Increased systemic levels of inflammatory mediators following one-stage full-mouth scaling and root planing.

BACKGROUND AND OBJECTIVE: Full-mouth scaling and root planing (FM-SRP) acts as a potent inflammatory stimulus immediately after treatment; however, systemic inflammation typically improves in the long term. The contribution of FM-SRP to systemic biological and acute-phase responses is largely unknown. The purpose of this prospective intervention study was to assess the systemic and local biological responses after FM-SRP. MATERIAL AND METHODS: Thirty-one patients with generalized moderate-to-severe chronic periodontitis received 1-stage FM-SRP. Measurement of clinical parameters and body temperature as well as collection of subgingival plaque, peripheral blood and gingival crevicular fluid was performed before and after treatment 2 or 3 times. Quantification of periodontopathic bacteria in the sulcus and measurement of corresponding serum IgG titers were performed. Systemic and local inflammatory markers such as endotoxin, high-sensitive C-reactive protein (hs-CRP) and 6 inflammatory cytokines were assessed using high-sensitivity assays. RESULTS: Compared to baseline values, FM-SRP resulted in a substantial improvement in clinical parameters (P < .05), lower bacterial counts (P < .01) and a significant decrease of IgG titers against Porphyromonas gingivalis (P < .001) 6 weeks after treatment. Comparing baseline parameters to those at 1 day post-treatment, there was a statistically significant elevation in body temperature (P = .007). In addition, a 5-fold increase in hs-CRP (P < .001), a remarkable increase in interferon-γ (P < .001) and a slight increase in interleukin (IL)-12p70 (P = .001) were detected in serum samples. In the gingival crevicular fluid, marked increases in hs-CRP (P < .001), IL-5 (P = .001), IL-6, IL-12p70 and tumor necrosis factor-α (P < .001 for the latter 3 markers) were noted 1 day after treatment. Endotoxin levels were below measurable limits for most time points. CONCLUSION: FM-SRP resulted in clinical and microbiological improvement 6 weeks post-treatment, but produced a moderate systemic acute-phase response including elevated inflammatory mediators 1 day post-treatment.

Guillain-Barré syndrome in a local area in Japan, 2006-2015: an epidemiological and clinical study of 108 patients.

BACKGROUND AND PURPOSE: Many epidemiological studies of Guillain-Barré syndrome (GBS) and Fisher syndrome (FS) have been conducted in Europe and America. In contrast, epidemiological studies are rare in Asia where the GBS subtypes differ from those in Western countries. This study was undertaken to clarify the incidence of GBS and FS in a local area in Japan as well as their seasonal trends. METHOD: Seventy-one GBS and 37 FS patients were recorded from 2006 to 2015 in an area of approximately 1.5 million inhabitants in Japan. The incidence, seasonal trends and clinical features of GBS and FS were examined. RESULTS: The incidence rate of GBS was 0.42 cases per 100 000 person-years and that of FS was 0.22 cases per 100 000 person-years. The incidence of GBS increased with age and FS affected predominantly patients aged from 45 to 64 years old. There was some seasonal clustering of acute motor axonal neuropathy (AMAN) and FS in spring and summer, but it was not significant. AMAN and FS patients had a high frequency of preceding infection (AMAN, 68% gastrointestinal infection; FS, 65% upper respiratory infection). Antecedent respiratory infection was significantly associated with FS as an outcome. Serum antibodies to ganglioside GM1 were detected in 71% of AMAN patients and antibodies to GQ1b were detected in 81% of FS patients. CONCLUSIONS: Our study offers evidence of a lower incidence of GBS and a higher incidence of FS in a local area in Japan than in Western countries.

Observation and determination of periodontal tissue profile using optical coherence tomography.

BACKGROUND AND OBJECTIVE: Diagnosis is a crucial step in periodontal treatment. The aim of this study was to evaluate the effectiveness of optical coherence tomography (OCT) for observation and determination of periodontal tissue profiles in vivo. MATERIAL AND METHODS: In experiment 1, refractive indices of purified water, porcine gingiva and human gingiva at 1330 nm were determined for the analysis of OCT images of periodontal tissues. In experiment 2, OCT examination was performed in the midlabial apico-coronal plane of mandibular anteriors in 30 Asian volunteers with healthy gingiva. Sulcus depth was measured on intra-oral photographs taken during probing. In the OCT images, the gingival, epithelial and connective tissue thickness, and the position of alveolar bone crest were determined and finally, the biologic width was measured. RESULTS: Refractive indices of purified water, porcine gingiva and human gingiva were 1.335, 1.393 and 1.397, respectively. Cross-sectional images of gingival epithelium, connective tissue and alveolar bone were depicted in real-time. The sulcular and junctional epithelium could be visualized occasionally. Laser penetration and reflection were limited to a certain depth with an approximate maximal imaging depth capability of 1.5 mm and OCT images of the periodontal structure were not clear in some cases. The average maximal thickness of gingiva and epithelium and biologic width at the mandibular anteriors were 1.06 ± 0.21, 0.49 ± 0.15 and 2.09 ± 0.60 mm, respectively. CONCLUSION: OCT has promise for non-invasive observation of the periodontal tissue profile in detail and measurement of internal periodontal structures including biologic width in the anterior region.

Associations among tooth loss, systemic inflammation and antibody titers to periodontal pathogens in Japanese patients with cardiovascular disease.

BACKGROUND AND OBJECTIVE: It is well known that there is a strong relationship between periodontitis and cardiovascular disease (CVD). Tooth loss reflects an end-stage condition of oral diseases, such as periodontitis. Infection with specific periodontal pathogens is known as a possible factor that influences development of CVD. The aim of this study was to assess the relationship between the number of residual teeth and systemic inflammatory conditions in patients with CVD. MATERIAL AND METHODS: We divided 364 patients with CVD into four groups, according to the number of residual teeth: (i) ≥20 teeth; (ii) 10-19 teeth; (iii) 1-9 teeth; and (iv) edentulous. We recorded medical history, blood data and periodontal conditions. Serum samples were obtained and their IgG titers against three major periodontal pathogens were measured. RESULTS: Smoking rate and the prevalence of diabetes mellitus were higher in edentulous patients and in subjects with a few teeth compared with patients with many teeth. The levels of C-reactive protein were higher in patients with 1-9 teeth than in those with 10-19 teeth and with ≥20 teeth. The level of Porphyromonas gingivalis IgG in the group with 10-19 teeth was statistically higher than that in the group with ≥20 teeth. The level of P. gingivalis IgG in the edentulous group tended to be lower than that in the other groups. CONCLUSION: The patients with 1-9 teeth had the highest level of C-reactive protein among the four groups, and the patients with 10-19 teeth had the highest level of IgG to periodontal bacteria. We conclude that the number of remaining teeth may be used to estimate the severity of systemic inflammation in patients with CVD.

Association of NOD2 Mutations with Aggressive Periodontitis.

Aggressive periodontitis (AgP) is characterized by rapid alveolar bone destruction and tooth loss early in life, and its etiology remains unclear. To explore the genetic risk factors of AgP, we performed genome-wide single-nucleotide polymorphism genotyping for identity-by-descent mapping and identified 32 distinct candidate loci, followed by whole exome sequencing with 2 pedigrees of AgP consisting of 3 cases and 1 control in 1 family and 2 sibling cases in the other. After variant filtering procedures and validation by targeted Sanger sequencing, we identified 2 missense mutations at 16q12 in NOD2 (p.Ala110Thr and p.Arg311Trp), which encodes nucleotide-binding oligomerization domain protein 2. We further examined 94 genetically unrelated AgP patients by targeted sequencing of NOD2 and found that 2 patients among them also carried the p.Arg311Trp variant. Furthermore, we found 3 additional missense mutations in this gene (p.His370Tyr, p.Arg459Cys, and p.Ala868Thr). These mutations either had not been previously observed or are extremely rare (frequency <0.001) in Asian populations. NOD2 plays a crucial role in innate immunity as an intracellular receptor initiating nuclear factor κB-dependent and mitogen-activated protein kinase-dependent gene transcription. These results demonstrated NOD2 as a novel gene involved in AgP.

Increased oral inflammation, leukocytes, and leptin, and lower adiponectin in overweight or obesity.

OBJECTIVES: The association between body mass index (BMI) and oral diseases was investigated, and levels of obesity-related inflammatory mediators were evaluated. SUBJECTS AND METHODS: Participants (n = 160) were clinically and radiographically examined for oral diseases. Blood profiles were recorded. Levels of adiponectin, leptin, and C-reactive protein (CRP) were measured. RESULTS: One hundred and thirteen (70.6%) participants had overweight or obese status (BMI ≥ 23.0 kg/m2 ). Sum of dental diseases and severe periodontitis were higher in overweight or obese individuals than in normal-weight participants (p = .037 and p = .002, respectively). A significant difference in oral mucosal disorders between normal weight and overweight or obesity was not found. Plasma leukocyte counts, liver enzymes, leptin, and CRP levels were increased while adiponectin levels were decreased in individuals with BMI≥23.0 kg/m2 compared with normal-weight participants. After adjusting for age, sex, fasting plasma glucose level, smoking, and exercise, obesity was associated with sum of dental diseases (ß = 0.239, p = .013), severe periodontitis (OR=4.52; 95% CI 1.37, 14.95, p = .013), adiponectin (ß = -0.359, p < .001), leptin (ß = 0.630, p < .001), and CRP levels (OR=12.66; 95% CI 3.07, 52.21, p < .001). CONCLUSION: Overweight or obese Thai people were related to an increase in inflammatory dental and periodontal diseases with an altered health profile and plasma inflammatory mediators.

Biodegradable gelatin/beta-tricalcium phosphate sponges incorporating recombinant human fibroblast growth factor-2 for treatment of recession-type defects: A split-mouth study in dogs.

BACKGROUND AND OBJECTIVE: Tissue engineering by using recombinant human (rh) growth factor technology may offer a promising therapeutic approach for treatment of gingival recession. Fibroblast growth factor-2 (FGF-2) has shown the ability to promote periodontal regeneration. Gelatin/beta-tricalcium phosphate (gelatin/ß-TCP) sponges have been developed to control the release of growth factors. The present study evaluated the periodontal regenerative efficacy of rhFGF-2 by comparing gelatin/ß-TCP sponges incorporated with rhFGF-2 to the scaffolds alone in artificially created recession-type defects in dogs. MATERIAL AND METHODS: Critically sized buccal gingival recession defects were surgically created on maxillary canine teeth of five dogs. In each animal, defects were randomized to receive either a gelatin/ß-TCP sponge soaked with rhFGF-2 (gelatin/ß-TCP/rhFGF-2) or phosphate-buffered saline (gelatin/ß-TCP). Eight weeks after surgery, biopsy specimens were obtained and subjected to microcomputed tomography and histological analyses. RESULTS: Complete root coverage was achieved in both groups. Microcomputed tomography revealed significantly greater new bone volume in the gelatin/ß-TCP/rhFGF-2 group. Histologically, both groups achieved periodontal regeneration; however, gelatin/ß-TCP/rhFGF-2 sites exhibited more tissue regeneration, characterized by significantly larger amounts of new cementum and new bone. Gelatin/ß-TCP sites featured increased long junctional epithelium and connective tissue attachment. In the gelatin/ß-TCP/rhFGF-2 sites, new bone exhibited many haversian canals and circumferential lamellae as well as remarkably thick periosteum with blood vascularization and hypercellularity. CONCLUSION: Within the limitations of this study, rhFGF-2 in gelatin/ß-TCP sponges exhibits an increased potential to support periodontal wound healing/regeneration in canine recession-type defects.

Assessing the progression of chronic periodontitis using subgingival pathogen levels: a 24-month prospective multicenter cohort study.

BACKGROUND: The diagnosis of the progression of periodontitis presently depends on the use of clinical symptoms (such as attachment loss) and radiographic imaging. The aim of the multicenter study described here was to evaluate the diagnostic use of the bacterial content of subgingival plaque recovered from the deepest pockets in assessing disease progression in chronic periodontitis patients. METHODS: This study consisted of a 24-month investigation of a total of 163 patients with chronic periodontitis who received trimonthly follow-up care. Subgingival plaque from the deepest pockets was recovered and assessed for bacterial content of Porphyromonas gingivalis, Prevotella intermedia, and Aggregatibacter actinomycetemcomitans using the modified Invader PLUS assay. The corresponding serum IgG titers were measured using ELISA. Changes in clinical parameters were evaluated over the course of 24 months. The sensitivity, specificity, and prediction values were calculated and used to determine cutoff points for prediction of the progression of chronic periodontitis. RESULTS: Of the 124 individuals who completed the 24-month monitoring phase, 62 exhibited progression of periodontitis, whereas 62 demonstrated stable disease. The P. gingivalis counts of subgingival plaque from the deepest pockets was significantly associated with the progression of periodontitis (p < 0.001, positive predictive value = 0.708). CONCLUSIONS: The P. gingivalis counts of subgingival plaque from the deepest pockets may be associated with the progression of periodontitis.

Bone metabolic microarray analysis of ligature-induced periodontitis in streptozotocin-induced diabetic mice.

BACKGROUND AND OBJECTIVE: Periodontal disease is a chronic infectious disease that results in bone loss. Many epidemiological studies have reported the progression of periodontal tissue destruction in patients with diabetes; however, the associated mechanism remains unclear. In this study, we comprehensively investigated how diabetes affects the periodontal tissue and alveolar bone loss using a ligature-induced periodontitis model in streptozotocin-induced diabetic (STZ) mice. MATERIAL AND METHODS: Diabetes was induced by intraperitoneal injection with streptozotocin in 6-wk-old C57/BL6J male mice. A silk ligature was tied around the maxillary left second molar in 9-wk-old wild-type (WT) and STZ mice. Bone loss was evaluated at 3 and 7 d after ligation. mRNA expression levels in the gingiva between the two groups were examined by DNA microarray and quantitative polymerase chain reaction at 1, 3 and 7 d post-ligation. Tartrate-resistant acid phosphatase and alkaline phosphatase staining of the periodontal tissue was performed for evaluation of osteoclasts and osteoblasts in histological analysis. RESULTS: In the gingiva, hyperglycemia upregulated the osteoprotegerin (Opg) mRNA expression and downregulated Osteocalcin mRNA expression. In the ligated gingiva, tumor necrosis factor-α (Tnf-α) mRNA expression was upregulated at 1 d post-ligation in STZ mice but not in WT mice. At 3 d post-ligation, alveolar bone loss was observed in STZ mice, but not in WT mice. Significantly severe alveolar bone loss was observed in STZ mice compared to WT mice at 7 d post-ligation. Bone metabolic analysis using DNA microarray showed significant downregulation in the mRNA expression of glioma-associated oncogene homologue 1 (Gli1) and collagen type VI alpha 1 (Col6a1) at the gingiva of the ligated site in STZ mice compared to that in WT mice. Quantitative polymerase chain reaction showed that Gli1 and Col6a1 mRNA expression levels were significantly downregulated in the gingiva of the ligated site in STZ mice compared to WT mice. Histological analysis showed lower alkaline phosphatase activity in STZ mice. In addition, an increased number of tartrate-resistant acid phosphatase-positive multinucleated cells were observed at the ligated sites in STZ mice. CONCLUSIONS: These results suggest that an imbalance of bone metabolism causes osteoclastosis in insulin-deficient diabetes, and that alveolar bone loss could occur at an early phase under this condition.

C-reactive protein levels and the association of carotid artery calcification with tooth loss.

OBJECTIVES: The relationship between carotid artery calcification (CAC) and tooth loss was investigated and its association with inflammatory mediator levels was evaluated. SUBJECTS AND METHODS: Ninety-two participants were examined for health and periodontal status. Panoramic radiographs were obtained for CAC identification. C-reactive protein (CRP), intercellular cell adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) levels were measured. RESULTS: Fifteen participants (16.3%) had CAC, 12 (80.0%) of whom were female. Mean age of participants with CAC was 55.3 ± 12.2 years, while that of participants without CAC was 48.9 ± 9.4 years. Median number of tooth loss in participants with CAC was 11, whereas that of individuals without CAC was 3 (P = 0.008). Age and presence of CAC were associated with the number of tooth loss, independent of health status (ß = 0.452, P = <0.001 and ß = 0.257, P = 0.005). Based on CRP levels, 10 participants (71.4%) were at intermediate risk of coronary heart disease (range, 1.0-2.3 µg ml-1 ), while four participants (28.6%) were at low risk (<1.0 µg ml-1 ). CRP, ICAM-1, or VCAM-1 levels were not significantly related to the presence of CAC or tooth loss. CONCLUSIONS: Patients with higher tooth loss have a greater prevalence of CAC. Patients with CAC should be referred for medical consultation.

Preferential changes of skeletal muscle echogenicity in myotonic dystrophy type 1.

BACKGROUND AND PURPOSE: In myotonic dystrophy type 1 (DM1), weakness of distal limb muscles affects quality of life. Non-invasive evaluation of muscular involvement by muscle sonography could be useful for characterizing muscle-specific involvement. METHODS: Sonography of the lower leg and forearm was performed in 19 patients with DM1 and 10 control subjects. The mean echo intensities (EIs) of seven limb muscles were obtained by computer-assisted histogram analysis and compared within DM1 according to the overall clinical severity. RESULTS: The EIs of the muscles were significantly higher in DM1 than in the controls (P < 0.01), except for the soleus (P = 0.4). Comparison of adjacent muscles showed the following: (i) greater EIs in flexor digitorum profundus than flexor carpi ulnaris (P < 0.01) and flexor digitorum superficialis (P = 0.02), and (ii) greater EIs in the medial head of the gastrocnemius than the soleus (P < 0.00001). In a subgroup analysis of DM1 according to the modified Rankin Scale (mRS), the more severe subgroup (mRS = 4-5) had lower mean EIs than the less severe subgroup (mRS from 1-3) (P = 0.01) in the flexor digitorum superficialis but not in other muscles. CONCLUSIONS: Preferential high echogenicity in the medial gastrocnemius and deep finger flexors is suggestive of DM1. Muscle echogenicity is not generally related to functional dysfunction in DM1.

Development of fast neutron pinhole camera using nuclear emulsion for neutron emission profile measurement in KSTAR.

We have developed a compact fast neutron camera based on a stack of nuclear emulsion plates and a pinhole collimator. The camera was installed at J-port of Korea superconducting tokamak advanced research at National Fusion Research Institute, Republic of Korea. Fast neutron images agreed better with calculated ones based on Monte Carlo neutron simulation using the uniform distribution of Deuterium-Deuterium (DD) neutron source in a torus of 40 cm radius.

Salivary pathogen and serum antibody to assess the progression of chronic periodontitis: a 24-mo prospective multicenter cohort study.

BACKGROUND AND OBJECTIVE: A diagnosis of periodontitis progression is presently limited to clinical parameters such as attachment loss and radiographic imaging. The aim of this multicenter study was to monitor disease progression in patients with chronic periodontitis during a 24-mo follow-up program and to evaluate the amount of bacteria in saliva and corresponding IgG titers in serum for determining the diagnostic usefulness of each in indicating disease progression and stability. MATERIAL AND METHODS: A total of 163 patients with chronic periodontitis who received trimonthly follow-up care were observed for 24 mo. The clinical parameters and salivary content of Porphyromonas gingivalis, Prevotella intermedia and Aggregatibacter actinomycetemcomitans were assessed using the modified Invader PLUS assay, and the corresponding serum IgG titers were measured using ELISA. The changes through 24 mo were analyzed using cut-off values calculated for each factor. One-way ANOVA or Fisher's exact test was used to perform between-group comparison for the data collected. Diagnostic values were calculated using Fisher's exact test. RESULTS: Of the 124 individuals who completed the 24-mo monitoring phase, 62 exhibited periodontitis progression, whereas 62 demonstrated stable disease. Seven patients withdrew because of acute periodontal abscess. The ratio of P. gingivalis to total bacteria and the combination of P. gingivalis counts and IgG titers against P. gingivalis were significantly related to the progression of periodontitis. The combination of P. gingivalis ratio and P. gingivalis IgG titers was significantly associated with the progression of periodontitis (p = 0.001, sensitivity = 0.339, specificity = 0.790). CONCLUSIONS: It is suggested that the combination of P. gingivalis ratio in saliva and serum IgG titers against P. gingivalis may be associated with the progression of periodontitis.

Intramuscular dissociation of echogenicity in the triceps surae characterizes sporadic inclusion body myositis.

BACKGROUND AND PURPOSE: Differential diagnosis of sporadic inclusion body myositis (s-IBM) and polymyositis (PM)/dermatomyositis (DM) is difficult and can affect proper disease management. Detection of heterogeneous muscular involvement in s-IBM by muscle sonography could be a unique diagnostic feature. METHODS: Sonography of the lower leg and forearm was performed in patients with s-IBM, PM/DM and control subjects (n = 11 each). Echo intensities (EIs) of the adjacent muscles [medial head of the gastrocnemius versus soleus and the flexor digitorum profundus (FDP) versus flexor carpi ulnaris (FCU)] were scored by three blinded raters. The mean EIs of these muscles were compared using computer-assisted histogram analysis. RESULTS: Both evaluation methods showed high echoic signals in the gastrocnemius of patients with s-IBM. EIs were significantly different between the gastrocnemius and soleus in patients with s-IBM, but not in those with DM/PM and the controls. In the forearm, although the EI of the FDP was higher in the s-IBM group than in the other groups, the EI differences between the FDP and FCU did not differ significantly between disease groups. The difference in area under the curves to differentiate between s-IBM and DM/PM was greatest between the gastrocnemius-soleus EIs (0.843; P = 0.006). CONCLUSIONS: High echoic signals in the medial gastrocnemius compared with those of the soleus are suggestive of s-IBM over PM/DM.

Is the Susceptibility Vessel Sign on 3-Tesla Magnetic Resonance T2*-Weighted Imaging a Useful Tool to Predict Recanalization in Intravenous Tissue Plasminogen Activator?

The aim of this study was to investigate the independent factors associated with the absence of recanalization approximately 24 h after intravenous administration of tissue-type plasminogen activator (IV TPA). The previous studies have been conducted using 1.5-Tesla (T) magnetic resonance imaging (MRI). We studied whether the characteristics of 3-T MRI findings were useful to predict outcome and recanalization after IV tPA. Patients with internal carotid artery (ICA) or middle cerebral artery (MCA) (horizontal portion, M1; Sylvian portion, M2) occlusion and treated by IV tPA were enrolled. We studied whether the presence of susceptibility vessel sign (SVS) at M1 and low clot burden score on T2*-weighted imaging (T2*-CBS) on 3-T MRI were associated with the absence of recanalization. A total of 49 patients were enrolled (27 men; mean age, 73.9 years). MR angiography obtained approximately 24 h after IV tPA revealed recanalization in 21 (42.9 %) patients. Independent factors associated with the absence of recanalization included ICA or proximal M1 occlusion (odds ratio, 69.6; 95 % confidence interval, 5.05-958.8, p = 0.002). In this study, an independent factor associated with the absence of recanalization may be proximal occlusion of the cerebral arteries rather than SVS in the MCA or low T2*-CBS on 3-T MRI.

Ridge augmentation using recombinant human fibroblast growth factor-2 with biodegradable gelatin sponges incorporating ß-tricalcium phosphate: a preclinical study in dogs.

BACKGROUND AND OBJECTIVE: Fibroblast growth factor-2 (FGF-2) regulates the proliferation and differentiation of osteogenic cells, resulting in the promotion of bone formation. Biodegradable gelatin sponges incorporating ß-tricalcium phosphate (ß-TCP) have been reported as a scaffold, which has the ability to control growth factor release, offering sufficient mechanical strength and efficient migration of mesenchymal cells. In this study, we evaluated the effects of the combined use of recombinant human FGF-2 (rhFGF-2) and gelatin/ß-TCP sponge on ridge augmentation in dogs. MATERIAL AND METHODS: Six male beagle dogs were used in this study. Twelve wk after tooth extraction, bilateral 10 × 5 mm (width × depth) saddle-type defects were created 3 mm apart from the mesial side of the maxillary canine. At the experimental sites, the defects were filled with gelatin/ß-TCP sponge infiltrated with 0.3% rhFGF-2, whereas gelatin/ß-TCP sponge infiltrated with saline was applied to the control sites. Eight wk after surgery, qualitative and quantitative analyses were performed. RESULTS: There were no signs of clinical inflammation at 8 wk after surgery. Histometric measurements revealed that new bone height at the experimental sites (2.98 ± 0.65 mm) was significantly greater than that at the control sites (1.56 ± 0.66 mm; p = 0.004). The total tissue height was greater at the experimental sites (6.62 ± 0.66 mm) than that at the control sites (5.95 ± 0.74 mm), although there was no statistical significant difference (p = 0.051). Cast model measurements revealed that the residual defect height at the experimental sites (2.31 ± 0.50 mm) was significantly smaller than that at the control sites (3.51 ± 0.78 mm; p = 0.012). CONCLUSION: The combined use of rhFGF-2 and gelatin/ß-TCP sponge promotes ridge augmentation in canine saddle-type bone defects.

The identification of raft-derived tau-associated vesicles that are incorporated into immature tangles and paired helical filaments.

AIMS: Neurofibrillary tangles (NFTs), a cardinal pathological feature of neurodegenerative disorders, such as Alzheimer's disease (AD) are primarily composed of hyper-phosphorylated tau protein. Recently, several other molecules, including flotillin-1, phosphatidylinositol-4,5-bisphosphate [PtdIns(4,5)P2] and cyclin-dependent kinase 5 (CDK5), have also been revealed as constituents of NFTs. Flotillin-1 and PtdIns(4,5)P2 are considered markers of raft microdomains, whereas CDK5 is a tau kinase. Therefore, we hypothesized that NFTs have a relationship with raft domains and the tau phosphorylation that occurs within NFTs. METHODS: We investigated six cases of AD, six cases of other neurodegenerative diseases with NFTs and three control cases. We analysed the PtdIns(4,5)P2-immunopositive material in detail, using super-resolution microscopy and electron microscopy to elucidate its pattern of expression. We also investigated the spatial relationship between the PtdIns(4,5)P2-immunopositive material and tau kinases through double immunofluorescence analysis. RESULTS: Pretangles contained either paired helical filaments (PHFs) or PtdIns(4,5)P2-immunopositive small vesicles (approximately 1 µm in diameter) with nearly identical topology to granulovacuolar degeneration (GVD) bodies. Various combinations of these vesicles and GVD bodies, the latter of which are pathological hallmarks observed within the neurons of AD patients, were found concurrently in neurons. These vesicles and GVD bodies were both immunopositive not only for PtdIns(4,5)P2, but also for several tau kinases such as glycogen synthase kinase-3ß and spleen tyrosine kinase. CONCLUSIONS: These observations suggest that clusters of raft-derived vesicles that resemble GVD bodies are substructures of pretangles other than PHFs. These tau kinase-bearing vesicles are likely involved in the modification of tau protein and in NFT formation.

mTOR signaling controls VGLUT2 expression to maintain pain hypersensitivity after tissue injury.

Mammalian target of rapamycin (mTOR) is a serine-threonine protein kinase that controls protein synthesis in the nervous system. Here, we characterized the role of protein synthesis regulation due to mTOR signaling in rat dorsal root ganglion (DRG) following plantar incision. The number of phosphorylated mTOR (p-mTOR)-positive neurons was increased 2-4days after the incision. Rapamycin inhibited p-mTOR expression in the DRG and thermal hypersensitivity 3days but not 1day after the incision. Vesicular glutamate transporter 2 (VGLUT2) expression was increased after the plantar incision, which was inhibited by rapamycin. These results demonstrated that tissue injury induces phosphorylation of mTOR and increased protein level of VGLUT2 in the DRG neurons. mTOR phosphorylation involves in maintenance of injury-induced thermal hypersensitivity.

A genome-wide association study of periodontitis in a Japanese population.

Periodontitis is a multifactorial disease in which bacterial, lifestyle, and genetic factors are involved. Although previous genetic association studies identified several susceptibility genes for periodontitis in European populations, there is little information for Asian populations. Here, we conducted a genome-wide association study and a replication study consisting of 2,760 Japanese periodontitis patients and 15,158 Japanese controls. Although single-nucleotide polymorphisms that surpassed a stringent genome-wide significance threshold (P < 5 × 10(-8)) were not identified, we found 2 suggestive loci for periodontitis: KCNQ5 on chromosome 6q13 (rs9446777, P = 4.83 × 10(-6), odds ratio = 0.82) and GPR141-NME8 at chromosome 7p14.1 (rs2392510, P = 4.17 × 10(-6), odds ratio = 0.87). A stratified analysis indicated that the GPR141-NME8 locus had a strong genetic effect on the susceptibility to generalized periodontitis in Japanese individuals with a history of smoking. In conclusion, this study identified 2 suggestive loci for periodontitis in a Japanese population. This study should contribute to a further understanding of genetic factors for enhanced susceptibility to periodontitis.