OBJECTIVE: In our previous study, glass-fiber-reinforced plastics (GFRPs) made from polycarbonate and glass fibers were prepared for esthetic orthodontic wires using pultrusion. These laboratory GFRP wires are more transparent than the commercially available nickel-titanium wire; however, an investigation of the color stability of GFRP during orthodontic treatment is needed. Accordingly, in the present study, the color stability of GFRP was assessed using colorimetry. METHODS: Preparation of GFRP esthetic round wires (diameter: 0.45 mm [0.018 inch]) using pultrusion was described previously. Here, to investigate how the diameter of fiber reinforcement affects color stability, GFRPs were prepared by incorporating either 13-microm (GFRP-13) or 7-microm glass (GFRP-7) fibers. The color changes of GFRPs after 24 h, and following 1, 2, and 4 weeks of coffee immersion at 37degrees C, were measured by colorimetry. We evaluated the color stability of GFRPs by two evaluating units: the color difference (DeltaE*) and National Bureau of Standards (NBS). RESULTS: After immersion, both GFRPs showed almost no visible color change. According to the colorimetry measurements, the DeltaE* values of GFRP-13 and GFRP-7 were 0.73-1.16, and 0.62-1.10, respectively. In accordance with NBS units, both GFRPs showed "slight" color changes. As a result, there were no significant differences in the DeltaE* values or NBS units for GFRP-13 or GFRP-7. Moreover, for both GFRPs, no significant differences were observed in any of the immersion periods. CONCLUSIONS: Our findings suggest that the GFRPs will maintain high color stability during orthodontic treatment, and are an attractive prospect as esthetic orthodontic wires.
Coffee ; Colorimetry ; Esthetics ; Glass ; Immersion ; Orthodontic Wires* ; Plastics*

OBJECTIVE: Root mobility due to reciprocating movement of the tooth (jiggling) may exacerbate orthodontic root resorption (ORR). "Jiggling" describes mesiodistal or buccolingual movement of the roots of the teeth during orthodontic treatment. In the present study, buccolingual movement is described as "jiggling." We aimed to investigate the relationship between ORR and jiggling and to test for positive cell expression in odontoclasts in resorbed roots during experimental tooth movement (jiggling) in vivo. METHODS: Male Wistar rats were divided into control, heavy force (HF), optimal force (OF), and jiggling force (JF) groups. The expression levels of cathepsin K, matrix metalloproteinase (MMP)-9 protein, interleukin (IL)-6, cytokine-induced neutrophil chemoattractant 1 (CINC-1; an IL-8-related protein in rodents), receptor activator of nuclear factor κB ligand (RANKL), and osteoprotegerin protein in the dental root were determined using immunohistochemistry. RESULTS: On day 21, a greater number of root resorption lacunae, which contained multinucleated odontoclasts, were observed in the palatal roots of rats in the JF group than in rats from other groups. Furthermore, there was a significant increase in the numbers of cathepsin K-positive and MMP-9-positive odontoclasts in the JF group on day 21. Immunoreactivities for IL-6, CINC-1, and RANKL were stronger in resorbed roots exposed to jiggling than in the other groups on day 21. Negative reactivity was observed in the controls. CONCLUSIONS: These results suggest that jiggling may induce ORR via inflammatory cytokine production during orthodontic tooth movement, and that jiggling may be a risk factor for ORR.
Animals ; Cathepsin K ; Cathepsins ; Humans ; Immunohistochemistry ; Interleukin-6 ; Interleukins ; Male ; Models, Animal* ; Neutrophils ; Osteoclasts ; Osteoprotegerin ; Rats* ; Rats, Wistar ; Risk Factors ; Root Resorption* ; Tooth Movement* ; Tooth*

OBJECTIVE: To determine the interleukin (IL)-6 levels in gingival crevicular fluid (GCF) of patients with severe root resorption after orthodontic treatment and investigate the effects of different static compressive forces (CFs) on IL-6 production by human periodontal ligament (hPDL) cells and the influence of IL-6 on osteoclastic activation from human osteoclastic precursor (hOCP) cells in vitro. METHODS: IL-6 levels in GCF samples collected from 20 patients (15 and 5 subjects without and with radiographic evidence of severe root resorption, respectively) who had undergone orthodontic treatment were measured by ELISA. The levels of IL-6 mRNA in hPDL cells and IL-6 protein in conditioned medium after the application of different uniform CFs (0, 1.0, 2.0, or 4.0 g/cm2 for up to 72 h) were measured by real-time PCR and ELISA, respectively. Finally, the influence of IL-6 on mature osteoclasts was investigated by using hOCP cells on dentin slices in a pit-formation assay. RESULTS: Clinically, the IL-6 levels were significantly higher in the resorption group than in the control group. In vitro, IL-6 mRNA expression significantly increased with increasing CF. IL-6 protein secretion also increased in a time- and magnitude-dependent manner. Resorbed areas on dentin slices were significantly greater in the recombinant human IL-6-treated group and group cultured in hPDL cell-conditioned medium with CF application (4.0 g/cm2) than in the group cultured in hPDL cell-conditioned medium without CF application. CONCLUSIONS: IL-6 may play an important role in inducing or facilitating orthodontically induced inflammatory root resorption.
Culture Media, Conditioned ; Dentin ; Enzyme-Linked Immunosorbent Assay ; Gingival Crevicular Fluid ; Humans* ; Interleukin-6* ; Interleukins ; Osteoclasts ; Periodontal Ligament ; Real-Time Polymerase Chain Reaction ; RNA, Messenger ; Root Resorption*

OBJECTIVE: Orthodontic root resorption (ORR) due to orthodontic tooth movement is a difficult treatment-related adverse event. Caspases are important effector molecules for apoptosis. At present, little is known about the mechanisms underlying ORR and apoptosis in the cementum. The aim of the present in vivo study was to investigate the expression of tartrate-resistant acid phosphatase (TRAP), caspase 3, caspase 8, and receptor activator of nuclear factor kappa-B ligand (RANKL) in the cementum in response to a heavy or an optimum orthodontic force. METHODS: The maxillary molars of male Wistar rats were subjected to an orthodontic force of 10 g or 50 g using a closed coil spring. The rats were sacrificed each experimental period on days 1, 3, 5, and 7 after orthodontic force application. And the rats were subjected to histopathological and immunohistochemical analyses. RESULTS: On day 7 for the 50-g group, hematoxylin and eosin staining revealed numerous root resorption lacunae with odontoclasts on the root, while immunohistochemistry showed increased TRAP- and RANKL-positive cells. Caspase 3- and caspase 8-positive cells were increased on the cementum surfaces in the 50-g group on days 3 and 5. Moreover, the number of caspase 3- and caspase 8-positive cells and RANKL-positive cells was significantly higher in the 50-g group than in the 10-g group. CONCLUSIONS: In our rat model, ORR occurred after apoptosis was induced in the cementum by a heavy orthodontic force. These findings suggest that apoptosis of cementoblasts is involved in ORR.
Acid Phosphatase ; Animals ; Apoptosis ; Caspase 3 ; Caspase 8 ; Caspases* ; Dental Cementum ; Eosine Yellowish-(YS) ; Hematoxylin ; Humans ; Immunohistochemistry ; Male ; Models, Animal ; Molar ; Osteoclasts ; Rats ; Rats, Wistar ; Root Resorption* ; Tooth Movement

We reported nine cases of metastatic skin carcinoma experienced at the Department of Dermatology, Obihiro Kosei Hospital during the period from April 1991 to March 1993. Lung was the most common primary lesion (four out of nine cases), followed by uterus (two) and stomach, breast, and kidney (one each). The clinical features of the metastases were classified into nodular (five cases), inflammatory (one case) and sclerotic (three cases) types. Peculiar zoster-like inflammation was seen in metastatic gastric cancer. Pathologically, adenocarcinoma was more common than squamous cell carcinoma. The average interval between the diagnosis of the primary cancers and the development of the skin metastases was about 30±25 months. The average life span after the detection of the skin metastases was 6.8±5.6 months. Poor prognosis of skin metastasis was thus reconfirmed.

Background: The anti-programmed death 1 (PD-1) antibody has led to durable clinical responses in a wide variety of human tumors. We have previously developed the caninized anti-canine PD-1 antibody (ca-4F12-E6) and evaluated its therapeutic properties in dogs with advance-staged oral malignant melanoma (OMM), however, their therapeutic effects on other types of canine tumors remain unclear. Objective: The present clinical study was carried out to evaluate the safety profile and clinical efficacy of ca-4F12-E6 in dogs with advanced solid tumors except for OMM. Methods: Thirty-eight dogs with non-OMM solid tumors were enrolled prospectively and treated with ca-4F12-E6 at 3 mg/kg every 2 weeks of each 10-week treatment cycle. Adverse events (AEs) and treatment efficacy were graded based on the criteria established by the Veterinary Cooperative Oncology Group. Results: One dog was withdrawn, and thirty-seven dogs were evaluated for the safety and efficacy of ca-4F12-E6. Treatment-related AEs of any grade occurred in 13 out of 37 cases (35.1%).Two dogs with sterile nodular panniculitis and one with myasthenia gravis and hypothyroidism were suspected of immune-related AEs. In 30 out of 37 dogs that had target tumor lesions, the overall response and clinical benefit rates were 6.9% and 27.6%, respectively. The median progression-free survival and overall survival time were 70 days and 215 days, respectively. Conclusions The present study demonstrated that ca-4F12-E6 was well-tolerated in nonOMM dogs, with a small number of cases showing objective responses. This provides evidence supporting large-scale clinical trials of anti-PD-1 antibody therapy in dogs.

We have previously reported on a predictive model for deficiency-excess pattern diagnosis that was unable to predict the medium pattern. In this study, we aimed to develop predictive models for deficiency, medium,and excess pattern diagnosis, and to confirm whether cutoff values for diagnosis differed between the clinics. We collected data from patients' first visit to one of six Kampo clinics in Japan from January 2012 to February 2015. Exclusion criteria included unwillingness to participate in the study, missing data, duplicate data, under 20 years old, 20 or less subjective symptoms, and irrelevant patterns. In total, 1,068 participants were included. Participants were surveyed using a 153-item questionnaire. We constructed a predictive model for deficiency, medium, and excess pattern diagnosis using a random forest algorithm from training data, and extracted the most important items. We calculated predictive values for each participant by applying their data to the predictive model, and created receiver operating characteristic (ROC) curves with excess-medium and medium-deficiency patterns. Furthermore, we calculated the cutoff value for these patterns in each clinic using ROC curves, and compared them. Body mass index and blood pressure were the most important items. In all clinics, the cutoff values for diagnosis of excess-medium and medium-deficiency patterns was > 0.5 and < 0.5, respectively. We created a predictive model for deficiency, medium, and excess pattern diagnosis from the data of six Kampo clinics in Japan. The cutoff values for these patterns fell within a narrow range in the six clinics.