the experiment, an oral glucose tolerance test (OGTT) was performed. Rats were fed once and then dissected. According to the OGTT results, plasma glucose levels in the LR group were 10% and 9% lower at 15 min and 30 min, respectively, than those in the NC group, whereas plasma insulin levels did not differ between the groups at either time point. Upon dissection, plasma leptin levels in the LR group were higher than those in the NC group, while plasma adiponectin levels did not differ between groups. With the exception of retinol palmitate, no carotenoids were detected in the liver by HPLC analysis. Hepatic retinol palmitate levels and hepatic triacyl glyceride levels did not differ between the groups. We concluded that in normal rats, a lycopene-rich tomato variety improved glucose tolerance via an increase in plasma leptin levels that enhanced insulin sensitivity but did not affect carotenoid accumulation or lipid metabolism.

High-fructose diets are associated with not only fat accumulation in liver but also blood adipokine levels. Some studies have shown the involvement of humoral factors in the regulation of adipokines. However, the role of the vagus nerve in expression of adipokines is not fully understood. We attempted to investigate the involvement of the hepatic branch of the vagus nerve (HBVN) in the regulation of plasma adipokine levels in rats fed a high-fructose (HFr) diet. Rats underwent hepatic vagotomy (Vx) or sham operation; thereafter, they were fed a control diet (CT) or HFr diet for 6 weeks. At the sixth week, the oral glucose tolerance test (OGTT) was performed. In the sham-operated group, plasma leptin and adiponectin levels were significantly lower in the HFr group than those in the control group. In contrast, in the Vx group, there was no difference in the respective adipokine levels of the two dietary groups. In OGTT, plasma leptin levels were significantly correlated to the area under the curve (AUC) of plasma insulin levels and insulin levels at some points. Further, the ratio of plasma leptin levels to plasma adiponectin levels was correlated with the AUC of plasma insulin levels. However, the plasma adiponectin level itself did not correlate with plasma insulin levels and insulin AUC. Thus, we showed that HBVN played a key role in down-regulating plasma leptin and adiponectin levels in HFr-fed rats.

Pru p 1 and Pru p 3 are proteins found in peach (Prunus persica (L.) Batsch), and they are members of the pathogenesis-related protein 10 (PR-10) and non-specific lipid transfer protein (nsLTP) families, respectively. They are the main allergens of peach. In this paper, we describe a quantitative method for these proteins based on protein absolute quantification with liquid chromatography–tandem mass spectrometry, and LVASPSGGSIIK[13C6,15N2] and ISASTNC[CAM]ATVK[13C6,15N2] (C[CAM]: carbamidomethyl-modified C), stable isotope-labelled internal standard peptides. We show that this method exhibits linearity with r2 > 0.97 in a dose range of 3.1–200 fmol/μL for LVASPSGGSIIK[13C6,15N2] and 13–200 fmol/μL for ISASTNC[CAM]ATVK[13C6,15N2]), and overall coefficients of variation for multiple tests of 11.6–30.1%. This approach is therefore helpful for screening and breeding low allergenic peach cultivars.

Objectives: : Compared with vancomycin trough concentration (Cmin)-guided dosing, area under the concentration–time curve (AUC)-guided dosing is associated with decreased acute kidney injury (AKI). However, whether Cmin-guided or AUC-guided dosing should be used in patients other than those with serious MRSA infections remains uncertain. The purposes of this multicentre study were to identify risk factors for early- and late-phase vancomycin-induced AKI and to identify candidates for AUC-guided dosing, rather than Cmin-guided dosing, who require a more accurate dose titration to reduce the AKI risk. Methods: : A multivariate logistic regression analysis was applied to identify risk factors for AKI. Additionally, the cut‑off day for AKI onset, cut-off Cmin for AKI, safe Cmin for reduced AKI risk and probability of AKI were calculated. Results: : In total, 8.4% (159/1882) of patients developed AKI. AKI occurred within the first 7 days of therapy (early phase) in the vast majority of patients. Significant risk factors for AKI during the early phase were identified as Cmin > 20 mg/L, ICU stay, concurrent diuretic or piperacillin/tazobactam use, and pre-existing renal dysfunction. A temporarily elevated Cmin (>15–20 mg/L) was not associated with a greater risk of AKI. In patients with risk factors, the cut-off Cmin for AKI and the estimated safe Cmin for reduced AKI risk were 18.8–21.0 mg/L and

β-Conglycinin, a major protein in soybeans, shows improvement effect of lipid metabolism. Moreover, this protein influences the processing properties of soybeans. β-Conglycinin is a hetero-trimer constituted by α, α′, and β subunits. In this work, a method for the selective quantification of these subunits was developed by means of protein absolute quantification (AQUA) technology using liquid chromatography/tandem mass spectrometry with the stable isotope-labelled internal standard peptides LQSGDALR[13C6,15N4], NILEASYDTK[13C6,15N2], and NPIYSNNFGK[13C6,15N2]. This method exhibited linear relationships (r2 > 0.99) in the concentration range of 1.2–300 fmol/μL for LQSGDALR[13C6,15N4] and NILEASYDTK[13C6,15N2], and of 4.7–300 fmol/μL for NPIYSNNFGK[13C6,15N2]. As a result, the content of these subunits in β-conglycinin-rich and both α and α′ subunit-deficient soybean cultivars was successfully determined. This quantitative assay is promising for the evaluation of the food functionality and processing properties of soybeans.

ATP binding cassette transporters, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), are expressed in skin, but their involvement in transdermal absorption of clinically used drugs remains unknown. Here, we examined their role in transdermal absorption of corticosteroids. Skin and plasma concentrations of dexamethasone after dermal application were reduced in P-gp and BCRP triple-knockout (Mdr1a/1b/Bcrp−/−) mice. The skin concentration in Mdr1a/1b/Bcrp−/− mice was reduced in the dermis, but not in the epidermis, indicating that functional expression of these transporters in skin is compartmentalized. Involvement of these transporters in dermal transport of dexamethasone was also supported by the observation of a higher epidermal concentration in Mdr1a/1b/Bcrp−/− than wild-type mice during intravenous infusion. Transdermal absorption after dermal application of prednisolone, but not methylprednisolone or ethinyl estradiol, was also lower in Mdr1a/1b/Bcrp−/− than in wild-type mice. Transport studies in epithelial cell lines transfected with P-gp or BCRP showed that dexamethasone and prednisolone are substrates of P-gp, but are minimally transported by BCRP. Thus, our findings suggest that P-gp is involved in transdermal absorption of at least some corticosteroids in vivo. P-gp might be available as a target for inhibition in order to deliver topically applied drugs and cosmetics in a manner that minimizes systemic exposure. © 2017 Elsevier B.V., Embargo Period 12 months

Background It was reported that left atrial (LA) remodeling is occurred in patients with heart failure (HF), and increased LA volume index (LAVI) is a feasible predictor for poor prognosis of HF. It was reported that LA remodeling is associated with LA appendage (LAA) dysfunction. We previously reported that LAA wall motion velocity (LAWV) obtained by transthoracic echocardiography (TTE) can noninvasively evaluate LAA dysfunction. However, it remains to be determined whether LAWV is useful for predicting poor prognosis in patients with HF. Purpose We investigated whether LAA dysfunction assessed by LAWV is associated with poor prognosis in patients with HF. Methods We performed TTE at discharge in 217 consecutive patients who hospitalized for HF (126 males, 71±13 years) and prospectively followed them up. LAWV was measured using Doppler tissue imaging at the LAA tip from the parasternal short-axis view on TTE imaging. Results There were 86 patients with cardiac events including 14 cardiac deaths and 72 rehospitalizations for HF during a median follow-up period of 404 days (interquartile range 168–748 days). LAWV was significantly lower in patients with cardiac events than in those without. LAWV was significantly decreased with advancing left ventricular diastolic dysfunction grade. Kaplan-Meier analysis demonstrated that significantly higher cardiac event rate was observed in patients with low LAWV (log-rank test, P=0.004). Cox multivariate hazard analysis revealed that LAWV was an independent predictor for cardiac events after adjusting for confounding factors (hazard ratio 0.57, 95% confidence interval 0.40–0.82, P Figure 1 Conclusion LAWV may be a feasible parameter for predicting cardiac prognosis in patients with HF.

P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are xenobiotic transporters which pump out variety types of compounds, but information on their interaction with endogenous substrates in the skin is limited. The purpose of the present study was to clarify possible association of these transporters in dermal accumulation of inflammatory mediators. Dermatitis model was constructed by repeated topical application of oxazolone in wild-type, and P-gp and BCRP gene triple knockout (Mdr1a/1b/Bcrp−/−) mice to observe difference in phenotype. Target metabolome analysis of 583 metabolites was performed using skin and plasma. Dermatitis and scratching behavior in dermatitis model of Mdr1a/1b/Bcrp−/− mice were more severe than wild-type mice, suggesting protective roles of these transporters. This hypothesis was supported by the metabolome analysis which revealed that concentration of histamine and other dermatitis-associated metabolites like urate and serotonin in the dermatitis skin, but not normal skin, of Mdr1a/1b/Bcrp−/− mice was higher than that of wild-type mice. Gene expression of P-gp and BCRP was reduced in oxazolone-treated skin and the skin of patients with atopic dermatitis or psoriasis. These results suggest possible association of these efflux transporters with dermal inflammatory mediators, and such association could be observed in the dermatitis skin.

Flavonoids purportedly have a role in improving lipid metabolism. In our preliminary study, highly concentrated flavonoid metabolites appeared in bile juice in rats, which also contains various lipids. Biliary flavonoid metabolites generally have amphiphilic properties, may influence lipid solubility, and possibly contribute to the improvement of dyslipidemia. However, the influence of biliary flavonoid metabolites on the biliary lipid profile is not well known. Therefore, we hypothesized that the amphiphilic property of biliary flavonoid metabolites alters biliary lipid profiles. To estimate the influence of flavonoids on the biliary lipid profile, we laparotomized rats under anesthesia, intraduodenally injected them with cyanidin-3-glucoside chloride (C3G) or quercetin, and analyzed their biliary metabolite concentrations for 2 hours. Concentrations of C3G and quercetin metabolites peaked at 30 minutes after the injection; those of quercetin were 6 to 10 times higher than those of C3G throughout the sampling period up to 2 hours. Biliary triglyceride (TG) concentrations were higher in the C3G group at 30 and 45 minutes; biliary cholesterol and phospholipid concentrations were lower in the quercetin group at 30 minutes than those in the control group. Hepatic TG content after the 2-hour sampling was lower in the C3G group than in the control group. These results suggest that C3G, but not quercetin, may transiently promote TG excretion into bile, with a reduction in hepatic TG content. This C3G effect may be involved in improvement of TG metabolism.

Transdermal or as also referred to cutaneous or skin microdialysis is a sampling and monitoring technique for testing drug concentrations in the extracellular fluid of the skin, has been developed during the last decades. Its early applications aimed to determine the transdermal drug delivery by pharmacokinetic and/or toxicokinetic characterization of drug penetration through the skin. Being a minimally invasive technique its employment in human volunteers run in parallel with the preclinical animal experiments. With the discovery of topical drug absorption enhancers (both active and passive) it became more and more important to study the dermal absorption of the unbound, pharmacologically active form of certain molecules in vivo in the living tissue. This review gives an overview about iontophoretic drug delivery studies and also on the assessment of dermal drug formulations followed and evaluated by transdermal microdialysis. The new foci of the application of skin microdialysis techniques are the drug transporter interaction studies on the cutaneous barrier and the disease-related biomarker studies in dermatological research. At the final part of this review complementary technologies are presented and compared with transdermal microdialysis. In summary, transdermal microdialysis technique is a traditional in vivo method for investigating the alterations of the biochemical milieu in the skin. It is an important element of the toolbox of preclinical and clinical dermal pharmacokinetic/pharmacodynamic assays. The advancement in dermatopharmacology and pharmaceutical formulation technology, disease biomarker studies and also the development of drug–drug, drug–transporter interaction research open new horizons both for the experimental and clinical applications of this assay.

β-Conglycinin, one of the main proteins found in soybeans, improves lipid metabolism and influences the processing properties of soybeans. Recently, we developed a method to determine β-conglycinin content quantitatively via the use of liquid chromatography/tandem mass spectrometry (LC/MS/MS) and stable isotope-labelled internal standard (SIIS) peptides. In this study, we compared the efficacy of different protein extraction methods for β-conglycinin by comparing the yields of β-conglycinin extracted by each of these methods, using the developed LC/MS/MS analysis. The method using trichloroacetic acid (TCA) and acetone for protein extraction (TCA/acetone method) produced the highest yields of β-conglycinin from the soybean cultivars ‘Enrei’, ‘Fukuyutaka’, ‘Ryuho’, and ‘Satonohohoemi’, all of which were evaluated by LC/MS/MS analysis. We then investigated the applicability of each of these protein extraction methods to kinako (Japanese name, roasted soybean flour), natto (fermented soybeans), soybean milk, and tofu (soybean curd) to obtain information about these soybean products. The TCA/acetone method is judged to be an appropriate method of protein extraction for these products as well as for raw soybeans.

Prolonged total atrial conduction time is caused by atrial remodeling. Left atrial remodeling is associated with poor outcome in patients with heart failure (HF). This study aimed to investigate whether prolonged total atrial conduction time predicts poor prognosis in patients with HF. We performed transthoracic echocardiography in 100 patients (65 men; mean age 68 ± 13 years) who were hospitalized for HF. Total atrial conduction time was defined as the duration from P wave onset on electrocardiography to peak A′ wave on tissue Doppler imaging (TDI) echocardiography (PA-TDI duration). There were 37 cardiac events (37%) during a median follow-up period of 414 days. The PATDI duration was significantly longer in patients with cardiac events than in those without (150 ± 18 ms vs 133 ± 19 ms; P

Since our work on corrin synthesis was intended to be a model study for the construction of the ligand system of vitamin B12 (cf. Part I of this series), the choice of an A/D component that would contain an angular Me group at the junction between rings A and D seemed crucial. Such a Me group was expected to direct (through its steric impact) a regioselective functionalization of the two carbonyl groups of a corresponding dilactam structure that appeared to be the obvious type of intermediate in the construction of an A/D component. The target A/D structure envisaged originally was the methyl ester derivative 1a (cf. Fig. 1). However, observations in an early phase of our work made it clear that we better aim at the nitrile derivative 1b, instead of the corresponding methyl ester. Nitrile 1b was in fact synthesized, but not used as A/D component, because, on the way to its synthesis, the opportunity emerged to prepare structure 2. As A/D component, 2 differs from 1b by the isomeric positioning of the angular Me group, it could be prepared regio- as well as stereoselectively and, therefore, much more efficiently than 1b.

Oxidative stress reduces cell viability and contributes to disease processes. Flavonoids including anthocyanins and proanthocyanidins reportedly induce intracellular antioxidant defence systems. Thus, in this study, we examined the antioxidant effects of a commercial extract from black soybean seed coats (BE), which are rich in anthocyanin and proanthocyanidin, and investigated the associated intracellular mechanisms in HepG2 cells. HepG2 cells treated with hydrogen peroxide (HPO) showed 60% viability, whereas pretreatment with BE-containing media for 2 h ameliorated HPO-mediated cell death by up to 90%. Pretreatment with BE for 2 h partially blocked HPO-mediated activation of ERK in HepG2 cells, and that for 1 h led to a 20% increase in intracellular total protein phosphatase (PP) activity, which is known to deactivate protein kinases. These results indicate that BE prevents HPO-mediated cell damage by inhibiting ERK signalling, potentially via PPs.

The effect of purple potato flake on cholesterol metabolism was investigated in rats fed a high-cholesterol diet. The hypocholesterolemic action of dietary purple potato flake might be related with caecal fermentation and steroid excretion due to the phosphorus and polyphenols including anthocyanin.

The role of two ATP binding cassette transporters, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), in transdermal absorption of a typical common substrate was examined in vivo. Skin and plasma concentrations of rhodamine123 (Rho123) after dermal application were reduced in P-gp knockout (mdr1a/1b⁻/⁻) mice and were below the detection limit in P-gp and BCRP triple-knockout (mdr1a/1b/bcrp⁻/⁻) mice. Lower epidermal-to-hypodermal permeation of Rho123 in mdr1a/1b/bcrp⁻/⁻ mouse skin compared to the wild-type mouse skin was confirmed in an Ussing-type chamber experiment. The reduction in skin concentration after dermal application in mdr1a/1b/bcrp⁻/⁻ mice was greater in the dermis than in the epidermis, suggesting functional expressions of these transporters in two distinct skin compartments. Coadministration of the inhibitor itraconazole reduced the skin and plasma concentrations of Rho123 in the wild-type mice, but not in mdr1a/1b/bcrp⁻/⁻ mice, and a marked decrease of Rho123 concentration was seen in the dermis, demonstrating that the functional activities of these transporters can be modulated in vivo. On the other hand, the distribution of Rho123 after intravenous infusion was higher in mdr1a/1b/bcrp⁻/⁻ mice than in the wild-type mice. This supports the occurrence of vectorial transport from the skin into systemic circulation, and is consistent with the immunohistochemical localization of P-gp and BCRP in mouse dermal endothelial cells. BCRP was immunohistochemically identified in human epidermis and dermal endothelial cells. Thus, our findings show that ABC transporters in different compartments of the skin contribute to transdermal absorption of a typical substrate in vivo and can be modulated by a specific inhibitor. These findings have implications for transdermal drug delivery.

To clarify the functional properties of potato pulp (PP), a waste product resulting from extraction of starch from potatoes, we examined the effects of PP on cholesterol metabolism and cecal conditions in rats. Plasma total cholesterol (T-Chol) levels were lower in rats fed a PP-supplemented diet for four weeks than in those fed a control diet. Cecal pH was lowered due to an increase in the levels of cecal total short-chain fatty acids, especially butyrate, in the PP group compared to the control group. Furthermore, animals fed with the PP-supplemented diet showed increased cecal ratios of Lactobacillus and Clostridia and decreased cecal ratios of Bacteroides and Gammaproteobacteria with slightly negative and positive correlations with plasma T-Chol levels, respectively. In conclusion, ingestion of PP for four weeks is likely to improve both cecal conditions and cholesterol metabolism, suggesting that PP has prebiotic effects.

Rats fed a diet containing Shadow Queen (SQ), an anthocyanin-rich potato cultivar, previously showed an increase in the hepatic superoxide dismutase (SOD)-2 mRNA level. We investigated whether an extract of SQ would directly increase the hepatic SOD-2 mRNA level in HepG2 cells. Furthermore, we estimated the intracellular signaling pathway for the induction of SOD-2 mRNA expression. HepG2 cells were stimulated using extracts of four crops, including SQ, for 12 h; only extracts of colored potatoes induced SOD-2 mRNA expression significantly. This induction of SOD-2 mRNA expression was blocked by an inhibitor of the extracellular signal-related kinase (ERK) 1/2 pathway. Furthermore, an extract of SQ increased the phosphorylation of ERK1/2 after 15 or 30 min of stimulation. These data indicate that an extract of SQ directly induces hepatic SOD-2 mRNA expression via activation of ERK1/2 pathway in HepG2 cells.

BACKGROUND: Relationships between buckwheat (Fagopyrum esculentum Moench) flour lipase, lipoxygenase and peroxidase activity, along with levels of individual free fatty acids (FFAs) and levels of headspace volatile compounds of boiled buckwheat noodles, were investigated for 12 different buckwheat varieties. Enzyme activities and FFA levels in flour were correlated with their respective varietal arrays of boiled noodle headspace volatile compounds, measured by gas chromatography–mass spectrometry. RESULTS: The volatiles hexanal, tentative butanal, tentative 3-methylbutanal and tentative 2-methylbutanal showed significant positive correlation with one another, indicating that they may be generated through similar mechanisms. These important volatile components of buckwheat flavor were also positively correlated with lipase and/or peroxidase activity, indicating that enzymatic reactions are important in flavor generation in boiled buckwheat noodles. On the other hand, pentanal, which showed no significant correlation with any enzyme activity, showed a significant positive correlation to the levels of C18:2 and C18:3 FFAs, suggesting the existence of a ‘non-enzymatic’ and/or ‘uncertain enzymatic pathway’ for flavor generation in boiled buckwheat noodles. CONCLUSION: Lipase and peroxidase in buckwheat flour are important for flavor generation of boiled buckwheat noodles. This information is important for increasing desirable flavor of buckwheat products as well as for selecting varieties with improved flavor. Copyright © 2010 Society of Chemical Industry

To investigate whether yam improves glucose metabolism, yam-containing diets were given to Wistar rats. In a short-term experiment, fasted-rats were given 1.0 g of a control and 20% yam-containing diets. At 60 min after start of the feeding, glucose level in the yam diet group was lower or tended to be lower than that in the control diet. Insulin levels at 30 min and 60 min were significantly lower than those in the control group. In a long-term experiment, a normal diet (N) or 25% high fat diets with (Y) or without 15% yam powder (HF) were given to rats for 4 weeks. At 4 weeks, in an oral glucose tolerance test, the area under the curve (AUC) of plasma glucose level was higher in the HF group than that in the N group, whereas those in the Y groups did not differ from that in the N group. Glycosylated hemoglobin levels had similar tendency to the AUCs. Plasma leptin levels in the Y groups were significantly higher than that in the N group. In conclusion, yam may contribute to improvement of glucose metabolism. Additionally, we speculated that leptin level is possibly involved in the insulin-response to yam diets.

We examined the effects of white wheat bread powder (BP) and white wheat bread powder containing sugar beet fiber (BBP) on serum cholesterol. The total cholesterol (-11%, -16%), HDL-cholesterol (-12%, -11%), non-HDL-cholesterol (-9%, -18%) and triacylglycerol (-44%, -58%) concentrations in the BP and BBP groups, respectively, were significantly different from those in the control group. The fecal excretion of neutral sterols in the BP and BBP groups and of acidic sterols in the BBP group was significantly higher than that in the control group. The hepatic cholesterol 7alpha-hydroxylase (CYP7A1) mRNA level in the BP and BBP groups was significantly higher than that in the control group. The cecal total short-chain fatty acid concentrations in the BBP group were significantly higher than those in the control group. These results indicate that the observed changes in serum lipid levels in the BP and BBP groups were due to the increased fecal lipid and CYP7A1 mRNA levels.

To manufacture low-malt beer using potato starch, we selected the potato starch suited for low-malt beer brewing from several potato starches. Moreover, the componential and functional characteristics of the low-malt beer obtained thus were evaluated. As extremely fine potato starch obtained by air-classification (median size 13.6 μm) had high phosphorus content but low peak viscosity of Rapid Visco Analyser (RVA), we regarded it as the most suitable material for low-malt beer brewing of the 10 potato starches examined. Phosphoryl-oligosaccharides, which are obtainable after digestion of a starch with phosphate, were obviously found (600 ppm) in low-malt beer using such potato starch. In contrast, no or very little phosphoryl-oligosaccharide was found in low-malt beers using corn or sweet potato starches. Thus, novel type functional low-malt beer would be manufactured by using extremely fine potato starch.

Intestinal condition and ethanol toxicity have been discussed as predictors of alcoholic liver damage. In this study, we investigated the association of hepatic antioxidant enzymes and cecal condition, including intestinal bacteria estimated by terminal restriction fragment length polymorphism (T-RFLP), in the early stage of alcoholic fatty liver. Three liquid isocaloric diets, control (CT) diet, ethanol (ET) diet, or ethanol diet including modified beet fiber (MBF), were prepared and administered to rats for 4 weeks. At 4 weeks, the plasma alanine aminotransferase (ALT) levels in the ET group were higher and that in MBF groups tended to be higher than the CT group, but endotoxin was not detected in the portal vein in any of the samples. The hepatic thiobarbituric acid reactive substances (TBARS) concentration in the MBF group was higher than that in the CT group. Hepatic cytochrome P450 2E1 (CYP2E1) was induced in ethanol-fed rats. The hepatic catalase levels in the ET and MBF groups were lower than that in the CT group. The hepatic superoxide dismutase-2 (SOD-2) level did not differ among the groups. Plasma ALT level and/or hepatic TBARS level correlated positively with CYP2E1 and negatively with catalase level and SOD-2 level. Indicators of cecal condition, including the bacterial population estimated by T-RFLP, may not give any explanation for the hepatic damage. In conclusion, the hepatic CYP2E1 induced by ethanol, rather than the cecal conditions, may influence the early stage of alcoholic hepatic damage in rats; hepatic catalase may provide protective effects.

小麦胚芽，小ブスマ，米糠をGABA合成酵素源に用い，グルタミン酸ナトリウム及びピリドキサルリン酸から高価なGABAの効率的な生成条件を調べた．次いで小麦胚芽を用いたGABA生産条件について検討した．グルタミン酸濃度とGABAの生成率の関係において，反応液中のグルタミン酸濃度を100g/lまで増加させてもGABAの生成率は4時間の反応で95％以上得られた．酵素反応条件は，pH 5.6～5.8，温度40℃，反応時間4時間がそれぞれ最適であった．

The rapid hydrolysis of potato starches differing in phosphorus content, as well as sweet potato, cassava and yam starches, was accomplished by treatment of gelatinised starches with bacterial liquefying α-amylase at 50 °C for 1 h, followed by Bacillus licheniformis α-amylase at 55 °C up to 24 h, and then by glucoamylase at 40 °C for a further 24 h. Among the potato starches, the high-phosphorus starches showed higher starch resistant capacity than the medium-phosphorus starches, as well as other tuber and root starches. The hydrolysis rate of tuber and root starches was not greatly influenced by their amylose content and median granule size. Only glucose was detected in the almost completely hydrolysed tuber and root starch samples, indicating that the concomitant enzymes treatment could hydrolyse both the α-1,4 and α-1,6 linkages of the starches examined.

The phenolic compositions of non-germinated/germinated seeds and seed sprouts (at 6–10 day-old) of common (Fagopyrum esculentum Moench) and tartary (Fagopyrum tataricum Gaertn.) buckwheats were investigated. Phenolic compounds, including chlorogenic acid, four C-glycosylflavones (orientin, isoorientin vitexin, isovitexin), rutin and quercetin, were determined in the seed sprouts by high-performance liquid chromatography (HPLC). In the edible parts of common buckwheat sprouts, individual phenolics significantly increased during sprout growth from 6 to 10 days after sowing (DAS), whereas in tartary buckwheat sprouts they did not. While the sum contents of phenolic compounds in the edible part (mean 24.4 mg/g DW at 6–10 DAS) of tartary buckwheat sprouts were similar to those of common buckwheat sprouts, rutin contents in the non-germinated/germinated seeds (mean 14.7 mg/g DW) and edible parts (mean 21.8 mg/g DW) of tartary buckwheat were 49- and 5-fold, respectively, higher than those of common buckwheat. Extracts of the edible parts of both species showed very similar free radical-scavenging activities (mean 1.7 μmol trolox eq/g DW), suggesting that the overall antioxidative activity might be affected by the combination of identified phenolics and unidentified (minor) components. Therefore, buckwheat seed sprouts are recommended for their high antioxidative activity, as well as being an excellent dietary source of phenolic compounds, particularly tartary buckwheat sprouts, being rich in rutin.

The dough characteristics of mixtures of wheat flour and potato starches from three different cultivars (Eniwa, Benimaru and Norin No. 1) were investigated using a Brabender farinograph. The water absorption of control wheat dough was higher than that for all mixture doughs and decreased significantly with increases in potato starch. The peak time of wheat flour-potato starch mixtures ranged from 21.0 to 22.5 min, with no large difference with increase of potato starch. Dough stability significantly increased with increase of potato starch. The increase of potato starch in the mixtures decreased the tolerances of mixing, indicating that they were weaker than the control flour. Breakdown time of mixtures tended to be the same as for control wheat flour up to 5 % potato starch, above which it increased significantly. Results are applicable to the substitution of potato starch in certain wheat-based foods such as noodles, breads, biscuits, and crackers.

Background/Aims: Feeding rats potato resistant starch improves large bowel health; however, there is little information on the physiological effects of preprocessed starch like potato flakes in animal experiments. The present study was designed to investigate the effects of the consumption of various colored potato (white, red and purple) flakes on cecal fermentation and fecal bile acid excretions in rats. Methods: The control group was fed a basal diet (BD) containing α-cornstarch for 4 weeks. The potato flake-treated groups were fed one of the following diets containing a mixture of 299.5 g/kg α-cornstarch plus 250 g/kg Hokkai kogane flakes (HK, white), Hokkai No. 91 flakes (H91, red) or Hokkai No. 92 flakes (H92, purple). Results: There were no significant differences in the body weight, food intake and cecum weight among the groups. Cecal pH values in the HK, H91 and H92 groups were significantly lower than that in the BD group, and matter excretion in the H91 group was significantly higher than in the BD and HK groups. Cecal short-chain fatty acid (SCFA) concentrations in the HK, H91 and H92 groups were significantly higher than in the BD group, and the molar ratio of butyrate to total SCFA in the HK, H91 and H92 groups was greatly increased compared with the BD group. Rats fed the HK, H91 and H92 potato flake diets presented significantly higher counts of total anaerobes in the cecum than rats fed the BD. The cecal Lactobacillus count in the H91 group was significantly increased compared to the BD group and the Bifidobacterium count was similar for all groups. Fecal total bile acid excretion in the H92 flake group and secondary bile acid excretions in the H91 and H92 groups were significantly greater than those in the other groups and in the BD and HK groups, respectively. Conclusion: The results indicate that potato flakes act like resistant starch and raise bowel SCFA, probably through anaerobic bacterial activities and fermentation of residual starch. These actions are helpful for the improvement of the colonic environment.

The evolution, from 1 to 10 days after germination, of flavonoid content in sprouts of tartary buckwheat (Fagopyrum tataricum Gaertn.), grown in a greenhouse under low light conditions (16 μmol m−2 s−1), was investigated. Chlorogenic acid and flavonoids including C-glycosylflavones (orientin, isoorientin, vitexin, isovitexin), rutin and quercetin were separated from the sprouts by HPLC and quantified with their commercial standards. Rutin content in the edible portion of the sprouts (mean 20 and 37 mg g−1 DW in ‘Hokkai T 8’ and ‘Hokkai T 10’, respectively) was 3- to 31-fold greater than that in the roots or pericarp. The free radical scavenging activity of seed sprouts was assessed through the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. From 6 to 10 days after sowing, the free radical scavenging activity in the edible portions rose significantly from 1.52 to 2.33 μmol Trolox equiv. g−1 DW in ‘Hokkai T 8’ and from 1.46 to 2.09 μmol Trolox equiv. g−1 DW in ‘Hokkai T 10’, but differences between ‘Hokkai T 8’ and ‘Hokkai T 10’ were not significant. As the results, the sprouts of tartary buckwheat, particularly those of ‘Hokkai T 10’ are strongly recommended as new high rutin food.

The anthocyanin profiles and variety/breeding-line differences of anthocyanin concentrations in petals of common buckwheat flowers have been studied. Four anthocyanins, cyanidin 3-O-glucoside, cyanidin 3-O-rutinoside, cyanidin 3-O-rhamnoside, and cyanidin 3-O-galactosyl-rhamnoside were isolated from the petals of common buckwheat (Fagopyrum esculentum Moench), separated using high performance liquid chromatography and identified using reversed-phase liquid chromatography-electrospray ionization-tandem mass spectrometry techniques. In every variety/breeding line tested, cyanidin 3-O-rutinoside was detected as the major anthocyanin and the next is cyanidin 3-O-glucoside whereas cyanidin 3-O-rhamnoside and cyanidin 3-O-galactosyl-rhamnoside were trace or not detectable in white and pink flowered buckwheat. Of all the varieties/breeding lines tested, Gan-Chao, a Chinese variety, contained the highest amount of anthocyanins. The largest part of cyanidin moiety was presented as a proanthocyanidin form (PAs-Cy). Anthocyanins and PAs-Cy in petals were increased along with increase of flower development stages. Therefore, fully developed petals of red flowered buckwheat, especially Gan-Chao, are promising as a new anthocyanin-rich material for food processing.

The research presented herein provides valuable data with respect to the phosphorus content of starches from many potato (Solanum tuberosum L.) cultivars using an energy-dispersive X-ray fluorescence technique. In all starches examined, the phosphorus content ranged from 308 to 1244 ppm. Furthermore, the estimation of the starch characteristics of representative samples differing manifestly in their phosphorus content indicated that enhancing the starch phosphate resulted in significant increases in the swelling power, peak viscosity, and breakdown and significant but small increases in the onset and peak temperatures of gelatinization. Other starch quality parameters, such as the amylose content, median granule size, and the gelatinization enthalpy, did not change significantly due to the degree of phosphate substitution of starch.

A rapid visco analysis (RVA) system was used to study the pasting properties of mixtures of wheat flour and potato starches with high phosphorus (HPS), medium phosphorus (MPS) and low phosphorus (LPS) contents, different granule sizes and different amylose contents. The peak viscosities, trough and breakdown, final viscosities, setback viscosities and peak times of control potato starches were found to be higher than those of wheat flour. The peak viscosities were increased significantly with increase of potato starches in the mixtures. Thus, the peak times decreased with increase of potato starch in the mixtures. The breakdown viscosities increased significantly with increase of potato starches in the mixtures and the values were found to be higher in HPS-wheat, followed by MPS-wheat and LPS-wheat mixtures. The final viscosities of HPS-wheat mixtures were highest, followed by MPS-wheat and LPS-wheat mixtures. The setback viscosities of LPS-wheat were significantly higher than those of MPS-wheat and HPS-wheat mixtures at 30 to 50% potato.

The effects of high-molecular-weight glutenin (HMWG) subunits on the physical properties of yellow alkaline noodles (YAN) were investigated by using 10 near-isogenic lines (NILs) that only differed in HMWG composition and the recurrent parent Harunoakebono (HA). Although there were some differences among NILs, including HA, regarding protein content, other characteristics of the flours, such as the ash content and the starch traits, were not notably different. Differences in HMWG composition had a significant effect on the micro SDS-sedimentation volume (MSDSS), breaking force (BF, an index of hardness) and breaking deformation (BD, an index of extensibility) of raw noodles and the BF and BF/BD (an index of elasticity) of boiled noodles. In particular, the BF of raw and boiled noodles were significantly and positively correlated with MSDSS, which is an index of flour protein strength (the quality of flour protein). There were no significant differences in the physical properties of YAN between HMWG subunits 1 and 2 at the Glu-A1 allele. In a comparison of all subunits at the Glu-B1 allele, subunits 17+18 and 20 had significantly higher and lower BF than subunits 7+9 (HA) in raw noodles, respectively, and the BD of subunits 6+8 and 20 was also significantly lower than that of other subunits. No large differences were observed in the physical properties of subunits at the Glu-B1 allele in boiled noodles, with a few exceptions. At the Glu-D1 allele, subunits 2+12, 4+12, and 2.2+12 basically had smaller BF and BF/BD in raw and boiled noodles than subunits 5+10 (HA). The physical properties of NILs with subunits 17+18 and 2.2+12 were similar to those of HA with subunits 7+9 and 5+10. Conversely, those of NIL with subunits 20 and 2.2+12 were extremely small compared to those of HA. The results obtained in this study indicate that the dough strength (the quality of flour protein), as evaluated by MSDSS, has a significant effect on the physical properties of YAN, and that a desirable texture of boiled YAN with a large BF and BF/BD, especially BF, was obtained from flour with HMWG subunits with positive effects on dough strength. Regarding HMWG composition, subunits 2+12, 4+12, and 2.2+12 had the most negative effect on texture, particularly BF, of YAN, followed by subunits 20 and 7+8. In contrast, subunits 5+10 and 17+18, especially the former, had positive effects. NILs with both subunits 5+10 and 17+18 had the best YAN texture (the largest BF and moderate BF/BD values for boiled noodles) among all NILs.

The bread-making quality of flour made from two new Japanese bread wheat varieties, Haruyokoi and Kitanokaori, was evaluated, and the staling and texture of bread made from these flour types were compared with those of flour made from representative bread wheat classes, No.1 Canada western red spring (1CW) and Hard red winter (HRW). There was not a large difference in the bread-making quality of the above four flour types, except that the water absorption of the Kitanokaori flour was high, and the gassing power of the dough was low. Bread made from the two above-mentioned Japanese flour types (two new bread varieties) were quite soft after baking, and the degree of staling (changes in hardness) were somewhat lower than those made with 1CW and HRW. The cohesiveness of the two new bread varieties, i.e., the index of bread elasticity, showed higher values than those of others up to 1 day of storage. From the analysis of bread staling and the retrogradation of starch in bread, it was proven that the staling rate and starch retrogradation rate constants of the two new bread varieties were approximately the same as those of bread made from 1CW and HRW but the starch retrogradation of the new bread varieties was somewhat slower than that of the others up to 2 days of storage. The analysis of hardness and cohesiveness of the flour and starch gel from the above four flour types indicated that the softness and high cohesiveness of the two new bread varieties after baking were, to a great extent, the result of the soft texture of starch gel in these varieties. These results showed that the somewhat slow staling, especially staling in the early stage, and the extreme softness after baking of the two new bread varieties were attributed to the soft texture and low retrogradation of starch gel in the bread, which was related to the lower amylose content of these new flour types.

We examined the relationship between flour/starch properties and the yellow alkaline noodle (YAN) color or physical properties of Kitanokaori, a Hokkaido hard wheat cultivar, and four other samples. Regarding flour properties, Kitanokaori had low polyphenol oxidase (PPO) activity and low amylose content. A time-course experiment showed that a raw noodle sheet made from Kitanokaori had less reduction in color brightness than sheets made from other flour samples that had high PPO activity. This finding suggests that the brightness stability of the Kitanokaori noodle is caused by its low PPO activity. Regarding physical properties and texture, Kitanokaori had high breakdown and low setback viscosity, as measured with a Rapid Visco Analyzer (RVA), and high elastic indices of the starch gel and YAN as a result of the low amylose content. In assessment of the eating quality, the total score of YAN made from Kitanokaori was higher than that obtained from other samples. This was because Kitanokaori had high elasticity and smoothness, which was related to its low amylose content, and the reduction in hardness related to low amylose was suppressed, since the protein properties of Kitanokaori are relatively strong. The results of comparison demonstrated that the superior qualities of YAN made from Kitanokaori could be attributed to the low PPO activity and low amylose content of the flour.