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Clinical pharmacokinetics profile of ivermectin 1% cream after dermal applications on the face

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World Journal of dermatology 2016年第1期5卷 57-64页

作者： Khaled Benkali Fran?ois Rony michael Graeber Jean Jacovella Jean-Paul Chappuis Marie-Helene Peirone Michel Poncet Stéphane delage Ronan Bouer Nathalie Wagner Galderma R and d

AIM: To investigate the pharmacokinetics profile of Ivermectin 1% cream after topical treatment in patients with papulopustular rosacea(PPR).METHOdS: Ivermectin 1% cream is a new, effective, and safe treatment for PPR. The human pharmacokinetic(PK) profile of ivermectin and its circulating metabolites were assessed following topical application of ivermectin 1% cream to the face. Clinical PK assessments were conducted after 4 wk of treatment using healthy volunteers and PPR subjects. Additionally, PK sampling was conducted up to 1 year of treatment in clinical phase 3 studies. Plasma concentrations of ivermectin and ivermectin metabolites were determined using high-performance liquid chromatography with fluorescence detection after a specific derivation to increase ***: Systemic exposure to ivermectin was quantifiable at low levels in healthy and moderate to severe PPR subjects following the first topical application of ivermectin 1% cream(mean Cmax of 0.5 ± 0.2 ng/mL and 0.7 ± 0.5 ng/mL in healthy volunteers and PPR subjects, respectively). Ivermectin plasma levels reached a plateau after 2 wk of repeated topical application, indicating that steady-state concentrations had been reached. No further ivermectin plasma accumulation was observed during the long-term clinical studies that investigated ivermectin treatment up to 1 year. Investigation of ivermectin metabolites indicated that 2 circulating metabolites represented more than 10% of parent drug systemic exposure at steady state. Repeated topical application of ivermectin 1% cream resulted in lower systemic exposure levels when compared with orally administered ivermectin, suggesting limited transdermal absorption of ivermectin. Topically applied ivermectin is cleared from the plasma slowly(with a prolonged plasma half-life when compared to the oral route).CONCLUSION: Applications of ivermectin 1% cream result in low systemic exposure levels. Steady–state conditions are achieved by 2 wk without

关键词： Ivermectin Pharmacokinetic maximal usage trial Metabolites Plasma and rosacea

AB090. MOG1, the genetic modifier at 20q13, delays the age-at-onset of glaucoma by 8 to 10 years

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Annals of Eye Science 2018年第1期 496-496页

作者： Vincent Raymond Pascal Belleau Rose Arseneault Stéphane dubois Jean-Louis Anctil Gilles Côté Marcel Amyot Fahed Elian michael AWalter Québec Glaucoma Network département d’ophtalmologie Centre de rechrechr du CHU de QuébecQuébecQCCanada

Background:Primary open-angle glaucoma(POAG)is a genetically complex disorder caused primarily by gene-gene *** identify these interactions,we studied the CA family,a large French-Canadian pedigree in which the myocilin K423E mutation(MYOCK423E)causes autosomal dominant glaucoma with diagnoses ranging from juvenile-onset OAG(JOAG)to late adult-onset POAG in the heterozygotes(HTZ).To explain this extreme variability,we hypothesized that a second gene,called a modifier,was interacting with MYOC,the primary disease *** goals were(I)to map the modifier on the human genome and;(II)to characterize the symptoms affected genetically by the *** symptoms are called ***:Three hundred seventy-five CA members were studied using four quantitative endophenotypes:age of maximal intra-ocular pressures(IOPmax),IOPs progression,progression of cup to disk ratios and age-at-onset(AAO)defined as age at which ocular hypertension(OHT)was first detected with IOP≥22 ***-wide linkage analysis was performed by genotyping 408 genetic markers in 184 CA *** unbiased pedigree-based algorithm was designed to identify the individuals who were double-mutants,i.e.,these individuals carried one MYOCK423E mutation(i.e.,they were HTZ,affected or not)and they also carry simultaneously a dNA mutation within the ***:Out of the 375 CA family members investigated,156 were HTZ for the MYOCK423E mutation.120 HTZ were affected with OAG or OHT with treatment while the remaining 36 HTZ were *** ranged from 7 to 63 years old;4 individuals over 50 years old were still *** preceded optic nerve damage in>98%of the HTZ carriers,confirming that AAO reflected the true severity of the *** modifier showed strong inherited effects on 2 of the 4 endophenotypes:AAO and *** next mapped with very high confidence the modifier locus for AAO at chromosome *** genotyping with additional markers refined th

关键词： Blindness genomics complex genetic disorder gene-gene interactions biostatistics

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活体中共焦显微镜下的角膜后沉着物

美国医学会眼科杂志（中文版） 2005年第3期17卷 191-191页

作者： michael S. Wertheim William d. Mathers Stephen J. Planck Tammy M .Martin Eric B. Suhler Justine R. Smith James T. Rosenbaum 许珂（译）

目的：在活体中用共焦显微镜（IVCM）观察不同葡萄膜炎亚型的角膜后沉着物（KP）成分。方法：用扫描共焦显微镜观察患者（n=33）的KP，这些患者来自第三级转诊的葡萄膜炎门诊部，患有免疫介导或感染性的葡萄膜炎，包括HIJA-B27相关的葡... 详细信息

目的：在活体中用共焦显微镜（IVCM）观察不同葡萄膜炎亚型的角膜后沉着物（KP）成分。方法：用扫描共焦显微镜观察患者（n=33）的KP，这些患者来自第三级转诊的葡萄膜炎门诊部，患有免疫介导或感染性的葡萄膜炎，包括HIJA-B27相关的葡萄膜炎、结节病、Vogt—Koyanagi—Harada综合征，青少年慢性关节炎，Fuchs异色性虹膜腱状体炎，巨细胞病毒性视网膜炎、眼部带状疱疹、眼部弓形体病和先天葡萄膜炎。图像被采集并行实时数字化处理。

关键词：角膜显微镜检查电子扫描/仪器和设备

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粘附设备有望帮助我们攀墙越壁

今日电子 2010年第4期 27-27页

作者： Christina d’Airo

美国康奈尔大学的研究人员发明了一种开关可控的粘附设备，可望使物体——甚至是人附着在墙壁上。该掌上型设备的发明者是化学与生物工程学教授保罗·斯蒂恩（Paul Steen）和曾做过博士后研究的迈克尔·沃格尔（michael Vogel）。该设... 详细信息

美国康奈尔大学的研究人员发明了一种开关可控的粘附设备，可望使物体——甚至是人附着在墙壁上。该掌上型设备的发明者是化学与生物工程学教授保罗·斯蒂恩（Paul Steen）和曾做过博士后研究的迈克尔·沃格尔（michael Vogel）。该设备利用水面张力作为附着力。

关键词：设备粘附墙壁美国康奈尔大学生物工程学研究人员发明者附着力

Potential factors influencing lymphatic filariasis transmission in"hotspot"and"control"areas in Ghana:the importance of vectors

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Infectious diseases of Poverty 2019年第1期8卷 45-55页

作者： Sellase Pi-Bansa Joseph Harold Nyarko Osei Kwadwo Kyeremeh Frempong Elizabeth Elhassan Osei Kweku Akuoko david Agyemang Collins Ahorlu Maxwell Alexander Appawu Benjamin Guibehi Koudou michael david Wilson dziedzom Komi de Souza Samuel Kweku dadzie Jurg Utzinger daniel Adjei Boakye Swiss Tropical and Public Health Institute BaselSwitzerland University of Basel BaselSwitzerland Noguchi Memorial Institute for Medical Research College of Health SciencesUniversity of GhanaLegonGhana department of Animal Biology and Conservation Science University of GhanaLegonGhana SightSavers International Ghana OfficeAccraGhana African Regional Postgraduate Programme in Insect Science University of GhanaLegonGhana Vector Biology department Liverpool School of Tropical MedicineLiverpoolUK Centre Suisse de Recherches Scientifiques en Cote d'Ivoire AbidjanCote d'Ivoire

Background:Mass drug administration(MdA)programmes for the control of lymphatic filariasis in Ghana,have been ongoing in some endemic districts for 16 *** current study aimed to assess factors that govern the success of MdA programmes for breaking transmission of lymphatic filariasis in ***:The study was undertaken in two"hotspot"districts(Ahanta West and Kassena Nankana West)and two control districts(Mpohor and Bongo)in *** were collected and identified using morphological and molecular tools.A proportion of the cibarial armatures of each species was *** were performed onAnopheles gambiae for filarial worm detection.A questionnaire was administered to obtain information on MdA compliance and vector control *** were compared between districts to determine factors that might explain persistent transmission of lymphatic ***:High numbers of mosquitoes were sampled in Ahanta West district compared to Mpohor district(F=16.09,P=0.002).There was no significant difference between the numbers of mosquitoes collected in Kassena Nankana West and Bongo districts(F=2.16,P=0.185).Mansonia species were predominant in Ahanta West *** mosquitoes were prevalent in all *** with infected and infective filarial worms was found only in Ahanta West *** differences were found in cibarial teeth numbers and shape for mosquito species in the surveyed *** MdA coverage was high in all *** average use of bednet and indoor residual spraying was 82.4 and 66.2%,*** was high compliance in the five preceding MdA rounds in Ahanta West and Kassena Nankana West districts,both considered hotspots of lymphatic filariasis ***:The study on persistent transmission of lymphatic filariasis in the two areas in Ghana present information that shows the importance of local understanding of factors affecting control and elimination of lymphatic

关键词： Ghana Hotspots Lymphatic filariasis Mass drug administration Microfilariae Systematic non-compliance Vector control

红曲对中度血脂升高美国人调节血脂作用的临床研究

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上海预防医学 2013年第9期25卷 501-506页

作者：陆继红 Kermit Bonovich Harry Colfer michael davidson Carlos A.dujovne david L.Fried Mitchell Greenspan Ronald P.Karlsberg Stephen P.King Craig F.LaForce Marc Litt J.Robert McGhee 曾润海朱佳石谈宁芝华茂北京临床药理研究中心北京100088 Healthy Options Burns Clinic Rush-Presbyterian-St. Luke's Medical Center Kansas University Medical Center and Kansas Foundation for Clinical Pharmacology Omega Medical Research Lifemark Medical Center Cardiovascular Research Institute of So. CA Future Scripts North Carolina Clinical Research Jacksonville Heart Center Mediquest Research Group Nu Skin Center for Anti-aging Research 香港理工大学

[目的]评价在饮食控制的情况下红曲（RYRCholestin）对美国高血脂人群的降脂作用和安全性。[方法]开放标记，自身对照，多中心临床试验。187名美国高血脂人群入选（血清低密度脂蛋白胆固醇3．50—4．92mmol／L，总胆固醇5．18—7．25mmo... 详细信息

[目的]评价在饮食控制的情况下红曲（RYRCholestin）对美国高血脂人群的降脂作用和安全性。[方法]开放标记，自身对照，多中心临床试验。187名美国高血脂人群入选（血清低密度脂蛋白胆固醇3．50—4．92mmol／L，总胆固醇5．18—7．25mmol／L；男116人，女71人），162入完成试验。在整个试验中受试者遵照美国国家胆固醇教育计划的饮食要求。试验的前4周仅控制饮食，第5周至第12周连续服用8周RYRCholestin（每日2．4g）。[结果]经前4周饮食控制，血清脂质各指标无显著变化。口服RYRCholestin8周后，血清总胆固醇、低密度脂蛋白胆固醇和三酰甘油分别降低16．6％，24．O％和25．2％，高密度脂蛋白胆固醇升高14．3％（P〈0．001）。显效率为79．0％，有效率为97．5％。停服14d（2周）后，血脂各指标回到试验前水平。试验中共发现可能与服用产品相关的、轻度的29项不良反应。[结论]RYRCholestin的耐受性良好，它可降低血清总胆固醇、低密度脂蛋白胆固醇和三酰甘油，升高血清高密度脂蛋白胆固醇。停服2用后受试者的血脂各项指标均恢复到试验前水平。

关键词：红曲高脂血症低密度脂蛋白胆固醇三酰甘油高密度脂蛋白胆固醇

大剂量阿托伐他汀与常规剂量辛伐他汀在心肌梗死二级预防中的比较——IdEAL研究：随机对照试验

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美国医学会杂志（中文版） 2006年第1期25卷 3-10页

作者： Terje R．Pedersen Ole Faergeman John J. P. Kastelein Anders G．Olsson Matti J. Tikkanen Ingar Holme Mogens Lytken Larsen Fridrik S. Bendiksen Christina Lindahl michael Szarek John Tsai 王淑敏（译）仝其广（译）胡大一（校） Centre for Preventive Medicine Ulleval University Hospital Oslo Norway department of MedicineCardiology A Arhus University Hospital Arhus Denmark Academic Hospital Amsterdam Amsterdam the Netherlands department of Internal Medicine University Hospital Linkoping Sweden department of Medicine Helsinki University Central Hospital Helsinki Finland Pfizer Sweden Taby Sweden Pfizer Inc New York NY dr Bendiksen is in private practice in Hamar Norway. 不详

背景：证据显示，与临床常规降脂比较，对稳定性冠状动脉疾病患者施行强化降脂降低低密度脂蛋白胆固醇（low—density lipoprotein cholesterol，LdL—C）可进一步获益。目的：比较2种降脂治疗策略对既往有心肌梗死（MyocardialInfarct... 详细信息

背景：证据显示，与临床常规降脂比较，对稳定性冠状动脉疾病患者施行强化降脂降低低密度脂蛋白胆固醇（low—density lipoprotein cholesterol，LdL—C）可进一步获益。目的：比较2种降脂治疗策略对既往有心肌梗死（MyocardialInfarction，MI）病史患者心血管事件危险的影响。设计、地点及研究对象：IdEAL研究是一项前瞻性、随机、开放、盲法终点评价试验。试验于1999年3月至2005年3月在北欧190个心脏病急救单位和专家诊所进行，中位随访时间为4．8年。试验人选8888例有急性MI病史的患者，年龄≤80岁。干预：患者随机分配接受大剂量阿托伐他汀（80mg／d；n=4439）或常规剂量辛伐他汀（20mg／d；n=4449）治疗。主要终点：主要冠脉事件的发生定义为冠脉死亡、证实有非致命性急性MI或心脏骤停复苏。结果：治疗期间，辛伐他汀组平均LdL—C水平为104mg／dL（SE，0．3），阿托伐他汀组为81mg／dL（SE，0．3）。辛伐他汀组有463例（10．4％）患者发生了主要冠脉事件，阿托伐他汀组为411例（9．3％）（风险比[hazardratio，HR]，0．89；95％CI，0．78—1．01；P=0．07）。两组发生非致命性MI者分别为321例（7．2％）和267例（6．0％）（HR，0．83；95％CI，0．71—0．98；P=0．02）。但是另外两个一级终点组分的发生率两组末见显著差异。两组发生主要心血管事件者分别为608例和533例（HR，0．87；95％CI，0．77—0．98；P=0．02）。辛伐他汀组发生任何一种冠脉事件的患者有1059例，阿托伐他汀组898例（HR，0．84；95％CI，0．76—0．91；P〈0．001）。两组发生非心血管死亡者分别为156例（3．5％）和143例（3．2％）（HR，0．92；95％CI，0．73—1．15；P=0．47）。各种原因所致死亡：辛伐他汀组374例（8．4％），阿托伐他汀组366例（8．2％）（HR，0．98；95％CI，0．85—1．13；P=0．81）。阿托伐他汀组患者凶非严重性不良事件而停药的比例较高；因转氨酶升高分别导致43例（1．0％）和5例（0．1％）患者停药（P（0．001）。两组罕见严重肌病及横纹肌溶解。结论：研究表明，在既往有MI的患者，强化降低LdL—C并不能显著降低主要冠脉事件的一级终点，但是能降低其他复合二级终点及非致命性急性MI的危险。心血管死亡率或全因死亡率没有差异。强化降低LdL—C可使MI患者获益，而且不增加非心血管死亡率或其他严重不良反应。

关键词：随机对照试验阿托伐他汀辛伐他汀二级预防心肌梗死常规剂量大剂量低密度脂蛋白胆固醇心血管死亡率心血管事件

Orally administered extract from Prunella vulgaris attenuates spontaneous colitis in mdr1a^(-/-) mice

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World Journal of Gastrointestinal Pharmacology and Therapeutics 2015年第4期6卷 223-237页

作者： Kelley MK Haarberg Meghan J Wymore Brand Anne-Marie C Overstreet Catherine C Hauck Patricia A Murphy Jesse M Hostetter Amanda E Ramer-Tait michael J Wannemuehler department of Veterinary Microbiology and Preventive Medicine College of Veterinary Medicine Iowa State University department of Food Science and Human Nutrition Iowa State University department of Veterinary Pathology College of Veterinary Medicine Iowa State University department of Food Science and Technology University of Nebraska-Lincoln

AIM: To investigate the ability of a Prunella vulgaris(P. vulgaris) ethanolic extract to attenuate spontaneous typhlocolitis in mdr1a-/- mice. METHOdS: Vehicle(5% ethanol) or P. vulgaris ethanolic extract(2.4 mg/d) were administered daily by oral gavage to mdr1a-/- or wild type FVBWT mice from 6 wk of age up to 20 wk of age. Clinical signs of disease were noted by monitoring weight loss. Mice experiencingweight loss in excess of 15% were removed from the study. At the time mice were removed from the study, blood and colon tissue were collected for analyses that included histological evaluation of lesions, inflammatory cytokine levels, and myeloperoxidase activity. RESULTS: Administration of P. vulgaris extracts to mdr1a-/- mice delayed onset of colitis and reduced severity of mucosal inflammation when compared to vehicle-treated mdr1a-/- mice. Oral administration of the P. vulgaris extract resulted in reduced(P d TNFα(9.9 ± 3 vs 14.8 ± 1) as well as reduced gene expression by more than two-fold for Ccl2, Ccl20, Cxcl1, Cxcl9, IL-1 α, Mmp10, VCAM-1, ICAM, IL-2, and TNFα in the colonic mucosa of mdr1a-/- mice compared to vehicle-treated mdr1a-/-mice. Histologically, several microscopic parameters were reduced(P d mdr1a-/-mice, as was myeloperoxidase activity in the colon(2.49 ± 0.16 vs 3.36 ± 0.06, P d4+ T cells(2031.9 ± 412.1 vs 5054.5 ± 809.5) and germinal center B cells(2749.6 ± 473.7 vs 4934.0 ± 645.9) observed in the cecal tonsils of P. vulgaris-treated mdr1a-/- were significantly reduced(P d mdr1a-/- mice. Vehicle-treated mdr1a-/- mice were found to produce serum antibodies to antigens derived from members of the intestinal microbiota, indicative of severe colitis and a loss of adaptive tolerance to the members of the microbiota. These serum antibodies were greatly reduced or absent in P. vulga

关键词： Prunella vulgaris Spontaneous colitis Inflammatory

农业健康研究中阳光暴露、维生素d受体基因变异与乳腺癌风险

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环境与职业医学 2014年第5期31卷 341-341页

作者： Lawrence S.Engel Jaya Satagopan Camelia S.Sima Irene Orlow Urvi Mujumdar Joseph Coble Pampa Roy Sarah Yoo dale P.Sandler michael C.Alavanja

[背景]流行病学证据表明,阳光暴露与乳腺癌风险之间存在负性相关。假设其机制是阳光诱导皮肤合成维生素d。[目的]探讨阳光暴露及其与维生素d受体(VdR)基因变异的交互作用对乳腺癌风险的影响。[方法]在前瞻性农业健康研究队列的入组人群... 详细信息

[背景]流行病学证据表明,阳光暴露与乳腺癌风险之间存在负性相关。假设其机制是阳光诱导皮肤合成维生素d。[目的]探讨阳光暴露及其与维生素d受体(VdR)基因变异的交互作用对乳腺癌风险的影响。[方法]在前瞻性农业健康研究队列的入组人群中,研究31 021位持有私人执照的杀虫剂从业人员的妻子受到的阳光暴露与乳腺癌发病率,其中包括578个病例,平均随访8.6年。在一项由293名病例和586名匹配对照组成的巢式病例-对照研究中,评估阳光暴露、VdR变异体与乳腺癌之间的交互作用。有关阳光暴露的信息来自于队列入组时的问卷调查。对队列数据采用Cox比例风险回归估计相对风险,对巢式病例-对照数据采用条件logistic回归估计相对风险。[结果]在所有参与者中,患乳腺癌风险的小幅度下降与随访前10年中平时阳光暴露≥1 h/d相关(与d相比)[风险比(HR)=0.8;95%CI:0.6～1.0]。这一相关性在雌激素受体阳性肿瘤(HR=0.7;95%CI:0.5～0.9)中比雌激素受体阴性肿瘤(HR=1.1;95%CI:0.6～2.1)中稍强。阳光暴露≥1 h/d和一个VdR单倍型的联合HR低于预期,因为单一暴露的HR为负值(交互作用,P=0.07)。[结论]上述研究结果提示,阳光暴露可能与乳腺癌风险降低相关,但是研究中并没有发现通过VdR变异体修饰的明确证据。需要进行更大规模的研究,特别是平时阳光暴露水平低的人群中可能能够更精确描述。

关键词：相对风险回归估计激素受体阳性流行病学证据雌激素受体风险降低交互作用单倍型受体基因病例-对照研究