D-Tagatose Effectively Reduces the Number of Streptococcus mutans and Oral Bacteria in Healthy Adult Subjects: A Chewing Gum Pilot Study and Randomized Clinical Trial.

We examined the effect of D-Tagatose on the growth of oral bacteria including Streptococcus mutans (S. mutans). Saliva collected from 10 healthy volunteers was plated on BHI medium (to culture total oral bacteria) and MBS medium (to culture S. mutans, specifically). Agar plates of BHI or MBS containing xylitol or D-Tagatose were cultured under aerobic or anaerobic conditions. We then counted the number of colonies. In BHI plates containing D-Tagatose, a complete and significant reduction of bacteria occurred under both aerobic and anaerobic conditions. In MSB medium, significant reduction of S. mutans was also observed. We then performed a doubleblind parallel randomized trial with 19 healthy volunteers. They chewed gum containing xylitol, D-Tagatose, or both for 4 weeks, and their saliva was collected weekly and plated on BHI and MSB media. These plates were cultured under anaerobic conditions. Total bacteria and S. mutans were not effectively reduced in either the D-Tagatose or xylitol gum group. However, S. mutans was significantly reduced in volunteers chewing gum containing both D-Tagatose and xylitol. Thus, D-Tagatose inhibited the growth of S. mutans and many types of oral bacteria, indicating that D-Tagatose intake may help prevent dental caries, periodontitis, and many oral diseases.

The utility of bone scintigraphy in the assessment of mandibular metabolism during long-term bisphosphonate administration.

The duration of antiresorptive therapy is an important risk factor for medication-related osteonecrosis of the jaw. We performed a pilot study using quantitative analysis by bone scintigraphy to test the hypothesis that mandibular metabolism is affected by long-term bisphosphonate (BP) therapy. Our primary objectives were to assess changes in bone metabolism of the mandible in response to long-term BP therapy and compare the bone metabolism changes of the mandible with other bone sites. We compared the metabolic difference at the site in the mandible unaffected by disease, the humerus and the femur between 14 osteoporosis patients who were being treated with BP (BP group) and 14 patients who were not being treated with BP (control group) using a quantitative analysis and bone scintigraphy. Study endpoints were the mean and maximum bone uptake values (BUVs) quantified using bone scintigraphy images of the mandible, humerus and femur. Quantified images of the site in the mandible unaffected by disease had significantly higher mean and maximum BUVs compared to the controls (mean, 0.74 vs. 0.49, p = 0.019; max., 1.29 vs. 0.85, p = 0.009, respectively). The mean and maximum BUV of femur ROIs in the BP group were significantly lower than those in control patients (mean BUV, 0.23 vs. 0.30, p = 0.039; max. BUV, 0.43 vs. 0.53, p = 0.024, respectively). This is the first report of mandible changes in response to long-term BP treatment, using bone scintigraphy. The results using bone scintigraphy demonstrated that the bone metabolism of the intact mandible is affected by a long-term administration of BP.

Potent inhibitory effects of D-tagatose on the acid production and water-insoluble glucan synthesis of Streptococcus mutans GS5 in the presence of sucrose.

We examined and compared the inhibitory effects of D-tagatose on the growth, acid production, and water-insoluble glucan synthesis of GS5, a bacterial strain of Streptococcus mutans, with those of xylitol, D-psicose, L-psicose and L-tagatose. GS5 was cultured for 12h in a medium containing 10% (w/v) of xylitol, D-psicose, L-psicose, D-tagatose or L-tagatose, and the inhibitory effect of GS5 growth was assessed. Each sugar showed different inhibitory effects on GS5. Both D-tagatose and xylitol significantly inhibited the acid production and water-insoluble glucan synthesis of GS5 in the presence of 1% (w/v) sucrose. However, the inhibitory effect of acid production by D-tagatose was significantly stronger than that of xylitol in presence of sucrose.

Symposium: Imaging modalities for drug-related osteonecrosis of the jaw (6), assessment of mandibular metabolism due to long-term administration of an anti-resorptive agent by bone scintigraphy (secondary publication).

It is not yet known why anti-resorptive agent-related osteonecrosis specifically affects the jaw. Here we assessed changes in the bone metabolism of the mandible in response to long-term bisphosphonate (BP) therapy, and we compared the bone metabolism changes of the mandible with those of other bone sites using a quantitative analysis by bone scintigraphy. The region of interest was selected by identifying without an abnormal accumulation of the mandible, humerus, second and fourth lumbar vertebrae, iliac crest, intertrochanteric femur and diaphysis. Bone scintigraphy images were quantified using a value we termed the 'bone uptake value (BUV)'. In the low-dose bisphosphonate (LBP) group (n = 21), the patients were undergoing osteoporosis treatment with low-dose BP. The high-dose BP (HBP) group consisted of 12 bone metastasis patients undergoing high-dose BP treatment. The Control group was 47 subjects with oral disease who had never been treated with an anti-resorptive agent. Our analyses demonstrated that with long-term BP administration, the bone metabolism of the iliac crest and intertrochanteric femur was suppressed but that of the mandible was enhanced. There was no significant difference in bone metabolism with either the low-dose BP or high-dose BP treatment. The effects of the long-term administration of BP were site-specific.

D­Tagatose inhibits the growth and biofilm formation of Streptococcus mutans.

Dental caries is an important global health concern and Streptococcus mutans has been established as a major cariogenic bacterial species. Reports indicate that a rare sugar, D­tagatose, is not easily catabolized by pathogenic bacteria. In the present study, the inhibitory effects of D­tagatose on the growth and biofilm formation of S. mutans GS­5 were examined. Monitoring S. mutans growth over a 24 h period revealed that D­tagatose prolonged the lag phase without interfering with the final cell yield. This growth retardation was also observed in the presence of 1% sucrose, although it was abolished by the addition of D­fructose. S. mutans biofilm formation was significantly inhibited by growth in sucrose media supplemented with 1 and 4% D­tagatose compared with that in a culture containing sucrose alone, while S. mutans formed granular biofilms in the presence of this rare sugar. The inhibitory effect of D­tagatose on S. mutans biofilm formation was significantly more evident than that of xylitol. Growth in sucrose media supplemented with D­tagatose significantly decreased the expression of glucosyltransferase, exo­ß­fructosidase and D­fructose­specific phosphotransferase genes but not the expression of fructosyltransferase compared with the culture containing sucrose only. The activity of cell­associated glucosyltransferase in S. mutans was inhibited by 4% D­tagatose. These results indicate that D­tagatose reduces water­insoluble glucan production from sucrose by inhibiting glucosyltransferase activities, which limits access to the free D­fructose released during this process and retards the growth of S. mutans. Therefore, foods and oral care products containing D­tagatose are anticipated to reduce the risk of caries by inhibiting S. mutans biofilm formation.

FDG PET as a procedure for detecting simultaneous tumours in head and neck cancer patients.

AIM: The presence of simultaneous primary tumours in other regions affects the prognosis and management decisions of head and neck cancer patients. Therefore, early detection of these tumours is necessary. Recent improvements in positron emission tomography (PET) have made it possible to examine the patient's whole body. The present study was undertaken to evaluate the clinical contribution of whole-body PET using fluorodeoxyglucose (FDG) for head and neck cancer patients. METHODS: Fifty-three consecutive patients with previously untreated head and neck cancer were examined. Whole-body FDG PET imaging was performed at 1 h after injection of (18)F-FDG. A 3-D acquisition was undertaken and iterative reconstruction was performed. The final diagnosis of simultaneous primary tumour was established by histological findings or clinical follow-up. RESULTS: Of 53 patients, six (11%) had evidence of simultaneous primary tumour. In five of these six patients, simultaneous primary tumours (two gastric cancer; one colon cancer; one pancreatic cancer; one thyroid cancer) were found by FDG PET. One more patient was found to have prostate cancer on the basis of blood test but this was not detected by FDG PET. In none of the remaining 47 patients, were additional simultaneous primary tumours found by FDG PET or any of the other routine examinations or during follow-up. CONCLUSIONS: The results of this study show a high rate of simultaneous primary tumour in patients with primary head and neck cancer. FDG PET appears to be a promising imaging modality for the detection of simultaneous tumours in head and neck cancer patients.

[Clinical study of the area under the blood concentration-time curve of targeting intra-arterial infusion chemotherapy with nedaplatin for primary oral cancer].

We treated oral cancer using a targeting intra-arterial infusion chemotherapy with CDGP (nedaplatin); dosages were determined by the original formula. We compared the expected AUC (area under the curve) with the actual AUC in primary oral cancer cases to assess the optimal dosage of CDGP for intra-arterial chemotherapy and to study relevance of AUC, effectiveness of independent chemotherapy and side effects. Eleven cases were treated at the Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Kagawa Medical University, from October 1998 to June 2002. The results are as follows. 1) A correlation was seen between the AUC and degree of thrombocytopenia. 2) AUC may reveal renal function, especially for GFR. 3) The response rate of the targeted intra-arterial infusion chemotherapy with CDGP was remarkably high and serious side effects were not observed. It appears that the set-up of the optimum dose should be decided based on the actual AUC. 4) There was about a 4/3 difference between the value of the expected AUC and the actual AUC. The equation for dosages based on the actual AUC needs to be studied further.

[Clinical study for determination of the dosage formula for intra-arterial infusion chemotherapy with nedaplatin].

Area under the curve (AUC) is a very important parameter for determination of optimal dosage of antineoplastic agents in order to avoid side effects and achieve high effectiveness. Also, even if a certain dosage is administered, measured AUC is different in each individual. Therefore, it is important to determine the formula of the dosage of antineoplastic agents. We treated oral cancer using an intra-arterial infusion chemotherapy with nedaplatin (CDGP). Eighteen patients were treated with CDGP at the Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Kagawa Medical University, from October 1998 to June 2002. The correlation among expected AUC, dosage, CDGP clearance and 24 hr creatinine clearance in all chemotherapy was monitored and examined. The obtained formula in the dosage of intra-arterial infusion chemotherapy with Nedaplatin was as follows. dosage = AUC x (0.027 x CCr + 7.17).

Multivariate analysis of factors influencing oral mucositis in allogeneic hematopoietic stem cell transplantation.

Little information is available regarding the effect of oral intervention on the outcome of hematopoietic stem cell transplantation (HSCT). We retrospectively analyzed the incidence of oral mucositis after allogeneic HSCT with or without oral intervention among 96 consecutive patients in our hospital between January 1988 and March 2006. We combined two oral intervention strategies: cryotherapy and oral health care. The former was applied beginning in 2003 for patients being treated with melphalan, and the latter, which was the study's main strategy, was applied to all HSCT recipients beginning in 2004. Oral mucositis was evaluated according to NCI CTCAE v3.0. The incidence of oral mucositis was 30.9% (17/55) in reduced-intensity stem cell transplantation (RIST), which was significantly lower than the 90.2% (37/41) in conventional stem cell transplantation (CST; P < 0.001). Among these 96 patients, severe oral mucositis was observed in 19 (46.3%) CST cases and in 6 (10.9%) RIST cases (P < 0.001). The occurrence of oral mucositis apparently decreased after oral health care instructions were given. Multiple logistic analysis revealed that the conditioning regimen and oral health care were independent risk factors for the incidence of oral mucositis. The cryotherapy did not exert enough potency to prevent oral mucositis in patients who had undergone CST or RIST. We concluded that oral health care improved tissue damage due to an overall upgrade in oral hygiene during chemotherapy.

Risk Factors for Methicillin-Resistant Staphylococcus aureus (MRSA) and Use of a Nasal Mupirocin Ointment in Oral Cancer Inpatients.

PURPOSE: Elimination of methicillin-resistant Staphylococcus aureus (MRSA) is of critical importance in oral and maxillofacial surgery because control is very difficult once infection of an oral tumor or oral wound with MRSA is established. PATIENTS AND METHODS: We retrospectively investigated the risk factors for acquiring MRSA in 518 patients with oral cancer among 1,877 inpatients in our department between 1984 and 2005. RESULTS: The patients with oral cancer demonstrated a high rate of MRSA colonization and infection (77.8%) relative to the population as a whole with MRSA isolated percentage in our department after 1991. The risk factors for MRSA in oral cancer patients are also related to systemic diseases and physiological and iatrogenic conditions, including cerebrovascular diseases (77.8%), peripheral arterial catheterization (69.2%), diabetes (50.0%), tracheotomy (50.0%), renal failure (50.0%), long-term broad-spectrum antibiotic use (45.7%), and malnutrition (43.3%). However, the highest risk of MRSA seems to be related to poor hygienic care. CONCLUSIONS: Beginning in 1999, we implemented a strategy for reducing infection by MRSA that included nasal mupirocin ointment for patients at high risk of MRSA; since then, the detection rate has decreased. We suggest that the administration of nasal mupirocin ointment and provision of scrupulous hygienic care for high-risk patients are useful and effective measures for decreasing the incidence of MRSA infection.