Tratamiento de fugas biliares mediante colocación transparietohepática de endoprótesis metálicas recubiertas / Treatment of benign biliary leaks with transhepatic placement of coated self-expanding metallic stents

Objetivo. Analizar la seguridad y eficacia en el uso percutáneo de endoprótesis metálicas autoexpandibles recubiertas (EMAR) en pacientes con fuga biliar. Material y métodos. Este estudio ha sido aprobado por el Comité de Ética de nuestro centro. Se realizó una revisión retrospectiva de las EMAR colocadas entre octubre de 2008 y septiembre de 2015. Se analizaron la enfermedad primaria subyacente, los procedimientos hepáticos previos y el éxito clínico. Se evaluó la localización, el número, el tipo de fuga y las características del procedimiento intervencionista (número de prótesis empleadas, localización, éxito técnico y funcionalidad primaria). Se recogieron las complicaciones registradas. Resultados. Se estudiaron 14 pacientes. El seguimiento medio fue de 375,5 días (rango de 15-1920 días). En 12 pacientes las fugas biliares fueron posquirúrgicas. Un paciente presentó una fístula arteriobilioportal. En otro paciente, la fuga biliar fue post-CPRE. Se colocaron un total de 23 EMAR: 21 prótesis tipo Fluency® (Bard, Tempe, Arizona, EE.UU.) y dos prótesis tipo Wallflex® (Boston Scientific, Galway, Irlanda). Se consiguió éxito técnico total en el 78,6% (n=11), parcial en el 14,3% (n=2) y no se obtuvo éxito en el 7,2% (n=1). Se consiguió éxito clínico en 13 de 14 pacientes. La media de funcionalidad primaria de las EMAR fue de 331 días (rango de 15-1920 días). Once pacientes no presentaron ninguna complicación mayor. Conclusiones. La colocación percutánea de EMAR es un método seguro y eficaz en el tratamiento de fugas biliares benignas, con una alta tasa de éxito técnico y clínico y un nivel moderado de complicaciones (AU)

Objectives. To analyze the safety and efficacy of percutaneous placement of coated self-expanding metallic stents (SEMS) in patients with biliary leaks. Material and methods. This ethics committee at our center approved this study. We retrospectively reviewed all coated SEMS placed between October 2008 and September 2015. We analyzed patient-related factors such as the primary underlying disease, prior hepatic procedures, and clinical outcome. We evaluated the location, the number and type of leak (anastomotic or non-anastomotic), and the characteristics of the interventional procedure (number of stents deployed, location of the stents, technical success, and primary functionality). We recorded the complications registered. Results. We studied 14 patients (11 men and 3 women). The mean follow-up period was 375.5 days (range 15-1920 days). Leaks were postsurgical in 12 patients. One patient developed an arteriobilioportal fistula. In another, the biliary leak occurred secondary to the rupture of the common bile duct after ERCP. A total of 23 coated SEMS were placed, including 21 Fluency® stents (Bard, Tempe, AZ, USA) and 2 Wallflex® stents (Boston Scientific, Galway, Republic of Ireland). The technical success of the procedure was considered total in 11 (78.6%) patients, partial in 2 (14.3%) patients, and null in 1 (7.2%) patient. The clinical outcome was good in 13 of the 14 patients. The mean period of primary functionality of the coated SEMS was 331 days (range 15-1920 days). No major complications were observed in 11 (78.6%) patients. Conclusions. Percutaneous placement of coated SEMS for the treatment of benign biliary leaks is safe and efficacious, with a high rate of technical and clinical success and a moderate rate of complications (AU)

Treatment of benign biliary leaks with transhepatic placement of coated self-expanding metallic stents. / Tratamiento de fugas biliares mediante colocación transparietohepática de endoprótesis metálicas recubiertas.

OBJECTIVES: To analyze the safety and efficacy of percutaneous placement of coated self-expanding metallic stents (SEMS) in patients with biliary leaks. MATERIAL AND METHODS: This ethics committee at our center approved this study. We retrospectively reviewed all coated SEMS placed between October 2008 and September 2015. We analyzed patient-related factors such as the primary underlying disease, prior hepatic procedures, and clinical outcome. We evaluated the location, the number and type of leak (anastomotic or non-anastomotic), and the characteristics of the interventional procedure (number of stents deployed, location of the stents, technical success, and primary functionality). We recorded the complications registered. RESULTS: We studied 14 patients (11 men and 3 women). The mean follow-up period was 375.5 days (range 15-1920 days). Leaks were postsurgical in 12 patients. One patient developed an arteriobilioportal fistula. In another, the biliary leak occurred secondary to the rupture of the common bile duct after ERCP. A total of 23 coated SEMS were placed, including 21 Fluency® stents (Bard, Tempe, AZ, USA) and 2 Wallflex® stents (Boston Scientific, Galway, Republic of Ireland). The technical success of the procedure was considered total in 11 (78.6%) patients, partial in 2 (14.3%) patients, and null in 1 (7.2%) patient. The clinical outcome was good in 13 of the 14 patients. The mean period of primary functionality of the coated SEMS was 331 days (range 15-1920 days). No major complications were observed in 11 (78.6%) patients. CONCLUSIONS: Percutaneous placement of coated SEMS for the treatment of benign biliary leaks is safe and efficacious, with a high rate of technical and clinical success and a moderate rate of complications.

Hallazgos de angiografía por tomografía computarizada de la mediólisis arterial segmentaria / Segmental arterial mediolysis: findings at computed tomography angiography

Objetivo. Repasar los principales hallazgos de angiografía por tomografía computarizada de la mediólisis arterial segmentaria y enfatizar aquellos puntos que ayuden a diferenciarla de otras vasculopatías, como las vasculitis. Asimismo, se repasarán los protocolos de seguimiento y las diversas opciones terapéuticas. Conclusión. La mediólisis arterial segmentaria es una enfermedad rara que se define como una vasculopatía no ateroesclerótica, no hereditaria y no inflamatoria, caracterizada por la lisis de la capa media de la pared arterial. Debe sospecharse en pacientes de edad media con aneurismas, disecciones o roturas espontáneas de arterias viscerales de etiología desconocida, que no cumplen los criterios clínicos y analíticos de vasculitis. Las arterias viscerales abdominales son las más frecuentemente afectadas, entre ellas el tronco celíaco y las arterias mesentéricas superior e inferior. Sus formas de presentación radiológica incluyen la dilatación arterial, los aneurismas (saculares o fusiformes) únicos o múltiples, las estenosis y las disecciones (AU)

Objective. To review the principal findings on computed tomography angiography for segmental arterial mediolysis, and to emphasize the points that help to differentiate it from other vasculopathies such as vasculitis. We also review the protocols for follow-up and the various treatment options. Conclusion. Segmental arterial mediolysis is a rare disease that is defined as a non-atherosclerotic, non-hereditary, and non-inflammatory vasculopathy characterized by lysis of the medial layer of the arterial wall. It should be suspected in middle-aged patients with aneurysms, dissections, or spontaneous ruptures of visceral arteries of unknown etiology who do not fulfill the clinical and laboratory criteria for vasculitis. The arteries of the abdominal organs are the most commonly affected, including the arteries of the celiac trunk and the superior and inferior mesenteric arteries. Radiologically, segmental arterial mediolysis can present as arterial dilation; single or multiple, saccular or fusiform aneurysms; stenoses; or dissections (AU)

Complications associated with radiofrequency ablation of pulmonary veins. / Complicaciones asociadas a la ablación mediante radiofrecuencia de venas pulmonares.

OBJECTIVE: Radiofrequency ablation is an efficacious alternative in patients with symptomatic atrial fibrillation who do not respond to or are intolerant to at least one class I or class III antiarrhythmic drug. Although radiofrequency ablation is a safe procedure, complications can occur. Depending on the location, these complications can be classified into those that affect the pulmonary veins themselves, cardiac complications, extracardiac intrathoracic complications, remote complications, and those that result from vascular access. The most common complications are hematomas, arteriovenous fistulas, and pseudoaneurysms at the puncture site. Some complications are benign and transient, such as gastroparesis or diaphragmatic elevation, whereas others are potentially fatal, such as cardiac tamponade. CONCLUSION: Radiologists must be familiar with the complications that can occur secondary to pulmonary vein ablation to ensure early diagnosis and treatment.

Segmental arterial mediolysis: findings at computed tomography angiography. / Hallazgos de angiografía por tomografía computarizada de la mediólisis arterial segmentaria.

OBJECTIVE: To review the principal findings on computed tomography angiography for segmental arterial mediolysis, and to emphasize the points that help to differentiate it from other vasculopathies such as vasculitis. We also review the protocols for follow-up and the various treatment options. CONCLUSION: Segmental arterial mediolysis is a rare disease that is defined as a non-atherosclerotic, non-hereditary, and non-inflammatory vasculopathy characterized by lysis of the medial layer of the arterial wall. It should be suspected in middle-aged patients with aneurysms, dissections, or spontaneous ruptures of visceral arteries of unknown etiology who do not fulfill the clinical and laboratory criteria for vasculitis. The arteries of the abdominal organs are the most commonly affected, including the arteries of the celiac trunk and the superior and inferior mesenteric arteries. Radiologically, segmental arterial mediolysis can present as arterial dilation; single or multiple, saccular or fusiform aneurysms; stenoses; or dissections.

Functional expression of mammalian bitter taste receptors in Caenorhabditis elegans.

Bitter taste has evolved as a central warning signal against the ingestion of potentially toxic substances appearing in the environment. The molecular events in the perception of bitter taste start with the binding of specific water-soluble molecules to G protein-coupled receptors (GPCR) called T2Rs and expressed at the surface of taste receptor cells. The functional characterisation of T2R receptors is far from been completed due to the difficulty to functionally express them in heterologous systems. Taking advantage of the parallelisms between the Caenorhabditis elegans (C. elegans) and mammalian GPCR signalling pathways, we developed a C. elegans-based expression system to express functional human and rodent GPCRs of the T2R family. We generated transgenic worms expressing T2Rs in ASI chemosensory neurons and performed behavioural assays using a variety of bitter tastants. As a proof of the concept, we generated transgenic worms expressing human T2R4 or its mouse ortholog T2R8 receptors, which respond to two bitter tastants previously characterised as their functional ligands, 6-n-propyl-2-thiouracil and denatoniun. As expected, expression of human T2R4 or its mouse ortholog T2R8 in ASI neurons counteracted the water-soluble avoidance to 6-n-propyl-2-thiouracil and denatoniun observed in control wild-type worms. The expression in ASI neurons of human T2R16, the ligand of which, phenyl-beta-d-glucopyranoside, belong to a chemically different group of bitter tastants, also counteracted the water-soluble avoidance to this compound observed in wild-type worms. These results indicate that C. elegans is a suitable heterologous expression system to express functional T2Rs providing a tool to efficiently search for specific taste receptor ligands and to extend our understanding of the molecular basis of gustation.

Identification and characterization of human taste receptor genes belonging to the TAS2R family.

The sense of taste is a chemosensory system responsible for basic food appraisal. Humans distinguish between five primary tastes: bitter, sweet, sour, salty and umami. The molecular events in the perception of bitter taste are believed to start with the binding of specific water-soluble molecules to G-protein-coupled receptors encoded by the TAS2R/T2R family of taste receptor genes. TAS2R receptors are expressed at the surface of taste receptor cells and are coupled to G proteins and second messenger pathways. We have identified, cloned and characterized 11 new bitter taste receptor genes and four new pseudogenes that belong to the human TAS2R family. Their encoded proteins have between 298 and 333 amino acids and share between 23 and 86% identity with other human TAS2R proteins. Screening of a mono-chromosomal somatic cell hybrid panel to assign the identified bitter taste receptor genes to human chromosomes demonstrated that they are located in chromosomes 7 and 12. Including the 15 sequences identified, the human TAS2R family is composed of 28 full-length genes and 16 pseudogenes. Phylogenetic analyses suggest a classification of the TAS2R genes in five groups that may reflect a specialization in the detection of specific types of bitter chemicals.

Ramón y Cajal: a century after the publication of his masterpiece.

Santiago Ramón y Cajal published the first of the three volumes of his principal life's work in 1899, and published the last volume in 1904. This book remains the definitive work on the morphology of the vertebrate nervous system. In it, Ramón y Cajal describes the structure and organization of virtually all parts of the nervous system and discusses his theories, including the neuron doctrine and the law of functional polarization, which are the cornerstones of modern neurobiology. A century later, Ramón y Cajal's work is still fundamental to understanding the nervous system.

Id genes in nervous system development.

Id genes encode helix-loop-helix proteins that function to mediate processes important for normal development including cellular differentiation, proliferation and apoptosis. Id proteins act as negative regulators of other transcription factors, which are essential for cell determination and differentiation in diverse cell types, and interact with proteins important for cell cycle regulation. Studies of Id gene expression in the nervous system and in neural cells in culture indicate that Id proteins contribute to the regulation of mammalian nervous system development. Also, recognition of a wide variety of proteins with which Id transcription factors are capable of interacting suggests that it will be possible to understand more precisely their specific functions and importantly how these are integrated.

Id gene expression as a key mediator of tumor cell biology.

Id genes encode members of the helix-loop-helix (HLH) family of transcription factors that inhibit transcription by forming inactive heterodimers with basic HLH (bHLH) proteins. There are four members of the Id gene family recognized in mammals, and the proteins they encode share homology primarily in their HLH domain. bHLH proteins typically form heterodimers with other bHLH proteins, and their basic domain binds to a DNA sequence element, the E-box, activating transcription. Products of Id genes lack the basic DNA binding domain of the bHLH transcription factors, and when they heterodimerize with bHLH proteins, the complexes are inactive. Generally, high levels of Id mRNA are detected in proliferative undifferentiated, embryonal cells and lower levels are detected in well-differentiated, mature, adult tissues. In vitro, these genes are generally expressed at lower levels in cells after the induction of differentiation. Recently, high levels of expression of Id genes have been identified in cell lines derived from a wide variety of different tumors and in tumor tissues as well. These findings suggest that not only the inappropriate proliferation of tumors but also the anaplastic characteristics that contribute to their malignant behavior may be regulated by Id gene expression.

Id4 expression induces apoptosis in astrocytic cultures and is down-regulated by activation of the cAMP-dependent signal transduction pathway.

The Id family of helix-loop-helix transcription factors has been implicated in the regulation of cellular differentiation in several different lineages. We have explored the potential regulatory role of the cyclic AMP-dependent signaling pathway on Id gene expression in astroglial primary cultures. We found that primary cultures of mouse forebrain astrocytes constitutively expressed the four known members of the Id gene family, Id1, Id2, Id3, and Id4. During culture in presence of serum for 4 weeks, the expression of Id4 was up-regulated. In these same cultures, treatment with dibutyryl-cyclic AMP, a cyclic AMP analogue known to promote astrocyte differentiation, dramatically and selectively decreased Id4 gene expression. This effect was detectable after short-term treatment and was maintained during long-term treatment. Forskolin and pentoxifylline, two other agents known to elevate intracellular cyclic AMP through different mechanisms, also potently decreased Id4 gene expression. Furthermore, overexpression of Id4 in an astrocyte-derived cell line induced cells to round up and die by apoptosis. These results indicate that the cyclic AMP pathway acts as an inhibitor of Id4 gene expression in astrocytes, identify a new function for Id4, and suggest that Id4 is strategically positioned in the chain of molecular events regulating astrocyte differentiation and apoptosis.

Cloning of human ENC-1 and evaluation of its expression and regulation in nervous system tumors.

We recently identified and characterized a novel murine gene, ENC-1, that is expressed primarily in the nervous system and encodes an actin-binding protein. To gain insight into a potential role for ENC-1 gene in the processes of cell differentiation and malignant transformation in the human nervous system, we first cloned and characterized the human homologue of ENC-1. The human ENC-1 gene appeared to be highly expressed in adult brain and spinal cord, and in a number of cell lines derived from nervous system tumors we detected low steady-state levels of ENC-1 mRNA. We used a neuroblastoma differentiation model, the retinoic acid-induced neuronal differentiation of SMS-KCNR cells, to study the regulation of the ENC-1 gene during neural crest cell differentiation. We found that the expression of ENC-1 increased dramatically in the differentiated SMS-KCNR cells as compared to control undifferentiated cells. These results suggest that ENC-1 expression plays a role during differentiation of neural crest cells and may be down regulated in neuroblastoma tumors.

Injury selectively down-regulates the gene encoding for the Id4 transcription factor in primary cultures of forebrain astrocytes.

Astrogliosis is an important component of the response to injury of the central nervous system (CNS). The Id family of helix-loop-helix (HLH) transcription factors has been implicated in the regulation of cellular differentiation in several different lineages and may contribute to the regulation of astrogliosis. We examined the expression of Id genes in primary cultures of mouse forebrain astrocytes under experimental conditions in which astrogliosis was elicited by mechanical injury. Astrocyte cultures expressed the four known members of the Id gene family, Id1, Id2, Id3, and Id4. After injury, at a time when astrocytes developed the characteristic phenotypic changes of astrogliosis, Id4 expression decreased dramatically. Id1, Id2, and Id3 mRNA levels did not change. These results identify Id4 as a candidate marker of astroglial activation in culture and suggest that Id4 expression plays a role in the process of astrogliosis.

ENC-1: a novel mammalian kelch-related gene specifically expressed in the nervous system encodes an actin-binding protein.

We have identified and characterized a novel murine gene, Ectoderm-Neural Cortex-1 (ENC-1), that is an early and highly specific marker of neural induction in vertebrates. ENC-1, which encodes a kelch family related protein, is expressed during early gastrulation in the prospective neuroectodermal region of the epiblast and later in development throughout the nervous system (NS). ENC-1 expression is highly dynamic and, after neurulation, preferentially defines prospective cortical areas. The only apparent expression of ENC-1 outside the NS is restricted to the rostral-most somitomere of the presomitic mesoderm, at the times corresponding to the epithelialization that precedes somite formation. Cellular expression of epitope-tagged ENC-1 shows extensive co-localization of ENC-1 with the actin cytoskeleton, and immunoprecipitation studies demonstrate a physical association between ENC-1 and actin. ENC-1 functions as an actin-binding protein that may be important in the organization of the actin cytoskeleton during neural fate specification and development of the NS.

Id genes encoding inhibitors of transcription are expressed during in vitro astrocyte differentiation and in cell lines derived from astrocytic tumors.

Id proteins belong to a class of nuclear transcription factors known as helix-loop-helix proteins. It has been reported that Id genes function as negative regulators of differentiation, and Id gene expression is down-regulated during cell differentiation. We examined the regulation of Id genes during astrocyte differentiation in a murine nervous system precursor cell line, NSEHip2-28, which is able to differentiate along the astroglial lineage, as well as in human astroglial tumor cell lines. Upon induction of NSEHip2-28 differentiation, at a time when glial fibrillary acidic protein expression became detectable, the expression of all four Id family members initially increased dramatically, and subsequently decreased. Furthermore, varying levels of Id gene expression were found in astroglial tumor cell lines displaying variable degrees of lineage-specific differentiation. These results suggest that the expression of Id family members may play an important role in the control of astrocyte differentiation.

Molecular cloning of the cDNA encoding a helix-loop-helix protein, mouse ID1B: tissue-specific expression of ID1A and ID1B genes.

A cDNA encoding a 168 amino acid mouse ID1B helix-loop-helix protein, the longest among the ID family of proteins so far identified, was cloned and its nucleotide sequence determined. Mouse ID1B mRNA is distinguishable from the mRNA encoding ID1A at its 3' end, and the relative level of expression of these two different mRNAs is similar in most tissues, with exception of skeletal muscle and kidney. Comparison of the most carboxyl terminal predicted amino acid sequences of ID1 proteins reveals 100% identity for ID1A, but the predicted Id1B proteins of several species are different.

Expression of glial fibrillary acidic protein and glutamine synthetase genes in the natural scrapie of sheep.

Gene expression of two astroglial markers, glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS), was investigated in cerebellum and brainstem from scrapie-affected sheep. The GFAP and GFAP-mRNA concentrations were increased in the two cerebral regions studied in the scrapie-affected animals as compared to the controls. The good correlation between the increase in GFAP and GFAP-mRNA concentrations found in scrapie-affected sheep indicates a significant de novo synthesis of GFAP in this pathology. In contrast to these results, in scrapie no significant differences in GS-mRNA content appeared in either brain area from scrapie-affected sheep as compared to the controls. This fact could suggest some specificity of GFAP expression changes in this pathology. The overexpression of GFAP gene could be related to a possible interaction between GFAP and scrapie infectious agent in astrocytes. The relative increase in the GFAP and its encoding message in affected animals was higher in the cerebellum than in the brainstem, which would suggest regional comparative differences in the effect here described.

Thyroid hormones influence the astroglial plasticity: changes in the expression of glial fibrillary acidic protein (GFAP) and of its encoding message.

Normal development of the brain requires the presence of thyroid hormones. To progress in the understanding of the contribution of astrocytes to brain pathophysiology we investigated the effect of T3, on the astroglial plasticity through the expression of two astroglial proteins: the Glial fibrillary acidic protein (GFAP) and the glutamine synthetase (GS). Western and northern blots were performed using astroglial primary cultures initiated from neocortex and cerebellum of new-born mice. Treatment with T3 caused a decrease of GFAP and of its encoding message level in both areas, suggesting a transcriptional regulation of its expression, whereas it had no apparent effect on GS expression. This reduction in GFAP expression was developmentally regulated; it was significant in proliferating but not in more mature astrocytes. T3 effect on astrocytes was higher in the cerebellum compared to the neocortex, suggesting the presence of astroglial subpopulations differing by their sensitivity to T3. The astroglial specific response to T3, corresponds to a precise, targetted and regulated adaptation of the cell. Factors of the microenvironment may modulate this specific astroglial response in vivo.