RESUMEN
Gingival overgrowth is caused in response to the antiepileptic drug phenytoin (PHT). PHT-induced gingival overgrowth is characterized by the proliferation of fibroblasts and increased collagen formation in gingiva. Fibroblast proliferation is regulated through the cell cycle. Thus, in the present study, we examined the effects of PHT on the cell cycle, the expression of cell cycle control proteins and the proliferation in human gingival fibroblasts (hGFs). Cells were stimulated in serum-free DMEM with or without 0.25 µm PHT. Subsequently, the cell cycle phase distribution and the protein expression after 24 h and the cell proliferation after 24, 48 and 72 h were evaluated. PHT significantly inhibited synchronization at the G0/G1 phase of the cell cycle in hGFs through serum starvation. Stimulation with PHT for 48 and 72 h significantly induced a proliferative response in hGFs. PHT decreased the expression of the Cdk-inhibitory proteins p21 and p27 and increased the levels of the S phase-promoting proteins phospho-Thr160-Cdk2 and phospho-Ser807/811-Rb in serum-free DMEM. The inhibition of G1 cell cycle arrest in hGFs may result from an increase in phosphorylated Cdk2 and Rb proteins and decreased levels of p21 and p27 proteins by PHT. The gingival overgrowth may be caused by the failure of the G1 cell cycle arrest in GFs exposed to PHT.
Asunto(s)
Fibroblastos/efectos de los fármacos , Puntos de Control de la Fase G1 del Ciclo Celular/efectos de los fármacos , Encía/efectos de los fármacos , Fenitoína/farmacología , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Sobrecrecimiento Gingival/inducido químicamente , HumanosRESUMEN
Sublingual gland tumors, especially mesenchymal tumors, are extremely rare. We describe the first reported case of schwannoma arising from the sublingual gland with details of the histopathologic and immunohistochemical features. A 70-year-old woman developed a painless swelling on the floor of the mouth. The excised material was sublingual gland tissue with an ovoid, grayish-yellow solid tumorous mass at the cut surface. The tumor was composed of proliferated spindle-shaped tumor cells exhibiting palisading patterns. In the center of the tumor, a small salivary gland component was recognized. Immunohistochemically, the tumor cells were strongly positive for S-100 protein but negative for neurofilament protein. The Ki-67 labeling index was 4.58. The clear presence of a remnant sublingual gland lobule in the present tumor provided convincing evidence that it was a schwannoma arising from the sublingual gland and thus the first of its type to be reported.
Asunto(s)
Neurilemoma/patología , Neoplasias de la Glándula Sublingual/patología , Anciano , Femenino , Humanos , Inmunohistoquímica , Neurilemoma/metabolismo , Neoplasias de la Glándula Sublingual/metabolismoRESUMEN
OBJECTIVE: Porphyromonas gingivalis has been shown to accelerate atherosclerotic lesion development in atherosclerotic apo E-deficient mice. Here, we investigated whether repeated P. gingivalis injection affected the inflammatory and atherosclerotic responses of C57BL/6 mice fed a high-fat diet (HFD). MATERIALS AND METHODS: Eight-week-old C57BL/6 mice fed either HFD or a regular chow diet (RD) were inoculated intravenously with P. gingivalis or phosphate-buffered saline three times per week for 10 weeks and sacrificed at 19 weeks of age. Atheromatous lesions in the proximal aorta of each animal were analyzed histomorphometrically, and the serum cytokine and C-reactive protein (CRP) levels were determined. RESULTS: Long-term HFD feeding as compared to RD feeding led to a slight increase in atheromatous lesions in the aortic sinus as well as increases in the levels of serum monocyte chemoattractant protein 1. Further, P. gingivalis injection significantly enhanced the formation of atherosclerotic plaque, and increased CRP and inflammatory cytokine levels, in mice fed the HFD, although no further increase in LDL was observed. CONCLUSION: These results suggest that bacteremia-induced by repeated injection with P. gingivalis accelerates atherosclerosis in normal C57BL/6 mice by initiating inflammation, and is therefore implicated in chronic infection-related pathogenicity.
Asunto(s)
Aterosclerosis/inmunología , Infecciones por Bacteroidaceae/inmunología , Grasas de la Dieta/efectos adversos , Placa Aterosclerótica/inmunología , Porphyromonas gingivalis/inmunología , Animales , Aterosclerosis/inducido químicamente , Aterosclerosis/microbiología , Aterosclerosis/patología , Infecciones por Bacteroidaceae/patología , Grasas de la Dieta/farmacología , Femenino , Ratones , Placa Aterosclerótica/inducido químicamente , Placa Aterosclerótica/microbiología , Placa Aterosclerótica/patologíaRESUMEN
Sialolithiasis of the minor salivary glands, especially in the lower lip, is rare. We report a case of sialolithiasis of the lower lip simulating a mucocele as well as review four additional cases affecting the lower lip and 39 cases affecting the upper lip, together with details of the clinical and histopathologic findings.
Asunto(s)
Enfermedades de los Labios/diagnóstico , Mucocele/diagnóstico , Cálculos de las Glándulas Salivales/diagnóstico , Glándulas Salivales Menores/patología , Diagnóstico Diferencial , Humanos , Enfermedades de los Labios/patología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Mucocele/patología , Cálculos de las Glándulas Salivales/patologíaRESUMEN
OBJECTIVE: We have previously demonstrated that the mechanism of nifedipine (NIF)-induced gingival overgrowth is related to the observation that proliferation and cell cycle progression of gingival fibroblasts derived from NIF reactive patient (NIFr) are greater than those from NIF non-reactive patient (NIFn). Gingival overgrowth has also been reported to be a result of inhibited apoptosis of gingival fibroblasts. Apoptosis in fibroblasts is induced by lipopolysaccharide (LPS). Thus, we focused upon evaluating whether there is a difference in LPS-induced apoptosis between NIFn and NIFr. METHODS: Both NIFn and NIFr were arrested in DMEM containing 0.5% FBS, stimulated by LPS, and assayed for apoptosis, cell cycle analysis, Western blotting, and caspase activity. RESULTS: Compared to NIFn, the number of apoptotic cells was significantly decreased and the percentage of cells in S and G(2)/M phase was significantly increased in NIFr. The levels of Bax and cytochrome c proteins in NIFr were not up-regulated by LPS compared with NIFn. Both NIFn and NIFr displayed the following changes in protein expression: increased Bad, decreased Bcl-xL, and unchanged Bcl-2 and p53. Caspase-3 and -9 activities were significantly increased by LPS in NIFn but were unchanged in NIFr. Caspase-2 activity remained constant whilst caspase-8 activity significantly increased upon LPS treatment in both NIFn and NIFr. CONCLUSION: Bad, Bax, cytochrome c, p53, and caspases-2, -3, -8, and -9 are pro-apoptotic proteins. Bcl-2 and Bcl-xL are anti-apoptotic proteins. Thus, the mechanism of NIF-induced gingival overgrowth might be related to decreased apoptosis in NIFr through a reduction of Bax, cytochrome c, and caspase-3 and -9.
Asunto(s)
Apoptosis/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Encía/efectos de los fármacos , Sobrecrecimiento Gingival/patología , Lipopolisacáridos/farmacología , Nifedipino/efectos adversos , Vasodilatadores/efectos adversos , Caspasa 2/análisis , Caspasa 2/efectos de los fármacos , Caspasa 3/análisis , Caspasa 3/efectos de los fármacos , Caspasa 8/análisis , Caspasa 8/efectos de los fármacos , Caspasa 9/análisis , Caspasa 9/efectos de los fármacos , Técnicas de Cultivo de Célula , Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Cisteína Endopeptidasas/análisis , Cisteína Endopeptidasas/efectos de los fármacos , Citocromos c/análisis , Citocromos c/efectos de los fármacos , Escherichia coli , Fase G2/efectos de los fármacos , Encía/patología , Sobrecrecimiento Gingival/inducido químicamente , Humanos , Metafase/efectos de los fármacos , Proteínas Proto-Oncogénicas c-bcl-2/análisis , Proteínas Proto-Oncogénicas c-bcl-2/efectos de los fármacos , Fase S/efectos de los fármacos , Proteína p53 Supresora de Tumor/análisis , Proteína p53 Supresora de Tumor/efectos de los fármacos , Proteína X Asociada a bcl-2/análisis , Proteína X Asociada a bcl-2/efectos de los fármacos , Proteína Letal Asociada a bcl/análisis , Proteína Letal Asociada a bcl/efectos de los fármacos , Proteína bcl-X/análisis , Proteína bcl-X/efectos de los fármacosRESUMEN
Sialolipoma is a new variant of salivary gland lipoma, which was first described in 2001. We report a rare case of sialolipoma of the palate, and review another 10 cases affecting the minor salivary gland and 13 affecting the major salivary gland, together with details of the clinical and histopathological findings.
Asunto(s)
Lipoma/patología , Neoplasias Palatinas/patología , Paladar Duro/patología , Neoplasias de las Glándulas Salivales/patología , Glándulas Salivales Menores/patología , Tejido Adiposo/patología , Anciano , Biopsia , Diagnóstico Diferencial , Femenino , Humanos , Imagen por Resonancia Magnética , Conductos Salivales/patologíaRESUMEN
The purpose of this study was to determine the clinicopathological and immunohistochemical features of lipoma/fibrolipoma with rare occasions as osseous and/or chondroid differentiation in the oral cavity. Two cases of the tumors, who presented with a painless, relatively hard mass on the oral mucosa, were studied. These were consisted of a well-circumscribed mass of fatty tissue with chondroid and significant fibrous component intermixed with the lobules of fat cells with chondroid and woven bone component, respectively. Immunohistochemical study revealed that peripheral spindle cells around chondroid tissue stained diffusely for S-100 alpha & beta and Sox-9, though peripheral spindle cells around osteoid tissue only stained for RUNX-2. According to review of the literature, lipoma/fibrolipoma with osseous and/or chondroid differentiation was 18 cases. Also fibrolipoma with osseous and chondroid differentiation is the first to be reported here. These results indicated that the cartilage/bone is produced by differentiation of undifferentiated mesenchymal cells of stroma.
RESUMEN
Hypodontia of permanent teeth was evaluated from orthopantomograms of 2072 apparently healthy pediatric patients at The Hospital of Nihon University School of Dentistry at Matsudo. The prevalence of congenitally missing teeth (CMT) was 8.7% in boys and 10.8% in girls, and 9.4% for both sexes combined. Most cases (67.8%) involved either one or two missing teeth. There were in total 574 CMT, and on average 2.8 teeth were missing per child. The most commonly absent tooth was the mandibular second premolar. On the other hand, no first molars were missing in any case. A high frequency of CMT mandibular incisors (18.82%) was observed, and this seems to be a characteristic peculiar to individuals of Asian ethnicity. Oligodontia (6 or more CMT excluding the third molar) ranged from 6 to 14 teeth, with a prevalence of 1.4% in general: 1.8% for girls and 0.9% for boys. Symmetry of CMT was predominant: 214 pairs for bilateral symmetry and 107 pairs for symmetry between two antagonistic quadrants. The distribution of CMT between maxillary and mandibular hypodontia in the right and left quadrants for boys and girls no had significant association (P < 0.05).
Asunto(s)
Anodoncia/epidemiología , Radiografía Panorámica/estadística & datos numéricos , Adolescente , Anodoncia/diagnóstico por imagen , Diente Premolar/anomalías , Niño , Preescolar , Estudios Transversales , Diente Canino/anomalías , Femenino , Humanos , Incisivo/anomalías , Japón/epidemiología , Masculino , Mandíbula/diagnóstico por imagen , Maxilar/diagnóstico por imagen , Diente Molar/anomalías , Prevalencia , Estudios Retrospectivos , Factores SexualesRESUMEN
We have previously demonstrated bone loss of the mandible and femur in experimental osteoporotic rats and its prevention by medication, using peripheral quantitative computed tomography (pQCT). In the present study, the mechanical properties of the mandible and femur and the correlation to their geometric and densitometric properties were studied in ovariectomized rats with or without etidronate treatment. Fifty-four Wistar strain SPF female rats, 26 weeks old, were randomly assigned to four groups: (1) Basal group (12 rats, 1.0% Ca diet); (2) Sham group (Sham-operated, 12 rats, 0.1% Ca diet); (3) OVX group (ovariectomized, 15 rats, 0.1% Ca diet); (4) Treated group (OVX + etidronate, 15 rats, 0.1% Ca diet). Total bone mineral density (BMD), cortical BMD, cross-sectional cortical bone area, cross-sectional cortical bone thickness, crosssectional moment of inertia (CSMI), and polar strength index (SSI) of the mandible and femur were measured by pQCT. The failure load of mandible and femur was evaluated by three-point bending. The failure load of both bones was significantly lower in the Sham group compared with the Basal group. The OVX group further had a 8% and 7% decrease in the failure load for mandible and femur, respectively, compared to the Sham group. Treatment with etidronate led to an increase in the failure load compared with the OVX group. The failure load was related to the pQCT-assessed variables, especially with cortical bone area and total BMD. Moreover, the geometric and densitometric properties and failure load in the mandible showed a correlation to those in the femur.
Asunto(s)
Densitometría/métodos , Fémur/fisiopatología , Mandíbula/fisiopatología , Osteoporosis/fisiopatología , Animales , Fenómenos Biomecánicos , Densidad Ósea , Femenino , Ratas , Ratas Wistar , Tomografía Computarizada por Rayos X , Soporte de PesoRESUMEN
Differences of cell proliferation, cell cycle, and G(1)/S transition regulatory proteins of gingival fibroblasts derived from nifedipine-reactive patient (NIFr) and nifedipine-non-reactive patient (NIFn) in the presence of basic fibroblast growth factor (bFGF) were investigated to elucidate the mechanism of gingival overgrowth associated with nifedipine, one of the Ca(2+)-channel blockers. The proliferation rate of NIFr cells in the presence of bFGF significantly increased than NIFn cells. The proportion of NIFr cells that had undergone progression to the S and G(2)/M phases from the G(0)/G(1) phase significantly increased compared to that in NIFn cells. Increases of pRB (Ser807/811), pCDK2 (Thr160), CDK2, and cyclin E protein levels in NIFr cells were greater than those in NIFn cells. The elevations of pRB (Ser780), RB, and cyclin A protein levels in NIFr cells did not differ from those of NIFn cells. The growth of NIFr cells was greater than that of NIFn cells as a result of the active G(1)/S transition of NIFr cells, as assessed by the increments of cyclin E, pCDK2, and pRB (ser807/811) protein in NIFr cells.
Asunto(s)
Bloqueadores de los Canales de Calcio/farmacología , Proteínas de Ciclo Celular/fisiología , Factor 2 de Crecimiento de Fibroblastos/farmacología , Nifedipino/farmacología , Antimetabolitos , Western Blotting , Bromodesoxiuridina , Ciclo Celular/efectos de los fármacos , Proteínas de Ciclo Celular/genética , Línea Celular , Proliferación Celular , ADN/biosíntesis , ADN/genética , Fase G1/efectos de los fármacos , Encía/citología , Humanos , Fase S/efectos de los fármacosRESUMEN
The effect of nifedipine and interleukin-alpha (IL-1alpha) on the cell proliferation and DNA synthesis was studied in human gingival fibroblasts derived from 5 patients who developed gingival overgrowth (nifedipine responders) and 5 patients who did not develop gingival overgrowth (nifedipine non-responders) in response to nifedipine. Epidermal growth factor was used as a positive control. The fibroblasts derived from nifedipine responders tended to have a numerically greater rate of cell proliferation and DNA synthesis (3H-thymidine incorporation) than those from nifedipine nonresponders in the presence of nifedipine and IL-lalpha. Fibroblasts derived from nifedipine responders showed significantly higher cell proliferation rate in the presence of nifedipine and IL-1alpha, than nifedipine or IL-lalpha alone on both the second and the fourth day of incubation (P < 0.05). A combination of IL-1alpha and epidermal growth factor also showed significantly greater cell proliferation than IL-lalpha alone on the second day (P < 0.05). The DNA synthesis rate with a combination of nifedipine and IL-1alpha was higher than that for nifedipine alone on the second day (P < 0.01), and IL-1alpha alone on the fourth day (P < 0.05) in gingival fibroblasts originating from nifedipine responders. These results suggest that the interaction between nifedipine and gingival inflammation might play an important role in the pathogenesis of nifedipine-induced gingival overgrowth.
Asunto(s)
Bloqueadores de los Canales de Calcio/farmacología , Encía/efectos de los fármacos , Sobrecrecimiento Gingival/inducido químicamente , Interleucina-1/farmacología , Nifedipino/farmacología , Anciano , Estudios de Casos y Controles , Proliferación Celular/efectos de los fármacos , Células Cultivadas , ADN/biosíntesis , Replicación del ADN/efectos de los fármacos , Sinergismo Farmacológico , Femenino , Fibroblastos/efectos de los fármacos , Encía/citología , Líquido del Surco Gingival/química , Gingivitis/metabolismo , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The effect of therapeutic agents on trabecular bone loss in the mandible was investigated in ovariectomized rats. Eighty-seven Wistar SPF female rats were ovariectomized (OVX) or given a sham operation (Sham), and maintained on a diet containing 0.1% calcium. Four weeks later, groups of OVX rats were treated with estriol (E3), calcitonin (CT), etidronate, or 2-carboxyethylgermanium sesquioxide (Ge-132). The Basal group was maintained on a diet containing 1.0% calcium, and the OVX and sham groups on a diet containing 0.1% calcium. The trabecular bone mineral density (BMD) and trabecular bone mineral content (BMC) in 11 mandibular slices from 0.5 mm at the mesial margin of the first molar to 0.5 mm at the distal margin of the third molar, were measured using peripheral Quantitative Computed Tomography (pQCT). The BMD in the OVX group was lower than that in the Sham group, and decreased BMC was observed only in the molar region. BMD and BMC were increased in the etidronate-treated group, but only BMC was increased in the CT group. E3 treatment increased BMD and BMC; significant increases were also observed beneath the molar. Ge-132 treatment increased both BMD and BMC, especially the latter.
Asunto(s)
Enfermedades Mandibulares/prevención & control , Osteoporosis/prevención & control , Ovariectomía , Animales , Densidad Ósea/efectos de los fármacos , Calcitonina/uso terapéutico , Calcio de la Dieta/administración & dosificación , Estriol/uso terapéutico , Ácido Etidrónico/uso terapéutico , Femenino , Germanio/uso terapéutico , Minerales/análisis , Compuestos Organometálicos/uso terapéutico , Propionatos , Ratas , Ratas Wistar , Tomografía Computarizada por Rayos XRESUMEN
Buccal mucosa carcinoma-derived cell line, HO-1-N-1, epithelial-like cells, was obtained in order to investigate the characteristics of oral cancer cells and examine the [Ca2+]i responses to stimulants, such as bradykinin (BK), histamine (HIST), thapsigargin (TG), epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha ). Intracellular Ca2+ influx was observed by all stimulants that enhanced the [Ca2+]i response. However, intracellular Ca2+ release was not observed in response to growth factors. The [Ca2+]i response of BK (100 nM) was inhibited by 10 micro M of the BKB2 antagonist, D-Arg-[Hyp3, Thi5,8, D-Phe7]-BK, and HIST (1 mM) was completely inhibited by 100 nM of the H1 antagonist, (+)-chlorpheniramine, in the presence and absence of extracellular Ca2+ (1.5 mM).
Asunto(s)
Señalización del Calcio/efectos de los fármacos , Calcio/metabolismo , Carcinoma/metabolismo , Células Epiteliales/metabolismo , Neoplasias de la Boca/metabolismo , Células Tumorales Cultivadas/metabolismo , Bradiquinina/antagonistas & inhibidores , Bradiquinina/farmacología , Carcinoma/patología , Factor de Crecimiento Epidérmico/farmacología , Células Epiteliales/efectos de los fármacos , Histamina/farmacología , Antagonistas de los Receptores Histamínicos H1/farmacología , Humanos , Mucosa Bucal/patología , Neoplasias de la Boca/patología , Receptores de Superficie Celular/metabolismo , Estimulación Química , Tapsigargina/farmacología , Factor de Crecimiento Transformador alfa/farmacología , Células Tumorales Cultivadas/efectos de los fármacosRESUMEN
A rare case of primary intraosseous carcinoma (PIOC) arising from an odontogenic cyst in a 58-year-old man is reported. Clinical and radiological examinations revealed an odontogenic cyst of the maxilla. Histopathologically, the lesion was composed of a cyst with a parakeratotic epithelial lining and well-differentiated squamous cell carcinoma, showing continuity between them without a connection to the oral mucosa. Twenty-eight well-documented Japanese cases of Type-1 PIOC, including the present case, were reviewed. The mean age of the 28 patients was 56.1 years, and the male to female ratio was 1.8:1.0. Compared with currently reported Japanese reviews of Type-3, foreign Type-1 and Type-3, there were no significant differences in mean patient age and sexual predominance, and no racial difference. The pathogenesis of Type-1 PIOC is also discussed.