Pereskia sacharosa Griseb. (Cactaceae) Prevents Lipopolysaccharide-Induced Neuroinflammation in Rodents via Down-Regulating TLR4/CD14 Pathway and GABAA γ2 Activity.

Pereskia sacharosa Griseb. is a plant used in traditional herbal medicine to treat inflammation. We analyzed the phenolic content of P. sacharosa leaves (EEPs) by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and investigated the anti-inflammatory properties of EEPs and its flavonoid fraction (F10) in animal models subjected to acute neuroinflammation induced by bacterial lipopolysaccharide (LPS). Coronal brain sections of C57BL/6JN male mice or Wistar male rats administered with EEPs or F10 before LPS were subjected to in situ hybridization to determine c-fos and CD14 mRNA levels in the hypothalamus or GABAA γ2 mRNA levels in the hippocampus. Theta oscillations were recorded every 6 h in the hippocampus of Wistar rats. In total, five flavonoids and eight phenolic acids were identified and quantified in P. sacharosa leaves. Either EEPs or F10 crossed the blood-brain barrier (BBB) into the brain and reduced the mRNA expression of c-fos, CD14, and GABAA γ2. A decrease in theta oscillation was observed in the hippocampus of the LPS group, while the F10 + LPS group overrode the LPS effect on theta activity. We conclude that the bioactive compounds of P. sacharosa reduce the central response to inflammation, allowing the early return of ambulatory activity and well-being of the animal.

BioPrint meets the AI age: development of artificial intelligence-based ADMET models for the drug-discovery platform SAFIRE.

Background: To prioritize compounds with a higher likelihood of success, artificial intelligence models can be used to predict absorption, distribution, metabolism, excretion and toxicity (ADMET) properties of molecules quickly and efficiently. Methods: Models were trained with BioPrint database proprietary data along with public datasets to predict various ADMET end points for the SAFIRE platform. Results: SAFIRE models performed at or above 75% accuracy and 0.4 Matthew's correlation coefficient with validation sets. Training with both proprietary and public data improved model performance and expanded the chemical space on which the models were trained. The platform features scoring functionality to guide user decision-making. Conclusion: High-quality datasets along with chemical space considerations yielded ADMET models performing favorably with utility in the drug discovery process.

Good machine learning practices: Learnings from the modern pharmaceutical discovery enterprise.

Machine Learning (ML) and Artificial Intelligence (AI) have become an integral part of the drug discovery and development value chain. Many teams in the pharmaceutical industry nevertheless report the challenges associated with the timely, cost effective and meaningful delivery of ML and AI powered solutions for their scientists. We sought to better understand what these challenges were and how to overcome them by performing an industry wide assessment of the practices in AI and Machine Learning. Here we report results of the systematic business analysis of the personas in the modern pharmaceutical discovery enterprise in relation to their work with the AI and ML technologies. We identify 23 common business problems that individuals in these roles face when they encounter AI and ML technologies at work, and describe best practices (Good Machine Learning Practices) that address these issues.

Determinantes sociales de la salud y prevención de infecciones de transmisión sexual en estudiantes de una institución educativa del Perú / Social determinantsof health and prevention of sexually transmitted infections in students of an educational institution in Perú

Objetivo: Establecer la relación entre los determinantes sociales de la salud y prevención de infecciones de transmisión sexual en estudiantes de una Institución Educativa del Perú. Material y métodos: Estudio descriptivo, con enfoque cuantitativo, nivel correlacional y diseño no experimental, donde se contó con una muestra de 144 estudiantes, evaluados mediante un instrumento como el cuestionario estructurado, validado y con un nivel alto de confiabilidad. Resultados: Evidenciaron que la prevención de ITS mostró una relación significativa con las dimensiones biológico, estilo de vida y el sistema sanitario, donde el p valor alcanzado fue de 0,000, así como una correlación positiva media, donde los coeficientes obtenidos fueron 0,500, 0.485 y 0,434 respectivamente. Conclusiones: Predominó una relación significativa, así como una correlación positiva considerable entre las variables evaluadas, por lo mismo que se contó con un p valor de 0.000 y un coeficiente de 0,642 correspondientemente

Objective: To establish the relationship between the social determinants of health and the prevention of sexually transmitted infections in students of an educational institution in Peru. Material and method:descriptive study, with a quantitative approach, correlational level and non-experimental design, where there was a sample of 144 students, evaluated using an instrument such as the structured questionnaire, validated and with a high level of reliability. Results:Showed that STI prevention showed a significant relationship with the biological, lifestyle and health system dimensions, where the p value achieved was 0.000, as well as a mean positive correlation, where the coefficients obtained were 0.500, 0.485 and 0.434 respectively. Conclusions: A significant relationship predominated, as well as a considerable positive correlation between the variables evaluated, for the same reason that there was a p value of 0.000 and a coefficient of 0.642 respectively

Terapia de revascularización percutánea en pacientes portadores de estenosis crítica carotídea-coronaria: resultados en un hospital y a largo plazo / Percutaneous revascularization therapy in patients of critical carotid-coronary stenosis: results in hospital and long term

Objetivo: Analizar la morbimortalidad a 30 días y 6 meses en pacientes sometidos a una intervención percutánea (IP) por estenosis critíca carotídea (EAC)-coronaria (EACo) en un centro hospitalario de alto volumen, experto en el tratamiento de la enfermedad multivascular. Antecedentes: El tratamiento óptimo de los pacientes con EAC y EACo concomitante sigue siendo controvertido. Ha sido reportada una variedad de estrategias terapéuticas, incluyendo a la cirugía de revascularización coronaria (BACo), sola o en combinación con la revascularización percutánea o quirúrgica de la arteria carótida. Material y métodos: Entre enero de 1998 y junio de 2013 fueron tratados 118 (149 lesiones) pacientes consecutivos con EAC (estenosis carotídea sintomática en el 37.6%) y EACo en forma estadiada o simultánea a IP carotídeo-coronario con stent. El objetivo primario (PP) fue evaluar la incidencia de los eventos cardiacos y cerebro-vasculares mayores (ECVM) (muerte, infarto al miocardio y accidente vascular cerebral mayor) en los 30 días posteriores, tanto al primero como segundo procedimiento. Con un EuroSCORE (ES) promedio de 2.75 ± 1.5. Resultados: A 30 días, la incidencia de PP fue de 4.02%; la muerte global infarto agudo al miocardio (IAM) y accidente vascular cerebral mayor (AVCM) ocurrieron en el 2.01, 1.34 y 0.67% respectivamente; no observamos diferencia en AVC mayor y muerte en el grupo Sx versus Asx, 2.14% versus 2.14%, p = 0.809; ambos grupos, sin embargo, en el infarto fue mayor en Asx versus Sx 4.3% versus 0%, p = 0.053. Se hizo un seguimiento a seis meses de 140 lesiones tratadas; cuatro pacientes se sometieron a revascularización coronaria, uno falleció, tres de ellos presentaron IAM y muerte cardiovascular, 0% de AVC ipsilaterales; 1.4% presentó reestenosis in stent carotídeo tratándose con angioplastia balón (ATP). Conclusiones: En los pacientes con EAC y EACo concomitante, un tratamiento percutáneo combinado se compara muy favorablemente con las experiencias quirúrgicas o híbridos con evidente menor ECVM. Tal estrategia puede ser especialmente más adecuada a pacientes complejos con alto riesgo quirúrgico.

Objectives: To analyze the morbidity and mortality at 30 days and 6 months in patients taken to a Percutaneous Intervention (PI) for critical Carotid and coronary stenosis in a center of high volume expert in the treatment of multivessel disease. Background: The optimal treatment of patients with Carotid and Coronary disease concomitant remains controversial. A variety of therapeutic strategies, including coronary artery bypass surgery (CABG), alone or in combination with percutaneous or surgical revascularization of the carotid artery have been reported. Material and methods: Between January 1998 and June 2013, 118 patients with (149 lesions) carriers of Coronary and Carotid disease (symptomatic carotid stenosis in 37.6%) were treated as staged or simultaneous PI Carotid-Coronary stenting. The primary endpoint (EP) to assess the incidence of major cerebrovascular and cardiac events (MACE) (death, myocardial infarction, cerebral vascular accident major) within 30 days after the first and second proceedings, with EuroSCORE (ES) 2.75 ± 1.5 avg. Results: The incidence of EP was 4.02%, global death, acute myocardial infarction (AMI) and cerebral vascular accident major (CVAM) occurred in 2.01, 1.34 and 0.67% respectively. In group Asx versus Sx we not observed a greater difference in the CVAM and death 2.14% versus 2.14%, p = 0.809 both groups, however in AMI was higher in Asx versus Sx group 4.3% versus 0%, p = 0.053. At 6 month follow up 4 patients underwent CABG one dies, 3 patients more presented AMI and death, 0% ipsilateral CVA, 1.4% had carotid stent restenosis with being treated PTA. Conclusions: In patients with carotid and coronary stenosis concomitant, combined percutaneous treatment compares very favorably to previous surgical or hybrid experiences less obvious MACE. This strategy may be particularly suited to more complex patients with high surgical risk.

Cierre percutáneo primario del defecto del tabique interventricular postinfarto con el dispositivo de Amplatzer: resultados inmediatos y seguimiento a largo plazo / Primary percutaneous closure of postinfarction septal defect with Amplatzer device: immediate results and long-term follow-up

Introducción: La reparación quirúrgica inmediata de una comunicación interventricular que complica el infarto agudo del miocardio (CIV post-IAM) se asocia con la alta mortalidad. El cierre con dispositivo percutáneo parece ser seguro y efectivo en pacientes con CIV post-IAM; reportamos los resultados inmediatos y a largo plazo en la utilización del dispositivo Amplatzer en el cierre primario de una CIV post-IAM. Material y métodos: De junio del 2006 a enero del 2014, 17 pacientes portadores de una CIV post-IAM se sometieron a un cierre percutáneo con Amplatzer a una edad promedio de 66.8 ± 5.5, 82.4% en shock cardiogénico (ShC), el 35.3% recibieron tratamiento trombolítico (TT) en ventana, el tiempo promedio del diagnóstico de CIV al cierre percutáneo (IP) fue de 8.7 ± 5.8 días. Resultados: Con un seguimiento actual de 13.25 ± 12.6 meses, el éxito del procedimiento fue del 100%, el shunt (QP:QS) se redujo de 2.9 ± 0.95 a 1.5 ± 0.40 L/min p = 0.0001, 12 pacientes (70.6%) se sometieron a una Angioplastía Coronaria Transluminal Percutánea (ACTP) del vaso culpable posterior al cierre de la CIV. La mortalidad a 30 días fue de 52.9%, siendo más alta en el paciente con ShC versus no-ShC 64.3 versus 0% p = 0.043 OR 2.8 (IC 95% 1.38-5.6). Conclusión: El cierre primario de CIV post-IAM es una técnica muy promisoria que puede ser realizada con una alta tasa de éxito y mínimas complicaciones y puede ser tomado como una alternativa a la cirugía. Sin embargo, a pesar de ser una técnica menos invasiva, la mortalidad permanece alta y muy evidente en el paciente en ShC.

Introduction: The immediate surgical repair of a ventricular septal defect complicating acute myocardial infarction (VSD post-AMI) is associated with high mortality. The percutaneous closure device is safe and effective in patients with post-infarction VSD; we report the immediate and long term results in the use of the Amplatzer device in the primary closure of post infarction VSD. Material and methods: From June 2006 to January 2014, 17 patients carriers of post-infarction VSD underwent percutaneous Amplatzer closure with a mean age 66.8 ± 5.5, 82.4% in cardiogenic shock (CS), 35.3% were thrombolyzed (TT) in window, the average time to percutaneous closure of VSD 8.7 ± 5.8 days. Results: With a current monitoring of 13.25 ± 12.6 months procedural success were in 100% shunt (QP:QS) was reduced from 2.9 to 1.5 ± 0.40 ± 0.95 L/min p = 0.0001, 12 patients (70.6%) undergoing PTCA the culprit vessel post-closure of the VSD. Global mortality at 30 days was 52.9%, being higher in patients with CS versus 64.3 versus 0% no-CS p = 0.043 OR 2.8 (CI 95% 1.38-5.6). Conclusion: The primary closure of postinfarction VSD is a very promising technique that can be performed with a high success rate and minimal complications and may be taken as an alternative to surgery. However despite being a less invasive technique remains high mortality very evident in patients in CS.

Utilidad de la biopsia fría ureteral durante la cistectomía radical como predictor de riesgo de recidiva: revisión de nuestra serie / Usefulness of cold ureteral biopsy during radical cystectomy as a predictor of recurrence risk: Review of our series

OBJETIVOS: Evaluar la asociación de márgenes positivos en la biopsia intra-operatoria al tiempo de la cistectomía radical (CR) con el riesgo de recidiva en la anastomosis urétero-ileal o a nivel del tracto urinario superior (TUS), y estudiar posibles factores de riesgo preoperatorios asociados con el margen ureteral positivo. MÉTODO: Estudio descriptivo retrospectivo de pacientes tratados mediante CR debido a carcinoma de células transicionales (CCT), a los que se les realizó al tiempo de la CR una biopsia fría del margen ureteral. Se realizó un análisis descriptivo y distribuciones de frecuencias. Se empleó el test de Fisher, se calcularon los valores de sensibilidad (Se) y especificidad (Sp) de la prueba, y se realizó un análisis de supervivencia. RESULTADOS: Se incluyeron 230 pacientes que fueron sometidos a CR. Previamente a la CR se les realizó resección transuretral (RTU) de vejiga y tomografía axial computarizada (TC). El porcentaje de márgenes positivos fue de 4,8% para el uréter derecho y de 4,7% para el izquierdo. Se detectó recidiva en la anastomosis en el 2,6% de los casos. En un 0,8% se encontró recidiva en el TUS (2 casos) a nivel de pelvis renal izquierda (1 caso) y riñón izquierdo (1 caso). En el análisis multivariante, ni la recidiva en la anastomosis (p=1) ni a nivel del TUS (p=1) a lo largo del seguimiento, se asociaron de forma significativa con la presencia de márgenes positivos. De forma secundaria se estudiaron los posibles factores anatomopatológicos preoperatorios asociados con el riesgo de margen positivo, encontrando asociación entre la anatomía patológica (A-P) intraoperatoria del uréter derecho y CIS en la RTU vesical y con tumor del TUS asociado. La reimplantación con margen positivo no se asoció estadísticamente con recidiva en la anastomosis ni con recidiva en el TUS. Hubo relación entre A-P intraoperatoria de ambos uréteres y la definitiva. CONCLUSIONES: En nuestro estudio, la presencia de márgenes ureterales positivos no se asociaron con mayor riesgo de recidiva en la anastomosis o en el TUS. Aunque sigue siendo un tema a debate, una estrategia a seguir puede ser adaptar la biopsia fría ureteral al riesgo individual y realizarla a pacientes con CIS vesical

OBJECTIVES: To evaluate the association of positive margins in the intraoperative biopsy during radical cystectomy (RC) with the risk of recurrence in the uretero-ileal anastomosis or upper urinary tract (UUT), and identify potential risk factors for positive ureteral margins. METHODS: A retrospective, descriptive study was performed in patients treated with radical cystectomy due to transitional cell carcinoma (TCC), who underwent a cold biopsy of the ureteral margin at the time of cystectomy. A descriptive analysis and frequency distribution was performed. Fisher's test was used to calculate sensitivity and specificity and a survival analysis was performed. RESULTS: 230 patients were included. Prior to RC, transurethral resection of the bladder tumor and a CT scan were done. The percentage of positive margins was 4.81% for the right ureter and 4.27% for the left. Recurrence was detected in the anastomosis in 2.64% of the cases. In a 0.88% recurrence was found in the UUT (2 cases) at the level of left renal pelvis (1 case) and left kidney (1 case). In the multivariate analysis, neither recurrence in the anastomosis (p=1) or at the UUT (p=1) level during follow-up were significantly associated with the presence of positive margins. An association was found between the pathological biopsy of the right ureter and carcinoma in situ (CIS) of the bladder wall with UUT involvement. We found only association between the cold biopsy of the left ureter and tumor in left UTT. Reimplantation with positive margins was not statistically associated with neither ureteroileal anastomosis or UTT relapse. A relationship was found between the cold biopsy of both ureters and the definitive pathology. CONCLUSIONS: In our study, the presence of positive ureteral margins was not associated with an increased risk of recurrence in the anastomosis or UUT. Although it remains a topic for debate, a strategy to follow may be to adapt ureteral cold biopsies to individual risk, thus perform it in patients with bladder CIS

Ablación septal con alcohol en la miocardiopatía hipertrófica: Experiencia de 10 años de un centro de cardiología. Resultados inmediatos y seguimiento a 12 meses / Septal ablation with alcohol in hipertrophic miocardiopathy: Ten years experience in a cardiologic center. Immediate and long term results

Objetivo: Conocer las características demográficas, clínicas, hemodinámicas y su evolución intrahospitalaria a mediano plazo en la miocardiopatía hipertrófica septal obstructiva. Material y métodos: Estudio observacional, longitudinal con dirección retrospectiva, descriptivo y no comparativo (serie de casos) que incluye 21 pacientes con diagnóstico de miocardiopatía hipertrófica septal obstructiva con los siguientes criterios: clase funcional III-IV de la New York Heart Association refractarios a tratamiento y/o con gradiente ≥ 30 mmHg en reposo o ≥ 60 mmHg provocado y además con movimiento sistólico anterior o insuficiencia mitral > GII esto, por ecocardiografía. Resultados: Variables demográficas: edad promedio de la cohorte fue de 50 ± 16; distribución por género: hombres n = 8 (38.1%), mujeres n = 13 (61.9%); síntomas: angor n = 9 (42.9%), disnea n = 18 (85.7), síncope n = 5 (23.8); clases funcionales (New York Heart Association) (preablación): clase funcional 3 n = 12 (57.1%), clase funcional 4 n = 1 (4.8%); uso de fármacos: BB n =15 (71.4%), Verapamil n = 13 (61.9%), IECA n = 3 (14.3%), ECG: HVI n = 17 (81%), FA n = 1 (4.8%), BCRIHH n = 3 (14.3%); ecocardiográficas: eco basal PPVI 14.9 ± 4.4 mm, SIV 22.7 ± 4.9 mm, FE 65.5 + 7%, Gte.TSVI 106.9 ± 29.9 mmHg, grado IM-3 n = 7 (33.3%), grado IM-4 n = 10 (47.6%); postintervención Eco Gte TVSI 44.6 ± 24.3 mm, grado IM-3 n = 3 (14.3%), grado IM-4 n = 1 (4.8%), alcohol 3.4 ± 0.9 mL; estancia intrahospitalaria 5.9 ± 3 días, CPK-total 1466 ± 924, CK-MB 215 ± 128; complicaciones eléctricas BAV transitorio n = 11(52.9%), MCPD n = 1 (4.8), hemodinámicas-FE basal 65.5 + 16, FE post 62.2 ± 6.5, gte basal 106.33 ± 37 mmHg, Gte-post 44 ± 34 mmhg; evolución: 1 año CF-NYHA, CF1: n = 19 (90.5%), CF2: n = 2 (9.5%), eco Gte TSVI 22.0 ± 5.7 mmHg, SIV 20.7 ± 3.1 mm, FE (68.7 ± 6.2%), IM-0 n = 11 (52.4%), IM-1 n = 6 (28.6%), IM-2 n = 4 (19%); mortalidad intrahospitalaria del 0%. Conclusión: La ablación septal con alcohol es un método que tiene una alta tasa de éxito con una mejoría en cuanto a la calidad de vida del paciente y con un índice de complicaciones baja.

Objective: To know the demographic, clinical, hemodynamic, and hospital course, and medium term septal obstructive hypertrophic cardiomyopathy. Material and methods: Observational, longitudinal direction retrospective, descriptive and comparative (case series), including 21 patients with septal obstructive hypertrophic cardiomyopathy with the following criteria: functional class III-IV New York Heart Association refractory to treatment and/or ≥ 30 mmHg gradient at rest or ≥ 60 mm Hg provoked, and others have systolic anterior motion or mitral insufficiency > GII this by echocardiography. Results: Demographic variables: population-average age of the cohort was 50 ± 16 years, distribution by gender: men n = 8 (38.1%), women n = 13 (61.9%) symptoms: angor n = 9 (42.9%), dyspnea n = 18 (85.7), syncope n = 5 (23.8) CF-NYHA (pre-ablation): CF3 n = 12 (57.1%), CF4 n = 1 (4.8%); drug use: BB n = 15 (71.4%), verapamil n = 13 (61.9%), ACE inhibitors n = 3 (14.3%), ECG LVH n = 17 (81%), FA n = 1 (4.8%), LBHH n = 3 (14.3%); ecocardiogaphic-eco baseline: 14.9 ± 4.4 mm WPLV, IVS 22.7 ± 4.9 mm, EF: 65.5 ± 7%, Gte.TVG: 106.9 ± 29.9 mmHg, MI-3 grade n = 7 (33.3%), grade MI-4 n = 10 (47.6%) Post-intervention-eco gte TVG 44.6 ± 24.3 mm, grade MI-3 n = 3 (14.3%), grade MI-4 n = 1 (4.8%) 3.4 ± 0.9 ml alcohol, hospital stay 5.9 ± 3 days, CPK-total 1466 ± 924; CK-MB 215 ± 128, LVB transient electrical complications n = 11 (52.9%), permanent cardiac pacemaker n = 1 (4.8)-FE hemodynamic baseline: 65.5% ± 16, post-FE 62.2% ± 6.5; Gte Basal: 106.33 ± 37 mmhg GTE-post 44 ± 34 mmHg, evolution: 1 year follow-up CF-NYHA, CF1: n = 19 (90.5%), CF2: n = 2 (9.5%); Eco Gte 22.0 ± 5.7 mm Hg LVOT, 20.7 ± 3.1 mm SIV, FE (68.7 ± 6.2%), IM-0 n = 11 (52.4%), IM-1 n = 6 (28.6%), IM-2 n = 4 (19%), hospital mortality of 0%. Conclusion: The alcohol septal ablation is a method that has a high success rate, with an improvement in the quality of life of patients with a low complication rate.

Contaminantes ambientales neurotóxicos cercanos a nuestra vida diaria / Neurotoxic enviromental contaminants near our daily life

Chemical substances play an important role in life quality; they are present in household items and consumer products like furniture, cloths, toys, etc. However some of these substances could be dangerous for health and environment. Among the best known are the organohalogens pollutants like the polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs). These substances persist in the enviroment, they bioaccumulate and may cause adverse effects in humans health. There is increasing evidence that organohalogens cause neurotoxicity in rats and human brains during development. We have been studying the neurotoxicity of Aroclor 1254 (PCB mixture) and DE-71 (PBDE mixture) in collaboration with Currás-Collazo team (UC-MEXUS/CONACYT grants). We show in this paper the principal results of our research related with molecules that participate in the osmoregulatory system, learning and memory as vasopressin, PACAP and nitric oxide synthase. We exposed pregnant rats to this organohalogens perinatally; the pups were allowed to grow until three months old for an osmotic challenge. Brains were processed for immunfloures-cence, other group was used to evaluate memory with the passive inhibitory avoidance test and Western-blot was done for presynaptic proteins Synapsin I and Synaptophysin. We found a disruption in the content of VP, PACAP and nNOS suggesting that the PCB and PBDE exposure alter the function of hypothalamic neurons that regulates osmosis and water balance. We demonstrated also that PBDE treatment modifies systolic pressure and plasmatic osmolality compared with controls suggesting a cardiovascular alteration caused by PBDEs. We found an alteration in the nNOS activity in Aroclor-1254 treated rats. Memory test and presynaptic proteins expression showed an important reduction in males, suggesting that PCBs alters the expression and activity of nitric oxide and learning and memory. Therefore, due to the neurotoxicity of the organohalogens and its constant contact with humans there is a big concern about the lack of adequate legislation in Mexico and monitoring programs to evaluate the degree of contamination in the population, especially in infants as well as the regions most affected by such contamination.

Las sustancias químicas son importantes en nuestra calidad de vida; éstas están presentes en artículos domésticos y de consumo humano. Algunas son nocivas para la salud y el medio ambiente, como los contaminantes organohalogenados, los bifenilos policlorinados (PCB) y los éteres difenílicos polibrominados (PBDE). Existe evidencia de su neurotoxicidad en las ratas y los humanos sobre todo cuando la exposición es durante el desarrollo. Nuestro grupo se ha interesado en estudiar la neurotoxicicidad de los PCB y PBDE sobre la regulación del equilibrio hidroelectrolítico, el aprendizaje y la memoria, en colaboración con la doctora Currás-Collazo. En este artículo presentamos los hallazgos principales de estos estudios. Expusimos a ratas gestantes a estos organohalogenados y las crías se estudiaron a los tres meses de edad; se sometieron al modelo de estrés osmótico o a la prueba de aprendizaje y memoria (evitación pasiva). Los cerebros se procesaron para inmunofluorescencia para VP, nNOS, PACAP o histoquímica de la NADPH-d, Western-blot para nNOS y las proteínas presinápticas sinapsina I y sinaptofisina. Nuestros resultados mostraron en las ratas tratadas con los PCB y PBDE sometidas a estrés osmótico alteraciones en el contenido de VP, PACAP y NOS y un incremento en la presión sistólica y la osmolaridad plasmática al compararla con controles, sugiriendo que los PBDE alteran la función cardiovascular y osmorregulatoria. La prueba de aprendizaje mostró una disminución significativa de la adquisición y/o consolidación del aprendizaje y memoria en las ratas macho tratadas y alteraciones en la actividad de la NOS, la expresión de la nNOS y las sinapsina y sinaptofisina, lo que sugiere que la exposición perinatal a los PCB altera el aprendizaje y la memoria. Debido a la neurotoxicidad de los organohalogenados y a que estamos expuestos a ellos en nuestra vida diaria existe una gran preocupación por la falta de una legislación adecuada en México y programas de monitoreo para evaluar el grado de contaminación en la población mexicana especialmente en los infantes, así como las regiones más afectadas por dicha contaminación.

Los contaminantes ambientales bifenilos policlorinados (PCB) y sus efectos sobre el Sistema Nervioso y la salud / The polychlorinated biphenyls (PCBS) environmental pollutants and their effects on the Nervous System and health

Environmental pollution is a world-wide issue which is a matter for concern among the international community. Great industrialized cities are the most polluted and Mexico City is among them. However, pollution affects places which are far away from contaminated urban areas, thus damaging eco-systems. Environmental pollution is responsible for an alarming and increasing list of illnesses in humans, animals and plants. This has generated an international interest in this problem. From the 187 chemical agents considered toxic for living organisms, the Inter-Government Committee for the Negotiation of Persistent Organic Pollutants (Pops) has catalogued 12 as the most hazardous for life. Among them are the so-called polychlorinated biphenyls (PCBs). PCBs are a family of 209 structurally chlorinated compounds made up of chlorine, carbon and hydrogen. These compounds are chemically and thermally stable, insoluble in water, non-flammable, electrically resistant, with low volatility at normal temperatures, and bio-degradable only at high temperatures (1200°C). One of their main disadvantages is that they are subject to a process of bioaccumulation where their concentration increases along the food chain. Their physical properties make them widely used in industry, mainly in the electrical and building areas. Not long after PCBs were manufactured, it was determined that food for human intake such as milk, fish and eggs, to mention just a few, presented higher PCBs concentrations than those allowed by the Organism for US Environmental Protection (0.0005mg/l). It has been demonstrated that PCBs can cause damage to the endocrine, immunologic and Nervous Systems, among others. The underlying mechanism of action of these compounds is through the activation of the aril hydrocarbon receptor (AhR), a ligand-dependent cytosolic transcription factor. PCBs act like ligands and, given their lipophilic properties, enter cells by passive diffusion. Two co-chaperone proteins are bound to AhR to form an oligomer which dissociates when binding to a PCB. After ligand binding, a heterodimer is formed which translocates into the nucleus and links to specific DNA regions; this in turn regulates the transcription velocity of specific genes and produces genetic alterations that modify processes and functions in the cell. PCBs belong in the group of chemicals considered endocrine disruptors. Damage caused by these compounds can be irreversible. In the endocrine system they interfere with the production and regulation of steroid and thyroid hormones, acting as agonists or antagonists of hormone receptors. They impair endocrine metabolic pathways, such as those of thyroid hormones (T3 and T4), and inhibit carrier proteins such as transthyretin. Contaminants that harm the endocrine system also affect the reproductive function and disrupt various aspects of sexuality. In males, PCBs inhibit the synthesis of testosterone, alter masculinity, reduce sperm motility and the capacity of binding and penetrating the ovule, induce changes in the shape of the penis as well as its size, retard or inhibit testicle descent, and can generate testicular cancer. In females, they can cause early menarche (first menstruation), enhanced duration of menstrual bleeding, urogenital malformations, endometriosis, spontaneous abortion, fetal death, premature delivery and low-weight in offspring. Our group, as well as other research groups, has encountered that PCB administration to gestating rats causes an increment in offspring mortality, fetal miscarriages, low bodily weight of the offspring and a reduction in the number of males per litter. The immunological system is sensitive to chemicals such as PCBs which originate an immunological response; they act as immunotoxins that cause thymus atrophy, affect innate immunity, compromise host resistance and immunity mediated by B and T cells, as well as humoral immunity. PCBs and their metabolites are carcinogenic and act as general cancer promoters by enhancing the effects of other substances through the generation of oxygen reactive compounds that can induce DNA oxidative damage. Chronic PCB exposure can cause chromosomal aberrations; these compounds have been related to all types of cancer: mammary gland, liver, biliary tract, gastrointestinal, skin (especially malignant melanomas), lung, pancreas and brain. There is evidence that organisms are more vulnerable to PCB exposure during the early embryonic stages. These compounds can cross the placenta and affect the fetus; when they are present in human milk they keep the offspring under high PCB levels thus altering development. In addition, they can contribute to the interruption of growth and development of brain, organs and tissues. As a result, malfunctions or miscarriage occur. PCBs are involved in the neurodegeneration process since they affect dopaminergic neurons in caudate nucleus, ventral tegmental area and substantia nigra. These compounds disrupt neuronal mechanisms such as vesicular transport and dopamine release which lead to cellular death similar to that described for diseases such as Parkinson's. Perinatal exposure to PCBs is associated with neurodevelopmental deficiencies of infants which consist of dysfunctions at the neuropsychological level such as in verbal learning (syllables, words and concepts), performance functions, changes in attention and psychomotor development. Acute or chronic exposure to PCBs is associated with cephalea, insomnia, nervousness, irritability, depression and anxiety; these symptoms in turn modify behavior. At the neurophysiological level, these contaminants impair excitatory and inhibitory synaptic transmission in the hippocampus, inhibit long-term potentiation and synaptic plasticity, alter some mechanisms of cell signaling (GABAergic pathway), and deteriorate learning and memory. Recently, these compounds have been related to cognitive alterations. Our group demonstrated that the administration of PCB-77 and Aroclor 1254 during gestation inhibits the enzymatic activity of nitric oxide synthase (NOS) in 10-day postnatal pups. These rats presented degenerative morphological neuronal changes such as shrinking, picnosis, loss of neurites, neuronal death and decrease in the number of nitrergic neurons in the paraventricular and supraoptic hypothalamic nuclei. We also reported that in these nuclei a decrease in immunoreactivity to vasopressin and neuronal NOS is observed. The evidence in PCB studies is conclusive. The exposure to these environmental toxins interferes with the functioning of various organs and systems such as the endocrine and Nervous Systems, not only in humans but also in animals. These contaminants pose a risk factor for a wide number of neurodegenerative alterations.

La contaminación ambiental es un grave problema mundial que actualmente preocupa a la comunidad internacional. Las grandes ciudades industrializadas, como la de México, son las más contaminadas. Sin embargo, la contaminación llega hasta zonas alejadas de donde se produce y afecta los ecosistemas. La contaminación es responsable de una alarmante y creciente lista de enfermedades en el hombre, los animales y las plantas. Los bifenilos policlorados (PCB) se catalogaron dentro de los 12 contaminantes orgánicos más tóxicos para los organismos vivos. Sus propiedades físicas hicieron que se usaran ampliamente en la industria. No son biodegradables y se acumulan en el ambiente, se transfieren dentro de la cadena alimenticia y tienden a concentrarse más al final de ésta, por lo que en los alimentos se determinaron concentraciones que sobrepasaban los límites establecidos por el Organismo de Protección del Ambiente de los Estados Unidos. Se demostró que los PCB afectan la función de los sistemas endocrino, inmunológico y nervioso, entre otros. El mecanismo de acción descrito para los PCB, es por medio de la activación del receptor aril hidrocarburo, un factor de transcripción citosólico dependiente de ligando. Los PCB actúan como ligandos y son lipofílicos, por lo que entran a la célula y llegan al núcleo para unirse al ADN, lo cual altera la trascripción de genes específicos y provoca alteraciones genéticas que conducen a cambios en los procesos y funciones celulares. Los PCB interfieren con la producción y regulación de las hormonas esteroides y tiroideas al actuar como antagonistas o agonistas de los receptores hormonales. Afectan la función reproductora y alteran diferentes aspectos de la sexualidad. Como otros grupos de investigación, el nuestro ha observado que la administración de PCB a ratas gestantes causa un incremento de la mortalidad de las crías, pérdida fetal, peso corporal bajo y una reducción en el número de machos por camada. Los PCB actúan como inmunotoxinas que causan la atrofia del timo y afectan la respuesta inmune. Los PCB y sus metabolitos son carcinogénicos debido a la generación de especies reactivas de oxígeno que pueden producir daño oxidativo al ADN, provocar aberraciones cromosómicas y generar cáncer de mama, hígado, tracto biliar, gastrointestinal, cerebral, etc. Los organismos son más vulnerables a la exposición de los PCB durante las etapas tempranas del desarrollo embrionario. Los PCB atraviesan la placenta y llegan al feto, permanecen en la leche materna y mantienen niveles altos en las crías. Los PCB afectan así el desarrollo del Sistema Nervioso, los órganos y los tejidos, y pueden llevar a la pérdida fetal. También se asocian a deficiencias en el neurodesarrollo del niño y a alteraciones neuropsicológicas en la atención, el aprendizaje y el desarrollo psicomotor. La exposición aguda o crónica a los PCB se asocia con cefalea, insomnio, nerviosismo, irritabilidad, depresión y ansiedad. Los PCB participan en el proceso de neurodegeneración al afectar el sistema dopaminérgico. En el nivel neurofisiológico, afectan la transmisión sináptica excitatoria e inhibitoria hipocampal; inhiben la potenciación a largo plazo y la plasticidad sináptica; alteran mecanismos de señalización celular como el GABAérgico, en el aprendizaje y la memoria, y producen alteraciones cognoscitivas. Nuestro grupo demostró que la administración de los PCB durante la gestación inhibe la actividad de la enzima sintasa del óxido nítrico y provoca cambios neuronales morfológicos degenerativos en los núcleos paraventricular y supraóptico hipotalámicos. Las evidencias de los estudios realizados con los PCB son concluyentes en cuanto a que la exposición a estos tóxicos ambientales interfiere con el funcionamiento de diferentes órganos y sistemas y a que son un factor de riesgo para un amplio número de alteraciones neurodegenerativas. Actualmente, las poblaciones están expuestas a concentraciones que exceden los niveles límite tolerables recomendados por la Organización Mundial de la Salud. Nuestro grupo está analizando las alteraciones de estos contaminantes en el nivel neuroendocrino y en algunos aspectos del aprendizaje y la memoria. Dada la relevancia de los efectos de los PCB en la salud y de la falta en México de una valoración de los niveles de los PCB existentes en personas y alimentos, es importante que las instituciones de salud fomenten y apoyen las investigaciones en esta área.

Doble sistema pielocalicial completo bilateral / Complete bilateral pelvicalyceal system duplication

No disponible

Anomalía de Ebstein / Ebstein anomaly

We evaluated the results for primary repair of Ebstein anomaly in 61 patients, both adults and children. The records were reviewed of patients undergoing repair of Ebstein anomaly at the Congenital Heart Surgery Service of the National Institute of Cardiology [quot ]Ignacio Chávez[quot ] from January 1993 to August 2003. Functional, demographic, and echocardiographic parameters were studied both preoperatively and postoperatively, along with functional status and adverse events. The repair technique involved vertical plication of the atrialized ventricle and valve leaflet reimplantation after clockwise rotation or replacement of tricuspid valve. Ebstein repair has good functional outcomes in patients despite residual tricuspid regurgitation, likely because of reduction in right ventricular volume loading and relative annular and ventricular plasticity. Intraoperative radiofrequency ablation represents an important adjunctive treatment for intractable arrhythmias, which may now represent relative indications for operative intervention.

Tratamiento quirúrgico de lafibrilación auricular crónica asociada a valvulopatía mitral / Surgical treatment of atrial fibrillation associated with mitral valve disease

The modified Cox maze procedure is the gold standard for ablation of atrial fibrillation in patients undergoing mitral valve surgery, and new approaches to atrial fibrillation ablation must be compared with it. Therefore, we sought to determine the time-related prevalence of atrial fibrillation and its risk factors after combined Cox maze and mitral valve surgery. In some patients undergoing mitral valve surgery and a Cox maze procedure, atrial fibrillation recurs over time, mandating close, long-term follow-up of heart rhythm. Earlier operation should be considered to improve results in selected patients.

Aspectos clínicos de criss-cross: A propósito de un caso / Clinic aspect of criss-cross: a case report

A 1-month-old girl was referred at our Institution with a history of heart failure and cyanosis. We established diagnosis of multiple congenital heart disease with criss-crossed atrioventricular connections but concordant. This type of anomaly has a variety of presentations of high diagnostic complexity. The multiple lesions included double outlet of the right ventricle, right subaortic stenosis, ventricular septal defect, coarctation of the aorta with hypoplasia of the arch, and persistent patency of the arterial duct, established through echocardiography, angiocardiography and magnetic resonance. These findings prompted palliative surgery and correction of the aortic arch.

Origen anómalo de la arteria pulmonar derecha y estenosis de vena pulmonar superior izquierda / Anomalous origin of the right pulmonary artery and left pulmonary vein stenosis

We present a case of a 9 month old female with a history of cyanosis. The cardiovascular evaluation included angiocardiogram and magnetic resonance. The diagnosis was: origin of the right pulmonary artery from the ascending aorta, stenosis of the left superior pulmonary vein, patent ductus arteriosus and severe pulmonary hypertension. Surgical treatment consisted in correcting all congenital heart defects. The patient is doing well at home.

Resultados del reimplante coronario para la corrección del origen anómalo de la coronaria izquierda a partir de la arteria pulmonar / Outcomes of coronary reimplantation for correction of anomalous origin of left coronary artery from pulmonary artery

Introducción y objetivos. Describir nuestra experiencia en la corrección quirúrgica del origen anómalo de la arteria coronaria izquierda del tronco de la arteria pulmonar (ALCAPA), con énfasis en la técnica del reimplante coronario y sus resultados. Métodos. Se realizó un estudio descriptivo, longitudinal y retrospectivo de los pacientes con ALCAPA operados con técnica de reimplante coronario en un periodo de 19 años. Se exponen tres técnicas del reimplante coronario, dependiendo de la situación de la coronaria izquierda anómala, y la evolución postoperatoria en términos de morbimortalidad. Resultados. Se analizó a 15 pacientes (el 86% mujeres) con una media de edad de 6,2 años (2 meses-24 años). El 80% se hospitalizó por insuficiencia cardiaca. El 67% tenía disfunción ventricular izquierda y el 27%, insuficiencia mitral importante o grave. Se practicó cirugía valvular mitral concomitante en 4 pacientes. Las principales complicaciones postoperatorias inmediatas fueron bajo gasto cardiaco (38%), derrame pleural (17%) e isquemia transitoria (13%). No hubo mortalidad operatoria ni a medio plazo. Conclusiones. El reimplante coronario es la opción quirúrgica de elección para el manejo de los pacientes con ALCAPA por su excelente supervivencia posquirúrgica y su baja morbilidad operatoria (AU)

Introduction and objectives. We report our experience in the surgical correction of anomalous origin of left coronary artery from pulmonary artery (ALCAPA), with an emphasis on the coronary reimplantation technique and its outcome. Methods. We designed a retrospective, longitudinal, descriptive study that included patients with ALCAPA who underwent surgery involving coronary reimplantation over a 19-year period. We describe perioperative details such as variations in the surgical technique and the postoperative outcome in terms of morbidity and mortality. Results. We studied 15 patients (86% females) with a mean age of 6.2 years (range, 2 months to 24 years). Heart failure was the principal cause for hospitalization in 80% of our patients. Left ventricular dysfunction was present in 67%, and 27% had significant or severe mitral valve regurgitation. We describe 3 surgical techniques for coronary reimplantation, the choice of which depends on the site of origin of the anomalous left coronary artery. Four patients underwent an additional mitral valve procedure. The most common immediate postoperative complications were low cardiac output (38%), pleural effusion (17%), and transient ischemia (13%). There was no operative or medium-term mortality. Conclusions. Coronary reimplantation is the technique of choice for surgical correction of ALCAPA due to the excellent postoperative survival and low operative morbidity (AU)

Ablación transquirúrgica de vía accesoria atrioventricular en anomalía de Ebstein / Surgical radioerequency catheter ablation of accessory pathways in Ebstein's anomaly

Fueron estudiados 13 pacientes con anomalía de Ebstein con taquicardia por reentrada atrioventricular y al menos una vía accesoria. En 7 pacientes (53.8%) existía una vía accesoria y en 6 pacientes (46.1%) vías múltiples. En 5 pacientes (38.4%) se encontró vía accesoria tipo Mahaim. Un total de 22 vías accesorias fueron identificadas de las cuales 2 (9%) eran ocultas. El 100% se localizaron en el anillo tricuspídeo. Los sitios más frecuentes de ubicación fueron: región lateral derecha con 11 (50%) y postero-septal derecha con 5 (22.7%). Diez pacientes recibieron tratamiento mediante ablación con radiofrecuencia vía transquirúrgica y tres mediante sección quirúrgica. Se obtuvo un éxito de 100%. No se presentaron complicaciones durante los procedimientos. Conclusión: La ablación transquirúrgica de vías accesorias atrioventriculares en pacientes con anomalía de Ebstein es un procedimiento seguro y eficaz.

Thirteen patients with Ebstein anomaly and atrioventricular reentrant tachycardia and at least one accessory pathway were included in this study. One accessory pathway in 7 (53.8%) patients and multiple accessory pathways in 6 (46.1%) were found. Mahaim accessory pathway was observed in 5 (38.4%) patients. A total of 22 accessory pathways was found, 2 (9%) were concealed. In all (100%), the accessory pathways were located in the tricuspid ring. The most frequent regions were right lateral free wall with 11 (50%) and 5 right posteroseptal (22.7%). Ten patients underwent surgical radiofrequency catheter ablation and three subjected to surgical section. We obtained success in 100%. No complications were observed during the procedures. In conclusion, surgical ablation therapy in patients with accessory pathways and Ebstein's anomaly is safe and effective.

Diverticulum of Kommerell / Divertículo de Kommerell

A case of an 11-months-old girl with vomiting and laryngeal stridor is presented, and in whom a Kommerell diverticulum was demonstrated, which is a rare variant of the incomplete vascular ring. It is well known that the magnetic resonance is the best study to define this malformation. In this patient, it was the cardiac catheterization which allowed to define the structures that constituted the vascular ring. The patient was surgically treated in a successful way. The embryological knowledge of the transformations of the aortic arches offers great assistance in the understanding of all the types of vascular rings.

Se presenta el caso de lactante de 11 meses con historia de vómitos y estridor laríngeo secundaria a una rara variante de anillo vascular, divertículo de Kommerell. La resonancia magnética es considerada como el estudio ideal para definir la malformación, sin embargo, en este paciente, fue la angiografía la que permitió definir las estructuras del anillo vascular. El paciente fue tratado quirúrgicamente de manera exitosa. El conocimiento embriológico permite un adecuado entendimiento de los diferentes tipos de anillo vascular.

Cirugía de Fontan: Factores de riesgo a corto y mediano plazo / Fontan operation: factors influencing early and late outcomes

Se presenta un análisis retrospectivo de pacientes sometidos a cirugía de Fontan, de enero de 1989 a diciembre 2003, con el fin de evaluar los resultados, así como las variables clínicas y hemodinámicas que inciden en su morbilidad y mortalidad. Se estudiaron un total de 81 pacientes con los siguientes diagnósticos: 53 con atresia tricuspídea, 14 con atresia pulmonar con septum intacto, 11 con conexión atriouniventricular y 3 con anomalía de Ebstein. A 61 pacientes se les realizó Fontan con túnel intra-atrial y en 20 se utilizó un tubo extracardíaco, fenestrados en 53 pacientes. La mortalidad operatoria (< 30 días) fue 13% para atresia tricuspídea y 25% en el resto, siendo básicamente ésta por choque cardiogénico y arritmias graves. La sobrevida global fue de 71% en 55 meses de seguimiento. Hubo que desmantelar el Fontan en 5 casos. De las diversas variables analizadas se encontró 2.8 veces más riesgo de morir en pacientes sin fenestración y 3.6 veces cuando a las 72 hrs postquirúrgicas la presión de atrio izquierdo fue > 10 mmHg y la presión media de la arteria pulmonar > 20 mmHg. Las complicaciones más relevantes fueron: arritmias (38%), enteropatía perdedora de proteínas (8%) y eventos trombóticos cerebrales (1 %). El 52% de los pacientes han reingresado siendo las principales causas falla hemodinámica e infecciones.

The purpose of this retrospective study was to determine the outcome of patients who underwent a Fontan procedure at National Heart Institute "Ignacio Chavez", Mexico, from January 1989 to December 2003. We had 81 patients with a mean age of 7 years old: 53 with tricuspid atresia, 14 with pulmonary atresia and intact septum, 11 with univentricular atrioventricular connection and 3 with Ebstein's anomaly. An intra-atrial tunnel was performed on 61 patients and an extracardiac conduit on the rest. Of all, 53 underwent a fenestration. The surgical mortality was 13% fortricuspid atresia and 25% for the other diseases. We had an overall mortality of 28.4%, being the main causes cardiogenic shock and arrhythmia. The global survival was 71% in 55 months of following. Takedown was indicated on 5 patients. The patients without fenestration showed to have 2.8 times more risk of death. The mean pulmonary artery pressure > 20 mm Hg plus the left atrium pressure > 10 mmHg increased the death risk 3.6 times. Of the 52% who required readmission, the main causes were hemodynamical failure and infections. The more relevant complications were: arrhythmia (38%), protein-losing enteropathy (8%) and thrombotic cerebral events (1.4%).