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Pharmacology & Pharmacy 2021年第2期12卷 43-54页

作者： Toshio Kurihara Honami Kojima Miyako Yoshida Mizuho Oshio Rino Kunikata Haruka nishikawa Takahiro Uchida Faculty of Pharmaceutical Sciences Mukogawa Women’s University Nishinomiya Japan

The purpose of this study was to evaluate the palatability of dry syrups for pediatric use by human gustatory sensation testing and the artificial taste sensor. The bitterness intensities of dry syrups mixed with various beverages were also evaluated using the taste sensor. Twenty dry-syrup formulations of antibacterial and anti-allergic drugs containing bitter active ingredients, frequently used in pediatric medicine in Japan, were selected for testing. The main factors influencing palatability were determined by factor analysis of data from human gustatory sensation testing using the semantic differential method. It was shown that the bitterness intensity of dry syrups in water could be predicted by the artificial taste sensor. The influence of different beverages (orange juice, milk or cocoa) mixed with the dry syrups was evaluated using the artificial taste sensor. Taste and texture were found to be the principal factors influencing the palatability of dry syrups. While the bitterness intensities of some dry syrups were increased by mixing with orange juice, the bitterness intensities of most dry syrups were decreased by mixing with milk or cocoa. This suggests that one or more constituents of milk or cocoa may reduce the bitterness intensities of dry syrups.

关键词： Palatability Semantic Differential Method Dry Syrup Taste Sensor

Preparation and Characterization of Orally Fast-Disintegrating Mini-Tablets Containing Diphenhydramine Hydrochloride and Aspartic or Glutamic Acid as an Umami Amino Acid

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Pharmacology & Pharmacy 2021年第12期12卷 283-292页

作者： Kyoko Ohkawa Haruka nishikawa Honami Kojima Takayoshi Okuno Rio Uno Miyako Yoshida Takahiro Uchida Faculty of Pharmaceutical Sciences Mukogawa Women’s University Nishinomiya Japan

The aim of this study was to prepare diphenhydramine hydrochloride (DPH)-loaded orally fast-disintegrating mini-tablets (OFDMTs) containing either L-aspartic acid (Asp) or L-glutamic acid (Glu) as bitterness-suppressant, to characterize the prepared tablets and to evaluate their bitterness under conditions mimicking those of the oral cavity. The preparation of five formulation batches of the OFDMTs involved mixing DPH, with or without two different concentrations of Asp or Glu, and a premix containing a disintegrating agent. When all ingredients were well mixed, the mixture was directly compacted to form small (4 mm diameter) DPH-loaded OFDMTs. There were only small differences between the tablets with respect to mass, diameter, width and hardness. The disintegration times of the five formulation batches of DPH-loaded OFDMTs were measured using the OD-mate, a disintegration test apparatus in which conditions resemble those of the oral cavity. The disintegration times were all within 10 s of exposure to a medium representing the inside of the oral cavity. Rapid release profiles were observed for DPH, Asp and Glu in these dissolution tests. The taste sensor outputs of samples taken at different times (5 - 30 s) from the dissolution test solutions of the four DPH-loaded OFDMTs containing Asp or Glu were significantly inhibited compared with those of control DPH-loaded OFDMT. These results suggest that the inclusion of Asp or Glu in DPH-loaded OFDMTs is sufficient to mask bitterness in the oral cavity for the first 30 s after the tablet is placed in the mouth. It is anticipated that swallowing will have taken place within 30 s.

关键词： Orally Fast Disintegrating Mini-Tablets Diphenhydramine Aspartic Acid Glutamic Acid OD-Mate

Porcine Placenta Extract Enhances Ceramide Synthase 3 Expression through the PPARδ/ILK/Akt/mTOR/STAT3 Pathway

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Journal of Cosmetics, Dermatological Sciences and Applications 2022年第3期12卷 131-144页

作者： Akihiro Aioi Ryuta Muromoto Jun-ichi Kashiwakura Sho Mogami Megumi nishikawa Shigeyuki Ogawa Tadashi Matsuda Septem-Soken 2-4-27 Dojima Kita-ku Osaka Japan Laboratory of Immunology Faculty of Pharmaceutical Sciences Hokkaido University Sapporo Japan

Porcine placenta extract (PPE) is widely accepted as an ingredient in complementary and alternative medicine and previous studies have reported its availability, however, its underlying action mechanism remains unclear. In this study, we investigated the underlying mechanism of PPE-induced ceramide synthase 3 upregulation. PPE enhanced the expression of ceramide synthase 3 at both the mRNA and protein levels in HaCaT cells. Moreover, PPE-induced ceramide synthase3 upregulation was suppressed by the Akt inhibitor, suggesting the involvement of Akt in the underlying mechanism. As the PI3K inhibitor did not affect PPE-induced ceramide synthase 3 upregulation, the factors upstream of Akt were estimated. Inhibition and small interfering RNA experiments demonstrated that the peroxisome proliferator-activated receptors δ (PPARδ) and integrin-linked kinase (ILK) are involved in the phosphorylation of Akt. Next, we explored the factors downstream of Akt and found that PPE induced phosphorylation of the STAT3 while PPE-induced upregulation of ceramide synthase 3 was significantly suppressed by the inhibitor of the mTOR, suggesting that the mTOR/STAT3 pathway is involved in the downstream of Akt. These results demonstrate that PPE upregulates CerS3 expression via the PPARδ/ILK/Akt/mTOR/STAT3 pathway.

关键词： Porcine Placenta Ceramide Synthase 3 Signaling Pathway

Outcomes and Prognostic Factors for Adenocarcinoma/Adenosquamous Carcinomas Treated with Radical Hysterectomy and Adjuvant Therapy

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Open Journal of Obstetrics and Gynecology 2014年第14期4卷 909-915页

作者： Masayuki Yamaguchi Yoko Yamagishi Nobumichi nishikawa Masayuki Sekine Takehiro Serikawa Katsunori Kashima Takayuki Enomoto Department of Obstetrics and Gynecology Graduate School of Medical and Dental Sciences Niigata University Niigata City Japan

Objective: To determine outcomes and prognostic factors for early-stage cervical adenocarcinoma/ adenosquamous carcinomas (AC/ASC) patients who are treated with radical hysterectomy and adjuvant therapy to optimize their treatment. Methods: We retrospectively reviewed the medical records of 26 patients with International Federation of Gynecologists and Obstetricians stage IB-IIB cervical AC/ASC who were treated with radical hysterectomy and adjuvant therapy. Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method and compared using the log-rank test. The prognostic significance of various clinical features was determined by using multivariate analysis with the Cox proportional hazards regression model. Results: Univariate analysis revealed that OS was significantly shorter in patients with lymph node metastasis and lymphovascular space invasion. Similarly, PFS was significantly shorter for patients with lymph node metastasis and parametrial invasion. Furthermore, multivariate analysis showed that lymph node metastasis was the only independent predictor for PFS (hazard ratio: 6.47, 95% confidence interval: 1.33 - 31.44, p = 0.021). However, the use of adjuvant chemoradiotherapy did not have any significant effect on either OS or PFS, regardless of lymph node metastasis. Conclusions: Lymph node metastasis is an independent prognostic factor for poor survival in cervical AC/ASC patients treated with radical hysterectomy and adjuvant therapy. In addition, adjuvant chemoradiotherapy does not improve their survival, regardless of lymph node metastasis, which suggests that novel or personalized adjuvant therapeutic strategies with fewer adverse effects than existing strategies are needed.

关键词： Adjuvant Therapy Cervical Adenocarcinoma Cervical Adenosquamous Carcinoma Lymph Node Metastasis Prognostic Factors

Bone Formation in a Scaffold Composed of Cylindrical Hydroxyapatite and Tryptophan- or Lysine-Coated Sponge <i>in Vivo</i>

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Journal of Biomedical Science and Engineering 2015年第6期8卷 389-398页

作者： Masataka Yoshikawa Hideyuki Kakigi Hiroshi Maeda Ikuo nishikawa Hideaki Ikenaga Takeshi Inamoto Norimasa Tsuji Department of Endodontics Osaka Dental University Osaka Japan

Because of the three-dimensional structure of bone or hard tissue such as a tooth, a scaffold is necessary for its regeneration by cellular engineering. Commonly, for in vivo examination, hydroxyapatite (HA) has been used as such a scaffold. Cylindrical HA with a hollow center, which included a columnar formalin-treated polyvinyl alcohol sponge, was used in this examination as a scaffold. The sponge had been coated with L-tryptophan or L-lysine before insertion into the hollow center of the HA. Rat bone marrow cells (rBMCs) derived from the femur were seeded in the sponge before insertion into the hollow center of HA. The number of rBMCs seeded in each sponge was 1.5 × 106. These scaffolds were implanted subcutaneously into the backs of Fischer 344 rats for 6 weeks. In the amino-acid-coated sponge in HA, osteogenesis was found histologically. An osteocalcin level of approximately 10 ug was measured in the scaffolds with L-tryptophan-coated formalized poly-vinyl alcohol sponge containing rBMCs, 4 ug on average in the scaffolds with L-lysine-coated sponge containing the cells and about 2 ug in each scaffold with uncoated sponge containing the cells. The structure of the scaffolds used in this study was thought to be suitable for osteogenesis by rBMCs. It was concluded that tryptophan, as a factor for bone formation by stem cells, functioned by promoting cell adhesion and the differentiation of stem cells into osteoblasts.

关键词： Scaffold Hydroxyapatite Bone Marrow Cells L-Tryptophan L-Lysine Poly-Vinyl Formal Sponge

Role of Akt isoforms on the resistance to radiotherapy in human salivary gland cancer cells

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中国口腔颌面外科杂志 2008年第B5期6卷 122-123页

作者： Shingo Hara Koh-ichi Nakashiro Hiroyuki Goda Hidetomo nishikawa Kimi Honma Hiroyuki Hamakawa Department of Oral and Maxillofacial Surgery Ehime University Graduate School of Medicine. Ehime 791-0295 Japan Koken Bioscience Institute Tokyo 115-0051 Japan

Purpose: Akt is a serine/threonine kinase, which in mammals comprises three highly homologous members known as Aktl, Akt2, and Akt3. Recent studies indicate that Akt is frequently constitutively active in many types of human malignancy. In this study, we sought to clarify the expression and function of Akt isoforms (Aktl, Akt2, and Akt3) in human SGC cells. Methods: First, we examined the expression of Akt isoforms (Aktl, Akt2, and Akt3) in normal salivary gland and human SGC tissues by Western blot analysis and then the expression of Aktl, 2, 3 in human SGC tissues using immunohistochemical analysis. Next, to evaluate the effect of Akt isoforms on the in vitro and in vivo growth of human SGC cells, we used synthetic siRNAs specific for each isoform (siAktl, 2, 3) and atelocollagen as the in vivo delivery tools of synthetic siRNAs. Tumor cells were inoculated at two sites s.c. in the flanks ofathymic nude mice and then the mixture of each siAktl, 2, 3 (8 pmol) and 0.05% atelocollagen was injected into the periorbital plexus venosus. Antitumor effect was evaluated by the measurement of tumor volume. Further, we examined the effects of irradiation on Akt-signaling by Western blot analysis. Irradiation caused upregulation of phospho-Akt in human SGC cells. Then, to evaluate the role of Akt isoforms in the regulation of human SGC cell radio-sensitivity, the in vitro and in vivo growth assays were performed using siAktl, 2, 3 with and without irradiation. Results: Any Akt isoform almost was not expressed in normal salivary gland, however all Akt isoforms were expressed in human SGC tumors. Using immunohistochemical analysis, expression of all Akt isoforms were detected in almost all human SGC tissues. Knockdown of only a single Akt isoform expression using siRNA inhibited Akt signaling in human SGC cells and supressed the in vitro and in vivo growth of human SGC cells, However, on irradiation, the effects of growth inhibition were marked because of inhibition of Akt phos

关键词：唾液腺癌细胞治疗方法放射线疗法

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上海“爱马仕之家”

现代装饰 2015年第2期 44-51页

作者： Denis Montel Masao nishikawa RDAI及RDAI建筑设计事务所

本案位于上海市中心的淮海中路和嵩山路的交汇处,闪烁的霓虹与林立的高楼中坐落着一幢二十世纪初的四层建筑,别致的屋顶与花园使其自成一格。顺着南面外墙向上望去,会发现一个熟悉的身影从红瓦屋顶上腾空而起,那正是爱马仕的烟火骑士。

关键词：上海交汇处市中心屋顶建筑高楼花园外墙

Latent Autoimmune Diabetes in Adults Complicated by Persistent Isolated Glucosuria in the Absence of Hyperglycemia

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Case Reports in Clinical Medicine 2017年第5期6卷 133-136页

作者： Kosuke Inoue Yuya Tsurutani Chiho Sugisawa Sachiko Suematsu Jun Saito Masao Omura Tetsuo nishikawa Endocrinology and Diabetes Center Yokohama Rosai Hospital Yokohama Japan

Latent autoimmune diabetes in adults (LADA) is an autoimmune diabetes of adult-onset with the presence of diabetes associated autoantibodies. Familial renal glucosuria (FRG) is an inherited renal tubular disorder that causes persistent isolated glucosuria in the absence of hyperglycemia. We report a novel case of LADA and certain FRG. A 44-year-old man was admitted to our hospital for uncontrolled diabetes. Before admission, he had never suffered from diabetic coma and showed an improvement in HbA1c only with diet therapy. His HbA1c was 11.9% (107 mmol/mol), and anti-glutamic acid decarboxylase antibody was 13.0 U/mL. A glucagon stimulation test showed the decrease of insulin secretion: plasma C-peptide (CPR) 0 min, 0.69 ng/mL;CPR 6 min, 0.90 ng/mL. Analysis of genomic DNA revealed a novel heterozygous mutation in the SGLT2 coding gene, SLC5A2 (c.875G >A, ***292Tyr), which was assessed as probably damaging with a score of 0.998 (sensitivity: 0.27;specificity: 0.99) by an in silico analysis. Therefore, he was diagnosed with LADA and certain FRG. He has not shown any symptoms and his HbA1c improved to 6.4% (46 mmol/mol) three months after the introduction of insulin therapy. Our case clearly implies the clinical effectiveness of SGLT2 inhibition in patients with LADA.

关键词： Latent Autoimmune Diabetes in Adults (LADA) Familial Renal Glucosuria (FRG) SLC5A2 Mutation Sodium-Glucose Cotransporter 2 (SGLT2) Insulin Therapy

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日本木格栅住宅

设计 2015年第10期28卷 30-31页

作者： Jacob Masao nishikawa

这栋住宅楼由阿波罗建筑师事务所设计,是一个坐落在日本横滨的可以容纳两个家庭的住宅。该地区中,有很多这样的建筑形式,该项目设计的主要目的是可以保护住户的隐私,从街上也完全看不到屋子的内部景象。房屋由钢筋混凝土结构的围墙与外... 详细信息

这栋住宅楼由阿波罗建筑师事务所设计,是一个坐落在日本横滨的可以容纳两个家庭的住宅。该地区中,有很多这样的建筑形式,该项目设计的主要目的是可以保护住户的隐私,从街上也完全看不到屋子的内部景象。房屋由钢筋混凝土结构的围墙与外面宁静开阔的户外庭院环绕着。

关键词：钢筋混凝土结构建筑师事务所栏栅日本横滨儿童房装饰材料外部空间层空间美观度遮风挡雨

A case of EMRC for basaloid squamous carcinoma of the cervical esophagus

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World Journal of Gastrointestinal Endoscopy 2012年第8期4卷 373-375页

作者： Munetaka Nakamura Jun nishikawa Shigeyuki Suenaga Takeshi Okamoto Fumiki Okamoto Osamu Miura Isao Sakaida Department of Gastroenterology and Hepatology Yamaguchi University Graduate School of Medicine 1-1-1 Minami-kogushi Ube Yamaguchi 755-8505 Japan Department of Surgery Hofu Institute of Gastroenterology 14-33 Ekiminamimachi Hofu Yamaguchi 747-0801 Japan

Basaloid squamous carcinoma (BSC) of the esophagus is a rare esophageal tumor. A 79-year-old man with a history of proximal gastrectomy for gastric adenocarcinoma in 2000 was followed-up by esophagogastroduodenoscopy (EGD) annually. In June 2010, EGD revealed a new protruding lesion in the cervical esophagus. The small lesion was approximately 5 mm in size. A biopsy specimen showed poorly differentiated squamous cell carcinoma. We performed endoscopic mucosal resection using a cap-fi tted endoscope (EMRC). The histological diagnosis of the endoscopically resected specimen was BSC and the invasion depth was limited to the muscularis mucosae. Horizontal and vertical margins were negative. We report the case of superfi cial BSC in the cervical esophagus successfully resected by EMRC.

关键词： Esophagus Basaloid squamous carcinoma Esophageal cancer Endoscopic mucosal resection using a cap-fitted endoscope