The aim of this study was to synthesize cyclopropene derivatives and evaluate their oral antimicrobial activities. Nine cyclopropene derivatives possessing various functional groups as substituents on a ring were prepared by rhodium-catalyzed cycloaddition reaction in moderate yields. Among them, six typical cyclopropenes were shown to have antimicrobial activities against Gram-positive and Gram-negative bacteria including Staphylococcus aureus, Bacillus cereus and Escherichia coli. We evaluated in turn their inhibitory effects against oral bacteria and all nine compounds were elucidated to have potent inhibitory effects on the growth of oral bacterial flora derived from human whole saliva under aerobic and anaerobic conditions. In addition, four typical cyclopropenes of these compounds were shown to exhibit strong antimicrobial activities against Porphyromonas gingivalis and Streptococcus sobrinus. These results indicate that cyclopropene derivatives were promising agents for the prevention and treatment of dental caries and periodontal diseases.

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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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Insulin-like growth factor-I (IGF-I), which mediates the synthesis of DNA and enters the S phase from the G₀/G₁ phase of the cell cycle, is a potent growth factor that promotes cell cycle progression in various types of mammalian cells in culture. On the other hand, when IGF-I is removed in the middle of the G1 phase, cells stop progressing the cell cycle. We have previously demonstrated that basic fibroblast growth factor (bFGF) accelerated the cell proliferation, cell cycle progression, and expression of cell cycle regulating proteins and genes in gingival fibroblasts derived from nifedipine reactive patients (nifedipine responder; NIFr) compared with those in nifedipine non-reactive patients (nifedipine non-responder; NIFn) . In the present investigation, we studied differences of cell growth, cell cycle, and expressions of cell cycle regulatory proteins and genes stimulated by IGF-I in NIFn and NIFr cells to demonstrate that cell growth, DNA synthesis, and progression to S and G₂/M from G₁ of the cell cycle were significantly enhanced in NIFr cells compared with those in NIFn cells in the presence of IGF-I. The phospho-ser780-Rb protein level of NIFr cells increased compared with that of NIFn cells by IGF-I stimulation. The expression levels of other cell cycle control factors, proteins (E2F-1, Rb) and genes (cdks 1, 2, 4, 6 and cyclins A, B1, D1, E), similarly increased in both NIFn and NIFr cells by IGF-I. Thus, the mechanism of gingival overgrowth caused by nifedipine may be related to ser780-phosphorylated Rb of NIFr cells.

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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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The interaction between cAMP level and intracellular Ca²⁺ levels elicited by isoprenaline and histamine, respectively, in human gingival fibroblasts, NIFr (gingival fibroblasts originated from a nifedipine reactive patient; nifedipine responder) and NIFn (gingival fibroblasts originated from a nifedipine non-reactive patient; nifedipine non-responder) cells, was investigated. Intracellular Ca²⁺ level was increased by 1 mM histamine, where NIFr cells were more susceptible than NIFn cells. NIFr cells showed increased cAMP level by isoprenaline and the cAMP increase was inhibited by propranorol, indicating that gingival fibroblasts possess β-adrenergic receptors that activate adenylate cyclase. The increase of intracellular Ca²⁺ level elicited by histamine was depressed by isoprenaline, where NIFn cells responded more than NIFr cells.

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In our previous report, we demonstrated that tenidap, (±) -5-chloro-2, 3-dihydro-3- (hydroxy- 2-thienylmethylene) -2-oxo-1H-indole-1-carboxamide, decreased total collagen in cultured gingival fibroblasts. Since tenidap might be one of the choices for treating overgrown gingiva, it was interesting to clarify whether tenidap accelerates collagen degradation. Thus, we investigated the effect of tenidap on MMP-1 formation, ERK1/2 phosphorylation, and also the effect of MAPK inhibitor on MMP-1 mRNA expression induced by tenidap in human gingival fibroblasts originated from a nifedipine-reactive patient (NIFr) . Tenidap enhanced MMP-l formation, MMP-1 mRNA expression, and increased phospho-ERK1 and phospho-ERK2 in NIFr cells. Therefore, the decreased total collagen might be explained by the increased formation of MMP-1 in NIFr cells. Thus, we propose that tenidap could be considered as an agent for controlling gingival overgrowth.

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