29 results on '"Fukumitsu S"'
Search Results
2. Flaxseed lignan attenuates high-fat diet-induced fat accumulation and induces adiponectin expression in mice.
- Author
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Fukumitsu S, Aida K, Ueno N, Ozawa S, Takahashi Y, and Kobori M
- Published
- 2008
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3. Helicobacter pylori-negative gastric and duodenal ulcers.
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Tsuji, Hideharu, Kohli, Yoshihiro, Fukumitsu, Shinji, Morita, Kiyoshi, Kaneko, Hiroto, Ohkawara, Tohru, Minami, Masahito, Ueda, Kazushige, Sawa, Yoshihiko, Matsuzaki, Haruki, Morinaga, Osamu, Ohkawara, Yasuo, Tsuji, H, Kohli, Y, Fukumitsu, S, Morita, K, Kaneko, H, Ohkawara, T, Minami, M, and Ueda, K
- Subjects
HELICOBACTER pylori infections ,PEPTIC ulcer ,HELICOBACTER pylori ,BIOPSY ,DISEASE incidence ,DUODENAL ulcers ,ENDOSCOPIC gastrointestinal surgery ,GASTRIC mucosa ,HELICOBACTER diseases - Abstract
It is unclear whether Helicobacter pylori infection is essential to the development of peptic ulcers. In this study, we examined the rates of H. pylori-negativity among patients with peptic ulcers. We also attempted to clarify the characteristics of H. pylori-negative peptic ulcers to throw light on the pathogenesis of peptic ulcers. The study included 215 consecutive patients with gastric ulcers (GUs) and 120 consecutive patients with duodenal ulcers (DUs). After routine endoscopic examination and phenol red dye endoscopy, forceps biopsies were performed for culture, histology, and the rapid urease test. A patient was considered H. pylori-negative when the serum anti-H. pylori IgG and the three tests on biopsied specimens were all negative. H. pylori-negative rates were 3.2% in the patients with GUs and 1.7% in the patients with DUs. Lack of atrophy of the gastric mucosa was significantly more common in the H. pylori-negative patients with GUs. A history of ulcer disease was less common and antral ulcers were more common in H. pylori-negative GU patients, but not significantly so. As the urea breath test had not been performed, the possibility of a false-negative result cannot be completely ruled out, but we believe that the H. pylori-negative rate in our study is more reliable than these rates in previous reports, because we visualized H. pylori distribution by phenol red dye endoscopy to avoid false-negative results in biopsies, and we used both biopsy and serum anti-H. pylori IgG findings to establish an H. pylori-negative diagnosis. Since H. pylori-negative peptic ulcers certainly exist, H. pylori infection is thought not to be essential to the development of peptic ulcers. There were few differences between the characteristics of H. pylori-negative and H. pylori-positive peptic ulcers in our study. A large-scale study is required to clarify the characteristics of H. pylori-negative peptic ulcers. [ABSTRACT FROM AUTHOR]
- Published
- 1999
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4. Are Antimuscarinic Drugs Effective Against Urinary Frequency Mediated by Atropine-Resistant Contractions?
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Fukumitsu Sakakibara, Mamoru Kiniwa, and Masato Nanri
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Therapeutics. Pharmacology ,RM1-950 - Abstract
In the disease states of urinary frequency and urgency, atropine-resistant contractions are known to be involved, in addition to contractions mediated by cholinergic nerves. This study was undertaken to investigate the mechanism underlying the development of atropine-resistant contractions using the representative antimuscarinic drugs solifenacin and tolterodine and also propiverine that has Ca2+ channel–antagonizing activity in addition to antimuscarinic activity. Rat models of urinary frequency were established by intravesical infusion of acetylcholine (ACh) (cholinergic nerve–mediated urinary frequency model), acetic acid (AcOH) [non-adrenergic noncholinergic nerve (NANC)-mediated urinary frequency model], or CaCl2 (atropine-resistant contractions-mediated urinary frequency model). Cystometrograms were obtained to measure the micturition parameters following oral administration of the aforementioned drugs. Propiverine increased the micturition weight in all the urinary frequency models. Solifenacin and tolterodine increased the micturition weight in the ACh-induced urinary frequency model but neither had any effect in the AcOH- or CaCl2-induced urinary frequency models. While antimuscarinic drugs are, in general, effective for the control of urinary frequency and incontinence, use of drugs possessing inhibitory effects on contractions mediated by cholinergic as well as NANC nerve transmission or Ca2+ influx into smooth muscles is recommended for management of the symptoms in disease states in which atropine-resistant contractions, such as Ca2+- and capsaicin-sensitive sensory nerves, are involved. Keywords:: urinary frequency, overactive bladder, propiverine, antimuscarinic, atropine-resistant contraction
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- 2011
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5. New method for esophageal varices- Simultaneous treatment of endoscopic injection sclerotherapy and variceal ligation (SSL)
- Author
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Takigawa, K., Akai, H., Morita, H., Tsuji, H., Fukumitsu, S., Fujino, H., Kohso, H., Akagi, H., Okano, H., Kodama, T., and Kashima, K.
- Published
- 1995
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6. Rosemary extract activates oligodendrogenesis genes in mouse brain and improves learning and memory ability.
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Sasaki K, Becker J, Ong J, Ciaghi S, Guldin LS, Savastano S, Fukumitsu S, Kuwata H, Szele FG, and Isoda H
- Abstract
Rosemary (Rosmarinus officinalis L.) is a rich source of dietary bioactive compounds such as rosmarinic acid and carnosol with a large repertoire of pharmacological properties, including anti-inflammatory and neuroprotective activities. In the present study, we investigated rosemary as a potential new therapeutic agent for cognitive function and other symptoms of aging. In this present study, we have aimed to investigate the effects of oral administration of rosemary extract (RME) on learning and memory in the context of other biomarkers-related cognitive function and neurotransmitter levels in senescent accelerated prone 8 (SAMP8) mouse, a model of accelerating aging and Alzheimer's disease. The Morris water maze (MWM) test showed improved spatial learning and memory behavior in RME treated SAMP8 mouse. Moreover, RME decreased Aβ
42 and inflammatory cytokine levels and increased BDNF, Sirt1, and neurotransmitter levels in SAMP8 mouse. Whole-genome microarray analysis revealed that RME significantly increased gene expression related to oligodendrocyte differentiation, myelination, and ATP production in the hippocampus and decreased gene expression related to stress, neuroinflammation, and apoptosis. Also, in the SAMP8 hippocampus, RME significantly increased Olig1 and Olig2 expression. Altogether, our study is the first to report improvement of spatial learning and memory of RME, modulation of genes important for oligodendrogenesis, and Anti-neuroinflammatory effect by suppressing Aβ42 levels in mouse brain and thus highlights the prospects of RME in the treatment of cognitive dysfunction and aging., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest., (Copyright © 2024. Published by Elsevier Masson SAS.)- Published
- 2024
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7. Usefulness of Olfactory Bulb Measurement in 3D-FIESTA in Differentiating Parkinson Disease from Atypical Parkinsonism.
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Ide S, Murakami Y, Futatsuya K, Anai K, Yoshimatsu Y, Fukumitsu S, Tsukamoto J, Hashimoto T, Adachi H, Ueda I, Kakeda S, and Aoki T
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- Humans, Male, Female, Aged, Diagnosis, Differential, Retrospective Studies, Middle Aged, Imaging, Three-Dimensional methods, Sensitivity and Specificity, Supranuclear Palsy, Progressive diagnostic imaging, Multiple System Atrophy diagnostic imaging, Olfactory Bulb diagnostic imaging, Olfactory Bulb pathology, Parkinson Disease diagnostic imaging, Magnetic Resonance Imaging methods, Parkinsonian Disorders diagnostic imaging
- Abstract
Background and Purpose: Parkinson disease is a prevalent disease, with olfactory dysfunction recognized as an early nonmotor manifestation. It is sometimes difficult to differentiate Parkinson disease from atypical parkinsonism using conventional MR imaging and motor symptoms. It is also known that olfactory loss occurs to a lesser extent or is absent in atypical parkinsonism. To the best of our knowledge, no study has examined olfactory bulb changes to differentiate Parkinson disease from atypical parkinsonism, even in an early diagnosis, and its association with conventional MR imaging findings. Hence, we aimed to assess the utility of olfactory bulb measurements in differentiating Parkinson disease from atypical parkinsonism even in the early stage., Materials and Methods: In this retrospective study, we enrolled 108 patients with Parkinson disease, 13 with corticobasal syndrome, 15 with multiple system atrophy, and 17 with progressive supranuclear palsy who developed parkinsonism. Thirty-nine age-matched healthy subjects served as controls. All subjects underwent conventional MR imaging and 3D FIESTA for olfactory bulb measurements using manual ROI quantification of the cross-sectional olfactory bulb area using the coronal plane. Bilateral olfactory bulb measurements were averaged. For group comparisons, we used the Welch t test, and we assessed diagnostic accuracy using receiver operating characteristic analysis., Results: Patients with Parkinson disease had a mean olfactory bulb area of 4.2 (SD, 1.0 mm
2 ), significantly smaller than in age-matched healthy subjects (6.6 [SD, 1.7 mm2 ], P < .001), and those with corticobasal syndrome (5.4 [SD, 1.2 mm2 ], P < .001), multiple system atrophy (6.5 [SD, 1.2 mm2 ], P < .001), and progressive supranuclear palsy (5.4 [SD, 1.2 mm2 ], P < .001). The receiver operating characteristic analysis for the olfactory bulb area measurements showed good diagnostic performance in differentiating Parkinson disease from atypical parkinsonism, with an area under the curve of 0.87, an optimal cutoff value of 5.1 mm2 , and a false-positive rate of 18%. When we compared within 2 years of symptom onset, the olfactory bulb in Parkinson disease (4.2 [SD, 1.1 mm2 ]) remained significantly smaller than in atypical parkinsonism (versus corticobasal syndrome (6.1 [SD, 0.7 mm2 ]), P < .001; multiple system atrophy (6.3 [SD, 1.4 mm2 ]), P < .001; and progressive supranuclear palsy (5.2 [1.3 mm2 ], P = .003, respectively)., Conclusions: 3D FIESTA-based olfactory bulb measurement holds promise for distinguishing Parkinson disease from atypical parkinsonism, especially in the early stage., (© 2024 by American Journal of Neuroradiology.)- Published
- 2024
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8. Effects of Oleanolic Acid Derived from Wine Pomace on Periodontopathic Bacterial Growth in Healthy Individuals: A Randomized Placebo-Controlled Study.
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Shimazu K, Ookoshi K, Fukumitsu S, Kagami H, Mitsuhata C, Nomura R, and Aida K
- Abstract
Periodontal disease is caused by oral pathogenic bacteria and is associated with systemic disease and frailty. Therefore, its prevention is crucial in extending healthy life expectancy. This study aimed to evaluate the effect of orally administered oleanolic acid, extracted from wine pomace, on periodontopathic bacterial growth in healthy individuals. In this randomized, placebo-controlled, double-blind, parallel-group comparison study, 84 healthy adults were assigned to a placebo ( n = 29), low-dose ( n = 29, 9 mg oleanolic acid), or high-dose ( n = 26, 27 mg oleanolic acid) groups. The number of oral bacteria in their saliva, collected before and 5 h after administration, was determined using the polymerase chain reaction-invader technique. The proportion of periodontopathic bacteria among the total oral bacteria in the saliva was calculated. Oleanolic acid significantly decreased the proportion of Porphyromonas gingivalis among the total oral bacteria in a dose-dependent manner ( p = 0.005 (low-dose) and p = 0.003 (high-dose) vs. placebo, Williams' test). Moreover, high-dose oleanolic acid decreased the proportion of Tannerella forsythia ( p = 0.064 vs. placebo, Williams' test). Periodontopathic bacteria are closely associated with the development and progression of periodontal disease; thus, the continuous daily intake of oleanolic acid derived from pomace may be helpful in maintaining a healthy oral microbiome by controlling the proportion of periodontopathic bacteria., Competing Interests: This study was conducted by Clinical Creative Co., Ltd. (Saitama, Japan), and the Nippn Corporation (Tokyo, Japan) provided the research funds and test foods. Authors, K.S., K.O., S.F. and K.A., were employed by the Nippn Corporation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
- Published
- 2024
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9. Availability of dietary secoisolariciresinol diglucoside on borderline blood cholesterol level in men: a randomized, parallel, controlled, double-blinded clinical trial.
- Author
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Ookoshi K, Sawane K, Fukumitsu S, and Aida K
- Abstract
Borderline low-density lipoprotein cholesterol levels (120-139 mg/dl) increase the risk of cardiovascular disease. Therefore, the use of functional dietary nutrients is expected to control blood low-density lipoprotein cholesterol levels. This study aimed to evaluate the effect of dietary secoisolariciresinol diglucoside on blood cholesterol in healthy adults with borderline low-density lipoprotein cholesterol levels. A randomized, parallel, controlled, double-blinded clinical trial was performed for participants with borderline low-density lipoprotein cholesterol levels, for 12 weeks with secoisolariciresinol diglucoside (60 mg/day) or placebo. Lipid profile [low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio, total cholesterol, and triglycerides] and liver disease risk markers were measured at weeks 0, 4, 8, and 12. Analyzing 36 participants in each group revealed a significant interaction between treatment and time, indicating reduced low-density lipoprotein cholesterol ( p = 0.049) and total cholesterol ( p = 0.020) levels in secoisolariciresinol diglucoside-receiving men but not women. However, no significant differences were observed in other markers regardless of gender. The results suggest that a daily intake of 60 mg of secoisolariciresinol diglucoside lowers low-density lipoprotein cholesterol and total cholesterol levels in men with borderline low-density lipoprotein cholesterol, proposing secoisolariciresinol diglucoside potential as a functional dietary nutrient for cardiovascular disease prevention. This study was registered in the UMIN-CTR database (UMIN000046202)., Competing Interests: All authors were employed by NIPPN Corporation. Clinical experiments were conducted by Clinical Creative Corporation and Sapporo Yurinokai Hospital with funds provided by NIPPN Corporation. The authors have no conflicts of interest to declare., (Copyright © 2024 JCBN.)
- Published
- 2024
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10. Feasibility of Breath-Hold Zero TE Magnetic Resonance Imaging Sequence for Evaluation of Pulmonary Arteriovenous Malformations After Embolotherapy.
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Hayashida Y, Murakami Y, Fukumitsu S, Yoshimatsu Y, Anai K, Todoroki Y, Fujisaki A, Ide S, and Aoki T
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- Humans, Feasibility Studies, Magnetic Resonance Imaging methods, Breath Holding, Artifacts, Arteriovenous Malformations diagnostic imaging, Arteriovenous Malformations therapy, Embolization, Therapeutic, Arteriovenous Fistula, Pulmonary Artery abnormalities, Pulmonary Veins abnormalities
- Abstract
Abstract: We obtained breath-hold zero TE (ZTE) magnetic resonance imaging for the evaluation of pulmonary arteriovenous malformations before and after embolotherapy. To the best of our knowledge, there have been no reports of ZTE for the entire lung imaging in single breath-hold scan time such as 20 seconds. Breath-hold ZTE magnetic resonance imaging can be a useful technique for magnetic resonance-based follow-up of vascular lung diseases without using contrast media, reducing the undesired artifacts from metallic devices., Competing Interests: Conflicts of Interest and Source of Funding: The authors have no conflicts of interest to declare that are relevant to the content of this article., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2024
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11. Zero Echo Time Magnetic Resonance Imaging; Techniques and Clinical Utility in Musculoskeletal System.
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Fujisaki A, Tsukamoto J, Narimatsu H, Hayashida Y, Todoroki Y, Hirano N, Takeda K, Shin S, Ota S, Anai K, Fukumitsu S, Yoshimatsu Y, Kono Y, Ueno M, Ide S, Murakami Y, and Aoki T
- Subjects
- Humans, Tomography, X-Ray Computed methods, Magnetic Resonance Imaging methods, Image Processing, Computer-Assisted methods, Musculoskeletal System diagnostic imaging
- Abstract
Zero echo time (ZTE) sequence is recent advanced magnetic resonance technique that utilizes ultrafast readouts to capture signals from short-T2 tissues. This sequence enables T2- and T2* weighted imaging of tissues with short intrinsic relaxation times by using an extremely short TE, and are increasingly used in the musculoskeletal system. We review the imaging physics of these sequences, practical limitations, and image reconstruction, and then discuss the clinical utilities in various disorders of the musculoskeletal system. ZTE can be readily incorporated into the clinical workflow, and is a promising technique to avoid unnecessary radiation exposure, cost, and time-consuming by computed tomography in some cases. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 1., (© 2023 International Society for Magnetic Resonance in Medicine.)
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- 2024
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12. Pharmacokinetics and effect of maslinic acid with physical exercise on grip strength and trunk muscle mass in healthy Japanese individuals.
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Yamauchi Y, Kinoshita T, Fukumitsu S, Aida K, Maruyama K, Saito I, and Yamamoto N
- Abstract
Age-related changes in physical function are closely associated with daily activity impairment among the elderly. Continuous maslinic acid intake may improve skeletal muscle mass; however, the concentration-dependent benefits of maslinic acid for physical functionality remain unclear. Therefore, we evaluated the bioavailability of maslinic acid and examined the effect of maslinic acid intake on skeletal muscle and quality of life in the healthy Japanese elderly. Five healthy adult men were administered test diets containing 30, 60, or 120 mg of maslinic acid. Analysis of plasma maslinic acid revealed concentration-dependent elevations in blood maslinic acid levels ( p <0.01). Next, 69 healthy Japanese adult men and women were administered a placebo or 30 or 60 mg of maslinic acid continuously for 12 weeks with physical exercise in a randomized, double-blind, placebo-controlled trial. The trunk muscle mass ( p <0.05) and vitality score according to the Short-Form-8 ( p <0.05) were significantly higher in the 60 mg maslinic acid group than in the placebo group. Additionally, grip strength was significantly higher in the 30 ( p <0.05) and 60 mg ( p <0.05) groups than in the placebo group. Overall, maslinic acid intake with physical exercise improved muscle strength, muscle mass, and quality of life in a maslinic acid-intake-dependent manner., Competing Interests: This study was based on a contract agreement between NIPPN Corporation and SOUKEN Co., Ltd. (Experiment 1) and the Institute of Community Life Sciences Co., Ltd. (Experiment 2). Tetsu Kinoshita is the head of the Institute of Community Life Sciences. Yuki Yamauchi, Satoshi Fukumitsu, and Kazuhiko Aida are employees of NIPPN Corporation. The other authors have no personal or financial conflicts of interest., (Copyright © 2023 JCBN.)
- Published
- 2023
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13. A Descriptive Whole-Genome Transcriptomics Study in a Stem Cell-Based Tool Predicts Multiple Tissue-Specific Beneficial Potential and Molecular Targets of Carnosic Acid.
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Ferdousi F, Sasaki K, Fukumitsu S, Kuwata H, Nakajima M, and Isoda H
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- Humans, Transcriptome, Abietanes pharmacology, Abietanes chemistry, Antioxidants pharmacology, Antioxidants chemistry, Diterpenes pharmacology
- Abstract
Carnosic acid (CA) is a phenolic diterpene widely distributed in herbal plants, rosemary and sage. Although its medicinal properties, such as antioxidant, antimicrobial, and neuroprotective effects, have been well-documented, its relevant biochemical processes and molecular targets have not been fully explored yet. In the present study, we conducted an untargeted whole-genome transcriptomics analysis to investigate CA-induced early biological and molecular events in human amniotic epithelial stem cells (hAESCs) with the aim of exploring its multiple tissue-specific functionalities and potential molecular targets. We found that seven days of CA treatment in hAESCs could induce mesoderm-lineage-specific differentiation. Tissue enrichment analysis revealed that CA significantly enriched lateral plate mesoderm-originated cardiovascular and adipose tissues. Further tissue-specific PPI analysis and kinase and transcription factor enrichment analyses identified potential upstream regulators and molecular targets of CA in a tissue-specific manner. Gene ontology enrichment analyses revealed the metabolic, antioxidant, and antifibrotic activities of CA. Altogether, our comprehensive whole-genome transcriptomics analyses offer a thorough understanding of the possible underlying molecular mechanism of CA.
- Published
- 2023
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14. A New Approach for Characterizing the Thixotropic Properties of Gel Formulations as Sprayable Agents Based on Rheological Analysis.
- Author
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Terukina T, Uchiyama Y, Kikuma F, Fukumitsu S, Iwata N, Kanazawa T, and Kondo H
- Subjects
- Rheology methods, Viscosity, Gels, Alginates
- Abstract
The present study evaluated the rheological properties of gel formulations composed of the thixotropic peptide amphiphile, palmitoyl-glycine-histidine (Pal-GH), and the thickener, propylene glycol alginate (PGA), to propose a proper approach to design sprayable gel formulations with good spray performance and high retention of a therapeutic agent. The hysteresis loop area (HLA), a conventional index of thixotropy, was determined from the relationship between the shear stress and shear rate of various formulations with different amounts of Pal-GH and PGA. In addition, a new assessment method for characterizing the thixotropy using the initial structure recovery speed was determined based on the time course of the complex modulus (G*) after structural breakdown of the gel formulations. The G* values increased with the increase in the amount of Pal-GH and PGA, indicating that the formulations were not deformable. Additionally, high HLA and high initial structure recovery speed are preferable when selecting a formulation with good spray performance and high retention. As suitable combinations of Pal-GH and PGA could exhibit both high HLA and high initial structure recovery speed, they are promising components for gel formulations to be used as sprayable agents with good spray performance and high retention. The results also suggested that the initial structure recovery speed would reflect the thixotropy for the formulation more appropriately than HLA. Thus, the initial structure recovery speed could be a useful scale for the preparation of sprayable gel formulations., (© 2022. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)
- Published
- 2022
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15. Antidepressant- and anxiolytic-like activities of Rosmarinus officinalis extract in rodent models: Involvement of oxytocinergic system.
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Sasaki K, Ferdousi F, Fukumitsu S, Kuwata H, and Isoda H
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- Animals, Anti-Anxiety Agents isolation & purification, Anti-Anxiety Agents pharmacology, Antidepressive Agents isolation & purification, Antidepressive Agents pharmacology, Anxiety drug therapy, Anxiety metabolism, Brain drug effects, Brain metabolism, Depression drug therapy, Depression metabolism, Dose-Response Relationship, Drug, Inflammation Mediators antagonists & inhibitors, Inflammation Mediators metabolism, Male, Mice, Mice, Inbred ICR, Oxytocin agonists, Plant Extracts isolation & purification, Plant Extracts pharmacology, Receptors, Oxytocin agonists, Anti-Anxiety Agents therapeutic use, Antidepressive Agents therapeutic use, Oxytocin metabolism, Plant Extracts therapeutic use, Receptors, Oxytocin metabolism, Rosmarinus
- Abstract
Background: Oxytocin (OXT), a neuropeptide involved in mammal reproductive and prosocial behaviors, has been reported to interact with various stressor-provoked neurobiological changes, including neuroendocrine, neurotransmitter, and inflammatory processes. In view of disturbances in psychosocial relationships due to social isolation and physical distancing measures amid the COVID-19 pandemic, being one of the triggering factors for the recent rise in depression and anxiety, OXT is a potential candidate for a new antidepressant., Methods: In this present study, we have aimed to investigate the effects of oral administration of Rosmarinus officinalis extract (RE), extracted from distillation residue of rosemary essential oil, on central OXT level in the context of other stress biomarkers and neurotransmitter levels in mice models. Tail suspension test (TST) and elevated plus maze test (EPMT) following LPS injection were employed to assess depressive- and anxiety-like behavior in mice, respectively., Findings: Pretreatment with RE for seven days significantly improved behavior in TST and EPMT. Whole-genome microarray analysis reveals that RE significantly reversed TST stress-induced alterations in gene expressions related to oxytocinergic and neurotransmitter pathways and inflammatory processes. In both models, RE significantly increased central Oxt and Oxtr expressions, as well as OXT protein levels. RE also significantly attenuated stress-induced changes in serum corticosterone, brain and serum BDNF levels, and brain neurotransmitters levels in both models., Interpretation: Altogether, our study is the first to report antidepressant- and anxiolytic-like activities of RE through modulating oxytocinergic system in mice brain and thus highlights the prospects of RE in the treatment of depressive disorders of psychosocial nature., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
- Published
- 2021
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16. Maslinic Acid Attenuates Denervation-Induced Loss of Skeletal Muscle Mass and Strength.
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Yamauchi Y, Ferdousi F, Fukumitsu S, and Isoda H
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- Animals, Gene Expression Profiling methods, Humans, Male, Mice, Mice, Inbred ICR, Muscle Denervation methods, Muscle Development genetics, Muscle, Skeletal innervation, Muscular Atrophy metabolism, Muscular Atrophy pathology, Muscular Diseases pathology, NF-kappa B metabolism, Olea chemistry, Sciatic Nerve injuries, Signal Transduction drug effects, Transforming Growth Factor beta metabolism, Tumor Necrosis Factor-alpha metabolism, Muscle Strength drug effects, Muscle, Skeletal drug effects, Muscular Atrophy drug therapy, Triterpenes pharmacology
- Abstract
Maslinic acid (MA) is a pentacyclic triterpene abundant in olive peels. MA reportedly increases skeletal muscle mass and strength in older adults; however, the underlying mechanism is unknown. This study aimed to investigate the effects of MA on denervated muscle atrophy and strength and to explore the underlying molecular mechanism. Mice were fed either a control diet or a 0.27% MA diet. One week after intervention, the sciatic nerves of both legs were cut to induce muscle atrophy. Mice were examined 14 days after denervation. MA prevented the denervation-induced reduction in gastrocnemius muscle mass and skeletal muscle strength. Microarray gene expression profiling in gastrocnemius muscle demonstrated several potential mechanisms for muscle maintenance. Gene set enrichment analysis (GSEA) revealed different enriched biological processes, such as myogenesis, PI3/AKT/mTOR signaling, TNFα signaling via NF-κB, and TGF-β signaling in MA-treated mice. In addition, qPCR data showed that MA induced Igf1 expression and suppressed the expressions of Atrogin-1, Murf1 and Tgfb . Altogether, our results suggest the potential of MA as a new therapeutic and preventive dietary ingredient for muscular atrophy and strength.
- Published
- 2021
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17. Vertebrobasilar Infarction Due to Bow Hunter's Syndrome in a Patient with Rheumatoid Arthritis: A Case Report.
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Yoshimatsu Y, Ide S, Kakeda S, Murakami Y, Fukumitsu S, Takeshita Y, Anai K, Hamamura T, Yoshida S, Sakai A, and Korogi Y
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- Female, Humans, Infarction, Middle Aged, Vertebral Artery diagnostic imaging, Arthritis, Rheumatoid complications, Arthritis, Rheumatoid diagnostic imaging, Mucopolysaccharidosis II, Vertebrobasilar Insufficiency diagnostic imaging, Vertebrobasilar Insufficiency etiology
- Abstract
A 60-year-old woman with a 37-year history of rheumatoid arthritis (RA) had a sudden onset of headache. Head MRI showed acute multiple infarctions in the vertebrobasilar region, and MR angiography showed stenosis of the right vertebral artery (VA). 3D-CT angiography of the craniovertebral junction showed atlantoaxial subluxation and stenosis of the right VA just distal to the transverse foramen of C2, which was due to osteophytes and degenerative changes secondary to RA. Digital subtraction angiography clearly demonstrated occlusion of the right VA during rightward head rotation. Based on those findings, rotatory instability at C1-2 was considered as the primary cause of the vertebrobasilar infarctions, and Bow Hunter's syndrome was diagnosed. The patient underwent C1-5 posterior fixation, and brain infarction has not recurred.
- Published
- 2021
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18. Modulation of cellular circadian clocks by triterpenoids.
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Suzuki C, Fukumitsu S, and Oike H
- Subjects
- Animals, Circadian Rhythm, Mice, NIH 3T3 Cells, Period Circadian Proteins metabolism, Circadian Clocks, Triterpenes pharmacology
- Abstract
Many living organisms on earth have clock systems in their body. It has increasingly become clear that a disturbance in the internal clocks has negative effects on our body. Terpenes are organic compounds found in various plants that are reported to have several pharmacological actions. In this study, we focused on commercially available 27 triterpenoids and evaluated their influence on the circadian rhythm of human U2OS cells and mouse NIH3T3 cells. The expression level of Per2, one of the core clock genes, was measured using luminescent reporters over the time period of a few days. We found that 8 triterpenoids reset the phase of the circadian clocks. Representative compounds were corosolic acid, cucurbitacin B, and celastrol; similar effects were also confirmed with some structural analogues of cucurbitacin B and celastrol. These compounds shifted the phase bilaterally depending on the stimulus timing and also acted as synchronizers in desynchronized cells. The effective concentrations of cucurbitacin B and celastrol were less than 0.5 μM. In addition, cucurbitacin B and celastrol were also found to be effective in tissue explants in mice. Furthermore, celastrol dose-dependently shortened the period length of NIH3T3 cells. Some of these compounds are found in edible and medicinal plants and may help regulate our circadian clocks in everyday life., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Published
- 2021
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19. Oxytocin Ameliorates Impaired Behaviors of High Fat Diet-Induced Obese Mice.
- Author
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Hayashi R, Kasahara Y, Hidema S, Fukumitsu S, Nakagawa K, and Nishimori K
- Subjects
- Animals, Anxiety physiopathology, Depression physiopathology, Diet, High-Fat, Fear physiology, Hypothalamus drug effects, Hypothalamus physiology, Male, Memory drug effects, Mice, Inbred C57BL, Neurons drug effects, Neurons physiology, Oxytocin administration & dosage, Receptors, Oxytocin physiology, Social Behavior, Behavior, Animal physiology, Memory physiology, Obesity physiopathology, Obesity psychology, Oxytocin physiology
- Abstract
Excessive intake of fat is a major risk factor for lifestyle-related diseases such as heart disease and also affects brain function such as object recognition memory, social recognition, anxiety behavior, and depression-like behavior. Although oxytocin (OXT) has been reported to improve object recognition, social recognition, anxiety behavior, and depression-like behavior in specific conditions, previous studies did not explore the impact of OXT in high-fat diet (HFD)-fed mice. Furthermore, it remains unclear whether intake of HFD affects OXT/oxytocin receptor (OXTR) in the brain. Here, we demonstrated that peripheral OXT administration improves not only social recognition but also object recognition and depressive-like behavior in HFD-fed mice. In contrast, peripheral OXT administration to HFD-fed male mice increased fear and anxiety-related behavior. In addition, we observed that intake of HFD decreased OXTR and c-fos mRNA expression in the hippocampus, specifically. Furthermore, peripheral OXT administration increased OXT mRNA expression in the hypothalamus. Altogether, these findings suggest that OXT has the potential to improve various recognition memory processes via peripheral administration but also has side effects that increase fear-related behavior in males., (Copyright © 2020 Hayashi, Kasahara, Hidema, Fukumitsu, Nakagawa and Nishimori.)
- Published
- 2020
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20. Dietary Omega-3 Fatty Acid Dampens Allergic Rhinitis via Eosinophilic Production of the Anti-Allergic Lipid Mediator 15-Hydroxyeicosapentaenoic Acid in Mice.
- Author
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Sawane K, Nagatake T, Hosomi K, Hirata SI, Adachi J, Abe Y, Isoyama J, Suzuki H, Matsunaga A, Fukumitsu S, Aida K, Tomonaga T, Arita M, and Kunisawa J
- Subjects
- Administration, Intranasal, Animals, Anti-Allergic Agents metabolism, Disease Models, Animal, Eicosapentaenoic Acid metabolism, Eicosapentaenoic Acid pharmacology, Eosinophils drug effects, Female, Inflammation drug therapy, Linseed Oil administration & dosage, Lipid Metabolism, Mice, Mice, Inbred C57BL, Anti-Allergic Agents pharmacology, Eicosapentaenoic Acid analogs & derivatives, Eosinophils metabolism, PPAR gamma metabolism, Rhinitis, Allergic drug therapy
- Abstract
The metabolism and generation of bioactive lipid mediators are key events in the exertion of the beneficial effects of dietary omega-3 fatty acids in the regulation of allergic inflammation. Here, we found that dietary linseed oil, which contains high amounts of alpha-linolenic acid (ALA) dampened allergic rhinitis through eosinophilic production of 15-hydroxyeicosapentaenoic acid (15-HEPE), a metabolite of eicosapentaenoic acid (EPA). Lipidomic analysis revealed that 15-HEPE was particularly accumulated in the nasal passage of linseed oil-fed mice after the development of allergic rhinitis with the increasing number of eosinophils. Indeed, the conversion of EPA to 15-HEPE was mediated by the 15-lipoxygenase activity of eosinophils. Intranasal injection of 15-HEPE dampened allergic symptoms by inhibiting mast cell degranulation, which was mediated by the action of peroxisome proliferator-activated receptor gamma. These findings identify 15-HEPE as a novel EPA-derived, and eosinophil-dependent anti-allergic metabolite, and provide a preventive and therapeutic strategy against allergic rhinitis.
- Published
- 2019
- Full Text
- View/download PDF
21. The Anti-Arthritis Effect of Olive-Derived Maslinic Acid in Mice is Due to its Promotion of Tissue Formation and its Anti-Inflammatory Effects.
- Author
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Shimazu K, Fukumitsu S, Ishijima T, Toyoda T, Nakai Y, Abe K, Aida K, Okada S, and Hino A
- Subjects
- Animals, Male, Mice, Mice, Inbred DBA, Synovial Membrane drug effects, Synovial Membrane metabolism, Anti-Inflammatory Agents pharmacology, Arthritis, Experimental drug therapy, Triterpenes pharmacology
- Abstract
Scope: A previous study demonstrated that intake of olive pomace extract containing maslinic acid (MA), a triterpene, effectively prevents and alleviates arthritis in animals and humans. Here, the molecular mechanisms involved in the anti-arthritis effect of MA have been elucidated by determining gene expression changes induced by olive-derived MA intake in collagen antibody-induced arthritis (CAIA) mice., Methods and Results: Mice are divided into the untreated (CT), CAIA (CA), and CAIA administered MA (CA + MA) groups. The CA + MA mice are fed MA at a daily dose of 200 mg kg
-1 of body weight from day 1. CAIA is then induced on day 8 and evaluated on day 12. Arthritis symptoms are alleviated, and the gene expression of inflammatory cytokines is reduced in the CA + MA group compared with the CA group. A DNA microarray analysis of synovial membranes reveals that MA alters the expression levels of genes related to inflammation, including glucocorticoid responses, immune responses, and the extracellular matrix., Conclusions: The preventive effect of MA on arthritis is attributable to the promotion of tissue formation as well as suppression of inflammation in the synovium via inactivation of Toll-like receptor signaling and downregulation of leukotrienes through the glucocorticoid receptor., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)- Published
- 2019
- Full Text
- View/download PDF
22. Maslinic acid improves quality of life by alleviating joint knee pain in the elderly: results from a community-based pilot study.
- Author
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Fukumitsu S, Kinoshita T, Villareal MO, Aida K, Hino A, and Isoda H
- Abstract
Chronic knee joint pain is common in the elderly and associated with poor quality of life. This study, an open-label clinical trial, aimed to examine how the intake on a daily basis of maslinic acid-containing product (30 mg maslinic acid) on 29 elderly residents (mean 70.7 ± 10.1 years) of Nakajima Island, Ehime, Japan. Study participants consumed 10 g jelly containing maslinic acid daily for 16 weeks and at 0 (baseline), 4, 8, 12 and 16 weeks, assessed for health-related quality of life (Short Form-8) and knee pain score (Japanese Knee Osteoarthritis Measure). After 16 weeks, the physical quality of life, more specifically, the level of Bodily Pain and Physical Component Summary, but not mental quality of life, was significantly improved by maslinic acid intake. Furthermore, maslinic acid intake significantly decreased the Japanese Knee Osteoarthritis Measure at week 8 and tended to decrease Visual Analogue Scale score at weeks 4 and 16. These results suggest that consumption of maslinic acid has a protective effect against chronic knee pain in elderly residents in a community where knee pain causes high quality of life burden., Competing Interests: This study was supported by funding from Nippon Flour Mills Co., Ltd. (Tokyo, Japan) based on the contract agreement between Nippon Flour Mills and the Institute of Community Life Sciences Co., Ltd. Tetsu Kinoshita is a head of Institute of Community Life Sciences. Nippon Flour Mills had no commitment in the data analysis and interpretation. Other authors had no personal or financial conflict of interest.
- Published
- 2017
- Full Text
- View/download PDF
23. Maslinic acid in olive fruit alleviates mild knee joint pain and improves quality of life by promoting weight loss in the elderly.
- Author
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Fukumitsu S, Villareal MO, Aida K, Hino A, Hori N, Isoda H, and Naito Y
- Abstract
Consumption of olives ( Olea europaea L.) is associated with a low incidence of inflammation-related diseases. Olive fruit is rich in bioactive pentacyclic triterpenoids, mainly maslinic acid. This study, a randomized, double-blind, and placebo-controlled trial, examined the effects of an orally administered maslinic acid supplement, olive fruit extract, on 20 middle-aged and elderly volunteers with mild knee joint pain. Each subject (58 ± 7 years) received either olive fruit extract, containing 50 mg maslinic acid ( n = 12), or placebo ( n = 8) daily for 12 weeks and evaluated for pain and physical functions as primary outcome measures. Secondary outcome measures included body composition and inflammatory biomarkers in serum. Although both groups exhibited improved pain visual analogue scale score and quality of life after supplementation, symptoms were better in the maslinic acid group than in the placebo group. After 12 weeks, maslinic acid group exhibited significant decrease in body weight and body mass index suggesting that maslinic acid affected the weight of volunteers with mild knee joint pain. Therefore, olive products containing maslinic acid may be useful as a new preventive and therapeutic food ingredient for arthritic diseases. Since this clinical study is a preliminary study, it was not registered in a publicly accessible database., Competing Interests: No potential conflicts of interest were disclosed.
- Published
- 2016
- Full Text
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24. Anti-inflammatory and anti-arthritic effects of pentacyclic triterpenoids maslinic acid through NF-κB inactivation.
- Author
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Fukumitsu S, Villareal MO, Fujitsuka T, Aida K, and Isoda H
- Subjects
- Animals, Arthritis, Experimental chemically induced, Arthritis, Experimental drug therapy, Carrageenan toxicity, Cell Line, Disease Models, Animal, Edema chemically induced, Edema drug therapy, Inflammation drug therapy, Inflammation genetics, Lipopolysaccharides toxicity, Macrophages drug effects, Male, Mice, Inbred BALB C, Olea chemistry, Plant Extracts pharmacology, Tumor Necrosis Factor-alpha metabolism, Anti-Inflammatory Agents, Non-Steroidal pharmacology, Antirheumatic Agents pharmacology, NF-kappa B metabolism, Triterpenes pharmacology
- Abstract
Scope: Consumption of olives (Olea europaea L.), including table olives and oil, is associated with low incidence of inflammation-related diseases. In this study, the effects of maslinic acid (MA), the main constituent of olive pomace, on the expression of genes and proteins involved in inflammatory activity in RAW 264.7 cells were investigated. Furthermore, the effect of MA on carrageenan-induced paw edema and collagen antibody induced arthritis in mice was determined., Methods and Results: We confirmed the suppressive effects of MA on LPS-induced tumor necrosis factor α production and on the expression of inflammatory response associated genes in RAW 264.7 cells. We also clarified the suppressive effect of MA on LPS-induced nuclear factor-kappa B activation as well as the phosphorylation of IκB-α. Furthermore, MA (200 mg/kg in the edema model or 100 mg/kg in the arthritis model) exerted anti-inflammatory and antiarthritis effects as shown by the suppression of paw edema, arthritis score, inflammatory cells, and destruction of synovium in knee joints., Conclusion: Olive products containing MA are useful as a new preventive and therapeutic food ingredient for inflammatory and arthritic diseases., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2016
- Full Text
- View/download PDF
25. α-Linolenic acid suppresses cholesterol and triacylglycerol biosynthesis pathway by suppressing SREBP-2, SREBP-1a and -1c expression.
- Author
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Fukumitsu S, Villareal MO, Onaga S, Aida K, Han J, and Isoda H
- Abstract
α-Linolenic acid (ALA), a major fatty acid in flaxseed oil, has multiple functionalities such as anti-cardiovascular and anti-hypertensive activities. In this study, we investigated the effects of ALA on lipid metabolism and studied the possible mechanisms of its action in differentiated 3T3-L1 adipocytes using DNA microarray analysis. From a total of 34,325 genes in the DNA chip, 87 genes were down-regulated and 185 genes were up-regulated at least twofold in differentiated 3T3-L1 adipocyte cells treated with 300 μM ALA for a week, 5-12 days after induction of cell differentiation, compared to ALA-untreated 3T3-L1 adipocytes (control). From the Reactome analysis results, eight lipid metabolism-related genes involved in cholesterol and triacylglycerol biosynthesis pathway and lipid transport were significantly down-regulated by ALA treatment. Furthermore, ALA significantly decreased the mRNA expressions of sterol regulatory element binding protein (SREBP)-2, SREBP-1a, SREBP-1c and fatty acid synthase (FAS) in 3T3-L1 adipocyte cells. On the other hand, the average levels of the gene expressions of carnitine palmitoyltransferase 1a (CPT-1a) and leptin in 300 μM ALA treatment were increased by 1.7- and 2.9-fold, respectively, followed by an increase in the intracellular ATP content. These results show that ALA is likely to inhibit cholesterol and fatty acid biosynthesis pathway by suppressing the expression of transcriptional factor SREBPs. Furthermore, ALA promotes fatty acid oxidation in 3T3-L1 adipocytes, thereby increasing its health benefits.
- Published
- 2013
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26. Four new cembrane diterpenes isolated from an Okinawan soft coral Lobophytum crassum with inhibitory effects on nitric oxide production.
- Author
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Wanzola M, Furuta T, Kohno Y, Fukumitsu S, Yasukochi S, Watari K, Tanaka C, Higuchi R, and Miyamoto T
- Subjects
- Animals, Anti-Inflammatory Agents isolation & purification, Cell Line, Diterpenes isolation & purification, Macrophages drug effects, Mice, Molecular Structure, Nitric Oxide immunology, Anthozoa chemistry, Anti-Inflammatory Agents chemistry, Anti-Inflammatory Agents pharmacology, Diterpenes chemistry, Diterpenes pharmacology, Nitric Oxide antagonists & inhibitors
- Abstract
Four new cembrane diterpenes (1-4) and fifteen known cembranoids (5-19) were isolated from an Okinawan soft coral Lobophytum crassum. The structures of these four new cembranoids were determined on the basis of spectroscopic evidence. In particular, the absolute stereochemistry of 1, 2, 5 and 6 were elucidated by the application of the modified Mosher's method and circular dichroism (CD) spectral data. The inhibitory effects of some isolates were evaluated on nitric oxide (NO) production against a murine macrophage-like cell line (Raw 264.7). Cembranoids consisting of alpha-methylene-gamma-lactone, exhibited the significant effect on NO production.
- Published
- 2010
- Full Text
- View/download PDF
27. Flaxseed lignan lowers blood cholesterol and decreases liver disease risk factors in moderately hypercholesterolemic men.
- Author
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Fukumitsu S, Aida K, Shimizu H, and Toyoda K
- Subjects
- Adult, Anthropometry, Cardiovascular Diseases complications, Cholesterol, HDL blood, Cholesterol, LDL blood, Double-Blind Method, Humans, Hypercholesterolemia blood, Liver Diseases blood, Liver Diseases etiology, Male, Metabolic Syndrome complications, Middle Aged, Phytotherapy, Placebos, Plant Extracts administration & dosage, Risk Factors, Flax chemistry, Hypercholesterolemia drug therapy, Lignans administration & dosage, Liver Diseases prevention & control
- Abstract
The effects of flaxseed lignan (secoisolariciresinol diglucoside [SDG]) intake on hypercholesterolemia and liver disease risk factors in moderately hypercholesterolemic men were investigated. In a previous study, we reported that SDG attenuates high-fat, diet-induced hypercholesterolemia in mice. Here, we report a double-blinded, randomized, and placebo-controlled study in moderately hypercholesterolemic men in which we investigated the hypothesis that oral administration of SDG (20 or 100 mg) would decrease the level of blood cholesterol and liver disease risk factors induced by hypercholesterolemia in humans. Thirty men with total cholesterol levels of 4.65 to 6.21 mmol/L (180-240 mg/dL) were randomly assigned to 3 groups; 2 groups received flaxseed lignan capsules (SDG, 20 or 100 mg/d) and the other received placebo capsules for 12 weeks. We found that, compared to the subjects who received placebo, those who received 100 mg of SDG exhibited a significant reduction in the ratio of low-density lipoprotein/high-density lipoprotein cholesterol at baseline (P < .05) and at week 12 (P < .05). In addition, in SDG-treated subjects, we also observed a significant percentage decrease in the levels of glutamic pyruvic transaminase and gamma-glutamyl transpeptidase relative to the levels at baseline (P < .01) and a significant percentage decrease in the level of gamma-glutamyl transpeptidase relative to the placebo-treated group (P < .05). These results suggest that daily administration of 100 mg SDG can be effective at reducing blood level of cholesterol and hepatic diseases risk in moderately hypercholesterolemic men., (Copyright 2010 Elsevier Inc. All rights reserved.)
- Published
- 2010
- Full Text
- View/download PDF
28. Differences in Cancer Risks in the South and North of Viet Nam.
- Author
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Ngaon LT, Fukumitsu S, Kaneko S, and Yoshimura T
- Abstract
Background: As there are few available data regarding cancers in Viet Nam, the aim of the present study was to evaluate cancer risk ratios and geographical differences in cancer incidences between the south and north populations in the 1990s. Methods: Data for cancer incidences in Ho Chi Minh (HCM) and Hanoi were derived from published reports. The method for comparison of cancer incidence in two groups used in the present study was the Mantel-Haenszel test. Results: In HCM, all cancers were observed to be lower in males, (RR = 0.87, 95% CI = 0.83-0.91) but higher in females, (RR = 1.06, 95% CI = 1.01-1.12) than in Hanoi. For males, significantly higher incidences in HCM were observed for cancers of the oesophagus (RR = 1.66, 95% CI = 1.19-2.32), liver (RR = 1.22, 95% CI = 1.09-1.36), gall bladder (RR = 5.95, 95% CI = 2.49-14.23), and larynx (RR = 3.54, 95% CI = 2.26-5.55). In contrast, there were much lower incidences in HCM for cancers of the nasopharynx (RR = 0.5, 95% CI = 0.41-0.61), stomach (RR = 0.76, 95% CI = 0.67-0.86), and lung (RR = 0.7, 95% CI = 0.64-0.78). For females, breast cancer incidence was much lower (RR = 0.65, 95% CI = 0.57-0.73) but that of cervical cancer was significantly higher in HCM than in Hanoi, (RR = 3.94, 95% CI = 3.36-4.62), especially for the age group 55-64, (RR = 8.7, 95% CI = 5.9-13.3). Conclusion: The present findings show that cancer risk is quite different in the south and north populations within Viet Nam.
- Published
- 2001
29. Role of insulin in the pathogenesis of hypertension associated with glucose intolerance.
- Author
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Takahashi H, Nakanishi T, Nishimura M, Fukumitsu S, and Yoshimura M
- Subjects
- Adult, Blood Pressure, Diabetes Complications, Humans, Hypertension complications, Hypertension physiopathology, Male, Middle Aged, Obesity complications, Reference Values, Regression Analysis, Glucose pharmacology, Hypertension etiology, Insulin physiology
- Abstract
The role of insulin in the pathogenesis of hypertension was explored in normal men and male patients with impaired glucose-tolerance. They were classified as normal (n = 94), borderline (n = 164), impaired tolerance (IGT, n = 104), or diabetes mellitus (n = 100) according to their response to an oral 75g glucose challenge. Besides routine laboratory examinations, fasting immunoreactive insulin and post-glucose insulin levels at 30 minutes were measured. Patients with impaired glucose tolerance were older and more obese than the normal subjects. Serum cholesterol and triglyceride concentrations increased with severity of the glucose tolerance impairment. However, renal function, as estimated by blood urea nitrogen levels did not differ among these four groups. Multiple regression analysis revealed that blood pressure correlates significantly with the obesity index, blood glucose, serum cholesterol and serum insulin in all four groups. Among these groups, the partial F ratios for the obesity index were the greatest in both normal and diabetic groups, but in both borderline and IGT groups those for insulin were the greatest. These results indicate that in patients with impaired glucose tolerance is hypertension associated more closely with hyperinsulinemia than it is in normal subjects or diabetic patients.
- Published
- 1993
- Full Text
- View/download PDF
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