Development of QSARs for cysteine-containing di- and tripeptides with antioxidant activity:influence of the cysteine position.

Antioxidants agents play an essential role in the food industry for improving the oxidative stability of food products. In the last years, the search for new natural antioxidants has increased due to the potential high toxicity of chemical additives. Therefore, the synthesis and evaluation of the antioxidant activity in peptides is a field of current research. In this study, we performed a Quantitative Structure Activity Relationship analysis (QSAR) of cysteine-containing 19 dipeptides and 19 tripeptides. The main objective is to bring information on the relationship between the structure of peptides and their antioxidant activity. For this purpose, 1D and 2D molecular descriptors were calculated using the PaDEL software, which provides information about the structure, shape, size, charge, polarity, solubility and other aspects of the compounds. Different QSAR model for di- and tripeptides were developed. The statistic parameters for di-peptides model (R2train = 0.947 and R2test = 0.804) and for tripeptide models (R2train = 0.923 and R2test = 0.847) indicate that the generated models have high predictive capacity. Then, the influence of the cysteine position was analyzed predicting the antioxidant activity for new di- and tripeptides, and comparing them with glutathione. In dipeptides, excepting SC, TC and VC, the activity increases when cysteine is at the N-terminal position. For tripeptides, we observed a notable increase in activity when cysteine is placed in the N-terminal position.

Cierre percutáneo de orejuela en paciente con antecedente de cierre percutáneo de comunicación interauricular / Left atrial appendage closure in a patient with prior atrial septal defect occlusion

Resumen La fibrilación auricular es la arritmia más prevalente en la práctica clínica, y se asocia con una morbimortalidad significativa, la cual, en parte, se explica por el riesgo de fenómenos embólicos. En la actualidad, el uso de anticoagulantes es el estándar de manejo en aquellos pacientes con riesgo embólico significativo (dado por un puntaje ≥ 2 en la escala CHA2DS2Vasc). Sin embargo, algunos pacientes tienen contraindicaciones que impiden recibir este tipo de tratamiento a largo plazo, en cuyo caso se considera el cierre percutáneo de la orejuela como medida para la disminución del riesgo de embolia. Al requerir una punción transeptal, la presencia de dispositivos de cierre de defectos del septo interauricular dificulta el procedimiento de manera significativa. Se presenta el caso de una paciente con contraindicación absoluta para recibir anticoagulantes debido a sangrado gastrointestinal y antecedente de cierre percutáneo de comunicación interauricular sometida a cierre percutáneo de orejuela como alternativa terapéutica a la anticoagulación.

Abstract Atrial fibrillation is the most prevalent arrythmia in clinical practice, associated with a significant morbimortality explained, in part, by the high risk of embolic phenomena. The use of anticoagulation is the standard of care in those patients with increased embolic risk (given by a score ≥ 2 in the CHA2DS2Vasc scale). However, some patients have contraindications to receiving this treatment long-term, in which case percutaneous left atrial appendage occlusion can be considered as a means of decreasing their embolic risk. Because the procedure requires transeptal puncture, the presence of devices for atrial septal defect closure can difficult the technique. We present the case of a patient with absolute contraindication to anticoagulation therapy given gastrointestinal bleeding, with history of percutaneous closure of interauricular communication, who was treated with percutaneous left atrial appendage occlusion as an alternative to oral anticoagulants.

Lymphocyte-driven regional immunopathology in pneumonitis caused by impaired central immune tolerance.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), a monogenic disorder caused by AIRE mutations, presents with several autoimmune diseases. Among these, endocrine organ failure is widely recognized, but the prevalence, immunopathogenesis, and treatment of non-endocrine manifestations such as pneumonitis remain poorly characterized. We enrolled 50 patients with APECED in a prospective observational study and comprehensively examined their clinical and radiographic findings, performed pulmonary function tests, and analyzed immunological characteristics in blood, bronchoalveolar lavage fluid, and endobronchial and lung biopsies. Pneumonitis was found in >40% of our patients, presented early in life, was misdiagnosed despite chronic respiratory symptoms and accompanying radiographic and pulmonary function abnormalities, and caused hypoxemic respiratory failure and death. Autoantibodies against BPIFB1 and KCNRG and the homozygous c.967_979del13 AIRE mutation are associated with pneumonitis development. APECED pneumonitis features compartmentalized immunopathology, with accumulation of activated neutrophils in the airways and lymphocytic infiltration in intraepithelial, submucosal, peribronchiolar, and interstitial areas. Beyond APECED, we extend these observations to lung disease seen in other conditions with secondary AIRE deficiency (thymoma and RAG deficiency). Aire-deficient mice had similar compartmentalized cellular immune responses in the airways and lung tissue, which was ameliorated by deficiency of T and B lymphocytes. Accordingly, T and B lymphocyte-directed immunomodulation controlled symptoms and radiographic abnormalities and improved pulmonary function in patients with APECED pneumonitis. Collectively, our findings unveil lung autoimmunity as a common, early, and unrecognized manifestation of APECED and provide insights into the immunopathogenesis and treatment of pulmonary autoimmunity associated with impaired central immune tolerance.

An endothelial growth factor receptor compound mutation of T790M substitution with exon 19 deletion in a previously untreated patient: a case report.

BACKGROUND: Endothelial growth factor receptor (EGFR) mutations are an essential driver of personalized therapy for patients with lung cancer and are detected in approximately 15% of Caucasian and 50% of Asian patients. EGFR tyrosine kinase inhibitors have been developed and used for this set of patients. T790M mutation in exon 20 is usually associated with secondary resistance to EGFR tyrosine kinase inhibitors therapy but is also present in treatment-naïve patients. The frequency for baseline T790M mutation varies from 4 to 35% according to the detection method used. Newer techniques have yielded higher rates, but concerns about false-positive results have been raised. Compound mutations account for 4-14% of all EGFR-mutated tumors, with no studies yet to provide a frequency rate for T790M + 19 deletion association due to the small number of cases. However, there are reports that pretreatment T790M + L858R association is significantly more frequent compared to T790M + exon 19 deletion mutations. Diagnostic challenges, current knowledge on the subject, and therapeutic decisions are discussed. CASE PRESENTATION: We present the case of a 43-year-old Hispanic woman, a treatment-naïve patient, with metastasized lung cancer adenocarcinoma harboring a T790M deletion along with the classic 19 mutation. The initial symptoms were monoparesis of her left leg, associated with hyperreflexia, and hypoesthesia. In the absence of third-generation tyrosine kinase inhibitors, a platinum-based therapy was initiated with no response and she died 4 months after diagnosis. CONCLUSIONS: Osimertinib seems to be a suitable therapy for treatment-naïve patients with sensitizing and resistant compound EGFR mutations. More studies regarding the clinical characteristics of these patients and the appropriate management of this condition are needed to provide the highest standard of care.

Bostezo como mecanismo protector y predictor de síncope: estudio observacional en una cohorte de pacientes / Yawning as a protective mechanism and predictor of syncope: observational study in a patient cohort

Resumen Introducción: el bostezo se presenta con frecuencia en los pacientes sometidos a prueba de mesa basculante. Estudios previos han demostrado que el bostezo estimula el sistema nervioso simpático con sus consecuentes cambios hemodinámicos, principalmente en la frecuencia cardíaca y la presión arterial. Objetivo: describir los efectos hemodinámicos y sobre el sistema nervioso autónomo del bostezo, así como establecer el bostezo como mecanismo protector de síncope o predictor de respuesta hemodinámica positiva. Métodos: estudio observacional de fuente secundaria, realizado a partir de una base de datos de pacientes que fueron sometidos a prueba de mesa basculante entre agosto de 2010 hasta diciembre de 2015 y presentaron al menos un bostezo durante la prueba. Se realizaron análisis estadísticos y pruebas pareadas para determinar correlaciones. Resultados: se incluyeron 156 pacientes, la mayoría mujeres, edad promedio 40 años. 43 pacientes presentaron síncope, 113 (72,4%) bostezo sin síncope, y de éstos, 50 (44,2%) tuvieron bostezo y prueba de mesa basculante con respuesta positiva. Se observó un aumento en la mayoría de variables hemodinámicas, sin embargo, hubo una disminución significativa de la frecuencia cardíaca. En 67 pacientes se observó bostezo como protector de síncope mientras que en 61 pacientes como predictor de respuesta hemodinámica positiva. Conclusión: el bostezo se asoció con activación del sistema nervioso simpático, con efectos hemodinámicos y sobre el sistema nervioso autónomo. Puede plantearse como un signo predictor de respuesta hemodinámica positiva de tipo mixto o vasodepresora y en otros casos como un mecanismo protector frente a la aparición de síncope.

Abstract Introduction: Yawning is often present in patients subjected to a tilt table test. Previous studies have demonstrated that yawning stimulates the sympathetic nervous system, with its subsequent haemodynamic changes, mainly heart rate and blood pressure. Objective: To describe the haemodynamic effects of yawning on the autonomic nervous system, as well as to establish yawning as a protective mechanism of syncope, or a predictor of a positive haemodynamic response. Methods: A secondary source observational study conducted using a database of patients that were subjected to the tilt table test between August 2010 and December 2015, and yawned at least once during the test. Statistical analyses and paired tests were performed to determine correlations. Results: A total of 156 patients were included, the majority women, and a mean age of 40 years. Syncope was presented in 43 patients. The remaining 113 (72.4%) yawned with no syncope, and of these, 50 (44.2%) had yawned and had a positive response to the tilt-table test. Although there was an increase in the majority of haemodynamic variables, a significant decrease was observed in the heart rate. Yawning was observed as a protector of syncope in 67 patients, whilst it was a predictor of a positive haemodynamic response in 61 patients. Conclusion: Yawning is associated with activation of the sympathetic nervous system, with haemodynamic effects and on the autonomic nervous system. It could be established as a predictive sign of a mixed type or vasodepressor positive haemodynamic response, and in other cases as a protective mechanism against the appearance of a syncope.

High immunological response against a Trypanosoma equiperdum protein that exhibits homology with the regulatory subunits of mammalian cAMP-dependent protein kinases.

Previously, we have identified a protein in Trypanosoma equiperdum that possesses homology with the regulatory (R) subunits of the mammalian cAMP-dependent protein kinase (PKA). The recombinant T. equiperdum PKA R-like protein was expressed in bacteria and purified to homogeneity. Mice polyclonal antibodies were raised against the recombinant R-like protein to serologically evaluate its humoral immune response. High titers of specific sera antibodies were obtained against the parasite R-like protein by indirect enzyme-linked immunosorbent assay (ELISA), and immunoblots revealed that this protein was specifically recognized by the hyperimmune mice sera. Cellular proliferation assays using splenic B cells from the immunized mice showed higher values when the recombinant T. equiperdum R-like protein was employed than when concanavalin A was utilized as an unspecific mitogen. Two healthy horses that were experimentally infected using either T. equiperdum or Trypanosoma evansi showed a curve response characterized by the appearance of anti-T. equiperdum PKA R-like protein antibody production in sera using indirect ELISA. The recombinant parasite PKA R-like protein was also recognized by sera from naturally trypanosome-infected horses using western blotting. These findings demonstrated that the T. equiperdum PKA R-like protein is an antigen that exhibits cross-reaction with T. equiperdum and T. evansi.

Prognostic impact of defibrillator shocks in a Colombian cohort / Impacto pronóstico de las descargas del desfibrilador en una cohorte colombiana

Abstract: Introduction: The implantable cardioverter defibrillator (ICD) has become the first-line treatment option for SCD prevention. In Colombia, while ICD therapy has been available for several years, extensive registries or studies documenting the impact of ICD therapy are lacking. Objective: To evaluate the association between appropriate and inappropriate ICD therapies and mortality in Colombian patients. Methods: Prospective observational cohort study including 530 patients with cardiomyopathy of varied etiology, from eight clinics in Medellin, Colombia, from 2013 to 2016. Adjusted and survival analyses were performed. Results: Of all participating patients, 72.1% were men, and median age was 64 years. Mean follow-up time was 1.5 ± 0.92 years, with a follow-up rate of 353.3 patients/year. The most common indication for ICD implantation was ischemic heart disease (48.7%), and indication of primary prevention (63.4%). Mortality was 12.8%, and patients with ischemic etiology had 1.8-times greater risk of death compared to non-ischemic patients. 14% of the patients received appropriate therapies, while 13.6% were inappropriate. There was a 65% greater risk of appropriate therapies in patients with ischemic heart disease. High blood pressure, being over 61 years of age, and having left ventricular ejection fraction < 35%, were risk factors for death, while use of beta-blockers was associated with a reduced risk of death. Conclusions: The main indication for ICD was ischemic etiology and primary prevention. Mortality is higher in patients with ischemic etiology, who in addition have increased risk of presenting appropriate therapies. The frequency of device therapies was decreased compared to previous reports.(AU)

Resumen: Introducción: El desfibrilador cardioversor implantable (DCI) se ha convertido en la opción de primera línea de tratamiento para la prevención de la MCS. En Colombia, aunque la terapia DCI ha estado disponible durante varios años, faltan extensos registros o estudios que documenten el impacto de la terapia DCI. Objetivo: Evaluar la asociación entre las terapias apropiadas e inapropiadas de DCI y la mortalidad en pacientes colombianos. Métodos: Estudio prospectivo observacional de cohorte que incluye 530 pacientes con cardiomiopatía de etiología variada, de ocho clínicas en Medellín, Colombia, de 2013 a 2016. Se realizaron análisis ajustados y de supervivencia. Resultados: De todos los pacientes participantes, el 72.1% fueron hombres y la edad mediana fue de 64 años. El tiempo medio de seguimiento fue de 1.5 ± 0.92 años, con una tasa de seguimiento de 353.3 pacientes/año. La indicación más común para la implantación del DCI fue la cardiopatía isquémica (48.7%) y la indicación de prevención primaria (63.4%). La mortalidad fue del 12.8% y los pacientes con etiología isquémica tuvieron un riesgo de muerte 1.8 veces mayor en comparación con los pacientes no isquémicos. Catorce por ciento de los pacientes recibieron terapias apropiadas, mientras que el 13.6% fueron inapropiadas. Hubo un riesgo 65% mayor de terapias apropiadas en pacientes con cardiopatía isquémica. La hipertensión arterial, el tener más de 61 años de edad y haber dejado la fracción de eyección ventricular < 35%, fueron factores de riesgo de muerte, mientras que el uso de betabloqueantes se asoció con un menor riesgo de muerte. Conclusiones: La principal indicación para la DCI fue etiología isquémica y prevención primaria. La mortalidad es mayor en pacientes con etiología isquémica, que además tienen mayor riesgo de presentar terapias apropiadas. La frecuencia de las terapias con dispositivos se redujo en comparación con los informes anteriores.(AU)

Marcapasos con sensor de asa cerrada en disautonomía secundaria a enfermedad de Sandhoff / Closed-loop pacemakers in dysautonomia secondary to Sandhoff disease

Resumen Introducción: en la enfermedad de Sandhoff se ha descrito el compromiso del sistema nervioso autónomo en piel y tracto gastrointestinal; sin embargo, las alteraciones autonómicas del sistema cardiovascular, como la disautonomía, no se han documentado en la literatura revisada. De otro lado, el síncope neuralmente mediado de características cardioinhibitorias, refractario al manejo médico, puede ser tratado con marcapasos con sensor de asa cerrada. Materiales y métodos: se describe el caso de una paciente de 42 años en quien se realizó el diagnóstico de enfermedad de Sandhof. Asociado a esta patología, presentó disautonomía con episodios de síncope diarios sin respuesta al tratamiento médico, que ameritaron el implante de un marcapasos con sensor de asa cerrada. Posteriormente se revisa la literatura existente sobre el tema. Conclusiones: hasta la fecha no se había reportado relación entre la enfermedad de Sandhoff y la disautonomía; en el caso de esta paciente el deterioro de la calidad de vida fue significativo. El uso del algoritmo CLS en síncope neuralmente mediado con características cardioinhibitorias, ha mostrado disminuir la cantidad de síncopes en este tipo de pacientes y mejorar la calidad de vida de los mismos.

Abstract Introduction: Although involvement of the autonomic nervous system in the skin and gastrointestinal tract has been described in Sandhoff disease, no reports of autonomic changes of the cardiovascular system, such as dysautonomia, have been documented in the literature reviewed. On the other hand, the neurally mediated cardioinhibitory syncope that is refractory to medical management can be treated with pacemakers with closed loop sensors. Materials and methods: The case is described of a 42 year-old patient who was diagnosed with Sandhoff disease. Associated to this condition, he presented with dysautonomia with daily episodes of syncope, with no response to medical treatment, which warranted the implant of a pacemaker with a closed loop sensor. The existing literature on this topic was subsequently reviewed. Conclusions: Up until now, there have been no reports on the relationship between Sandhoff disease and dysautonomia. In the case of this patient, the deterioration in the quality of life was significant. The use of the closed loop stimulation (CLS) algorithm in neurally mediated cardioinhibitory syncope has been shown to reduce the number of syncopes in this type of patient and improve their quality of life.

C-reactive protein as a marker of the surgical stress reduction within an ERAS protocol (Enhanced Recovery After Surgery) in colorectal surgery: A prospective cohort study.

BACKGROUND: The aim of this study is to evaluate the effectiveness of an Enhanced Recovery After Surgery Protocol (ERAS) in relation to reduce the Systemic Inflammatory Response (SIR) to surgery using C-reactive protein (CRP) in the first (POD1), second (POD2) and third (POD3) postoperative day. METHODS: We enrolled 121 patients (ERAS group) that underwent elective colorectal surgery with ERAS, and compared them with 135 patients (preERAS group) that had undergone surgery prior to the implementation. We made a univariate analysis to compare the CRP values in POD1, POD2, and POD3 between preERAS/ERAS group, laparoscopic/open surgery and the presence or not of Clavien Dindo complications. Multivariable lineal regression was used to assess if the ERAS had a decreasing effect on the CRP in POD1, POD2, and POD3, and was adjusted by age, male sex, use of laparoscopy, and complications. RESULTS: The presence of complications was independently associated with an increase in CRP values ​​in POD1, POD2, and POD3. Laparoscopy in POD1 and POD2, and ERAS in POD2 was independently associated with a decrease in CRP values. CONCLUSION: The analysis shows an increase in SIR measured as a CRP value in those patients that had complications. The SIR decreased with laparoscopy in POD1 and POD2 and with ERAS in POD2.

Síndrome de Bayés / Bayés syndrome

Resumen Introducción: El bloqueo interatrial avanzado, sumado a la aparición posterior de arritmias supraventriculares, principalmente fibrilación auricular y aleteo auricular, se conoce como síndrome de Bayés. Sus alteraciones anatómicas y eléctricas, así como sus complicaciones, son de gran impacto en este tipo de pacientes, y hasta la fecha se les había dado poca importancia. En lo que respecta al tratamiento, existen muchos interrogantes sobre la necesidad de anticoagulación en pacientes con bloqueo interatrial en ausencia de fibrilación auricular y flutter auricular. Métodos y materiales: Se presenta la primera revisión no sistemática de la literatura en Colombia y, posteriormente, se exponen tres casos de pacientes que inicialmente tenían bloqueo inter-atrial avanzado y que, a lo largo de los años de seguimiento, desarrollaron fibrilación auricular. Se muestran los electrocardiogramas que documentan el bloqueo inter-atrial, las características demográficas, los antecedentes personales relevantes, las imágenes de ecocardiografía y el manejo actual relacionado de los casos. Conclusiones: Los profesionales de la salud precisan mayor conocimiento sobre este síndrome, para así garantizar un diagnóstico temprano que lleve a un seguimiento adecuado y se logre impactar el pronóstico. Así mismo, es ideal que se fomenten estudios que faciliten la correcta caracterización demográfica de la población en pro de generar nuevas hipótesis con miras hacia el tratamiento óptimo.

Abstract Introduction: Bayés syndrome is characterised by the presence of an advanced inter-atrial block and the subsequent appearance of supraventricular arrhythmias, mainly, atrial fibrillation and atrial flutter. Its anatomical and electrical disturbances, as well as its complications, have a great impact on those who suffer from it, which, up until now have been given little importance. As regards treatment, there is a lot of controversy on the need for anticoagulants in patients with inter-atrial block in absence of atrial fibrillation or flutter. Methods and materials: The first non-systematic review in Colombia is presented, together with three cases of patients who initially had advanced interatrial block and over the years developed atrial fibrillation. The electrocardiograms documenting the advanced interatrial block, and tables showing demographic characteristics, echocardiography and relevant personal history of case management, are discussed. Conclusions: More knowledge about this syndrome is required in order to ensure an early diagnosis, which could lead to an appropriate follow-up, treatment and prevention of complications. Physicians should be encouraged to create and propose new trials regarding this condition, revealing more information about unknown risk factors and different treatment options.

Complejos ventriculares prematuros frecuentes luego de ablación de fibrilación auricular y su relación con el tono autonómico medido por parámetros del Holter / Frequent premature ventricular complexes following ablation of atrial fibrillation and their relationship to the autonomic tone measured with Holter parametres

Resumen Introducción: La ablación con catéter de radiofrecuencia es un tratamiento prometedor para la fibrilación auricular. Pese a su seguridad, se ha evidenciado incremento en la frecuencia de complejos ventriculares prematuros y taquicardia ventricular no sostenida, asociados tal vez con influencias autonómicas. Objetivo: Analizar la actividad autonómica mediante parámetros de monitorización Holter en pacientes llevados a esta intervención. Metodología: Análisis retrospectivo de pacientes con complejos ventriculares prematuros frecuentes luego de aislamiento eléctrico de venas pulmonares por fibrilación auricular, seguidos mediante monitorización Holter entre octubre de 2010 y noviembre de 2014, a fin de comparar parámetros de variabilidad de la frecuencia cardiaca. Resultados: 12,4% tuvo un incremento significativo del automatismo ventricular. Los datos demográficos en los grupos comparados no demostraron diferencias estadísticamente significativas. El promedio de complejos ventriculares prematuros durante las 24 horas fue de 5.363 con 237 por hora. En el grupo de estudio, 65% presentó taquicardia ventricular no sostenida. La variabilidad de la frecuencia cardiaca fue menor en los pacientes del grupo control (p = 0,000). La medida por frecuencias espectrales, evidenció una disminución en la frecuencia LF y HF para ambos grupos, con un valor menor para el grupo control (p = 0,000). La relación LF/HF para ambos grupos fue elevada (p = 0,612). Conclusión: La ablación de venas pulmonares en el tratamiento de la fibrilación auricular puede conducir al desarrollo de complejos ventriculares prematuros frecuentes y taquicardia ventricular. El impacto sobre el sistema parasimpático y simpático puede ser un factor que precipite esta condición.

Abstract Introduction: Radiofrequency catheter ablation is a promising treatment for atrial fibrillation. Despite its security, and increase in the frequency of premature ventricular complexes and nonsustained ventricular tachycardia has been evidenced, which could have autonomic influences. Motivation: To analyse autonomic activity using Holter monitoring parametres in patients who underwent this procedure. Methods: Retrospective analysis of patients with frequent premature ventricular complexes following electric isolation of pulmonary veins due to atrial fibrillation, followed up with Holter monitorisation between October 2010 and November 2014 with the goal of comparing heart rate variability parametres. Results: 12.4% had a significant increase of ventricular automacity. Demographic data in compared groups did not reveal statistically significant differences. The average of premature ventricular complexes within 24 hours was of 5,363, with 237 per hour. In the study group, 65% showed non-sustained ventricular tachycardia. Heart rate variability was lower in patients from the control group (p = 0.000). Evaluation of spectral frequency evidenced a decrease in LF and HF for both groups, with a lower value for the control group (p = 0.000). HF/LF relationship for both groups was high (p = 0.612). Conclusion: Ablation of pulmonary veins in the treatment of atrial fibrillation can lead to the development of frequent premature ventricular complexes and ventricular tachycardia. The impact on the parasympathetic and sympathetic system could be a factor that triggers this condition.

Asociación del tejido adiposo epicárdico con la fibrilación auricular y su pronóstico posterior a la ablación de venas pulmonares / Association of epicardial adipose tissue with atrial fibrillation and prognosis following pulmonary vein ablation

Resumen Introducción: la acumulación de tejido adiposo epicárdico se asocia con obesidad y aumento en la prevalencia, severidad y recurrencia posteriores a la ablación de la fibrilación auricular. Dentro de los mecanismos implicados se considera un estado proinflamatorio que lleva al remodelamiento estructural de la aurícula y a la alteración en las propiedades electrofisiológicas de los miocitos auriculares. Hasta la fecha no se ha estudiado este fenómeno en Colombia. Objetivo: demostrar esta asociación en un grupo de pacientes de nuestra población a quienes se les realizó ablación de venas pulmonares por radiofrecuencia. Materiales y métodos: se revisaron 170 angiotomografías de corazón realizadas previamente a la ablación de venas pulmonares en pacientes con antecedente de fibrilación auricular. Los pacientes con datos incompletos fueron excluidos para el análisis, 94 fueron analizados. Se cuantificó el grosor del tejido adiposo epicárdico y en conjunto con el índice de masa corporal se analizó su relación con los subtipos de fibrilación auricular, así como recaídas luego de la ablación. Resultados: la mayoría de la población se encontró con sobrepeso y obesidad. Tanto los pacientes obesos como aquellos con sobrepeso, tuvieron significativamente grosor mayor de tejido adiposo epicárdico total respecto a los pacientes con índice de masa corporal normal (p = 0,01). El grosor de la grasa epicárdica fue significativamente mayor en fibrilación auricular persistente respecto a la fibrilación auricular paroxística (p = 0,01). En los pacientes que presentaron recaídas no se observó una diferencia significativa pero sí una tendencia a tener mayor tejido adiposo epicárdico total (p = 0,08). El aumento del tamaño auricular se relacionó en forma significativa con el grosor del tejido adiposo epicárdico (p = 0,05). En el análisis de regresión logística multivariable mantuvo esta relación. Conclusiones: el aumento del tejido adiposo epicárdico se relaciona de manera independiente con el sobrepeso y la obesidad, así como con la severidad y el pronóstico de la fibrilación auricular. Deben hacerse estudios prospectivos de cohortes en los que se evalúe y establezcan valores de corte normales para nuestra población, al igual que seguimiento a largo plazo de la evolución posterior a ablación de venas pulmonares y a intervenciones como disminución de peso.

Abstract Introduction: Accumulation of epicardial adipose tissue is associated with obesity and an increase of prevalence, severity and recurrence following ablation of atrial fibrillation. Within the implicated mechanisms, a proinflammatory state is considered when it leads to the structural remodelling of the atrium and to the alteration of the electrophysiological properties of atrial myocytes. So far this phenomenon has not been studied in Colombia. Motivation: To prove the association in a group of patients of our population who underwent radiofrequency ablation of pulmonary veins. Material and methods: 170 coronary CT angiographies were reviewed prior to the pulmonary vein ablation in patients with a history of atrial fibrillation. Patients with incomplete data were excluded from the analysis, 94 were analysed. Epicardial adipose tissue thickness and body mass index were measured, and their relationship with atrial fibrillation subtypes was assessed, as well as relapses following the ablation. Results: Most participants were overweight or obese. Both obese and overweight patients had a significantly thicker total epicardial adipose tissue than those with a normal body mass index (p = 0.01). The thickness of epicardial fat was significantly higher in persistent atrial fibrillation in comparison with paroxysmal atrial fibrillation (p = 0.01). Patients with relapses did not show a significant difference but they did have a higher tendency to greater total epicardial adipose tissue. The increase in atrial size was significantly relates to the thickness of epicardial adipose tissue (p = 0.05). Multivariate logistic regression analysis kept this relationship. Conclusions: The increase in epicardial adipose tissue is independently related to being overweight and obese, as well as to severity and prognosis of atrial fibrillation. Prospective cohort studies must be conducted where normal cut-off values for our population group are assessed and established, and the long-term progress following pulmonary vein ablation and other procedures such as weight loss surgery is followed.

Antígenos Subdominantes de Anaplasma marginale: Nuevos Candidatos Vacunales Contra la Anaplasmosis Bovina / Subdominant Antigens of Anaplasma marginale: New Vaccine Candidates Against Bovine Anaplasmosis

La anaplasmosis es una enfermedad infecciosa que afecta a los bovinos y es causada por la rickettsia intraeritrocítica Anaplasma marginale. A pesar de su impacto global, hasta el momento, no se ha desarrollado una vacuna efectiva. Se ha postulado que la inmunización del ganado con la membrana externa de la rickettsia, genera protección parcial contra la exposición al Anaplasma marginale y que esta respuesta está dirigida a seis polipéptidos denominados Proteínas Principales de Superficie (MSPs del inglés, Major Surface Proteíns). Estas proteínas presentan un carácter inmunodominante cuando se emplean como antígenos en su forma nativa o recombinante, lo que ha hecho pensar que son los antígenos indicados para una vacuna. Sin embargo, la protección brindada fluctúa entre una protección total o parcial a ninguna protección. La búsqueda de antígenos alternativos a las MSPs, se ha visto limitada a consecuencia de su muy baja o ausente capacidad inductora de formación de anticuerpos o de linfocitos T reactivos, los cuales son indispensables para su identificación mediante inmunoensayos. El objetivo de este trabajo fue describir las estrategias aplicadas recientemente para identificar nuevos antígenos de A. marginale, denominados antígenos subdominantes, porque representan una pequeña porción del proteoma de la rickettsia, los cuales han demostrado ser buenos candidatos vacunales contra la anaplasmosis. Actualmente, diversos estudios moleculares y bioinformáticos han definido varias proteínas de superficie y componentes del Sistema de Secreción Tipo IV, como antígenos potenciales; entre ellos están las proteínas Ana17, Ana29, Ana32, Ana37 y Ana43, que le han brindado una protección parcial al ganado después de la exposición al proceso infeccioso; y las proteínas VirB9-1, VirB9-2 y VirB10 (Sistema de Secreción tipo IV), las cuales generan una fuerte respuesta inmune en el ganado, aunque se desconoce su nivel de protección.

The Anaplasmosis is an infectious disease of cattle caused by the intraerythrocytic rickettsia Anaplasma marginale. Despite its overall impact, no effective vaccine has been developed so far. It has been postulated that immunization of cattle with the native outer membrane of rickettsia generates partial protection against Anaplasma marginale challenge; and that this response is directed to six polypeptides known as Major Surface Proteins (MSPs). These proteins display an immunodominant character when they are used as immunogens in their native or recombinant form, which has suggested that they are the appropriate vaccine antigens. However, the protection provided varies from a total or partial protection to no protection. The search for alternative antigens to MSPs has been limited as a result of their very low or null capacity for inducing the production of potential antibodies or reactive T cells, which are essential for their identification through immunoassays. The objective of this review was to describe the recently applied strategies for the identification of new antigens of A. marginale, the so-called subdominant antigens, proteins that represent a small portion of the proteome of the rickettsia. These proteins have shown to be good vaccine candidates against anaplasmosis. Currently, molecular and bioinformatics studies have defined several surface proteins and components of the Type IV Secretion System as potential antigens; among them are the Ana17, Ana29, Ana32, Ana37, and Ana43 proteins, which have given partial protection to cattle after the infectious challenge; and VirB9-1, VirB9-2, and VirB10 proteins (Type IV Secretion System), which generate a strong immune response in cattle, although their level of protection is unknown.

Immunological identification of a cAMP-dependent protein kinase regulatory subunit-like protein from the Trypanosoma equiperdum TeAp-N/D1 isolate.

Polyclonal immunoglobulin Y (IgY) antibodies were produced in chicken eggs against the purified R(II)-subunit of the cAMP-dependent protein kinase (PKA) from pig heart, which corresponds to the Sus scrofa R(II)α isoform. In order to evaluate whether Trypanosoma equiperdum possessed PKA R-like proteins, parasites from the Venezuelan TeAp-N/D1 strain were examined using the generated anti-R(II) IgY antibodies. Western blot experiments revealed a 57-kDa polypeptide band that was distinctively recognized by these antibodies. Likewise, polyclonal antibodies raised in mice ascites against the recombinant T. equiperdum PKA R-like protein recognized the PKA R(II)-subunit purified from porcine heart and the recombinant human PKA R(I)ß-subunit by immunoblotting. However, a partially purified fraction of the parasite PKA R-like protein was not capable of binding cAMP, implying that this protein is not a direct downstream cAMP effector in T. equiperdum. Although the function of the S. scrofa PKA R(II)α and the T. equiperdum PKA R-like protein appear to be different, their cross-reactivity together with results obtained by bioinformatics techniques corroborated the high level of homology exhibited by both proteins. Moreover, its presence in other trypanosomatids suggests an important cellular role of PKA R-like proteins in parasite physiology.

Rotura de la cánula de traqueostomía: una causa rara de dificultad respiratoria en el nino traqueotomizado. Caso clínico / Fractured tracheostomy tube: a rare cause of respiratory distress in the tracheotomized child. Case report

La fractura y migración de la cánula de traqueostomía en el árbol traqueobronquial es una complicación poco frecuente de la traqueostomía. El diagnóstico precoz y el tratamiento adecuado son esenciales debido al riesgo potencial de obstrucción respiratoria fatal. El diagnóstico se debe sospechar en todo niño traqueotomizado que presenta dificultad respiratoria. Se confirma mediante radiografía de tórax y examen endoscópico. El tratamiento de elección es la remoción endoscópica de la cánula aspirada a través del estoma traqueal. Describimos la presentación clínica y el manejo de la rotura de cánula de traqueostomía que se presentó como cuerpo extrano en la vía aérea de un niño de 18 meses. También incluimos recomendaciones para el cuidado de la traqueostomía.

Fracture and migration of the tracheotomy tube in the tracheobronchial tree is an uncommon complication of tracheotomy. Early diagnosis and proper treatment are essential because of the potential risk of fatal respiratory obstruction. Diagnosis should be suspected in all tracheotomized children undergoing breathing difficulties. It is confirmed by chest x-ray and endoscopic examination. The recommended treatment includes the endoscopic removal of the aspirated cannula through the tracheal stoma. We describe the clinical presentation and the management of a broken tracheotomy tube which was presented as a foreign body in the airway of a 18-month-old child. Recommendations for tracheostomy care are listed.

Systematic evaluation of textural properties, activation temperature and gas uptake of Cu2(pzdc)2L [L = dipyridyl-based ligands] porous coordination pillared-layer networks.

In situ high temperature X-ray diffraction, nitrogen porosimetry and gas adsorption at room temperature were used to elucidate the effect of the degassing or activation temperature on the long-range and micropore textural properties of a series of coordination polymers with pillared-layer structures. Ramp-and-soak thermal gravimetric analysis performed at selected activation temperatures were used to verify the thermal stability of a CPL-n series [Cu(2)(pzdc)(2)L; pzdc = pyrazine-2,3-dicarboxylate; L = 4,4-azopyridine (apy) for CPL-4, 1,2-di-(4-pyridil)-ethylene (bpe) for CPL-5, N-(4-pyridyl)-isonicotinamide (pia) for CPL-6, and 1,2-di-(4-pyridyl)-glycol (dpyg) for CPL-7]. Although the activation temperatures were far below the decomposition point of the complexes, these resulted in significant and unique changes in micropore surface area and volume, even for CPL-4, -5 and -6, which contained pillar ligands with similar dimensions and similar structural long-range order. For the case of CPL-7, however, the framework appeared to be non-porous at any given activation temperature. Pure component equilibrium adsorption data gathered for CO(2), CH(4), and N(2) were used to elucidate the CPL-n materials potential for storage and separations at room temperature. All of the materials exhibited considerable selectivity toward CO(2), particularly at moderate pressures. Meanwhile, CO(2) isosteric heats of adsorption indicated that the pore functionalities arising from the pillar ligands provided similar interactions with the adsorbate in the cases of CPL-4 and -5. For CPL-6, the presence of the carbonyl (C[double bond, length as m-dash]O) group appeared to enhance interactions with CO(2) at low loadings.

Apoptosis and acute cellular rejection in human heart transplants.

INTRODUCTION AND OBJECTIVES: Apoptosis has been implicated in the pathophysiology of various forms of heart disease. Acute cellular rejection leads to morbidity after heart transplantation and invasive techniques are needed for its diagnosis. We investigated the presence of cardiomyocyte apoptosis in transplanted hearts, its progression, its relationship with rejection, and the possibility that serological markers of apoptosis can be used to detect rejection noninvasively. METHODS: Overall, 130 endomyocardial biopsies obtained sequentially from 14 consecutive patients during the first 6 months following heart transplantation underwent histochemical analysis. The degree of acute rejection was determined, myocyte apoptosis was assessed using the TUNEL method, and caspase-3 activity was measured. In the first 10 patients, soluble Fas, tumor necrosis factor-alpha (TNFα) and interleukin 6 levels were determined in serum collected at biopsy. RESULTS: Apoptotic cells were detected in 81.5% of biopsies. No significant correlation was found between the apoptotic index and either the degree of rejection or the time from transplantation; there was only a trend to higher values during prolonged episodes of rejection, which did not reach statistical significance. An inverse correlation was observed between the degree of rejection and the TNFα level (rs=-0.33; P=.003). There was no correlation with any other variable. CONCLUSIONS: Cardiomyocyte loss due to apoptosis was observed in transplanted hearts, but no correlation was observed with either acute rejection or the time from transplantation. Our findings suggest there could be an inverse correlation between rejection and the serum TNFα level. No serum parameter evaluated was regarded as suitable for the noninvasive diagnosis of acute rejection.

Accidente cerebrovascular isquémico asociado con ablación por radiofrecuencia de reentrada nodal / Ischemic stroke associated with radio frequency ablation for nodal reentry

La taquicardia por reentrada nodal es la causa más común de taquicardia supraventricular paroxística; en aquellos pacientes en quienes el manejo farmacológico no es efectivo o deseado la ablación por radiofrecuencia es un excelente método terapéutico dada su alta tasa de curación. Aunque en términos generales dichos procedimientos son rápidos y seguros, se han descrito varias complicaciones entre las que sobresale el accidente cerebrovascular isquémico. Se presenta el caso de una paciente de 41 años con episodios de taquicardia por reentrada nodal a repetición, que fue llevada a ablación por radiofrecuencia. En el post-operatorio inmediato se evidenció déficit neurológico focal con isquemia en el territorio de la arteria cerebral media derecha, tras lo cual se realizó angiografía con intento de angioplastia y abxicimab y posteriormente infusión local de activador de plasminógeno tisular (rtPA) con adecuado resultado clínico y angiográfico.

Atrioventricular nodal reentry tachycardia is the most common type of paroxismal supraventricular tachycardia. In those patients in whom drug therapy is not effective or not desired, radio frequency ablation is an excellent therapeutic method. Although overall these procedures are fast and safe, several complications among which ischemic stroke stands out, have been reported. We present the case of a 41 year old female patient with repetitive episodes of tachycardia due to nodal reentry who was treated with radiofrequency ablation. Immediately after the procedure she presented focal neurologic deficit consistent with ischemic stroke in the right medial cerebral artery territory. Angiography with angioplastia and abxicimab was performed and then tissue plasminogen activator (rtPA) was locally infused, with appropriate clinical and angiographic outcome.

Características pre-destete de bovinos simmental (Bos Taurus) y sus cruces con brahman (Bos indicus) en el trópico mexicano / As características pré-desmame gado simental (Bos taurus) e seus cruzamentos com brahman (Bos indicus), no trópico de México / Pre-weaning traits in simmental and simmental (Bos taurus) x brahman (Bos indicus) cross breed cattle in the Mexican tropic

El objetivo del presente estudio fue determinar el comportamiento productivo del nacimiento al destete de terneros simmental y sus cruzas con brahman en un rebaño productor de carne en el sur de Tamaulipas, México. Se analizaron los registros de los años 1994 a 2005, peso al nacimiento (PN, n = 947), peso al destete ajustado a 205 días (PD205, n = 802), y ganancia diaria predestete (GDP, n = 802), utilizando el método de mínimos cuadrados para determinar los efectos de grupo racial (GR), año (AP) y época (EP) de parto, número de parto (NP), sexo de la cría (SX), y las interacciones de primer orden sobre PN; mientras que para GDP y PD205 se consideró además el PN como covariable. Las medias generales para PN, GDP y PD205 fueron 35.2 ± 6.7, 0.774 ± 0.175 y 194.3 ± 37.3 kg, respectivamente. El GR afectó significativamente (p<0.01) la GDP y el PDA205. El AP y el NP fueron fuentes de variación con efecto estadístico significativo (p<0.01) en el PN, la GDP y el PD205. La EP sólo afectó de manera significativa (p<0.05) la GDP y el PD205, mientras que el SX no presentó un efecto significativo (p>0.05) en ninguna de las variables de respuesta.

The objective of this study was to determine the productive performance in body weight change from birth to weaning, of calves simmental and their crosses with brahman in a beef cattle in the south of Tamaulipas, Mexico. Data were analyzed from 1994 to 2005 years (birth weight BW, n = 947; weaning weight adjusted to 205 days WW205, n = 802; and pre-weaning daily gain weight DGW, n = 802) using the method of minimum square to determine the effects of breed group (BG), year (YC), and season (SC) calving, parity number of cow (PC), and sex of calves (SX); and the interaction of first order on the variables of BW, DGW and WW205. In DGW and WW205 were considered the covariable of BW. The averages for BW, DGW and WW205 were 35.2 ± 6.7, 0.774 ± 0.175 and 194.3 ± 37.3 kg, respectively. The BG was affected (p<0.01) the DGW and WW205. The YC and SC were important variation sources (p<0.01) in BW, DGW and WW205. The SC affected (p<0.05) DGW and WW205. The SX did not have an effect (p>0.05) on anyone’s variables.

O objetivo deste estudo foi determinar a eficiência produtiva do nascimento de bezerros na desmama Simental e seus cruzamentos com Brahman, em um rebanho produtor de carne de bovino no sul do Tamaulipas, México. Foram analisados os registros dos anos de 1994 a 2005, peso ao nascer (PN, n = 947), desmame peso ajustado para 205 dias (PD205, n = 802), eo ganho diário predestete (PIB n = 802), utilizando o método dos mínimos quadrados para determinar os efeitos de grupo racial (GR), ano (PA) e tempo (EP) de nascimento, número de partos (NP), o sexo de criação (SX) e as interações de primeira ordem em PN, enquanto que para o PIB e PD205 também é considerado como o PN covariable. e as interações de primeira ordem em PN, enquanto que para o PIB e PD205 também é considerado como o PN covariable. O CR afetados significativamente (p<0.01) e do PIB PDA205. A AP e NP foram as fontes de variação estatística com efeito significativo (p<0.01) no PN, o PIB e PD205. O PE só afectou significativamente (p<0.05) e do PIB PD205. O PE só afectou significativamente (p<0.05) e do PIB PD205, enquanto o SX não apresentou um efeito significativo (p>0.05) em nenhuma das variáveis resposta.

p27Kip1 is expressed in proliferating cells in its form phosphorylated on threonine 187.

BACKGROUND: G1/S cell cycle progression requires p27Kip1 (p27) proteolysis, which is triggered by its phosphorylation on threonine (Thr) 187. Since its levels are abundant in quiescent and scarce in cycling cells, p27 is an approved marker for quiescent cells, extensively used in histopathology and cancer research. METHODS: However here we showed that by using a specific phosphorylation site (pThr187) antibody, p27 is detectable also in proliferative compartments of normal, dysplastic and neoplastic tissues. RESULTS: In fact, whereas un-phosphorylated p27 and MIB-1 showed a significant inverse correlation (Spearman R = -0.55; p < 0,001), pThr187-p27 was positively and significantly correlated with MIB-1 expression (Spearman R = 0.88; p < 0,001). Thus proliferating cells only stain for pThr187-p27, whereas they are un-reactive with the regular p27 antibodies. However increasing the sensitivity of the immunocytochemistry (ICH) by the use of an ultra sensitive detection system based on tiramide signal amplification, simultaneous expression and colocalisation of both forms of p27 was shown in proliferating compartments nuclei by double immunofluorescence and laser scanning confocal microscopy studies. CONCLUSION: Overall, our data suggest that p27 expression also occurs in proliferating cells compartments and the combined use of both regular and phospho- p27 antibodies is suggested.