First-in-human evaluation of a biological regenerative vascular conduit for hemodialysis access.

INTRODUCTION: The long-term survival and low complication rate of autogenous fistulas for hemodialysis access is often offset by early thrombosis and slow or failed maturation leading to the use of central venous catheters. A regenerative material may have the potential to overcome these limitations. A completely biological acellular vascular conduit was investigated in this first-in-human clinical study. METHODS: With approval of the ethics board and patients' informed consent, five subjects were enrolled based on predetermined inclusion criteria. Five patients underwent implant of a novel acellular, biological tissue conduit (TRUE AVC™) in the upper arm in a curved configuration between brachial artery and axillary vein. After maturation, standard dialysis was commenced through the new access. Patients were followed up to 26 weeks with ultrasound and physical exam. Serum samples were evaluated for an immune response to the novel allogeneic human tissue implant. RESULTS: This new tissue conduit handled well surgically, with properties similar to that of native human vein. Post procedure conduit flow was excellent in all cases, averaging 1098 ± 388 ml/min at week 4 and remaining stable through 1248 ± 355 ml/min at 26 weeks. Surgical site healing was normal with no edema or erythema by week 4. Six-month primary assisted patency was 80% and secondary patency was 100%. Prescribed dialysis was successfully delivered without infection, and there was no significant change in conduit diameter. Serum testing showed no increase in PRA or IgG specific to the TRUE AVC. One implant required intervention at 5 months with thrombectomy and covered stent procedure. CONCLUSION: This first-in-human 6-month study with favorable patency and low complication rate establishes the initial safety and feasibility of this novel biological tissue conduit for dialysis access in patients with end-stage kidney disease. Its mechanical durability and lack of immune response establishes TRUE AVC as a potential regenerative material for clinical use.

High cortactin expression in B-cell acute lymphoblastic leukemia is associated with increased transendothelial migration and bone marrow relapse.

Cancer is a major cause of death in children worldwide, with B-lineage cell acute lymphoblastic leukemia (B-ALL) being the most frequent childhood malignancy. Relapse, treatment failure and organ infiltration worsen the prognosis, warranting a better understanding of the implicated mechanisms. Cortactin is an actin-binding protein involved in cell adhesion and migration that is overexpressed in many solid tumors and in adult B-cell chronic lymphocytic leukemia. Here, we investigated cortactin expression and potential impact on infiltration and disease prognosis in childhood B-ALL. B-ALL cell lines and precursor cells from bone marrow (BM) and cerebrospinal fluid (CSF) of B-ALL patients indeed overexpressed cortactin. In CXCL12-induced transendothelial migration assays, transmigrated B-ALL cells had highest cortactin expression. In xenotransplantation models, only cortactinhigh-leukemic cells infiltrated lungs, brain, and testis; and they colonized more easily hypoxic BM organoids. Importantly, cortactin-depleted B-ALL cells were significantly less efficient in transendothelial migration, organ infiltration and BM colonization. Clinical data highlighted a significant correlation between high cortactin levels and BM relapse in drug-resistant high-risk B-ALL patients. Our results emphasize the importance of cortactin in B-ALL organ infiltration and BM relapse and its potential as diagnostic tool to identify high-risk patients and optimize their treatments.

[Multidetector computed tomography of coronary arteries: state of the art. Second part: clinical applications]. / Tomografía computada multidetector de arterias coronarias: estado del arte. Parte II: Aplicaciones clínicas.

At the beginning of the evaluation of Coronary Artery Disease (CAD), Coronary Multidetector Computed Tomography (MDCT) was exclusively used to detect calcified plaques in coronary arteries through the Calcium Score, whose value by itself is limited. Nowadays, thanks to the technological advancements, potential clinical applications, with this method, include detection of coronary arterial stenosis, assessment of coronary bridges, and evaluation of anomalous coronaries. The intraluminal coronary stent evaluation is not possible yet, but this might become possible with the new-generation scanners. At the moment, the published results seem to be promising, nonetheless, the enthusiasm generated by this method should be accompanied by adequate training, as well as by its validation and certification.

[Computer multidetector tomography of coronary arteries. State-of-the-art. Part 1. Technical aspects]. / Tomografía computada multidetector de arterias coronarias: estado del arte. Parte I: aspectos técnicos.

The study of atherosclerotic disease in coronary arteries is fundamental since it is the first cause of death in the Western hemisphere. The gold standard for its diagnosis is invasive angiography, but it contributes to an increase in costs for this group of patients. Nowadays fourth generation computed tomography (CT) equipments can construct acquisition data of up to 256 images in only 400 milliseconds (ms), which is 900 to 1000 times faster than first generation apparatus. CT multidetector (CTMD) is the noninvasive choice diagnosis method for a vascular evaluation of the thorax. Its role in the study of the heart was limited, but today it is possible to obtain three-dimensional heart and whole body images in only seconds. CTMD is a fast, low-cost, noninvasive method that generates cardiac and extra cardiac images without adjacent structure interference. The higher temporal resolution due to an increase of the gantry's rotation and new reconstruction algorithms, as well as its higher spatial resolution and elevated time acquisition due to the presence of more detectors, have permitted CTMD to give significantly better and precise diagnosis of coronary arteries.

HS1 deficiency impairs neutrophil recruitment in vivo and activation of the small GTPases Rac1 and Rap1.

Neutrophil extravasation is a critical step of the innate immune system's response to inflammation. This multistep process is tightly regulated by adhesion and signaling molecules in the endothelium and neutrophils. Activation of the ß2 integrin LFA-1 is critical for adhesion of leukocytes to postcapillary venules. This step requires coordinated activation of signaling pathways in chemokine-stimulated neutrophils, including GTPase activation and cytoskeletal remodeling, leading to conformational changes in LFA-1. Hematopoietic cell-specific lyn substrate 1 (HS1) is a cortactin-related and leukocyte-specific actin-binding protein (ABP) that regulates several processes in various immune cells. It has been shown in vitro that HS1 is important for neutrophil chemotaxis and transendothelial migration of NK cells, but its role in neutrophil extravasation in vivo has not been investigated yet. Intravital microscopy of CXCL1-stimulated cremaster venules revealed an increased rolling velocity and reduced neutrophil adhesion and transmigration in HS1 knockout (KO) mice. CXCL1-induced rapid neutrophil arrest in vivo and adhesion under flow conditions in vitro were also reduced significantly. Whereas random motility of neutrophils was unaffected, chemotaxis toward a CXCL1 gradient was reduced in the absence of HS1. Further analysis of the underlying mechanisms demonstrated that HS1 controls CXCL1-induced activation of the small GTPases Ras-related C3 botulinum toxin substrate 1 (Rac1) and Ras-related protein 1 (Rap1), thus supporting LFA-1-mediated neutrophil adhesion. Importantly, with the use of Rac1 KO neutrophils, we could show that Rac1 acts upstream of Rap1. Our results establish HS1 as an important regulator of proper Rac1 and Rap1 activation and neutrophil extravasation.

A Human Lin- CD123+ CD127low Population Endowed with ILC Features and Migratory Capabilities Contributes to Immunopathological Hallmarks of Psoriasis.

Innate lymphoid cells (ILC) are members of a heterogeneous family with a lymphoid origin that mimics the T helper (Th) cytokine profile. ILC are involved in early effector cytokine-mediated responses during infections in peripheral tissues. ILC also play an important role in chronic skin inflammatory diseases, including psoriasis. Although classical ILC express CD127, it has been recently reported that the presence of non-classical CD127- ILC populations and an early ILC precursor (EILP) CD127low. ILC development has predominately been investigated in mouse models. However, in humans, different transcription factors have been described for ILC identification. NFIL3 (nuclear factor, IL-3 regulated) is crucial for ILC development in response to IL-7. CD123 (IL-3Rα) is usually used to exclude basophils during ILC identification, however, it is unknown if in response to IL-3, NFIL3 could be relevant to induce ILC features in Lin- CD123+ populations in addition, is also unknown whether peripheral blood (PB) population with ILC features may have skin-homing potential to participate in skin inflammatory chronic diseases. Here, we report a Lin- CD123+ CD127low CD7+ CLA+ population that share some phenotypic properties with basophils, but expresses several transcription factors for ILC commitment such as inhibitor of DNA binding 2 (Id2), NFIL3, promyelocytic leukemia zinc finger (PLZF), thymocyte selection-associated high-mobility group box protein (TOX), and T cell factor-1 (TCF-1). In addition, this population expresses different ILC markers: CD132, CD90, CD161, α4 integrin, c-Kit, CRTH2, AhR, and IL-23R. IL-3 prevents apoptosis and increases their NFIL3, TOX, and PLZF expression. In PB, the CD123+ CD127low population is predominantly a conspicuous population that expresses T-bet and RORγt. The Lin- CD123+ CD127low population in PB has a limited Th type cytokine expression and highly expresses IL-8. The Lin- CD123+ CD127low population expresses skin-homing receptors (cutaneous lymphocyte antigen and CXCR4) and transmigrates through endothelial cells in response to SDF-1. An equivalent Lin- CD123low population was identified in control skin, which shows a broader phenotypic diversity and cytokine production, including IL-22 and IL-17. Remarkably, the CD123low population in the lesion and non-lesion skin of psoriasis patients expresses IL-17 and IL-22. Our findings suggest the identification of an alternative Lin- CD123+ CD127low population with ILC features endowed with migratory capabilities that might contribute to immunopathological hallmarks of psoriasis.

The role of actin-binding proteins in the control of endothelial barrier integrity.

The endothelial barrier of the vasculature is of utmost importance for separating the blood stream from underlying tissues. This barrier is formed by tight and adherens junctions (TJ and AJ) that form intercellular endothelial contacts. TJ and AJ are integral membrane structures that are connected to the actin cytoskeleton via various adaptor molecules. Consequently, the actin cytoskeleton plays a crucial role in regulating the stability of endothelial cell contacts and vascular permeability. While a circumferential cortical actin ring stabilises junctions, the formation of contractile stress fibres, e. g. under inflammatory conditions, can contribute to junction destabilisation. However, the role of actin-binding proteins (ABP) in the control of vascular permeability has long been underestimated. Naturally, ABP regulate permeability via regulation of actin remodelling but some actin-binding molecules can also act independently of actin and control vascular permeability via various signalling mechanisms such as activation of small GTPases. Several studies have recently been published highlighting the importance of actin-binding molecules such as cortactin, ezrin/radixin/moesin, Arp2/3, VASP or WASP for the control of vascular permeability by various mechanisms. These proteins have been described to regulate vascular permeability under various pathophysiological conditions and are thus of clinical relevance as targets for the development of treatment strategies for disorders that are characterised by vascular hyperpermeability such as sepsis. This review highlights recent advances in determining the role of ABP in the control of endothelial cell contacts and vascular permeability.

Production and characterization of extracellular α-amylase produced by Wickerhamia sp. X-Fep.

A yeast isolate able to produce high levels of extracellular α-amylase was selected from a collection of 385 yeasts and identified as Wickerhamia sp. by the sequence of the D1/D2 domain of the 26 S rDNA gene. Part of the nucleotide sequence of the amy1-W gene was cloned, and a sequence of 191 amino acids deduced from this gene was analyzed. The peptide contains three characteristic well-conserved regions in the active sites of α-amylases (EC 3.2.1.1). The enzyme was purified and in situ activity showed only one band with amylolytic activity. The molecular mass of the α-amylase was estimated at 54 kDa by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Enzymatic activity on soluble starch as substrate was optimal at pH 5-6 and 50 °C. This thermostable enzyme was inhibited by EDTA-Na(2) and 1,10-phenanthroline; the activity of the dialyzed enzyme was reactivated with Ca(2+) and Mg(2+) cations, which indicates that the α-amylase is a metalloenzyme. α-Amylase production was induced by starch and maltose and repressed by glucose. The high yield and productivity found in this work makes this Wickerhamia sp. strain a promising candidate for the biotechnological production of α-amylase.

Aparelho disjuntor fusionado em leque / Fan-type fused palatal expander

A correção da mordida cruzada posterior é realizada na maioria dos casos por aparelhos disjuntores, em especial o Hyrax e o Haas. Ambos têm efeitos semelhantes no complexo dentofacial, ligeiramente dentoalveolar com Hyrax e ortopédico com Haas. Modificações foram feitas com o objetivo de incorporar as vantagens de ambos, e o aparelho disjuntor fusionado de Almeida e Almeida se diferencia pela quantidade mínima de resina que recobre o parafuso. O presente caso descreve uma adolescente de 14 anos, com mordida cruzada bilateral, pré-molares e dentes anteriores em mordida topo-a-topo, que utilizou o aparelho disjuntor fusionado em leque, para maior expansão na região anterior. Após 14 dias de ativações de » de volta duas vezes por dia, o aparelho foi mantido como contenção por seis meses. Terminado esse período, o aparelho foi removido para a continuação do tratamento ortodôntico. Logo após a expansão, observou-se correção da mordida cruzada, com pouca extrusão dentária e fechamento da mordida topo-a-topo anterior durante a retração, devido à necessidade de exodontia dos segundos pré-molares. Comparando-se à opção da cirurgia ortognática, houve resposta favorável demonstrando que a indicação e a construção do aparelho disjuntor fusionado foram oportunas.

Correction of posterior crossbite in most cases is performed with disjunction appliances, in special, Hyrax and Haas. Both of them have similar effects on dentofacial complex, slightly dentoalveolar with Hyrax and orthopedic with Haas. Changes have been done on the appliances in order to incorporate advantages of both appliances in only one, and the Almeida & Almeida’s fusioned disjunction appliance is different regarding by minimum amount resin that covers the screw. The actual case describes a 14 years-old female adolescent, with bilateral posterior crossbite, bicuspids and anterior teeth in cusp-to-cusp relationship, who has worn a fan type fusioned disjunction appliance, in order to have more anterior lateral expansion. During 14 days of activation, » turn twice a day, the appliance was kept in position acting as retention for six months, after that it was removed for following orthodontic treatment. Finished the expansion, correction of the posterior crossbite was observed, with little dental extrusion and closure of the anterior cusp-to-cusp relationship during the retraction, due to necessity of second upper bicuspids extraction. When it is compared to the option of orthognathic surgery, there was favorable result suggesting the indication and building of the fusioned disjunction appliance were delivered in an appropriate time.

Baixa fricção do sistema autoligado associado ao uso estratégico dos stops / Self-ligating system low friction associated with the strategic use of the stops

O uso dos braquetes autoligados tem sido cada vez mais difundido entre os ortodontistas de todo o mundo por apresentar muitas vantagens, como baixa fricção e níveis baixos de forças. O presente trabalho descreveu o tratamento ortodôntico de um paciente de 17 anos e um mês de idade, com apinhamento superior e inferior, e desvio de linha média dentária, cujos resultados demonstraram a efetividade do tratamento realizado com o sistema autoligado, otimizado por meio do uso estratégico dos stops.

The use of self-ligating brackets has been increasingly widespread among orthodontists from around the world by presenting many advantages such as low friction and low levels of forces. This paper describes the orthodontic treatment of a patient of 17 years and 1 month old, with upper and lower crowding and dental midline deviation, which results demonstrate the effectiveness of the treatment with the selfligating system, optimized by the strategic use of the stops.

Fundamentos de un programa comunitario para promover comportamientos saludables y prevenir enfermedades crónicas en Bogotá / Fundamentals of a community program to promote healthy behaviors and prevent chronic diseases in Bogotá

Las condiciones crónicas y sus factores de riesgos son altamente prevalentes en la población colombiana. Sin embargo, en la literatura se reportan pocos programas orientados a su prevención en el país, lo cual puede estar relacionado con la escasa información disponible acerca de cómo fundamentarlos conceptual, teórica y metodológicamente. Los objetivos de este artículo son describir los fundamentos conceptuales, teóricos y metodológicos de un programa comunitario para la prevención de las condiciones crónicas en Bogotá y dar cuenta de la aplicación de estos fundamentos en la ejecución del programa. Con este fin, entre abril de 2005 y noviembre de 2007 se llevó a cabo una evaluación de proceso que centró en analizar la coherencia entre el desarrollo del programa y sus fundamentos. Esta evaluación se llevó a cabo mediante un análisis de contenido temático, a partir de la recolección de información a través de entrevistas, fichas de sistematización y grupos focales. Emergieron cuatro categorías de análisis relacionadas con la ejecución del programa, las cuales estuvieron relacionadas con el uso del concepto positivo de salud, los modelos ecológicos en salud, las teorías críticas y el enfoque constructivista. La evaluación del proceso del programa muestra la importancia de conocer los elementos que fundamentan los programas de educación en salud, para poder analizar su desarrollo y valorarlos. En este caso los conceptos y constructos aplicados provienen de modelos contemporáneos en salud pública que exploran potenciales caminos para promover comportamientos saludables.

Chronic diseases and its risks factors are highly prevalent in the Colombian population. However, few programs have been oriented to their prevention in the country, which could be related to the little information available as to how to ground them conceptually, theoretically and methodologically. The objectives of this study are to describe the conceptual, theoretical, and methodological fundamentals of a program to prevent these diseases in Bogota and to assess the application of these fundamentals. In order to achieve these objectives between April 2005 and November 2007 was conducted a process evaluation focused on establishes the coherence between the above fundamentals and the implantation of this program. The evaluation was carried out through a thematic content analysis. The information was collected mediating interviews, systematisation tools and focal groups. Four categories emerged from the analyses. These categories were related with the use of a positive concept of health, the ecological model in health and the critical theories and the constructivist approach. The process evaluation reveals the importance of knowing the program’s foundations to analyze and asses its implementation. In this case the concepts and constructs applied belong to contemporary models in public health that explore ways to promote healthy behaviours.

Tomografía computada multidetector de arterias coronarias: estado del arte. Parte II: Aplicaciones clínicas / Multidetector computed tomography of coronary arteries: state of the art. Second part: clinical applications

At the beginning of the evaluation of Coronary Artery Disease (CAD), Coronary Multidetector Computed Tomography (MDCT) was exclusively used to detect calcified plaques in coronary arteries through the Calcium Score, whose value by itself is limited. Nowadays, thanks to the technological advancements, potential clinical applications, with this method, include detection of coronary arterial stenosis, assessment of coronary bridges, and evaluation of anomalous coronaries. The intraluminal coronary stent evaluation is not possible yet, but this might become possible with the new-generation scanners. At the moment, the published results seem to be promising, nonetheless, the enthusiasm generated by this method should be accompanied by adequate training, as well as by its validation and certification.

Tomografía computada multidetector de arterias coronarias: estado del arte. Parte I: aspectos técnicos / Computer multidetector tomography of coronary arteries: state-of-the-art. Part 1: technical aspects

The study of atherosclerotic disease in coronary arteries is fundamental since it is the first cause of death in the Western hemisphere. The gold standard for its diagnosis is invasive angiography, but it contributes to an increase in costs for this group of patients. Nowadays fourth generation computed tomography (CT) equipments can construct acquisition data of up to 256 images in only 400 milliseconds (ms), which is 900 to 1000 times faster than first generation apparatus. CT multidetector (CTMD) is the noninvasive choice diagnosis method for a vascular evaluation of the thorax. Its role in the study of the heart was limited, but today it is possible to obtain three-dimensional heart and whole body images in only seconds. CTMD is a fast, low-cost, noninvasive method that generates cardiac and extra cardiac images without adjacent structure interference. The higher temporal resolution due to an increase of the gantry's rotation and new reconstruction algorithms, as well as its higher spatial resolution and elevated time acquisition due to the presence of more detectors, have permitted CTMD to give significantly better and precise diagnosis of coronary arteries.

Toxicidad y efecto hipotensor de oxoborolidinona de L-arginina y su modulación por azul de metileno. Comparación con L-arginina, nitrito y nitrato / Toxicity and hypotensor effect of Oxoborolidinona of L-arginine and its modulation by methylene blue as compared to L-arginine

El óxido nítrico es sintetizado a partir de L-arginina, reacción catalizada por la enzima óxido nítrico sintasa, esta molécula de vida efímera participa en varios procesos como: regulación de presión arterial, citotoxicidad y comunicación celular. Un gran número de sus acciones son inhibidas por azul de metileno, inhibidor de la guanilato ciclasa. Moléculas análogas a la L-arginina con grupo guanidino libre, pueden funcionar como aportadores de óxidos de nitrógeno y tener acciones semejantes al óxido nítrico. En este trabajo se reporta el efecto hipotensor y toxicidad aguda de oxoborolidinona de L-arginina comparativamente con L-arginina, nitrito y nitrato, y su modulación con azul de metileno. La dosis letal media, en rata Wistar, para oxoborolidinona fue 169.0 ñ 5 mg kg-1 vía intraperitoneal y la dosis hipotensora media 10 hmoles kg-1 vía femoral; ambos parámetros fueron desplazados claramente a la derecha por el pretratamiento con azul de metileno, juzgado por las dosis letal y dosis efectiva medias, la oxoborolidinona tuvo un efecto más potente que la L-arginina y nitrato pero semejante a nitrito. En todos los casos, excepto para nitrato, los efectos fueron modulados por azul de metileno, lo que sugiere que los efectos estudiados son mediados vía óxidos de nitrógeno.

Insuficiencia renal aguda intrahospitalaria / intrahospitable acute renal Insufficiency

La insuficiencia renal aguda, es una entidad patológica frecuente en nuestro medio y más aún en el área hospitalaria, donde el médico debe enfrentar situaciones graves, pero en su mayoría reversibles, generalmente asociada a yatrogenia, por lo cual nos proponemos determinar las principales causas. Estudiamos todos los casos de insuficiencia renal aguda ocurridos en el Hospital Pablo Arturo Suárez, en las áreas clínicas y quirúrgicas, excepto en Ginecobstetricia, en un período de seis meses, 35 pacientes (2.33 por ciento) presentaron elevación de la creatinina sérica con valores mayores del 50 por ciento del valor basal. Se analizó su etiología, factores desencadenantes, patologías preexistentes y tiempo de evolución. Se presentó con más frecuencia en mayores de 60 años, con una edad media de presentación de 62.9. Entre las causas que adquieren mayor importancia se encuentran las de tipo hemodinámico...