Malformaciones del sistema nervioso central: correlación neuroquirúrgica / Central nervous system malformations: neurosurgery correlates

Las malformaciones congénitas del sistema nervioso central se relacionan con alteraciones en la formación del tubo neural, en las que se incluyen la mayoría de las entidades de tratamiento neuroquirúrgico, disrafismos y craneosinostosis, alteraciones de la proliferación neuronal, microcefalias y megalencefalias, anomalías de la migración neuronal, lisencefalia, paquigiria, esquisencefalia, agenesia del cuerpo calloso, heterotopías y displasias corticales, malformaciones raquimedulares y disrafias medulares. En el presente trabajo se clasifican las diferentes malformaciones del sistema nervioso central susceptibles de corregirse mediante cirugía en el menor tiempo posible y se exponen los mecanismos de génesis de estas lesiones cada vez mejor estudiadas desde las áreas neurogenética y neuroembriológica. Esto involucra la posible conexión de áreas de conocimiento novedosas, como los mecanismos de alteración de la inducción dorsal (cierre del tubo neural) y ventral (telencefalización) con los mecanismos actuales de corrección, y también las anomalías de la proliferación y diferenciación celular de la migración neuronal y, finalmente, el complejo de malformaciones que afectan la fosa posterior y las posibilidades actuales de corrección de éstas (AU)

Congenital malformations of the central nervous system are related to alterations in neural tube formation, including most of the neurosurgical management entities, dysraphism and craniosynostosis; alterations of neuronal proliferation; megalencefaly and microcephaly; abnormal neuronal migration, lissencephaly, pachygyria, schizencephaly, agenesis of the corpus callosum, heterotopia and cortical dysplasia, spinal malformations and spinal dysraphism. We expose the classification of different central nervous system malformations that can be corrected by surgery in the shortest possible time and involving genesis mechanisms of these injuries getting better studied from neurogenic and neuroembryological fields, this involves connecting innovative knowledge areas where alteration mechanisms in dorsal induction (neural tube) and ventral induction (telencephalization) with the current way of correction, as well as the anomalies of cell proliferation and differentiation of neuronal migration and finally the complex malformations affecting the posterior fossa and current possibilities of correcting them (AU)

Diversidad de clones de Staphylococcus aureus resistentes a meticilina y emergencia de nuevos clones encontrados en comunidades de Tenerife, punto caliente de turismo en España / High diversity of methicillin-resistant Staphylococcus aureus clones and emergence of newly described ones in communities of Tenerife Island, a travel hub in Spain

Objetivo: Analizar una colección de aislados de Staphylococcus aureus resistentes a meticilina (SARM) recogidos en Tenerife e identificar aquellas cepas estrictamente comunitarias. Materiales y Métodos: Estudio retrospectivo de los aislados SARM recogidos entre julio de 2004 y mayo de 2007, que encajaron como SARM adquiridos en la comunidad, según las normas del Centro para la Prevención y Control de Enfermedades. Se realizó la identificación fenotípica y los perfiles de susceptibilidad antimicrobiana para una amplia gama de antibióticos empleando un sistema automatizado, confirmando los resultados posteriormente mediante PCR. Resultados: Se detectaron en la comunidad perfiles típicos de aislados SARM hospitalarios, como la multirresistencia y el SCCmecII. La toxina característica de aislados comunitarios, el PVL, se halló en un bajo porcentaje concentrado en el sur de la isla. Se describieron dos linajes nuevos: ST1433-SASM y ST1434-SARM-IVA. Conclusiones: Aislados de SARM con características hospitalarias y comunitarias se encuentran circulando en ambos ambientes. Desaconsejamos aplicar terapia empírica sin previo análisis molecular del microorganismo (AU)

Objective: To analyse a set of MRSA isolates collected from Tenerife Island in order to distinguish among them CA-MRSA and others. Materials and methods: A retrospective study was performed with MRSA isolates collected from July 2004 to May 2007 which adhered to CDC’s rules for defining CA-MRSA. The phenotipic characterization and the antimicrobial susceptility profile for a wide variety of antibiotics was carried out with an automated system and confirmed by PCR. Results: Typical profiles of hospital MRSA, as the multirresistance and the SCCmecII, were found in the community of Tenerife. The PVL, proposed characteristic of MRSA, was detected in a low percentage, located in the south of the island. Also, two new lineages were described: ST1433-MSSA y ST1434-MRSA-IVA. Conclusions: MRSA isolates with hospital and community features are circulated now in both environments. Therefore, we advise against applying a empiric therapy without a previous molecular analysis of the microorganism (AU)

Alternate PAX3 and PAX7 C-terminal isoforms in myogenic differentiation and sarcomagenesis

OBJECTIVE: Pax3 and Pax7 are closely related genes that are involved in commitment of cells to a myogenic lineage during skeletal muscle development and regeneration. Several Pax3 and Pax7 transcripts are expressed from the genes, generating different isoforms with potentially distinct DNA binding and transactivation properties. The aim of this study was to investigate the implication of Pax3 and Pax7 C-terminal isoforms during myogenic differentiation and tumorigenesis, since fusions involving these genes are commonly associated with alveolar rhabdomyosarcoma (ARMS). METHODS: Uncommitted (mouse mesenchymal stem cells, MSCs) and committed (C2C12) myogenic precursor cells were stably transfected with PAX3/FKHR and PAXC7/ FKHR fusion genes. We analysed gene and protein expression comparing the newly generated cells with the parental cells, to determine the functional importance of Pax3 and Pax7 C-terminal isoforms. RESULTS: We found that the transcript Pax3c was expressed at low levels in undifferentiated C2C12 and MSCs cells, but its expression levels increased considerably at later stages of differentiation. However, expression levels of Pax3d transcript increased only slightly after differentiation. Pax7 transcripts, present before differentiation in committed C2C12 cells, but absent in uncommitted MSCs, increased noticeably in MSCs after differentiation. We also found that the presence of PAX/FKHR fusions prevented both C2C12 and MSC cells from terminal myogenic differentiation and increased the expression of discrete endogenous Pax3/7 transcripts, in particular Pax3d and Pax7B. CONCLUSIONS: Our results suggest that both Pax3 and Pax7 transcripts are required for commitment of cells to the myogenic lineage, with each transcript having a distinct role. More specifically, the Pax3c isoform may be required for terminal myogenic differentiation whereas the Pax3d isoform may be involved in undifferentiated cell maintenance and/or proliferation (AU)

Liquen plano oral y dendrocitos dérmicos / Oral lichen Planus and Dermal Dendrocytes

Introducción: El liquen plano oral (LPO) es una enfermedad inflamatoria relativamente frecuente que se presenta con un amplio abanico de formas clínicas. Todavía no se ha determinado completamente su patogenia, aunque se sabe que los linfocitos actúan de mediadores con la participación de citoquinas y otras células inflamatorias, entre ellas los dendrocitos dérmicos (DD) tipo I y tipo II (DD positivos para el factor XIIIA y CD34, respectivamente).Objetivos. Describir la presencia y distribución de estas células en el tejido, mediante técnicas inmunohistoquímicas, en 23 muestras procedentes de pacientes que reunían los criterios clínicos e histopatológicos de LPO. Resultados: Los DD factor XIII+ estaban localizados principalmente en la dermis superficial (p < 0,0001) y no en la submucosa profunda. Dichas células se encontraban en abundancia en toda la unión dermoepidérmica y se relacionaban estrechamente con la infiltración linfocitaria. Los DD factor XIIIa+ se encontraban además en el epitelio y la dermis profunda. En cambio, los DD CD34+ se distribuyeron principalmente en la dermis profunda, directamente por debajo del infiltrado linfocitario, con pocas células en la zona subepitelial. Conclusiones: Los DD estaban presentes en el LPO, con diferentes distribuciones en los tejidos. Así, los DD factor XIIIa+ predominaban en la dermis superficial, mientras que los DD CD34+ se encontraban principalmente en la dermis profunda. Esto apunta a que los DD, y sobre todo los DD factor XIIIa+ debido a su capacidad para expresar moléculas de adhesión intercelulares-1 (ICAM-1) y el factor de necrosis tumoral alfa (TNF-α), pueden desempeñar una función destacada en la patogénesis del LPO (AU)

Introduction: Oral lichen planus (OLP) is a relatively common inflammatory disease with a wide range of clinical forms. Its pathogenesis has not been fully elucidated although it is known to be mediated by lymphocytes with the participation of cytokines and other inflammatory cells, including type I and type II dermal dendrocytes (DD) (factor xiIIa+ DD and CD34+ DD, respectively). Objectives: To describe the presence and tissue distribution of these cells, through immunohistochemistry, in 23 specimens from patients with clinical and histopathological criteria of OLP. Results: Factor xiIIa+ DD were mainly located in the superficial dermis (p < 0.0001) as opposed to the deep submucosa. These cells were abundant throughout the dermal-epidermal junction and closely related to lymphocyte infiltration. Moreover, factor xiIIa+ DD were also found in the epithelium and deep dermis. CD34+ DD were distributed mostly to the deep dermis directly below the lymphocyte infiltrate with few cells in the subepithelial region. Conclusions: DD were present in OLP, with distinct tissue distributions. Factor xiIIa+ DD were predominant in the superficial dermis while CD34+ DD could be found mostly in the deep dermis. These findings suggest that DD, and those positive for factor xiIIa+ in particular in view of their ability to express intercellular adhesion molecule-1 (ICAM-1) and tumor necrosis factor α (TNF-α), may play an important role in pathogenesis of OLP (AU)

Origin of renal cell carcinomas

Cancer is a heritable disorder of somatic cells: environment and heredity are both important in the carcinogenic process. The primal force is the "two hits" of Knudson's hypothesis, which has proved true for many tumours, including renal cell carcinoma. Knudson et al. [1, 2] recognised that familial forms of cancer might hold the key to the identification of important regulatory elements known as tumour-suppressor genes. Their observations (i.e., that retinoblastoma tend to be multifocal in familial cases and unifocal in sporadic presentation) led them to propose a two-hit theory of carcinogenesis. Furthermore, Knudson postulated that patients with the familial form of the cancer would be born with one mutant allele and that all cells in that organ or tissue would be at risk, accounting for early onset and the multifocal nature of the disease. In contrast, sporadic tumours would develop only if a mutation occurred in both alleles within the same cell, and, as each event would be expected to occur with low frequency, most tumours would develop late in life and in a unifocal manner [3, 4]. The kidney is affected in a variety of inherited cancer syndromes. For most of them, both the oncogene/tumour-suppressor gene involved and the respective germline mutations have been identified. Each of the inherited syndromes predisposes to distinct types of renal carcinoma. Families with hereditary predisposition to cancer continue to provide a unique opportunity for the identification and characterisation of genes involved in carcinogenesis. A surprising number of genetic syndromes predispose to the development of renal cell carcinoma, and genes associated with five of these syndromes have been already identified: VHL, MET, FH, BHD and HRPT2. Few cancers have as many different types of genetic predisposition as renal cancer, although to date only a small proportion of renal cell cancers can be explained by genetic predisposition (AU)

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Epidermal stem cells in skin homeostasis and cutaneous carcinomas

Skin and squamous epithelia regulate water and heat homeostasis and constitute our first barrier of protection against pathogens. Cells from the outermost layer of the skin, the cornified envelope (stratum corneum), are constantly being shed, imposing a constant demand for replenishment to maintain homeostasis. Hair follicles and sebaceous glands provide protective hair growth and skin sebum, and continuously undergo cycles of growth and regression. The outstanding ability of the epidermis, hair follicles and sebaceous glands to self-renew relies on a population of adult stem cells that are maintained throughout our life span. In this review we will provide an overview of our current knowledge about epidermal stem cells, and some of the molecular mechanisms that identify them and dictate their behaviour. We will also summarise our view on the possible link between adult epidermal stem cells and cancer stem cells within skin and squamous neoplasias. The potential of epidermal stem cells in regenerative medicine and for designing targeted antitumoral therapies will be discussed (AU)

Prostate carcinoma and stem cells

Stem cells, as classically defined, are cells with a capacity to self-renew and to generate daughter cells that can differentiate down several cell lineages to form all of the cell types that are found in the mature tissue. Stem cells and tumour cells have many similar features, including infinite lifespan, self-renewal, multidrug resistance, telomerase expression and, in the instance of the prostate, androgen independence. Evidence supports a role for stem cells in the etiology of many types of cancer. The evolution of androgen-independent prostate carcinoma may reflect the emergence of stemlike prostate tumour cells. Because cancer may be a disease of stem cell lineages and Shh-Gli signalling controls the behaviour of precursors and of cells with stem cell properties in the mammalian tissues, prostate cancer might derive from inappropriate expansion of prostatic epithelial stem cell lineages caused by abnormal Shh-Gli function. This review attempts to integrate these recent results (AU)

Origen de las interneuronas de la corteza cerebral: conceptos básicos e implicaciones clínicas / Origin of cortical interneurons: basic concepts and clinical implications

Introducción y desarrollo. Las interneuronas gabérgicas desempeñan un papel fundamental en la función de la corteza cerebral, no sólo porque permiten la sincronización de las neuronas piramidales, sino también porque ejercen una gran influencia en la diferenciación y la maduración de estas neuronas durante el desarrollo. Durante mucho tiempo se ha pensado que las neuronas gabérgicas y las neuronas piramidales tenían su origen en células progenitoras de la región dorsal del telencéfalo, el palio. Estudios recientes han demostrado, sin embargo, que un gran número de las neuronas gabérgicas de la corteza cerebral tienen su origen en el subpalio -la misma región del telencéfalo que genera los ganglios basales-, y que llegan a la corteza cerebral a través de una larga migración tangencial. Objetivos. En esta revisión se ha resumido el conocimiento actual sobre los factores que regulan la especificación de las interneuronas corticales, así como los mecanismos que dirigen su migración hasta la corteza cerebral (AU)

Mecanismos de la formación de regionesen el cerebro anterior / Forebrain regionalization mechanisms

¿De dónde vienen las regiones del cerebro anterior? El paradigma que va saliendo a la luz en los últimos diez años es el de una placa neural subdivida por factores solubles que (a través de gradientes o de un entramado molecular) transmiten información posicional a las células madre neurales. Algunos de esos factores solubles son Fgf8, Sonic hedgehog y proteínas de la familia BMP.Las células madre neurales interpretan la información posicional en términos de expresión de combinaciones de factores de la transcripción. Tales combinaciones serían finalmente responsables de la formación de linajes neuronales específicos (corticales, talámicos, etc.) a partir de regiones neuroepiteliales específicas. Además, la información posicional `primaria' puede hacer que determinadas regiones del primordio neural (organizadores secundarios) segreguen nuevos factores solubles. Éstos darían a su vez lugar a nueva información posicional, de influencia más restringida, y así se repetiría el proceso localmente, añadiendo `detalle' a una cierta región. El torrente de nuevos conocimientos adquiridos mediante genética molecular nos está ayudando a comprender la causa de algunas malformaciones congénitas cerebrales, y tal vez pronto se pueda aplicar también a su diagnóstico precoz y a su prevención (AU)