We often worry about oral lichen planus (OLP) with chronic inflammation, which is an intractable disease in the treatment. A study was carried out to evaluate the efficacy of allopurinol mouthwash (ALP) on OLP.
We studied 9 cases (1 male and 8 females) of OLP that were clinically diagnosed in our ambulatory practice during the period from July 1996 to July 1997. The average age was 58.7, ranging from 23 to 82 years. The effect measurement was carried out after 4 weeks of administration, and there were 3 complete responses, 4 partial responses, and 2 minor responses.
ALP was reported to be effective for prevention and treatment of the stomatitis, which develops during cancer chemotherapy. ALP can be easily used by gargling only, and no side effects were seen, so it seemed to be a useful drug.

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Phenytoin is one of the most widely used anticonvulsant drugs for epileptic patients. Osteomalacia and osteoporosis are well known side effects of long-term administration of phenytoin. It is generally accepted that phenytoin mediates degradation of serum active vitamin D metabolites in the liver, and inhibition of calcium absorption in the intestine. We predicted that phenytoin stimulated bone resorption in the bone microenvironment, and attempted to determine whether phenytoin directly induced osteoclastic bone resorption utilizing reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of osteoclast differentiation factor (ODF/RANKL) and a co-culture system of osteoblasts and bone marrow cells.
Phenytoin transiently induced the expression of ODF/RANKL mRNA in osteoclastic MC3T3-E1 cells. The mRNA level reached a peak at 6h after addition of phenytoin, and returned to the basal level after 12h, and then increased again after 24h. The effect of phenytoin on ODF/RANKL mRNA was dose-dependent. The up-regulation of ODF/RANKL mRNA by phenytoin did not requirede novoprotein synthesis and involved a transcriptional mechanism. In the co-cultures of mouse bone marrow cells and osteoblasts, phenytoin markedly induced the formation of tartrate-resistant acid phosphatase-positive multinucleated osteoclast-like cells, in the presence of 10^-7M 1, 25-dihydroxyvitamin D₃and 10^-8M dexamethasone, whose effect was significantly reversed by a neutralizing antibody against ODF/RANKL.
These results suggest that phenytoin up-regulates osteoclastogenesis, at least in part, through the induction of ODF/RANKL by osteoblasts in the local environment.

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As carbapenems-resistant bacteria increase with the frequent use of carbapenems, we studied the isolation frequency and the resistant mechanism of imipenem-resistant bacteria in pus from oral infectious diseases, using CDC blood agar culture plates containing 2.0μg/mL of imipenem. Carbapenem-resistant bacteria were detected from all 8 patients, and imipenem-resistant anaerobic gram-negative rods were detected from 5 patients. These rods showed resistance to carbapenems, cefmetazole, and ampicillin. β-Lactamase was detected in 3 strains ofPrevotella, by nitrocefin. The β-lactamase gene was different fromblaIMP.
The study suggests that highly carbapenem-resistant bacteria are isolated from oral infection. However, the DNA sequence of β-lactamase in imipenem-resistantPrevotellawas different from that of facultative gram negative rods.

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An oral malignant melanoma appears to have an extremely poor prognosis, and the five-year survival rate has been reported to be about 17% in Japan. The response rate belongs to the worst group in malignant tumors. Previous studies have shown that the combination chemotherapy of dacarbazine (DTIC), cisplatin (CDDP), nimustine (ACNU), and Tamoxifen, an anti-estrogen agent, produced a more than 50% overall response rate in patients. We present a case of malignant melanoma of the palate that had been treated with 4 courses of the combination of DTIC, ACNU, vincristine, and interferon-β, although the tumor has increased progressively to the skull base in the patient. It was thought that the tumor was becoming resistant to the chemoimmunotherapy.
Therefore, targeting the intra-arterial infusion of DTIC and CDDP with ACNU, Tamoxifen chemotherapy with high-dose administration of interferon- β was carried out. As a result, PR was obtained with 2 courses of the above regimen. We believe that the regimen for malignant melanoma may be useful in oral lesions combined with either radiotherapy or surgery.

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The purpose of this study was to investigate the action of hPTH (1-34) on bone reactions after placement of a titanium screw implant into the tibiae of ovariectomized rats. Twelve-week-old female Wistar rats were divided into 3 groups of 9 animals each. The first group (Sham) was sham-operated ; the second group (Ovx) was ovariectomized only, and the third group (PTH) was ovariectomized and received hPTH (1-34) at a dose of 30i/kg of body weight. Titanium screw implants were placed in the proximal metaphyses of the tibiae 168 days after surgery. The animals were sacrificed 7, 14, and 56 days after implantation. Undecalcified sections were prepared and evaluated by light microscopy.
Ovariectomies reduced implant-bone contact and the bone volume around the implant. However, intermittent hPTH (1-34) administration can not only prevent resorption of newly generated trabeculae around the implant but also recover bone volume lost due to ovariectomy. These results suggested that intermittent hPTH (1-34) administration might be useful to facilitate postoperative bone formation, increasing the bone volume around the implant, and improving the clinical results.

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A multicenter, double-blind, placebo-controlled, parallel group comparative study was conducted to demonstrate the dose-response relationship of YM177, and to determine its recommended dose. YM177 is a selective inhibitor of COX-2, Which is associated with pain following the extraction of mandibular-impacted wisdom teeth. Global improvement rates and patients' subjective impressions were established as primary parameters. Five doses of YM177 (25, 50, 100, 200, and 400 mg), plus a placebo, were studied. Global improvement rates and subjective efficacy rates, as reported by patients, demonstrated significant differences when compared with placebo in patients receiving doses of 25 mg or more. Moreover, among the five YM177 dose groups, we found greater improvement and efficacy rates with increasing doses. In addition, the YM177 200 mg group, and the YM177 400 mg group, showed improvement rates of 70% or greater in all primary parameters of evaluation, demonstrating significant efficacy of YM177 as a therapeutic drug. As to the drug's safety, no serious adverse events developed in any patient of the YM177 dosage groups.
It is therefore considered that both 200 mg and 400 mg are clinically effective doses, in line with the definition of “dose selection” pre-determined in this study.

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The purpose of this study was to investigate the effect of insulin therapy on bone reactions after placement of titanium screw implants into the tibias of streptozotocininduced diabetic rats. Twelve-week-old male Wistar rats were divided into 3 groups of 12 animals each. The first group (Control) was injected with citrate buffer only; the second group (DM) was induced with a single intraperitoneal injection of streptozotocin, and the third group (Insulin) was insulin-controlled diabetic rats. Tianium screw implants were placed in the proximal metaphyses of the tibias 21 days after the injection. The animals were sacrificed 14 and 56 days after implantation. Undecalcified sections were prepared and evaluated under light microscopy. Histomorphometric measurements were obtained with a computer-based image analyzer, to magnify the unit bone mass around the implant and the rate of implant-bone contact. The DM group significantly reduced implant-bone contact and bone volume around the implants. However, in the Insulin group, only slight differences in both bone contact and bone volume were noted when compared with the Control group. These results suggested that insulin therapy prevented a decrease of implant-bone contact and bone volume around the implants in the tibial metaphyses of streptozotocin-induced diabetic rats. Therefore, insulin therapy is useful to prevent reduction of bone attributable to surrounding dental implant that may occur with diabetes mellitus patients.

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The effects of repetitive administration of Cevimeline (SNI-2011), a novel muscarinic receptor agonist, (±) -cis-2-methylspilo [1, 3-oxathiolane-5, 3'-quinuclidine] hydrochlo-ride hemihydrate, on salivary secretion were studied in Balb/cA mice. Saliva flow, protein secretion and amylase activity were measured. Saliva was collected from the oral cavity at intervals of 5 min over 30 min after intraperitoneal injection of 10mg /kg of Cevimeline. The effects of 7 days of Cevimeline administration were compared with the effects of single injection.
Seven-day administration of Cevimeline tended to increase saliva flow over 30-min saliva collection compared with single injection. The rate of saliva release increased significantly in the first 10-min period. Protein concentration in the secreted saliva showed no significant change. The total amylase secretion over 30 min tended to increase.
The results of the present study showed the effects of chronic administration of Cevimeline in salivary function, and suggested that Cevimeline administration twice a day does not evoke tolerance in the salivary gland receptor.

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Ascites sarcoma 180 (S180A) is a transplantable tumor that induces hypercalcemia in tumor-bearing mice without producing parathyroid hormone-related protein (PTHrP) and stimulates bone resorption in cultured neonatal mouse calvaria. To investigate the effects of S180A on bone formation, bone marrow cells were cultured in the presence of ascorbic acid, dexamethasone and β -glycerophosphate and then cell proliferation and mineralized nodule formation were evaluated. Serum-free conditioned media of ascites cell cultures greatly stimulated the ³H-thymidine uptake (5.5-fold on day 10) throughout the experimental period up to 14 days. On the other hand, they limited the rise in alkaline phosphatase activity significantly compared to control (44.1% and 70.8% of control on day 10 and 14, respectively) . After 14 days of culture, many mineralized nodules were observed in control and recombinant human TGF groups, whereas nodule formation was completely abolished by the addition of S180A CM. Thus the results of the present study indicate that tumor-produced factors cause hypercalcemia by inhibiting bone formation, which cooperates with the stimulation of bone resorption in S180A-bearing mice.

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Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly used classes of medications worldwide. Diclofenac sodium is a kind of NSAIDs advocated for use in dental medicine. It is also well known to prevent osteoporosis in postmenopausal females. The purpose of the present study was to investigate the possible inhibitory effect on osteoclastogenesis in the presence of diclofenac sodium. Nonadherent Sephadex G10-passed bone marrow cells were cultured in a-MEM containing the final concentration of 15% FBS, 60ng/mL RANKL, 20ng/mL CSF-1 for 6 days. Treatment with diclofenac sodium blocked osteoclastogenesis in vitro dose-dependently. The results suggested that diclofenac sodium may act on the precursor of osteoclast directly to prevent osteoporosis.

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The effect of xylitol on growth, acid production and water-insoluble glucan formation of mutans streptococci under the additional condition of another monosaccharide was studied. The growth of mutans streptococci was measured by nephelometry using a spectrometer-20, and water-insoluble glucan was observed by inverted conf ocal laser scanning microscope (LSM) and transmission electron microscope (TEM) . The full growth of mutans streptococci required the further addition of glucose or fructose in trypticase soy broth, and the growth of mutans streptococci was inhibited or delayed by the addition of xylitol in trypticase soy broth. Upon the addition of 1% glucuse or 1% fructose in trypticase soy broth, the growth of mutans streptococci was not inhibited by the addition of 1-10% xylitol. However, the addition of 20% xylitol caused the carbohydrate chain of water-insoluble glucan, which was synthesized by mutans streptococci from sucrose, to shorten as shown by TEM observation, and changes in the quantity of nucleic acid were recognized by LSM observation.
The results suggested that the caries preventive effect of xylitol was remarkably inhibited by the existence of another monosaccharide which could be metabolized by mutans streptococci.

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