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An Overview on the Third Annual Pharmacovigilance Forum 第三届年度药物警戒论坛综述
Pub Date : 2015-12-07 DOI: 10.4172/2167-065X.1000E122
I. Magyar
Pharmacovigilance is the fourth steps (the last phase) in clinical development of the drugs –after the drug is marketed. New prescription drugs are only marketed after carefully controlled clinical trials have shown them to be safe and effective. Farmacovigilance is the postmarketing surveillance and study of ADRs, with the ultimate goal of preventing or minimizing their occurrence. It is a continuous process that involve both health authorities and pharmaceutical industry. It is a necessary interface between therapeutics and clinical epidemiology. The costs (billions of dollars annually) includes collection, compilation, quality control, and analysis of the spontaneus reports. Although it is the ′′poor relative′′ of pharmacology and the ′′bogeyman′′ of the sellers of new drugs, pharmacovigilance is, neverthless, very important component for the rational use of drugs [1-3].
药物警戒是药物上市后临床开发的第四步(最后一个阶段)。新的处方药只有在经过严格控制的临床试验证明其安全有效后才会上市。药物警戒是对药品不良反应的上市后监测和研究,其最终目标是预防或尽量减少其发生。这是一个涉及卫生当局和制药工业的持续过程。它是治疗学和临床流行病学之间的必要接口。成本(每年数十亿美元)包括收集、汇编、质量控制和分析自发报告。虽然是药理学的“穷亲戚”,是新药销售商的“妖怪”,但药物警戒却是合理用药的重要组成部分[1-3]。
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引用次数: 8
Genomic Control of Upregulation of GRP78 Expression for Promotion of Neurite Elongation and Attenuation of Cell Death via PKA-Mediated Signaling in PC12 Cells 基因组调控GRP78表达上调,通过pka介导的PC12细胞信号传导促进神经突延长和细胞死亡的衰减
Pub Date : 2015-11-23 DOI: 10.4172/2167-065X.1000150
Ryosuke Yamazoe, Y. Nishihata, K. Nakagawa, Hiroki Aoyama, K. Shimoke
Neurodegeneration occurs due to neuronal cell death and subsequently disrupts neuronal networks. In current medicine, methods for interruption of neuronal cell death and avoidance of disruption of neuronal networks have potential as therapy for neurodegenerative disorders. Development of this therapy requires analysis of the molecular mechanism of neurite extension that leads to network formation. Here, we show that forskolin (fsk), an activator of adenylate cyclase, increases the intracellular cAMP concentration and induces neurite outgrowth in PC12 cells. The effect of fsk on neurite outgrowth was diminished by H89, an inhibitor of protein kinase A (PKA), and by PD98059 and U0126, which are inhibitors of the mitogen-activated protein kinase (MAPK) signaling pathway. With fsk treatment in the presence of tunicamycin, an inducer of cell death, the activity of the glucose-regulated protein 78 (GRP78) promoters was upregulated. Interestingly, this effect was completely abolished by H89 and by PD98059 and U0126. This phenomenon was confirmed using a dominant-negative PKA-expressing PC12 cell line, in which the PKA-mediated signaling pathway was completely eliminated. These lines of evidence suggest that GRP78 promotes neuronal elongation that is regulated by fsk and mediated by PKA.
神经退行性变的发生是由于神经元细胞死亡,随后破坏神经网络。在目前的医学中,阻断神经元细胞死亡和避免神经网络破坏的方法有可能成为神经退行性疾病的治疗方法。这种疗法的发展需要分析导致神经网络形成的神经突延伸的分子机制。在这里,我们发现福斯克林(fsk),腺苷酸环化酶的激活剂,增加细胞内cAMP浓度并诱导PC12细胞的神经突生长。蛋白激酶A (PKA)抑制剂H89和丝裂原活化蛋白激酶(MAPK)信号通路抑制剂PD98059和U0126可以减弱fsk对神经突生长的影响。在有tunicamycin(一种细胞死亡诱导剂)存在的fsk处理下,葡萄糖调节蛋白78 (GRP78)启动子的活性上调。有趣的是,H89、PD98059和U0126完全消除了这种效应。这一现象在pka显性阴性表达的PC12细胞系中得到证实,pka介导的信号通路被完全消除。这些证据表明GRP78促进由fsk调节并由PKA介导的神经元伸长。
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引用次数: 1
Decreasing Incidence of Gastric Cancer and H. pylori Infection a 10- Year Study from an Asian Population 降低胃癌和幽门螺杆菌感染的发生率:一项亚洲人群10年的研究
Pub Date : 2015-11-20 DOI: 10.4172/2167-065X.1000E121
J. Sollano, Karen Estelle C de Lunas, F. Marotta
Worldwide, cancer of the stomach is the fourth most common cancer and is the second leading cause of cancer deaths. Gastric cancer is common in many regions of Asia and one of the many factors associated with it is the high prevalence of Helicobacter pylori [Hp] infection. Hp has been designated by the WHO as a class 1 (definite) carcinogen and the association between chronic Hp infection and the development of gastric cancer has been established by numerous publications. Up to 76-95% of gastric cancers are associated with Hp infection [1-3]. Among the many factors expressed by Hp, gastric carcinogenesis via the cag A pathway is the most studied. In individuals infected with CagA-positive strains, a meta-analysis of 16 case-control studies showed a further increase in the risk for gastric cancer by 1.64 fold [4] However, due to improved sanitation amidst better living conditions, heightened patients and physician awareness and widespread Hp eradication practices, a decreasing prevalence of Hp infection is observed even in previous high-prevalence regions. We have also noted that the number of patients with gastric cancer consulting our institution, a tertiary academic hospital, has diminished remarkably in the last several decades. Thus, we designed a study to determine the incidence of gastric cancer, as well as, Hp infection over a ten-year period as seen in our tertiary referral center and evaluated the relationship between Hp infection and gastric cancer.
在世界范围内,胃癌是第四大最常见的癌症,也是癌症死亡的第二大原因。胃癌在亚洲许多地区很常见,与之相关的众多因素之一是幽门螺杆菌(Hp)感染的高发率。Hp已被WHO指定为1类(明确的)致癌物,慢性Hp感染与胃癌发展之间的关联已被许多出版物所证实。高达76-95%的胃癌与Hp感染有关[1-3]。在Hp表达的众多因子中,通过cag A途径发生胃癌的研究最多。在感染caga阳性菌株的个体中,一项对16例病例对照研究的荟萃分析显示,胃癌的风险进一步增加了1.64倍[4]。然而,由于生活条件改善、卫生条件改善、患者和医生意识提高以及广泛的Hp根除措施,即使在以前的高流行地区,Hp感染率也在下降。我们还注意到,在过去几十年里,向我们这个三级学术医院咨询的胃癌患者数量显著减少。因此,我们设计了一项研究,以确定我们三级转诊中心在十年期间的胃癌发病率,以及Hp感染,并评估Hp感染与胃癌之间的关系。
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引用次数: 1
Green synthesis and antibacterial activity of novel azomethines 新型偶氮亚胺的绿色合成及抗菌活性研究
Pub Date : 2015-11-16 DOI: 10.4172/2167-065X.C1.012
Sridevi Chigurupati
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引用次数: 0
Assessing prescribing patterns for the prevention of chemotherapy-induced nausea and vomiting in the National Center for Cancer Care and Research 在国家癌症护理和研究中心评估预防化疗引起的恶心和呕吐的处方模式
Pub Date : 2015-11-16 DOI: 10.4172/2167-065X.C1.013
M. Zaidan
Purpose: Chemotherapy is the mainstay of cancer treatment; however, chemotherapy treatment may cause nausea and vomiting, which could cause 25 -50% PRESCRIBING PATTERNS FOR PREVENTION OF CHEMOTHERAPY INDUCED NAUSEA AND VOMITING 3 of patients to consider delaying or refusing further cancer treatment. Chemotherapyinduced nausea and vomiting (CINV), can be prevented in 70-80% of patients with evidence. –based anti-emetic regimen. The purpose of this study is to assess prescribing patterns with regard to prevention of CINV, in the national center for cancer care and research (NCCCR), and develop and implement a standardized evidencebased guideline for the management of CINV. Methods: 25 anti-emetic prescriptions were audited to assess their conformity with either of the published guidelines; Multinational Association of Supportive Care in Cancer (MASCC), American Society of Clinical Oncology (ASCO), or the National Comprehensive Cancer Network (NCCN), to establish baseline data. A multidisciplinary team of clinical pharmacists and oncologists developed and implemented a guideline for the prevention of CINV. The guideline was promoted using a variety of strategies; education, pocket cards, academic detailing and pharmacist intervention. Physician antiemetic orders were audited by pharmacists, to assess their conformity with NCCCR antiemetic guidelines. A data collection form was developed to capture relevant information including; patient demographics, type and emetogenic level of chemotherapy, and the conformity of anti-emetic order with NCCCR guidelines. SPSS statistical software was used to analyze the data. Results: The conformity of anti-emetic physician order with NCCCR anti-emetic guidelines increased from 0% baseline in June 2008 to an average of 60.006% (n=331) by December 2010 and consistently increased reaching 94.3827% (n=792) by December 2013, (p value 0.0002). PRESCRIBING PATTERNS FOR PREVENTION OF CHEMOTHERAPY INDUCED NAUSEA AND VOMITING 4 Conclusion: The introduction of anti-emetic guidelines succeeded in standardizing CINV management, towards an evidence-based approach.
目的:化疗是癌症治疗的主要手段;然而,化疗可能引起恶心和呕吐,这可能导致25 -50%的患者考虑推迟或拒绝进一步的癌症治疗。有证据表明,70-80%的患者可预防化疗引起的恶心和呕吐(CINV)。基础止吐方案。本研究的目的是评估国家癌症护理和研究中心(NCCCR)预防CINV的处方模式,并制定和实施标准化的CINV管理循证指南。方法:对25份止吐处方进行审核,评估其是否符合已发表的指南;多国癌症支持治疗协会(MASCC)、美国临床肿瘤学会(ASCO)或国家综合癌症网络(NCCN)建立基线数据。一个由临床药师和肿瘤学家组成的多学科团队制定并实施了预防CINV的指南。该指导方针通过各种策略得到推广;教育,袖珍卡片,学术细节和药剂师干预。医师止吐单由药剂师审核,以评估其是否符合NCCCR止吐指南。制定了数据收集表格,以收集相关信息,包括:患者人口统计学,化疗类型和致吐水平,以及止吐顺序与NCCCR指南的一致性。采用SPSS统计软件对数据进行分析。结果:止吐医嘱对NCCCR止吐指南的符合性从2008年6月基线的0%上升至2010年12月的平均60.006% (n=331),到2013年12月持续上升至94.3827% (n=792), p值为0.0002。结论:抗吐指南的引入成功地规范了CINV的管理,朝着循证的方向发展。
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引用次数: 8
Anticholinesterase and Antioxidant Potentials of a Medicinal Plant Abroma augusta: Implications for the Alternative Treatment Therapy of Cognitive Deficits in Alzheimers disease 药用植物奥古斯塔抗胆碱酯酶和抗氧化潜能:对阿尔茨海默病认知缺陷的替代治疗的意义
Pub Date : 2015-10-28 DOI: 10.4172/2167-065X.1000148
Mst. Marium Begum, K. Biswas, A. Sarker, Tamanna Binte Huq, Abeer Sarwar, Md. Belal Hossain, H. Tarek, Md. Noor A-Alam, Asma Rahman
Oxidative stress and low level of neurotransmitter (especially acetylcholine) are main characteristics of Alzheimer’s disease (AD), a progressive neurodegenerative disease. Prolonging the function of acetylcholine by inhibiting acetylcholinesterase or butyrylcholinesterase enzyme and reducing oxidative stress with antioxidants are most effective treatment therapy of AD. Abroma augusta is a well-known medicine plant with a variety of medicinal uses. In this study we examine cholinesterase inhibitory activity as well as antioxidant activity of dried fruit extract including crude methyl extract and its sub fractions (Chloroform fraction, Petroleum ether fraction, Ethyl acetate fraction and aqueous fraction) of A. augusta. Both cholinergic inhibitory activity and antioxidant activity of various fractions suggested that, ethyl acetate fraction are most prominent among all fractions and can be used in symptomatic treatment of AD.
氧化应激和低水平的神经递质(尤其是乙酰胆碱)是阿尔茨海默病(AD)的主要特征,它是一种进行性神经退行性疾病。通过抑制乙酰胆碱酯酶或丁基胆碱酯酶来延长乙酰胆碱的功能,并用抗氧化剂减轻氧化应激是AD最有效的治疗方法。奥古斯塔是一种著名的药用植物,具有多种药用价值。本文研究了奥古斯塔干果提取物的胆碱酯酶抑制活性和抗氧化活性,包括粗甲基提取物及其亚组分(氯仿组分、石油醚组分、乙酸乙酯组分和水组分)。各组分的胆碱能抑制活性和抗氧化活性均表明,乙酸乙酯组分在各组分中最突出,可用于AD的对症治疗。
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引用次数: 10
Is Kava Safe to Be Used by the Public 公众使用卡瓦茶安全吗
Pub Date : 2015-10-19 DOI: 10.4172/2167-065X.1000E120
A. Al-Achi
The use of botanical products in the United States and European countries is extensive. While the original intention of the Dietary Supplements and Health Education Act of 1994 (DSHEA) by the US Congress was to use these products for the purpose of “supplementing” the diet, however many consumers use them for managing their disease states. Among the dietary supplements that have been popular among individuals who suffer from anxiety or insomnia is kava (Piper methysticum Frost F.) (The word “methysticum” is Greek for intoxicant, and “Piper” is for pepper. Taken together, kava is an “intoxicating pepper”) [1]. The herb is native to South Pacific region (Melanesia, Micronesia, Polynesia, and Hawaii) where it has been in use for centuries as a traditional beverage. The natives prepare kava drink by masticating the rhizomes which are further diluted with either coconut milk or water [2]. South Pacific islanders use the drink to connect to their gods and ancestors through religious and ceremonial gatherings, to alleviate fatigue, and as a relaxant [3]. The word kava when used by the natives refers to both the shrub itself and the psychoactive drink that is made from its rhizomes [2]. Kava beverage has a bitter and acrid taste which is known by the natives as ‘awa’ [2].
植物产品在美国和欧洲国家的使用是广泛的。虽然美国国会1994年膳食补充剂和健康教育法(DSHEA)的初衷是将这些产品用于“补充”饮食的目的,但许多消费者使用它们来管理他们的疾病状态。在患有焦虑症或失眠症的人群中很受欢迎的一种膳食补充剂是卡瓦(Piper methysticum Frost F.)(“methysticum”这个词在希腊语中是“麻醉剂”的意思,“Piper”是胡椒的意思)。加在一起,卡瓦是一种“令人陶醉的辣椒”)[1]。这种草药原产于南太平洋地区(美拉尼西亚、密克罗尼西亚、波利尼西亚和夏威夷),在那里它作为一种传统饮料被使用了几个世纪。当地人通过咀嚼根茎来制作卡瓦饮料,根茎再用椰奶或水进一步稀释[2]。南太平洋岛民用这种饮料通过宗教和仪式聚会与他们的神和祖先联系,缓解疲劳,并作为一种放松剂[3]。当地人使用的卡瓦这个词时,既指灌木本身,也指由其根茎制成的精神饮料[2]。卡瓦饮料有一种苦涩的味道,当地人称之为“awa”[2]。
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引用次数: 1
Assessment of Drug Interaction Potential between LCZ696, an Angiotensin Receptor Neprilysin Inhibitor, and Digoxin or Warfa rin 血管紧张素受体Neprilysin抑制剂LCZ696与地高辛或华法林药物相互作用潜力的评估
Pub Date : 2015-10-14 DOI: 10.4172/2167-065X.1000147
S. Ayalasomayajula, P. Jordaan, Mbchb, P. Pal, Priyamvada Ch, Ra, D. Albrecht, T. Langenickel, I. Rajman, G. Sunkara
LCZ696 (sacubitril/valsartan) is a first-in-class angiotensin receptor neprilysin inhibitor that simultaneously inhibits neprilysin and blocks the angiotensin II receptor. LCZ696 has been recently approved for treatment of HF and likely be co-administered with digoxin or warfarin. The drug interaction potential between LCZ696 and digoxin or warfarin was evaluated because of their potentially shared metabolic/elimination pathways. Two separate drug-drug interaction studies were conducted in healthy subjects: LCZ696 200 mg twice daily was co-administered with digoxin 0.25 mg once daily (n=24) and warfarin 25 mg single dose (n=26), respectively. The pharmacokinetic profiles of the LCZ696 analytes (sacubitril, LBQ657 and valsartan), digoxin and R- and S-warfarin, the pharmacodynamic effects of warfarin and the safety and tolerability of the investigational drugs were assessed. The geometric mean ratio (GMR) and 90%confidence interval (90% CI) for Cmax and AUCs of R- and S-warfarin, digoxin, and pharmacologically active LCZ696 analytes were within the bioequivalence range of 0.8-1.25 when co-administered. The GMR and 90% CI of warfarin pharmacodynamics effects were also within 0.8-1.25 range when co-administered with LCZ696. LCZ696 was generally safe and welltolerated when administered alone or in combination with digoxin/warfarin. No drug-drug interaction was observed upon co-administration of LCZ696 with digoxin/warfarin in healthy subjects.
LCZ696 (sacubitril/valsartan)是一种一流的血管紧张素受体neprilysin抑制剂,同时抑制neprilysin和阻断血管紧张素II受体。LCZ696最近被批准用于治疗心衰,可能与地高辛或华法林合用。由于LCZ696与地高辛或华法林可能共享代谢/消除途径,因此评估了它们之间的药物相互作用潜力。在健康受试者中进行了两项独立的药物-药物相互作用研究:LCZ696 200 mg,每日2次,分别与地高辛0.25 mg,每日1次(n=24)和华法林25 mg单剂量(n=26)联合给药。对LCZ696分析物(苏比利、LBQ657和缬沙坦)、地高辛、R-华法林和s -华法林的药动学特征、华法林的药效学效应以及研究药物的安全性和耐受性进行评估。R型和s型华法林、地高辛与药理活性物LCZ696共给药时,Cmax和auc的几何平均比(GMR)和90%置信区间(90% CI)在0.8 ~ 1.25的生物等效性范围内。与LCZ696合用华法林药效学效应的GMR和90% CI也在0.8 ~ 1.25范围内。LCZ696在单独或与地高辛/华法林联合使用时通常是安全且耐受性良好的。在健康受试者中,LCZ696与地高辛/华法林合用未见药物相互作用。
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引用次数: 14
Tyrosine Kinase: Targeted Anti-Cancer Therapy 酪氨酸激酶:靶向抗癌治疗
Pub Date : 2015-10-14 DOI: 10.4172/2167-065X.1000E119
Varun Khurana, Ravi Vaishya
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引用次数: 3
Blood brain barrier: Cracking the hard nut 血脑屏障:破解难题
Pub Date : 2015-10-06 DOI: 10.4172/2167-065X.C1.011
M. Nounou
T increase in incidence of brain disease, including cancer is alarming. In the Middle East, the incidence of primary brain cancer and secondary brain metastases originating mainly from breast, lung and/or ovarian cancer is on the rise because of increasing prevalence of these types of cancer. On the other hand, noninvasive drug therapy is hampered by poor access of most drugs to the brain due to the insurmountable blood–brain barrier (BBB). Nanotechnology holds great promise for a non-invasive therapy of severe brain diseases. Indeed, the literature reports provided evidence for enhanced drug transport across the BBB using nanocarriers, especially surface-modified polymeric nanoparticles (NPs).
包括癌症在内的脑部疾病发病率的增加令人担忧。在中东,主要源于乳腺癌、肺癌和/或卵巢癌的原发性脑癌和继发性脑转移的发病率正在上升,因为这些类型的癌症越来越流行。另一方面,由于血脑屏障(BBB)难以逾越,大多数药物难以进入大脑,这阻碍了非侵入性药物治疗。纳米技术有望成为严重脑部疾病的非侵入性治疗方法。事实上,文献报告提供了使用纳米载体,特别是表面修饰的聚合物纳米颗粒(NPs)增强药物在血脑屏障中的转运的证据。
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引用次数: 12
期刊
Clinical Pharmacology & Biopharmaceutics
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