この研究の目的は, シクロプロペン誘導体の合成及びその口腔内細菌に対する抗菌作用の評価である.環上に種々の官能基を置換基として有するシクロプロペン誘導体9化合物をロジウム触媒による環化異性化反応を用いて良好な収率で合成した.これらの化合物の中で, 典型的な特徴を有する6化合物が, 黄色ブドウ球菌, セレウス菌, 大腸菌などのグラム陽性菌及びグラム陰性菌に対して抗菌作用を示した.次に, これらの化合物について口腔内細菌に対する抗菌作用の検討を行った.その結果, 合成した9化合物全てにおいてヒト全唾液を用いた好気及び嫌気培養条件下での口腔内細菌叢に対する発育阻止作用を示すことが明らかとなった.さらに, これらの化合物の中で典型的な特徴を有する4化合物が, 歯周病原性細菌である、Porphyromonas gingivalisおよび齲蝕原性細菌であるStreptococcus sobrinusに対し, 強力な抗菌作用を示すことが明らかとなった.
以上の結果より, シクロプロペン誘導体は, 齲蝕及び歯周病に対する有用性が示唆された.

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The trend of using analgesic, antipyretic, and anti-inflammatory medicines in dentistry was surveyed and the results in 1982 (in 17 private dental university hospitals) and in 1992 (in 29 national public and private university hospitals) were reported. After over ten years, because the analgesic antipyretic medicines have been effective for toothache, we surveyed the trend of using them in 17 private dental university hospitals.
A questionnaire survey was conducted on the amount of consumption of anodyne resolutives and anti-inflammatory enzyme medicines for three months from July to September 2006, and a survey was conducted on the cases of concomitant use of anti-inflammatory medicines, stomach medicine using anodyne resolutives together, and one dose volume of analgesic and antipyretic medicines by age in 10 days of September 2006.
After the investigation in 17 hospitals a list of 20 analgesic, antipyretic, and anti-inflammatory medicines was prepared and the largest consumption was found to be loxoprofen sodium and diclofenac sodium. Acetaminophen was ranked third in this investigation although it had a higher position in previous investigations. An increase in the amount of consumption with loxoprofen sodium and diclofenac sodium was expected because of an adaptation of these drugs to toothache. However, loxoprofen sodium accounted for 63% of all anodyne resolutives, substantially exceeding the previous investigation of 32.6%. There were many examples of continuous taking of anodyne resolutives and the use rate was 3.3%. More than 50% of older patients used a single dose of 2 tablets of loxoprofen sodium and diclofenac sodium. There were also many uses of powdered stomachic medicine for an anodyne resolutive and stomach medicine together although there were large differences in the use rate by facilities. For manufacturing anti-inflammatory enzyme pills, lysozyme chloride was mostly used. This may be due to abolition of dental adaptation of serapeptase, which exhibited a large amount of consumption last time.

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We clinically evaluated extraction of tooth in patients undergoing antithrombotic therapy. The subjects consisted of 47 patients undergoing antithrombotic therapy, aged from 33 to 91 years old. Fifteen patients received warfarin therapy, including 6 who also received antiplatelet medication. The other 32 patients received antiplatelet medication alone. The mean of PT-INR (International Normalized Ratio) in patients who received warfarin therapy was 2.00 ± 0.57.
Seventy-two extractions of 129 teeth, including one impacted tooth, were performed on 47 patients. Sixteen of the 72 cases took more than 10 minutes to stop bleeding after surgical treatment (22%) . However, local hemostasis in each of the 16 cases was successfully controlled by local measures, such as application of pressure by biting on gauze, suturing, and the application of atelocollagen. Thirteen of the 72 cases showed postoperative hemorrhage (18%) . However, in all of those cases hemorrhage had stopped by the time of re-examination on the day following surgical treatment, and so no special treatments were required. Except for two cases of small subcutaneous hematoma, there was no fatal problematic complication such as serious embolic complication. In conclusion, extraction of tooth should be performed under antithrombotic therapy by local hemostasis measures.

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DNA合成に関与し, 細胞周期のG₀/G₁相からS相へ移すインスリン様成長因子-I (IGF-1) は哺乳動物の多くの細胞の細胞周期を回転させる強力な成長因子である.他方, G₁相の途中でIGF-Iを除去すると細胞周期が停止する.われわれは, 塩基性線維芽細胞成長因子 (bFGF) がNIFr細胞においてNIFn細胞よりも細胞増殖, 細胞周期回転, 細胞周期制御タンパクおよびその遺伝子の発現を亢進することを報告している.本報告では, ニフェジピンによって歯肉肥厚を起こした患者の歯肉から得られた線維芽細胞 (NIFr) と歯肉肥厚を起こさなかった患者の歯肉から得られた線維芽細胞 (NIFn) においてIGF-1による細胞増殖, 細胞周期, 細胞周期制御タンパクおよびその発現について両細胞の比較をした.その結果, NIFrにおいてDNA合成, 細胞周期においてG₁からSまたはG₂/M相への移行がNIFnよりも明らかに増加したことを認めた.NIFrにおいてPhospho-ser780-Rbタンパクレベルが増加した.他の細胞周期制御タンパク (E2F-Rb) および遺伝子 (cdks1, 2, 4, 6およびcyclins A, B1, D1, E) の発現もIGF-1により両細胞で増加した.したがって, ニフェジピンによって引き起こされる歯肉肥厚にser-780-phosphorylated Rbが関与している可能性が示唆された.

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The present study surveyed the application of antimicrobials in dental practice in 17 private dental college or university hospitals in Japan, in order to investigate the actual conditions of using antimicrobials.
According to the medicinal virtues, a drug list with percentage was prepared depending upon the number of actual use of internal medicine, injections provided in the prescription or instructions for the 10-day period from September 4 to 15, 2006. Furthermore, a survey of the kind of antimicrobials with consumption for each hospital was also done for the six-month period from April 1, 2006 to September 30, 2006.
Classified by medicinal virtues by internal use medicines, the proportion of antibacterial and anti-inflammatory analgesic drugs accounted for 32% each, and gargle and gastrointestinal medicine for 12% and 10% respectively. Among the internal use antimicrobials, usage of the cephem system was 54% whereas penicillin and macrolide system were 23% and 21%, respectively. The largest consumption was cefcapene pivoxil hydrochloride for antibacterial medicines. This drug was widely used in 10 out of 17 hospitals. Erythromycin ethylsuccinate was in second position, followed by cefdinir, rifampicin and ampicillin.
The method of marking order of each hospital and order of the total consumption were analyzed and some differences in consumption of different drugs were observed. Many hospitals suggested the use of clarithromycin, cefaclor and amoxicillin although consumption was low.
According to the medicinal virtues of injectable medicines, the frequency of use of antimicrobials was the highest (34%) . Among the injectable antimicrobials, the cephem based system (60%) and penicillin system (33%) accounted for more than 90% of the total use. Cefazolin was the most consumed drug, followed by asoxicillin, flomoxef sodium and ceftriaxone.

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ヒト歯肉線維芽細胞 (NIFr: ニフェジピン感受性患者から得られた歯肉線維芽細胞, およびNIFn: ニフェジピン非感受性患者から得られた歯肉線維芽細胞) におけるイソプレナリンで誘導されたcAMPレベルとヒスタミンで誘導された細胞内カルシウム濃度の関係を検討した.NIFr, NIFn細胞においてヒスタミンにより細胞内カルシウムの増加が認められ, NIFr細胞の方がNIFn細胞よりもヒスタミンに対する感受性が高かった.NIFrにおいて, イソプレナリンによりcAMPの増加が認められたが, その増加はプロプラノロールによって抑制されたことから, アデニル酸シクラーゼを活性化するβ受容体の存在が示唆された.また, ヒスタミンにより誘導される細胞内カルシウム濃度がイソプレナリンにより低下し, その低下はNIFr細胞よりNIFn細胞で強くみられる傾向にあった.

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われわれはすでにtenidap, (±) -5-chloro-2, 3-dihydro-3- (hydroxy-2-thienylmethylene) -2-oxo-1H-indole1-carboxamide, が培養ヒト歯肉線維芽細胞において総コラーゲン量を低下させることを報告している.Tenidapが歯肉肥厚に対して使用する薬物の1つと考えられるので, tenidapがコラーゲン分解を促進するか否か検討することは興味深い.そこで, われわれはニフェジピン感受性ヒト歯肉線維芽細胞 (NIFr) において, tenidapのMMP-1生成, ERK1/2のリン酸化, およびtenidapによって活性化されたMMP-1mRNA発現に対するMAPK阻害薬の影響を検討した.TenidapはNIFr細胞においてMMP-1生成, MMP-1mRNA発現を亢進し, リン酸化ERK1/2合成を促進した.したがって, 総コラーゲン量を低下は, MMP-1生成の亢進によるものと考えられた.このことから, tenidapの歯肉肥厚を制御する薬物としての可能性が示唆された.

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