A novel Alaska pollack-derived peptide, which increases glucose uptake in skeletal muscle cells, lowers the blood glucose level in diabetic mice.

We found that the tryptic digest of Alaska pollack protein exhibits a glucose-lowering effect in KK-Ay mice, a type II diabetic model. We then searched for glucose-lowering peptides in the digest. Ala-Asn-Gly-Glu-Val-Ala-Gln-Trp-Arg (ANGEVAQWR) was identified from a peak of the HPLC fraction selected based on the glucose-lowering activity in an insulin resistance test using ddY mice. ANGEVAQWR (3 mg kg(-1)) decreased the blood glucose level after intraperitoneal administration. Among its fragment peptides, the C-terminal tripeptide, Gln-Trp-Arg (QWR, 1 mg kg(-1)), lowered the blood glucose level, suggesting that the C-terminal is critical for glucose-lowering activity. QWR also enhanced glucose uptake into C2C12, a mouse skeletal muscle cell line. QWR did not induce the phosphorylation of serine/threonine protein kinase B (Akt) and adenosine monophosphate-activated protein kinase (AMPK). We also demonstrated that QWR lowered the blood glucose level in NSY and KK-Ay, type II diabetic models.

Preparation of chiral ligands connected with quaternary ammonium group for recyclable catalytic asymmetric transfer hydrogenation in ionic liquid.

Reuse of chiral ruthenium catalyst in catalytic asymmetric transfer hydrogenation (CATH) has attracted attention from economic and environmental viewpoints, and reactions using ionic liquids (ILs) as solvent are recognized as one of the most useful methods for reuse of the catalyst. We synthesized (1S,2S)-N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine (TsDPEN) derivatives with various ionic moieties, and investigated the effect of their structure with respect to catalytic ability and recyclability in CATH with ILs. Ligand 3a having an imidazolium group showed the best results, and significant differences were observed depending on the structure of the ionic moiety or the length of the alkyl chain connecting the ligand site and the ionic moiety. Among various prochiral ketones used as substrates at various cycles, 3a showed a relatively good result.

Fish protein intake induces fast-muscle hypertrophy and reduces liver lipids and serum glucose levels in rats.

In our previous study, fish protein was proven to reduce serum lipids and body fat accumulation by skeletal muscle hypertrophy and enhancing basal energy expenditure in rats. In the present study, we examined the precise effects of fish protein intake on different skeletal muscle fiber types and metabolic gene expression of the muscle. Fish protein increased fast-twitch muscle weight, reduced liver triglycerides and serum glucose levels, compared with the casein diet after 6 or 8 weeks of feeding. Furthermore, fish protein upregulated the gene expressions of a fast-twitch muscle-type marker and a glucose transporter in the muscle. These results suggest that fish protein induces fast-muscle hypertrophy, and the enhancement of basal energy expenditure by muscle hypertrophy and the increase in muscle glucose uptake reduced liver lipids and serum glucose levels. The present results also imply that fish protein intake causes a slow-to-fast shift in muscle fiber type.

Supplementation with eicosapentaenoic acid-rich fish oil improves exercise economy and reduces perceived exertion during submaximal steady-state exercise in normal healthy untrained men.

Based on the effects of n-3 polyunsaturated fatty acids (PUFA) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on reduction of blood viscosity, we theorized that PUFA could improve aerobic performance by increasing oxygen supply to tissues. Twenty male subjects were randomly divided into two groups (n = 10): a fish oil group (FG) and a control (CG). Maximal oxygen uptake and oxygen uptake during submaximal exercise were measured using a cycle ergometer. For 8 weeks, the FG then ingested capsules containing 3.6 g/day of EPA-rich fish oil, while the CG took 3.6 g/day of a medium-chain triglyceride. After supplementation, erythrocyte EPA and DHA in the FG were significantly increased. In the FG, a negative linear correlation was detected in the change between erythrocyte EPA and whole oxygen uptake during submaximal exercise pre- and post-supplementation. The present study showed that EPA-rich fish oil supplementation improves exercise economy in humans.

Effects of dietary supplementation with fish oil on dry eye syndrome subjects: randomized controlled trial.

The purpose of this study was to evaluate the efficacy of fish oil supplementation added to usual dry eye treatment in dry eye subjects in a randomized controlled trial. Twenty-seven typical dry eye subjects were selected from 43 candidates by the diagnostic criterion for dry eye in this study. They were assigned to the randomized fish oil group (n = 15) or the placebo group (n = 12). Fish oil group ingested fish oil capsules containing eicosapentaenoic acid (EPA, 1245 mg/day) and docosahexaenoic acid (DHA, 540 mg/day) for 12 weeks. Placebo group ingested placebo capsules without EPA or DHA. A visual analog scale test estimating subjective symptoms, the Schirmer I test, tear film break-up time (BUT) measurement, fluorescein staining, and rose bengal staining were performed every 4 weeks during the 12-week supplementation period and 4-week washout period. The subjective symptom of "eye pain", BUT, and changes in rose bengal staining score of the fish oil group were significantly improved after 8-12 weeks of supplementation and/or 4 weeks of washout, compared to those of the placebo group. These results suggest that fish oil supplementation added to usual care may be effective in the treatment of dry eye.

Effects of krill oil containing n-3 polyunsaturated fatty acids in phospholipid form on human brain function: a randomized controlled trial in healthy elderly volunteers.

BACKGROUND: Krill oil, rich in n-3 (omega-3) polyunsaturated fatty acids (PUFAs) incorporated in phosphatidylcholine, has been reported to have many effects on physiological function. However, there are few studies using psychophysiological methods published that describe the effects of krill oil on brain function. We investigated the influence of ingestion of krill oil on cognitive function in elderly subjects by using near-infrared spectroscopy and electroencephalography. METHODS: A randomized, double-blind, parallel-group comparative study design was adopted. Forty-five healthy elderly males aged 61-72 years were assigned to receive 12 weeks of treatment with: medium-chain triglycerides as placebo; krill oil, which is rich in n-3 PUFAs incorporated in phosphatidylcholine; or sardine oil, which is abundant in n-3 PUFAs incorporated in triglycerides. Changes in oxyhemoglobin concentrations in the cerebral cortex during memory and calculation tasks were measured. The P300 component of event-related potentials was also measured during a working memory task. RESULTS: During the working memory task, changes in oxyhemoglobin concentrations in the krill oil and sardine oil groups were significantly greater than those in the medium-chain triglyceride group at week 12. The differential value for P300 latency in the krill oil group was significantly lower than that in the medium-chain triglyceride group at week 12. With regard to the calculation task, changes in oxyhemoglobin concentrations in the krill oil group were significantly greater than those in the medium-chain triglyceride group at week 12. CONCLUSION: This study provides evidence that n-3 PUFAs activate cognitive function in the elderly. This is especially the case with krill oil, in which the majority of n-3 PUFAs are incorporated into phosphatidylcholine, causing it to be more effective than sardine oil, in which n-3 PUFAs are present as triglycerides.

Construction of an integrated high density simple sequence repeat linkage map in cultivated strawberry (Fragaria × ananassa) and its applicability.

The cultivated strawberry (Fragaria × ananassa) is an octoploid (2n = 8x = 56) of the Rosaceae family whose genomic architecture is still controversial. Several recent studies support the AAA'A'BBB'B' model, but its complexity has hindered genetic and genomic analysis of this important crop. To overcome this difficulty and to assist genome-wide analysis of F. × ananassa, we constructed an integrated linkage map by organizing a total of 4474 of simple sequence repeat (SSR) markers collected from published Fragaria sequences, including 3746 SSR markers [Fragaria vesca expressed sequence tag (EST)-derived SSR markers] derived from F. vesca ESTs, 603 markers (F. × ananassa EST-derived SSR markers) from F. × ananassa ESTs, and 125 markers (F. × ananassa transcriptome-derived SSR markers) from F. × ananassa transcripts. Along with the previously published SSR markers, these markers were mapped onto five parent-specific linkage maps derived from three mapping populations, which were then assembled into an integrated linkage map. The constructed map consists of 1856 loci in 28 linkage groups (LGs) that total 2364.1 cM in length. Macrosynteny at the chromosome level was observed between the LGs of F. × ananassa and the genome of F. vesca. Variety distinction on 129 F. × ananassa lines was demonstrated using 45 selected SSR markers.

Predicting efficacy of dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes: Association of glycated hemoglobin reduction with serum eicosapentaenoic acid and docosahexaenoic acid levels.

This study was initiated to identify clinical and dietary parameters that predict efficacy of dipeptidyl peptidase-4 inhibitors. A total of 72 untreated Japanese patients with type 2 diabetes who received DPP-4 inhibitors (sitagliptin, alogliptin or vildagliptin) for 4 months were examined for changes of glycated hemoglobin (HbA1c) and body mass index (BMI), and self-administered 3-day food records, as well as serum levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). DPP-4 inhibitors significantly reduced HbA1c (before initiation of DPP-4 inhibitors 7.2 ± 0.7%, 4 months after initiation of DPP-4 inhibitors 6.7 ± 0.6% [paired t-test, P < 0.01 vs before]). Multiple regression analysis showed that changes of HbA1c were significantly correlated with baseline HbA1c, as well as estimated intake of fish. Furthermore, changes of HbA1c were significantly correlated with serum levels of EPA (r = -0.624, P < 0.01) and DHA (r = -0.577, P < 0.01). HbA1c reduction by DPP-4 inhibitors is significantly correlated with estimated intake of fish and serum levels of EPA and DHA. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2012.00214.x, 2012).

Effects of dietary supplementation with a combination of fish oil, bilberry extract, and lutein on subjective symptoms of asthenopia in humans.

The aim of this study was to determine the effects of dietary supplementation with a combination of fish oil, bilberry extract, and lutein on subjective symptoms of asthenopia in humans by a double- blind, randomized, parallel-group, and placebo-controlled trial. In the Active group, eleven subjects ingested a supplement containing omega-3 fatty acid-rich fish oil (docosahexaenoic acid 783 mg/day, eicosapentaenoic acid 162 mg/day), bilberry extract (anthocyanidin 59 mg/day), and lutein (17.5 mg/day) in soft gel capsule form, every day for 4 weeks. In the Placebo group, nine subjects ingested placebo capsules. Before and after supplementation, subjects completed a questionnaire to determine their asthenopia symptoms and were also assessed for mental fatigue symptom by the visual analog scale (VAS) test. Asthenopia symptoms such as "stiff shoulder, low back pain", "frustration", "dry-eye", and "stuffy head" were improved in the Active group. Furthermore, a score of mental fatigue was improved after 4 weeks of supplementation, and no side effects were observed after the 4-week supplementation and a 2-week washout period in the Active group. These results suggest that dietary supplementation with the combination of omega-3 fatty acid-rich fish oil, bilberry extract, and lutein may safely improve subjective symptoms of asthenopia and mental fatigue in humans.

Fast-twitch muscle hypertrophy partly induces lipid accumulation inhibition with Alaska pollack protein intake in rats.

Fish protein is a source of animal protein that is consumed worldwide. Although it has been reported that the intake of Alaska pollack protein (APP) reduces serum triglyceride and body fat accumulation in rats, the mechanisms underlying these effects are poorly understood. In the present study, we fed 5-week-old male Sprague-Dawley rats a high-fat diet with APP or casein for 4 weeks. We reconfirmed that the intake of APP decreases serum triglycerides and inhibits visceral body fat accumulation in rats. We found that APP had a higher non-digestive protein content than casein, and the amount of protein in feces was higher in the APP group than in the casein group. However, the amount of total lipids in feces did not differ significantly between the groups. We also found that the gastrocnemius muscle, a fast-twitch muscle, tended to increase in weight, and that the epididymal fat weight correlated negatively with gastrocnemius muscle weight in the APP group. These results imply that the enhancement of basal energy expenditure by fast-twitch muscle hypertrophy, rather than the enhancement of lipid excretion via feces, partly causes APP-induced inhibition of lipid accumulation in rats.

Chiisanoside is not absorbed but inhibits oil absorption in the small intestine of rodents.

Chiisanoside is the main component of Acanthopanax sessiliflorus leaves. Simultaneous administration of chiisanoside resulted in a decrease in the plasma TG level and increase of undigested TG in the intestinal lumen after oil gavage to mice. This suggests that chiisanoside has the potential to prevent obesity as a lipase inhibitor which suppresses fat absorption in vivo.

Metabolic syndrome, insulin resistance, and atherosclerosis in Japanese type 2 diabetic patients.

The aim of the present study was to investigate the relationships between metabolic syndrome and atherosclerosis in 57 Japanese type 2 diabetic patients. Metabolic syndrome was diagnosed based on the criteria raised by the Japan Internal Medicine Society. Insulin resistance was estimated by the insulin resistance index of homeostasis model assessment. Ultrasonographically measured carotid atherosclerosis, brachial-ankle pulse wave velocity (ba-PWV), and ankle brachial index (ABI) were used to assess the degree of atherosclerosis. Of 57 patients, 25 were diagnosed as having metabolic syndrome. The patients with metabolic syndrome had significantly higher levels of waist circumference, insulin, insulin resistance index of homeostasis model assessment, systolic and diastolic blood pressures, and serum triglycerides, and lower concentrations of adiponectin. However, there was no significant difference in age, sex, glycosylated hemoglobin (hemoglobin A1c), fasting glucose, leptin, and tumor necrosis factor system activities including tumor necrosis factor alpha between the 2 groups. Furthermore, no significant difference was observed in the degree of carotid atherosclerosis (intimal-medial thickness in plaque-free segments: 0.72+/-0.03 vs 0.72+/-0.02 mm, P=.435; carotid stenosis in plaque segments: 6.6%+/-3.0% vs 6.6%+/-1.7%, P=.497), ba-PWV (1676+/-56 vs 1654+/-44, P=.380), and ABI (1.16+/-0.01 vs 1.15+/-0.01, P=.245) between the 2 groups. From these results, it can be suggested that metabolic syndrome, an insulin-resistant state, is not associated with carotid atherosclerosis, ba-PWV, or ABI in Japanese type 2 diabetic patients.

Lupane-type saponins from leaves of Acanthopanax sessiliflorus and their inhibitory activity on pancreatic lipase.

Three known saponins, chiisanoside, 11-deoxyisochiisanoside, and isochiisanoside, and one novel saponin, 3,4-seco-4(23),20(29)-lupadiene-3,28-dioic acid 28-O-alpha-l-rhamnopyranosyl (1-->4)-beta-d-glucopyranosyl (1-->6)-beta-d-glucopyranoside, referred to as sessiloside, were isolated from a hot water extract of Acanthopanax sessiliflorus leaves. All of these saponins were lupane-type triterpene triglycosides, and their concentrations were 4.1, 1.0, 0.5, and 0.4% (w/w) of the total extract, respectively. Sessiloside and chiisanoside inhibited pancreatic lipase activity in vitro, and addition of the saponin-rich fraction to a high-fat diet suppressed the body weight gain of mice. The possibility of application of the lupane-type saponins from A. sessiliflorus leaves to the treatment of obesity is discussed.

A recyclable catalyst for asymmetric transfer hydrogenation with a formic acid-triethylamine mixture in ionic liquid.

A novel task-specific ionic ligand with an imidazolium salt moiety was synthesized, and its catalytic ability and recyclability for asymmetric transfer hydrogenation of acetophenone derivatives with a formic acid-triethylamine azeotropic mixture in an ionic liquid [bmim][PF6] was examined.

[Xanthine oxidase inhibitory activity and hypouricemia effect of propolis in rats].

The xanthine oxidase (XOD) inhibitory activity of propolis from China and Brazil was measured. The propolis from both place were seen to have XOD inhibitory activity. However, a stronger tendency was shown in the propolis from China. The compounds in each the propolis were measured quantitatively. A great deal of chrysin, galangin, and caffeic acid phenetyl ester were found in the propolis from China, an abundance of p-coumaric acid and artepillin C in the propolis from Brazil. Therefore it was revealed that the propolis compounds are very different depending on their place of origin. The XOD inhibitory activity of these five compounds was measured. Caffeic acid phenetyl ester had the strongest activity, with chrysin and galangin next; p-coumaric acid and artepillin C showed weak XOD inhibitory activity. We evaluated the hypouricemic effect of propolis from China on hyperuricemia induced by the uricase inhibitor, oxonic acid (500 mg/kg p.o., 1 h before the test drugs), and measured plasma uric acid values in rats. Oral propolis had a hypouricemic effect 2 h after its administration to oxonate-pretreated rats. These results suggested that a continuous intake of propolis may be effective for the prevention and the treatment of gout and hyperuricemia.

Singlet oxygen quenching activity of human serum.

Singlet oxygen is regarded as contributing to the pathogenesis of various diseases including light-induced skin disorders and inflammatory response. In this study, the correlation between singlet oxygen quenching activity (SOQA) of human serum and blood biochemistry or life-style was evaluated. Healthy volunteers were recruited and carried out a measurement of SOQA by using electron paramagnetic resonance (EPR) and a questionnaire survey about a smoking. It was demonstrated that major quenchers of singlet oxygen in serum are proteins, and small molecular anti-oxidants relatively play a minor role. SOQA of whole sera showed no correlation with protein concentration, but positively correlated with SOQA of small molecular fraction. In vitro studies demonstrated that the decrease of sulfhydryl groups by NO or superoxide significantly attenuated SOQA of albumin. Together, these results may imply that the underlying oxidative condition in each individual influences both small molecular antioxidant states and the sulfhydryl content of serum proteins. SOQA of sera from women with a smoking history was significantly lower compared to non-smoking women, suggesting that the smoking habit impaired the defense mechanism against singlet oxygen.

Bilateral vocal fold paralysis and adhesion in anterior spinal artery syndrome.

The purpose of this report is to present a rare case of anterior spinal artery syndrome (ASAS) in which there proved to be a combined lesion of paralysis and adhesion. A 26-year-old woman with a history of ASAS complained of difficulty of tracheal decannulation. In 1988, she was intubated and underwent tracheotomy because of respiratory muscle weakness, and she was decannulated in 1990. In 1998, she had cesarean delivery under general anesthesia, and postdelivery dyspnea necessitated tracheotomy again. On her first visit to us, endoscopic examination revealed bilateral vocal fold immobility at the midline without an apparent web. Direct laryngoscopy under general anesthesia revealed a posterior glottic adhesion and scarring, which were treated by excision of the scar and local steroid injection. The left vocal fold gradually regained mobility, permitting decannulation 3 months after treatment. This complicated vocal fold immobility was found to be due to adhesion and partial paralysis combined.

Development of Fertilized Starfish Eggs in Which Cytokinesis is Prevented by Iturin A-2: (starfish embryos/iturin A-2/cytokinesis/blastulation/1-methyladenine).

Iturin A-2, a cyclic peptide obtained from cultures of Bacillus subtilis inhibited cell division but not nuclear divisions of fertilized eggs of the starfish Asterina pectinifera, resulting in the formation of non-cleaving eggs containing all the embryonic nuclei in a common cytoplasm. Fertilized eggs in which cleavage was prevented by iturin A-2 (50µg/ml) synthesized DNA, RNA and protein at comparable rates to those of normal embryos up to the onset of blastulation. In single-cell embryos, however, elevation of the level of transcription, which is a characteristic marker of blastulation, did not take place and the chromatin masses eventually dispersed in the cytoplasm. Treatment of oocytes with iturin A-2 (50µg/ml) resulted in loss of their response to the maturation-inducing substance 1-methyladenine, whose receptors are located in the cell membrane or other components of the oocyte cortex. Furthermore, iturin A-2 bound to oocyte cortices quantitatively, suggesting that its site of action is the cortices of oocytes and eggs, and that its arrest of cleavage of fertilized eggs is due to loss of the ability of the cell membrane to form a cleavage furrow.