A multicenter prospective cohort study on the effect of smoking cessation on periodontal therapies in Japan.

Few prospective studies have reported the effects of periodontal therapy on patients who attempted to quit smoking. This study aimed to assess how smoking cessation affects periodontal therapy. Twenty-five smokers with periodontitis were investigated by dividing them into two groups, a smoking cessation support group and a continued smoking group. Those in the support group received counseling and nicotine replacement therapy, followed by periodontal treatment conducted by dentists who had completed an e-learning course on smoking cessation. Clinical parameters were measured at baseline, 3, and 6 months. Most clinical parameters improved for those in the smoking cessation support group. There were no significant improvements in bleeding on probing (BOP) or the number of severe periodontal disease sites in the continued smoking group. Probing pocket depth (PPD) and clinical attachment levels (CAL) at sites that received scaling and root planing (SRP) significantly improved in all subjects. BOP did not improve at reevaluation in the smoking relapse subgroup. Patients in the smoking cessation support program led by dental professionals showed more improvement in BOP than those in the continued smoking group.

Targeted drug delivery system for oral cancer therapy using sonoporation.

Ultrasound-mediated destruction of microbubbles has been proposed as an innovative non-invasive drug delivery system for cancer therapy. We developed a specific drug delivery system for squamous cell carcinoma that uses sonoporation with the anti-epidermal growth factor receptor (EGFR) antibody. Administration of a low dose of bleomycin (BLM) by sonoporation with the anti-EGFR antibody produced a marked growth inhibition of Ca9-22 cells in vitro. In addition, scanning electron microscopic analysis revealed apparent surface deformation of Ca9-22 cells treated with sonoporation in the presence of the antibody. Interestingly, the population of apoptotic cells was remarkably increased when a low dose of BLM was delivered using sonoporation with the Fab fragment of the anti-EGFR antibody. These findings indicate that sonoporation with the Fab fragment makes it possible to administer drugs into cells more efficiently and specifically, suggesting a novel application for chemotherapy and gene therapy treatments for oral squamous cell carcinoma.

Influence of altered occlusal plane on rabbit temporomandibular joint cartilage.

BACKGROUND: There is limited knowledge relating to the influence of mechanical stress on the temporomandibular joint (TMJ) and the degree of damage this stress can induce in the case of an altered occlusal plane on the extracellular matrix cartilage and chondrocytes. The aim of this study was to examine the histopathological influence of an altered occlusal plane on rabbit TMJ cartilage. METHODS: Fifteen male Japanese white rabbits were used in this study. In 12 cases, the upper right and lower left teeth were ground to their cervical level so that the occlusal plane was tilted right side up. Their temporomandibular joints (TMJs) harvested at 3 days, 1, 2 and 4 weeks were analyzed immunocytochemically and immunohistochemically. The terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick endlabeling (TUNEL) method was used for immunocytochemical study to detect DNA fragmentation in chondrocytes. An immunohistochemical study was also performed to evaluate the metabolism of type 2 collagen in the extracellular matrix in the TMJ cartilage. RESULTS: The number of apoptotic cells increased in all experimental animals. More apoptotic cells were observed in the articular eminences than in the condyles. The type 2 collagen-positive area in the condyles was reduced at the beginning but recovered within 4 weeks, and remained small throughout this experimental period in the articular eminences. CONCLUSIONS: These findings suggest that histopathological changes occurred in response to alteration of the occlusal plane. The influence decreased as the occlusal plane recovered in the condyles, but the immunocytochemical and immunohistochemical influence continued in the articular eminences.

Vertical ramus versus sagittal split osteotomies: comparison of stability after mandibular setback.

PURPOSE: Intraoral vertical ramus osteotomy (IVRO) offers some advantages over sagittal split ramus osteotomy (SSRO) for treatment of the prognathic patient. The purpose of this study was to compare the postoperative changes of proximal and distal segments after IVRO and SSRO with semirigid internal fixation. PATIENTS AND METHODS: Thirty Japanese adults with a diagnosis of prognathic mandible were randomized to undergo either IVRO (n = 15) or SSRO (n = 15) according to an adaptive random assignment procedure. The postoperative changes of the proximal and distal segments were assessed with posteroanterior and lateral cephalograms. RESULTS: Compared with the SSRO group, the B-point and pogonion moved significantly posteriorly and inferiorly in the IVRO group from 1 month to 3 months after surgery. At 1 year after surgery, there was no significant difference between the 2 groups in the horizontal and vertical stability of the B-point and the pogonion. In the IVRO group, the gonion deviated significantly laterally from 1 week until 1 month after surgery as compared with that of the SSRO group. There was a significant correlation between the amount of setback and the amount of lateral gonial deviation in the IVRO group from 1 week to 1 year after surgery. CONCLUSIONS: Although in IVRO cases, distal segments moved posteriorly and inferiorly immediately after the release of maxillomandibular fixation, the stability after IVRO is equal to that after SSRO with semirigid internal fixation.

Relationship between cortical bone formation on mandibular condyles and alternation of the magnetic resonance signals characteristic of growth.

INTRODUCTION: The purpose of this study was to elucidate the significance of double contour-like structures (DCLS) relative to the maturity of mandibular condyles and the possible constituents of DCLS. We evaluated the relationship between the alternation of DCLS and the ossification on the top of mandibular condyles. METHODS: In 36 subjects, aged 9 to14 years at the first examination, magnetic resonance imaging characteristics of the mandibular condyles were obtained from fast spin echo intermediate-weighted images and T2-weighted images; 2 or 3 years later, magnetic resonance images were again obtained from 23 of the same 36 subjects. RESULTS: A significant relationship was found between the absence of DCLS and the continuity of void-signal lines on the tops of the mandibular condyles. DCLS disappeared, and the void-signal lines on the tops of the mandibular condyles became continuous as the children grew. The top of DCLS was seen as a hypersignal on T2-weighted images. CONCLUSIONS: Alternations of DCLS might be a useful criterion for evaluating the maturity of mandibular condyles in children. Possible constituents of DCLS might be hypervascular loose fibrous tissue and a proliferation of cartilage accompanied by active ossification on the tops of the mandibular condyles.

Growth/differentiation factor-5 induces growth arrest and apoptosis in mouse B lineage cells with modulation by Smad.

Bone morphogenetic proteins, including growth/differentiation factor-5 (GDF-5), are multifunctional cytokines. Recent studies of intracellular signal transduction mechanisms for the transforming growth factor-beta superfamily have focused on Smad proteins. However, scant attention has been given to the mechanism by which GDF-5 exerts its negative growth effect on immunological competent cells. In the present study, we demonstrated that GDF-5 induced cell cycle arrest in the G1 phase before the appearance of apoptosis in mouse B cell hybridoma HS-72 cells, while the ectopic expression of Smad6 and Smad7 in HS-72 cells suppressed the GDF-5-induced G1 cell cycle arrest by abolishing the expression of p21(CIP-1/WAF-1) and hypophosphorylation of retinoblastoma protein. Moreover, we found that Smad6 and Smad7 suppressed GDF-5-induced apoptosis in HS-72 cells. These findings indicated that Smad6 and Smad7 exhibit inhibitory effects toward GDF-5-mediated signaling in B lineage cells.

IL-1 beta, IL-1 receptor antagonist and soluble type II IL-1 receptor in synovial fluid of patients with temporomandibular disorders.

Among the members of the interleukin-1 (IL-1) family, IL-1 beta, which is a major agonist, has been detected in synovial fluid (SF) of the temporomandibular joint (TMJ) of patients with temporomandibular joint disorders (TMD). However, there is little knowledge regarding suppressive molecules, such as IL-1 receptor antagonist (IL-1ra) and the soluble form of type II IL-1 receptor (sIL-1RII), in TMD patients. The aim of this study was to investigate the levels of IL-1 beta, IL-1ra and sIL-1RII in the TMJ SF of patients with TMD and their relationship. Fifty-two SF samples from TMD patients and nine samples from asymptomatic volunteers were examined. Detected levels of IL-1 beta and sIL-1RII were significantly higher in the TMD group compared with the volunteer group. There was no significant difference in IL-1ra levels between the TMD and volunteer groups. The IL-1 beta/IL-1ra ratio in the TMD group, however, was higher than that in the volunteer group. In the TMD group, positive correlations were found between IL-1 beta and IL-1ra, IL-1ra and sIL-1RII, and IL-1 beta and sIL-1RII. In addition to increased IL-1 beta, development of TMD may also lead to decreased IL-1ra and increased sIL-1RII in response to increasing IL-1.

Alternation of the magnetic resonance signals characteristic of mandibular condyles during growth.

OBJECTIVE: In a previous study, we named the magnetic resonance imaging (MRI) signal that is characteristic of mandibular condyles in growing children the "double contour-like structure" (DCLS). In the current study, we evaluated the alternating appearance and disappearance of the DCLS in children as they grow to elucidate the significance of the DCLS. STUDY DESIGN: In 11 subjects who were 9-14 years old at the time of the first examination, MRI characteristics of mandibular condyles were sought from fast spin-echo intermediate-weighted images; 2 or 3 years later, repeat MRI were obtained from the same subjects. RESULTS: At the second examination, 10 of the 16 DCLSs detected at the first examination had disappeared. A significant relationship was found between the alternation of the DCLS and the bone marrow conversion from red to yellow in mandibular condyles. Alternation of the DCLS tended to coincide with eruption of the permanent maxillary second molars. The DCLS was also shown to appear as a hypersignal on T2-weighted images. CONCLUSIONS: Double contour-like structure signals in mandibular condyles appeared and disappeared as children grew, and these signal alternations may be useful as a criterion for the staging of mandibular condyle development in children. Possible constituents of the DCLS may be hypervascular loose fibrous tissue and a proliferation of cartilage.

Prevalence of hepatitis viral infection in dental patients with impacted teeth or jaw deformities.

OBJECTIVE: The prevalence of infection with hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis G virus (HGV), and transfusion-transmitted viruses (TTV) was evaluated in patients with impacted teeth or jaw deformities. STUDY DESIGN: Of 486 patients, 268 had serum samples available for retrospective TTV DNA and HGV RNA assays. In addition, the sera of 404 patients were assayed for HB surface antigen and the sera of 340 were assayed for HCV antibody. RESULTS: HGV RNA was detected in 3 of 268 patients (1.1%), and TTV DNA was detected in 60 of 268 (22.4%). Of 404 patients, 3 had HB surface antigens (0.7%). Furthermore, 13 of 340 were HCV-seropositive (3.8%). The rate of infection was similar between patients with impacted teeth and those with jaw deformities, respectively, as follows: 1.1% versus 0%, respectively, for HBV prevalence; 4.1% versus 3.2% for HCV prevalence; 1.8% versus 0% for HGV prevalence; and 22.9% versus 21.4% for TTV prevalence. CONCLUSIONS: Universal precautions to prevent hepatitis and TTV infection during oral surgical procedures are important.

Biomechanical evaluation of different types of rigid internal fixation techniques for subcondylar fractures.

PURPOSE: The aim of this study was to evaluate the biomechanical stability of various internal fixation systems for subcondylar fractures. MATERIALS AND METHODS: Eighteen identical synthetic mandibles were used. Left condylar processes were cut to mimic perpendicular subcondylar fracture and right sides were mimicked oblique subcondylar fracture. The fixation systems used included single 4-hole mini adaptation plate, double fixation with the same plates, single 4-hole mini dynamic compression plate (DCP), Eckelt lag screw system, Wurzburg lag screw plate system and double 4-hole biodegradable miniplates made of poly L-lactide (PLLA). In oblique fractures, one of the screws fixing plates was used bicortically through bone fragments. The loading vector simulated physiologic forces to the condyle on biting with servohydraulic testing machine until failure was reached. Load-displacement curve, maximum load for failure, and stiffness were measured. RESULTS: In perpendicular fracture, double adaptation plate showed the highest level of tolerance load followed by Eckelt lag and double PLLA plate. In stiffness, double adaptation plate and Eckelt lag screw showed higher level of stiffness, whereas double PLLA was almost at the same level of single DCP. In oblique fracture, double adaptation plate showed the highest strength. CONCLUSIONS: In this laboratory setting, double adaptation plates fixation proved to have superior biomechanical stability in both fracture conditions. Eckelt lag screw showed good stability in the perpendicular fracture, however, it was weak in the oblique fracture.

Relationship between TNF-alpha and TUNEL-positive chondrocytes in antigen-induced arthritis of the rabbit temporomandibular joint.

BACKGROUND: Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end-labeling (TUNEL) staining is a widely accepted method for the detection of DNA fragmentation in nuclei of apoptotic cells. Tumor necrosis factor (TNF)-alpha is closely associated with changes in condylar cartilage and modulates apoptosis in various tissues including cartilage. The aim of this study was to investigate the relationship between apoptotic chondrocytes and TNF-alpha in a rabbit model of arthritis. METHOD: Unilateral temporomandibular joint (TMJ) arthritis was induced in 20 adult New Zealand White rabbits. From 1 day to 6 weeks after the induction of arthritis, immunohistochemical analysis for TNF-alpha and TUNEL was performed. RESULTS: In condylar cartilage, TNF-alpha-positive cells and TUNEL-positive cells were localized together. TNF-alpha-positive chondrocytes seemed to precede TUNEL-positive cells. CONCLUSIONS: The results of the present study suggest that TNF-alpha may be involved in apoptosis and/or apoptotic necrosis of chondrocytes as TMJ arthritis progresses from the acute to chronic stage.

Utility of diffusion-weighted images using fast asymmetric spin-echo sequences for detection of abscess formation in the head and neck region.

OBJECTIVE: The objective of this study was to evaluate the utility of new diffusion-weighted magnetic resonance images (DWI) using fast asymmetric spin-echo (FASE) sequences for the detection of abscess formation in patients with phlegmon in the oral and maxillofacial regions. METHODS: We compared diffusion-weighted images using FASE sequences with those using the gradient-echo type of echo-planar images (EPI) in 10 control volunteers and 10 patients with phlegmon in the oral and maxillofacial regions. RESULTS: Many kinds of tissues in the oral and maxillofacial regions were relatively well visualized in all subjects on FASE-DWI, but not well on EPI-DWI. Apparent diffusion coefficients calculated from FASE sequences in abscess areas of patients with phlegmon were significantly lower than those in abscess-free areas; however, apparent diffusion coefficients calculated from EPI were not significantly different due to prominent distortion in small sample size study. CONCLUSIONS: We could accurately recognize the presence of abscess formation within inflammatory tissue in 5 patients with phlegmon using FASE-DWI. As an additional magnetic resonance examination, FASE-DWI might be useful in the detection of abscess formation in the oral and maxillofacial regions.

Three-dimensional identification of hemangiomas and feeding arteries in the head and neck region using combined phase-contrast MR angiography and fast asymmetric spin-echo sequences.

OBJECTIVE: To evaluate a proposed technique for the 3-dimensional (3D) detection of hemangiomas, including vascular malformation and their feeding arteries, in the head and neck. The new technique combines phase-contrast magnetic resonance angiography (PCMRA) without contrast medium and 3D fast asymmetric spin-echo (FASE) sequences. METHODS: The technique was applied to 3 patients having hemangiomas in the head and neck region. In 1 patient the image obtained with the proposed technique was compared to that obtained by standard contrast angiography. RESULTS: In all 3 patients, the 3D presence of the hemangiomas and the feeding arteries were well defined in images created by the proposed technique. Additionally, the characterization of the hemangioma's 3D structure and distribution of the feeding arteries coincided with those observed using contrast angiography in the case for which contrast angiography was also performed. CONCLUSIONS: Preliminary experience shows that the proposed technique combining 3D-FASE and 3D-PCMRA is useful to visualize both the 3D structure of hemangiomas and to identify the 3D distribution of the feeding arteries without using contrast medium.

Prevalence of hepatitis virus infection in association with oral diseases requiring surgery.

OBJECTIVE: We evaluated the prevalence of hepatitis virus infection in a large population of patients in terms of diseases requiring oral surgery. DESIGN: Retrospective case survey. SUBJECTS AND METHODS: Prevalence of hepatitis B and C virus (HBV, HCV) infection were compared between oral diseases such as inflammation, cysts, cancer, trauma, benign tumors, impacted teeth, or jaw deformity in dental inpatients (n = 5830) with adjustment for age, gender, and history of surgery. RESULTS: Of 4402 inpatients, 94 had HB surface(s) antigen (2.1%), while 151 of 2613 were seropositive for HCV (5.8%). Prevalences of HBs antigen and HCV antibody exceeded those in the general population. HBs antigen was more prevalent in patients with benign oral tumors than in patients with impacted teeth, whether or not adjustment was made for age (odds ratios, 4.246 and 5.055 with and without age adjustment, respectively; P < 0.05). On the other hand, HCV antibody was more prevalent in patients with oral cancer than in those with impacted teeth before adjustment for age (odds ratios, 2.433; P < 0.05), but this difference was reversed with age adjustment (odds ratios, 0.443; P < 0.05). CONCLUSION: HBs antigen was more prevalent in patients with benign oral tumors, while HCV antibody was higher in patients with oral cancer. However, this increased incidence of HCV antibody apparently was a reflection of age. HCV infection may not have an etiologically important association with oral cancer.

A decrease in the molecular weight of hyaluronic acid in synovial fluid from patients with temporomandibular disorders.

BACKGROUND: The molecular weight (MW) of hyaluronic acid (HA) in joints generally declines in inflammatory arthritis. As inflammation exists in certain temporomandibular disorders (TMD), we measured the MW of HA in synovial fluid (SF) recovered from patients with TMD and compared it with that from normal controls. METHODS: Synovial fluid was obtained from patients with TMD (21 TMJs) and normal controls (5 TMJs). The MW of HA was measured using high-performance liquid chromatography (HPLC). RESULTS: In the controls, the MW of HA in SF exceeded the detection limit, 3000 kDa. In contrast, 19 (90.5%) of 21 SF samples from patients showed a decreased MW of HA. The median MW of HA (1570 kDa) in TMD was significantly lower than that in the controls (P < 0.01). CONCLUSION: The MW of HA in SF from patients with TMD is decreased.

Immunohistochemical study of interleukin-1beta and interleukin-1 receptor antagonist in an antigen-induced arthritis of the rabbit temporomandibular joint.

BACKGROUND: In temporomandibular joint (TMJ) arthritis, there is limited knowledge of the relationship between interleukin-1beta (IL-1beta) and interleukin-1 receptor antagonist (IL-1ra), as well as the source of these cytokines. We investigated the development of an antigen-induced arthritis in the rabbit TMJ immunohistochemically. METHODS: Unilateral TMJ arthritis was induced in 32 adult New Zealand White rabbits. From 6 h to 12 weeks after induction of arthritis, topology of IL-1beta and IL-1ra were observed. RESULT: The acute stage of induced arthritis lasted for one week after induction, thereafter it became chronic. In the early phase of the acute stage, infiltrating inflammatory cells, as well as synovial cells, produced IL-1beta and IL-1ra. In the late phase of the acute stage, the main source of these cytokines was subsynovial fibroblasts. In this phase of arthritis, IL-1beta and IL-1ra did not appear to be produced by synovial cells. From the early to intermediate phase of the chronic stage, proliferating synovial cells produced IL-1beta and IL-1ra. In this phase of the arthritis, these cytokines were also observed in a cluster formation in chondrocytes. CONCLUSION: This arthritis model shows a staging of the joint inflammation process with time. IL-1beta and IL-1ra are produced by a certain kind of cells depending on the stage of inflammation.

Involvement of tumor necrosis factor-alpha and interleukin-8 in antigen-induced arthritis of the rabbit temporomandibular joint.

BACKGROUND: In temporomandibular joint (TMJ) arthritis, knowledge is limited about the source of the inflammatory mediators. The aim of this study was to investigate the immunohistochemical role of tumor necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8) in the development of the antigen-induced arthritis of the rabbit TMJ. METHODS: Unilateral TMJ arthritis was induced in 28 adult rabbits. From 6 h to 6 weeks after induction of arthritis, the topology of TNF-alpha and IL-8 was observed. RESULTS: Positive reaction for TNF-alpha of synovial cells was observed within 3 days after induction and at 3 weeks after induction. TNF-alpha positive vascular endothelial cells and chondrocytes were identified throughout the observation period. IL-8 was detected only during the acute stage. CONCLUSIONS: The cytokines TNF-alpha and IL-8 were observed in specific cells depending on the stage. TNF-alpha was particularly related with angiogenesis and cartilage destruction and IL-8 was involved in the acute stage of inflammation.

Morphological evaluation of changes in velopharyngeal function following maxillary distraction in patients with repaired cleft palate during mixed dentition.

OBJECTIVE: To describe the morphological changes of nasopharyngeal components after maxillary distraction and clarify whether the morphological characteristics are related to velopharyngeal function (VPF). DESIGN: Perceptual judgments of hypernasality and nasendoscopy were performed before and after treatment. Lateral cephalograms were obtained to describe the morphological changes. SETTING: Department of Oral and Maxillofacial Surgery, Miyazaki Medical College, Miyazaki, Japan. PARTICIPANTS: Nine patients with repaired cleft palate in the mixed dentition stage underwent maxillary distraction using a face mask and an intraoral fixed appliance system. OUTCOME MEASURES: The severity of hypernasality, velopharyngeal insufficiency, and measurements such as pharyngeal depth, velar length, and the rotation of the palatal plane were evaluated. RESULTS: Increase in pharyngeal depth was not always proportional to the amount of advancement. It depended on the posture of the posterior pharyngeal wall and the rotation of palatal plane. CONCLUSION: Cephalometric measurements of the nasopharynx before and after surgery confirmed subsequent changes in VPF. These were suggested to be useful in predicting future VPF. When performing maxillary distraction in patients with cleft palate in the mixed dentition stage, and when velopharyngeal closure is found to occur by velar contact against the hypertrophied adenoid, patients should be counseled about risks of subsequent deterioration in their speech before surgery.

Delivery of cytolethal distending toxin B induces cell cycle arrest and apoptosis in gingival squamous cell carcinoma in vitro.

The cytolethal distending toxin (Cdt) from Actinobacillus actinomycetemcomitans consists of three proteins, CdtA, CdtB, and CdtC, which are responsible for cell cycle arrest and apoptosis. In the present study, local delivery systems of recombinant CdtB and CdtB-expressing plasmid were established using Ca9-22, human gingival squamous cell carcinoma cell line. When CdtB was delivered to Ca9-22 cells using a BioPORTER, a 32-kDa protein was detected by Western blotting, and G2 cell cycle arrest and apoptosis occurred. In addition, the CdtB delivered upregulated the expression of phosphorylated p53 and the cyclin-dependent kinase inhibitor p21(CIP1/WAF1) in Ca9-22 cells, suggesting that these intracellular molecules might contribute to the induction of G2 cell cycle arrest and apoptosis. When the CdtB-expressing plasmid was transfected into Ca9-22 cells by lipofection or electroporation, CdtB (32 kDa) was clearly detected. Further, TdT-mediated dUTP nick end labeling positive cells were observed after transfection of the CdtB-expressing plasmid. These findings indicated that delivery of the CdtB protein and transfection of the cdtB gene induced cell cycle arrest and apoptosis in Ca9-22 cells in vitro, and we conclude that it may be possible to induce apoptosis in human gingival squamous cell carcinoma by electroporation of the cdtB gene.

Hypercalcemia associated with parathyroid hormone-related protein at the terminal stage of uncomplicated squamous cell carcinoma in the head and neck region.

BACKGROUND: Parathyroid hormone-related protein (PTHrP) is mainly responsible for hypercalcemia in squamous cell carcinomas (SCCs). METHODS: We retrospectively checked the appearance of hypercalcemia among 33 patients who died with head and neck SCC. Serum concentrations of C-terminal region of PTHrP (C-PTHrP) were measured in 15 of them. The intracellular PTHrP expression was immunohistochemically stained in 42 SCC sections obtained from the 33 before the appearance of hypercalcemia. RESULTS: Hypercalcemia appeared in 24 of the 33, and increased serum C-PTHrP levels were confirmed in 11 of 12 hypercalcemic patients. PTHrP was identified in all SCC sections, and a stronger intensity than in normal squamous epithelia was observed in 50% of those obtained within 1 year before the onset of hypercalcemia. CONCLUSION: A high incidence of PTHrP-induced hypercalcemia was shown among patients dying with head and neck SCCs. The intracellular increase in PTHrP might be observed preceding hypercalcemia.