Brief exposure of volatile anesthetics before prolonged ischemia exerts cardioprotective effects mimicking ischemic preconditioning (Anesthetic preconditioning: APC). We previously reported that in contrast to isoflurane-induced myocardial preconditioning, phosphatidylinositol-3-kinase (PI3K)/Akt signaling, which plays a central role in the reperfusion injury salvage kinase cascade, was not involved in sevoflurane-induced preconditioning. Mitogen-activated protein kinases such as extracellular signal-regulated kinase 1/2 (ERK) and stress-activated protein kinase/c-Jun NH 2-terminal kinase (JNK) have also been implicated in APC. The mitogen-activated protein kinase (MEK)/ERK pathway is another reperfusion salvage kinase pathway in ischemic preconditioning. It remains unclear whether this signaling cascade is involved in sevoflurane-induced preconditioning. Isolated perfused guinea pig hearts were subjected to 30min global ischemia and 120min reperfusion (Control group: CTL). Sevoflurane-induced preconditioning was elicited by administration of sevoflurane for 10min at one minimum alveolar concentration with 10min washout before ischemia (Sevoflurane group: SEVO). Contractile recovery was monitored by left ventricular developed pressure (LVDP) and left ventricular end-diastolic pressure (LVEDP). Infarct size was determined by triphenyltetrazolium chloride stain. Phosphorylation of ERK and JNK were assessed by western blot. After ischemia-reperfusion, SEVO had higher LVDP and lower LVEDP than CTL. Infarct size was significantly reduced in SEVO compared to CTL (42±5% vs 21±6%). Phosphorylation of ERK at 10min after reperfusion was significantly increased compared with CTL. Phosphorylation of JNK was the same for the two groups. The MEK/ERK pathway was more important than PI3/Akt signaling in sevoflurane-induced preconditioning.

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We assessed the psychological impact of orthognathic surgery on 13 male and 19 female patients with dento-facial deformities who were between 17 and 35 years of age. MINI automated psychological tests (Gakken Tosyo, Inc., Tokyo) were used to measure the psychological status of each patient before and after surgery. The data was collected and analyzed, and the difference between each score over two periods was determined. We found that more than 50% of the patients had improved scores after surgery. Positive outcomes were seen in 84% of the females and 75% of the males based on the Si score. Fewer showed changes on the D score than on other scores. Positive psychological changes were more common in female patients. There were significant differences in scores on the Pd, Pa, Pt and Si Scales.
These findings suggested that orthognathic surgery can improve a patient's psychological state, especially in interpersonal relationships. The survey showed that treatment was more likely to improve the psychological outcome for females.

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This study was performed to clarify the mechanism of generating retentive force in the electroformed telescope crown. The inner crowns were made of gold alloy with 0゜, 2゜, 4゜ and 6゜ taper and five outer crowns were made by electroforming on the inner crown. We measured the retentive force and the negative pressure generated between the inner and outer crowns with glycerin solution of different viscosity instead of saliva during removal of the outer crown of the electroformed telescope in order to evaluate the relation between retentive force, negative pressure and the viscosity of saliva. The peak retentive force was significantly greater at glycerin concentration of 20% or greater, when compared with no solution. The increase in maximum negative pressure was greater at 0゜ and 2゜ than at 4゜ and 6゜, and greater increases were observed with glycerin concentrations of 60% and 80% compared with lower concentrations. At 2゜, the retentive force did not increase significantly as the concentration increased when holes were present in the outer crowns. However, when there were no holes, significant increases in the peak retentive force were observed at 60% and 80% glycerin concentration compared with no solution. The above findings suggest that the viscosity of saliva and the negative pressure generated between the inner and outer crowns increases the retentive force effectively in a 2゜ tapered electroformed telescope.

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We analyzed and investigated the relationship of maxillofacial morphology with the volume and axial inclination of the medial pterygoid muscle in 23 adult males of average age 26 years, who were diagnosed with skeletal mandibular prognathism at the Osaka Dental University Hospital. Various maxillofacial parameters were measured in the frontal and lateral cephalograms of each subject. Also, using head MRI, the medial pterygoid muscle was reconstructed in three dimensions and its volume and axial inclination were ascertained. Using these data, correlation analysis was conducted at the 5% significance level. When the mandible was inclined laterally, analysis in the coronal plane showed no significant correlation between maxillofacial morphology and the asymmetry index for the volume (Al-volume). Also, a greater asymmetry index for the inclination (Al-inclination) resulted in a greater Ag line angle and a greater distance of ORP to Me. Furthermore, rotation of the mandible did not significantly change the relationship between maxillofacial morphology and asymmetry in volume and inclination. Analysis in the sagittal plane showed that the greater the muscle volume, the greater the A-B plane angle; and the greater the anterior axial inclination, the greater the posterior facial height. However, a greater anterior axial inclination caused a smaller FMA, FH-occlusal plane angle and SN-GoGn. This implies that in patients with skeletal mandibular prognathism, the type of mandibular displacement affects the axial inclination of the medial pterygoid muscle. Also, the results suggest that the axial inclination of the medial pterygoid muscle correlates to the inclination of the occlusal and mandibular planes.

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We investigated the mRNA expression of osteoprotegerin, receptor activator of nuclear factor-_κB (RANK) and RANK ligand (RANKL) in human leukemia cell lines. When the cells took on a macrophage-like morphology after treatment with a phorbol ester, mRNA for osteoprotegerin was clearly induced. In contrast, RANK or RANKL mRNA expression did not change significantly.
Considering that monocytic leukocytes are often found in periodontitis and osteoprotegerin inhibits maturation of osteoclast precursor cells into osteoclasts, our data suggest that differentiation of monocytes into macrophages in periodontitis may prevent local osteoclastogenesis. This could be a defensive mechanism against bone resorption during the course of periodontitis.

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We investigated the effect of risedronate pre-dosage on healing of the tooth extraction socket in ovariectomized rats. The formation of new bone and osteoid tissue was examined over time using histological findings and statistical processing. Thirty-six, 8 weeks old female Wistar rats were divided into: a sham operation (Sham) group, an ovariectomized (OVX) group, and a risedronate pre-dosage after ovariectomy (Ris) group of 12 animals each. On days 3, 7, 14 and 28 after tooth extraction, we measured the percentage of the area of new bone, and the percentage of the area of new bone occupied by osteoid. We found that the percentage new bone formation was significantly lower in ovariectomized rats than in the non-ovariectomized animals, throughout the study regardless of whether risedronate was injected. The effect of risedronate pre-dosage in ovariectomized rats was not apparent until 7 days after the extraction, and it increased the percentage of the amount of mature bone to that of new bone formed within the extraction socket at 14 days. These results suggest that risedronate pre-dosage affects healing of the extraction socket in ovariectomized rats.

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We investigated the influence of propofol, which has peripheral vasodilative action, on vascular absorption of local anesthetics in an animal experiment. Propofol was infused intravenously in 18 rabbits at a rate of 45 mg/kg/h to achieve sedation under spontaneous respiration. Lidocaine (6 mg/kg) was used as the local anesthetic. The rabbits were randomly divided into three groups of six animals each and received submucosal infiltration of the following drugs in the lower lip: lidocaine without adrenalin (Group L), lidocaine with 1:160,000 adrenalin (Group LA-L), or lidocaine with 1:80,000 adrenalin (Group LA-H). Arterial blood lidocaine concentrations were measured at regular intervals. The plasma lidocaine concentrations of Group LA-L and Group LA-H were lower than those of Group L for the first 30 minutes after administration. These results suggest that sustaining the vascular absorption inhibition effect of adrenalin was caused by vasoconstriction despite propofol administration. On the other hand, no difference was observed in plasma lidocaine concentrations between Group LA-L and Group LA-H, suggesting that both had a similar degree of vascular absorption. In conclusion, propofol is thought to have peripheral vasodilative action that offsets the concentration-dependent vasoconstriction of adrenalin.

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We investigated the changes in regional cerebral blood flow and myocardial blood flow during hyperventilation. Japanese white rabbits were anesthetized with a mixture of 50% oxygen and 50% nitrous oxide with 1.0% sevoflurane. Hyperventilation (with hypocapnia) was induced by adjusting the ventilation to achieve a PaCO₂ of 25〜30 mmHg. Following hypocapnia, normocapnia was attained by loading CO₂ gas without changing the conditions of ventilation to increase PaCO₂ to 40〜45 mmHg. Blood flow in the cerebral cortex, cerebellum, thalamus, pons, hippocampus, right ventricle, and left ventricle were measured using the colored microsphere method in each rabbit during hypocapnia and 30 minutes after establishing normocapnia. The findings during hypocapnia and normocapnia were compared.
Blood flow in the cerebral cortex and the cerebellum during hypocapnia was lower than during normocapnia, while myocardial blood flow was not affected by PaCO₂. These findings suggest that changes in blood flow in the cerebral cortex and cerebellum contribute to a large extent to the decrease in cerebral blood flow leading to loss of consciousness in patients with hyperventilation syndrome.

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We examined the expression of the human papillomaviruses (HPV), p53, mutant type p53, Rb and p16 in oral dysplasia and oral squamous cell carcinoma (SCC). We used 10 samples each of irritation fibroma (IF), low grade dysplasia (LGD), high grade dysplasia (HGD) and SCC obtained from Osaka Dental University Hospital. We detected the DNA of HPV-16 and -18 by polymerase chain reaction (PCR) and the mRNA of HPV by in situ hybridization (ISH). We also studied the immunohistochemical expression of p53, mutant type p53, Rb and p16. HPV-16 was detected in almost all cases of LGD and SCC, but in no cases of ISH. Marked expression of mutant type p53 and Rb was seen in HPV-16 positive LGD and SCC. HPV infections were detected by PCR in almost all cases of HGD and SCC. Specimens that showed over expression of mutant type p53 and Rb were almost all positive for HPV-16. These results suggest that HPV-16 may play an important role in the transformation of p53 and Rb.

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We quantified the degree of discomfort induced by plates of different thicknesses placed under an experimental acrylic plate (exp. plate) covering the palatal mucosa in an attempt to model ill-fitting dentures. Both salivary cortisol concentration and α-amylase activity were measured in response to the discomfort caused by varying localized pressure on the experimental acrylic plate. Nineteen healthy subjects with an average age of 25±2 years were included in this study. All subjects were seated and examined under the five experimental conditions of N (not wearing an exp. plate), D (wearing an exp. plate), DP 1 (wearing an exp. plate with a 0.1-mm-thick localized pressure plate), DP 2 (wearing an exp. plate with a 0.2-mm-thick localized pressure plate) and DP 3 (wearing an exp. plate with a 0.5-mm-thick localized pressure plate). Subjects were then asked to complete a Visual Analogue Scale (VAS) during each condition. Saliva samples were collected at 0, 5, 10, 15 and 20 min after the start of each condition. Cortisol concentration and α-amylase activity were measured using enzyme-linked immunosorbent assay and kinetic analysis. Salivary cortisol concentration and α-amylase activity significantly increased as the pain and discomfort resulting from localized pressure increased. Cortisol concentration and α-amylase activity for condition D were significantly greater than that for N. Although the pain score, as measured by VAS, was the same for conditions N and D, significant differences in discomfort were found between N and D. We concluded that the severity of palatal mucosa stimulation and discomfort may be objectively assessed using salivary cortisol concentration and α-amylase activity.

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It is known that the N-methyl-D-aspartate (NMDA) receptor is important for learning/memory capability and neuropathic pain. Although it has been reported that NMDA receptor antagonists cause learning/memory disorders, they are effective for neuropathic pain. We investigated the relation between the NMDA receptor and learning/memory capability using neuropathic pain chronic constriction injury (CCI) model rats on the 8-arm radial maze and the step-through type passive avoidance apparatus. The CCI model rats performed better on the tests than either the normal animals or those that had received NMDA receptor antagonists. These findings suggest that the neuropathic pain of the CCI rats raised their learning/memory ability through the NMDA receptor.

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We investigated the relation between periodontal tissue and type 2 diabetes mellitus and attempted to clarify the distribution of osteoclasts, macrophages, collagens and blood capillaries in periodontal tissue with the diabetes. We immunohistochemically examined CD68-positive cells, type 3 and type 4 collagens, and enzyme histochemically examined TRAP-positive cells in the periodontal tissues of the Goto-Kakizaki (GK) rat, which is a type 2 diabetes model rat. Wistar rats were used as controls.
There were many macrophages and osteoclasts in the periodontal tissue of the diabetes mellitus rats at 2 months of age (DM-2M), whereas localization of type 3 collagen was the same as in the controls. There was an increased tendency for localization of type 4 collagen in the experimental animals compared DM-2M with the controls (NDM-2M). These results suggest that diabetes plays an important role as a risk factor for periodontitis.

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In order to understand the differences in cell-cycle progression between well differenciated squamous cell carcinomas (SCC) and mucoepidermoid carcinomas (MEC) we examined formalin-fixed, paraffin-embedded sections of 27 SCCs and 22 MECs immunohistochemically with anti-human p53, p21, p27, cyclin D 1 and thymidylate synthase (TS) antibodies. The sections were stained with DAB and hematolyin. Positivities of p53, p21 cyclin D 1, and TS in SCC were greater than in MEC. On the other hand, p27 positivity was greater in MEC. These results indicate that MEC has fewer p53 mutations or damaged DNA, many cells in MEC are arrested in the G₀ phase by p27 and rarely progress to the S phase in comparison with SCC.

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There are several methods for regeneration of periodontal tissue damaged by periodontal disease. Although use of enamel matrix derivative (EMD) is one of the most effective, its mechanism is not well understood. The present study was designed to elucidate the mechanism of EMD. We explored how the proliferation, differentiation and gene expression of human periodontal ligament fibroblasts (HPdLF) are influenced by synthetic peptides derived from EMD. In addition, we carried out probe-target hybridization labeled by fluorophore to the expressed target genes and their microarray analysis. The amount of HPdLF cell DNA was increased and alkaline phosphatase activity was decreased during culture in the medium with synthetic peptides. A total number of 28,563 instances of gene expression were observed. Microarray analysis showed that although bone morphogenetic protein (BMP) receptor type 1 A, BMP 4, osteonectin, and BMP receptor type 1 B gene expression were increased, fibroblast growth factor receptor-like protein 1 gene was decreased. Thus, microarray analysis showed that the expression of genes related to osteogenesis was increased with the use of the peptides. The present results indicate that the peptide derived from EMD is effective in periodontal tissue regeneration.

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During anesthesia, muscarinic parasympathetic antagonists can be used as a preoperative medication on order to reduce salivary flow, tracheobronchial secretions, and pharyngeal secretions, as well as to decrease the acidity of gastric secretions. We did an in vivo study to examine whether muscarinic receptor subtypes play a role in the exocrine function of the rat submandibular gland. The effects of muscarinic antagonists (pirenzepine, methoctramine, 4-diphenylacetoxy-N-dimethylpiperidinium (4-DAMP) and glycopyrrolate) were examined on secretion from the submandibular gland evoked by acetylcholine in pentobarbital-anesthetized rats. Glycopyrrolate caused less elevation in heart rate than the other anticholinergics. 4-DAMP and glycopyrrolate markedly inhibited the acetylcholine-evoked fluid responses.
Pirenzepine showed significantly lower inhibitory potency than 4-DAMP or glycopyrrolate, while methoctramine had even less of an inhibitory effect. Pirenzepine, 4-DAMP and glycopyrrolate significantly inhibited both protein concentration and amylase activity in the acetylcholine-evoked submandibular saliva, while methoctramine did not affect the responses. The reduction of the protein concentration and amylase activity in submandibular saliva caused by pirenzepine, 4-DAMP and glycopyrrolate were inhibited by N^G-nitro-L-arginine methyl ester (L-NAME). Thus, it might be effective to administer anti-cholinergic drugs together with L-NAME as premedication. These results suggest that glycopyrrolate significantly decreases salivary secretion, and has significantly fewer side effects than other muscarinic parasympathetic antagonists. Further controlled studies are required to determine the safety, efficacy and patient tolerance of glycopyrrolate.

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