Enfermedad periodontal como signo clínico precoz de la arteriopatía cerebral autosómica dominante con infartos subcorticales y leucoencefalopatía (CADASIL) / Periodontal disease as an early clinical sign of cerebral autosomal, dominant arteriopathy with subcortical, infarcts and leudoencephalopathy (CADASIL)

Introducción. Los signos clínicos de la arteriopatía cerebral autosómica dominante con infartos subcorticales y leucoencefalopatía (CADASIL) se expresan principalmente en el sistema nervioso y recientemente se han descrito en la retina. Objetivo. Establecer la prevalencia y el riesgo de enfermedad periodontal en sujetos de familias con historia de presencia de mutación CADASIL del departamento de Antioquia, Colombia. Sujetos y métodos. Se realizó un estudio transversal (crosssectional), con asignación al grupo CADASIL y grupo control según genotipificación de cada sujeto para la mutación R1031C y C455R en Notch3. Cada participante firmó voluntariamente el consentimiento informado y recibió evaluación clínica neurológica,neuropsicológica y periodontal. Resultados. No existieron diferencias significativas entre los dos grupos según edad, sexo, escolaridad, tabaquismo, estado cognitivo, estado funcional y presencia de dientes naturales. La frecuencia de placa blanda, gingivitis y enfermedad periodontal fue significativamente mayor en el grupo de portadores de mutación CADASILque en el grupo control. El grupo CADASIL presentó seis veces más riesgo de tener placa blanda mayor o igual al 20% que el grupo control. La prevalencia de gingivitis mayor o igual al 10% se presentó en el total de los integrantes del grupo CADASIL. Las personas que conformaron el grupo CADASIL presentaron cinco veces más riesgo de tener enfermedad periodontal que el grupo control. Conclusión. Las personas portadoras de mutación CADASIL presentan mayor prevalencia y riesgo de enfermedad periodontal (AU)

Introduction. The clinical signs of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) are expressed mainly in the nervous system and recently reports also situate them in the retina. Aim. To determine the prevalence and risk of periodontal disease in subjects from families with a history of CADASIL mutation in the department of Antioquia, Colombia. Subjects and methods. A cross-sectional study was conducted, with subjects being assigned to the CADASIL group or a control group according to genotyping for the R1031C AND C455R mutation in Notch3. Each participant voluntarily signed the informed consent document and was submitted to neurological, neuropsychological and periodontal evaluation. Results. No significant differences were found between the two groups according to age, sex, schooling, tobacco smoking, cognitive status, functional status and the presence of natural teeth. The frequency of soft plaque, gingivitis and periodontal disease was significantly higher in the group of carriers of the CADASIL mutation than in the control group. The CADASIL group had six times more risk of having soft plaque above or equal to 20% than the control group. Prevalence of gingivitis above or equal to 10% was observed in all the members of the CADASIL group. The people in the CADASIL group had five times more risk of suffering periodontal disease than the control group. Conclusions. Carriers of the CADASIL mutation displayed a higher prevalence and risk of periodontal disease (AU)

[Periodontal disease as an early clinical sign of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)]. / Enfermedad periodontal como signo clínico precoz de la arteriopatía cerebral autosómica dominante con infartos subcorticales y leucoencefalopatía (CADASIL).

INTRODUCTION: The clinical signs of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) are expressed mainly in the nervous system and recently reports also situate them in the retina. AIM: To determine the prevalence and risk of periodontal disease in subjects from families with a history of CADASIL mutation in the department of Antioquia, Colombia. SUBJECTS AND METHODS: A cross-sectional study was conducted, with subjects being assigned to the CADASIL group or a control group according to genotyping for the R1031C and C455R mutation in Notch3. Each participant voluntarily signed the informed consent document and was submitted to neurological, neuropsychological and periodontal evaluation. RESULTS: No significant differences were found between the two groups according to age, sex, schooling, tobacco smoking, cognitive status, functional status and the presence of natural teeth. The frequency of soft plaque, gingivitis and periodontal disease was significantly higher in the group of carriers of the CADASIL mutation than in the control group. The CADASIL group had six times more risk of having soft plaque above or equal to 20% than the control group. Prevalence of gingivitis above or equal to 10% was observed in all the members of the CADASIL group. The people in the CADASIL group had five times more risk of suffering periodontal disease than the control group. CONCLUSIONS: Carriers of the CADASIL mutation displayed a higher prevalence and risk of periodontal disease.

[Neuronal DNA damage correlates with a positive detection of c-Jun, nuclear factor kB, p53 and Par-4 transcription factors in Alzheimer's disease]. / El daño nuclear neuronal se correlaciona con la detección in situ de los factores de transcripción c-Jun, factor nuclear kB, p53 y Par-4 en la enfermedad de Alzheimer.

INTRODUCTION AND OBJECTIVES: Alzheimer s disease is a neurodegenerative disorder characterized neuropathologically by beta amyloid plaques, neurofibrillary tangles, gliosis and neuronal loss. Recently, we have elucidated a molecular cascade of cell death induced by A beta 25 35 involving the activation of nuclear factor kappa B (NF kB), p53, and c Jun transcription factors in vitro. At present, no comparative reports have been published to establish a similar cell death signalization pathway in in vitro and in in vivo. The aim of this investigation was to determine if AD brains might activate NF kB, p53, c Jun, Par 4 transcription factors and to establish whether there exist a relationship between neuronal DNA damage and transcription factors activation. PATIENTS AND METHODS: We investigated Ab plaques, neurofibrillary tangles and NF kB, p53, and c Jun transcription factor activation in five cerebral regions from 3 normal subjects and from six demented patient with sporadic AD and one patient with AD familiar according to CERAD criteria. Using TUNEL we determine neuronal damage. RESULTS: We demonstrated neuronal damage in 17 out of 50 regions evaluated as TUNEL positive, and their distribution was heterogeneous in all brain regions evaluated; and the activation of NF kB, p53, c Jun and Par 4 transcription factors from case # 24 and #22, corresponding to TUNEL positive. CONCLUSIONS: We found a correlation between severity of DNA damage and nuclear activation of the transcription factors. These findings suggest that the AD brain may induce cell death by a molecular signalization similar to a non neuronal model by Ab exposure. This in situ study might validate previous Ab induced cell death observations in vitro.

El daño nuclear neuronal se correlaciona con la detección in situ de los factores de transcripción c-Jun, factor nuclear B, p53 y Par-4 en la enfermedad de Alzheimer / Neuronal DNA damage correlates with a positive detection of c-Jun, nuclear factor kB P53 and Par-4 transcription factors in Alzheimer´s disease

Introducción y objetivos. La enfermedad de Alzheimer (EA) se caracteriza neuropatológicamente por placas de Beta-amiloide, ovillos neurofibrilares (ONF), gliosis y pérdida neuronal. Recientemente, hemos elucidado una cascada de muerte celular inducida por el Alfa-Beta A25-35 que involucra la activación de los factores de transcripción nuclear B (FN-B), p53 y c-Jun in vitro. Actualmente, no se han comunicado estudios comparativos entre los eventos moleculares de muerte celular in vitro e in vivo. El objetivo fue determinar si en los cerebros con EA se activan el FN-kB, p53, c-Jun y Par-4,y establecer si esta activación se relaciona con la fragmentación del ADN neuronal. Pacientes y métodos. Se investigó la presencia de placas, ONF y activación de los factores de transcripción en cinco regiones de tejido post mortem en tres cerebros de sujetos normales, en seis pacientes diagnosticados de Alzheimer esporádico y en uno dignosticado de Alzheimer familiar con los criterios de CERAD. El daño neuronal se determinó con TUNEL. Resultados. Evidenciamos daño neuronal en 17 de 50 regiones analizadas positivas para TUNEL, con una distribución heterogénea en todas las regiones evaluadas. También se puso de manifiesto la activación del FN-kB, p53, Par-4 y c-Jun en los casos n.º 22 y 24, correspondientes a las regiones positivaspara TUNEL. Conclusión. Demostramos una correlación entre la gravedad del daño neuronal y la activación nuclear de los factores de transcripción. Estos hallazgos sugieren que en los cerebros afectados de EA se podría inducir muerte neuronal por una señalización molecular similar a modelos no neuronales por exposición al A25-35. Este estudio in situ valida observaciones previas de muerte celular inducida por el A25-35 in vitro (AU)