Comparison of food mixing ability among mandibulectomy patients.

Many papers have been published on surgical mandibulectomy and reconstruction. However, only a few reports refer to masticatory function after prosthodontic treatment in mandibulectomy patients. The aim of this study was to investigate the masticatory function of mandibulectomy patients. Twenty-three subjects (10 males and 13 females, with an average age of 63 years) participated in this study: 11 subjects who had undergone unilateral marginal mandibulectomy, six subjects with unilateral segmental mandibulectomy with reconstruction and six subjects with hemimandibulectomy without reconstruction. Mixing Ability Index (MAI) was used to measure masticatory function on the non-defect side and on the defect side with a prosthesis installed. Comparisons were carried out among the marginal, segmental and hemimandibular groups and between the non-defect side and the defect side. Consequently, our study indicates these results. On the non-defect side, a significant difference was found between the marginal and the segmental groups, and between the marginal and the hemimandibular groups. In the marginal and the segmental groups, a significant difference was found between the non-defect and the defect sides. In conclusion, our study suggests that MAI is an adequate tool to study the masticatory function in mandibulectomy patients, the masticatory function of the mandibulectomy patients is more impaired than that of the ordinary removable partial denture patients, and that surgical intervention affects the masticatory function on not only the defect side but also the non-defect side in mandibulectomy patients.

The vibratory characteristics of obturators with different bulb height and form designs.

The aim of the present study was to investigate whether the vibratory characteristics of obturator prostheses are affected by bulb design, i.e.: the hollow or buccal flange type, and different lateral and medial bulb heights. Buccal flange and hollow bulb obturator prostheses were fabricated with two different lateral bulb wall heights and two different medial bulb wall heights. Ultimately, eight obturator prostheses were prepared for evaluation of their vibratory characteristics. The frequency-response functions were recorded on an FFT analyzer to identify their vibratory characteristics. A transient response simulation was carried out in which an impact was applied to the non-defect side. The decay rate, damping time and maximum amplitude of the retainers were statistically analysed by anova with Scheffé's test (P < 0.05). The decay rate of every buccal flange type was higher and damping time was shorter than those of every hollow type, except between a pair with low lateral and low medial bulb walls. The maximum amplitude values of four obturators with low medial bulb walls were significantly lower than those of four obturators with high medial walls. The buccal flange obturator prosthesis with high lateral and low medial walls showed the maximum decay rate and the minimum amplitude of the retainers on molars. Vibration analysis suggests that a buccal flange obturator prosthesis with high lateral and low medial walls is preferable.

Rehabilitation of a bilateral maxillectomy patient with a free fibula osteocutaneous flap.

Rehabilitation of patients who have undergone bilateral maxillectomy is difficult because of extensive loss of bone and soft tissue. In this clinical report, prosthodontic rehabilitation of oral function in a bilateral maxillecitomy patient combined with a new fibular osteocutaneous flap, which was designed to have two oronasal slits for the retention of an obturator prosthesis, was described. A 58-year-old man with a maxillary alveolar carcinoma underwent bilateral maxillectomy. The defect was reconstructed using a vascularized fibular bone wrapped circumferentially with a peroneal flap, which was fixed with miniplates between the right malar prominence and cut edge of the left zygoma remaining two slits anterior and posterior to the graft. Two and half weeks after the surgery, a delayed surgical obturator was delivered and an obturator prosthesis was delivered 6 weeks after the surgery. This obturator prosthesis could be extended into the slits to engage the tissue undercuts, and was stable during use. Mastication, deglutition, articulation and the mid-facial profile of the patient were rehabilitated. After installation of the obturator prosthesis, relining of the prosthesis base was carried out alongside the healing process of the graft, and adjustment of occlusions and high-pressure spots was carried out. No clinical disorders were observed either in the grafted tissue or the obturator prosthesis with a 3-year prognosis. Newly designing a fibular osteocutaneous flap combined with tissue-borne obturator prosthesis is one successful approach to the restoration of oral function, and increases the patient's quality of life after bilateral maxillectomy.

Bone mineral density of the mandible in ovariectomized rats: analyses using dual energy X-ray absorptiometry and peripheral quantitative computed tomography.

INTRODUCTION: Although previous studies have shown that maxillary molar extraction in ovariectomized (OVX) animals causes mandibular loss of bone, it is still questionable as to whether estrogen deficiency affects mandibles with functional occlusion. MATERIALS AND METHODS: To answer this question, 13-week-old female Sprague-Dawley rats were bilaterally OVX or sham-operated. After 109 days, the bone mineral density (BMD) of the femurs and mandibles was measured using dual-energy X-ray absorptiometry (DEXA) and peripheral quantitative computed tomography (pQCT). RESULTS: In DEXA analysis, although the BMD of the total mandible of the OVX rats was similar to that of the sham-operated rats, the BMD of the condylar region in the OVX rats had decreased by 12.5%. In pQCT analysis, decrease in trabecular BMD of the mandibular bone was detectable but low in the molar region (maximal 13%), whereas no difference was seen in cortical BMD. In the femurs, the trabecular bone prominently decreased in OVX rats (30% decrease in pQCT analysis) as previously reported. CONCLUSION: This study revealed regional differences in the mandibular bone decrease in OVX rats. Although the mechanism of low susceptibility of the mandible to estrogen-deficient conditions remains unknown, it is likely that mechanical stress derived from functional occlusion is preventing bone loss in this pathological condition. Furthermore, this study demonstrated the advantage of pQCT in analyzing rat mandibular bone.

Digital acoustic analysis of five vowels in maxillectomy patients.

The aim of the study was to characterize the acoustics of vowel articulation in maxillectomy patients. Digital acoustic analysis of five vowels, /a/, /e/, /i/, /o/ and /u/, was performed on 12 male maxillectomy patients and 12 normal male individuals. A simple set of acoustic descriptions called the first and second formant frequencies, F1 and F2, were employed and calculated based on linear predictive coding. The maxillectomy patients had a significantly lower F2 for all five vowels and a significantly higher F1 for only /i/ vowel. From the data plotted on an F1-F2 plane in each subject, we determined the F1 range and the F2 range, which are the differences between the minimum and the maximum frequencies among the five vowels. The maxillectomy patients had a significantly narrower F2 range than the normal controls. In contrast, there was no significant difference in the F1 range. These results suggest that the maxillectomy patients had difficulty in controlling F2 properly. In addition, the speech intelligibility (SI) test was performed to verify the results of this new frequency range method. A high correlation between the F2 range and the score of SI test was demonstrated, suggesting that the F2 range is effective in evaluating the speech ability of maxillectomy patients.

Characterization of the bone-resorptive effect of interleukin-11 in cultured mouse calvarial bones.

Interleukin-11 (IL-11) is a stromal cell-derived cytokine that can enhance osteoclast formation and stimulate bone resorption. In the present study, the characteristics of the resorptive effect of IL-11 in mouse calvarial bones were investigated. Both recombinant mouse IL-11 and human IL-11 caused concentration- and time-dependent stimulations of (45)Ca release from prelabeled mouse calvariae. Half-maximal responses were obtained at 0.7 ng/mL (approximately 40 pmol/L). Mouse and human IL-11 also stimulated release of (3)H from [(3)H]-proline-labeled bones. The magnitude of the (45)Ca and (3)H release (1.4-1.6-fold) caused by a maximally effective concentration of IL-11 was less than the stimulation (2.5-4.0-fold) elicited by a maximum concentration of parathyroid hormone (PTH). Release of (45)Ca by IL-11 was unaffected by the mitotic inhibitors, hydroxyurea and aphidicolin. In addition to resorption of bone, IL-11 caused a small (1.5-2.0-fold) enhancement of prostaglandin E(2) (PGE(2)) biosynthesis in calvariae, but had no effect on the mRNA expression of cyclooxygenase-1 and -2, or cytosolic phospholipase A(2). Indomethacin and flurbiprofen abolished the formation of PGE(2) and partially reduced (45)Ca release stimulated by IL-11. When either mouse interleukin-4 (IL-4) or interleukin-13 (IL-13) was added to calvariae treated with IL-11, (45)Ca release was inhibited. Resorption caused by IL-11 was also inhibited by both anti-mouse glycoprotein 130 (gp130) and an antibody neutralizing IL-11, but these agents had no effect on (45)Ca release caused by PTH or 1,25(OH)(2)vitamin D(3) (D(3)). Real-time, quantitative polymerase chain reaction (PCR) analysis (TaqMan PCR) and semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) demonstrated that IL-11 caused concentration-dependent enhancements of receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin (OPG) mRNA, without affecting the mRNA expression of RANK. Mouse RANKL stimulated (45)Ca release in the calvarial bones. The stimulatory effects of RANKL and IL-11 were inhibited by mouse OPG. These data demonstrate that IL-11 stimulates osteoclastic resorption in mouse calvariae by mechanisms that are independent of cell proliferation; partially dependent on prostaglandin biosynthesis; sensitive to inhibition by IL-4, IL-13, and OPG; and associated with enhanced expression of RANKL and OPG. In addition, IL-11 was not found to play an essential role in resorption stimulated by other calciotropic agents in calvariae.

Bone-resorbing activity from cholesterol-exposed macrophages due to enhanced expression of interleukin-1alpha.

The presence of cholesterol crystals, macrophages, and foreign giant cells has been associated with impaired bone healing of periapical lesions. Therefore, we investigated whether macrophages exposed to cholesterol crystals can release factors changing the activity of bone-resorbing osteoclasts. Mouse peritoneal macrophages treated with cholesterol crystals in vitro produced factor(s) that stimulated the release of 45Ca and 3H from mouse calvariae pre-labeled with 45Ca(CaCl2) or [3H]-proline, respectively. No bone-resorbing activity was released by epithelial cells, fibroblasts, or osteoblasts exposed to cholesterol crystals. Interleukin-1 receptor antagonist protein and antiserum neutralizing mouse interleukin-1alpha (IL-1alpha) inhibited 45Ca release induced by cholesterol-activated macrophages. The addition of cholesterol to the macrophages augmented the release of IL-1alpha protein and the expression of IL-1alpha mRNA. These findings indicate that frustrated phagocytosis by macrophages exposed to cholesterol crystals results in release of factors stimulating osteoclastic bone resorption, primarily due to increased transcription of the IL-1alpha gene.

Vasoactive intestinal peptide (VIP)/pituitary adenylate cyclase-activating peptide receptor subtypes in mouse calvarial osteoblasts: presence of VIP-2 receptors and differentiation-induced expression of VIP-1 receptors.

Three distinct complementary DNAs for vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) receptors have been cloned and designated VIP-1 receptor (VIP-1R), VIP-2 receptor (VIP-2R), and PACAP receptor (PACAP-R). In the present study, we have characterized the binding sites on primary mouse calvarial osteoblasts for VIP and related peptides. By analyzing the cAMP response, the rank order of response observed was PACAP 38 > PACAP 27 > helodermin > VIP > helospectin > glucagon > PHI >>> secretin. The VIP-2R/PACAP-R antagonist, PACAP 6-38, inhibited both VIP- and PACAP-stimulated cAMP formation. Binding studies using an atomic force microscopy (AFM) technique showed high affinity binding for VIP and PACAP 38, but not for secretin. Radioligand binding studies using (125)I-VIP and (125)I-PACAP 38 demonstrated a more specific and higher affinity binding for PACAP 38 than for VIP. Secretin failed to inhibit both (125)I-VIP and (125)I-PACAP 38 binding. RT-PCR demonstrated that undifferentiated mouse calvarial osteoblasts express messenger RNA for VIP-2R, but not for VIP-1R or PACAP-R. When the osteoblasts were cultured for 20 days to induce bone noduli formation, VIP-1R, in addition to VIP-2R, were expressed when the nodules started to mineralize at 12 days. Taken together, these data demonstrate that mouse calvarial osteoblasts express functional VIP-2R with higher affinity binding for PACAP than for VIP and that the VIP-1R expression is induced during osteoblastic differentiation.

Modal analysis of the maxillary dentition in cleft lip and palate patients before and after bone grafting.

The aim of this study was to analyze the vibratory characteristics in the maxillary dentition of 4 cleft lip and palate (CLP) patients before and after bone grafting. First, the central incisor on the noncleft side was impacted with an impact hammer, and the responses were received using an acceleration sensor from the teeth between the upper first molars on both sides. The transfer functions were then obtained from each measurement point using a fast Fourier transform analyzer. Finally, a computer analysis and simulation were performed based on the measured transfer functions to obtain the natural frequency, modal shape, decay rate (DR) and maximum displacement (MDP). Before bone grafting, distinct phase differences between the major and minor dental arches (MDA and mDA) were observed in the modal shapes. After surgery, however, both the MDA and mDA vibrated in phase. These results were identical in all subjects. The MDPs of the central incisors conspicuously decreased after bone grafting in 3 subjects. From the standpoint of vibratory characteristics, this study indicated that bone grafting had a favorable effect on prosthodontic treatment using a fixed prosthesis across the cleft in CLP patients.

Microisolated mouse osteoclasts express VIP-1 and PACAP receptors.

Skeletal tissue contains a network of nerve fibers expressing several neuropeptides, including vasoactive intestinal peptide (VIP) and the related peptide pituitary adenylate cyclase activating peptide (PACAP). These peptides have been demonstrated to regulate osteoclast formation and osteoclast activity. Using atomic force microscopy and by analysing changes of the intracellular calcium concentrations, we have recently demonstrated that multinucleated rat osteoclasts have cell membrane binding sites recognising VIP and PACAP. In the present study, we have further studied the expression of VIP receptor subtypes in mouse bone marrow cultures and isolated osteoclasts. A micromanipulation technique was used to isolate pure populations of osteoclasts formed in PTH-stimulated mouse bone marrow cultures. By reverse transcriptase polymerase chain reaction (RT-PCR), we studied the expression of mRNA for VIP-1, VIP-2, and PACAP receptors. The purity of the microisolated osteoclasts was determined by studying the expression of specific mRNA associated with the phenotypic trait of osteoclasts or osteoblasts/stromal cells. In this study, we show that mouse osteoclasts express VIP-1 and PACAP, but not VIP-2, receptor mRNA.

The inhibitory effects of vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide on osteoclast formation are associated with upregulation of osteoprotegerin and downregulation of RANKL and RANK.

The presence of a network of peptidergic nerve fibers in the skeleton, expressing several neuropeptides including vasoactive intestinal peptide (VIP), has been demonstrated. This observation, together with our findings in vitro showing that VIP can regulate the activities of osteoblasts and osteoclasts as well as the recruitment of osteoclasts, has suggested the existence of a neuro-osteogenic interplay in bone metabolism. In the present study, the effects of VIP and pituitary adenylate cyclase-activating polypeptide (PACAP), two members of the VIP/secretin/glucagon superfamily, on osteoclast formation and mRNA expression of three key regulatory proteins involved in osteoclast formation have been investigated. VIP, PACAP-27, and PACAP-38, at concentrations of 10(-6) M, all significantly inhibited formation of tartrate-resistant acid phosphatase-positive multinuclear cells (TRAP + MNC) in mouse bone marrow cultures stimulated by 1, 25(OH)(2)-vitamin D3 (D3; 10(-8) M). By using semiquantitative RT-PCR, it was found that D3 upregulated the mRNA expressions of receptor activator of NF-kappaB ligand (RANKL) and receptor activator of NF-kappaB (RANK), whereas the expression of osteoprotegerin (OPG) was downregulated in mouse bone marrow cultures stimulated by D3 for 7 days. Both VIP and PACAP-38 decreased the stimulatory effects of D3 on RANKL and RANK expression, whereas the inhibitory effect of D3 on OPG expression was reversed by VIP and PACAP-38. These observations indicate that the inhibitory effects of VIP and PACAP on osteoclast recruitment are due to regulation of the expression of key proteins involved in later stages of osteoclast differentiation.

Neuro-hormonal control of bone metabolism: vasoactive intestinal peptide stimulates alkaline phosphatase activity and mRNA expression in mouse calvarial osteoblasts as well as calcium accumulation mineralized bone nodules.

Based upon the immunohistochemical demonstration of neuropeptides in the skeleton, including vasoactive intestinal peptide (VIP), we have addressed the question of whether neuropeptides may exert regulatory roles on bone tissue metabolism or not. In the present communication, we have investigated if VIP can affect anabolic processes in osteoblasts. Osteoblasts were isolated from neonatal mouse calvariae by time sequential enzyme-digestion and subsequently cultured for 2-28 days in the presence of VIP and other modulators of cyclic AMP formation. VIP (10(-6) M) stimulated ALP activity and calcium content. The cyclic AMP phosphodiesterase inhibitors ZK 62 711 (10(-4) M) and isobutyl-methylxanthine (10(-4) M) stimulated ALP activity and synergistically potentiated the effect of VIP. Neither VIP, nor isobutyl-methylxanthine or ZK 62 711, in the absence or presence of VIP, affected cell number. The stimulatory effect of VIP on ALP activity, in the presence of ZK 62 711, was dependent on time and concentration of VIP. The stimulatory effects of VIP and ZK 62 711 on ALP activity was seen also in cells stained for ALP. VIP (10(-6) M), in the presence of ZK 62 711 (10(-6) M), significantly enhanced mRNA for tissue non-specific ALP. VIP (10(-6) M), in the presence of ZK 62 711, stimulated cyclic AMP production. Forskolin and choleratoxin stimulated ALP activity and cyclic AMP formation in a concentration-dependent manner, without affecting cell number. VIP (10(-6) M) and ZK 62 711 (10(-5) M) stimulated, and their combination synergistically enhanced, calcium content in bone noduli. These data show that VIP, without affecting cell proliferation, can stimulate osteoblastic ALP biosynthesis and bone noduli formation by a mechanism mediated by cyclic AMP. Our observations suggest a possibility that anabolic processes in bone are under neurohormonal control.

Prosthodontic treatment for patients with large mandibular defects; porous hydroxyapatite grafts.

It is difficult for both prosthodontists and their patients with large marginal defects to achieve a satisfactory prosthodontic result, because retention, support, and stability of the prosthesis are limited and recovery of esthetics is unsatisfactory owing to large mandibular defects. Alveolar ridge augmentation therapy is performed to compensate for such problems. We have experienced a good prognosis of prosthodontic treatment for over 10 years in two patients with large marginal defects of the partially edentulous mandible, who had undergone grafting of porous hydroxyapatite blocks to their bone defects. It has been reported that porous hydroxyapatite blocks are unsuitable for edentulous patients, because the mucosa covering the hydroxyapatite block is too thin and delicate to support dentures. We, therefore, designed the denture to prevent concentration of occlusal stress on the mucosa. In both of these two cases, we achieved recovery of occlusal function and esthetics by affixing denture to the large marginally resected defect augmented with a graft of porous hydroxyapatite block.

[Fundamental study on hybrid-type dental implant--effects of glass-ceramics on growth and differentiation of human periodontal ligament-derived cells].

The hybrid-type dental implants which are composed of substrates and periodontal ligament-derived cells are expected to form the periodontal ligament-like tissue around the dental implant. The purpose of this study was to investigate the possibility of the application of glass-ceramics (GC) as the substrate using the human periodontal ligament-derived cells (PL cells). The growth and differentiation of the PL cells on the GC were investigated, as compared to the hydroxyapatite plates and the conventional plastic dishes. The Ca concentration of the media was also measured. The results were as follows: 1) The PL cells were fibroblastic of spindle shape. The population doubling time was approximately 26 hours. 2) The PL cells exhibited an alkaline phosphatase (ALPase) activity, collagen productivity and responsiveness to 1 alpha,25-dihydroxyvitamin D3. 3) The PL cells proliferated favorably both on the mirror-polished and #2000-polished GC plates as well as on the hydroxyapatite plates. 4) The ALPase activity of the PL cells on the GC increased in a time-dependent manner. 5) The GC released Ca into the media. The PL cells possessed some characteristics of periodontal ligaments, and the growth and differentiation of the PL cells were not impaired significantly on the GC. The GC also provided the dental implant with enough biocompatibility and strength. These results promised the usefulness of the GC as the possible substrate for the hybrid-type dental implants.