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Purpose Music therapy is widely used to enhance well-being, reduce pain, and distract patients from unpleasant symptoms in the clinical setting. However, the degree to which music modulates pain perception is unknown. The medial pain pathway including the limbic system is associated with emotion, but how music alters pathway activity is unclear. The aim of the study was to investigate pain thresholds and pain-related responses in the anterior cingulate cortex (ACC) and whether they were modulated when subjects listened to their favorite music genre. Subjects and Methods First, 30 subjects were examined for left forearm pain threshold using electrical stimulation with Pain Vision PS-2011N. The pain thresholds with and without music were compared. Second, when an 80-μA current from Pain Vision was applied to the left ankle of eight women, the pain-related responses of the ACC with and without music were observed with functional magnetic resonance device (fMRI). The changes in the pain-related activity in both parameters were discussed. Results The median pain threshold with favorite music was 38.9 μA, compared to 29.0 μA without, which was significantly different (p

Introduction: The oral function with many teeth affects the health maintenance of the whole body and brain activation of the older people. This study investigates the relationship between cognitive and oral functions, and the effect of tongue and lip motor training on cognitive function. Methods: One hundred subjects (age > 65) were investigated Mini-Mental State Examination (MMSE), their number of present teeth, masticatory function, occlusal force, and oral diadochokinesis (ODK), and correlations between their MMSE scores and the other factors were discussed. Fifteen subjects (5 non-impairment group: NIG, 10 impairment group: IG) participated in tongue and lip motor training three times daily for 15 months. Their MMSE scores, masticatory function, occlusal force, and ODK times were measured every three months. Results: Their MMSE scores correlated with age, number of present teeth, masticatory function, and ODK. Furthermore, multiple regression analysis showed that MMSE scores were strongly related to age and ODK. MMSE scores of IG were significantly higher after 15 months of pronunciation than before training and three months after training started. In both groups, ODK times after 15 months of training were significantly higher than before the training and three months training started. Their masticatory function and occlusal force in the IG showed no significant differences during the 15 months of training. Conclusions: The findings suggest that cognitive function may be related to oral function, especially pronunciation, and those 15 months of tongue and lip motor training is effective in improving cognitive and pronunciation functions.

Iulia Antioch,1 Tsumugu Furuta,2 Ryutaro Uchikawa,3 Masayo Okumura,4 Junichi Otogoto,2 Eiji Kondo,4 Norio Sogawa,5 Alin Ciobica,1 Mihoko Tomida2 1Department of Research, Faculty of Biology, “Alexandru Ioan Cuza” University of Iasi, Iasi, Romania; 2Department of Oral Health Promotion, Graduate School of Oral Medicine, Matsumoto Dental University, Nagano, Japan; 3Department of Dental Conservation, Matsumoto Dental University, Nagano, Japan; 4Department of Oral Anatomy, Matsumoto Dental University, Nagano, Japan; 5Department of Dental Pharmacology, Matsumoto Dental University, Nagano, JapanCorrespondence: Mihoko TomidaDepartment of Oral Health Promotion, Graduate School of Oral Medicine, Matsumoto Dental University, 1780 Gobara Hirooka, Shiojiri-Shi, Nagano 399-0781, JapanTel +81-263-51-2208Email mihoko.tomida@mdu.ac.jpPurpose: Music therapy is widely used to enhance well-being, reduce pain, and distract patients from unpleasant symptoms in the clinical setting. However, the degree to which music modulates pain perception is unknown. The medial pain pathway including the limbic system is associated with emotion, but how music alters pathway activity is unclear. The aim of the study was to investigate pain thresholds and pain-related responses in the anterior cingulate cortex (ACC) and whether they were modulated when subjects listened to their favorite music genre.Subjects and Methods: First, 30 subjects were examined for left forearm pain threshold using electrical stimulation with Pain Vision PS-2011N. The pain thresholds with and without music were compared. Second, when an 80-μA current from Pain Vision was applied to the left ankle of eight women, the pain-related responses of the ACC with and without music were observed with functional magnetic resonance device (fMRI). The changes in the pain-related activity in both parameters were discussed.Results: The median pain threshold with favorite music was 38.9 μA, compared to 29.0 μA without, which was significantly different (p< 0.0001). The men’s thresholds were significantly higher than women’s both with music (p< 0.05) and without music (p< 0.01). The pain threshold in women was more strongly affected by music than in men. The fMRI results showed that the pain-related response in the ACC in five of eight subjects was attenuated while they listened to their favorite music. No change was observed in the other three subjects.Conclusion: The present findings suggest that pain perception might be strongly affected by listening to favorite music, possibly through modulation of pain-related responses in the ACC.Keywords: pain threshold, music, forearm, anterior cingulate cortex, medial pathway

The present study examined the effect of melatonin on prostaglandin E2-induced pro-inflammatory cytokine production in human gingival fibroblasts. Human gingival fibroblasts were cultured in melatonin in the presence/absence of prostaglandin E2 for 1h. The levels of mRNA for IL-1β, IL-8 and osteoprotegerin/osteoclastogenesis inhibitory factor were quantitatively evaluated by reverse transcriptase-PCR using a LightCycler method. While melatonin did not significantly alter the levels of osteoprotegerin/osteoclastogenesis inhibitory factor mRNA, either in the presence or absence of prostaglandin E2, it markedly decreased the levels of prostaglandin E2-stimulated IL-1β and IL-8 mRNA. These results suggest that melatonin has the potency to reduce the production of pro-inflammatory cytokines from prostaglandin E2-activated human gingival fibroblasts in the inflamed periodontal tissues and may act as a new potent drug for the treatment for periodontal disease.

This study examined the modulating effect of PGE2 on LPS-induced IL-8 production by human gingival fibroblasts in vitro. The expression of IL-8 mRNA, after stimulation with PGE2, was determined by RT-PCR. IL-8 production by HGFs was shown to be related to the time of incubation and the dose of LPS. A slight increase in IL-8 levels was observed when cells were exposed to PGE2 alone compared to controls. When HGFs were pre-stimulated with PGE2 and then exposed to LPS, IL-8 production was increased 2-3 fold compared to non-treated cells. Herbimycin A completely abolished the secretion of IL-8. These results indicate that PGE2 can modulate cytokine secretion from HGFs and increase IL-8 production from cells exposed to LPS. IL-8 production induced by LPS was dependent on the tyrosine phosphorylation pathway.

Dipeptidyl peptidase II (DPP II; EC 3.4.14.2) from rat kidney was purified to a specific activity of 65.4µmol/min per mg of protein for Lys-Ala-β-naphthylamide. The N-terminal and partial amino acid sequences of the enzyme were determined. The peptide sequences were used to identify expressed sequence tag (EST) clones. By using the cDNA fragment of one of the EST clones as a probe, we isolated a cDNA clone with 1710bp encoding DPP II from a rat kidney cDNA library. The cDNA of rat DPP II contained an open reading frame of 1500bp, coding for a protein of 500 amino acids. The first 10 residues of the purified enzyme matched the deduced protein sequence starting with residue 37, suggesting the presence of a signal peptide. The mature enzyme (464 residues) had a calculated molecular mass of 51400Da, which was lower than the value (about 60000Da) determined by SDS/PAGE; and the deduced amino acid sequence showed six potential N-glycosylation sites. The deduced amino acid sequence of rat DPP II shared high similarity with quiescent-cell proline dipeptidase (78% identity) and prolyl carboxypeptidase (38% identity) and bore the putative catalytic triad (Ser, Asp, His) conserved in serine peptidase families. We transiently transfected COS-7 cells with pcDNA3.1 containing the cloned cDNA and obtained the overexpression of an immunoreactive protein (of about 60000Da). The transfected cells showed Lys-Ala-methylcoumarinamide-hydrolysing activity that was 50 times higher than the control cells.

Inflammatory mediators are central to the pathogenesis of periodontal diseases and may be used as markers in diagnosis. The aim of this study was to identify and quantify the various growth factors, apoptosis-related modifiers [soluble form of Fas (sFas) and bcl-2] and cytokines in the gingival crevicular fluid (GCF) of patients with different severities of periodontitis as compared with those of controls. GCF samples were taken from patients with periodontal disease and from controls. The concentrations of epidermal growth factor, transforming growth factor (TGF)-alpha, interleukin (IL)-1 beta, IL-6, interferon-gamma, beta 2-microglobulin (beta 2-MG), and apoptosis-related modifiers sFas and bcl-2 in the samples were determined by enzyme-linked immunosorbent assay. TGF-alpha was significantly lower in patients with periodontal disease than in the controls. In contrast, the concentrations of IL-1 beta, IL-6; and beta 2-MG were significantly higher in the group with severe periodontal disease than in the controls. The amount of total protein in the GCF was considerably higher in the disease group than the controls (p < 0.05). TGF-alpha, IL-1 beta, and beta 2-MG concentrations were associated (Spearman rank correlation, r < 0.05 for all) with clinical measures of disease severity (pocket depth) and inflammation (bleeding when probed). Apoptosis-related modifiers (sFas and bcl-2) could not be detected in any samples. These results suggest that the growth factor TGF-alpha and certain cytokines are associated with the presence of periodontal disease.

An activated Nd:YAG fiber tip using fiber-tip enhanced device (FTED) makes an activated and scattered irradiation beam. The enhanced (activated) fiber tip could be irradiated parallel to the target surface. The purpose of this study was to determine the effect of the activated laser fiber tip for calculus removal compared with other techniques. Specimens of extracted teeth with or without calculus were prepared. Nd:YAG laser power pulse 1 (SLT Japan, Tokyo, Japan) was used. The diameter of the optimal fiber was 400 μm. The enhanced condition was firstly examined using irradiation power from 100 to 900 mJ, 1 to 10 pps, in order to verify which is the best condition for calculus removal with scattering irradiation beam. Four types of calculus removal methods were compared: (1) hand curette; (2) ultrasonic scaler; (3) laser irradiation through a normal optimal fiber tip at 900 mJ, 10 pps, using a perpendicular irradiation mode with water coolant; (4) laser irradiation through the active fiber tip at 900 mJ, 10 pps, using a parallel irradiation mode with water coolant. After the roughness of the surfaces was clinically measured, the specimens were then prepared for scanning electron microscopy (SEM) observation. These results indicated that the best enhanced condition of the FTED for calculus removal with scattering irradiation beam was 800 mJ, 10 pps. The FTED was more useful for calculus removal than the normal fiber tip. However, it was less effective than hand and ultrasonic scaling considering the treatment time.

Inflammatory mediators, especially cytokine, play a central role in the pathogenesis of gingivitis. The aim of this study was to identify and quantify the various growth factors, and cytokines in the gingival crevicular fluid (GCF) of patients with gingivitis, as compared with those of control subjects. The levels of cytokine in the samples were determined by their respective ELISAs. The transforming growth factor (TGF)-α and osteoprotegerin (OPG) level were significantly lower in patients with gingivitis than in the controls (p

Cathepsin-K is a highly expressed cysteine protease, and it plays a key role in bone remodeling and cartilage breakdown in bone. Cathepsin-K is used as a well-known marker of osteoclast activity, because this enzyme is mainly derived from osteoclasts. The receptor activator for NF-kappaB ligand (RANKL) plays an important role in osteoclast formation. Although a recent study suggests the involvement of RANKL in the pathogenesis of periodontal disease, no one has previously examined the level of cathepsin-K in the body fluid of human subjects. If the presence of cathepsin-K, as well as RANKL, can be detected in body fluids, it would be indirect proof of the differentiation and/or activation of osteoclasts in the tissues bathed by these fluids. This communication reports on the in vivo concentrations of cathepsin-K and RANKL in the gingival crevicular fluid (GCF) of normal subjects and those patients with severe, moderate, and mild forms of the disease. Increased concentrations of cathepsin-K and RANKL were detected in the GCF from patients with periodontitis (P0.005 versus control subjects). Also, there was a positive correlation between cathepsin-K and RANKL levels (r=0.726), suggesting that both of them contribute to osteoclastic bone destruction in periodontal disease.

The receptor activator for NF-κB ligand (RANKL) plays an important role in osteoclast formation. A recent study with animal models suggests the involvement of RANKL in the pathogenesis of this periodontal disease. However, no one has examined the level of RANKL in the body fluid of human subjects. This communication reports on the in vivo concentrations of RANKL and the RANKL decoy receptor osteoprotegerin (OPG) in the gingival crevicular fluid (GCF) of periodontal subjects with severe, moderate, and mild forms of the disease. An increased concentration of RANKL and a decreased concentration of OPG were detected in GCF from patients with periodontitis (*p < 0.05 vs. control subjects). The ratio of the concentration of RANKL to that of OPG in the GCF was significantly higher for periodontal disease patients than for healthy subjects (*p < 0.01). Taken together, these data suggest that RANKL and OPG contribute to osteoclastic bone destruction in periodontal disease. Abbreviations: GCF, gingival crevicular fluid; IL, interleukin; OPG, osteoprotegerin; RANKL, receptor activator for NF-κB ligand.