We administered tetrodotoxin (TTX) to the rat neuropathic pain model, and investigated changes in neuropathic pain behavior. One hour after administration by intraperitoneal injection of 1 μg/kg, the mechanical hyperesthesia response time was prolonged compared to the pretreatment value, indicating exacerbation of symptoms. In contrast, the response time was shortened one hour after intraperitoneal administration of TTX at 3μg/kg, indicating improvement in the symptoms. Intraperitoneal injection of both 1μg/kg and 3μg/kg prolonged the cold allodynia response time one hour after administration compared to the pretreatment value. However, three hours after administration, the response time was shortened for the 3μg/kg dose. Administration of 1 ng/kg teirodotoxin in the main sciatic nerve improved cold allodynia for four days. Both systemic and local administration improved neuropathic pain behavior. Therefore, tetrodotoxin-sensitive sodium channels should be further investigated.(J Osaka Dent Univ 2003; 37: 99-102.)

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We investigated the relationship between proliferation and mutation of tumor-suppresive genes in oral verrucous carcinomas (n=16), papillomas (n=8), and hyperkeratosis (n=7). Double staining for histone H3 mRNA and p53 protein was carried out in formalin-fixed, paraffin-embedded sections. In the paraffin sections (4μm), histone H3 mRNA and p53 protein were detected in the cytoplasm and nucleus, respectively. However, double expression of histone H3 mRNA and p53 protein was not found in hyperkeratosis. Increased expression of histone H3 mRNA and p53 protein was seen in the basal cell layer of the papilloma sections. In verrucous carcinoma, co-expression of histone H3 mRNA and p53 protein increased not only in the basal cell layer, but also in the spinous cell region. These results indicate that proliferative and aberrant cellular activities characteristically increase in large areas of verrucous carcinoma.(J Osaka Dent Univ 2003; 37: 103-107.)

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The purpose of this study was to investigate oral environmental risk factors involved in caries incidence in the elderly. The subjects were 91 elderly subjects with fixed prostheses and 65 who wore removable partial dentures. We examined oral environmental factors by medical interview, clinical examination and saliva tests. The following 11 oral environmental factors were judged to be related to caries incidence: number of medicines taken daily, frequency of meals, frequency of brushing, amount of plaque on natural teeth, stimulated and unstimulated salivary flow rate, stimulated and unstimulated salivary buffer capacity, and salivary microbial counts of Streptococcus mutans (SM), Lacto-bacilli (LB) and Candida (CA). We compared these factors for subjects with fixed prostheses (the fixed group) and those wearing removable partial dentures (the denture group). Significant differences were observed between the two groups in plaque adhesion on the natural teeth and salivary microbial counts of SM, LB and CA. These finding demonstrate the importance of carefully selecting a prosthetic appliance for elderly by taking into consideration of oral hygienic conditions and salivary microbial counts. We found that fixed prostheses are less cariogenic. (J Osaka Dent Univ 2003; 37: 109-114.)

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We previously a rat sciatic neuropathy model using paclitaxel developed cold-allodynia. Cold-allodynia is thought to result from degradation of Aδ or C fibers. We investigated which nerves are involved by measuring thermal hyperalgesia. Thermal hyperalgesia did not develop and the C fibers appeared normal. Based on our findings, local administration of paclitaxel caused nerve degeneration of only myelinated Aδ and Aβ fibers, such as demyelination. The effect on unmyelinated nerves (C fibers) may be low. (J Osaka Dent Univ 2003; 37: 115-117.)

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Hepatocyte growth factor (HGF), a multifunctional cytokine produced by mesenchymal cells, is known to mediate the mesenchymal-epithelial interaction in a paracrine manner. Little is known about the direct effect of the factor on the function of mesenchymal cells. We investigated mRNA expression of type I collagen and decorin in human gingival fibro-blasts stimulated by HGF. Quantitative analysis using a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) detection system demonstrated that HGF increased both the mRNA expression levels for type I collagen and for decorin in cultured gingival fibroblasts. The mRNA expression of decorin was increased significantly (p<0.05) 12h after HGF stimulation, and then that of type I collagen was markedly increased (p<0.01) at 24 h. These results suggest that HGF is likely to directly accelerate the extracellular matrix production by gingival fibroblasts. (J Osaka Dent Univ 2003; 37: 119-122.)

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Matrix metalloproteinase-3 (MMP-3, stromelysin) is known to degrade certain matrix components, including proteoglycans, fibronectin, laminin and collagens. We investigated the early signs of cartilage degradation by assaying MMP-3 in the synovial fluid of human temporomandibular joints with internal derangement (ID) or osteoarthritis (OA). Synovial fluid was collected from the upper joint space by direct aspiration (nondiluted synovial fluid) or by pumping with lidocaine (diluted synovial fluid). MMP-3 was visualized by casein enzymography and measured by one-step sandwich enzyme immunoassay using an anti-human MMP-3 antibody that recognizes both active enzyme and inactive proenzyme. The concentration of MMP-3 with ID in both diluted and non-diluted synovial fluid was significantly greater than that with OA or in the asymptomatic controls (p<0.001). Enzymatically active components were detected in the non-diluted synovial fluid, but not in the diluted synovial fluid. Active MMP-3 was detected only in the nondiluted synovial fluid with OA, while inactive MMP-3 was observed in the non-diluted synovial fluid both with ID and with OA. These results indicate that MMP-3 may be released as proenzyme into the synovial fluid during the early stages of degenerative changes in the TMJ. Subsequently, progressive TMJ destruction may induce the release of active MMP-3. We concluded that MMP-3 assay using synovial fluid may be a useful marker for the diagnosis of TMJ disorders. (J Osaka Dent Univ 2003; 37: 123-127.)

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We studied how one stage prosthetic treatment (immediate and early placement of prostheses) and two stage (delayed placement of prostheses) affected implants. We used the two dimensional finite element method (FEM) of analysis to investigate the effect of several different prostheses on the stress distribution in implants, teeth and the supporting bone. We also analyzed data from an electronic dynamometer apparatus to clinically measure the forces on the dental implants during the healing phase. The FEM indicated that there were low compressive stresses with bridges made of acrylic materials. These stresses were even lower when we used a new design removable fixed prosthesis. Results obtained using the electronic ignatodynamometer apparatus indicated that the masticatory forces on the implants during healing were different for the maxilla and mandible, and for males and females. In addition, the forces gradually increased during healing, which continued for three to six months. We concluded that immediate and early loading of dental implants was possible and beneficial when a special removable fixed temporary prosthesis was placed during the healing period. This technique significantly shortens the treatment period. (J Osaka Dent Univ2003; 37: 129-133.)

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Since the mandibular position during the first phase of swallowing in edentulous patients with complete dentures essentially corresponds to the intercuspal position, the swallowing method has been used clinically for determining intercuspal position. However, occlusal force varies depending on the shape of the intermaxillary wax occlusal rims used during the measurements, causing changes in the jaw position. We measured the contact pressure between the maxillary and mandibular occlusal rims in the appropriate intercuspal position during swallowing to obtain an objective evaluation index for determining occlusal vertical dimension. We also evaluated the occlusal force during swallowing in normal dentulous subjects by changing the vertical dimension of occlusion. We found that the mean occlusal force during swallowing in intercuspal position for the subjects we studied was 96.8±40.0 N, and that changes in the vertical dimension significantly affected the occlusal force during swallowing. (J Osaka Dent Univ 2003; 37: 135-139.)

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