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Influence of Renal ABC and SLC Transporter Polymorphisms on Cisplatin-induced Nephrotoxicity in Patients with Esophageal Cancer 食管癌患者肾ABC和SLC转运蛋白多态性对顺铂所致肾毒性的影响
Pub Date : 2016-08-09 DOI: 10.4172/2167-065X.1000158
K. Fujita, T. Niioka, S. Motoyama, M. Miura
Background: The individual and collective contributions of genetic polymorphisms in drug transporter genes in human renal proximal tubules to cisplatin-induced nephrotoxicity are still unclear. Methods: In this study, we investigated the effects of polymorphisms in SLC22A2 (808G>T), SLC31A1 (rs10981694A>C, rs12686377G>T, rs7851395A>G), SLC47A1 (rs2289669G>A), ABCB1 (1236C>A, 2677G>T/A, 3435C>T), ABCC2 (-24C>T), and ABCG2 (421C>A) on cisplatin-induced nephrotoxicity in 131 patients with esophageal cancer receiving 5-fluorouracil and cisplatin (FP) chemotherapy. The change rate of the estimated glomerular filtration rate (eGFR) was calculated according to the following formula: eGFR before FP chemotherapy-lowest eGFR during first cycle after FP chemotherapy)/eGFR before FP chemotherapy. Results: In univariate analysis, there was a significant correlation between patient age and the change rate of the eGFR by cisplatin (P = 0.021). However, there were no significant differences in the change rate of the eGFR by cisplatin between SLC22A2, SLC47A1, SLC31A1, ABCB1, ABCC2, and ABCG2 polymorphisms. Multivariate analysis revealed that only age was an independent variable predicting a higher risk of cisplatin-induced acute renal dysfunction. Conclusion: In FP chemotherapy for esophageal cancer patients, cisplatin-induced nephrotoxicity was not affected by polymorphisms in the uptake transporters OCT2 and Ctr1 or efflux transporters MATE1, P-glycoprotein, MRP2, and BCRP. Since degradation of renal function due to aging reduces cisplatin clearance, the cisplatin dosage should be carefully chosen in elderly patients.
背景:人类肾近端小管药物转运体基因遗传多态性对顺铂引起的肾毒性的个体和集体贡献尚不清楚。方法:在本研究中,我们研究了SLC22A2 (808G>T)、SLC31A1 (rs10981694A>C、rs12686377G>T、rs7851395A>G)、SLC47A1 (rs2289669G>A)、ABCB1 (1236C>A、2677G>T/A、3435C>T)、ABCC2 (-24C>T)、ABCG2 (421C>A)基因多态性对131例接受5-氟尿嘧啶和顺铂化疗的食管癌患者顺铂所致肾毒性的影响。估计肾小球滤过率(eGFR)的变化率按以下公式计算:FP化疗前eGFR (FP化疗后第一个周期最低eGFR) / FP化疗前eGFR。结果:单因素分析中,患者年龄与顺铂治疗后eGFR变化率存在显著相关(P = 0.021)。然而,SLC22A2、SLC47A1、SLC31A1、ABCB1、ABCC2和ABCG2基因多态性在顺铂作用下的eGFR变化率无显著差异。多变量分析显示,只有年龄是预测顺铂所致急性肾功能障碍高风险的独立变量。结论:食管癌患者FP化疗中,顺铂所致肾毒性不受摄取转运蛋白OCT2和Ctr1或外排转运蛋白MATE1、p糖蛋白、MRP2和BCRP多态性的影响。由于衰老导致的肾功能退化降低了顺铂的清除率,因此老年患者应谨慎选择顺铂的剂量。
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引用次数: 1
Recent Outbreak of Zika Virus Threat for Pregnant Women 最近爆发的寨卡病毒对孕妇构成威胁
Pub Date : 2016-05-31 DOI: 10.4172/2167-065X.1000157
B. Ramu, Ameedi
In Uganda in the year 1947, Zika virus was identified from a febrile sentinel rhesus monkey and from a group of Aedes africanus mosquitoes which are frequently found in Zika forest (in Uganda) which was noted at the time of investigation of yellow fever [1]. In east Africa 1952 Zika virus was firstly detected in humans by using neutralizing antibody testing in sera. Zika virus was initially identified in the population of Uganda people [1-4]. This Zika virus is caused by RNA flavivirus closely related to that of dengue infected to human by Aedes aegyptis and Aedes albopictus mosquitoes. Most of the infections caused by Zika virus are asymptomatic, symptomatic infections are caused by a self limiting febrile illness of 4-7 days accompanied by various symptoms.
1947年在乌干达,从发热的前哨恒河猴和一群经常在寨卡森林(乌干达)发现的非洲伊蚊中发现了寨卡病毒,这是在调查黄热病疫情时注意到的。在东非,1952年通过在血清中使用中和抗体检测首次在人类中检测到寨卡病毒。寨卡病毒最初是在乌干达人群中发现的[1-4]。该寨卡病毒是由RNA黄病毒引起的,与埃及伊蚊和白纹伊蚊感染人类的登革热病毒密切相关。寨卡病毒引起的感染多数为无症状感染,有症状感染是由4-7天的自限性发热性疾病引起,并伴有各种症状。
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引用次数: 5
Oral Films: A Look Back 口语电影:回顾
Pub Date : 2016-05-26 DOI: 10.4172/2167-065X.1000E124
S. Shanmugam
Oral films, a promising novel drug delivery system, are a strip of single or multilayered, mucoadhesive or non-mucoadhesive, thin polymeric films that are intended to deliver active therapeutic moieties either locally or systemically in oral cavity through sublingual, buccal, palatal, or gastrointestinal absorption [1-3]. In general, films are known by several names including but not limited to orodispersible films [4], orally disintegrating/dissolving films [5,6], rapid/fast/quick dissolving films [7-10], oral soluble films [11], oral thin films [12], strip films [1,13,14], quick disintegrating/dissolving films [8], buccal or buccal soluble film [15], mucoadhesive films [16], transmucosal films [17], sublingual films [18], etc. Strip films or thin films could be considered as a broad spectrum of classification or superset of films that might include all kinds of film applications for oral, topical/transdermal, vaginal, etc. Consequently, the focus of this topic, oral films, are generally strip or thin films intended for oral application, i.e., either oral cavity or gastrointestinal tract, and can generally be classified into oromucosal films and orodispersible films.
口服薄膜是一种很有前景的新型药物递送系统,它是一种单层或多层、黏附或非黏附的薄聚合物薄膜,旨在通过舌下、口腔、腭或胃肠道吸收在口腔局部或全身递送有效的治疗成分[1-3]。一般来说,膜有几个名称,包括但不限于口分散膜[4]、口腔崩解/溶解膜[5,6]、快速/快速/快速溶解膜[7-10]、口腔溶膜[11]、口腔薄膜[12]、条状膜[1,13,14]、快速崩解/溶解膜[8]、口腔或口腔溶膜[15]、黏附膜[16]、粘膜膜[17]、舌下膜[18]等。条状薄膜或薄膜可以被认为是一个广泛的分类或超集的薄膜,可能包括各种各样的薄膜应用于口服,局部/透皮,阴道等。因此,本课题的重点是口腔膜,一般是用于口腔或胃肠道的条状或薄膜,一般可分为口粘膜膜和口分散膜。
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引用次数: 7
Does The Mediterranean Diet or Botanicals Influence Alzheimer’s Disease? 地中海饮食或植物药对阿尔茨海默病有影响吗?
Pub Date : 2016-05-26 DOI: 10.4172/2167-065X.1000E123
Hannah M. Jester, A. Al-Achi
Dementia is a condition that currently affects over 46 million people worldwide [1]. It is a growing problem of epidemic proportions and while efforts are being made to treat it, the prevalence is estimated to affect over 131 million by the year 2050 [1]. Alzheimer’s disease (AD) is the most common form of dementia seen today, comprising 60-70% of all diagnosed cases of dementia [2]. The purpose of this editorial is to review the potential benefits of the Mediterranean diet and some botanicals on AD.
痴呆症目前影响着全球4600多万人。这是一个日益严重的流行病问题,虽然正在努力治疗这一问题,但估计到2050年将有超过1.31亿人受到影响。阿尔茨海默病(AD)是当今最常见的痴呆形式,占所有痴呆诊断病例的60-70%。这篇社论的目的是回顾地中海饮食和一些植物药对AD的潜在益处。
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引用次数: 5
A Prospective Pharmacokinetic Study of Docetaxel in Breast Cancer Patients in Relation to CYP3A4 Activity 多西紫杉醇对乳腺癌患者CYP3A4活性影响的前瞻性药代动力学研究
Pub Date : 2016-05-17 DOI: 10.4172/2167-065X.1000156
Mervat Mostafa Omran, O. Badary, A. Helal, S. Shouman
Abstract Purpose: To study the correlation between pharmacokinetics & pharmacodynamic of docetaxel and CYP3A4 activity in Egyptian cancer patients. Patients and methods: Fourteen Egyptian female Patients with metastatic breast cancer, World Health Organization (WHO) performance status 0 to 2, had received prior chemotherapy regimen, were treated with single-agent docetaxel (100 mg/m2), given every 21 days. Hydrocortisone 300 mg IV was administered 2 days before docetaxel treatment and Cytochrome 3A4 activity was determined by measuring the level of urinary metabolites of 6β-hydroxy cortisol (6β-OHF) and cortisol (FC). For the pharmacokinetic study, Blood samples were taken before and after IV infusion for 1 hr of 100 mg/m2 docetaxel. The level of the drug was determined using HPLC and the correlation between pharmacokinetics and CYP3A4 activity were determined. Results: After cortisol administration, the total amount of 24-hour urinary 6β-OHF and FC were19.97 ± 10.43 and 16.84 ± 10.36 mg/24 h (mean ± SD) respectively. On the other hand, the 6β-OHF/FC ratio after cortisol administration was 1.86 ± 1.933. The pharmacokinetic parameters of docetaxel were clearance 19.9 ± 4.5 L/hr, the volume of distribution 65.6 ± 28.6 L (mean ± SD) and AUC 7.2 μg/ml.hr (range 5-8.8 μg/ml.hr) ± SD). A significant correlation was found between 6β-OHF/FC ratio and neutropenia (p=0.04) in addition correlation between 6β-OHF and Cmax (p=0.04). Conclusion: The interpatient variability of CYP3A4 activity in each patient could be predicted by measuring the total amount of 24 hour urinary 63-OHF after cortisol administration. Individualized dosing to optimize drug exposure for each patient could be performed based on this method. A farther study of fixed versus individualized dosing of docetaxel is needed to determine whether individualized chemotherapy with the application of this method can reduce PK and toxicity variability.
摘要目的:研究多西他赛药动学和药效学与埃及肿瘤患者CYP3A4活性的相关性。患者和方法:14例埃及女性转移性乳腺癌患者,世界卫生组织(WHO)评分为0 ~ 2,既往接受化疗方案,多西他赛单药治疗(100 mg/m2),每21天给药一次。在多西他赛治疗前2天给予氢化可的松300 mg IV,通过测定尿中6β-羟基皮质醇(6β-OHF)和皮质醇(FC)的代谢物水平来测定细胞色素3A4的活性。为了进行药代动力学研究,在静脉输注100 mg/m2多西紫杉醇1小时前后取血样。采用高效液相色谱法测定药物水平,并测定药代动力学与CYP3A4活性的相关性。结果:皮质醇给药后,24小时尿6β-OHF和FC总量分别为19.97±10.43和16.84±10.36 mg/24 h (mean±SD)。另一方面,皮质醇处理后6β-OHF/FC比值为1.86±1.933。多西他赛的清除率为19.9±4.5 L/hr,分布容积为65.6±28.6 L (mean±SD), AUC为7.2 μg/ml。(范围5-8.8 μg/ml.hr)±SD)。6β-OHF/FC与中性粒细胞减少症有显著相关(p=0.04), 6β-OHF与Cmax有显著相关(p=0.04)。结论:通过测量皮质醇给药后24小时尿63-OHF总量,可以预测患者间CYP3A4活性的变异性。个体化给药以优化每位患者的药物暴露,可基于该方法进行。需要进一步研究多西他赛的固定剂量和个体化剂量,以确定应用该方法进行个体化化疗是否可以降低PK和毒性变异性。
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引用次数: 5
Oxytocin Nasal Spray in the Treatment of Binge Eating Disorder and Obesity: A Pilot, Randomized, Double-Blind Trial 催产素鼻喷雾剂治疗暴食症和肥胖症:一项先导、随机、双盲试验
Pub Date : 2016-04-12 DOI: 10.4172/2167-065X.1000155
R. Agabio, Anna Maria Giulia Farci, Olga Curreli, Raffaele Deidda, S. Mercuro, Romina Naitana, A. Restivo, E. Tronci, G. Gessa, M. R. Melis
Background Preclinical studies suggest that the neuropeptide oxytocin reduces food intake and body weight, but only a few clinical studies have investigated the translatability of these findings in humans. The present study investigated the safety and efficacy of oxytocin nasal spray in patients affected by binge eating disorder and obesity. Methods Seventeen outpatients affected by binge eating disorder and obesity participated in a 8 week double-blind trial and received oxytocin (n=8; 24 IU, four times a day, 20 min before each of three meals and before going to bed) or placebo (n=9) with an energy-restricted diet. Primary outcomes included adverse events and the number of binge eating episodes per week. Secondary measures included body weight, BMI, severity of BED, craving for food, quality of sleep, quality of life, anxiety, and depressive symptoms. Results One patient of oxytocin group discontinued prematurely the trial before the first post-randomization efficacy measure. Among the other 16 participants, 13 (81.2%) completed the trial, and 3 (18.8%) discontinued [3 in the oxytocin group; 0 in the placebo group (p=0.0625, Fisher’s exact test)]. No significant difference between groups was found in any outcome evaluated. Patients of the placebo group performed slightly better than patients of the oxytocin group in some secondary outcomes, but these differences were not significant. Conclusion Oxytocin nasal spray resulted to be safe, including in women of childbearing age but did not significantly reduce the number of binge eating episodes per week in outpatients affected by binge eating disorder and obesity. These findings are discussed in light of the human oxytocin literature.
临床前研究表明,神经肽催产素可以减少食物摄入和体重,但只有少数临床研究调查了这些发现在人类中的可翻译性。本研究探讨了催产素鼻喷雾剂对暴饮暴食症和肥胖症患者的安全性和有效性。方法17例暴食症合并肥胖症门诊患者参加为期8周的双盲试验,并给予催产素治疗(n=8;24 IU,一天四次,每餐前20分钟,睡前服用)或安慰剂(n=9)搭配能量限制饮食。主要结局包括不良事件和每周暴食发作次数。次要测量包括体重、身体质量指数、BED的严重程度、对食物的渴望、睡眠质量、生活质量、焦虑和抑郁症状。结果1例催产素组患者在第一次随机化后疗效测量前提前终止试验。在其他16名参与者中,13名(81.2%)完成了试验,3名(18.8%)停止了试验[催产素组3名;安慰剂组为0 (p=0.0625, Fisher精确检验)。在评估的任何结果中,两组间均未发现显著差异。在一些次要结果中,安慰剂组患者的表现略好于催产素组患者,但这些差异并不显著。结论催产素鼻喷雾剂对育龄妇女是安全的,但对患有暴食症和肥胖症的门诊患者每周暴食发作次数没有显著减少。这些发现是根据人类催产素文献进行讨论的。
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引用次数: 12
Transport Mechanism of Intestinal Absorption of ü Opioid Recept or Agonists and Contribution of P-Glycoprotein in Rats and Human Intestinal Epithelial Caco-2 ü阿片受体或激动剂在大鼠和人肠上皮Caco-2肠道吸收的转运机制及p -糖蛋白的贡献
Pub Date : 2016-03-24 DOI: 10.4172/2167-065X.1000154
K. Naruhashi, Akiko Kamino, E. Ochi, Erina Kusabiraki, M. Ueda, Yuusuke Sugihara, T. Urushidani, Hirokazu Nakanishi, N. Shibata
Abstract 1.1. Introduction: The μ opioid receptor agonists, morphine and loperamide, are widely used orally and are suggested to be P-glycoprotein (P-gp) substrates. P-gp is expressed in the brain, intestine, and various tissues in human and rats. In the intestine, P-gp limits the absorption of certain drugs such as opioids; however, the underlying mechanism has not been elucidated. The aim of the present study was to examine the intestinal transport characteristics of morphine and loperamide and the role of P-gp in their transport process. 1.2. Method: Transcellular transport studies were conducted using isolated rat intestinal tissue mounted in an Ussing-type chamber. Bidirectional permeability and inhibition transport studies were performed using Caco-2 cell lines. The intestinal absorption was examined by an in situ closed-loop method in rats. 1.3. Results: Loperamide showed secretory transport across rat intestinal tissue and Caco-2 cells, and P-gp substrates cyclosporine A and rhodamine 123 inhibited this transport. In the intestinal loop experiment in rats, the accumulation of loperamide in the intestinal tissue increased upon adding cyclosporine A and rhodamine 123. In contrast, morphine showed no directional transport and P-gp inhibitory effects across rat intestinal tissue. In Caco-2 cells, morphine transport was found to be secretory-directed and this transport was inhibited by cyclosporine A and rhodamine 123, but to a much lesser extent than that of loperamide. Morphine disappearance and accumulation were unaffected upon the addition of cyclosporine A and rhodamine 123. 1.4. Conclusion: These results suggest that P-gp contributes significantly to the secretory transport of loperamide but negligibly to that of morphine in the small intestine. In conclusion, intestinal transport of both morphine and loperamide is found to be secretory-directed. P-gp partially contributes to this secretory-directed transport. Thus, P-gp is prominent in loperamide rather than morphine transport.
抽象的1.1。μ阿片受体激动剂吗啡和洛哌丁胺被广泛口服,被认为是p -糖蛋白(P-gp)底物。P-gp在人和大鼠的脑、肠和各种组织中均有表达。在肠道中,P-gp限制某些药物(如阿片类药物)的吸收;然而,其潜在机制尚未阐明。本研究的目的是研究吗啡和洛哌丁胺的肠转运特性以及P-gp在其转运过程中的作用。1.2. 方法:采用分离大鼠肠组织置于ussing型腔内进行跨细胞转运研究。用Caco-2细胞系进行了双向通透性和抑制转运研究。采用原位闭环法检测大鼠肠道吸收。1.3. 结果:洛哌丁胺在大鼠肠组织和Caco-2细胞间具有分泌性转运,P-gp底物环孢素A和罗丹明123抑制了这种转运。在大鼠肠袢实验中,添加环孢素A和罗丹明123后,洛哌丁胺在肠组织中的蓄积增加。相比之下,吗啡在大鼠肠道组织中没有定向转运和P-gp抑制作用。在Caco-2细胞中,吗啡转运被发现是分泌导向的,这种转运被环孢素A和罗丹明123抑制,但比洛哌丁胺的程度要小得多。添加环孢素A和罗丹明123对吗啡的消失和积累没有影响。1.4. 结论:P-gp对洛哌丁胺在小肠内的分泌转运有显著作用,对吗啡的分泌转运作用可忽略不计。综上所述,吗啡和洛哌丁胺的肠道转运都是由分泌导向的。P-gp在一定程度上促进了这种秘书导向的运输。因此,P-gp在洛哌丁胺转运中比在吗啡转运中更重要。
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引用次数: 6
The Search for genomic markers for coffee consumption 寻找咖啡消费的基因组标记
Pub Date : 2016-01-01 DOI: 10.4172/2167-065X.C1.021
R. Santos
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引用次数: 0
Coffee consumption: A genetic approach 喝咖啡:一种基因方法
Pub Date : 2015-12-24 DOI: 10.4172/2167-065X.C1.015
R. Santos
ISSN: 2573-3664 Coffee is among the most widely consumed beverages in the world. The consumption of coffee has been receiving a lot of attention in regards its potential health benefits and risks as well. Caffeine and phenolic compounds such as chlorogenic acids are some of the most investigated constituents from coffee. It has been attributed various properties to those compounds such as central nervous system stimulant and antioxidants respectively. Coffee is in fact a very complex mixture that varies according with the origin of the beans and roasting process.
咖啡是世界上消费最广泛的饮料之一。饮用咖啡在潜在的健康益处和风险方面受到了很多关注。咖啡因和酚类化合物,如绿原酸,是咖啡中研究最多的成分。人们认为这些化合物分别具有中枢神经系统兴奋剂和抗氧化剂的特性。咖啡实际上是一种非常复杂的混合物,根据咖啡豆的产地和烘焙过程而有所不同。
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引用次数: 0
Clinical pharmacy experience in ophthalmology setting by utilizing collaborative drug therapy management (CDTM) 协同药物治疗管理(CDTM)在眼科的临床药学应用
Pub Date : 2015-12-24 DOI: 10.4172/2167-065X.C1.016
F. Al-Saikhan
N antimicrobial stewardship is continuous work to optimize antimicrobial usage to improve patient outcomes and prevent antimicrobial related problems. General Administration of Pharmaceutical Care established the program in 2013 by formulate Central Antibiotic Committees, this committee established National Antimicrobial Stewardship program consisting of formulating peripheral antibiotics, infectious diseases team, antibiotics physician order form, antibiotics consumption and usages, antibiogram regulations, and USA General of Disease Control Antimicrobial stewardship monitoring outcome indicators. In 2014, Peripheral Antibiotics Committees were established at twenty regions to follow up the implementation of the program national wide, and started with antimicrobial stewardship education and orientation. In 2015, the real applications of the program were started in more than ten regions and more than forty hospitals. Antimicrobial stewardship will be expanded to cover 20 regions and more ninety biggest hospitals, medical cities and private hospitals and primary care centers in Saudi Arabia. The program is excepting to reduce antimicrobial consumption more than 50% with reduction of bugs resistance to medication, reduction of antimicrobial related problems, better patients care with tremendous reduction of unnecessary cost.
抗菌药物管理是一项持续的工作,旨在优化抗菌药物的使用,以改善患者的治疗效果并预防与抗菌药物相关的问题。国家药品监督管理总局于2013年成立了中央抗生素委员会,该委员会制定了国家抗菌药物管理方案,包括制定周边抗生素、传染病小组、抗生素医生处方、抗生素消费和使用、抗生素谱规定和美国疾病控制与预防总局抗菌药物管理监测结果指标。2014年,在全国20个地区成立了周边抗菌药物委员会,以跟进该计划的实施情况,并开始开展抗菌药物管理教育和指导工作。2015年,该项目在十多个地区、四十多家医院开始实际应用。抗菌药物管理将扩大到沙特阿拉伯的20个地区和90多家最大的医院、医疗城市、私立医院和初级保健中心。该计划旨在通过减少细菌对药物的耐药性,减少与抗菌药物相关的问题,通过大幅减少不必要的费用,更好地照顾患者,从而减少50%以上的抗菌药物消耗。
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引用次数: 15
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