The integral assessment of neurobehavioral, cardiovascular and respiratory (NCR) system in telemetered conscious animals is becoming more widely employed in safety pharmacology studies. The purpose of this study was to assess the feasibility of performing a NCR safety pharmacology study with amphetamine and acepromazine, compounds known to modulate neurobehavior, when administered orally to conscious beagle dogs and to validate procedures.

0.5% methylcellulose (5 mL/kg), 1 mg/kg amphetamine (5 mL/kg) or 2-3 mg/kg acepromazine (two 10 mg tablets per animal) were administered orally to 4 male beagle dogs. The cardiovascular parameters (DSI ART: blood pressure, heart rate) waveforms), respiratory parameters (EMKA IOX RIP: respiratory rate, tidal volume and minute volume) and neurobehavior (EMKA IOX video) were monitored for 2 hours prior to and 24 hours following the dose administration. In addition, animals were observed for potential neurobehavioral effects using a standard observation battery which allows the assessment for both peripheral and central nervous system in dogs. At 2 and 24 hours postdose after the completion of the cardiovascular and respiratory data collection, the neurobehavioral assessments were performed while animals were in and out of their cages. Following amphetamine or acepromazine administration, the expected changes in NCR systems were observed, thus demoinstrated the validity of the procedures used.

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A critical but challenging aspect of inhalation cardiorespiratory safety pharmacology studies is the collection of high quality cardiovascular and respiratory data immediately prior to, during and immediately after dose in order to recognize any acute effects of the inhaled test article. This poster describes methods for achieving a successful outcome in studies, including factors that must be considered in the design and execution. Effects of proper habituation to equipment and carefully scheduled study activities were assessed based on the overall character of cardiorespiratory response from 3 different studies. Prior to data collection, all animals were surgically implanted with telemetry transmitters and habituated to the exposure/data collection system. Telemetry data were collected continuously for 2 hours while animals were in their home cage, after transfer to the exposure suite for 0.5 hours prior to air or vehicle exposure, during the 1 hour exposure, 0.5 hour after exposure and for 24 hours post dose. Each study used a different vehicle and an air (sham) control was administered for assessment of the vehicle effect. Administration of the vehicle produced no effects on blood pressure, heart rate, body temperature, respiratory rate, tidal and minute volume, when compared to the air control in all 3 studies. These data confirm we have developed a reliable method of collecting cardiorespiratory parameters in inhalation safety studies.

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The common marmoset has been used extensively in biomedical research for more than 40 years and more recently, studies in this species have been used as part of the safety assessment to support clinical trials and registration of new pharmaceuticals. The common marmoset is an easily-bred primate that typically weighs 300-500g, approximating to the size of an adult rat. Consequently, it is a popular model for research and many technologies and methodologies used in the rat can also be performed in the marmoset. The dog is the non-rodent species of choice for pre-clinical toxicology studies but there may be reasons why, for certain products, it is unsuitable. For protein-based biopharmaceuticals the most appropriate non-rodent species is often the primate. Certain features of the common marmoset give it some advantages over the other commonly used primates (Cynomolgus and Rhesus monkey). For example, it becomes sexually mature at approximately 14-18 months (compared to approximately 4-years in the cynomolgus and rhesus monkey), therefore all studies can be conducted in sexually mature animals. Its small size also permits performance of some techniques, such as whole-body autoradiography, that are not practical in larger primates. The increasing use of the common marmoset has resulted in the availability of extensive background data and a summary of data for the most commonly measured parameters (haematology, plasma biochemistry, urinalysis, electrocardiography and organ weights) is presented. The extensive information available for the common marmoset and its many similarities to man make it an ideal primate model for pre-clinical studies in drug development.

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Noise and artifact in ECGs collected from ambulatory preclinical subjects has been an obstacle to accurate and efficient automated ECG interval analysis for cardiotoxicity assessment. Most troublesome is noise that is within the bandwidth of the ECG signal (e.g. in-band noise) because it can’t be removed by traditional filtering techniques without distorting the ECG. In-band noise is most often caused by EMG and movement artifact. A new technology, Multi-Domain Signal Processing<SUP>TM</SUP> (MDSP filtering), has been shown to reduce the amplitude of in-band noise by up to 95% without distorting ECG morphology. In this work, the impact of MDSP filtering on ECG analysis of ambulatory telemetered preclinical subjects is evaluated using the EMKA ECGauto. Subcutaneous ECG recordings obtained using DSI D70-PCTs and Dataquest were analyzed by an experienced operator using EMKA ECGauto before and after MDSP filtering. Results show that MDSP filtering prior to analysis increases the number of analyzable beats by up to 98%. Further, the number of beats that can be analyzed in a 24-hour recording increases from about 60% for unfiltered ECGs to about 90% for filtered ECGs. A significant reduction in labor required to analyze recordings was also observed. These results demonstrate that MDSP filtering of ECG recordings prior to analysis with EMKA ECGauto may render it practical to routinely perform continuous analysis of interval measurements from subcutaneous ECG recordings, without the need for intravascular or epicardial sensing electrodes.

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【目的】国内の非臨床安全性試験にはSprague Dawleyラットが広く用いられているが，海外ではWistar Hannover (Wistar Han)ラットが主要な系統の一つであり，国内においても注目されている。生殖発生毒性試験では，交配に性成熟動物を用いることが推奨されているが，両系統間における雄の性成熟時期の違いが指摘されており，用いる系統によって，この点を考慮する必要がある。そこで，雄性Wistar Hanラットの交配適期を明らかにするため，週齢による生殖能及び精子形成能等の比較を行った。【材料と方法】RccHan:WISTラットの雌12週齢を8，10あるいは12週齢の雄のケージに一晩同居させ，翌朝交尾判定した。雄は交尾成立当日に剖検し，精巣上体尾部の精子検査（精子数，精子運動性，精子形態等）及び精巣における1日当たりの精子産生数を算出するとともに，精巣，精巣上体，精嚢及び前立腺を組織学的に検索した。雌は交尾成立後20日に子宮内を観察し，受胎の有無を確認した。【結果】交尾率に差は認められなかったが，受胎率に8週齢で低い傾向が認められた。精子検査では8週齢は精子数，精子運動性及び精子形態において，10週齢は精子数及び精子形態において12週齢に比べて未熟であった。組織学的検査では，精巣上体尾部において8週齢では10及び12週齢に比べて精巣上体管上皮が未熟であった。子宮内観察の結果，8週齢の雄と交配した雌では着床前胚損失率が高く，同腹生存児数が少なかった。【結論】Wistar Hanラットの雄は，8週齢から10週齢にかけて性成熟過程にあり，12週齢で成熟することが示唆されたことから，生殖発生毒性試験の交配には12週齢以降の雄を用いることが推奨される。

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イミベンコナゾール原体, 15%水和剤および5%乳剤の安全性評価のために各種毒性試験を実施した.
ラットおよびマウスにおける急性毒性はきわめて低く, いわゆる普通物に相当した.
眼に対する一次刺激性は, 原体はきわめて軽微の刺激性であったが, 製剤は中等度の刺激性であった. しかし, 製剤の実際使用濃度では, まったく刺激性は認められなかった. 皮膚一次刺激性は, 原体および製剤とも認められなかった. 皮膚感作性は, 原体, 製剤とも軽度ないし中等度の感作性が認められた.
ラット, マウスおよびイヌを用いた亜急性毒性, 慢性毒性および発がん性試験では, 体重増加抑制, 血液に対する影響 (貧血), および脾臓, 腎臓, 肝臓への影響が認められたが, いずれの動物種でも催腫瘍性は認められなかった. ラットを用いた繁殖試験, ラットおよびウサギを用いた催奇形性試験では, 繁殖に及ぼす影響, 催奇形性とも認められなかった. 各種変異原性試験では, いずれも陰性であった. 薬理試験においては, 哺乳動物に対するおもな薬理作用として, 大量経口投与による自発運動抑制などの一般的な中枢神経系に対する抑制作用が認められた.
イミベンコナゾールは, 1994年4月に果樹等作物の病害防除剤として農薬登録された. 本剤は定められた使用方法および一般的注意事項を遵守すれば, 安全性の高い有用な農業資材の一つであると考えられる.

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This paper focuses on the relation between the Methodist itinerant preacher George Whitefield and the literary publishing activities of African-Atlantic writers such as Phillis Wheatley, Olaudah Equiano, and John Marrant during the First Great Awakening period. The 18^th-century consumer revolution opened the age of mass publishing, which attracted writers and readers from across the boundaries of class, race and ethnicity. Whitefield reached people from different social and racial backgrounds in the North American coastal cities through an itinerant ministry that addressed them in the variety of their lived contexts. Such Puritan descendants as Jonathan Edwards, Benjamin Coleman, and Benjamin Franklin aided Whitefield in this ministry and in his publishing activities.

The years of the British-American slave trade coincided with the early phase of the Protestant missionary movement led by Moravians and Methodists. About two hundred years later than the Jesuits, Protestants started their missionary work directed to the territories opened up through exploration as well as colonization in the West Indies and North America. Both in Britain and in North America, the emphasis fell on a religion of the heart, characteristic of the First Great Awakening. This ‘heart religion’ or ‘evangelicalism,’ as it is generally called, had much in common with a similar religious movement promoted with equal ardor in Europe, namely the Pietism that had spread from Lutheran Germany, as well as the associated movement of the Moravian Brethren in Bohemia, who retained a memory of the teaching of Jan Huss. The German Pietists influenced the Methodist movement in England led by John and Charles Wesley. Whitefield joined the Methodists while he was a student at Oxford and eventually became one of the leading Methodist ministers.

Some of the English planters in Barbados and in North America viewed with disquiet the evangelizing and Christianizing of slaves in the West Indies. In spite of the objections, the numbers of converts among slaves increased both in the West Indies and in North America throughout the 18thcentury. The fraught relations between religion and race in the 18^th-century Atlantic World have been clarified in the work of recent scholars such as Katharine Gerbner, Paul Lovejoy, and Paul Gilroy. Although racial boundaries were rather loose at the beginning of the century, they had become rigid by the time of the American Revolution, as is shown by references to race and ethnicity from the pen of the “enlightened” Thomas Jefferson in his Notes on the State of Virginia.

In his Interesting Narrative, Equiano states that he heard Whitefield preach in Philadelphia, although his biographer Vincent Carretta estimates that this was in Savannah, Georgia. Savannah was Whitefield’s American home where he dedicated his utmost energy to building an orphanage, Bethesda. “An Elegiac Poem” composed by Phillis Wheatley on the death of Whitefield in 1770, was the breakthrough work that eventually led her to the publication of Poems on Various Subjects, Religious and Moral in London in 1773. Both Equiano and Wheatley belonged to the transatlantic evangelical circle and made their literary voices heard through its publication networks. This paper attempts to clarify how this network developed during and after the Great Awakening by closely studying several of the important 18^th century literary texts.

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The thesis is an attempt to extract aspects of mercantile activities in seventeenth century England, through an archive of Wood Family Papers deposited at the Middlesex County Record Office.The records consist mainly of various bundles of letters exchanged between Edward Wood at Littleton, Middlesex, and his servant, John Pack, in London,concentrated in the period between 1663 and 1665. The correspondences were continued, although what is left is smaller in volume, between Edward Wood's son, Thomas Wood, and the same John Pack until 1965, when the latter passed away. The archive also contains two small leather bound account books; one which John Pack kept for his masters as well as for himself, and the other which he kept for Thomas's mother-in-law, Lady Dorothy Dicer, between 1671 and 1680, until her death.After John Pack's death, Thomas Birchall, a scrivener related to the East India Company, kept another account book in the period between 1695 and 1698 for Thomas Wood. An estate account left by a Singer between 1667 and 1717 also falls within the scope of the present thesis.Apart from the earliest records, only very small number of documents give direct evidence of Edward Wood's activities as a merchant until his retirement to his residence in Littleton, and thus the related evidence was sought outside the Middldsex County Record Office, in the Guildhall Library and the India Office.The available documents seem to illustrate two main trends, namely the activities of the retired merchant and his son, and the activity of John Pack who obviously carried other businesses besides serving the Woods, as the records shall reveal. The thesis is an attempt, in more general terms, as a case study of accumulation of wealth in the mercantile community in the period under discussion.Although the suggested scope available from the documents may be limited,they may throw light or a contemporary context on the lamentation of Sir Josiah Child as to the merchants' tendency to retire early. as well as the activities of agents such as Pack in the seventeenth century.

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20世紀の反捕鯨運動は、おもに商業捕鯨を対象としたものであった。しかし、動物福祉や動物の権利を強調する動物保護運動は、年々、エスカレートし、その余波は先住民生存捕鯨にも及びつつある。本発表では、イヌピアットのホッキョククジラ漁とマカーのコククジラ漁を事例として、動物福祉団体や環境保護団体による反捕鯨運動の先住民生存捕鯨に及ぼす諸影響と先住民側からの対応について検討を加える

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シクロプロトリン原体, 1%粉剤, 2%粒剤および10%乳剤の急性毒性は弱く, 普通物相当である. 原体の眼および皮膚に対する刺激性は陰性であるが, 1%粉剤, 2%粒剤および10%乳剤は刺激性を有する. ただし, 10%乳剤の使用時濃度 (1000倍) 希釈液では陰性であった. 皮膚感作性は1%粉剤は陰性であるが, 原体, 2%粒剤および10%乳剤は陽性であった. ラットの亜急性毒性試験ならびに慢性毒性・発癌性試験では, 高用量投与群で体重増加抑制, 肝臓, 腎臓および副腎重量増加が認められた. マウスの慢性毒性・発癌性試験では高用量投与群で体重増加抑制, 肝臓重量増加が, イヌの亜急性毒性試験では体重増加抑制とそれに随伴した前立腺の可逆的低機能性萎縮が認められた. 繁殖性に及ぼす影響, 催奇形性および変異原性については特記すべき所見を認めなかった.
シクロプロトリンの登録保留基準値は, 米0.1ppm, 果実 (ナツミカンの外果皮を除く) 0.2ppm, ナツミカンの外果皮15ppm, 豆類0.1ppm, 茶0.5ppmである.
シクロプロトリンは農薬登録されている各製剤に貼付したラベルに記載されている使用方法および注意事項を遵守すれば, 使用場面において, 残留毒性面においても安全な農薬である.

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In 13th century England, many feudal lords held regular markets. The Hundred Rolls of 1279, which covered Oxfordshire, Huntingdonshire and South Cambridgeshire, shows how the multiplication of markets influenced the labour and money rents of the villeins. In the Midlands, a highly manorialized region, some large "classic manors", such as Witney, Yaxley and Alwalton, were the sites for markets held by great ecclesiastical lords. In these manors, as in most manors of this region, rigid virgate systems were maintained and the villeins bore heavy labour rents. These markets were probably used for the shipment of demesne products. In Watlington and Holm, markets were held by the Earl of Cornwall. These manors lay in woodland areas, where the process of manorialization was far from complete. They acquired great sums of money by selling their products in the local markets. In other manors, where "primary markets" existed, for example Bampton, Charlbury and Gamlingay, the virgate system did not exist. The villeins' rents were very light and were paid mainly in money. These markets promoted the liberalization of the villeins. But even at these markets, the lords took the profits, such as rents for the stall and pitches, tolls on goods bought or sold, and dues for the use of standard measures. And from the burgages, they collected substantial rental fees. In the 13th century, the lords could benefit from holding markets. The feudal society was compatible with the market economy of both the lords and the peasants.

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Before mid-19 th century, many attempts were made to improve brickmaking. They were not confined in moulding but covered wide field from preparing clay to drying and burning. As a result, the basic part of the modern plastic brickmaking process was devised at this period.

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