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Low-Dose of the Sulforaphane Precursor Glucoraphanin as a Dietary Supplement Induces Chemoprotective Enzymes in Humans

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Food and Nutrition Sciences 2015年第17期6卷 1603-1612页

作者： yusuke ushida Hiroyuki Suganuma Akinori Yanaka Research & Development Division Kagome Co. Ltd. Tochigi Japan Hitachi Medical Education and Research Center Faculty of Medicine University of Tsukuba Hospital Ibaraki Japan

Broccoli sprout (BS) supplements have been marketed for over a decade for the promising health beneficial effects of sulforaphane (SFN), which induces Nrf2 signaling and downstream chemoprotective genes, including phase 2 enzymes. Most commercially available BS supplements encapsulate heat-processed BS containing glucoraphanin (GR), which is hydrolyzed to SFN by the intestinal microbiota. However, the absorption behavior of SFN following the intake of such BS supplements is still unclear. Additionally, the GR dose (around 30 mg) recommended by many manufacturers of BS supplements is relatively lower than the effective dose determined in previous intervention studies. The aims of this study were to assess the effects of a single administration of a typical BS supplement containing lower doses of GR (30 or 60 mg from 3 or 6 capsules, respectively) on SFN absorption, and also to assess the serum activities of phase 2 enzymes as possible surrogate markers of the beneficial effects of SFN. Urinary excreted isothiocyanates and dithiocarbamates showed that the SFN absorption following administration of BS supplement was prolonged and varied among individuals, which conforms to the well-known characteristics of intestinal microbiota-mediated SFN absorption. The amount of SFN absorbed increased dose-dependently but not linear fashion (9.27 μmol and 13.5 μmol for 3 and 6 capsules, respectively). There was no significant difference in SFN bioavailability and the number of capsules consumed. Serum activities of phase 2 enzymes glutathione S-transferase (GST) and NAD(P)H: quinone oxidoreductase 1 (NQO1), which have been reported to display “chemoprotected states” in organs such as the liver, were dose-dependently and synchronously elevated (p < 0.05) following BS supplement intake. This suggests that a low dose of GR (30 mg) exerts chemoprotective effects in humans. In conclusion, our findings will be useful in future clinical studies investigating the chemoprotective effects of

关键词： Sulforaphane Glucoraphanin Chemoprotection Broccoli Sprout Phase 2 Enzymes

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Aqueous Components of Tomato Accelerate Alcohol Metabolism by Increasing Pyruvate Level

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Food and Nutrition Sciences 2014年第10期5卷 870-879页

作者： yusuke ushida Shunji Oshima Koichi Aizawa Hiroyuki Suganuma Akihiro Nemoto Hiroko Ishikiriyama Yasushi Kitagawa Research & Development Division Kagome Co. Ltd. Tochigi Japan Research Laboratories for Fundamental Technology of Food Asahi Group Holdings Ltd. Ibaraki Japan

Consumption of food while drinking alcohol has been suggested to play important roles in alleviating the physiological and pharmacological influences of alcohol. Vegetables are believed to provide health benefits, but there is little evidence for their influence on the effects of alcohol consumption. The present study aimed to investigate the effect of a common vegetable, tomato, on alcohol metabolism. In a randomized, controlled, crossover study with12 Japanese healthy men aged between 24 and 56 years, drinking tomato juice containing 5% (v/v) alcohol (TJAlc) significantly attenuated the elevation of blood ethanol level and subsequently increased the level of acetate compared with a water-based alcoholic beverage with an equal dose of alcohol (0.4 g/kg body weight). Significantly higher levels of blood pyruvate and lactate were also observed in subjects who had consumed TJAlc compared with those consuming the water-based beverage. Additionally, a biphasic alcohol effects scale method showed that subjective feelings for alcohol-induced stimulant effects were significantly enhanced by drinking TJAlc. Animal experiments using male Sprague Dawleyrats suggested that the effect on blood biomarkers was attributable to the serum fraction of tomato (TS), which largely consisted of aqueous compounds, but not lipophilic compounds such as the carotenoid lycopene. Furthermore, it was suggested the TS possibly included potent compound(s) in addition to alanine, glutamine, and citric acid, all of which have previously been reported to affect alcohol metabolism. Administration of TS clearly increased the activity of NAD (H)-dependent enzymes such as lactate-(LDH), alcohol-, and aldehyde-dehydrogenase in rat liver cytosols. These findings suggest that aqueous compound(s) in tomato promote alcohol metabolism, probably through increasing pyruvate level, enhancing LDH activity, and improving the ratio of NAD to NADH.

关键词： Tomato Blood Ethanol Level Pyruvate Lactate Dehydrogenase Alcohol Metabolism

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Sulforaphane-rich broccoli sprout extract improves hepatic abnormalities in male subjects

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World Journal of Gastroenterology 2015年第43期21卷 12457-12467页

作者： Masahiro Kikuchi yusuke ushida Hirokazu Shiozawa Rumiko Umeda Kota Tsuruya Yudai Aoki Hiroyuki Suganuma Yasuhiro Nishizaki Digestive and Liver Disease Center Tokai University Tokyo Hospital Research and Development Division Kagome Co.Ltd. Department of Clinical Health Science Tokai University Tokyo Hospital

AIM: To evaluate effects of dietary supplementation of sulforaphane(SF)-rich broccoli sprout(BS) extract on hepatic abnormalities in Japanese male ***: In a randomized,placebo-controlled,double blind trial,male participants with fatty liver received either BS capsules containing glucoraphanin [GR; a precursor of SF(n = 24)] or placebo(n = 28) for 2 mo. Liver function markers,serum levels of aspartate and alanine aminotransferases(AST and ALT,respectively) and γ-glutamyl transpeptidase(γ-GTP) and an oxidative stress marker,urinary levels of 8-hydroxydeoxyguanosine(8-OHd G),were measured and compared in participants before and after the trial period. In an animal model,chronic liver failure was induced in Sprague-Dawley rats by successive intraperitoneal injection with N-nitrosodimethylamine(NDMA) for 4 wk. Concomitantly,rats received AIN-76 diets supplemented with or without BS extract. Thereafter,rats were sacrificed,and their sera and livers were collected to measure serum liver function markers and hepatic levels of thiobarbituric acid reactive substances(TBARS) levels and hepatic glutathione S-transferase(GST) activity,a prototypical phase 2 antioxidant ***: Dietary supplementation with BS extract containing SF precursor GR for 2 mo significantly decreased serum levels of liver function markers,ALT [median(interquartile range),before: 54.0(34.5-79.0) vs after supplementation: 48.5(33.3-65.3) IU/L,P < 0.05] and γ-GTP [before: 51.5(40.8-91.3) vs after: 50.0(37.8-85.3) IU/L,P < 0.05],as well as the alkali phosphatase activity. Placebo showed no significant effects on the markers. The urinary level of 8-OHd G,an established oxidative stress marker,was significantly reduced in participants who had received BS capsules but not the placebo [before: 6.66(5.51-9.03) vs after: 5.49(4.89-6.66) ng/mg-creatinine,P < 0.05]. The reduction of urinary 8-OHd G was significantly correlated with decreased levels of both ALT and γ-GTP [?8-OHd G and ?ALT: S

关键词： Sulforaphane Glucoraphanin Broccoli sprout Nrf2 He

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Broccoli sprout extract induces detoxification-related gene expression and attenuates acute liver injury

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World Journal of Gastroenterology 2015年第35期21卷 10091-10103页

作者： Kazutaka Yoshida yusuke ushida Tomoko Ishijima Hiroyuki Suganuma Takahiro Inakuma Nobuhiro Yajima Keiko Abe Yuji Nakai Research and Development Division Kagome Co.Ltd. Department of Applied Biological Chemistry Graduate School of Agricultural and Life ScienceThe University of Tokyo Faculty of Contemporary Human Life Science Department of Food and NutritionTezukayama University Institute for Food Science Hirosaki University

AIM: To investigate the effects of broccoli sprout extract(BSEx) on liver gene expression and acute liver injury in the ***: First, the effects of BSEx on liver gene expression were examined. Male rats were divided into two groups. The Control group was fed the AIN-76 diet, and the BSEx group was fed the AIN-76 diet containing BSEx. After a 10-d feeding period, rats were sacrificed and their livers were used for DNA microarray and realtime reverse transcription-polymerase chain reaction(RT-PCR) analyses. Next, the effects of BSEx on acute liver injury were examined. In experiments using acute liver injury models, 1000 mg/kg acetaminophen(APAP) or 350 mg/kg D-galactosamine(D-Gal N) was used to induce injury. These male rats were divided into four groups: Control, BSEx, Inducer(APAP or D-Gal N), and Inducer+BSEx. The feeding regimens were identical for the two analyses. Twenty-four hours following APAP administration via p.o. or D-Gal N administration via i.p., rats were sacrificed to determine serum aspartate transaminase(AST) and alanine transaminase(ALT) levels, hepatic glutathione(GSH) and thiobarbituric acid-reactive substances accumulation and glutathioneS-transferase(GST) activity. RESULTS: Microarray and real-time RT-PCR analyses revealed that BSEx upregulated the expression of genes related to detoxification and glutathione synthesis in normal rat liver. The levels of AST(70.91 ± 15.74 IU/m L vs 5614.41 ± 1997.83 IU/m L, P < 0.05) and ALT(11.78 ± 2.08 IU/m L vs 1297.71 ± 447.33 IU/m L, P < 0.05) were significantly suppressed in the APAP + BSEx group compared with the APAP group. The level of GSH(2.61 ± 0.75 nmol/g tissue vs 1.66 ± 0.59 nmol/g tissue, P < 0.05) and liver GST activity(93.19 ± 16.55 U/g tissue vs 51.90 ± 16.85 U/g tissue, P < 0.05) were significantly increased in the APAP + BSEx group compared with the APAP group. AST(4820.05 ± 3094.93 IU/m L vs 12465.63 ± 3223.97 IU/m L, P < 0.05) and ALT(1808.95 ± 1014.04 IU/m L vs 3936.46 ± 777.52 IU/

关键词： Broccoli sprout Galactosamine Acute liver injury G

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BEM Analysis of Wave Propagation in a Water-Filled Borehole in an Anisotropic Solid

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Tsinghua Science and Technology 2007年第5期12卷 520-526页

作者： S. Hirose Y. ushida C. Y, Wang Department of Mechanical and Environmental Engineering Tokyo Institute of Technology Tokyo 152-8552 Japan Schlumberger-Doll Research 36 Old Quarry Road Ridgefield CT 06877-4108 USA

This paper describes a time-domain boundary element method developed to analyze the interactions of acoustic and elastic waves near the interfaces between water and an anisotropic elastic solid. Two models are analyzed with one being the interface between two half spaces of fluid and solid and the other being a fluid region sandwiched by half space domains of anisotropic elastic solids. Both monopole and dipole point sources are used to generate an initial pressure wave in the fluid. Some snapshots of the transient wave behavior near the fluid-solid interfaces are given. The effect of the anisotropy in the solid on the pressure waveforms in the fluid is discussed. The numerical results allow detailed arrival identification and interpretation of acoustic and elastic waves propagating along the fluid-solid interfaces.

关键词： boundary element method wave propagation anisotropic solid fluid-solid interface

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Surgical Outcomes of a Small Incision Limbus-Based Revision for Failed Trabeculectomies

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Open Journal of Ophthalmology 2022年第1期12卷 121-127页

作者： Marcus Suehiro Fabio Luis de Arruda Zantut Flavio Siqueira Lopes Michele ushida Barbosa Syryl Dorairaj Tiago Santos Prata Paulista School of Medicine Federal University of Sao Paulo Sao Paulo Brazil

Background: Trabeculectomy does not always work as long as necessary to control glaucoma. This study aimed to describe the initial outcomes of a surgical technique for restoring failed trabeculectomies. Methods: We reviewed patients with failed trabeculectomy with mitomycin (MMC) who underwent limbus-based revision. After the dissection of the subconjunctival area through a smaller incision (3 mm), MMC was applied and episcleral fibrosis was excised. Each criterion was classified as complete or qualified for glaucoma medication. Results: Nineteen patients (19 eyes) were included in this study. The mean follow-up was 9.4 ± 8.6 months. At the last follow-up visit, the mean intraocular pressure was reduced from 20.9 ± 8.4 (range, 12 - 44 mmHg) to 11.6 ± 3.6 mm Hg (range, 6 - 19 mmHg) (p Conclusions: Our initial results suggest that limbus-based revision is an effective alternative to restoring failed trabeculectomies with minor postoperative complications.

关键词： Glaucoma Surgery Trabeculectomy Revision Mitomycin

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Relationship between biological factors and catastrophizing and clinical outcomes for female patients with knee osteoarthritis

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World Journal of Orthopedics 2017年第3期8卷 278-285页

作者： Tatsunori Ikemoto Hirofumi Miyagawa Yukiko Shiro Young-Chang Park Arai Machiko Akao Kenta Murotani Takahiro ushida Masataka Deie Institute of Physical Fitness Sports Medicine and Rehabilitation Aichi Medical University Department of Physical Therapy Faculty of Rehabilitation Sciences Nagoya Gakuin University Department of Orthopedic Surgery Aichi Medical University Division of Biostatistics Clinical Research Center Aichi Medical University

AIM To investigate the correlations between clinical outcomes and biopsychological variables in female patients with knee osteoarthritis(OA).METHODS Seventy-seven patients with symptomatic knee OA were enrolled in this *** investigated the age,body mass index(BMI),pain catastrophizing scale(PCS)and radiographic severity of bilateral knees using a Kellgren-Lawrence(K-L)grading system of the ***,a multiple linear regression was conducted to determine which variables best correlated with main outcomes of knee OA,which were pain severity,moving capacity by measuring timed-up-and-go test and Japanese Knee Osteoarthritis Measure(JKOM).RESULTS We found that the significant contributor to pain severity was PCS(β=0.555)and BMI(β=0.239),to moving capacity was K-L grade(β=0.520)and to PCS(β=0.313),and to a JKOM score was PCS(β=0.485)and K-L grade(β=0.421),*** The results suggest that pain catastrophizing as well as biological factors were associated with clinical outcomes in female patients with knee OA,irrespective of radiographic severity.

关键词： Osteoarthritis Pain catastrophizing Knee pain Physical function Japanese Knee Osteoarthritis Measure

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Flow Properties of Ultra-Fine Bubble Mixtures Passing through Micro-Apertures

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Journal of Flow Control, Measurement & Visualization 2015年第3期3卷 111-121页

作者： Akiomi ushida Tomiichi Hasegawa Takatsune Narumi Itaru Kourakata Yoshinori Nakamoto Faculty of Engineering Niigata University Niigata-shi Japan Niigata College of Technology Niigata-shi Japan Institute for Research Collaboration and Promotion Niigata University Niigata-shi Japan TECH CORPORATION Co. Ltd. Hiroshima-shi Japan

The flow properties of fine bubble mixture flows are investigated and reported. Few previous studies have focused on ultra-fine bubble (UFB) mixtures, which contain sub-micrometer sized bubbles. In this study, UFB mixtures of water and glycerol solution are passed through micro-sized slits and capillaries, and the resultant pressure drops are evaluated in comparison with those for water and aqueous glycerol alone. The experimentally measured pressure drop for slits (≤51 μm) and capillaries (≤81 μm) is less for UFB mixtures than for water and aqueous glycerol alone. This phenomenon is considered in terms of interface behavior and attributed to the electric interaction between an electric double layer and the UFBs. Furthermore, numerical observation for slip wall conditions is conducted, and the results for UFB mixtures agree with the predicted values for slip wall conditions.

关键词： Micro-Aperture Ultra-Fine Bubble Water Glycerol Pressure Drop

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Strategies for Managing Chronic Pain: Case of a Skilled Orthopaedic Physician and Mini-Review

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Open Journal of Orthopedics 2015年第5期5卷 109-114页

作者： Tatsunori Ikemoto Young-Chang P. Arai Makoto Nishihara Takahiro ushida Multidisciplinary Pain Center Aichi Medical University Nagakute Aichi Japan Institute of Physical Fitness Sports Medicine and Rehabilitation School of Medicine Aichi Medical University Nagakute Aichi Japan

Epidemiological surveys have recently revealed a high prevalence of chronic musculoskeletal pain in Japan;however, 30% of the patients in the survey were not satisfied with their pain treatment. This indicates that standard strategies in the management of chronic pain are poorly shared among physicians in Japan. Herein we report a case of a patient with intractable chronic pain who is a skilled orthopaedic physician. A 43-year-old man who was a skilled orthopaedic surgeon presented at our center complaining of severe buttock pain especially around the right hip region for more than three years. At begging of pain onset, he was diagnosed with femoacetabular impingement syndrome (FAI) with labral tear. Despite biophysical interventions including twice surgeries and alternative conservative treatment, his pain persisted, and he occasionally had to take a day off work due to the severe pain. Therefore we had to evaluate his pathological condition using a multidimensional approach based on a biopsychosocial model. We had provided him with cognitive behavioral therapy (CBT) approach, and simultaneously suggestion for short leaving from work. Three months after the start of CBT training, his disabilities had begun to improve. About six months later, he could continue to do his work. Finally, 19 months have passed since we started implementing the CBT approach;he has regained both his previous work-life balance and his health, although the pain has not completely subsided. In conclusion, we think it is important for physicians treating chronic pain to learn the management strategies for chronic pain and to re-consider their management policy when conventional biomedical interventions were not succeeded, even in cases where medication and surgical intervention are warranted.

关键词： Chronic Pain Cognitive Behavioral Therapy Biomedical Biopsychosocial

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求解非线性电路的代换算法

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南邮科技译丛 1989年第3期 110-134页

作者： ushida,A 胡瑞嘉

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