RESUMEN
The periodontal ligament (PDL) is a fibrillar connective tissue that lies between the alveolar bone and the tooth and is composed of highly specialized extracellular matrix (ECM) molecules and a heterogeneous population of cells that are responsible for collagen formation, immune response, bone formation, and chewing force sensation. Type VI collagen (COL6), a widely distributed ECM molecule, plays a critical role in the structural integrity and mechanical properties of various tissues including muscle, tendon, bone, cartilage, and skin. However, its role in the PDL remains largely unknown. Our study shows that deficiency of COL6 impairs PDL fibrillogenesis and exacerbates tissue destruction in ligature-induced periodontitis (LIP). We found that COL6-deficient mice exhibited increased bone loss and degraded PDL in LIP and that fibroblasts expressing high levels of Col6α2 are pivotal in ECM organization and cell-ECM interactions. Moreover, COL6 deficiency in the PDL led to an increased number of fibroblasts geared toward the inflammatory response. We also observed that cultured COL6-deficient fibroblasts from the PDL exhibited decreased expression of genes related to collagen fiber turnover and ECM organization as well as migration and proliferation. Our findings suggest that COL6 plays a crucial role in the PDL, influencing fibroblast function in fibrillogenesis and affecting the immune response in periodontitis. These insights advance our understanding of the molecular mechanisms underlying PDL maturation and periodontal disease.
Asunto(s)
Colágeno Tipo VI , Fibroblastos , Ligamento Periodontal , Periodontitis , Animales , Ligamento Periodontal/patología , Ratones , Colágeno Tipo VI/deficiencia , Colágeno Tipo VI/genética , Periodontitis/patología , Matriz Extracelular/metabolismo , Pérdida de Hueso Alveolar/patología , Ratones Noqueados , Modelos Animales de Enfermedad , Proliferación CelularAsunto(s)
Penfigoide Ampolloso , Humanos , Colágenos no Fibrilares , Autoantígenos , Prurito , Biomarcadores , Quimiocinas , AutoanticuerposRESUMEN
Progressive supranuclear palsy - Richardson syndrome (PSP-RS) was first described in 1964 by Steele et al. Tau pathology has not been reported in the hypoglossal nuclei of PSP-RS patients, whereas Steele et al. described gliosis with no remarkable neuronal losses in the hypoglossal nucleus. This study aimed to investigate the distribution and degree of tau pathology-associated neurodegeneration, with an emphasis on the hypoglossal nucleus, in patients with PSP-RS. Six clinicopathologically proven PSP-RS cases were included in this study. All patients were clinicopathologically and immunohistochemically re-evaluated. This study confirmed the following neuropathological characteristics of PSP-RS: (1) neurodegeneration usually affects the striatonigral system and cerebellar dentate nucleus; (2) the cerebellar afferent system in PSP-RS is affected by absent-to-mild neurodegeneration; and (3) the extent of tau distribution throughout the central nervous system is greater than the extent of neurodegeneration. Furthermore, we found that subthalamic neurodegeneration was more prominent in the ventromedial region than in the dorsolateral region. Nevertheless, the tau pathology showed no remarkable differences between these two sites. Interestingly, the tau pathology was frequently observed in the hypoglossal nuclei of PSP-RS patients. Gradient neurodegeneration of the subthalamus and tau pathology in the hypoglossal nucleus could be regarded as essential pathological features of PSP-RS.
Asunto(s)
Biomarcadores , Degeneración Nerviosa/patología , Subtálamo/patología , Parálisis Supranuclear Progresiva/diagnóstico , Tauopatías/patología , Anciano , Anciano de 80 o más Años , Autopsia , Biomarcadores/análisis , Biomarcadores/metabolismo , Cerebelo/patología , Progresión de la Enfermedad , Femenino , Humanos , Nervio Hipogloso/patología , Masculino , Persona de Mediana Edad , Degeneración Nerviosa/diagnóstico , Neuronas/metabolismo , Neuronas/patología , Parálisis Supranuclear Progresiva/patología , Tauopatías/diagnóstico , Proteínas tau/análisis , Proteínas tau/metabolismoRESUMEN
Root amputation, immunosuppressive therapy, mandibular tooth extraction, pre-existing inflammation, and longer duration of treatment with bone-modifying agents were significantly associated with an increased risk of medication-related osteonecrosis of the jaw. Hopeless teeth should be extracted without drug holiday before the development of inflammation in cancer patients receiving high-dose bone-modifying agents. INTRODUCTION: No studies have comprehensively analyzed the influence of pre-existing inflammation, surgical procedure-related factors such as primary wound closure, demographic factors, and drug holiday on the incidence of medication-related osteonecrosis of the jaw (MRONJ). The purpose of this study was to retrospectively investigate the relationships between these various factors and the development of MRONJ after tooth extraction in cancer patients receiving high-dose bone-modifying agents (BMAs) such as bisphosphonates or denosumab. METHODS: Risk factors for MRONJ after tooth extraction were evaluated with univariate and multivariate analyses. The following parameters were investigated in all patients: demographics, type and duration of BMA use, whether BMA use was discontinued before tooth extraction (drug holiday), the duration of such discontinuation, the presence of pre-existing inflammation, and whether additional surgical procedures (e.g., incision, removal of bone edges, root amputation) were performed. RESULTS: We found that root amputation (OR = 22.62), immunosuppressive therapy (OR = 16.61), extraction of mandibular teeth (OR = 12.14), extraction of teeth with pre-existing inflammation, and longer duration (≥ 8 months) of high-dose BMA (OR = 7.85) were all significantly associated with MRONJ. CONCLUSIONS: Tooth extraction should not necessarily be postponed in cancer patients receiving high-dose BMA. The effectiveness of a short-term drug holiday was not confirmed, as drug holidays had no significant impact on MRONJ incidence. Tooth extraction may be acceptable during high-dose BMA therapy until 8 months after initiation.
Asunto(s)
Osteonecrosis de los Maxilares Asociada a Difosfonatos/etiología , Neoplasias/tratamiento farmacológico , Extracción Dental/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Conservadores de la Densidad Ósea/efectos adversos , Denosumab/efectos adversos , Difosfonatos/efectos adversos , Femenino , Humanos , Inmunosupresores/efectos adversos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Raíz del Diente/cirugíaRESUMEN
BACKGROUND: Kidney transplantation is performed as a useful treatment to improve the quality of life (QOL) of patients with end-stage renal failure; however, the correlation between mood status and QOL among recipients post-kidney transplantation have yet to be clarified. METHODS: Sixty-eight post-kidney transplantation patients who visited our institution between March and December 2016 were enrolled in this study. The QOL of the participants as measured by the Short Form-36 Health Survey Version 2 (SF-36v2) questionnaire was compared to results gathered from hemodialysis patients in a previous study. To identify the factors associated with QOL, a multiple regression analysis was performed, including some physical, mental, and socioeconomic characteristics as well as the Profile of Mood States as independent variables. RESULTS: The QOL of the transplantation group was significantly higher for all 8 subscales of SF-36v2 compared to the hemodialysis group. Among the factors, greater age and higher Confusion levels were related to lower physical QOL. In addition, higher Vigor and lower Fatigue levels were related to higher mental QOL, while the condition of having an occupation was related to higher role/social QOL. CONCLUSION: The QOL of recipients after kidney transplantation was better than that of hemodialysis patients. It is important to pay attention to mood status, especially confusion and fatigue, in order to maintain and improve the QOL of the recipient after kidney transplantation. Kidney transplantation can be a beneficial treatment not only physically but also psychologically and socially.
Asunto(s)
Trasplante de Riñón/psicología , Calidad de Vida , Receptores de Trasplantes/psicología , Adulto , Fatiga , Femenino , Humanos , Fallo Renal Crónico/psicología , Masculino , Persona de Mediana Edad , Diálisis Renal , Encuestas y CuestionariosRESUMEN
Little research has been conducted into hypoesthesia, and no studies have elucidated the risk factors for refractory hypoesthesia and compared treatment modalities. The purpose of this multicentre retrospective cohort study was to investigate the relationships between various risk factors, treatment modalities, and refractory hypoesthesia. Risk factors for refractory hypoesthesia after oral surgery were evaluated using univariate and multivariate analysis. To minimize the selection bias associated with a retrospective data analysis, a propensity score analysis was performed between the medication and non-medication groups (65 sites in each group). Moderate or severe hypoesthesia (odds ratio 13.42) and no or late administration of ATP/vitamin B12 (odds ratio 2.28) were significantly associated with refractory hypoesthesia. In the propensity score analysis, the incidence rate of refractory hypoesthesia in the medication group was lower than that in the non-medication group (P<0.001). This study demonstrated the multivariate relationships between various risk factors, treatment modalities, and refractory hypoesthesia. Moderate or severe hypoesthesia and no or late administration of ATP/vitamin B12 were significantly associated with refractory hypoesthesia. Therefore, clinicians should consider these risk factors and initiate early oral administration of ATP/vitamin B12 in cases of hypoesthesia.
Asunto(s)
Hipoestesia/etiología , Procedimientos Quirúrgicos Orales , Complicaciones Posoperatorias/etiología , Traumatismos del Nervio Trigémino/etiología , Adenosina Trifosfato/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Hipoestesia/diagnóstico por imagen , Hipoestesia/tratamiento farmacológico , Masculino , Nervio Mandibular , Persona de Mediana Edad , Complicaciones Posoperatorias/diagnóstico por imagen , Complicaciones Posoperatorias/tratamiento farmacológico , Puntaje de Propensión , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento , Traumatismos del Nervio Trigémino/diagnóstico por imagen , Traumatismos del Nervio Trigémino/tratamiento farmacológico , Vitamina B 12/uso terapéuticoRESUMEN
Root amputation, extraction of a single tooth, bone loss or severe tooth mobility, and an unclosed wound were significantly associated with increased risk of developing medication-related osteonecrosis of the jaw (MRONJ). We recommend a minimally traumatic extraction technique, removal of any bone edges, and mucosal wound closure as standard procedures in patients receiving bisphosphonates. INTRODUCTION: Osteonecrosis of the jaws can occur following tooth extraction in patients receiving bisphosphonate drugs. Various strategies for minimizing the risk of MRONJ have been advanced, but no studies have comprehensively analyzed the efficacy of factors such as primary wound closure, demographics, and drug holidays in reducing its incidence. The purpose of this study was to retrospectively investigate the relationships between these various risk factors after tooth extraction in patients receiving oral bisphosphonate therapy. METHODS: Risk factors for MRONJ after tooth extraction were evaluated using univariate and multivariate analysis. All patients were investigated with regard to demographics; type and duration of oral bisphosphonate use; whether they underwent a discontinuation of oral bisphosphonates before tooth extraction (drug holiday), and the duration of such discontinuation; and whether any additional surgical procedures (e.g., incision, removal of bone edges, root amputation) were performed. RESULTS: We found that root amputation (OR = 6.64), extraction of a single tooth (OR = 3.70), bone loss or severe tooth mobility (OR = 3.60), and an unclosed wound (OR = 2.51) were significantly associated with increased risk of developing MRONJ. CONCLUSIONS: We recommend a minimally traumatic extraction technique, removal of any bone edges, and mucosal wound closure as standard procedures in patients receiving bisphosphonates. We find no evidence supporting the efficacy of a pre-extraction short-term drug holiday from oral bisphosphonates in reducing the risk of MRONJ.
Asunto(s)
Osteonecrosis de los Maxilares Asociada a Difosfonatos/etiología , Osteonecrosis de los Maxilares Asociada a Difosfonatos/prevención & control , Conservadores de la Densidad Ósea/administración & dosificación , Difosfonatos/administración & dosificación , Extracción Dental/efectos adversos , Técnicas de Cierre de Heridas , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Conservadores de la Densidad Ósea/efectos adversos , Difosfonatos/efectos adversos , Esquema de Medicación , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Extracción Dental/métodos , Privación de Tratamiento , Cicatrización de Heridas , Adulto JovenAsunto(s)
Acantólisis/inducido químicamente , Acantólisis/diagnóstico , Antineoplásicos/efectos adversos , Melanoma/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Vemurafenib/efectos adversos , Biopsia , Diagnóstico Diferencial , Femenino , Humanos , Persona de Mediana Edad , HombroAsunto(s)
Antineoplásicos Inmunológicos/efectos adversos , Erupciones por Medicamentos/etiología , Liquen Plano/inducido químicamente , Nivolumab/efectos adversos , Traumatismos por Radiación/etiología , Anciano , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/radioterapia , Terapia Combinada/efectos adversos , Erupciones por Medicamentos/patología , Femenino , Humanos , Liquen Plano/patología , Traumatismos por Radiación/patología , Radioterapia/efectos adversosRESUMEN
The prevalence of human papillomavirus (HPV)-related oropharyngeal cancers has been increasing in developed countries. We recently demonstrated that members of the apolipoprotein B mRNA-editing catalytic polypeptide 3 (APOBEC3, A3) family, which are antiviral factors, can induce hypermutation of HPV DNA in vitro. In the present study, we found numerous C-to-T and G-to-A hypermutations in the HPV16 genome in oropharyngeal cancer (OPC) biopsy samples using differential DNA denaturation PCR and next-generation sequencing. A3s were more abundantly expressed in HPV16-positive OPCs than in HPV-negative, as assessed using immunohistochemistry and reverse transcription quantitative PCR. In addition, interferons upregulated A3s in an HPV16-positive OPC cell line. Furthermore, quantitative PCR analysis of HPV DNA suggests that APOBEC3A (A3A) expression is strongly correlated with the integration of HPV DNA. These results suggest that HPV16 infection may upregulate A3A expression, thereby increasing the chance of viral DNA integration. The role of A3A in HPV-induced carcinogenesis is discussed.
Asunto(s)
Citidina Desaminasa/metabolismo , Genoma Viral , Neoplasias Orofaríngeas/etiología , Neoplasias Orofaríngeas/metabolismo , Papillomaviridae/fisiología , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/virología , Proteínas/metabolismo , Línea Celular Tumoral , Citidina Desaminasa/genética , Proteínas de Unión al ADN/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Mutación , Proteínas Oncogénicas Virales/genética , Papillomaviridae/clasificación , Papillomaviridae/genética , Proteínas/genéticaRESUMEN
The purpose of this study was to retrospectively investigate the outcomes of Brånemark System Mk III TiUnite/Groovy implants placed in patients at Kobe University Hospital. Various risk factors for implant failure, including mechanical coupling, were investigated by univariate and multivariate analysis. The predictive variables investigated included age, sex, smoking habit, general health, history of radiation therapy, application of a dentomaxillary prosthesis, type of prosthesis, use of alveolar bone augmentation, site of implant insertion, mechanical coupling between implants, and the length and diameter of the implants. Of the 907 implants investigated, only 23 were unsuccessful; the overall survival rate was 96.7%. Increased age, radiation therapy, application of a removable prosthesis or dentomaxillary prosthesis, lack of mechanical coupling between implants, and shorter implants (≤8.5mm) were significant risk factors for implant failure according to univariate analysis (P<0.05). Multivariate analysis identified a significant association (P<0.05) between dental implant failure and a lack of mechanical coupling between implants (odds ratio 6.88) and shorter implants (≤8.5mm) (odds ratio 3.43). The findings of this study demonstrated multivariate relationships between various risk factors and dental implant failure.
Asunto(s)
Implantación Dental Endoósea/efectos adversos , Implantes Dentales/efectos adversos , Fracaso de la Restauración Dental , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Factores SexualesRESUMEN
Since glucocorticoids remain an effective therapeutic option for the treatment of many inflammatory and autoimmune diseases, glucocorticoid-induced osteoporosis is the most common form of secondary osteoporosis. Fractures may occur in as many as 30-50% of patients receiving chronic glucocorticoid therapy. Under physiological conditions, glucocorticoids are required for normal bone development due to their regulation of osteoblast differentiation, possibly via the Wnt/ß-catenin pathway and TSC22D3. However, serum levels of endogenous corticosterone are elevated in aged mice and glucocorticoids exert negative effects on the survival of osteoblasts and osteocytes as well as angiogenesis. Glucocorticoid treatments impair bone formation and enhance bone resorption. Excess glucocorticoids induce osteoblast and osteocyte apoptosis by increasing pro-apoptotic molecules, reactive oxygen species, and endoplasmic reticulum stress and suppressing the Wnt/ß-catenin pathway. Autophagy protects osteocytes from glucocorticoid-induced apoptosis, but passed some threshold, the process of autophagy leads the cells to apoptosis. Excess glucocorticoids impair osteoblastogenesis by inducing Wnt antagonists, including Dkk1, Sost, and sFRP-1. However, the findings are controversial and the involvement of Wnt antagonists requires further study. Excess glucocorticoids reduce the phosphorylation of Akt and GSK3ß, which enhances the degradation of ß-catenin. Excess glucocorticoids have been shown to modulate the expression of miRNAs, including miR-29a, miR-34a-5p, and miR-199a-5p, which regulate the proliferation and differentiation of osteoblast lineage cells. Excess glucocorticoids also enhance bone resorption by reducing OPG expression, increasing Rankl expression and reactive oxygen species, and prolonging the life span of osteoclasts; however, they also suppress the bone-degrading capacity of osteoclasts by disturbing the organization of the cytoskeleton.
Asunto(s)
Glucocorticoides/farmacología , Osteogénesis/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Animales , Humanos , RatonesRESUMEN
This retrospective study was performed to investigate the influence of occlusal support and the presence, state, and position of mandibular third molars on the incidence of mandibular angle and condylar fractures. The following variables were investigated: age, sex, cause of fracture, presence and state (impaction, angulation, and the number of roots) of the mandibular third molars, site of the mandibular fracture, presence of occlusal support, duration of intermaxillary fixation, and postoperative complications. Various risk factors for mandibular angle and condylar fractures were investigated by univariate analysis. The risk of mandibular angle fracture was significantly higher in patients with occlusal support and mandibular third molars. The risk of condylar fracture was significantly higher in patients without occlusal support or mandibular third molars. The position and angulation of the mandibular third molars were not significant risk factors in mandibular angle and condylar fractures. This study demonstrated the influence of occlusal support and the presence of mandibular third molars on the incidence of mandibular angle and condylar fractures. The presence of occlusal support may be a more important factor affecting mandibular angle or condylar fractures than the position of the mandibular third molars.
Asunto(s)
Oclusión Dental , Cóndilo Mandibular/lesiones , Fracturas Mandibulares/etiología , Tercer Molar/anatomía & histología , Diente Impactado/complicaciones , Adolescente , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Humanos , Incidencia , Masculino , Fracturas Mandibulares/epidemiología , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenRESUMEN
Only a few reports on the level of progression of extracapsular spread (ECS) have been published. The aim of this study was to evaluate the efficacy of the level of progression of ECS in identifying those patients with oral squamous cell carcinoma (OSCC) at a high risk of recurrence who would benefit most from the intensification of adjuvant therapy. The level of progression of ECS for cervical lymph node metastasis in OSCC was divided into three types (A-C), and their relationships with patient prognosis were examined. ECS was observed in 87 of 441 patients with OSCC. The recurrence rate in patients with type C, which was defined as macroscopic tumour invasion into perinodal fat or muscle tissue, was high (69.8%), with 13 cases of death due to distant metastasis. The 3-year disease-specific survival rate for patients with type C was 49.0% and these patients also had a significantly poorer prognosis (P<0.01). The results of the multivariate analysis suggested that the prognosis of ECS in OSCC patients was associated with the level of progression of ECS, especially type C (P<0.01). Overall, the results of this study suggest that the level of progression of ECS is a useful prognostic factor in OSCC patients.