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AIM: To examine the role of palmitic acid in lipopolysaccharide (LPS)-stimulated chemotaxis of macrophages and the potential contribution of saturated fatty acid in signalling during the pathogenesis of apical periodontitis. METHODOLOGY: J774, a mouse macrophage cell line, was used in the experiments. After treatment with LPS, proteolytic maturation of sterol regulatory element-binding protein-1c (SREBP-1c) and expression of fatty acid synthase (FASN) were examined by Western analysis. Levels of palmitic acid were measured by reverse phase-high performance liquid chromatography-mass spectrometry. Knockdown of SREBP-1c and FASN was accomplished by small interfering RNA technology. Secretion of CC-chemokine ligand 2 (CCL2) and cellular chemotaxis were assessed by enzyme-linked immunosorbent assay and transwell migration assay, respectively. Sulfo-N-succinimidyl oleate (SSO) treatment was used to inhibit fatty acid signalling in vitro and also in a rat model of apical periodontitis. All data were first subjected to Levene's test. In vitro data were then analysed using ANOVA followed by Tukey's multiple comparison test. Data from animal experiments were analysed by independent t-tests. The significant level was set at 0.05. RESULTS: LPS stimulated proteolytic maturation of SREBP-1c and FASN expression in macrophages and significantly enhanced palmitic acid synthesis (P < 0.05). Knockdown of SREBP-1c attenuated LPS-enhanced FASN expression. Knockdown of FASN significantly suppressed LPS-enhanced palmitic acid synthesis (P < 0.05). LPS and exogenous palmitic acid significantly enhanced CCL2 secretion and macrophage chemotaxis (all P < 0.05). Inhibition of FASN expression significantly alleviated LPS-augmented CCL2 secretion (P < 0.05). SSO significantly suppressed CCL2 secretion and macrophage chemotaxis augmented by LPS and palmitic acid (all P < 0.05). In a rat model of induced apical periodontitis, SSO treatment significantly attenuated progression of apical periodontitis and macrophage recruitment (all P < 0.05). CONCLUSIONS: LPS/SREBP-1c/FASN/palmitic acid signalling contributed to tissue destruction caused by bacterial infection. Modulation of lipid metabolism and signalling may be helpful for the management of apical periodontitis.
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Lipopolisacáridos , Periodontitis Periapical , Animales , Ácidos Grasos , Macrófagos , Ratones , Ratas , Proteína 1 de Unión a los Elementos Reguladores de EsterolesRESUMEN
Jaw deviation is frequently seen in Class III patients. The aim of the study was to investigate asymmetric features of skeletal, dental and soft tissues in three types of jaw asymmetry based on our previously reported classification system. The cone-beam computed tomography (CBCT) images of 70 Class III patients were analysed. Group 1 patients showed large shift of menton and synchronous but smaller ramus deviation. The maxillomandibular complex had roll and yaw rotations to the menton-deviation side. Maxillary and dental asymmetry was obvious in transverse and vertical dimensions. Cant of occlusal plane and lip line was apparent. Group 2 patients also exhibited menton and ramus deviation to the same side but the discrepancy in ramus width was larger than menton shift. Asymmetry in Group 2 resulted from a bodily side shift of the maxillomandibular complex without obvious rotation. Group 3 patients had menton and ramus deviated in opposite directions which seemed secondary to a yaw rotation. Double-jaw surgery is generally required for Groups 1 and 3 while Group 2 patients may be successfully treated by mandibular surgery only provided that arch width discrepancy can be managed by orthodontic measures.
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Asimetría Facial , Maloclusión de Angle Clase III , Cefalometría , Tomografía Computarizada de Haz Cónico , Humanos , Imagenología Tridimensional , Mandíbula , MaxilarRESUMEN
AIM: To assess the connection between mitophagy and hypoxia-induced apoptosis in osteoblasts and whether simvastatin alleviates bone resorption in apical periodontitis through modulation of mitophagy-related apoptosis. METHODOLOGY: Hypoxia-induced generation of reactive oxygen species in mitochondria and changes in mitochondrial membrane potential were evaluated, respectively, by MitoSOX and JC-1 fluorescence dye signalling. Accumulation of mitophagy markers PTEN-induced putative kinase 1 (PINK1) and Parkin in mitochondria was examined by Western blotting and immunofluorescence microscopy. Osteoblast apoptosis was assessed by Western analysis of cleaved-poly (adenosine diphosphate ribose) polymerase (PARP). In a rat model of induced apical periodontitis, the therapeutic effect of simvastatin and its action on osteoblast mitophagy and apoptosis were examined. anova, Fisher's and Student's t-test were used for data analysis. RESULTS: Hypoxia-induced mitochondrial dysfunction and stimulated mitophagy in osteoblasts. Hypoxia also provoked apoptosis in osteoblasts and inhibition of mitophagy decreased hypoxia-augmented apoptotic activity. Simvastatin alleviated hypoxia-induced mitochondrial dysfunction, mitophagy and apoptosis. The protective action of simvastatin against apoptosis was related to its antimitophagy activity. Experiments in the rat model of induced apical periodontitis supported the laboratory findings. Simvastatin treatment mitigated periapical bone loss and reduced the activities of apoptosis and mitophagy in regional osteoblasts. CONCLUSIONS: The results suggest that modulation of osteoblast mitophagy may help diminish bone loss associated with inflammation and has potential as an auxiliary therapy for apical periodontitis.
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Resorción Ósea , Periodontitis Periapical , Animales , Apoptosis , Humanos , Mitofagia , Osteoblastos , Ratas , SimvastatinaRESUMEN
AIM: To investigate the attenuating effect of sirtuin 6 (SIRT6) on hypoxia-induced production of chemokine (C-C motif) ligand 2 (CCL2) by osteoblasts and the relevance of this action on the pathogenesis of periapical lesions. METHODOLOGY: Sirtuin 6 was overexpressed in MC3T3-E1 murine osteoblasts by lentivirus-mediated gene transfer. The relationship between the antiglycolytic/antioxidative activities of SIRT6 and its effect on hypoxia-induced CCL2 production were examined. Pathogenetic relevance of the actions of SIRT6 was assessed in a rat model of induced apical periodontitis. The data were analysed statistically using Student's t-test or one-way analysis of variance (anova) and then a Tukey's multiple comparison test. RESULTS: In cultured murine osteoblasts, 24-h hypoxic treatment significantly enhanced the generation of reactive oxygen species (P = 0.003), expression of lactate dehydrogenase A (LDHA) and production of lactate (P = 0.007). A reciprocal effect between hypoxia-induced redox imbalance and hypoxia-enhanced glycolysis was noted which in turn augmented the secretion of CCL2. Through its antiglycolytic and antioxidative effects, SIRT6 blocked the vicious cycle to suppress CCL2 production. In normal periapical tissues of rats, strong expression of SIRT6 and low levels of LDHA and 8-OHdG (a marker of oxidative DNA damage) were found in osteoblasts. In induced apical periodontitis, osteoblastic expression of SIRT6 was significantly suppressed (P = 0.001) which was associated with significantly elevated levels of LDHA (P = 0.003) and 8-OHdG (P = 0.004) and significantly enhanced recruitment of macrophages (P = 0.004). CONCLUSIONS: Sirtuin 6 has a therapeutic effect on periapical lesions through suppression of CCL2 synthesis. The anti-inflammatory action of SIRT6 is closely related to its regulatory activities in cellular metabolism and redox homoeostasis.
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Quimiocina CCL2/metabolismo , Hipoxia/metabolismo , Osteoblastos/metabolismo , Periodontitis Periapical/metabolismo , Sirtuinas/metabolismo , Animales , Western Blotting , Células Cultivadas , Ácido Láctico/metabolismo , Ratones , Mitocondrias/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Tumour growth is closely related to the development of new blood vessels to supply oxygen and nutrients to cancer cells. Without the neovascular formation, tumour volumes cannot increase and undergo metastasis. Antiangiogenesis is one of the most promising approaches for antitumour therapy. The exploration of new antiangiogenic agents would be helpful in antitumour therapy. Quinoline is an aromatic nitrogen compound characterized by a double-ring structure which exhibits a benzene ring fused to pyridine at two adjacent carbon atoms. The high stability of quinoline makes it preferable in a variety of therapeutic and pharmaceutical applications, including antitumour treatment. This work is to examine the potential antiangiogenic activity of the synthetic compound 2-Formyl-8-hydroxy-quinolinium chloride. We found that 2-Formyl-8-hydroxy-quinolinium chloride could inhibit the growth of human umbilical vein endothelial cells in vitro. Using the diethylnitrosamine-induced hepatocarcinogenesis model, 2-Formyl-8-hydroxy-quinolinium chloride showed strong antiangiogenic activity. Furthermore, 2-Formyl-8-hydroxy-quinolinium chloride could inhibit the growth of large Hep3B xenografted tumour from the nude mice. We assume that 2-Formyl-8-hydroxy-quinolinium chloride could be a potential antiangiogenic and antitumour agent and it is worthwhile to further study its underlying working mechanism.
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Inhibidores de la Angiogénesis/farmacología , Hidroxiquinolinas/farmacología , Compuestos de Quinolinio/farmacología , Inhibidores de la Angiogénesis/química , Inhibidores de la Angiogénesis/uso terapéutico , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Carcinogénesis/patología , Carcinoma Hepatocelular/irrigación sanguínea , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Muerte Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Dietilnitrosamina , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Humanos , Hidroxiquinolinas/química , Hidroxiquinolinas/uso terapéutico , Neoplasias Hepáticas/irrigación sanguínea , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Ratones Endogámicos C57BL , Ratones Desnudos , Compuestos de Quinolinio/química , Compuestos de Quinolinio/uso terapéutico , Carga Tumoral/efectos de los fármacos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Aspergillus niger (A. niger) is a common species of Aspergillus molds. Cutaneous aspergillosis usually occurs in skin sites near intravenous injection and approximately 6% of cutaneous aspergillosis cases which do not involve burn or HIV-infected patients are caused by A. niger. Biomaterials and biopharmaceuticals produced from microparticle-based drug delivery systems have received much attention as microencapsulated drugs offer an improvement in therapeutic efficacy due to better human absorption. The frequently used crosslinker, glutaraldehyde, in gelatin-based microencapsulation systems is considered harmful to human beings. In order to tackle the potential risks, agarose has become an alternative polymer to be used with gelatin as wall matrix materials of microcapsules. In the present study, we report the eco-friendly use of an agarose/gelatin-based microencapsulation system to enhance the antifungal activity of gallic acid and reduce its potential cytotoxic effects towards human skin keratinocytes. We used optimal parameter combinations, such as an agarose/gelatin ratio of 1:1, a polymer/oil ratio of 1:60, a surfactant volume of 1% w/w and a stirring speed of 900 rpm. The minimum inhibitory concentration of microencapsulated gallic acid (62.5 µg/ml) was significantly improved when compared with that of the original drug (>750 µg/ml). The anti-A. niger activity of gallic acid -containing microcapsules was much stronger than that of the original drug. Following 48 h of treatment, skin cell survival was approximately 90% with agarose/gelatin microcapsules containing gallic acid, whereas cell viability was only 25-35% with free gallic acid. Our results demonstrate that agarose/gelatin-based microcapsules containing gallic acid may prove to be helpful in the treatment of A. niger-induced skin infections near intravenous injection sites.
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Antifúngicos/farmacología , Aspergilosis/tratamiento farmacológico , Aspergillus niger/crecimiento & desarrollo , Dermatomicosis/tratamiento farmacológico , Ácido Gálico/farmacología , Gelatina/farmacología , Sefarosa/farmacología , Antifúngicos/química , Cápsulas , Células Cultivadas , Evaluación Preclínica de Medicamentos , Ácido Gálico/química , Gelatina/química , Humanos , Queratinocitos/citología , Queratinocitos/metabolismo , Sefarosa/químicaRESUMEN
l-ascorbic acid is an abundant water-soluble nutrient found in vegetables and fruits. It enhances the cell proliferation, which is helpful in wound healing process. However, it is relatively unstable and easily degraded under external environments including acidity, alkalinity, evaporation, heat, oxidization, light or moisture. Its storage remains challenged. This study reported the development of l-ascorbic acid microcapsules using the natural protein, gelatin, and the natural polysaccharide, agar, as the wall protection carrier. The physical properties including entrapment efficiency, particle size, surface morphology, chemical compositions and release profile were identified. The cell proliferation of l-ascorbic acid microcapsules was stronger than the free drug. Significant cell growth in microencapsulated l-ascorbic acid-treated human epithelial HaCaT cells was observed when compared with untreated control. Since cell proliferation and wound repair are closely related, it is believed that l-ascorbic acid microcapsules would effectively increase the potential effect of wound healing activity in human skin.
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Antioxidantes/farmacología , Ácido Ascórbico/farmacología , Proliferación Celular/efectos de los fármacos , Células Epiteliales/metabolismo , Cicatrización de Heridas/efectos de los fármacos , Ácido Ascórbico/química , Cápsulas , Línea Celular , Células Epiteliales/citología , HumanosRESUMEN
Gelatin/Collagen-based matrix and reservoir nanoparticles require crosslinkers to stabilize the formed nanosuspensions, considering that physical instability is the main challenge of nanoparticulate systems. The use of crosslinkers improves the physical integrity of nanoformulations under the-host environment. Aldehyde-based fixatives, such as formaldehyde and glutaraldehyde, have been widely applied to the crosslinking process of polymeric nanoparticles. However, their potential toxicity towards human beings has been demonstrated in many previous studies. In order to tackle this problem, D-glucose was used during nanoparticle formation to stabilize the gelatin/collagen-based matrix wall and reservoir wall for the deliveries of Calendula officinalis powder and oil, respectively. In addition, therapeutic selectivity between malignant and normal cells could be observed. The C. officinalis powder loaded nanoparticles significantly strengthened the anti-cancer effect towards human breast adenocarcinoma MCF7 cells and human hepatoma SKHep1 cells when compared with the free powder. On the contrary, the nanoparticles did not show significant cytotoxicity towards normal esophageal epithelial NE3 cells and human skin keratinocyte HaCaT cells. On the basis of these evidences, D-glucose modified gelatin/collagen matrix nanoparticles containing C. officinalis powder might be proposed as a safer alternative vehicle for anti-cancer treatments.
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Calendula/química , Colágeno/química , Sistemas de Liberación de Medicamentos , Gelatina/química , Glucosa/química , Nanopartículas/química , Extractos Vegetales/farmacología , Animales , Antineoplásicos/farmacología , Muerte Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Humanos , Queratinocitos/citología , Queratinocitos/efectos de los fármacos , Células MCF-7 , Nanopartículas/ultraestructura , Tamaño de la Partícula , Aceites de Plantas/farmacología , Polvos , Espectroscopía Infrarroja por Transformada de Fourier , Sus scrofaRESUMEN
A series of ruthenium(II) bis(2,2'-bipyridyl) complexes containing N-phenyl-substituted diazafluorenes (Ru-C1, Ru-C6, Ru-C7 and Ru-F) was synthesized and their potential antibacterial activity against methicillin resistant Staphylococcus aureus (MRSA) was investigated. The Ru-C7 complex showed significant improvement in both minimum inhibitory concentration (MIC, 6.25 µg mL(-1)) and minimum bactericidal concentration (MBC, 25 µg mL(-1)) towards MRSA when compared with those of methicillin (positive control) (MIC = 25 µg mL(-1) and MBC = 100 µg mL(-1)). The Ru-C7 complex possessed much stronger antibacterial effects than the Ru-C6 complex (MIC, 25 µg mL(-1), MBC, >100 µg mL(-1)). Both Ru-C6 and Ru-C7 complexes were also demonstrated to be biologically safe when tested on normal human skin keratinocytes.
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Antibacterianos/farmacología , Complejos de Coordinación/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Rutenio/farmacología , Administración Tópica , Antibacterianos/administración & dosificación , Antibacterianos/química , Línea Celular , Supervivencia Celular/efectos de los fármacos , Complejos de Coordinación/administración & dosificación , Complejos de Coordinación/química , Fluorenos/química , Humanos , Queratinocitos/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Rutenio/administración & dosificación , Rutenio/químicaRESUMEN
OBJECTIVE: Placenta growth factor (PlGF) is associated with the progression and prognosis of oral cancer. MATERIALS AND METHODS: This study used ELISA, quantitative polymerase chain reaction, and Western blotting to study the arecoline-stimulated (PlGF) protein or mRNA expression in human gingival epithelial S-G cells. RESULTS: Arecoline, a major areca nut alkaloid and an oral carcinogen, could stimulate PlGF protein synthesis in S-G cells in a dose- and time-dependent manner. The levels of PlGF protein secretion increased about 3.1- and 3.8-fold after 24-h exposure to 0.4 and 0.8 mM arecoline, respectively. Pretreatment with antioxidant N-acetyl-l-cysteine (NAC) and ERK inhibitor PD98059, but not NF-κB inhibitor Bay 11-7082, JNK inhibitor SP600125, p38 MAPK inhibitor SB203580, and PI3-K inhibitor LY294002, significantly reduced arecoline-induced PlGF protein synthesis. ELISA analyses demonstrated that NAC and PD98059 reduced about 43% and 38% of the arecoline-induced PlGF protein secretion, respectively. However, combined treatment with NAC and PD98059 did not show additive effect. Moreover, 10 µM curcumin and 4 mM NAC significantly inhibited arecoline-induced ERK activation. Furthermore, 10 µM curcumin completely blocked arecoline-induced PlGF mRNA expression. CONCLUSION: Arecoline-induced PlGF synthesis is probably mediated by reactive oxygen species/ERK pathways, and curcumin may be an useful agent in controlling oral carcinogenesis.
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Arecolina/farmacología , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Encía/citología , Proteínas Gestacionales/biosíntesis , Arecolina/antagonistas & inhibidores , Células Cultivadas , Curcumina/farmacología , Humanos , Factor de Crecimiento PlacentarioRESUMEN
Oral squamous cell carcinoma (OSCC) is common in many Asian countries. The immunopathogenesis of OSCC is unclear. The authors analyzed the lymphocyte subtypes and surface activation markers in healthy Taiwanese people (n=130) and patients with OSCC (n=97)/oral leukoplakia (OL, n=28) using flow cytometry. Univariate analysis found an elevation in the percentage of CD56+ NK cells, CD4+/CD69+ T cells, CD19+/CD69+ B cells and CD56+/CD69+ NK cells in OSCC patients relative to healthy people. The CD19+ and CD19+/CD25+ lymphocyte subtypes decreased in OSCC patients. CD56+ NK cells increased in OL patients. CD56+/CD69+ NK cells were elevated in recurrent and advanced OSCC. Multivariate analysis revealed an increase in CD56+ NK and CD19+/CD69+ cells in OL patients relative to controls. CD19+ B cells declined during progression from OL to OSCC. Betel quid chewing, alcohol, smoking, tumour location and staging showed little effect on lymphocyte subtypes. These results suggest that alterations and activation of NK cells, T and B cells are important and associated with disease status in oral carcinogenesis.
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Antígenos CD/inmunología , Carcinoma de Células Escamosas/inmunología , Leucoplasia Bucal/inmunología , Subgrupos Linfocitarios/citología , Neoplasias de la Boca/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Antígenos CD/clasificación , Antígenos CD/metabolismo , Antígenos de Superficie/clasificación , Antígenos de Superficie/inmunología , Antígenos de Superficie/metabolismo , Estudios de Casos y Controles , Femenino , Humanos , Modelos Logísticos , Subgrupos Linfocitarios/inmunología , Subgrupos Linfocitarios/metabolismo , Masculino , Persona de Mediana Edad , Lesiones Precancerosas/inmunología , Valores de Referencia , Taiwán , Adulto JovenRESUMEN
OBJECTIVE: To investigate the incidence and risk factors of post-tooth extraction sepsis in patients without locoregional infection. SUBJECTS AND METHODS: We assessed all claim records of the Taiwanese National Health Insurance program in 2005. Admissions for patients aged > or =16 years containing a discharge diagnosis of sepsis, and who received tooth extraction within 14 days before the admission were identified. Patient charts were reviewed to confirm the diagnosis of sepsis and rule out other infection sources. The relationship between postextraction sepsis (PES) and clinical parameters was analyzed. RESULTS: Thirty-three of the 2 223 971 extraction cases met the criteria of PES, an incidence of 1.48 per 100 000, and seven patients (21.2%) died of the disease. Aging significantly increased the risk of PES (P < 0.001). Pre-existing comorbidities were found in 20 of the 33 cases, with diabetes mellitus and hematologic diseases the most common. The method, number, and position of extraction had no influence on PES incidence. Blood cultures were positive in 25 patients (75.8%) and isolates included species of the Streptococcus, Actinomyces, Klebsiella, Bacteroides, Prevotella, and Enterococcus genera. CONCLUSION: Tooth extraction is associated with a low but significant risk of postoperative sepsis, especially in the elderly and patients with underlying diseases.
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Infección Focal Dental/epidemiología , Complicaciones Posoperatorias/epidemiología , Sepsis/epidemiología , Extracción Dental/efectos adversos , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Infección de la Herida Quirúrgica/epidemiología , Taiwán/epidemiología , Extracción Dental/estadística & datos numéricos , Adulto JovenRESUMEN
Posterior lingual glands consist of two sets of minor salivary glands that serve important functions in oral physiology. To investigate the hypothesis that the hypoglossal nerve provides sympathetic innervation to the posterior lingual glands, we examined ultrastructural changes in the glands following hypoglossal denervation. In the posterior deep lingual glands (of von Ebner), the serous acinar cells showed a decrease in the number of secretory granules and an increase in lipofuscin accumulation. The ratios of cells containing lipofuscin granules were 11.39, 36.49 and 50.46%, respectively, of the control, 3- and 7-day post-axotomy glands (P < 0.001). Intraepithelial phagocytotic activity was increased. The mucous acinar cells in the posterior superficial lingual glands (of Weber) also showed degenerative changes after hypoglossal denervation. One week after nerve transection, marked cytoplasmic vacuolation and fragmentation of organelles were frequently observed. Degenerative changes were also found in unmyelinated axons associated with the glands. We provide the first evidence of the structural and functional connections between the sympathetic component of the hypoglossal nerve and posterior lingual glands.
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Cricetinae/anatomía & histología , Traumatismos del Nervio Hipogloso , Glándulas Salivales Menores/ultraestructura , Lengua/inervación , Animales , Desnervación , Femenino , Nervio Hipogloso/ultraestructura , Masculino , Microscopía Electrónica de Rastreo , Terminales Presinápticos/ultraestructura , Sistema Nervioso Simpático/ultraestructuraRESUMEN
This study aimed to elucidate the modulation by nitric oxide (NO) of the apoptosis of macrophages and osteoblasts, the essential cellular components in the development of periapical lesions. Lipopolysaccharide (LPS) induced prominent nitrite synthesis in J774 mouse macrophage cell lines. Exposure to LPS induced obvious apoptosis in J774 cells, whereas transient transfection with murine inducible nitric oxide synthase (iNOS), small interfering RNA (siRNA) diminished this effect. Tumor necrosis factor-alpha (TNF-alpha) and S-nitroso-N-acetyl-DL-penicillamine (SNAP) (a NO donor) triggered apoptosis in UMR-106 rat osteoblastic cell lines and a synergistic effect was noted when TNF-alpha and SNAP were added to the medium together. Administration of siRNAs for c-Fos and c-Jun: components of activator protein-1 (AP-1) and transforming growth factor-beta1 attenuated the combined effect markedly. Terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL) stain in a rat model of induced periapical lesion showed positive apoptotic signals in macrophages and osteoblasts. Administration of N(G)-monomethyl-l-arginine markedly diminished the extent of bone loss and the amounts of apoptotic macrophages and osteoblasts. In conclusion, NO mediates LPS-stimulated apoptosis of macrophages. It also induces osteoblast apoptosis and augments the pro-apoptotic effect of cytokines. Inhibition of NO synthesis in vivo attenuates apoptosis and the size of periapical lesions. Taken together, these results suggest that NO may promote the progression of periapical lesion by inducing the apoptosis of macrophages and osteoblasts.
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Apoptosis/efectos de los fármacos , Depuradores de Radicales Libres/farmacología , Macrófagos/efectos de los fármacos , Óxido Nítrico/farmacología , Osteoblastos/efectos de los fármacos , Enfermedades Periapicales/fisiopatología , Animales , Línea Celular , Células Cultivadas , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Sinergismo Farmacológico , Inhibidores Enzimáticos/farmacología , Lipopolisacáridos/farmacología , Ratones , Donantes de Óxido Nítrico/farmacología , Óxido Nítrico Sintasa de Tipo II/farmacología , Nitritos/metabolismo , Proteínas Proto-Oncogénicas c-fos/farmacología , Proteínas Proto-Oncogénicas c-jun/farmacología , ARN Interferente Pequeño/farmacología , Ratas , Ratas Wistar , S-Nitroso-N-Acetilpenicilamina/farmacología , omega-N-Metilarginina/farmacologíaRESUMEN
The purpose of this study was to compare the periodontal healing of mandibular second molars after the removal of impacted mandibular third molars using distolingual alveolectomy and tooth division techniques. A total of 120 consecutive healthy patients who presented with bilaterally impacted mandibular third molars were included in this study. The same operator removed the impacted third molars on both sides in all patients. The third molar on one side was removed by distolingual alveolectomy using a chisel, whereas the contralateral tooth was removed by the tooth division technique using burs. Attachment level, periodontal pocket depth and bone healing distal to the mandibular second molars were assessed at 7 days, 3 months and 6 months after surgery. The results showed better periodontal healing and bone healing when distolingual alveolectomy was employed, especially in the removal of deeply impacted mandibular third molars.
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Tercer Molar/cirugía , Periodoncio/fisiología , Extracción Dental/métodos , Cicatrización de Heridas , Adolescente , Adulto , Alveolectomía , Regeneración Ósea , Femenino , Humanos , Masculino , Mandíbula , Pérdida de la Inserción Periodontal/etiología , Bolsa Periodontal/etiología , Periodoncio/patología , Extracción Dental/efectos adversos , Diente Impactado/complicaciones , Diente Impactado/cirugíaRESUMEN
Norcantharidin (NCTD) is the demethylated analogue of cantharidin. In this study, multi-parameter assessments of morphological alterations, clonogenic efficiency, cell growth curves, DNA synthesis, and DNA strand break were employed to determine and compare the cytotoxic effects of NCTD on oral cancer KB cell line and normal buccal keratinocytes. The results showed NCTD induced significant cytotoxicity in KB cells after 24 h of exposure. Normal buccal keratinocytes were more resistant to NCTD induced cytotoxicity. The IC(50) of 24 h NCTD treatment for KB and keratinocytes were 15.06 and 216.29 microg/ml, respectively with a keratinocyte/KB selective index of 14.36. Anoikis and membrane blebbing, morphological characterization of apoptosis, were observed in about 90% of KB cells after exposure to 100 microg/ml of NCTD for 24 h compared to about 30% in keratinocytes. In addition, inhibition of colony formation was noted in KB cells even when exposed to low concentration of drug (5 microg/ml) for a short period of time (6 h). NCTD inhibited subsequent cell proliferation in KB but growth of normal keratinocytes was retarded only temporarily. NCTD inhibited DNA synthesis in both KB and normal keratinocytes. However, keratinocytes were more sensitive to DNA synthesis inhibition by low dose of NCTD. Significant DNA strand break was noted in KB cells only after cell viability was reduced to less than 60% of the control. In comparison, normal keratinocytes were resistant to NCTD induced DNA strand break. These results indicated KB cells were more sensitive to NCTD induced cytotoxicity compared to normal keratinocytes. NCTD may be of value in treating oral cancers. The underlying mechanisms of the differential actions of NCTD on these two cell types are worthy of further investigations.
Asunto(s)
Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Neoplasias de la Boca/tratamiento farmacológico , División Celular/efectos de los fármacos , Daño del ADN , ADN de Neoplasias/biosíntesis , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Queratinocitos/efectos de los fármacos , Mucosa Bucal , Neoplasias de la Boca/patología , Células Tumorales Cultivadas/efectos de los fármacosRESUMEN
There are about 600 million betel quid (BQ) chewers in the world. BQ chewing is the major risk factor of oral cancer in India, Taiwan, South Africa and numerous other countries. Areca nut (AN) extract, the main component of BQ, exerts cytotoxicity and genotoxicity to several types of cells. In the present study, AN extract induced the unscheduled DNA synthesis (UDS) of gingival keratinocytes (GK). Vitamin C, at concentration of 50 and 200 microg/ml prevented the AN-induced UDS by 41 and 56%, respectively. Glutathione (GSH, 1-3 mM) and N-acetyl-L-cysteine (NAC, 1-3 mM) also protected the AN-induced UDS by 89-100 and 76-90%. These preventive effects were not due to cytotoxicity as analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. Deferoxamine (20 and 30 mM), an iron chelator and a free radical scavenger, also prevented AN extract induced UDS of GK by 30-55%. On the contrary, banthocuproine (50-200 microM, a copper chelator) and 1,10-phenanthroline (50, 100 microM, a lipid permeable iron chelator), lacked preventive effects. Specific reactive oxygen species scavengers such as dimethyl-sulfoxide (2%), mannitol (10-20 mM), dimethylthiourea (10-20 mM), pyruvate (10 mM), catalase (200 and 400 U/ml), and superoxide dismutase (50 and 200 U/ml) also lacked these preventive effects. Moreover, higher concentrations of H(2)O(2) (0.5-1 mM) inhibited the basal levels of UDS by 19-37%. Interestingly, NAC, GSH, Vitamin C and deferoxamine cannot prevent the AN-induced morphological changes of GK at similar concentrations. These results reveal that AN extract-induced UDS of GK is associated with free radical reactions. Possibly different ingredients of AN is responsible for genotoxicity and cytotoxicity. Vitamin C, GSH and NAC may be potentially used in the future for chemoprevention of BQ chewing related oral mucosal lesions.
Asunto(s)
Areca/química , Ácido Ascórbico/uso terapéutico , ADN/biosíntesis , Encía/metabolismo , Compuestos de Sulfhidrilo/uso terapéutico , Antioxidantes/uso terapéutico , Células Cultivadas , Quelantes/uso terapéutico , ADN/efectos de los fármacos , Deferoxamina/uso terapéutico , Encía/efectos de los fármacos , Humanos , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/prevención & control , Extractos Vegetales/efectos adversosRESUMEN
Various palatal flap procedures based on the greater palatine vessels have been advocated for the repair of oroantral communications (OACs). However, when the defect is located in the third molar region, difficulty is encountered in using the palatal flap because rotation is hindered by the vascular pedicle. In this study, we used random palatal flaps to repair OACs in the third molar area in 21 patients. The vascular pedicles were ligated and severed in all cases in order to evaluate whether it was necessary to preserve the greater palatine vessels when using the palatal rotation flap (PRF). The repair was successful in 16 cases (76.2%). The length/width ratio of the flap was the most important factor determining the outcome. The ratios were 2.23 +/- 0.12 and 2.40 +/- 0.14 in the success and failure groups, respectively and their difference was statistically significant (P<0.05). Other clinical parameters such as age, gender, antral infection, tooth displacement into the sinus and duration of the communication had no influence on the outcome (P>0.05). The study showed that the PRF with the appropriate length/width ratio can safely be used in a random fashion. This provided another option in the repair of oroantral communications of difficult locations such as in the tuberosity area.
Asunto(s)
Mucosa Bucal/trasplante , Fístula Oroantral/cirugía , Colgajos Quirúrgicos , Factores de Edad , Distribución de Chi-Cuadrado , Femenino , Humanos , Ligadura , Masculino , Sinusitis Maxilar/microbiología , Persona de Mediana Edad , Tercer Molar , Hueso Paladar , Reproducibilidad de los Resultados , Rotación , Seguridad , Factores Sexuales , Estadística como Asunto , Colgajos Quirúrgicos/irrigación sanguínea , Colgajos Quirúrgicos/patología , Factores de Tiempo , Avulsión de Diente/complicaciones , Resultado del TratamientoRESUMEN
Although techniques for repairing root fracture have been proposed, the prognosis is generally poor. If the fusion of a root fracture by laser is possible, it will offer an alternative to extraction. Our group has attempted to use lasers to fuse a low melting-point bioactive glass to fractured dentin. This report is focused on the phase, compositional, and morphological changes observed by means of X-ray diffractometer, Fourier transforming infrared spectroscopy, and scanning electron microscopy-energy dispersive X-ray spectroscopy in human dentin after exposure to Nd:YAG laser. The irradiation energies were from 150 mJ/ pulse-10 pps-4 s to 150 mJ/pulse-30 pps-4 s. After exposure to Nd:YAG laser, dentin showed four peaks on the X-ray diffractometer that corresponding to a-tricalcium phosphate (TCP) and beta-TCP at 20 = 30.78 degrees/34.21 degrees and 32.47 degrees/33.05 degrees, respectively. The peaks of a-TCP and beta-TCP gradually increased in intensity with the elevation of irradiation energy. In Fourier transforming infrared analysis, two absorption bands at 2200 cm(-1) and 2015 cm(-1) could be traced on dentin treated by Nd:YAG laser with the irradiation energies beyond 150 mJ/pulse-10 pps-4 s. The energy dispersive X-ray results showed that the calcium/phosphorus ratios of the irradiated area proportionally increased with the elevation of irradiation energy. The laser energies of 150 mJ/ pulse-30 pps-4 s and 150 mJ/pulse-20 pps-4 s could result in the a-TCP formation and collagen breakdown. However, the formation of glass-like melted substances without a-TCP at the irradiated site was induced by the energy output of 150 mJ/ pulse-10 pps-4 s. Scanning electron micrographs also revealed that the laser energy of 150 mJ/ pulse-10 pps-4 s was sufficient to prompt melting and recrystallization of dentin crystals without cracking. Therefore, we suggest that the irradiation energy of Nd:YAG laser used to fuse a low melting-point bioactive glass to dentin is 150 mJ/ pulse-10 pps-4 s.