In silico protein interaction screening uncovers DONSON's role in replication initiation.

CDC45-MCM2-7-GINS (CMG) helicase assembly is the central event in eukaryotic replication initiation. In yeast, a multi-subunit "pre-loading complex" (pre-LC) accompanies GINS to chromatin-bound MCM2-7, leading to CMG formation. Here, we report that DONSON, a metazoan protein mutated in microcephalic primordial dwarfism, is required for CMG assembly in vertebrates. Using AlphaFold to screen for protein-protein interactions followed by experimental validation, we show that DONSON scaffolds a vertebrate pre-LC containing GINS, TOPBP1, and DNA pol ε. Our evidence suggests that DONSON docks the pre-LC onto MCM2-7, delivering GINS to its binding site in CMG. A patient-derived DONSON mutation compromises CMG assembly and recapitulates microcephalic dwarfism in mice. These results unify our understanding of eukaryotic replication initiation, implicate defective CMG assembly in microcephalic dwarfism, and illustrate how in silico protein-protein interaction screening accelerates mechanistic discovery.

PRIM1 deficiency causes a distinctive primordial dwarfism syndrome.

DNA replication is fundamental for cell proliferation in all organisms. Nonetheless, components of the replisome have been implicated in human disease, and here we report PRIM1 encoding the catalytic subunit of DNA primase as a novel disease gene. Using a variant classification agnostic approach, biallelic mutations in PRIM1 were identified in five individuals. PRIM1 protein levels were markedly reduced in patient cells, accompanied by replication fork asymmetry, increased interorigin distances, replication stress, and prolonged S-phase duration. Consequently, cell proliferation was markedly impaired, explaining the patients' extreme growth failure. Notably, phenotypic features distinct from those previously reported with DNA polymerase genes were evident, highlighting differing developmental requirements for this core replisome component that warrant future investigation.

Sonic hedgehog accelerates DNA replication to cause replication stress promoting cancer initiation in medulloblastoma.

The mechanisms generating cancer-initiating mutations are not well understood. Sonic hedgehog (SHH) pathway activation is frequent in medulloblastoma (MB), with PTCH1 mutations being a common initiating event. Here we investigated the role of the developmental mitogen SHH in initiating carcinogenesis in the cells of origin: granule cell progenitors (GCPs). We delineate a molecular mechanism for tumor initiation in MB. Exposure of GCPs to Shh causes a distinct form of DNA replication stress, increasing both origin firing and fork velocity. Shh promotes DNA helicase loading and activation, with increased Cdc7-dependent origin firing. The S-phase duration is reduced and hyper-recombination occurs, causing copy number neutral loss of heterozygosity-a frequent event at the PTCH1/ptch1 locus. Moreover, Cdc7 inhibition to attenuate origin firing reduces recombination and preneoplastic tumor formation in mice. Therefore, tissue-specific replication stress induced by Shh promotes loss of heterozygosity, which in tumor-prone Ptch1+/- GCPs results in loss of this tumor suppressor-an early cancer-initiating event.

Recent advances in SHH medulloblastoma progression: tumor suppressor mechanisms and the tumor microenvironment.

Medulloblastoma, the most common of the malignant pediatric brain tumors, is a group of four molecularly and clinically distinct cancers with different cells of origin. One of these medulloblastoma groups displays activation of Sonic hedgehog (SHH) signaling and originates from granule cell precursors of the developing cerebellum. Ongoing basic and clinical research efforts are tailored to discover targeted and safer therapies, which rely on the identification of the basic mechanisms regulating tumor initiation, progression, and metastasis. In SHH medulloblastoma, the mechanisms regulating neural progenitor transformation and progression to advanced tumors have been studied in some detail. The present review discusses recent advances on medulloblastoma progression derived from studies using mouse models of SHH medulloblastoma. We focus on mechanisms that regulate progression from precancerous lesions to medulloblastoma, describing novel roles played by tumor suppressor mechanisms and the tumor microenvironment.

Overexpression of Desmoglein 2 in a Mouse Model of Gorlin Syndrome Enhances Spontaneous Basal Cell Carcinoma Formation through STAT3-Mediated Gli1 Expression.

Activation of the hedgehog pathway is causative of virtually all sporadic and Gorlin syndrome-related basal cell carcinomas (BCCs), with loss of function of Ptc1 being the most common genomic lesion. Sporadic BCCs also overexpress Dsg2, a desmosomal cadherin normally found in the basal layer. Using a mouse model of Gorlin syndrome (Ptc1+/lacZ mice), we found that overexpressing Dsg2 in the basal layer (K14-Dsg2/Ptc1+/lacZ mice) or the superficial epidermis (Inv-Dsg2/Ptc1+/lacZ mice) resulted in increased spontaneous BCC formation at 3 and 6 months, respectively. The tumors did not show loss of heterozygosity of Ptc1, despite high levels of Gli1 and phosphorylated Stat3. A panel of sporadic human BCCs showed increased staining of both Dsg2 and phosphorylated Stat3 in all nine samples. Overexpression of Dsg2 in ASZ001 cells, a Ptc1-/- BCC cell line, induced Stat3 phosphorylation and further increased Gli1 levels, in both an autocrine and paracrine manner. Three different Stat3 inhibitors reduced viability and Gli1 expression in ASZ001 cells but not in HaCaT cells. Conversely, stimulation of Stat3 in ASZ001 cells with IL-6 increased Gli1 expression. Our results indicate that Dsg2 enhances canonical hedgehog signaling downstream of Ptc1 to promote BCC development through the activation of phosphorylated Stat3 and regulation of Gli1 expression.

Muscle Activity and Muscle Strength in Atypical Swallowing / Actividad Muscular y Fuerza Muscular en la Deglución Atípica

Abstract Objective: To characterize muscle activity and muscle strength in patients with atypical swallowing (AS; n = 88) and competent lips (CL) or incompetent lips (IL) versus a control group (Ctrl; n = 90) Methods and materials: An analytical case-control study was conducted using surface electromyography (sEMG) of the orbicularis oris, mentalis and masseter muscles. Compression forces of the orbicularis oris, right and left masseters muscle (Cfrmm, Cflmm)), tongue tensile strength (Tts) via myoscan analysis and resistance of the orbicularis oris (Roo) via dynamo-metry were determined. Comparisons were made with the Mann-Whitney U test under a 95% confidence interval. Results: The amplitude of the sEMG record of the orbicularis oris muscle, in maximal contraction, was lower (p<0.01) in the atypical swallowing group (596.40 ± 175.83) compared to controls (659.83 ± 203.79). The muscle strength studied in the experimental group was lower (p<0.01) than in controls (CFo: AS: 0.31 ± 0.13; Ctrl: 0.38 ± 0,11; Cfrmm: AS: 0.40 ± 0.08; Ctrl: 0.50 ± 0.11; Cflmm: AS: 0.41 ± 0.08; Ctrl: 0.58 ± 0.59; Tts, AS: 0.52 ± 0.14, Ctrl: 0.65 ± 0.14, and Roo: AS: 2.47 ± 0.61; Ctrl: 2.73 ± 0.60). Patients with incompetent lips had a greater muscle activity of the orbicularis oris in swallowing (AS of IL: 197.01 ± 85.84; AS of CL: 160.54 ± 97.03; Ctrl: 147.18 ± 80.10). Conclusion: Patients with atypical swallowing showed differences in the strength of studied muscles and the muscle activity of the orbicular oris muscle compared to controls.

Resumen Objetivo: Caracterizar la actividad y fuerza muscular de pacientes con deglución atípica (DA; N=88) con competencia labial (CL) o incompetencia labial (IL) vs un grupo control (Ctrl; N=90). Materiales y métodos: Estudio analítico de casos y controles se realizó una electromiografía de superficie (sEMG) de los músculos orbicular, mental y maseteros; se determinaron las fuerzas compresiva del orbicular de los labios (FCo), contráctil del masetero derecho (FCmd) e izquierdo (FCmi), extensora del músculo lingual (FEl) por mioescanografía y la fuerza de resistencia del orbicular de los labios (FRo) por dinamometría. Resultados: La amplitud del registro sEMG del músculo orbicular de los labios, en contracción máxima, fue menor (p<0.01) en el grupo DA(596,40±175,83) con respecto a los controles(659,83±203,79); la fuerza de los músculos estudiados en el grupo experimental fue menor (p<0,01) que en los controles (FCo: DA: 0,31±0,13; Ctrl: 0,38±0,11; FCmd: DA: 0,40±0,08; Ctrl: 0,50±0,11; FCmi: DA: 0,41±0,08; Ctrl: 0,58±0,59; FEl; DA: 0,52±0,14; Ctrl: 0,65±0,14; y FRo: DA: 2,47±0,61; Ctrl: 2,73±0,60). Los pacientes con DA-IL presentaron mayor actividad muscular del orbicular en deglución (DA-IL: 197,01±85,84; DA-CL: 160,54±97,03; Ctrl: 147,18±80,10). Conclusiones: Los pacientes con DA difieren en la fuerza de los músculos estudiados y en la actividad muscular del orbicular con respecto a los controles. Los pacientes con DA-CL y DA-IL difieren en la actividad y fuerza muscular del orbicular.

Different brain structures exhibit the same caffeine levels after the administration of a single dose of caffeine / Estructuras encefálicas distintas muestran concentración de cafeína similar después de la administración de una dosis única

Caffeine is a highly consumed stimulant of the nervous system. Although caffeine has diverse effects on different brain functions, little is known about the specific pharmacokinetics of this substance in the brain. For instance, most studies that assessed caffeine distribution in the rat brain have only measured caffeine levels in the cortex and striatum but not in more specific brain areas. Aims: The purpose of this work was to measure the caffeine concentration in blood and different brain regions (i.e. cortex, striatum, hippocampus, cerebellum and brainstem) at different times after the administration of a single intraperitoneal dose of caffeine. Methods: Adult Wistar rats (250 to 300 gr) were injected with a single intraperitoneal dose of 30 mg/Kg of caffeine. 20, 40, 60 and 80 minutes after administration, subjects were sacrificed by decapitation and samples of plasma, cerebral cortex, striatum, hippocampus, cerebellum and brainstem were obtained. Caffeine levels in the blood and each brain structure were measured by RP-HPLC and statistical analysis was performed. Results: Caffeine levels were higher in the plasma compared to all the brain structures studied. Different brain regions displayed similar caffeine concentrations. For all brain regions, the maximal concentration levels of caffeine were reached in the first 40 minutes after caffeine administration. Conclusions: The results support previous studies that show similar caffeine concentration between cortex and striatum, but also extend the results to other brain structures. Furthermore, caffeine concentration increases similarly in the plasma and brain structures. 40, 60 and 80 minutes after administration, caffeine concentration in the blood is almost two times higher than in the brain. This suggests that the effects of caffeine on different brain functions do not depend on pharmacokinetic differences between brain areas and are rather explained by pharmacodynamics.

Antecedentes: La cafeína es el estimulante del sistema nervioso más consumido a nivel mundial. Aunque, la cafeína tiene diferentes efectos sobre las funciones cerebrales, poco se sabe acerca de su farmacocinética en el cerebro. Por ejemplo, la mayoría de estudios que evaluaron la distribución de cafeína en el cerebro de rata han medido niveles de cafeína en corteza y estriado, pero no en áreas cerebrales más específicas. Objetivo: El propósito del trabajo fue medir la concentración de cafeína en sangre y diferentes regiones encefálicas (corteza, estriado, hipocampo, cerebelo, tallo cerebral), a diferentes tiempos, después de administrar una única dosis de cafeína. Método: Ratas Wistar adultas (250-300 gr) recibieron una dosis intraperitoneal de cafeína de 30mg/Kg de peso. 20, 40 60 y 80 minutos después de la administración, los sujetos se sacrificaron por decapitación y se obtuvieron muestras de plasma, corteza cerebral, estriado, hipocampo, cerebelo y tallo cerebral. Los niveles de cafeína en plasma y estructuras encefálicas se determinaron por RP-HPLC y se realizó análisis estadístico. Resultados: Los niveles de cafeína fueron mayores en plasma que en las regiones encefálicas estudiadas. Las distintas regiones encefálicas presentaron concentraciones similares de cafeína. En todas las regiones, la mayor concentración de cafeína se obtuvo 40 minutos después de la administración de cafeína. Conclusiones: Este estudio soporta resultados previos que muestran concentraciones similares de cafeína entre la corteza y el estriado, además los extiende a otras regiones encefálicas. La concentración de cafeína aumenta similarmente en plasma y estructuras encefálicas. 40, 60 y 80 minutos después de la administración, la concentración de cafeína en plasma es casi el doble de la encontrada en el cerebro. Lo anterior sugiere que los efectos de la cafeína en distintas funciones cerebrales no dependen de diferencias farmacocinéticas entre regiones encefálicas sino que son más bien explicadas por factores farmacodinámicos.

Evasion of cell senescence in SHH medulloblastoma.

The mechanisms leading to brain tumor formation are poorly understood. Using Ptch1+/- mice as a medulloblastoma model, sequential mutations were found to shape tumor evolution. Initially, medulloblastoma preneoplastic lesions display loss of heterozygosity of the Ptch1 wild-type allele, an event associated with cell senescence in preneoplasia. Subsequently, p53 mutations lead to senescence evasion and progression from preneoplasia to medulloblastoma. These findings are consistent with a model where high levels of Hedgehog signaling caused by the loss of the tumor suppressor Ptch1 lead to oncogene-induced senescence and drive p53 mutations. Thus, cell senescence is an important characteristic of a subset of SHH medulloblastoma and might explain the acquisition of somatic TP53 mutations in human medulloblastoma. This mode of medulloblastoma formation contrasts with the one characterizing Li-Fraumeni patients with medulloblastoma, where TP53 germ-line mutations cause chromothriptic genomic instability and lead to mutations in Hedgehog signaling genes, which drive medulloblastoma growth. Here we discuss in detail these 2 alternative mechanisms leading to medulloblastoma tumorigenesis.

Evasion of Cell Senescence Leads to Medulloblastoma Progression.

How brain tumors progress from precancerous lesions to advanced cancers is not well understood. Using Ptch1(+/-) mice to study medulloblastoma progression, we found that Ptch1 loss of heterozygosity (LOH) is an early event that is associated with high levels of cell senescence in preneoplasia. In contrast, advanced tumors have evaded senescence. Remarkably, we discovered that the majority of advanced medulloblastomas display either spontaneous, somatic p53 mutations or Cdkn2a locus inactivation. Consistent with senescence evasion, these p53 mutations are always subsequent to Ptch1 LOH. Introduction of a p53 mutation prevents senescence, accelerates tumor formation, and increases medulloblastoma incidence. Altogether, our results show that evasion of senescence associated with Ptch1 LOH allows progression to advanced tumors.

[Differential effects of attention deficit/hyperactivity disorder subtypes in event-related potentials]. / Efecto diferencial del subtipo clínico en los potenciales evocados cognitivos de pacientes con déficit de atención e hiperactividad.

BACKGROUND: To better understand the neurophysiological substrates in attention deficit/hyperactivity disorder (ADHD), a study was performed on of event-related potentials (ERPs) in Colombian patients with inattentive and combined ADHD. METHODS: A case-control, cross-sectional study was designed. The sample was composed of 180 subjects between 5 and 15 years of age (mean, 9.25±2.6), from local schools in Manizales. The sample was divided equally in ADHD or control groups and the subjects were paired by age and gender. The diagnosis was made using the DSM-IV-TR criteria, the Conners and WISC-III test, a psychiatric interview (MINIKID), and a medical evaluation. ERPs were recorded in a visual and auditory passive oddball paradigm. Latency and amplitude of N100, N200 and P300 components for common and rare stimuli were used for statistical comparisons. RESULTS: ADHD subjects show differences in the N200 amplitude and P300 latency in the auditory task. The N200 amplitude was reduced in response to visual stimuli. ADHD subjects with combined symptoms show a delayed P300 in response to auditory stimuli, whereas inattentive subjects exhibited differences in the amplitude of N100 and N200. Combined ADHD patients showed longer N100 latency and smaller N200-P300 amplitude compared to inattentive ADHD subjects. CONCLUSIONS: The results show differences in the event-related potentials between combined and inattentive ADHD subjects.

Efecto diferencial del subtipo clínico en los potenciales evocados cognitivos de pacientes con déficit de atención e hiperactividad / Differential effects of Attention deficit/hyperactivity disorder subtypes in event-related potentials

Introducción: Con el fin de mejorar el conocimiento de las bases neurofisiológicas del trastorno por déficit de atención e hiperactividad (TDAH) se realizó un estudio de potenciales evocados cognitivos en pacientes colombianos con TDAH combinado y TDAH inatento. Métodos: Estudio no experimental, de casos y controles y corte transversal, con una muestra conformada por 180 niños (n -132) y niñas (n-48), entre 5 y 15 (media, 9,25 ± 2,6) años de edad, pertenecientes a instituciones educativas de la ciudad de Manizales. Se dividió a los sujetos en un grupo con diagnóstico de TDAH y otro de control apareados por edad y sexo. Los sujetos fueron evaluados con los criterios del DSM-IV-TR, test de Conners, WISC-III y entrevista psiquiátrica estructurada MINIKID. Se realizó una revisión médica y se tomaron los potenciales evocados relacionados con eventos en modalidad visual y auditiva de atención pasiva (sin respuesta motora) dentro del paradigma oddball. Resultados: Los sujetos con TDAH presentaron diferencias en la amplitud N200 y latencia P300 en la modalidad auditiva y en la amplitud N200 en la modalidad visual. El subtipo clínico combinado mostró prolongación de la latencia de P300 en Fz, Cz y Pz en la tarea auditiva. El subtipo inatento mostró diferencias en la amplitud de la onda N200 y N100. Al comparar estos dos subtipos en la modalidad auditiva, el subtipo combinado tuvo mayor latencia de N100 y menor amplitud de P300 en Pz. Conclusiones: Los resultados indican una modulación diferencial de los componentes de los potenciales evocados cognitivos entre TDAH combinado y TDAH inatento.

Background: To better understand the neurophysiological substrates in attention deficit/hyperactivity disorder (ADHD), a study was performed on of event-related potentials (ERPs) in Colombian patients with inattentive and combined ADHD. Methods: A case-control, cross-sectional study was designed. The sample was composed of 180 subjects between 5 and 15 years of age (mean, 9.25 ± 2.6), from local schools in Manizales. The sample was divided equally in ADHD or control groups and the subjects were paired by age and gender. The diagnosis was made using the DSM-IV-TR criteria, the Conners and WISC-III test, a psychiatric interview (MINIKID), and a medical evaluation. ERPs were recorded in a visual and auditory passive oddball paradigm. Latency and amplitude of N100, N200 and P300 components for common and rare stimuli were used for statistical comparisons. Results: ADHD subjects show differences in the N200 amplitude and P300 latency in the auditory task. The N200 amplitude was reduced in response to visual stimuli. ADHD subjects with combined symptoms show a delayed P300 in response to auditory stimuli, whereas inattentive subjects exhibited differences in the amplitude of N100 and N200. Combined ADHD patients showed longer N100 latency and smaller N200-P300 amplitude compared to inattentive ADHD subjects. Conclusions: The results show differences in the event-related potentials between combined and inattentive ADHD subjects.

The Shh receptor Boc promotes progression of early medulloblastoma to advanced tumors.

During cerebellar development, Sonic hedgehog (Shh) signaling drives the proliferation of granule cell precursors (GCPs). Aberrant activation of Shh signaling causes overproliferation of GCPs, leading to medulloblastoma. Although the Shh-binding protein Boc associates with the Shh receptor Ptch1 to mediate Shh signaling, whether Boc plays a role in medulloblastoma is unknown. Here, we show that BOC is upregulated in medulloblastomas and induces GCP proliferation. Conversely, Boc inactivation reduces proliferation and progression of early medulloblastomas to advanced tumors. Mechanistically, we find that Boc, through elevated Shh signaling, promotes high levels of DNA damage, an effect mediated by CyclinD1. High DNA damage in the presence of Boc increases the incidence of Ptch1 loss of heterozygosity, an important event in the progression from early to advanced medulloblastoma. Together, our results indicate that DNA damage promoted by Boc leads to the demise of its own coreceptor, Ptch1, and consequently medulloblastoma progression.

Estandarización de un protocolo para la combinación de técnicasneurohistológicas en cortes obtenidos con vibrátomo / Protocol for the combination of neurohistological techniques on vibratome obtained sections

Introducción. El estudio histológico del sistema nervioso ha requerido del uso de técnicas especiales. Esto se debe a que no existen métodos que permitan visualizar, simultáneamente, todos los constituyentes celulares del tejido nervioso. Objetivos. Adaptar un protocolo para llevar a cabo un método de coloración del tejido nervioso, previamente conocido pero poco utilizado hasta ahora, debido a las dificultades que presenta el procedimiento original. Materiales y métodos. Se trabajó con cortes de encéfalo y médula espinal de 4 mm de espesor, extraídas de ratones adultos previamente fijados mediante perfusión intracardiaca con paraformaldehído al 4 %. En un vibrátomo se obtuvieron cortes de 15 a 25 μm de espesor. Éstos se montaron sobre láminas portaobjeto preparadas con gelatina como adhesivo. Las preparaciones se sometieron al protocolo de coloración Luxol Fast Blue-PAS-Hematoxylin (LPH) y, su combinación, con un método de tinción argéntica (LPH-Holmes). Resultados. La técnica LPH permitió obtener una excelente diferenciación de la sustancia gris y la sustancia blanca en todas las regiones del sistema nervioso. En una vista panorámica, la sustancia gris se observa de color rosado, mientras que las fibras y tractos nerviosos con mielina se apreciaron de color azul claro. La combinación LPH-Holmes conservó las características de la tinción, pero mejoró ostensiblemente la demarcación de los axones y tractos. Conclusiones. Se estandarizó un protocolo para llevar a cabo la tinción LPH y su combinación LPH-Holmes en cortes obtenidos con un vibrátomo. Éste es más corto, menos dispendioso y menos costoso que el original y, además, preserva mejor la integridad del tejido nervioso.

Introduction. The histological study of the nervous system requires the use of special techniques. Currently, no methods are available to visualize simultaneously all the cellular constituents of nervous tissue.Objectives. A protocol was adapted for staining nervous tissue by modification of a formerly difficult procedure.Materials and methods. Slices of brain and spinal cord, 4 mm thick, were taken from adult mice, previously fixed by intracardiac perfusion with 4% paraformaldehyde. Vibratome sections were obtained with thickness of 15-25 μm. These were mounted on glass slides prepared with gelatin as an adhesive. The preparations were subjected to staining protocol Luxol Fast Blue-PAS-hematoxylin (LPH) combined with silver staining method (LPH-Holmes).Results. LPH technique yielded an excellent differentiation of gray and white matter in all regions of the nervous system. A panoramic view of the gray matter was colored pink in contrast to the myelinated nerve fibers and tracts which were light blue. The combination LPH-Holmes retained the staining characteristics but significantly improved the demarcation of axons and tracts.Conclusions. A protocol was standardized for the LPH and LPH-Holmes nervous tissue stains applied in combination to tissue slices obtained with a vibratome. The method was shorter, less wasteful and less expensive than the original and also better preserved the integrity of nervous tissue.

[Protocol for the combination of neurohistological techniques on vibratome obtained sections]. / Estandarización de un protocolo para la combinación de técnicas neurohistológicas en cortes obtenidos con vibrátomo.

INTRODUCTION: The histological study of the nervous system requires the use of special techniques. Currently, no methods are available to visualize simultaneously all the cellular constituents of nervous tissue. OBJECTIVES: A protocol was adapted for staining nervous tissue by modification of a formerly difficult procedure. MATERIALS AND METHODS: Slices of brain and spinal cord, 4 mm thick, were taken from adult mice, previously fixed by intracardiac perfusion with 4% paraformaldehyde. Vibratome sections were obtained with thickness of 15-25 µm. These were mounted on glass slides prepared with gelatin as an adhesive. The preparations were subjected to staining protocol Luxol Fast Blue-PAS-hematoxylin (LPH) combined with silver staining method (LPH-Holmes). RESULTS: LPH technique yielded an excellent differentiation of gray and white matter in all regions of the nervous system. A panoramic view of the gray matter was colored pink in contrast to the myelinated nerve fibers and tracts which were light blue. The combination LPH-Holmes retained the staining characteristics but significantly improved the demarcation of axons and tracts. CONCLUSIONS: A protocol was standardized for the LPH and LPH-Holmes nervous tissue stains applied in combination to tissue slices obtained with a vibratome. The method was shorter, less wasteful and less expensive than the original and also better preserved the integrity of nervous tissue.

Modulación del componente P300 de los potenciales evocados en un grupo de niños colombianos con trastorno de atención-hiperactividad / P300-wave modulation in a group of colombian children with attention deficit/hyperactivity disorder

IntroduccIón: en el trastorno de atención-hiperactividad (TDAH), uno de los desórdenes más frecuentes del neurodesarrollo, se han postulado varios marcadores biológicos, entre los cuales se encuentran los neurofisioló-gicos. Como ejemplo de esto, a continuación se presenta un estudio de potenciales evocados cognitivos en niños con TDAH.objetIvo: estudiar el componente P300 de los potenciales relacionados a eventos cognitivos en un grupo de pacientes colombianos con trastorno de atención-hiperactividad (TDAH). MaterIal y Métodos: treinta pacientes, pareados por edad y género, realizaron una prueba de atención auditiva y visual bajo el paradigma de disparidad “oddball”. Se registraron los potenciales en los electrodos Fz, Cz y Pz y se cuantificó la amplitud y latencia del componente P300. Los datos se compararon con la prueba t-Student y con la prueba U de Mann-Whitney. resultados: los pacientes con TDAH mostraron una prolongación de la latencia y una disminución de la amplitud del componente P300.Todas las diferencias fueron estadisticamente significativas (p<0,05), excepto en la amplitud de Fz en la prueba visual. conclusIones: existen cambios en la latencia y amplitud de la onda P300 en los pacientes con TDAH estudiados que pueden significar una modulación diferente de la información auditiva y visual por el cerebro.

Potenciales evocados en dos casos deesquizencefalia de borde abierto / Evoked potentials in two cases of open-lip schizencephaly

La esquizencefalia es una malformación cerebral producida por un trastorno en la migración neuronal. Se caracteriza por una hendidura que compromete todo el espesor del palio, desde la superficie pial hasta el sistema ventricular. Cuando los bordes de corteza alrededor de la hendidura están en contacto la esquizencefalia es de labio cerrado, pero cuando los bordes están separados la lesión se denomina de labio abierto. Las manifestaciones clínicas más frecuentes son: retraso psicomotor, déficit motor y epilepsia. Se presentan dos pacientes con esquizencefalia de labio abierto, uno unilateral y otro bilateral, a los que se les realizaron estudios de potenciales evocados auditivos, visuales, cognitivos y somatosensoriales. Estos estudios permitieron obtener correlaciones clínicas e imagenológicas. Cada caso presentó un patrón específico en los potenciales evocados somatosensoriales, los que pueden confirmar la sospecha de malformaciones hemisféricas. Por el contrario, los potenciales evocados cognitivos, visuales y auditivos son inespecíficos a para diferenciar los tipos de esquizencefalia.

Schizencephaly is a brain malformation caused by an abnormality of neuronal migration. It is characterized by a cleft spanning the pallium from the pial surface to the ventricular system that is lined by cortical gray matter. If the edges of the cortex around the cleft are in contact with each other, the lesion is named closed-lip schizencephaly; when the cleft borders are not in contact, the lesion is termed open-lip schizencephaly and the cleft is filled with cerebrospinal fluid. The most frequent clinical manifestations of the disease are psychomotor delay, motor impairmentand epilepsy. This is a report of two cases of patients with diagnosis of open-lip schizencephaly, the first oneunilateral and the second one bilateral . Various studies of evoked potentials (ERP) by different sensory modalitieswere done, correlations between clinical data, ERP and brain images were obtained too. Each case presented one specific pattern in the somatosensory evoked potentials that can be used to suspect haemispheric malformations. Auditory and visual evoked potencials were not useful to discriminate between different types of schizencephaly.

Caracterización de la onda P300 en pacientes colombianos con diagnóstico de esquizofrenia / Characterization of P300 Wave in Colombian patients with a schizophrenia diagnose

Objetivo: Evaluar la amplitud y latencia de la onda P300 en un grupo de pacientes con diagnóstico de esquizofrenia. Método: Se seleccionó un grupo de 36 pacientes con diagnóstico de esquizofrenia en período de remisión y el mismo número de controles, pareados por edad y sexo, sin antecedentes de enfermedad neurológica ni psiquiátrica. Se realizaron potenciales evocados cognitivos, para obtener la amplitud y latencia de la onda P300 en todos los sujetos, con cuatro electrodos activos ubicados en F3, Fz, Cz y Pz, según el sistema electroencefalográfico 10-20. Se realizó un análisis de varianzas de medidas repetidas para evaluar las diferencias entre los grupos. Resultados: En todos los electrodos se obtuvo una amplitud disminuida y una prolongación de la latencia en el grupo de pacientes; las diferencias fueron estadísticamente significativas (p<0,05). Conclusiones: Este es el primer estudio de la onda P300 en esquizofrenia realizado en una población colombiana. Se encontraron resultados similares a los reportados en otros estudios internacionales a partir de los cuales se concluye que las alteraciones de la onda P300 en pacientes con esquizofrenia se pueden considerar un endofenotipo o marcador biológico del trastorno, que podría permitir usar esta metodología en otro tipo de estudios biológicos. Sin embargo, la baja especificidad de la técnica es un gran limitante para su utilización como prueba diagnóstica...

Objetive: To assess the P300 wave amplitude and latency in a group of patients dianosed with schizophrenia. Methods: A group of 36 schizophrenic patients in remission stage and the same number of healthy controls were selected, paired by age and sex, with NO personal history of neurologic disease and NO family history of psychiatric disorders. Cognitive event-related potentials were performed to obtain the P300 wave amplitude and latency, USING four active electrodes PLACED at F3, Fz, Cz and Pz, according to the 10-20 electroencephalographic system. A repeatedmeasures ANOVA test was used to evaluate the differences between the groups Results: A decreased amplitud and a prolonged latency in all electrodes were found in the patient group. The differences were statistically significant (<0.05). Conclusion: This is the first study on P300 wave in schizophrenia performed in Colombia. Similar results to those reported in other international case-control studies were found and, as such, it was concluded that the P300 wave abnormalities in patients with schizophrenia may be considered as an endophenotype, or a biological marker of this disorder that would allow using this methodology in other types of biological studies. However, the low specificity of this technique limits its use as a diagnostic test...