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Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of E3024, a Novel and Selective Dipeptidyl Peptidase-IV Inhibitor, in Healthy Japanese Male Subjects: Rash Development in Men and Its Possible Mechanism

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Pharmacology & Pharmacy 2013年第9期4卷 663-678页

作者： Yutaka Takeuchi Masayuki Namiki Yasumi Kitahara Setsuo Hasegawa Akihiro ohnishi Nobuyuki Yasuda Takashi Inoue Richard Clark Kazuto Yamazaki Clinical Development Japan/Asia Clinical Research PCU Eisai Co. Ltd. Tokyo Japan Clinical Development Japan/Asia Clinical Research PCU Eisai Co. Ltd. Tokyo Japan Clinical Pharmacology Clinical Science SOCS CFU Eisai Co. Ltd. Tokyo Japan Department of Laboratory Medicine Daisan Hospital Jikei University School of Medicine Tokyo Japan Sekino Clinical Pharmacology Clinic Tokyo Japan Present Address: Pharmaspur Inc. Tokyo Japan Tsukuba Research Laboratories Eisai Co. Ltd. Tsukuba Japan.

E3024 (3-but-2-ynyl-5-methyl-2-piperazin-1-yl-3,5-dihydro-4H-imidazo[4,5-d]pyridazin-4-one tosylate) is a dipeptidyl peptidase-IV (DPP-IV) inhibitor that was expected to be an antidiabetic agent. Its safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) were investigated in a randomized, double-blind, placebo-controlled, ascending single-dose study in 48 healthy Japanese male subjects. Fasted subjects were orally administered E3024 (5, 10, 20, 40, or 80 mg) or placebo. E3024 was rapidly absorbed, with tmax values ranging between 0.33 and 3 h after dosing. The mean t1/2 ranged from 5.34 to 11.68 h. AUC0-inf and Cmax increased dose-proportionately. PK-PD relationship of E3024 was evaluated by using an Imax model, indicating that plasma E3024 concentrations and inhibitory effects of plasma DPP-IV activity were well correlated. The IC50 value was calculated as 33.7 ng/mL, which was consistent with in vitro data. Thus, E3024 showed a good PK profile and inhibited DPP-IV dose-dependently. Of 30 subjects administered E3024, 12 (40%) experienced adverse events (AEs). Dose escalation to 160 mg was abandoned owing to undesired subjective/objective findings in 4 of 6 subjects receiving 40 mg and 5 of 6 subjects receiving 80 mg. The most prominent AE was rash, but there were no serious AEs or deaths. The maximum tolerated dose was considered to be 20 mg. We hypothesized that histamine was a cause of the rash induction, and examined blood histamine levels of normal Fischer rats treated with E3024. Blood histamine levels were increased significantly by E3024 at 500 mg/kg (p < 0.001), but not by vildagliptin or valine-pyrrolidide (DPP-IV inhibitors) at the same dose. No blood histamine increases were observed in genetically mast cell-deficient Ws/Ws rats treated with E3024 at 500 mg/kg. In in vitro assays, E3024 induced histamine release from normal rat peritoneal mast cells in a concentration-dependent manner, but not from basophils. The structure-activity relati

关键词： Dipeptidyl Peptidase-IV Inhibitor Rash Histamine Structure-Activity Relationship

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S-3308L在葡萄里的残留量分析方法研究

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环境科学动态 1989年第6期 26-29页

作者： J.ohnishi 周德英

这个报告叙述了S-3308L在葡萄里的残留量的分析方法。这个分析方法适用于丙酮萃取,用硅胶色谱柱净化,用装有火焰热电子鉴定器的气相色谱测定。此测定方法的平均回收率为86.0％,97.7％,103％。这是分别测定葡萄的果实、葡萄汁和葡萄酱而... 详细信息

这个报告叙述了S-3308L在葡萄里的残留量的分析方法。这个分析方法适用于丙酮萃取,用硅胶色谱柱净化,用装有火焰热电子鉴定器的气相色谱测定。此测定方法的平均回收率为86.0％,97.7％,103％。这是分别测定葡萄的果实、葡萄汁和葡萄酱而得到的。它们的测定极限是0.005ppm0,005ppm,0.01ppm。这是分别测定葡萄果实、葡萄汁、葡萄酱的残留量而得到的。

关键词：葡萄农药残留量 S-3308L

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Anterior mediastinal abscess diagnosed in a young sumo wrestler after closed blunt chest trauma

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Chinese Journal of Traumatology 2015年第6期18卷 360-362页

作者： Tatsuro Sassa Ken-ichiro Kobayashi Masayuki Ota Takuya Washino Mayu Hikone Naoya Sakamoto Sentaro Iwabuchi Mizuto Otsuji Kenji ohnishi Department of Infectious Disease Tokyo Metropolitan Bokutoh General Hospital 4-23-15 kohtohbashi Sumida City Tokyo 130-0022 Japan

Most mediastinal abscesses result from infections after thoracotomy, esophageal perforation or pene- trating chest trauma. This disease is rarely caused by closed blunt chest trauma. All previously reported such cases after closed blunt chest trauma presented with hematoma and sternal osteomyelitis resulting from sternal fracture. Here we report a 15-year-old sumo wrestler who presented with an anterior mediastinal abscess without any mediastinal fracture. The mediastinal abscess resulted from the he- matogenous spread of Staphylococcus aureus to a hematoma that might have been caused by a closed blunt chest trauma incurred during sumo wrestling exercises.

关键词： Mediastinal abscess Staphylococcus aureus Sumo wrestler Chest trauma

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Transplantation of Olfactory Mucosa as a Scaffold for Axonal Regeneration Following Spinal Cord Contusion in Rats

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Neuroscience & Medicine 2013年第2期4卷 112-116页

作者： Koichi Iwatsuki Toshiki Yoshimine Yoshiyuki Sankai Masao Umegaki Yu-Ichiro ohnishi Masahiro Ishihara Takashi Moriwaki Noriko Oda Department of Neurosurgery Medical SchoolOsaka UniversityOsakaJapan Faculty of Engineering‚Information and Systems University of TsukubaTsukubaJapan

Object: The inability of the spinal cord to regenerate after SCI is due to the extremely limited regenerative capacity of most central nervous system (CNS) axons, along with the hostile environment of the adult CNS, which does not support axonal growth. It seems that for successful axonal regeneration to take place, a supportive local environment is required after the injury. We have previously reported that transplantation of the olfactory mucosa is effective in restoring functional recovery in rats following spinal cord transaction. In this study, we examined histological features of olfactory mucosa grafts in rats subjected to a spinal cord contusion protocol. Respiratory mucosa was utilized as a control, as we have previously found that respiratory mucosa does not support neuronal generation. Methods: The rats spinal cords were crash-injured by dropping a 10-g metal rod from a height of 7.5 cm, and a couple of weeks later, the injury sites were exposed, and both olfactory and respiratory mucosae were inserted into the posterior sulcuses of the spinal cord. The each number of olfactory and mucosa transplanted rats were five. The Basso, Beattie, and Bresnahan (BBB) score was observed. Immunohistochemical study for neurofilament was performed. Results: Olfactory mucosa transplanted rats following spinal cord injury can support at least partial hind limb motor recovery compared with respiratory mucosa transplanted rats and we identified numerous axons surrounding the transplanted olfactory mucosa cells, and penetrating the olfactory mucosa at the transplant site. Conclusion: Olfactory mucosa might be a suitable scaffold for axonal regeneration.

关键词： Olfactory Mucosa Spinal Cord Injury Transplantation Scaffold

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Some Investigations on Early Organization of Karst System

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Journal of Earth Science 1999年第4期18卷 314-321页

作者： Yu Qingchun(Geofront Laboratory, Department of Civil Engineering, Kyoto University, Kyoto 606-8501, Japan)Shen Jifang Wan Junwei(Department of Hydrogeology and Environmental Engineering, China University of Geosciences,Wuhan 430074, China)ohnishi Yuzo(Geo Geofront Laboratory Department of Civil EngineeringKyoto UniversityKyoto 606-8501Japan Department of Hydrogeology and Environmental Engineering China University of GeosciencesWuhan 430074China

Some investigations on the early organization of karst system are carried out through modeling the dissolution evolution processes of stochastic fracture networks in carbonate rock. It is assumed that water flow in fracture network is laminar, and the dissolution rate process can be described with an empirical equation, The results suggest that a karst system is a self-organization system. It can spontaneously create higher hierarchical level out of a relative homogeneous structure through amplifying the microscopic heterogeneity of initial flow field. Under given boundary conditions, a karst system with initial fracture network of varied hierarchical levels is likely to have stronger tendency to lead to a typical karst system featuring conduit passages than a system with initial network of unique hierarchical level. Through merging local flow systems, a karst system concentrates the limited flow into a few pathways to promote the formation of higher hierarchical level.

关键词： karst system self-organization hierarchical structure hierarchical level

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Jet-fluid string formation and decay in high-energy heavy-ion collisions

Jet-fluid string formation and decay in high-energy heavy-io...

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The 19th International Conference on Ultra-Relativistic Nucleus-Nucleus Collisions

作者： M. Isse T. Hirano Y. Nara A. ohnishi K. Yoshino Department of Physics Graduate School of ScienceOsaka UniversityToyonaka 560-0043Japan Institute of Physics Graduate School of Arts and SciencesUniversity of TokyoKomabaTokyo 153-8902Japan Institut fu¨r Theoretische Physik Johann Wolfgang Goethe-Universit¨at60438 Frankfurt am MainGermany Division of Physics Graduate School of ScienceHokkaido UniversitySapporo 060-0810Japan Division of Physics Graduate School of ScienceHokkaido UniversitySapporo 060-0810Japan

＜正＞One of the most intriguing findings at RHIC is suppression of hadron yield in high pT regions. Nowadays, this is commonly believed to be a direct consequence of parton energy loss in the dense deconfined matter. However, momentum anisotropy, v2, is not well understood yet in the high pT region: most theoretical results are smaller than experimental data. One may obtain a larger v2 by assuming a sharper density profile for produced matter compared to Woods-Saxon type density distribution. However, large eccentricity from a sharp density profile would spoil an agreement

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Involuntary muscle spasm expressed as motor evoked potential after olfactory mucosa autograft in patients with chronic spinal cord injury and complete paraplegia

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Journal of Biomedical Science and Engineering 2013年第9期6卷 908-916页

作者： Koichi Iwatsuki Toshiki Yoshimine Yoshiyuki Sankai Fumihiro Tajima Masao Umegaki Yu-Ichiro ohnishi Masahiro Ishihara Koshi Ninomiya Takashi Moriwaki Department of Neurosurgery Osaka University Medical SchoolOsakaJapan Faculty of Engineering‚Information and Systems University of TsukubaTsukubaJapan Department of Rehabilitation Wakayama Medical UniversityWakayamaJapan

Object: The efficacy of olfactory mucosa autograft (OMA) for chronic spinal cord injury has been reported. New activity in response to voluntary effort has been documented by electromyography (EMG), but the emergence of motor evoked potential (MEP) reflecting electrophysiological conductivity in the central nervous system, including the corticospinal pathway, after OMA, and the best indications for OMA, have not been clarified. Here, we report the emergence of MEPs after OMA and offer recom-mendations for appropriate indications based on the presence of involuntary muscle spasm (IMS). We used analysis of MEP to examine the efficacy of OMA for patients with complete paraplegia due to chronic spinal cord injury. To clarify the indications for OMA, we investigated the association of IMS and efficacy of OMA. Methods: Four patients, 3 men and 1 woman, were enrolled. The mean age of the cases was 30.3 ± 9.5 years (range, 19 to 40 years). All 4 cases were American Spinal Injury Association (ASISA) grade A. The mean duration from injury to OMA was 95.8 ± 68.2 months (range, 17 to 300 months). Samples of olfactory mucosa were removed, cut into smaller pieces, and grafted into the sites of spinal cord lesions after laminectomy. Postoperative subcutaneous fluid collection, postoperative meningitis, postoperative nosebleed, postoperative infection in the nasal cavity, impaired olfaction, neoplastic tissue overgrowth at the autograft site, new sensory disturbance, and involuntary muscle spasm were investigated as safety issues. Improvements in ASIA grade, variations in ASIA scores, EMG, SSEP, and improved urological function were evaluated as efficacy indicators. Results: There were no serious adverse events in this series. In 2 of the 4 cases, an improvement in motor function below the level of injury was recognized. In one, the motor score was 50 until 16 weeks after surgery, and it increased to 52 from 20 weeks after surgery. In the other, the motor score was 50 until 20 week

关键词： Olfactory Mucosa Autograft Spinal Cord Injury Transplantation Voluntary Movement Motor Evoked Potential

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Preparation of Antimicrobial Iron Oxide Nanostructures from Galvanizing Effluent

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World Journal of Nano Science and Engineering 2022年第1期12卷 1-11页

作者： Rajapakshe Babilage Sanjitha Dilan Rajapakshe Gonapala Deniyage Madhusha Chathurangi Gonapaladeniya Charith Anuruddha Thennakoon Prabath Nilan Gunasekara Nirosh Siriwardene Sudath Annasiwatte sayuri Sammanani Niyangoda Rajapakse Mudiyanselage Gamini Rajapakse Department of Chemistry Faculty of Science University of Peradeniya Peradeniya Sri Lanka Post Graduate Institute of Science University of Peradeniya Peradeniya Sri Lanka LTL Galvanizers Pvt. Ltd. Makola Sri Lanka

Galvanization is the process of applying a protective zinc coating to iron or steel to prevent rusting. In the batch hot-dip galvanizing process, large amounts of wastes originate in liquid, solid and gaseous forms. Acidic waste containing iron and zinc ions is produced due to the cleaning of steel prior to zinc coating, which is considered the galvanizing acid waste. The galvanizing effluent used was collected from LTL Galvanizers Pvt. Ltd., Sapugaskanda, Sri Lanka, and converted into antimicrobial hematite (α-Fe2O3) nanoparticles. These nanoparticles were synthesized using a chemical precipitation method. X-Ray Diffraction (XRD) and Scanning Electron Microscopy (SEM) were used to characterize the nanomaterials produced. Two pathogenic bacteria and one pathogenic fungus were used to analyze the antimicrobial activity of the nanomaterials. All the samples showed excellent antibacterial and antifungal properties. And the material can inhibit the growth of both Gram-positive and Gram-negative bacteria. According to the SEM images, some of the hematite particles were around 100 nm in size or less, which confirms that the describing method is viable in synthesizing hematite nanostructures. As shown in the XRD, the major diffraction peak, located at 2θ of 35.617° (110) in addition to minor peaks at 24.87° (012), 33.07° (104), 42.08° (113), 51.18° (024), 53.52° (116) and, 57.46° (018) confirm the spinel structure of iron oxide (α-Fe2O3). The estimated average crystallite size of the nanomaterial is calculated to be 36.74 nm. The durability of the manufactured nanomaterial is excellent. This method is a time-efficient, environmentally friendly, cost-effective and industrially viable way to manufacture antimicrobial hematite (α-Fe2O3) nanomaterials from a galvanizing effluent.

关键词： Wastewater Treatment Galvanizing Effluent Antimicrobial Hematite Nanomaterials Iron Oxide Nanostructures Coprecipitation

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岩体非连续裂隙网络三维面状渗流模型

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岩石力学与工程学报 2005年第4期24卷 662-668页

作者：于青春刘丰收大西有三中国地质大学水资源与环境学院北京100083 黄河水利委员会河南郑州450003 京都大学土木工程系

模拟了一个野外实际入渗试验的岩体裂隙网络及其中的渗流。通过逆方法建立岩体三维裂隙网络模型,其指导原则是使模型能够再现野外通过露头和钻孔所观察到的裂隙现象。逆方法由于可以对模拟和实测裂隙进行相同条件统计抽样,因此避免了实... 详细信息

模拟了一个野外实际入渗试验的岩体裂隙网络及其中的渗流。通过逆方法建立岩体三维裂隙网络模型,其指导原则是使模型能够再现野外通过露头和钻孔所观察到的裂隙现象。逆方法由于可以对模拟和实测裂隙进行相同条件统计抽样,因此避免了实测数据统计分析中复杂的误差矫正。裂隙面状渗流分析采用了任意多边形有限差分法。讨论了通过模型校正确定裂隙导水系数的方法,进行了随机模型重复实现,验证了模型的稳定性。

关键词：岩石力学非连续裂隙网络渗流逆方法模型校正

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应力腐蚀裂绞前端氢脆区的形成和消失

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轻合金加工技术 1985年第8期 37-40页

作者： T.ohnishi 孙建英

已经研究了氢脆在A1-Mg合金应力腐蚀开裂中所起的作用.根据实验结果,提出了应力腐蚀裂纹的形成和扩展的下述模型.第一,裂纹源心由机械-化学腐蚀产生的.第二,由腐蚀产生了氢气,而氢气由裂纹尖端前面的塑性区的位错运动向前输送.由于铝合... 详细信息

已经研究了氢脆在A1-Mg合金应力腐蚀开裂中所起的作用.根据实验结果,提出了应力腐蚀裂纹的形成和扩展的下述模型.第一,裂纹源心由机械-化学腐蚀产生的.第二,由腐蚀产生了氢气,而氢气由裂纹尖端前面的塑性区的位错运动向前输送.由于铝合金的晶界对腐蚀一般是敏感的,并且氢气也易于在晶界集中,所以,沿晶界形成了氢影响区.第三,在氢脆、应力集

关键词：应力腐蚀载荷位移曲线拉伸试验抗拉试验材料试验应力腐蚀开裂试验应力试验充氢裂纹长度最终断裂氢脆前端

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