出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2019/07/13 04:56:03」(JST)
Mellitus | |
|---|---|
| Archbishop of Canterbury | |
Stone marking the site of Mellitus' grave in St Augustine's Abbey, Canterbury | |
| Appointed | 619 |
| Term ended | 24 April 624 |
| Predecessor | Laurence |
| Successor | Justus |
| Other posts | Bishop of London |
| Orders | |
| Consecration | 604 by Augustine |
| Personal details | |
| Died | 24 April 624 Canterbury |
| Buried | St Augustine's Abbey, Canterbury |
| Sainthood | |
| Feast day | 24 April[1] |
| Venerated in | Roman Catholic Church[2] Anglican Communion[1] Eastern Orthodox Church[3] |
| Canonized | Pre-Congregation |
Mellitus (died 24 April 624) was the first Bishop of London in the Saxon period, the third Archbishop of Canterbury, and a member of the Gregorian mission sent to England to convert the Anglo-Saxons from their native paganism to Christianity. He arrived in 601 AD with a group of clergy sent to augment the mission, and was consecrated as Bishop of London in 604. Mellitus was the recipient of a famous letter from Pope Gregory I known as the Epistola ad Mellitum, preserved in a later work by the medieval chronicler Bede, which suggested the conversion of the Anglo-Saxons be undertaken gradually, integrating pagan rituals and customs. In 610, Mellitus returned to Italy to attend a council of bishops, and returned to England bearing papal letters to some of the missionaries.
Mellitus was exiled from London by the pagan successors to his patron, King Sæberht of Essex, following the latter's death around 616. King Æthelberht of Kent, Mellitus' other patron, died at about the same time, forcing him to take refuge in Gaul. Mellitus returned to England the following year, after Æthelberht's successor had been converted to Christianity, but he was unable to return to London, whose inhabitants remained pagan. Mellitus was appointed Archbishop of Canterbury in 619. During his tenure, he was alleged to have miraculously saved the cathedral, and much of the town of Canterbury, from a fire. After his death in 624, Mellitus was revered as a saint.
The medieval chronicler Bede described Mellitus as being of noble birth.[4][5] In letters, Pope Gregory I called him an abbot, but it is unclear whether Mellitus had previously been abbot of a Roman monastery, or this was a rank bestowed on him to ease his journey to England by making him the leader of the expedition.[4] The papal register, a listing of letters sent out by the popes, describes him as an "abbot in Frankia" in its description of the correspondence, but the letter itself only says "abbot".[6] The first time Mellitus is mentioned in history is in the letters of Gregory, and nothing else of his background is known.[4] It appears likely that he was a native of Italy, along with all the other bishops consecrated by Augustine.[7]
Pope Gregory I sent Mellitus to England in June 601,[8] in response to an appeal from Augustine, the first Archbishop of Canterbury. Augustine needed more clergy to join the Gregorian mission that was converting the kingdom of Kent, then ruled by Æthelberht, from paganism to Christianity.[9] The new missionaries brought with them a gift of books and "all things which were needed for worship and the ministry of the Church."[10][11] Thomas of Elmham, a 15th-century Canterbury chronicler, claimed that in his day there were a number of the books brought to England by Mellitus still at Canterbury. Examination of the remaining manuscripts has determined that one possible survivor of Mellitus' books is the St Augustine Gospels, now in Cambridge, as Corpus Christi College, MS (manuscript) 286.[4][a] Along with the letter to Augustine, the missionaries brought a letter for Æthelberht, urging the King to act like the Roman Emperor Constantine I and force the conversion of his followers to Christianity. The king was also encouraged to destroy all pagan shrines.[14]
The historian Ian Wood has suggested that Mellitus' journey through Gaul probably took in the bishoprics of Vienne, Arles, Lyons, Toulon, Marseilles, Metz, Paris, and Rouen, as evidenced by the letters that Gregory addressed to those bishops soliciting their support for Mellitus' party. Gregory also wrote to the Frankish kings Chlothar II, Theuderic II, Theudebert II, along with Brunhilda of Austrasia, who was Theudebert and Theuderic's grandmother and regent. Wood feels that this wide appeal to the Frankish episcopate and royalty was an effort to secure more support for the Gregorian mission.[15] While on his journey to England, Mellitus received a letter from Gregory allowing Augustine to convert pagan temples to Christian churches, and to convert pagan animal sacrifices into Christian feasts, to ease the transition to Christianity.[4] Gregory's letter marked a sea change in the missionary strategy,[16] and was later included in Bede's Ecclesiastical History of the English People.[17] Usually known as the Epistola ad Mellitum,[18] it conflicts with the letter sent to Æthelberht, which the historian R. A. Markus sees as a turning point in missionary history, when forcible conversion gave way to persuasion.[14] This traditional view, that the Epistola represents a contradiction of the letter to Æthelberht, has been challenged by the historian and theologian George Demacopoulos, who argues that the letter to Æthelberht was mainly meant to encourage the King in spiritual matters, while the Epistola was sent to deal with purely practical matters, and thus the two do not contradict each other.[19]
Exactly when Mellitus and his party arrived in England is unknown, but he was certainly in the country by 604,[4] when Augustine consecrated him as bishop[20] in the province of the East Saxons, making Mellitus the first Bishop of London after the Roman departure (London was the East Saxons' capital).[21] The city was a logical choice for a new bishopric, as it was a hub for the southern road network. It was also a former Roman town; many of the Gregorian mission's efforts were centred in such locations. Before his consecration, Mellitus baptised Sæberht, Æthelberht's nephew, who then allowed the bishopric to be established. The episcopal church built in London was probably founded by Æthelberht, rather than Sæberht. Although Bede records that Æthelberht gave lands to support the new episcopate, a charter that claims to be a grant of lands from Æthelberht to Mellitus is a later forgery.[4]
Although Gregory had intended London to be the southern archbishopric for the island, Augustine never moved his episcopal see to London, and instead consecrated Mellitus as a plain bishop there.[b] After Augustine's death in 604, Canterbury continued to be the site of the southern archbishopric, and London remained a bishopric. It may have been that the Kentish king did not wish greater episcopal authority to be exercised outside his own kingdom.[4]
Mellitus attended a council of bishops held in Italy in February 610, convened by Pope Boniface IV.[4] The historian N. J. Higham speculates that one reason for his attendance may have been to assert the English Church's independence from the Frankish Church.[23] Boniface had Mellitus take two papal letters back to England, one to Æthelbert and his people, and another to Laurence, the Archbishop of Canterbury.[24] He also brought back the synod's decrees to England.[25] No authentic letters or documents from this synod remain, although some were forged in the 1060s and 1070s at Canterbury.[4] During his time as a bishop, Mellitus joined with Justus, the Bishop of Rochester, in signing a letter that Laurence wrote to the Celtic bishops urging the Celtic Church to adopt the Roman method of calculating the date of Easter. This letter also mentioned the fact that Irish missionary bishops, such as Dagan, refused to eat with the Roman missionaries.[26]
Both Æthelberht and Sæberht died around 616 or 618, causing a crisis for the mission.[4] Sæberht's three sons had not converted to Christianity, and drove Mellitus from London.[27] Bede says that Mellitus was exiled because he refused the brothers' request for a taste of the sacramental bread.[4][c] Whether this occurred immediately after Sæberht's death or later is impossible to determine from Bede's chronology, which has both events in the same chapter but gives neither an exact time frame nor the elapsed time between the two events.[29] The historian N. J. Higham connects the timing of this episode with a change in the "overkingship" from the Christian Kentish Æthelberht to the pagan East Anglian Raedwald, which Higham feels happened after Æthelberht's death. In Higham's view, Sæberht's sons drove Mellitus from London because they had passed from Kentish overlordship to East Anglian, and thus no longer needed to keep Mellitus, who was connected with the Kentish kingdom, in office.[30]
Mellitus fled first to Canterbury, but Æthelberht's successor Eadbald was also a pagan, so Mellitus, accompanied by Justus, took refuge in Gaul.[4] Mellitus was recalled to Britain by Laurence, the second Archbishop of Canterbury, after his conversion of Eadbald.[31] How long Mellitus' exile lasted is unclear. Bede claims it was a year, but it may have been longer.[29] However, Mellitus did not return to London,[31] because the East Saxons remained pagan.[4] Although Mellitus fled, there does not seem to have been any serious persecution of Christians in the East Saxon kingdom.[32] The East Saxon see was not occupied again until Cedd was consecrated as bishop in about 654.[33]
Mellitus succeeded Laurence as the third Archbishop of Canterbury after the latter's death in 619.[34] During his tenure as archbishop, Mellitus supposedly performed a miracle in 623 by diverting a fire that had started in Canterbury and threatened the church. He was carried into the flames, upon which the wind changed direction, thus saving the building.[35] Bede praised Mellitus' sane mind, but other than the miracle, little happened during his time as archbishop.[36] Bede also mentioned that Mellitus suffered from gout.[25] Boniface wrote to Mellitus encouraging him in the mission, perhaps prompted by the marriage of Æthelburh of Kent to King Edwin of Northumbria. Whether Mellitus received a pallium, the symbol of an archbishop's authority, from the pope is unknown.[4]
Mellitus died on 24 April 624,[34] and was buried at St Augustine's Abbey in Canterbury that same day.[4] He became revered as a saint after his death, and was allotted the feast day of 24 April.[2] In the ninth century, Mellitus' feast day was mentioned in the Stowe Missal, along with Laurence and Justus.[37] He was still venerated at St Augustine's in 1120, along with a number of other local saints.[38] There was also a shrine to him at Old St Paul's Cathedral in London.[39] Shortly after the Norman Conquest, Goscelin wrote a life of Mellitus, the first of several to appear around that time, but none contain any information not included in Bede's earlier works. These later medieval lives do, however, reveal that during Goscelin's lifetime persons suffering from gout were urged to pray at Mellitus' tomb.[4] Goscelin records that Mellitus' shrine flanked that of Augustine, along with Laurence, in the eastern central chapel of the presbytery.[40]
| Christian titles | ||
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| Preceded by Theonus |
Bishop of London 604–619 |
Succeeded by Cedd |
| Preceded by Laurence |
Archbishop of Canterbury 619–624 |
Succeeded by Justus |
Bishops of London | |
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Italics indicate a person who was elected but not confirmed. | |
Members of the Gregorian mission of the Catholic Church | ||
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Saints of Anglo-Saxon England | |
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| British / Welsh |
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| East Anglian |
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| East Saxon |
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| Frisian, Frankish and Old Saxon |
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| Irish and Scottish |
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| Kentish |
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| Mercian |
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| Northumbrian |
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| Roman |
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| South Saxon |
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| West Saxon |
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| Unclear origin |
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| Authority control |
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| Portals Access related topics |
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| Find out more on Wikipedia's Sister projects |
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| リンク元 | 「血糖降下薬」「100Cases 27」「100Cases 16」 |
| 拡張検索 | 「slowly progressive insulin-dependent diabetes mellitus」「pregestational diabetes mellitus」 |
k氏より
インスリンの抽出は大変意図的に行われたのに対し、スルフォニルウレア薬(SU)は偶然に見つかりました。で、1950年代にはじめに二型糖尿病の患者に使われるようになりました。いまでは20種類くらいのSUが広く世界で使われています。 1997にはメグリチニドが臨床適用されました。食後高血糖の治療薬としてはじめて使用された薬です。 メタフォルミンというビグアナイド薬(BG)は、ヨーロッパで広く使われていましたが、1995年にアメリカでも認可されました。 チアゾリジン1997年に市場導入され、二番目にメジャーなインスリン刺激薬として使用されています。この種類の薬には、広汎な肝障害を起こしにくく、世界中で使われています。
膵臓のβ細胞の刺激によって、インスリンを放出させ、血糖値を下げます。 治療が長引くと、インスリン分泌というSUのβ細胞刺激性の効果が薄れてきますが、β細胞上のSU受容体のダウンレギュレーションによるものです。また、SUはソマトスタチンの放出を刺激します。ソマトスタチンはグルカゴン分泌を抑制しているので、これも関係SUの糖を下げる効果と関係しています。 SUはATP感受性Kチャンネルを抑制します。Kレベルが下がると、まく表面における、脱分極を促し、電位依存性カルシウムチャンネルを通じたカルシウムイオンの流入を促進します。 SUには無視できない膵臓外作用があるという議論があります。確かにありうべきことですが、2型糖尿病の患者の治療においては、それほど重要なことではないようです。
SU薬はそれぞれが似たような作用スペクトラムを持っているので、薬物動態的な特性がここの薬を区別する手がかりです。腸管からのSU薬の吸収の割合は薬によって違いますが、食物や、高血糖は、この吸収を抑制します。高血糖はそれ自身、腸管の運動を抑制するので、ほかの薬の吸収も阻害します。血漿濃度が効果的な値にまで達する時間を考えると、半減期の短いSUは、食前三十分に投与するのが適切です。SU薬は90から99パーセントくらい血中たんぱく質と結合し、特にアルブミンと結合します。 第一世代のSUは半減期や分布において、大きく違っています。この半減期や作用時間の不一致の理由はいまだはっきりしていません。 SUはすべて肝臓で代謝を受け、尿中に排泄されます。なので、肝不全、腎不全患者には要注意で処方します。
めったにありませんが、第一世代服用患者では、4パーセントの割合でおきます。第二世代ではもっと少ないでしょう。低血糖による昏睡がしばしば問題になります。腎不全や肝不全がある高齢者の患者でおきやすいです。 重症の低血糖は脳血管障害も起こしうる。急性の神経障害が見つかった高齢患者では血中グルコースレベルを測るのが大事です。半減期の長いSUもあるので、24から48時間のグルコースを輸液します。 第一世代は多くの薬物と相互作用を持っています。 ほかに、吐き気嘔吐、胆汁うっ滞性黄疸、脱顆粒球症、再生不良性・溶血性貧血、全身性のアレルギー症状があります。 SUが心血管障害による死亡率を上げるのかについては議論の余地あり。
SUは、食事療法だけでは十分なコントロールを得られない2型糖尿病患者の血糖コントロールに用いられます。禁忌はtype 1 DM(diabetes mellitus:糖尿病)、妊婦、授乳中の患者、腎障害や肝障害の患者です。 普通の患者なら五割から八割くらい、経口の糖尿病治療薬が効きます。インスリン療法が必要になる患者もいます。 トルブタマイドの一日量は500ミリグラムで、3000ミリグラムが最大の許容量です。SUの治療成績の評価は患者の様子を頻繁に観察しながら、行います。 SUとインスリンの併用療法はtype 1, type 2 両方の糖尿病で用いられていますが、βセルの残存能力がないとうまくいきません。
レパグリニドはメグリチニドクラスの経口インスリン分泌促進物質です。化学構造上、SUとは異なっており、安息香酸から分離されたものです。 SU薬と同様にレパグリニドは膵臓βセルにおけるATP依存性Kチャンネルを閉じることによりインスリン分泌を促進します。AEもSU薬と同様、低血糖です。
Dふぇにるアラニンから分離された薬。レパグリニドよりもSEとして低血糖が認められづらいです。
メトフォルミンとフェノフォルミンは1957年に市場導入され、ブフォルミンが1958年に導入されました。ブフォルミンは使用が制限されていますが、前者二つは広く使われています。フェノフォルミンは1970年代に乳酸アシドーシスのAEによって市場から姿を消しました。メトフォルミンはそのようなAEは少なく、ヨーロッパカナダで広く使われています。アメリカでは1995年に使用可能に。メトフォルミンは単独かSUと併用して使われます。
ものの言い方によると、メトフォルミンは抗高血糖であって、血糖を下げる薬ではありません。膵臓からのインスリン放出は促さないので、どんな大容量でも低血糖は起こしません。グルカゴン・コルチゾール・成長ホルモン・ソマトスタチンにも影響なし。肝での糖新生を抑制したり、筋や脂肪におけるインスリンの働きを増すことで、血糖を押さえます。
小腸から吸収。安定な構造で、血中の蛋白と結合しないで、そのまま尿中に排泄。半減期は二時間。2.5グラムを食事と一緒に飲むのがアメリカで最もお勧めの最大用量。
メトフォルミンは腎不全の患者には投与しないこと。肝障害や、乳酸アシドーシスの既往、薬物治療中の心不全、低酸素性の慢性肺疾患なども合併症として挙げられる。乳酸アシドーシスはしかしながら、めちゃくちゃまれである。1000人年(たとえば100人いたら、10年のうちにという意味の単位。または1000人いたら1年につき、ということ。)につき0.1という割合。 メトフォルミンの急性のAEは患者の20パーセントに見られ、下痢、腹部不快感、吐き気、金属の味、食欲不振などです。メタフォルミンを飲んでいる間はビタミンB12や葉酸のきゅうしゅうが 落ちています。カルシウムをサプリで取ると、ビタミンB12の吸収が改善されます。 血中乳酸濃度が3ミリMに達するとか、腎不全・肝不全の兆候が見られたら、メタフォルミンは中止しましょう。
PPARγに効く。(ペルオキシソーム・プロライファレーター・アクチベイティッド・受容体、つまりペルオキシソーム増殖活性受容体みたいな。)PPARγに結合して、インスリン反応性をまして、炭水化物とか、脂質の代謝を調整します。
ロジグリタゾンとピオグリタゾンは一日一度。チアゾリジンは肝にて代謝され、腎不全のある患者にも投与できますが、活動性の肝疾患があるときや肝臓のトランスアミナーゼが上昇しているときは、使用しないこと。 ロジグリタゾンはCYP2C8で代謝されますがピオグリタゾンはCYP3A4とCYP2C8で代謝されます。ほかの薬との相互作用や、チアゾリジン同士の相互作用はいまだ報告されていませんが、研究中です。
ピオグリタゾンとロジグリタゾンは肝毒性とはめったに関係しませんが、肝機能をモニターする必要があります。心不全のある患者はまずそちらを治療してから。
αGIは小腸の刷子縁におけるαグルコシダーゼの働きを阻害することによって、でんぷん・デキストリン・ダイサッカリダーゼの吸収を抑制します。 インスリンを増やす作用はないので、低血糖もおきません。吸収がよくない薬なので、食事の開始と一緒に飲むとよいです。 アカルボースとミグリトールは食後高血糖の抑制に使われます。 αGIは用量依存性に、消化不良・ガス膨満・下痢などをきたします。αGIとインスリンを併用中に低血糖症状が出たら、、グルコースを補充します。
経口から、グルコースが静脈を通ると、インスリンが上がることがわかっていました。消化管の上部からはGIP、消化管下部からはGLP1というホルモンが出ていて、糖依存性のインスリン放出を促していることがわかりました。これらのホルモンはインクレチンといわれています。この二つのホルモンは別の働き方でインスリンの放出を促進します。GIPはtype 2 DMではインスリン分泌を促進する能力がほとんど失われています。一方でGLP1は糖依存性のインスリン分泌を強く促しています。つまりtype 2 DMの治療ではGIPをターゲットにすればよいということになります。GLPはグルカゴンを抑制し。空腹感を押さえ、食欲を抑えます。体重減少も実現できます。この長所を相殺するように、GLP1は迅速にDPPIV(ヂペプチジルペプチダーゼ4エンザイム)によって負活化されます。つまり、GLP1を治療に使うなら、連続的に体に入れなければなりません。GLP1受容体のアゴニストが研究され、これはDPPIVにたいして抵抗性があります。 そのほかのGLP1療法のアプローチに仕方としては、DPPIVプロテアーゼの不活性化で、それによってGLP1の循環量を増やそうとするものです。type 2 DM治療に新しい薬がでるかもしれないですね。