Gingival hyperplasia (overgrowth) is a well-documented unwanted effect, associated with phenytoin, the calcium channel blockers, and cyclosporin. The pathogenesis of drug-induced gingival hyperplasia is uncertain. However, the identification of risk factors associated with both the prevalence and severity of drug-induced gingival hyperplasia is important for all parties involved with this unwanted effect. Prevalence of gingival hyperplasia with phenytoin, the calcium channel blockers, and cyclosporin is approximately 50%, 10-20%, and 8-70%, respectively. The inflammatory components of drug-induced gingival hyperplasia can be managed effectively for the majority of patients with a plaque control program and nonsurgical periodontal therapy including oral hygiene instruction, scaling and root planing coupled with continued periodontal maintenance procedures. After reevaluation, some patients may need surgical periodontal therapy and maintenance procedures. Maintenance therapy including appropriate oral home care appear to be effective in controlling the drug-induced gingival hyperplasia and in maintaining clinical improvements for a long time.

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The incidence of gingival overgrowth caused by calcium channel blockers was determined. The overgrowth was found in patients receiving amlodipine, diltiazem, manidipine, nicardipine, nifedipine and nisoldipine. The highest rate of gingival overgrowth was obtained by nifedipine (7.6%), followed by diltiazem (4.1%), manidipine (1.8%), amlodipine (1.l%), nisoldipine (1.1%) and nicardipine (0.5%) . The rate of nifedipine-induced gingival overgrowth was significantly higher than those of amlodipine, manidipine, nicardipine and nisoldipine, but not diltiazem.

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Gingival overgrowth is a serious adverse effect associated with the administration of phenytoin (PHT), with PHT-induced gingival overgrowth characterized by a massive accumulation of extracellular matrix components, especially collagen, in gingival connective tissues. However, the etiology of such collagen accumulation is still largely unknown. We examined the effects of PHT on the collagen degradation process leading to collagen accumulation in human gingival fibroblasts (HGF) . PHT causes an impaired degradation of collagen by suppression of enzymatic degradation with MMPs/TIMP-1 and α2 β1 integrin mediated endocytosis. These synergistic effects may cause collagen accumulation, leading to gingival overgrowth. It has also been reported that dental plaque is the most important factor to enhance deterioration caused by PHT-induced gingival overgrowth and low concentrations of TNF-α were found in chronically inflamed sites. We examined the synergistic effect of PHT and TNF-α on collagen metabolism in HGF. TNF-α and PHT together cause impaired collagen metabolism by suppression of enzymatic degradation via TIMP-1 upregulation and integrin-mediated endocytosis. These synergistic effects may also be involved in TNF-α-and PHT-induced severe gingival overgrowth.

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α2 Integrin on fibroblasts plays a critical role in the phagocytic regulation of collagen internalization, and drug-induced gingival overgrowth, which is characterized by excessive accumulation of type I collagen in connective tissue, is caused by inhibition of collagen phagocytosis by a reduction of α2 integrin expression on fibroblasts. Silent polymorphism 807 T/C within the α2 integrin gene is associated with high/low α2 integrin expression. We examined the correlation of α2 integrin 807 T/C polymorphism with drug-induced gingival overgrowth. A case-control study comparing 136 subjects taking calcium channel blockers (72 with vs. 64 without drug-induced gingival overgrowth) demonstrated that the frequency of the + 807 C allele was significantly higher in the case group than in the control group (odds ratio, 3.61; 95% confidence interval, 2.14-6.10, P < 0.05) . These findings suggest that the α2 +807 C allele is one of the genetic risk factors for drug-induced gingival overgrowth.

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Calcium antagonists such as nifedipine are used for the treatment of hypertension but are known to elicit gingival overgrowth. The enhanced proliferation of gingival fibroblasts, the increase of bFGF (basic fibroblast growth factor) production and the decrease of phagocytosis of collagen by fibroblasts are proposed to be the mechanism for drug-induced gingival overgrowth. Plaque control and gingivectomy in severe case are necessary for the treatment of gingival overgrowth, but gingival overgrowth recurs in cases of poor plaque control. Moreover, it is difficult to stop drug administration because treatment of hypertension is preferred.
Sai-rei-to is a Japanese traditional medicine used for the treatment of acute gastroenteritis and edema. Sai-rei-to has an inhibitory effect on cell proliferation such as rat mesangial cells and fibroblasts in idiopathic retroperitoneal fibrosis. Sai-rei-to has also an anti-inflammatory effect and is used for the treatment of rheumatoid arthritis, lupus erythematosus and glomerulonephritis. From these effects, we assumed that Sai-rei-to is effective for the treatment of drug-induced gingival overgrowth. We investigated the effects of Sa-rei-to on nifedipine-induced fibroblast proliferation and production of bFGF and type I collagen using an in vitro gingival overgrowth model in which human gingival fibroblasts, Gin-1, were treated with nifedipine.
Sai-rei-to decreased nifedipine-induced cell proliferation and productions of bFGF and type I collagen in a dose-dependent manner. These results suggest that Sai-re-to may be effective for the prevention and treatment of drug-induced gingival overgrowth.

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In the present study, the results of characters in nifedipine responders (NIFr) and nifedipine non-responders (NIFn) are summarized, and the possibility of using tenidap and 18α-glycyrrhetinic acid (18α-GA) as a therapeutic for gingival overgrowth caused by calcium channel blockers is investigated. 18α-GA inhibited cell proliferation and G₁/S transition were induced in NIFr cells. It was also shown that cell cycle control proteins were down-stream targets in the growth-inhibition activity of 18α-GA in NIFr cells. Tenidap discharges intracellular Ca²⁺ store, resulting in a depletion of intracellular Ca²⁺ store in NIFr cells. It also inhibits cell growth, DNA and collagen syntheses, lowered intracellular pH, and enhanced matrix metalloproteinase-1 formation in NIFr cells. These results suggest that 18α-GA and tenidap might be effective for the prevention of gingival overgrowth caused by calcium channel blockers.

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A high concentration of hydrogen peroxide (H₂O₂) or H₂O₂/titanium dioxide (TiO₂) is commonly used as a dental bleaching agent. The mechanism of tooth bleaching is that the reactive oxygen species (ROS), especially hydroxyl radical (HO^⋅), derived from H₂O₂ in the bleaching agent remove the color of teeth due to decomposition of organic substances. It has been reported that oxidative stress induced by ROS such as HO^⋅ could be involved in various oral diseases. Thus, H₂O₂ has been shown to be a risk factor for oral tissue injury during bleaching treatment. However, questions remain about the effects of ROS generated from bleaching treatment in detail. Electron spin resonance (ESR) is recognized as one of the most powerful techniques available for the detection of ROS in tissues and cells. We previously developed an ESR-based technique for the detection of ROS reactions in biological systems. In this study, we confirmed O₂^⋅- generated from a low concentration of H₂O₂ (0.3%) /TiO₂ with irradiation of UV light. It was observed that O₂^⋅- production from H₂O₂ (0.3%) /TiO₂ increased in a time-dependent manner of UV light irradiation. Both the L value and ΔE^*ab value rose in H₂O₂ (0.3%) /TiO₂ with irradiation of UV light. These results suggest that a low concentration H₂O₂/TiO₂ system could be applied more safely due to the formation O₂^⋅- but not HO^⋅ as a risk factor for bleaching. In addition, the ESR technique would be useful for characterizing ROS for dental bleaching agents.

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We conducted a study of judicial decisions on medical accidents covered between 1994 and 2000 by the Japanese press and Hanrei Times, a Japanese magazine specializing in judicial precedents, to obtain information on drug package inserts, and the extent to which these inserts are used as criteria for the judicial decisions.
During the period studied, judicial decisions were issued regarding 514 cases of medical accidents, and a total of 1, 238 articles covering the decisions were published in the media referred to above. Looking at the changes in the number of cases by year, there were between 51 and 81 cases yearly from 1994 through 1999, while this number significantly increased in 2000, to 121.
Out of the 514 cases, 34 (6.6%) were associated with drugs; drug package inserts were used as criteria for the decisions in four of the 34 cases, and 19 articles covering these four cases were carried in the media. Meanwhile, in 374 of the 514 cases (72.8%), it was judged that medical care personnel were to blame for the accidents, and these cases were covered in 1, 010 of the 1, 238 articles (81.6%) in the media.
Common cases of malpractice pointed out to doctors and other medical personnel included violation of due care in terms of drug package inserts. Furthermore, a link between medical practice and the level of medical care was also indicated, as well as a link between package inserts and the level of medical care. The level of medical care varies due both to differences in medical services and the individual circumstances surrounding medical care providers, and negligence in collecting the latest information for medical findings is also included among the various types of malpractice.
Other cases of malpractice included violations of accountability, in which medical care personnel neglected to inform patients of items mentioned in drug package inserts.
Doctors, dentists, and other medical personnel must fully understand the descriptious given in drug package inserts.

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We compared the effects of ropivacaine with those of lidocaine containing adrenalin on the hemodynamics, additional local anesthetic requirement, duration of anesthetic action and oral analgesic anodine requirement when used for inferior alveolar nerve block during implant surgery.
The subjects consisted of 40 patients (14 males and 26 females, aged 26-76 years) undergoing implant surgery in the unilateral mandibular molar area under intravenous sedation. The local anesthetics used in the present study were: 1) 3mL of 2% lidocaine containing 1/73000 adrenalin (Group L) and 2) 3 mL of 0.75% ropivacaine (Group R) .
The following results were obtained:
1. The incidence of changes in blood pressure (number of patients who experienced blood pressure changes in each group) did not differ significantly between the two groups (a change of more than 20% of the preoperative baseline blood pressure was regarded as“blood pressure change”) .
2. No patients in either group received additional local anesthetics.
3. The incidence of numbness of the lower lip was significantly higher in Group R than Group L at 6 and 9 hours postoperatively.
4. The duration of the analgesic effect was significantly longer in Group R (652.2 minutes) than in Group L (371.3 minutes) .
5. The time to initial oral analgesic anodyne administration was significantly longer in Group R (559.5 minutes) than in Group L (308.3 minutes) .
6. The number of times of oral anodyne consumption was significantly higher in Group L (1.15 times) than in Group R (0.70 times) .
These results suggest that more effective pain control can be achieved with 0.75% ropivacaine than with 2% lidocaine containing 1/73, 000 adrenalin when used for inferior alveolar nerve block during implant surgery.

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Erysipelas is a superficial edematous dermatitis. It is most commonly caused by β-hemolytic streptococci. Recently, it has become a rare disease because of the development of antibacterial agents. A case of facial erysipelas caused by odontogenic infection was presented. The patient visited our hospital with the chief complaint of flare and swelling of the right cheek. She felt weary, because her body temperature was 37.3°C. As intraoral findings, the maxillary right first premolar tooth had percussion pain and flare of the peripheral gum. It was treated by intravenous antibiotic therapy for three days, followed by antibiotics given orally for two months. After about one month, the facial erysipelas disappeared completely. The progress has remained good for six months after the medical therapy.

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