Leptin and its receptor in human dental pulp and periapical tissues

Texto completo descargado desde TESEOUno de los aspectos más interesantes a los que en la actualidad se enfrenta la comunidad científica médica y odontológica es la posible conexión entre los procesos inflamatorios orales de origen infeccioso y el estado de salud sistémico (Seymour et al. 2009). Son numerosos los estudios epidemiológicos que han encontrado asociación entre el estado de salud general y estos procesos inflamatorios orales ( Soskolne et al. 2001; Janket et al. 2003; Jiménez Pinzón et al. 2004; Segura-Egea et al. 2005; Caplan et al. 2006; Ridao-Sacie et al. 2007)). La evidencia de esta asociación ha conllevado a una mayor atención al diagnóstico y tratamiento de estas enfermedades orales en diversas situaciones clínicas, con la consiguiente mejora de la salud oral y sistémica de los pacientes. Sin embargo no se conoce en profundidad la fisiopatología de los procesos inflamatorios pulpo-periapicales (pulpitis y periodontitis apical) en cuanto a aspectos básicos, moleculares y celulares. Su mejor conocimiento conllevaría un mejor conocimiento de su posible repercusión a nivel sistémico. La pulpitis o inflamación pulpar se produce cuando, bien sea por caries o por traumatismos, las noxas y los microorganismos alcanzan el tejido pulpar desencadenando una respuesta inmune e inflamatoria (Jontell et al. 1998). Las bacterias causantes de la caries son también la causa principal de la infección y la inflamación pulpar, siendo la lesión que sufrirá el tejido pulpar el resultado de un proceso dinámico en el que, de un lado, están los microorganismos invasores y, de otro, la respuesta inmune e inflamatoria del huésped (Bergenholtz et al 2000). Para que se produzca la respuesta inflamatoria pulpar no es necesario que las bacterias alcancen físicamente la pulpa. Por el contrario, existen evidencias experimentales que demuestran que antígenos bacterianos y/o subproductos metabólicos pueden difundir a través de los túbulos dentinarios y provocar respuestas inmunes en la pulpa dental (Warfvinge et al 1985). Durante la respuesta inmune pulpar pueden formarse también complejos inmunes y liberarse, por fagocitosis, enzimas proteolíticos extracelulares que agravan y empeoran la inflamación pulpar (Bergenholtz et al 1977). En definitiva, la pulpitis se produce por un mecanismo inmunopatológico (Hahn et al 2007). Frente a agresiones leves o moderadas, la inflamación de la pulpa puede reparar el daño causado (pulpitis reversible), manteniéndose la vitalidad pulpar. En estos casos, el dolor aparece con ciertos estímulos y nunca es espontáneo. Por el contrario, si no se eliminan los factores agresivos y no se aplica una terapia de conservación y protección pulpar, terminará produciéndose una pulpitis irreversible y, en definitiva, la necrosis pulpar. La pulpitis irreversible es, pues, la respuesta inflamatoria aguda de la pulpa frente a la persistencia, crecimiento y progresión de las bacterias, u otro agente agresivo, en la cavidad pulpar (Canalda et al 2001). Cuando el proceso inflamatorio pulpar es irreversible, el paciente presenta dolor de intensidad creciente, espontáneo, episodios dolorosos cada vez más frecuentes y dolor que persiste después de eliminar el estímulo. Suele haber, antecedentes de lesiones cariosas profundas, exposición pulpar o restauraciones filtradas (Montgomery et al 1986). Sin embargo, en algunos casos la pulpitis irreversible puede cursar sin sintomatología, por lo que se distinguen dos formas clínicas de pulpitis irreversible: la sintomática y la asintomática (Pumarola et al. 2001) La periodontitis apical es la inflamación aguda o crónica del tejido que rodea a la raíz dentaria, generalmente entorno al ápice radicular, producida por la infección bacteriana de la pulpa dental (endodonto) (Eriksen et al.1998). La periodontitis apical se produce, en más del 90% de los casos, como secuela de la caries dental, una vez que ésta alcanza la pulpa dentaria provocando pulpitis y/o necrosis pulpar. El contenido polimicrobiano y/o antigénico del conducto radicular sale por el foramen apical, o por conductos laterales, e invade el tejido conectivo periapical o periradicular desencadenando una respuesta inflamatoria e inmune. La periodontitis apical puede ser aguda y sintomática o crónica y asintomática. La periodontitis apical aguda cursa con dolor y mínima reabsorción ósea, pudiendo, en ocasiones, ser reversible. La periodontitis apical crónica es una consecuencia de la necrosis pulpar y es, por ello, irreversible. Puede presentarse con cuatro cuadros anatomopatológicos: granuloma apical, absceso apical crónico, quiste apical y osteitis condensante (Pumarola et al 2001). Las lesiones osteolíticas periapicales o periradiculares, observables radiológicamente, son consecuencia de la destrucción ósea que conlleva el proceso inflamatorio crónico periapical o periradicular. La prevalencia de la periodontitis apical es muy alta en la población general, llegando en España al 61% de los individuos y al 4% de los dientes estudiados (Jiménez-Pinzón et al. 2004). La leptina es una hormona peptídica no glicosilada de 167 aminoácidos y 16 kDa, altamente hidrofílica, codificada en el gen Ob (Zhang et al. 1994). La leptina es sintetizada principalmente y secretada por el tejido adiposo (Ahima et Flier. 2000) y fue descrita originalmente como una hormona derivada de los adipocitos para regular de manera central el control de peso, a través de su receptor en el hipotálamo (Flier,1995). Sin embargo, la leptina ha sido clasificada como una citoquina debido a que su secuencia primaria de aminoácidos muestra similitudes estructurales con la familia de citoquinas de larga cadena helicoidal (Zhang et. Al 1994, Saánchez-Margalet et al. 2003a,b). Por otra parte, el receptor de leptina (Ob-R) se expresa no sólo en el sistema nervioso central, sino también en los tejidos periféricos, tales como los sistemas hematopoyético e inmune (Sánchez-Margalet et al. 2003a, b). Por lo tanto, se ha propuesto que la leptina tiene un papel en la hematopoyesis y en el sistema inmune (Cioffi et al. 1996, Sánchez-Margalet et al. 2003a,b). Asimismo, se ha sugerido de que la leptina dirige la respuesta inmune del huésped mejorando la producción de citoquinas y la fagocitosis por los macrófagos (Fantuzzi y Faggioni 2000, Sánchez-Margalet et al. 2003a, b, Fernández-Riejos et al. 2010). Se ha demostrado que la leptina regula la respuesta inmune innata y adaptativa tanto en condiciones normales como en patológicas (Fernández-Riejos et al. 2010). La presencia de leptina ha sido demostrada en tejidos gingivales sanos e inflamados (Johnson & Serio 2001), en el fluido crevicular gingival (Bozkurt et al. 2006, Karthikeyan y Pradeep 2007a, b, Dilsiza et al. 2010) y en lesiones periapicales crónicas humanas (Haghighi et al. 2010). Una concentración de leptina sérica elevada se ha asociado con un aumento de periodontitis crónica (Gundala et al. 2012). Recientemente, se ha descrito por primera vez que la leptina tiene efectos sobre las células madre de la pulpa dental, actuando como un importante modulador en la diferenciación de células madre mesenquimales pulpares (Um et al. 2011). Por todo lo expuesto anteriormente, es plausible hipotetizar de que la leptina y su receptor se expresa en la pulpa dental así como en el tejido periapical humano y que juega un papel en la modulación de las respuestas inflamatoria e inmune locales. Sin embargo, a pesar de que ha sido previamente demostrado de que la leptina es sintetizada y secretada in vitro por fibroblastos pulpares derivados de molares sanos extraídos (El Karim et. al 2009), hasta la fecha, ningún estudio ha investigado su presencia ni la de su receptor en los tejidos pulpar y periapical humanosPremio Extraordinario de Doctorado U

Chronic Obstructive Pulmonary Disease and Apical Periodontitis and Other Oral Health Variables: A Case-Control Study

Background: The relationship between chronic inflammatory diseases and their comorbidities and correlation with periodontal diseases has become an increasing focus of research. Objectives: The aim of this case-control study was to conclude if patients suffering from COPD (Chronic Obstructive Pulmonary Disease) tend to have more AP (Apical Periodontitis) than non-COPD patients. Materials and Methods: The study was conducted on 30 patients assigned as cases, associated with 30 control patients linked by age (+/-5 years) and sex. Results: A total of 60 patients were recorded, and a total of 12 radiographic variables were analyzed. A total of 43 (71.7%) patients were registered with PAI (Periapical Index) >= 3, and there was a slightly tendency in the patients from the control group 22 (73.3%) compared to those from the cases 21 (70%), respectively (p > 0.05). Conclusions: It was concluded that there was not a significant association between the levels of PAI (Periapical Index) >= 3 per patient in those suffering from COPD. In fact, it could be concluded that patients diagnosed with COPD tend to have more teeth with PAI >= 3, more endodontic treatments and their periodontitis tended to accumulate more caries. Clinical Significance: This study establishes, in a case-control study, some specific aspects of oral health in patients with COPD, as well as analyzing the importance of oral health in this disease

Pregabalin in the treatment of inferior alveolar nerve paraesthesia following overfilling of endodontic sealer

A case of orofacial pain and inferior alveolar nerve (IAN) paraesthesia after extrusion of endodontic sealer within the mandibular canal treated with prednisone and pregabalin is described. A 36-year-old woman underwent root canal treatment of the mandibular second right premolar tooth. Post-operative panoramic radiograph revealed the presence of radiopaque canal sealer in the mandibular canal. Damage to IAN consecutive to extrusion of endodontic sealer was diagnosed. Non-surgical management was decided, including: 1 mg/kg/day prednisone 2 times/day, once-daily regimen, and 150 mg/day pregabalin, two doses per day, monitoring the progress with periodic follow-up visits. Six weeks after the incident the signs and symptoms were gone. The complete resolution of paraesthesia and the control of pain achieved suggest that a non-surgical approach, combining prednisone and the GABA analogue pregabalin, is a good option in the management of the IAN damage subsequent to endodontic sealer extrusion

Pregabalin in the treatment of inferior alveolar nerve paraesthesia following overfilling of endodontic sealer

A case of orofacial pain and inferior alveolar nerve (IAN) paraesthesia after extrusion of endodontic sealer within the mandibular canal treated with prednisone and pregabalin is described. A 36-year-old woman underwent root canal treatment of the mandibular second right premolar tooth. Post-operative panoramic radiograph revealed the presence of radiopaque canal sealer in the mandibular canal. Damage to IAN consecutive to extrusion of endodontic sealer was diagnosed. Non-surgical management was decided, including: 1 mg/kg/day prednisone 2 times/day, once-daily regimen, and 150 mg/day pregabalin, two doses per day, monitoring the progress with periodic follow-up visits. Six weeks after the incident the signs and symptoms were gone. The complete resolution of paraesthesia and the control of pain achieved suggest that a non-surgical approach, combining prednisone and the GABA analogue pregabalin, is a good option in the management of the IAN damage subsequent to endodontic sealer extrusio

Leptin in Dental Pulp and Periapical Tissues: A Narrative Review

Abstract: Leptin is a non-glycosylated 16 kDa protein synthesized mainly in adipose cells. The main function of leptin is to regulate energy homeostasis and weight control in a central manner. There is increasing evidence that leptin also has systemic effects, acting as a link between innate and acquired immune responses. The expression of leptin and its receptor in human dental pulp and periradicular tissues have already been described, as well as several stimulatory effects of leptin protein expression in dental and periodontal tissues. The aim of this paper was to review and to compile the reported scientific literature on the role and effects of leptin in the dental pulp and periapical tissues. Twelve articles accomplished the inclusion criteria, and a comprehensive narrative review was carried out. Review of the available scientific literature concluded that leptin has the following effects on pulpal and periapical physiology: 1) Stimulates odontogenic differentiation of dental pulp stem cells (DPSCs), 2) Increases the expression of dentin sialophosphoprotein (DSPP) and dentin matrix protein-1 (DMP-1), odontoblastic proteins involved in odontoblastic differentiation and dentin mineralization, 3) Stimulates vascular endothelial growth factor (VEGF) expression in human dental pulp tissue and primary cultured cells of human dental pulp (hDPCs), 4) Stimulates angiogenesis in rat dental pulp cells, and 5) Induces the expression of interleucinas 6 and 8 in human periodontal ligament cells (hPDLCs). There is evidence which suggests that leptin is implicated in the dentin mineralization process and in pulpal and periapical inflammatory and reparative responses

Clinical measurement of tooth wear: tooth Wear Indices

Attrition, erosion, and abrasion result in alterations to the tooth and manifest as tooth wear. Each classification corresponds to a different process with specific clinical features. Classifications made so far have no accurate prevalence data because the indexes do not necessarily measure a specific etiology, or because the study populations can be diverse in age and characteristics. Tooth wears (attrition, erosion and abrasion) is perceived internationally as a growing problem. However, the interpretation and comparison of clinical and epidemiological studies, it is increasingly difficult because of differences in terminology and the large number of indicators/indices that have been developed for the diagnosis, classification and monitoring of the loss of dental hard tissue. These indices have been designed to identify increasing severity and are usually numerical, none have universal acceptance, complicating the evaluation of the true increase in prevalence reported. This article considers the ideal requirements for an erosion index. A literature review is conducted with the aim of analyzing the evolution of the indices used today and discuss whether they meet the clinical needs and research in dentistr

Green discoloration of the crown after internal root resorption treatment with grey mineral trioxide aggregate (MTA)

Root resorption (RR) is the loss of dental hard tissues as a result of clastic activities. Internal inflammatory root resorption (IRR) is a type of RR characterized by progressive loss of tooth substance starting from the root canal wall. IRR is usually asymptomatic, slowly progressing, and detectable upon routine radiographic examination or by the clinical sign of a ‘pink spot’ when the IRR involves the crown or the coronal third of the root canal. Mineral trioxide aggregate (MTA) is a biocompatible cement that has been used successfully in pulp capping, pulpotomy, treatment of traumatized teeth with immature apices, and for treatment of root resorption. The treatment and follow-up of a maxillary central incisor with perforating IRR managed by root canal treatment and grey MTA repair is reported. IRR affected tooth 11 (FDI World Dental Federation) in a 29-year-old female patient, with a history of previous trauma. Follow-up radiographs over 24 months demonstrated the maintenance of a functional tooth. However, the tooth showed a green discoloration of the crown after MTA treatment

Expression and immunohistochemical localization of leptin in human periapical granulomas

Background: Leptin, initially described as an adipocyte-derived hormone to regulate weight control, is expressed in normal and inflamed human dental pulp, being up-regulated during pulp experimental inflammation. Leptin receptor (LER) has been identified in human periapical granulomas. The aim of this study was to analyze and characterize the expression of leptin in human periapical granulomas. Material and Methods: Fifteen periapical inflammatory lesions were obtained from extracted human teeth and teeth which underwent periapical surgery. After their morphological categorization as periapical granulomas and gradation of the inflammatory infiltrate, they were examined by immunohistochemistry using human leptin policlonal antibodies. Leptin mRNA expression was also determined by quantitative real-time PCR (qRT-PCR) and the amount of leptin protein was analyzed by immunoblot. Results: All periapical lesions exhibited the characteristic of chronic granulomatous inflammatory process with inflammatory infiltrate grade III. Leptin+ cells were detected in 13 periapical granulomas (86.6%). The median number of Leptin+ cells in periapical granulomas was 1.70 (0.00-7.4). Amongst the inflammatory cells in the periapical granulomas, only macrophages were reactive to leptin antibodies. Western blot analysis revealed the presence in all samples of a protein with apparent molecular weight of approximately 16 kDa, corresponding to the estimated molecular weights of leptin. The expression of leptin mRNA was confirmed by qRT-PCR analysis and the size of the amplified fragment (296 bp for leptin and 194 bp for cyclophilin) was assessed by agarose gel electrophoresis. Conclusions: For the first time, it has been demonstrated that human periapical granuloma expresses the adipokine leptin

Postoperative pain after one-visit root-canal treatment on teeth with vital pulps : comparison of three different obturation techniques

Objectives. To investigate and compare postoperative pain after one-visit root canal treatment (RCT) on teeth with vital pulps using three different obturation techniques. Study Design. Two hundred and four patients (105 men and 99 women) aged 12 to 77 years were randomly assigned into three treatments groups: cold lateral compaction of gutta-percha (LC), Thermafil technique (TT), and Backfill - Thermafil obturation technique (BT). Postoperative pain was recorded on a visual analogue scale (VAS) of 0 - 10 after 2 and 6 hours, and 1, 2, 3, 4, 5, 6 and 7 days. Data were statistically analyzed using multivariate logistic regression analysis. Results. In the total sample, 87% of patients experienced discomfort or pain in some moment between RCT and the seventh day. The discomfort experienced was weak, light, moderate and intense in 6%, 44%, 20% and 6% of the cases, respectively. Mean pain levels were 0.4 ± 0.4, 0.4 ± 0.3, and 1.4 ± 0.7 in LC, BT, and TT groups, respectively. Patients of TT group experienced a significantly higher mean pain level compared to other two groups (p < 0.0001). In TT group, all patients felt some level of pain at six hours after RCT. Conclusions. Postoperative pain was significantly associated with the obturation technique used during root canal treatment. Patients whose teeth were filled with Thermafil obturators (TT technique) showed significantly higher levels of discomfort than patients whose teeth were filled using any of the other two techniques

Influencia del tensioactiu en la formació i estabilitat física d’emulsions ecològiques concentrades

El objetivo de esta investigación fue comparar tres tensoactivos ecológicos derivados del aceite de coco para la preparación de emulsiones aceite-en-agua concentradas formuladas con α-pineno. Los tensoactivos utilizados son ésteres polietoxilados de glicerina que presentan diferente número de grupos de óxido de etileno, que son responsables principales del carácter hidrófilo del tensoactivo. Las técnicas utilizadas para caracterizar las emulsiones fueron la reología, la difracción láser y el “multiple light scattering”. Se ha demostrado que el uso del tensoactivo no-iónico Levenol C-201 (17 grupos de óxido de etileno y valor HLB de 13), produce emulsiones con mayor estabilidad física debido a sus menores tamaños de gota y una mayor viscosidad, lo que ayuda a prevenir fenómenos de desestabilización como el cremado o la coalescencia. Por tanto, este estudio proporciona importantes resultados sobre las propiedades y estabilidad física de emulsiones formuladas con ésteres etoxilados de glicerina derivados del aceite de coco que pueden ser utilizadas para el desarrollo de nuevos productos bioaplicables.The goal of this work was to compare three different ecological surfactants derived from coconut oil for the preparation of concentrated oil-in-water emulsions formulated with alpha-pinene. The surfactants used were polyoxyethylene glycerol fatty acid esters with different number of oxyethylene groups. These are liable for the hydrophilic surfactant role. Rheology, laser diffraction and Multiple Ligh Sacttering were used in order to characterise the emulsions. It has been demonstrated that the use of Levenol C-201 (HLB: 13) lead to prepare emulsions with longer physical stability due to lower droplet size and higher viscosity. These facts help to slow down destabilization processes such as creaming or coalescence. Therefore, this study provides interesting results about the properties and physical stability of emulsions containing polyoxyethylene glycerol fatty acid esters derived from coconut oil, which can be used to develop new products with biological applications.L’objectiu d’aquesta investigació va ser comparar tres tensioactius ecològics derivats de l’oli de coco per a la preparació d’emulsions oli-en-aigua concentrades formulades amb α-pinè. Els tensioactius utilitzats són èsters polietoxilats de glicerina que presenten diferent nombre de grups d’òxid d’etilè, que són responsables principals del caràcter hidròfil del tensioactiu. Les tècniques utilitzades per caracteritzar les emulsions van ser la reologia, la difracció làser i el multiple light scattering. S’ha demostrat que l’ús del tensioactiu no-iònic Levenol C-201 (17 grups d’òxid d’etilè i valor HLB de 13), produeix emulsions amb més estabilitat física a causa de un volum més petit de gota i una major viscositat, el que ajuda a prevenir fenòmens de desestabilització com el cremat o la coalescència. Per tant, aquest estudi proporciona importants resultats sobre les propietats i la estabilitat física d’emulsions formulades amb èsters etoxilats de glicerina derivats de l’oli de coco que poden ser utilitzades per al desenvolupament de nous productes bioaplicables.(Project CTQ2015- 70700) from the Spanish Ministerio de Economía y CompetitividadEuropean Commission (FEDER Programme)KA