RESUMEN
BACKGROUND: Drug-induced gingival enlargement is a common condition which can be observed in patients taking immunosuppressive medications following organ transplant surgery. The disfiguring excessive tissue often hinders proper oral hygiene practices, therefore accompanied by periodontitis, tooth mobility, and even pathological tooth migration in extreme cases. This case report presents a conservative treatment protocol for a patient with the aforementioned conditions involving neither surgical nor orthodontic intervention. Few related studies have reported such a noninvasive protocol for managing these kinds of conditions. CASE PRESENTATION: A 51-year-old woman presented with bleeding gingiva, mobile teeth and complained of chewing difficulties. She had undergone renal transplant surgery 16 years prior to this dental visit and had been taking immunosuppressive drugs including cyclosporine ever since. After clinical and radiographic examinations, the patient was diagnosed with drug-induced gingival enlargement, pathological tooth migration, severe periodontitis, and missing teeth. Through careful and meticulous nonsurgical debridement, oral hygiene instruction, tooth extraction, and occlusal adjustment, the patient's periodontium was restored to a healthy state without surgical intervention. Moreover, the patient's chewing function was restored by means of removable partial dentures. Good adaptation of prostheses and satisfaction with overall treatment outcomes were reported. CONCLUSIONS: Through proper diagnosis, treatment, and with good patient cooperation, complex systemic and dental problems can be managed conservatively without invasive surgeries to attain a stable periodontium and eventually, occlusal function could be restored.
Asunto(s)
Hiperplasia Gingival/inducido químicamente , Inmunosupresores/efectos adversos , Trasplante de Riñón , Periodontitis/terapia , Terapia Combinada , Desbridamiento , Dentadura Parcial Removible , Femenino , Humanos , Persona de Mediana Edad , Higiene Bucal , Extracción DentalRESUMEN
PURPOSE: This retrospective study evaluated the localization, incidence, and dimensions of the mandibular lingual canal and the anterior loop in the Taiwanese population using the simulation and visual interpretation of cone-beam computed tomography to minimize complications during symphysis block surgical procedures. MATERIALS AND METHODS: The sample population consisted of 215 patients (105 men and 110 women; mean age, 57 yr). The median lingual canal, symphysis bone thickness, and anterior loop length were defined and calculated using cone-beam computed tomography and 3-dimensional reconstructed images. The correlation of all data for men and women was assessed and analyzed statistically using unpaired t tests. RESULTS: All patients exhibited at least 1 median lingual canal in the symphysis, and the diameter of the main branch ranged from 0.21 to 1.48 mm (mean, 0.85 mm), with relevant differences between genders (longer in men than in women). A harvesting depth of 4 mm for the distance from the buccal bone to the terminal end of the median lingual canal resulted in a risk of neurovascular injury (13.0%); this risk was notably higher in women (19.1%) than in men (6.7%). The right and left anterior loop lengths ranged from 0 to 5.46 mm (mean, 2.60 mm) and from 0 to 5.57 mm (mean, 2.61 mm), respectively, with no relevant differences between genders or sides. CONCLUSIONS: The results suggest that routine cone-beam computed tomographic examinations before surgical interventions in the symphysis region are necessary because of the numerous complicated anatomic variations.
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Tomografía Computarizada de Haz Cónico , Complicaciones Intraoperatorias/prevención & control , Mandíbula/diagnóstico por imagen , Mandíbula/cirugía , Nervio Mandibular/diagnóstico por imagen , Traumatismos del Nervio Trigémino/prevención & control , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Imagenología Tridimensional , Masculino , Mandíbula/anatomía & histología , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND/PURPOSE: In order to clarify the role of transforming growth factor beta 1 (TGF-ß1) in pulp repair/regeneration responses, we investigated the differential signaling pathways responsible for the effects of TGF-ß1 on collagen turnover, matrix metalloproteinase-3 (MMP-3), and tissue inhibitor of metalloproteinase-1 (TIMP-1) production in human dental pulp cells. METHODS: Pulp cells were exposed to TGF-ß1 with/without pretreatment and coincubation by 1,4-diamino-2,3-dicyano-1,4-bis(o-aminophenyl mercapto)butadiene (U0126; a mitogen-activated protein kinase kinase [MEK]/extracellular signal-regulated kinase [ERK] inhibitor) and 4-(5-benzol[1,3]dioxol-5-yl-4-pyrldin-2-yl-1H- imidazol-2-yl)-benzamide hydrate (SB431542; an activin receptor-like kinase-5/Smad signaling inhibitor). Sircol collagen assay was used to measure cellular collagen content. Culture medium procollagen I, TIMP-1, and MMP-3 levels were determined by enzyme-linked immunosorbent assay. RESULTS: TGF-ß1 increased the collagen content, procollagen I, and TIMP-1 production, but slightly decreased MMP-3 production of pulp cells. SB431542 and U0126 prevented the TGF-ß1-induced increase of collagen content and TIMP-1 production of dental pulp cells. CONCLUSION: These results indicate that TGF-ß1 may be involved in the healing/regeneration processes of dental pulp in response to injury by stimulation of collagen and TIMP-1 production. These events are associated with activin receptor-like kinase-5/Smad2/3 and MEK/ERK signaling.
Asunto(s)
Colágeno Tipo I/metabolismo , Colágeno/fisiología , Regeneración/fisiología , Inhibidor Tisular de Metaloproteinasa-1/metabolismo , Factor de Crecimiento Transformador beta1/fisiología , Benzamidas/farmacología , Butadienos/farmacología , Células Cultivadas , Pulpa Dental/citología , Dioxoles/farmacología , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/fisiología , Nitrilos/farmacología , Proteínas Serina-Treonina Quinasas/efectos de los fármacos , Proteínas Serina-Treonina Quinasas/fisiología , Receptor Tipo I de Factor de Crecimiento Transformador beta , Receptores de Factores de Crecimiento Transformadores beta/efectos de los fármacos , Receptores de Factores de Crecimiento Transformadores beta/fisiología , Regeneración/efectos de los fármacos , Proteínas Smad/efectos de los fármacos , Proteínas Smad/fisiologíaRESUMEN
BACKGROUND/PURPOSE: Betel quid (BQ) chewing is popular in Taiwan and many other countries. There are about 200-600 million BQ chewers in the world. BQ chewing is one major risk factor of oral cancer and oral submucous fibrosis (OSF). While areca nut (AN), a main component of BQ, exhibits genotoxicity, its transformation capacity and its role in the initiation and promotion stages of carcinogenesis are not fully clear. METHODS: Mouse C3H10T1/2 cells were exposed to AN extract (ANE) for 24 hours. Cytotoxicity was evaluated by colony forming efficiency. For the transformation assay, C3H10T1/2 cells were exposed to ANE for 24 hours and then incubated in medium with/without 12-O-tetradecanolylphorbol-13-acetate (TPA; a tumor promoter) for 42 days. Cells were stained with Giemsa and type II and type III transformed foci were counted for analysis of the transformation capacity of ANE. RESULTS: ANE exhibited cytotoxicity to C3H10T/12 cells at concentrations higher than 320 µg/mL as shown by a decrease in colony numbers. ANE (80-640 µg/mL) alone mildly stimulated the transformed foci formation (p > 0.05). In the presence of TPA, ANE (80-640 µg/mL) markedly stimulated the transformed foci formation. The percentage of dishes with foci increased from 0% in controls to 20% in ANE (80 µg/mL and 320 µg/mL)-treated groups and further increased to 65-94% in ANE plus TPA groups. CONCLUSION: These results indicate that ANE is a weak complete carcinogen. ANE is an effective tumor initiator and can induce malignant transformation of C3H10T1/2 cells in the presence of a tumor promoter. ANE may be involved in multistep chemical carcinogenesis by its malignant transformation capacity.
Asunto(s)
Areca/química , Nueces/química , Extractos Vegetales/toxicidad , Células Madre Pluripotentes/efectos de los fármacos , Animales , Línea Celular , Ratones , Neoplasias de la Boca/inducido químicamente , Especies Reactivas de Oxígeno/metabolismo , TaiwánRESUMEN
BACKGROUND/PURPOSE: In Taiwan, the combination of betel quid chewing, alcohol consumption, and smoking habits increases oral cancer risk by 123-fold compared to persons without these habits. Lymphocyte populations in patients may potentially affect the malignant transformation of oral precancer. METHODS: A total of 28 patients with oral precancer from our previous cohort were enrolled in this study, and their personal information and oral habits were documented. Their lymphocyte populations (CD4+, CD8+, CD19+, and CD56+) and activation markers (CD25 and CD69) were determined by flow cytometry from 1999 to 2004. After follow up till December 2014, data of patients with/without malignant transformation were recorded, and the relation between oral habits and percentage of initial lymphocyte markers was evaluated using the Student t test and Fisher's exact test. RESULTS: Ten precancer patients developed oral squamous cell carcinoma with a mean period of malignant transformation of 6.8 ± 2.1 years. Patients with malignant transformation had a mean age of 48.4 ± 5.0 years (n = 10), relatively more than that of patients without malignant transformation (41.6 ± 6.3 years, n = 18) (p < 0.05). An increase was noted in the population of peripheral blood mononuclear cells expressing CD4+CD69+, CD19+CD69+, and CD56+CD69+ (p < 0.05) in precancer patients with malignant transformation. Alcohol consumption showed an association with the malignant transformation of patients with precancer (p = 0.030), whereas betel quid and smoking showed little effect. CONCLUSION: These results suggest that age, alcohol consumption, and early activation of T cells, B cells, and natural killer cells are crucial in the malignant transformation of oral precancer. Analysis of patient's lymphocyte populations may help predict the malignant transformation of oral precancer.
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Consumo de Bebidas Alcohólicas/epidemiología , Areca/efectos adversos , Carcinoma de Células Escamosas/epidemiología , Subgrupos Linfocitarios/inmunología , Neoplasias de la Boca/epidemiología , Fumar/epidemiología , Adulto , Linfocitos B/inmunología , Biomarcadores/análisis , Humanos , Células Asesinas Naturales/inmunología , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/etiología , Taiwán/epidemiologíaRESUMEN
OBJECTIVE: Interleukin-1ß (IL-1ß) is an important inflammatory mediator of the dental pulp. IL-1ß stimulates cyclooxygenase-2 (COX-2) expression and prostanoid production of pulp cells and affects the inflammatory and healing processes of the dental pulp. There are two interleukin-1 (IL-1) receptors, IL-1RI and IL-1RII, with opposing effect after activation. However, the expression of IL-1Rs, the effects of IL-1ß on intercellular adhesion molecule-1 (ICAM-1) of dental pulp cells, and its relation to protein kinase B (Akt) signaling and COX activation are not clear. METHOD: Human dental pulp cells were treated with IL-1ß with/without pretreatment and co-incubation by LY294002 (a PI3K/Akt inhibitor), U0126 [a mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) inhibitor], aspirin (a COX inhibitor), or eugenol (a COX inhibitor) for different time periods. The expression of ICAM-1, IL-1RI, and IL-1RII messenger RNA (mRNA) was evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR). ICAM-1 protein expression was examined by western blotting. Soluble ICAM-1 (sICAM-1) level in the culture medium was determined by enzyme-linked immunosorbent assay (ELISA). Activation of Akt and ERK by IL-1ß was measured by Pathscan p-Akt ELISA or western blot. Viable cell number was evaluated by 3-(4,5-dimethyldiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. RESULTS: Dental pulp cells expressed IL-1RI, but little IL-1RII. IL-1ß stimulated COX-2 and ICAM-1 mRNA and protein expression as well as sICAM-1 production of pulp cells. Aspirin and eugenol enhanced the IL-1ß-induced sICAM-1 production and ICAM-1 expression. IL-1ß rapidly activated Akt and ERK. LY294002 and U0126 attenuated IL-1ß-induced ICAM-1 expression and sICAM-1 production. CONCLUSIONS: These results reveal that IL-1ß may be involved in the pulpal inflammatory processes by stimulating ICAM-1 expression and secretion. These events are associated with IL-1RI expression and differential activation of PI3K/Akt and MEK/ERK and COX. CLINICAL RELEVANCE: Pharmacological inhibition of IL-1ß, IL-1RI, COX-2, ICAM-1, and related signaling pathways (MEK/ERK and PI3K/Akt) may be useful for the control of pulpal inflammation.
Asunto(s)
Ciclooxigenasa 2/metabolismo , Pulpa Dental/citología , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Molécula 1 de Adhesión Intercelular/metabolismo , Interleucina-1beta/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Aspirina/farmacología , Western Blotting , Cromonas/farmacología , Ensayo de Inmunoadsorción Enzimática , Eugenol/farmacología , Humanos , Morfolinas/farmacología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal/efectos de los fármacosRESUMEN
Platelet dysfunction is a major risk factor of cardiovascular diseases such as atherosclerosis, stroke and myocardial infarction. Many antiplatelet agents are used for prevention and treatment of these diseases. In this study, phloroglucinol (2.5-25 µM) suppressed AA-induced platelet aggregation and thromboxane B(2) (TXB(2)) production, but not U46619-induced platelet aggregation. Phloroglucinol (100-250 µM) showed little cytotoxicity to platelets. Phloroglucinol inhibited the COX-1 and COX-2 activities by 45-74% and 49-72% respectively at concentrations of 10-50 µM. At concentrations of 1 and 5 µM, phloroglucinol attenuated the AA-induced ROS production in platelets by 30% and 53%, with an IC(50) of 13.8 µM. Phloroglucinol also inhibited the PMA-stimulated ROS production in PMN. Preincubation of platelets by phloroglucinol (10-25 µM) markedly attenuated the AA-induced ERK and p38 phosphorylation. Intravenous administration of phloroglucinol (2.5 and 5 µmol/mouse) suppressed the ex vivo AA-induced platelet aggregation by 57-71%. Phloroglucinol administration also elevated the mice tail bleeding time. Moreover, phloroglucinol inhibited the IL-1ß-induced PGE(2) production in pulp fibroblasts. These results indicate that antiplatelet and anti-inflammatory effects of phloroglucinol are related to inhibition of COX, ROS and TXA2 production as well as ERK/p38 phosphorylation in platelets. Phloroglucinol further suppress PMA-induced ROS production in PMN. The antiplatelet effect of phloroglucinol was confirmed by ex vivo study. Clinically, the consumption of phloroglucinol-containing food/natural products as nutritional supplement may be helpful to cardiovascular health. Phloroglucinol has potential pharmacological use.
Asunto(s)
Plaquetas/efectos de los fármacos , Floroglucinol/farmacología , Especies Reactivas de Oxígeno/metabolismo , Tromboxano A2/biosíntesis , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/farmacología , Animales , Ácido Araquidónico/farmacología , Plaquetas/metabolismo , Ciclooxigenasa 1/efectos de los fármacos , Ciclooxigenasa 1/metabolismo , Ciclooxigenasa 2/efectos de los fármacos , Ciclooxigenasa 2/metabolismo , Relación Dosis-Respuesta a Droga , Humanos , Concentración 50 Inhibidora , Interleucina-1beta/administración & dosificación , Masculino , Ratones , Ratones Endogámicos ICR , Floroglucinol/administración & dosificación , Fosforilación/efectos de los fármacos , Agregación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/farmacología , Conejos , Transducción de Señal/efectos de los fármacos , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
A cemental tear is a special kind of root fracture that may cause rapid and localized periodontal destruction. Most cemental tears have been reported on bicuspids and incisors. Here we present a case of cemental tears on both the right mandibular first and second molars. The patient was a 72-year-old man who showed gingival swelling and a deep pocket over his right mandibular second molar as well as a deep periodontal pocket on the distolingual aspect of the first molar. During exploratory flap surgery, a detached root fragment on the mesial side of the second molar and a small root fragment on the lingual surface of the first molar were found and removed for biopsy. After histopathological examination, both root fragments were confirmed to be cemental tears. The periodontal defects were treated by osseous grafting and guided tissue regeneration. A postoperative probing depth of 4 mm on the second molar was recorded at 3 months and remained stable for 5 years. Where marked periapical and periodontal bony destruction are present, a cemental tear should be considered as a possible diagnosis, even in the molar teeth, for early treatment to improve prognosis.
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Cemento Dental/lesiones , Diente Molar/lesiones , Fracturas de los Dientes/diagnóstico , Raíz del Diente/lesiones , Anciano , Periodontitis Agresiva/etiología , Pérdida de Hueso Alveolar/etiología , Trasplante Óseo , Estudios de Seguimiento , Regeneración Tisular Guiada Periodontal , Humanos , Masculino , Mandíbula , Pérdida de la Inserción Periodontal/etiología , Bolsa Periodontal/etiología , Fracturas de los Dientes/complicacionesRESUMEN
This study compared implant outcomes following maxillary sinus floor augmentation (MSFA) in edentulous patients with a residual alveolar bone height ≤3âmm. Four techniques were evaluated: 1-stage bone-added osteotome sinus floor elevation procedure (BAOSFE) with simultaneous implant placement; 2-stage BAOSFE with delayed implant placement; 1-stage lateral window sinus floor elevation with simultaneous implant placement; and 2-stage lateral window sinus floor elevation with delayed implant placement. Patients were followed for 18 to 72 months (mean: 52.5 months) after prosthesis placement. Data were analyzed with cone-beam computed tomography. A total of 96 implants from 71 patients were analyzed; pretreatment, there were no significant differences between patients. Total implant survival was 98.9%. The mean residual bone height was significantly higher in the 1-stage BAOSFE group than the other groups (Pâ<â.01); 1 implant in this group failed at 3 months. There was no significant difference in total bone height gain between groups. However, the bone height gain of 1st sinus lifting with 2-stage BAOSFE was significantly lower than the 2-stage lateral window procedure (Pâ<â.01). There was no prosthesis failure. The favorable implant outcomes suggest these 1-stage and 2-stage MSFA procedures should be considered as alternative treatment options for patients with extremely atrophic posterior maxilla.
Asunto(s)
Huesos/cirugía , Senos Paranasales/cirugía , Prótesis e Implantes/tendencias , Elevación del Piso del Seno Maxilar/estadística & datos numéricos , Pesos y Medidas , Huesos/anomalías , Distribución de Chi-Cuadrado , Femenino , Humanos , Masculino , Persona de Mediana Edad , Procedimientos Quírurgicos Nasales/instrumentación , Procedimientos Quírurgicos Nasales/métodos , Osteotomía/métodos , Radiografía/métodos , Radiografía/estadística & datos numéricos , Elevación del Piso del Seno Maxilar/instrumentación , Elevación del Piso del Seno Maxilar/métodos , Estadísticas no Paramétricas , Resultado del TratamientoRESUMEN
BACKGROUND: Tongue cancer metastasis is mainly through blood stream and possibly associated with tumor cell-induced platelet aggregation (TCIPA). METHODS: Platelet aggregation was induced by different amounts of SAS tongue cancer cells with/without inhibitors and the latent period for induction of platelet aggregation was recorded. Gene expression was analyzed by reverse transcriptase-polymerase chain reaction. RESULTS: SAS cells (4 x 10(4) to 1 x 10(6) cells/ml) induced platelet aggregation in a cell density-dependent manner. The latent period for induction of platelet aggregation reduced from 11.3 min (2 x 10(5) cells/ml) to 0.9 min (5 x 10(5) cells/ml). The extent of platelet aggregation increased from 39% to 76% by 2 x 10(5) and 5 x 10(5) SAS cells. Pre-treatment of SAS cells with aspirin showed little effect on its induction of platelet aggregation. SAS cells expressed tissue factor (TF) mRNA and the SAS cells-induced TCIPA was inhibited by TF neutralization antibody (5-20 microg/ml), heparin (5-10 U/ml), Hirudin fragment 54-65 (50 microg/ml) and D-Phenylalanyl-L-prolyl-L-arginine chloromethyl ketone. But areca nut (AN, a betel quid component known to generate reactive oxygen species (ROS)) extract showed little effect on TF expression in SAS cells. Pre-treatment with U73122 and 2-aminoethoxydiphenylborate inhibited SAS-induced TCIPA. Interestingly, catalase suppressed SAS cells-induced TCIPA, whereas AN extract enhanced this event. CONCLUSIONS: These results suggest that tongue cancer cells may induce TCIPA and enhance tumor metastasis. SAS-induced TCIPA is related to TF secretion, thrombin generation and associated with Phospholipase C-Inositol triphosphate signaling and ROS production. Betel quid chewing may potentially promote tongue cancer metastasis.
Asunto(s)
Areca , Extractos Vegetales/farmacología , Agregación Plaquetaria/fisiología , Tromboplastina/metabolismo , Neoplasias de la Lengua/metabolismo , Técnicas de Cocultivo , Células Epiteliales/metabolismo , Perfilación de la Expresión Génica , Encía/citología , Encía/metabolismo , Humanos , Mucosa Bucal/citología , Mucosa Bucal/metabolismo , Metástasis de la Neoplasia , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/farmacología , Agregación Plaquetaria/efectos de los fármacos , ARN Mensajero/análisis , Sistemas de Mensajero Secundario/efectos de los fármacos , Sistemas de Mensajero Secundario/fisiología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Estadísticas no Paramétricas , Tromboplastina/genética , Factores de Tiempo , Células Tumorales CultivadasRESUMEN
BACKGROUND: Cone-beam computed tomography (CBCT) presurgical assessment on the maxillary sinus can reduce the possibility of Schneiderian membrane perforation. This study examined Schneiderian membrane thickness (SMT) and its relationship with neighboring hard tissues for patients with and without membrane thickening. For patients with sinus infections, we evaluated dimensional changes of the SMT post-extraction relative to pre-extraction SMT and residual bone height (RBH). METHODS: CBCT images from 93 patients needing single-tooth implant reconstruction without (n = 83) and with (n = 14) odontogenic infected maxillary sinuses were assessed. SMT, RBH, and lateral wall thickness (LWT) were measured. Causes of extraction, RBH in the infection site, and retrospective post-extraction record of SMT were recorded for the thickened SMT group. RESULTS: Mean SMT for normal SMT group was 1.13 ± 0.43 mm, RBH was 6.26 ± 2.38 mm; upper and lower LWT was 1.85 ± 0.95 mm, and 3.07 ± 2.26 mm, respectively. RBH and LWT had no significant relationships with SMT. For thickened SMT group, mean values for SMT and RBH prior to extraction were 4.53 ± 2.46 mm and 1.97 ± 1.43 mm, respectively. Pre-extraction SMT had a moderately negative correlation with pre-extraction RBH. SMT resolution in thickened SMT group was observed by 2.80 ± 1.37 months post-extraction; post-extraction SMT was not significantly different from normal SMT group (p = .187). CONCLUSIONS: Within the limitation of the sample size, thickened SMT induced by odontogenic infection subsides about 3 months following tooth extraction, and further sinus lifting implant surgery may be considered.
Asunto(s)
Tomografía Computarizada de Haz Cónico , Infecciones/etiología , Seno Maxilar/diagnóstico por imagen , Mucosa Nasal/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Tomografía Computarizada de Haz Cónico/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Diente/diagnóstico por imagen , Diente/cirugíaRESUMEN
BACKGROUND: Protease-activated receptors (PARs) can be stimulated by thrombin and other proteases generated by periodontal pathogens. Activation of PARs in gingival fibroblasts (GFs) can modulate wound healing and inflammatory responses in gingival tissues. METHODS: The mRNA expression of PARs and early responsive genes in GFs and other oral cells was studied by reverse transcription-polymerase chain reaction. Western blotting was used to study the activation of p38 and cAMP responsive element binding protein (CREB)/activating transcription factor (ATF)-1 as well as Ras. RESULTS: GFs, dental pulp cells, and buccal mucosal fibroblasts expressed PAR-1 and -3 receptors, whereas gingival keratinocytes expressed PAR-1 and -2 receptors. Stimulation of GFs by thrombin rapidly activated Ras signaling and the phosphorylation of CREB/ATF-1 and p38. Thrombin also stimulated the expression of c-fos in GFs within 1 hour of exposure. Stimulation of c-jun mRNA expression showed biphasic responses with two peaks after 1 and 8 hours of exposure. Elevated c-myc expression in GFs by thrombin was noted after 2 hours of exposure. Moreover, the stimulation of c-fos and c-myc mRNA expression by thrombin can be attenuated by D-Phe-Pro-ArgCH(2)Cl, a serine-proteinase inhibitor. CONCLUSIONS: PAR activation during gingival wounding or inflammation may stimulate Ras-CREB/ATF-1 signaling and c-fos, c-jun, and c-myc expression. This might be due to the proteinase activity of thrombin. These signaling events are important for wound healing and inflammatory responses in gingival tissues.
Asunto(s)
Factor de Transcripción Activador 1/efectos de los fármacos , Proteína de Unión a CREB/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Encía/efectos de los fármacos , Proteínas Proto-Oncogénicas c-fos/efectos de los fármacos , Proteínas Proto-Oncogénicas c-jun/efectos de los fármacos , Proteínas Proto-Oncogénicas c-myc/efectos de los fármacos , Proteínas Proto-Oncogénicas p21(ras)/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Trombina/farmacología , Western Blotting , Células Cultivadas , Pulpa Dental/citología , Pulpa Dental/efectos de los fármacos , Fibroblastos/citología , Encía/citología , Humanos , Queratinocitos/efectos de los fármacos , Mucosa Bucal/citología , Mucosa Bucal/efectos de los fármacos , Oligopéptidos/farmacología , Receptor PAR-1/efectos de los fármacos , Receptor PAR-2/efectos de los fármacos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Inhibidores de Serina Proteinasa/farmacología , Trombina/antagonistas & inhibidores , Factores de Tiempo , Proteínas Quinasas p38 Activadas por Mitógenos/efectos de los fármacosRESUMEN
Transforming growth factor beta (TGF-beta) may regulate the biological activities of dental pulp cells. We found that human dental pulp cells expressed TGF-beta1, TGF-beta2, and a little amount of TGF-beta3 messenger RNA (mRNA). The exposure of pulp cells to TGF-beta2 induced the phosphorylation of Smad2/3, Smad1/5/8, and extracellular regulated-kinase 1/2 (ERK1/2) as observed by Western blotting. Exposure to TGF-beta2 decreased the alkaline phosphatase (ALP) mRNA expression and enzyme activity. Pretreatment of pulp cells with SB431542 (an inhibitor of TGF-beta ALK-4, ALK-5, and ALK-7 receptors) but not U0126 (a MEK1 inhibitor) prevented the inhibition of viable cell number, ALP activity, and mRNA expression by TGF-beta2 in dental pulp cells. These results suggest that TGF-beta may affect the growth and differentiation of dental pulp cells via an autocrine fashion by activation of the ALK/Smad2/3-signal transduction pathways. TGF-beta2 possibly regulates the differentiation of pulp cell at specific stages synergistically with other factors.
Asunto(s)
Pulpa Dental/metabolismo , Sistema de Señalización de MAP Quinasas/fisiología , Proteínas Serina-Treonina Quinasas/metabolismo , Receptores de Factores de Crecimiento Transformadores beta/metabolismo , Proteínas Smad Reguladas por Receptores/metabolismo , Factor de Crecimiento Transformador beta2/fisiología , Fosfatasa Alcalina/metabolismo , Benzamidas/farmacología , Diferenciación Celular , Proliferación Celular , Pulpa Dental/citología , Dioxoles/farmacología , Inhibidores Enzimáticos/farmacología , Quinasas MAP Reguladas por Señal Extracelular/fisiología , Humanos , Quinasas Quinasa Quinasa PAM/fisiología , Isoformas de Proteínas , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Receptor Tipo I de Factor de Crecimiento Transformador beta , Receptores de Factores de Crecimiento Transformadores beta/antagonistas & inhibidores , Factor de Crecimiento Transformador beta1/biosíntesis , Factor de Crecimiento Transformador beta2/biosíntesisRESUMEN
Transforming growth factor-ß1 (TGF-ß1) plays an important role in the pulpal repair and dentinogenesis. Plasminogen activation (PA) system regulates extracellular matrix turnover. In this study, we investigated the effects of TGF-ß1 on PA system of dental pulp cells and its signalling pathways. Dental pulp cells were treated with different concentrations of TGF-ß1. MTT assay, reverse transcription-polymerase chain reaction, Western blotting and enzyme-linked immunosorbant assay (ELISA) were used to detect the effect of TGF-ß1 on cell viability, mRNA and protein expression of urokinase-type plasminogen activator (uPA), uPA receptor (uPAR), plasminogen activator inhibitor-1 (PAI-1) as well as their secretion. The phosphorylation of Smad2 and TAK1 was analysed by Pathscan ELISA or Western blotting. Cells were pretreated with SB431542 (ALK5/Smad2/3 inhibitor), 5z-7-oxozeaenol (TAK1 inhibitor) and U0126 (MEK/ERK inhibitor) for examining the related signalling. TGF-ß1 slightly inhibited cell growth that was reversed by SB431542. TGF-ß1 upregulated both RNA and protein expression of PAI-1 and uPAR, whereas it downregulated uPA expression. Accordingly, TGF-ß1 stimulated PAI-1 and soluble uPAR (suPAR) secretion of pulp cells, whereas uPA secretion was inhibited. TGF-ß1 induced the phosphorylation of Smad2 and TAK1. In addition, SB431542, 5z-7-oxozeaenol and U0126 attenuated the TGF-ß1-induced secretion of PAI-1 and suPAR. These results indicate that TGF-ß1 is possibly involved in the repair/regeneration and inflammatory processes of dental pulp via regulation of PAI-1, uPA and uPAR. These effects of TGF-ß1 are related to activation of ALK5/Smad2, TAK1 and MEK/ERK signalling pathways. Clarifying the signal transduction for the effects of TGF-ß1 is helpful for pulpo-dentin regeneration and tissue engineering. Copyright © 2016 John Wiley & Sons, Ltd.
Asunto(s)
Pulpa Dental/metabolismo , Quinasas Quinasa Quinasa PAM/metabolismo , Sistema de Señalización de MAP Quinasas , Plasminógeno/metabolismo , Receptor Tipo I de Factor de Crecimiento Transformador beta/metabolismo , Proteína Smad2/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Pulpa Dental/citología , HumanosRESUMEN
Bisphosphonates (BPs) suppress bone resorption and increase bone strength, thus reducing the risk of fracture. Oral BPs are widely used for the prevention and treatment of osteoporosis and osteopenia. Here, we describe the case of a postmenopausal woman who took oral alendronate for >3 years for osteoporosis. The patient presented at the clinic with sharp jaw pain and swelling on the left mandible 4 months after extraction of the third molar. Clinical examinations identified an inflamed mucosal opening with pus over an area of necrotic bone. Initial images of cone beam computed tomography revealed a sequestrum at the extracted socket. The condition did not improve after 1 week of antibiotic treatment; therefore, the alendronate treatment was terminated and the patient was prescribed strontium ranelate instead. The patient gradually recovered and, at the 2-year follow-up, the site of BP-related osteonecrosis of the jaw healed completely as determined by both clinical and cone beam computed tomography measures. The bone mineral densities in the femoral neck and lumbar spine improved after 1 year, and were maintained at the 3-year follow-up. The serum C-terminal cross-linking telopeptide values also gradually increased from the initial 130 pg/mL to 320 pg/mL at the 3-year follow-up. Taken together, this case supports the use of strontium ranelate as an alternative treatment for postmenopausal women who receive long-term oral BP treatments and are at risk for serious complications of BP-related osteonecrosis of the jaw.
Asunto(s)
Alendronato/efectos adversos , Osteonecrosis de los Maxilares Asociada a Difosfonatos/tratamiento farmacológico , Conservadores de la Densidad Ósea/efectos adversos , Osteoporosis Posmenopáusica/tratamiento farmacológico , Tiofenos/uso terapéutico , Anciano de 80 o más Años , Alendronato/uso terapéutico , Osteonecrosis de los Maxilares Asociada a Difosfonatos/diagnóstico , Osteonecrosis de los Maxilares Asociada a Difosfonatos/etiología , Conservadores de la Densidad Ósea/uso terapéutico , Difosfonatos/efectos adversos , Femenino , Humanos , PosmenopausiaRESUMEN
INTRODUCTION: A vertical root fracture (VRF) is a root fracture extending along the longitudinal axis of roots and is often noted in endodontically treated teeth. However, the clinical and radiographic characteristics of VRFs are not completely known. METHODS: A total of 65 teeth with 68 vertical fractured roots in 58 Chinese patients were investigated. The clinical examination records and radiographic images were reviewed in detail. RESULTS: A total of 24 male (41.38%) and 34 female (58.62%) patients aged 25-90 years (average = 57 years) were included; 51 (87.93%) and 7 (12.07%) patients exhibited 1 tooth and 2 teeth with VRFs, respectively, in the dentition. VRFs occurred mainly in the mesial root (20 roots, 57.14%) of the mandibular molars (29 teeth, 44.62%). Clinically, teeth with VRFs usually presented a periodontal probing depth >5 mm (44 teeth, 91.67%, P < .001) with a prosthesis (55 teeth, 84.62%, P < .001) and a relatively intact dentition (42 patients exhibited <4 missing teeth in the dentition, 77.78%, P < .001). Most of the nonendodontically treated VRFs exhibited attrited occlusal surfaces. Radiographic characteristics of the teeth with VRFs were typically associated with prior root canal treatment (56 teeth, 86.15%, P < .001), periodontal bone loss (62 teeth, 95.38%, P < .001), apical bone loss (52 teeth, 80.00%, P < .001), and periodontal ligament widening (61 teeth, 93.85%, P < .001). The mesial roots of the mandibular molars were most susceptible to VRFs in both endodontically and nonendodontically treated teeth. CONCLUSIONS: These results elucidated some clinical and radiographic and diagnostic features that facilitate VRF identification.
Asunto(s)
Fracturas de los Dientes/diagnóstico por imagen , Raíz del Diente/lesiones , Diente no Vital/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radiografía Dental , Raíz del Diente/diagnóstico por imagenRESUMEN
INTRODUCTION: Basic fibroblast growth factor (bFGF) plays differential effects on the proliferation, differentiation, and extracellular matrix turnover in various tissues. However, limited information is known about the effect of bFGF on dental pulp cells. The purposes of this study were to investigate whether bFGF influences the cell differentiation and extracellular matrix turnover of human dental pulp cells (HDPCs) and the related gene and protein expression as well as the role of the mitogen-activated protein kinase (MEK)/extracellular-signal regulated kinase (ERK) signaling pathway. The expression of fibroblast growth factor receptors (FGFRs) in HDPCs was also studied. METHODS: The expression of FGFR1 and FGFR2 in HDPCs was investigated by reverse-transcription polymerase chain reaction. HDPCs were treated with different concentrations of bFGF. Cell proliferation was evaluated using the 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Cell differentiation was evaluated using alkaline phosphatase (ALP) staining. Changes in messenger expression of cyclin B1 and tissue inhibitor of metalloproteinase (TIMP) 1 were determined by reverse-transcription polymerase chain reaction. Changes in protein expression of cdc2, TIMP-1, TIMP-2, and collagen I were determined by Western blotting. U0126 was used to clarify the role of MEK/ERK signaling. RESULTS: HDPCs expressed both FGFR1 and FGFR2. Cell viability was stimulated by 50-250 ng/mL bFGF. The expression and enzyme activities of ALP were inhibited by 10-500 ng/mL bFGF. At similar concentrations, bFGF stimulates cdc2, cyclin B1, and TIMP-1 messenger RNA and protein expression. bFGF showed little effect on TIMP-2 and partly inhibited collagen I expression of pulp cells. U0126 (a MEK/ERK inhibitor) attenuated the bFGF-induced increase of cyclin B1, cdc2, and TIMP-1. CONCLUSIONS: bFGF may be involved in pulpal repair and regeneration by activation of FGFRs to regulate cell growth; stimulate cdc2, cyclin B1, and TIMP-1 expression; and inhibit ALP. These events are partly associated with MEK/ERK signaling.
Asunto(s)
Pulpa Dental/citología , Factor 2 de Crecimiento de Fibroblastos/farmacología , Fosfatasa Alcalina/metabolismo , Western Blotting , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Ciclina B1/metabolismo , Pulpa Dental/efectos de los fármacos , Pulpa Dental/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/metabolismo , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Inhibidor Tisular de Metaloproteinasa-1/metabolismoRESUMEN
Increased levels of oxidized low-density lipoprotein oxLDL) are shown to elevate the risk of cardiovascular diseases such as atherosclerosis, thrombosis, stroke, and myocardial infarction. This is possibly due to the toxic effects of oxLDLs on vascular cells. Various oxLDLs including lysophosphatidylcholine (LPC) and 7-ketocholesterol injure vascular endothelial cells and stimulate inflammatory reaction. However the toxicity of LPC on endothelial cells is not clear. In this study, human endothelial cells were exposed to LPC. Cytotoxicity was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. Propidium iodide (PI) staining or PI/Annexin V dual staining flow cytometry were used to determine cell cycle progression and apoptosis. Reactive oxygen species (ROS) level was analyzed by DCFH-DA labeling flow cytometry. RNA and protein expression of endothelial cells was studied by reverse transcriptase-polymerase chain reaction and western blotting. IL-8 secretion was measured by enzyme-linked immunosorbant assay. LPC showed cytotoxicity to endothelial cells (>50 µg/ml). LPC induced cell cycle arrest and apoptosis with concomitant inhibition of cdc2 and cyclin B1 expression. LPC stimulated intracellular ROS production and ATM/Chk2, ATR/Chk1 and Akt activation. IL-8 expression and secretion in endothelial cells were induced by LPC. LPC-induced apoptosis, and IL-8 expression/secretion was attenuated by LY294002, a PI3K/Akt inhibitor. These results reveal that LPC is involved in the pathogenesis of atherosclerosis and vascular diseases by stimulation of inflammation and injury to endothelial cells. These events are related to ROS, ATM/Chk2, ATR/Chk2 and PI3K/Akt signaling. Understanding the toxic mechanisms of LPC is useful for future prevention and treatment atherosclerosis.
RESUMEN
1.--Thrombin is activated during gingival tissue injury and inflammation. Thrombin (platelet)-rich plasma has been used for periodontal regeneration with success. Thrombin and other bacterial proteases also affect the functions of adjacent periodontal cells via stimulation of protease-activated receptors (PARs). 2.--We noted that thrombin (0.1-2 U ml(-1)), human, and frog PAR-1 agonist peptide (20-240 microM) induced the gingival fibroblast (GF)-populated collagen gel contraction within 2 h of exposure. However, PAR-2, PAR-3, and PAR-4 agonist peptide (20-240 microM) showed little effect on collagen gel contraction. U73122 (phospholipase C inhibitor) and 2-APB (IP3 antagonist) were effective in inhibition of GF contraction. 3.--Thrombin-induced GF contraction was inhibited by 5 mM EGTA (an extracellular calcium chelator) and verapamil (an L-type calcium channel blocker). In addition, W7 (10 and 25 microM, a calcium/calmodulin (CaM) inhibitor), ML-7 (50 microM, myosin light chain kinase (MLCK) inhibitor), and HA1077 (100 microM, Rho kinase inhibitor) completely inhibited the thrombin-induced collagen gel contraction. Thrombin also induced the phosphorylation of ERK1/ERK2 and elevated the Rho-GTP levels in GF. 4.--However, U0126 only partially inhibited the thrombin-induced GF contraction. Similarly, wortmannin (100 nM), LY294002 (20 microM) (two PI3K inhibitor) and genistein also showed partial inhibition. Moreover, NAC was not able to suppress the GF contraction, as supported by the slight decrease in reactive oxygen species production in GF by thrombin. 5.--Thrombin also stimulated metalloproteinase-2 (MMP-2) and MMP-3 production in GF. But addition of GM6001 or 1,10-phenanthroline, two MMP inhibitors, could not inhibit the thrombin-induced GF contraction. 6.--These results indicate that thrombin is crucial in the periodontal inflammation and wound healing by promoting GF contraction. This event is mainly mediated via PAR-1 activation, PLC activation, extracellular calcium influx via L-type calcium channel, and the calcium/CaM-MLCK and Rho kinase activation pathway.
Asunto(s)
Colágeno/fisiología , Fibroblastos/fisiología , Encía/citología , Trombina/fisiología , Calcio/metabolismo , Proteínas Quinasas Dependientes de Calcio-Calmodulina/antagonistas & inhibidores , Tamaño de la Célula , Células Cultivadas , Activación Enzimática , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Geles , Humanos , Metaloproteasas/biosíntesis , Quinasa de Cadena Ligera de Miosina/antagonistas & inhibidores , Oxidación-Reducción , Péptidos/farmacología , Especies Reactivas de Oxígeno/metabolismo , Receptores Proteinasa-Activados/agonistas , Transducción de Señal , Fosfolipasas de Tipo C/fisiología , Proteínas de Unión al GTP rho/metabolismoRESUMEN
BACKGROUND: Chronic infection and inflammation, including periodontitis, is linked to an increased risk for atherosclerosis. To investigate the possible adverse effects of periodontitis in maintenance hemodialysis patients, we compared periodontal severity with malnutrition and inflammation, which are associated with poor atherosclerotic outcome in hemodialysis patients. METHODS: Two hundred fifty-three hemodialysis patients were included in this study to evaluate clinical periodontal status by using the Plaque Index, Gingival Index, and Periodontal Disease Index. Geographic, hematologic, biochemical, and dialysis-related data also were collected. Values for nutritional and inflammatory markers, such as albumin, blood urea nitrogen, creatinine, transferrin, absolute lymphocyte count, normalized protein catabolic rate, high-sensitivity C-reactive protein, and ferritin, were included for analysis with the Periodontal Index. RESULTS: Poor oral health status was shown by 80.6% of hemodialysis patients with periodontal disease. In an analysis of geographic and disease-related parameters, we found that aging, smoking, diabetes, and longer dialysis duration were associated with severity of periodontitis. Parameters of malnutrition and inflammation also were associated with poor periodontal status. We next conducted multiple regression analysis and found that age, diabetes, smoking, albumin level, and dialysis duration were associated independently with periodontitis severity in hemodialysis patients. According to the severity of periodontitis, there were higher percentiles of patients with malnutrition (chi-square = 13.055; P = 0.005) and inflammation (chi-square = 10.046; P = 0.018) in the severe group. CONCLUSION: Periodontal health is poor in hemodialysis patients and correlates with markers of malnutrition and inflammation. Its diagnosis and treatment deserve better awareness.