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Investigation of fertility and early embryonic toxicity of caffeine in rats

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Investigation of fertility and early embryonic toxicity of c...

2013年（第三届）中国药物毒理学年会暨药物非临床安全性评价研究论坛

作者： WANG Hong-ping PAN Lei Sue MCPHERSON steve mason WuXi AppTec(Suzhou) Co. Ltd.

OBJECTIVE To investigate the fertility and early embryonic developmental toxicity of *** 160 rats were assigned to 4 groups of 20/sex/group,with vehicle or test article administered at dosages of 0,20,40 or 80 mg·kg·d once daily by oral *** were dosed for 4 weeks and females were dosed for 2 weeks prior to mating and dosing continued during the cohabitation *** were treated thereafter to termination after a dosing duration of 54 to 63 *** females mated successfully and were dosed thereafter up to gesation day(GD) *** were c-sectioned on *** Compared to the concurrent vehicle control group,the absolute body weight gain decreased significantly during the dosing period for males dosed at 40 -80 mg ? kg?d and for females dosed at 80 mg·kg·*** decreases were associated with decreased food *** of the test article was also noted to affect spermatogenesis in *** increases in sperm morphological abnormalities and decreases in sperm motility were observed following dosing at 40 -80 mg·kg·*** addition,a significant decrease in sperm count was also observed for animals dosed at 80 mg·kg·*** were no test article-related changes in cohabitation duration,estrus cycle(start from 7 d prior to mating,and continued during pairing period),fertility data,uterine observations (*** corpora lutea,implantations,live fetuses,embryonic resorptions,pre-implantation loss,post-implantation loss),reproductive organ weights,and macroscopic *** findings were considered to indicate that caffe- ine dosed at 20 -80 mg·kg·d did not affect female fertility and early embryonic development to *** The No-Observed-Adverse-Effect-Level(NOAEL) of caffeine on spermatogenesis was considered to be 20 mg·kg·d,and the NOAEL of caffeine on female fertility and early development to implantation was considered to be 80 mg·kg·d.

关键词： caffeine embryonic toxicity

Use of respiratory "head out" plethysmographs for evaluation of pulmonary function in rats

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Use of respiratory "head out" plethysmographs for evaluation...

2013年（第三届）中国药物毒理学年会暨药物非临床安全性评价研究论坛

作者： WU Rui QU Lin-hai Sue MCPHERSON steve mason Safety Pharmacology WuXi AppTec(Suzhou)Co.Ltd.

To evaluate the use of respiratory "head out" plethysmographys for use as a respiratory function assessment tool in rats as part of the respiratory system assessment required under the ICH S7A ***(20 mg ? kg iv) and Theophylline(10 mg·kg iv) were selected for use as reference compounds in this *** Sprague-Dawley rats,approximately 7 -8 weeks of age and in the weight range 246 -303 g were selected as the test *** approximate one week acclimation period preceded the study,during which animals were pre-selected for the suitability by assessment of their ability to stay in the restraint chambers("head-out" plethysmographys) for a target of about 2.5 h-Any rat demonstrating excessive excitability or abnormal breathing patterns were removed from the *** the day of dosing, animals were placed in "head out" plethysmographs and allowed to acclimate to the chambers for at least 5 min prior to each data collection *** following the acclimation period,ventilatory parameters(tidal volume,respiratory rate,and derived respiratory minute volume(RMV) were measured for an approximate 15 min period predose,continuously for the following approximate 2.5 h,then for approximate 15 min at approximately 4 and 24 h *** obtained were consistent with the literature and based on the results of this study,this assay,using respiratory "head out" plethysmographys to assess respiratory function,is considered acceptable for use in Pulmonary assessments under the ICH guideline.

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Use of respiratory "head out" plethysmographs for evaluation of pulmonary function in rats

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中国药理学与毒理学杂志 2013年第3期 604-604页

作者： WU Rui QU Lin-hai Sue MCPHERSON steve mason Safety Pharmacology WuXi AppTec(Suzhou) Co.Ltd.

To evaluate the use of respiratory ″head out″ plethysmographys for use as a respiratory function assessment tool in rats as part of the respiratory system assessment required under the ICH S7A ***(20 mg·kg-1 iv) and Theophylline(10 mg·kg-1 iv) were selected for use as reference compounds in this *** SpragueDawley rats,approximately 7-8 weeks of age and in the weight range 246-303 g were selected as the test *** approximate one week acclimation period preceded the study,during which animals were pre-selected for the suitability by assessment of their ability to stay in the restraint chambers(″head-out″ plethysmographys) for a target of about 2.5 h-Any rat demonstrating excessive excitability or abnormal breathing patterns were removed from the *** the day of dosing,animals were placed in ″head out″ plethysmographs and allowed to acclimate to the chambers for at least 5 min prior to each data collection *** following the acclimation period,ventilatory parameters(tidal volume,respiratory rate,and derived respiratory minute volume(RMV) were measured for an approximate 15 min period predose,continuously for the following approximate 2.5 h,then for approximate 15 min at approximately 4 and 24 h *** obtained were consistent with the literature and based on the results of this study,this assay,using respiratory ″head out″ plethysmographys to assess respiratory function,is considered acceptable for use in Pulmonary assessments under the ICH guideline.

关键词： head out Use of respiratory plethysmographs for evaluation of pulmonary function in rats

Investigation of a suitable method for monkey semen collection

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Investigation of a suitable method for monkey semen collecti...

2013年（第三届）中国药物毒理学年会暨药物非临床安全性评价研究论坛

作者： GUO Lei Sue McPHERSPM Charlie BARKER WAN Hong-ping steve mason Safety Pharmacology WuXi AppTec(Suzhou) Co.Ltd.

The cynomolgus monkey(Macaca facicularis) is routinely used in preclinical toxicity *** certain drug indications it is important to have sexually mature animals on the *** males the presence of sperm in the ejaculate is one of the criteria for determination of sexual *** intent of this study was to evaluate a reliable and repeatable method of semen collection.A total of 10 male cynomolgus monkeys,approximately 5 years of age or older and weighing 4.5 to 6.8 kg,were individually housed in stainless steel cages elevated off the floor,in HEPA-filtered rooms with a 12-h light *** monkeys received qualified feed and autoclaved water ad *** was collected using a modified penile electroejaculation method(Mattison,et al,2011).Semen collection was attempted in normal restraint chairs with additional restraint provided by the technician,if necessary,to minimize stress on the test subject.A gauze strip moistened in 0.9%saline was wrapped around the *** electrodes from the stimulator were attached to the *** stimulator settings were 10 to 30 pulses per second,and 1 to 3-ms *** voltage was varied from 0 to 50 *** lowest voltage was initially used and then gradually increased as *** head of the penis was held inside an appropriate volume tube opening to catch the entire ejaculate,which was immediately transported to the laboratory for sperm *** semen weight was also *** no ejaculation occurred the animal was allowed to rest for at least 1 min and the stimulation was *** no ejaculation occurred within 10 min,the animal was returned to his *** collection was attempted from the animal again with a minimum of 24-h of rest between collection attempts. The success rate for semen collection was 80%at the first attempt and 100%within 2 *** ejaculate parameters results obtained(weight and sperm number) were comparable to the *** results demonstrated that this semen collection

关键词： seme collection

Investigation of a suitable method for monkey semen collection

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Investigation of a suitable method for monkey semen collecti...

作者： GUO Lei Sue McPHERSPM Charlie BARKER WAN Hong-ping steve mason Safety Pharmacology WuXi AppTec(Suzhou)Co.Ltd

The cynomolgus monkey(Macaca facicularis) is routinely used in preclinical toxicity *** certain drug indications it is important to have sexually mature animals on the *** males the presence of sperm in the ejaculate is one of the criteria for determination of sexual *** intent of this study was to evaluate a reliable and repeatable method of semen collection.A total of 10 male cynomolgus monkeys,approximately 5 years of age or older and weighing 4.5 to 6.8 kg,were individually housed in stainless steel cages elevated off the floor,in HEPA-filtered rooms with a 12-h light *** monkeys received qualified feed and autoclaved water ad *** was collected using a modified penile electroejaculation method(Mattison,ef a/,2011).Semen collection was attempted in normal restraint chairs with additional restraint provided by the technician,if necessary,to minimize stress on the test subject.A gauze strip moistened in 0.9%saline was wrapped around the *** electrodes from the stimulator were attached to the *** stimulator settings were 10 to 30 pulses per second,and 1 to 3-ms *** voltage was varied from 0 to 50 *** lowest voltage was initially used and then gradually increased as *** head of the penis was held inside an appropriate volume tube opening to catch the entire ejaculate,which was immediately transported to the laboratory for sperm *** semen weight was also *** no ejaculation occurred the animal was allowed to rest for at least 1 min and the stimulation was *** no ejaculation occurred within 10 min,the animal was returned to his *** collection was attempted from the animal again with a minimum of 24-h of rest between collection attempts. The success rate for semen collection was 80%at the first attempt and 100%within 2 *** ejaculate parameters results obtained(weight and sperm number) were comparable to the *** results demonstrated that this semen collection

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Investigation of a suitable method for monkey semen collection

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中国药理学与毒理学杂志 2013年第3期 602-602页

作者： GUO Lei Sue McPHERSPM Charlie BARKER WAN Hong-ping steve mason Safety Pharmacology WuXi AppTec(Suzhou) Co.Ltd.

The cynomolgus monkey(Macaca facicularis) is routinely used in preclinical toxicity *** certain drug indications it is important to have sexually mature animals on the *** males the presence of sperm in the ejaculate is one of the criteria for determination of sexual *** intent of this study was to evaluate a reliable and repeatable method of semen collection.A total of 10 male cynomolgus monkeys,approximately 5 years of age or older and weighing 4.5 to 6.8 kg,were individually housed in stainless steel cages elevated off the floor,in HEPA-filtered rooms with a 12-h light *** monkeys received qualified feed and autoclaved water ad *** was collected using a modified penile electroejaculation method(Mattison,et al,2011).Semen collection was attempted in normal restraint chairs with additional restraint provided by the technician,if necessary,to minimize stress on the test subject.A gauze strip moistened in 0.9% saline was wrapped around the *** electrodes from the stimulator were attached to the *** stimulator settings were 10 to 30 pulses per second,and 1 to 3-ms *** voltage was varied from 0 to 50 *** lowest voltage was initially used and then gradually increased as *** head of the penis was held inside an appropriate volume tube opening to catch the entire ejaculate,which was immediately transported to the laboratory for sperm *** semen weight was also *** no ejaculation occurred the animal was allowed to rest for at least 1 min and the stimulation was *** no ejaculation occurred within 10 min,the animal was returned to his *** collection was attempted from the animal again with a minimum of 24-h of rest between collection *** success rate for semen collection was 80% at the first attempt and 100% within 2 *** ejaculate parameters results obtained(weight and sperm number) were comparable to the *** results demonstrated that this semen collecti

关键词： seme collection

用于药物安全性评价实验的Ponemah系统的GLP验证

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用于药物安全性评价实验的Ponemah系统的GLP验证

2012年全国安全药理遥测技术应用研讨会

作者：吕会田瞿林海刘琳 steve mason 胡正国苏州药明康德新药开发有限公司

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Identification and treatment of individuals with attentiondeficit/ hyperactivity disorder and substance use disorder: An expert consensus statement

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World Journal of Psychiatry 2023年第3期13卷 84-112页

作者： Susan Young Cyrus Abbasian Zainab Al-Attar Polly Branney Bill Colley Samuele Cortese Sally Cubbin Quinton Deeley Gisli Hannes Gudjonsson Peter Hill Jack Hollingdale steve Jenden Joe Johnson Deborah Judge Alexandra Lewis Peter mason Raja Mukherjee David Nutt Jane Roberts Fiona Robinson Emma Woodhouse Kelly Cocallis Department of Psychology Psychology Services LimitedCroydon CR97AEUnited Kingdom Department of Psychology Reykjavik UniversityReykjavikIceland Psychiatry-UK Limited Cornwall PL339ETUnited Kingdom ADHD and Autism Oxford ADHD&Autism CentreHeadington OX37BXUnited Kingdom CLC Consultancy Dunkeld PH80AYUnited Kingdom Center for Innovation in Mental Health School of PsychologyFaculty of Environmental and Life SciencesUniversity of SouthamptonSouthampton SO171BJUnited Kingdom Adult ADHD Adult ADHD Clinic LtdOxford OX37RPUnited Kingdom Forensic and Neurodevelopmental Science Institute of PsychiatryPsychology&NeuroscienceKing's College London Institute of PsychiatryLondon SE58AFUnited Kingdom Department of Psychology Institute of PsychiatryPsychology&NeuroscienceKing's College LondonLondon SE58AFUnited Kingdom Department of Psychiatry University of LondonLondon WC1E 7HUUnited Kingdom Department of Psychology Compass Psychology Services LtdLondon BR19DXUnited Kingdom Birribi Ltd Narberth SA677DUUnited Kingdom Halton and Knowsley Adult ADHD Team Merseycare NHS Foundation TrustWinwick WA29WAUnited Kingdom Department of Psychiatry Fulbourn HospitalCambridge CB215EFUnited Kingdom Department of Psychiatry Dr Peter Mason ADHD&Psychiatry Services LimitedLiverpool L19ARUnited Kingdom Adult Neurodevelopmental Service Horizon HouseEpsom KT174QJUnited Kingdom Department of Psychiatry Imperial College LondonLondon WS120NNUnited Kingdom Service User Representative Gloucestershire GL13NNUnited Kingdom Drug&Alcohol Services Surrey&Borders Partnership TrustLeatherhead KT227ADUnited Kingdom Forensic and Neurodevelopmental Sciences Institute of PsychiatryPsychology&NeuroscienceKing's College LondonLondon SE58AFUnited Kingdom Wansbeck General Hospital Northumbria Healthcare NHS Foundation TrustAshington NE639JJUnited Kingdom

Attention-deficit/hyperactivity disorder(ADHD)often co-occurs with substance use(SU)and/or substance use disorder(SUD).Individuals with concurrent ADHD and SU/SUD can have complex presentations that may complicate diagnosis and *** can be further complicated by the context in which services are ***,when working with young people and adults with co-existing ADHD and SU/SUD,there is uncertainty among healthcare practitioners on how best to meet their *** February 2022,the United Kingdom ADHD Partnership hosted a meeting attended by multidisciplinary experts to address these *** presentations providing attendees with an overview of the literature,group discussions were held synthesizing research evidence and clinical *** included:(1)A review of substances and reasons for use/misuse;(2)identification,assessment and treatment of illicit SU/SUD in young people and adults with ADHD presenting in community services;and(3)identification,assessment and treatment of ADHD in adults presenting in SU/SUD community and inpatient *** highlighted inter-service barriers and fragmentation of *** was concluded that a multimodal and multi-agency approach is *** consensus group generated a table of practice recommendations providing guidance on:identification and assessment;pharmacological and psychological treatment;and multi-agency interventions.

关键词： Attention-deficit/hyperactivity disorder Substance use Pharmacokinetics Assessment Treatment Comorbidity

Nature：大规模研究揭示生命所必需的基因

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现代生物医学进展 2016年第31期16卷 I0002-I0003页

作者： Dickinson, Mary E. Flenniken, Ann M. Ji, Xiao Teboul, Lydia Wong, Michael D. White, Jacqueline K. Meehan, Terrence F. Weninger, Wolfgang J. Westerberg, Henrik Adissu, Hibret Baker, Candice N. Bower, Lynette Brown, James M. Caddle, L. Brianna Chiani, Francesco Clary, Dave Cleak, James Daly, Mark J. Denegre, James M. Doe, Brendan Dolan, Mary E. Edie, Sarah M. Fuchs, Helmut Gailus-Durner, Valerie Galli, Antonella Gambadoro, Alessia Gallegos, Juan Guo, Shiying Horner, Neil R. Hsu, Chih-Wei Johnson, Sara J. Kalaga, Sowmya Keith, Lance C. Lanoue, Louise Lawson, Thomas N. Lek, Monkol Mark, Manuel Arschall, Susan M. mason, Jeremy McElwee, Melissa L. Newbigging, Susan Nutter, Lauryl M. J. Peterson, Kevin A. Ramirez-Solis, Ramiro Rowland, Douglas J. Ryder, Edward Samocha, Kaitlin E. Seavitt, John R. Selloum, Mohammed Szoke-Kovacs, Zsombor Tamura, Masaru Trainor, Amanda G. Tudose, Ilinca Wakana, Shigeharu Warren, Jonathan Wendling, Olivia West, David B. Wong, Leeyean Yoshiki, Atsushi MacArthur, Daniel G. Tocchini-Valentini, Glauco P. Gao, Xiang Flicek, Paul Bradley, Allan Skarnes, William C. Justice, Monica J. Parkinson, Helen E. Moore, Mark Wells, Sara Braun, Robert E. Svenson, Karen L. de Angelis, Martin Hrabe Herault, Yann Mohun, Tim Mallon, Ann-Marie Henkelman, R. Mark Brown, steve D. M. Adams, David J. Lloyd, K. C. Kent McKerlie, Colin Beaudet, Arthur L. Bucan, Maja Murray, Stephen A. Dept Mol Physiol & Biophys Houston TX 77030 USA Toronto Ctr Phenogen Toronto ON M5T 3H7 Canada Mt Sinai Hosp Toronto ON M5G 1X5 Canada Univ Penn Perelman Sch Med Genom & Computat Biol Program Philadelphia PA 19104 USA Med Res Council Harwell Mammalian Genet Unit Harwell OX11 0RD Oxon England Mary Lyon Ctr Harwell OX11 0RD Oxon England Hosp Sick Children Mouse Imaging Ctr Toronto ON M5T 3H7 Canada Wellcome Trust Sanger Inst Wellcome Trust Genome Campus Cambridge CB10 1SA England European Bioinformat Inst European Mol Biol Lab Wellcome Trust Genome Campus Cambridge CB10 1SD England Med Univ Vienna Ctr Anat & Cell Biol A-1090 Vienna Austria Hosp Sick Children 555 Univ Ave Toronto ON M5G 1X8 Canada Jackson Lab 600 Main St Bar Harbor ME 04609 USA Univ Calif Davis Mouse Biol Program Davis CA 95618 USA Italian Natl Res Council CNR Inst Cell Biol & Neurobiol Monterotondo Mouse Clin I-00015 Monterotondo Italy Massachusetts Gen Hosp Analyt & Translat Genet Unit Boston MA 02114 USA Broad Inst MIT & Harvard Program Med & Populat Genet Cambridge MA 02142 USA German Res Ctr Environm Hlth Helmholtz Zentrum Munchen Inst Expt Genet D-85764 Neuherberg Germany German Mouse Clin D-85764 Neuherberg Germany Baylor Coll Med Dept Mol & Human Genet Houston TX 77030 USA Nanjing Univ Nanjing Biomed Res Inst Collaborat Innovat Ctr Genet & Dev SKL Pharmaceut Biotechnol & Model Anim Res Ctr Nanjing 210061 Jiangsu Peoples R China Univ Strasbourg ICS Infrastruct Natl PHENOMIN F-67404 Illkirch Graffenstaden France Univ Strasbourg INSERM CNRS IGBMC F-67404 Illkirch Graffenstaden France RIKEN BioResource Ctr Tsukuba Ibaraki 3050074 Japan Childrens Hosp Oakland Res Inst Oakland CA 94609 USA IMPC San Anselmo CA 94960 USA Tech Univ Munich Sch Life Sci Weihenstephan Chair Expt Genet D-81675 Freising Weihenstephan Germany German Ctr Diabet Res DZD D-85764 Neuherberg Germany Francis Crick Inst Mill Hill Lab Mill Hill London NW1 1AT England Univ Penn Perlman

在哺乳动物基因组中。大约三分之一的基因是生命所必需的。在一项新的研究中，来自美国贝勒医学院等多个机构的研究人员描述了这些基因的大规模发现。以及它将如何影响对哺乳动物发育和人类疾病的理解。相关研究结果在线发表在Nature期... 详细信息

在哺乳动物基因组中。大约三分之一的基因是生命所必需的。在一项新的研究中，来自美国贝勒医学院等多个机构的研究人员描述了这些基因的大规模发现。以及它将如何影响对哺乳动物发育和人类疾病的理解。相关研究结果在线发表在Nature期刊上，论文标题为“High—throughput discovery of novel developmental phenotypes”。

关键词：动物基因组生命哺乳动物研究人员人类疾病医学院