Proteínas oxidadas de origen animal y su impacto sobre la salud intestinal / Oxidized proteins of animal origin and their impact on intestinal health / Proteínas oxidadas de origem animal e seu impacto na saúde intestinal

Los alimentos de origen animal como la carne de pollo, res, pescado y cerdo poseen una amplia demanda en todo el mundo debido, entre otros aspectos, a su valor nutricional, asociado al alto contenido proteico. No obstante, este tipo de proteínas son susceptibles de sufrir reacciones de oxidación, las cuales pueden mediar procesos de fragmentación, agregación, pérdida de solubilidad, funcionalidad y digestibilidad proteica; eventos implicados en la pérdida de su valor nutricional. En este sentido, las proteínas agrega­das tienden a no ser digeridas en el tracto gastrointestinal y acumularse en el intestino (colon), donde la microbiota colónica las degrada a productos mutagénicos como fenol y p-cresol, lo que incrementa el riesgo de cáncer colorrectal. Por otra parte, los ami­noácidos o péptidos oxidados liberados en la digestión podrían incorporarse en las vías de señalización celular intestinal y favorecer o exacerbar procesos intestinales crónicos como colon irritable o enfermedad de Crohn. Debido al gran interés de esta temática en los últimos años, el objetivo de esta revisión es realizar una descripción general del impacto de proteínas oxidadas de origen animal sobre la salud intestinal.

Animal foods such as chicken, beef, fish and pork are in wide demand throughout the world due, among other things, to their nutritional value, associated with their high protein content. However, this type of protein is susceptible to oxidation reactions, which can mediate processes of fragmentation, aggregation, loss of solubility, functionality, and protein digestibility, which are events involved in the loss of their nutritional value. In this sense, aggregated proteins tend not to be digested in the gastrointestinal tract and accumulate in the intestine (colon), where the colonic microbiota degrades them into mutagenic products such as phenol and p-cresol, which increases the risk of colorectal cancer. On the other hand, the oxidized amino acids or peptides released in digestion could be incorporated into intestinal cell signaling pathways and favor or exacerbate chronic intestinal processes such as irritable bowel syndrome or Crohn's disease. Due to the great interest in this topic in recent years, the objective of this review is to provide a general overview of the impact of oxidized proteins of animal origin on intestinal health.

Alimentos de origem animal como frango, carne bovina, peixe e carne suína são muito procurados em todo o mundo devido, entre outros fatores, ao seu valor nutricional, associado ao seu alto teor de proteínas. No entanto, esse tipo de proteína é suscetível a reações de oxidação, que podem mediar processos de fragmentação, agregação, perda de solubilidade, funcionalidade e digestibilidade da proteína; eventos envolvidos na perda de seu valor nutritivo. Nesse sentido, as proteínas agregadas tendem a não ser digeridas no trato gastrointestinal e se acumulam no intestino (cólon), onde a microbiota colônica as degrada em produtos mutagênicos como fenol e p - cresol, aumentando o risco de câncer colorretal. Por outro lado, os aminoácidos ou peptídeos oxidados liberados na digestão poderiam ser incorporados às vias de sinalização das células intestinais e favorecer ou exacerbar processos intestinais crônicos, como a síndrome do intestino irritável ou a doença de Crohn. Devido ao grande interesse neste tema nos últimos anos, o objetivo desta revisão é fornecer uma descrição geral do impacto das proteínas oxidadas de origem animal na saúde intestinal.

[Hypersensitivity reactions associated with the use of asparaginase in children with acute lymphoblastic leukemia]. / Reacciones de hipersensibilidad asociadas al uso de asparaginasa en niños con leucemia linfoblástica aguda.

INTRODUCTION: The treatment of acute lymphoblastic leukemia (ALL) includes the use of asparaginase (ASP), a drug associated with hypersensitivity reactions (HSR) that requires discontinuing its use. OBJECTIVE: To determine the incidence of HSR associated with ASP that require discontinuation of its use and des cribe them, and to verify if there is a relationship between HSR incidence and protocols or survival. PATIENTS AND METHOD: Retrospective study. Clinical records of all patients (1-15 years) diagnosed with ALL between January 2010 and December 2015 at the Hospital Luis Calvo Mackenna were reviewed. The incidence of HSR to ASP was determined and classified according to the CTCAE v5.0 severity score. We analyzed the relative risk of HSR using Fisher's test and the survival with the Kaplan-Meier estimator. RESULTS: 110 patients were collected. During the first treatment (ALL-IC- BFM), the incidence of HSR to L-ASP was 55%, therefore it was changed to PEG-ASP as second-line treatment, and 44% of them had HSR, and ASP should discontinued in 25% of patients. Of all the HSR to ASP, 77% were anaphylactic (CTCAE 3-5). Patients treated with augmented IB protocol were at higher risk of not completing ASP treatment due to HSR, RR 3.81 (95% CI, 1.98-7.31, p = 0.0001). Patients without HSR in ALL-IC-BFM were at lower risk of relapse, HR 0.29 (95% CI, 0.14-0.62, p = 0.0013). Considering all treatments (ALL-IC-BFM and relapse), patients who completed the ASP treatment had higher overall survival, HR 0.20 (95% CI, 0.07-0.57, p = 0.0026). CONCLUSIONS: HSR to ASP that require discontinuation of treatment are frequent in children with ALL, most of them were severe anaphylactic reactions. This study suggests a better prognosis in patients without HSR to ASP.

First report of Dermoglyphus passerinus (Analgoidea: Dermoglyphidae) and Strelkoviacarus sp.(Analgidae: Anomalginae) in canaries (Serinus canaria domestica) in Mexico.

Feather mites are the most numerous group of symbionts permanently associated to birds. They are highly specialized to particular microhabitats on their hosts and most of them may be considered as commensals, but several species are parasites. This manuscript documents for the first time a combined infestation by quill mites Dermoglyphus passerinusGaud, 1974 (Analgoidea: Dermoglyphidae) and feather mites Strelkoviacarus sp.(Analgidae: Anomalginae), in domestic canaries (Serinus canaria domestica) (Linnaeus, 1758) (Passeriformes: Fringillidae) in Mexico City, Mexico. Description of the case, the feather and skin lesions, and findings associated with the infection are presented. This manuscript aims to contribute to the knowledge of mite species that can affect the plumage of Serinus canaria domestica; as well as to the diagnosis and control of these infestations.

Características craneofaciales de pacientes obesos en Chile. Estudio Preliminar / Craniofacial characteristics of obese patients in Chile. Preliminary study

Resumen Introducción: La obesidad es un problema a nivel global que enfrenta el siglo XXI y Chile no se escapa de esta realidad. Así como existen características mórbidas de pacientes con obesidad, también existen características craneofaciales similares en estos pacientes. El estado nutricional es un factor que influencia el desarrollo de una persona en general, lo que tiene implicancias en el tratamiento ortodóncico, ortopédico y quirúrgico de las alteraciones maxilo - mandibulares de los pacientes. Objetivo: Investigar si la morfología craneofacial difiere entre los adolescentes obesos y los de peso normal. Métodos: Estudio retrospectivo, se basó en la comparación de medidas craneofaciales obtenidas del análisis cefalométrico, utilizando teleradiografías laterales, de dos grupos: grupo estudio (IMC mayor a 30, obeso) y grupo control (IMC normal). Resultados: Se observaron dimensiones maxilares y mandibulares mayores en el grupo estudio comparado con los pacientes del grupo control. Las medidas para la dimensión maxilar tuvieron diferencia significativamente estadística. Conclusiones: El aumento de peso es un factor importante que puede afectar los patrones de crecimiento craneofacial y debe ser tomado en consideración durante la planificación del tratamiento ortodoncico en pacientes adolescentes.

Abstract Introduction: Obesity is a global problem in the the 21st century and Chile does not escape this reality. Just as there are morbid characteristics of patients with obesity, there also share similar craniofacial characteristics. Nutritional status is a factor that influences the a person´s general development , which has implications in the orthodontic, orthopedic and surgical treatments of maxillo-mandibular alterations. Objective: Investigate whether craniofacial morphology differs between obese and average-weight adolescents. Methods: A retrospective study based on the comparison of craniofacial measures obtained from the cephalometric analysis, using lateral cephalograms, from two groups: study group (BMI over 30, obese) and control group (normal BMI). Greater maxillary and mandibular dimensions were observed in the study group compared to the patients in the control group. The measurements for de maxillary dimension had a statistically significant difference. Conclusions: Weight gain is an important factor that can affect craniofacial growth patterns and should be taken into consideration during the planning of orthodontic treatment in adolescent patients.

Outbreak of Systemic Avian Pox in Canaries (Serinus canaria domestica) Associated with the B1 Subgroup of Avian Pox Viruses.

This study reports an outbreak of avian pox in a quarantine of canaries imported from Europe, with a mortality of 30% and clinical signs of dyspnea and blepharoconjunctivitis. During necropsy, beak cyanosis, serous blepharitis, caseous sinusitis, oropharyngitis, tracheitis, pulmonary edema, pneumonia, fibrinous airsacculitis, and splenomegaly were observed. Microscopically, edema, epithelial hyperplasia, hydropic degeneration, and vacuolated eosinophilic intracytoplasmic inclusion bodies were found; similar lesions were observed in the thymus, spleen, and other organs. The virus was isolated in chicken embryos, and it was identified and characterized using a sequence of 913 nucleotides of the DNA polymerase gene. Pathologic characteristics and molecular biology indicate the systemic presence of avian pox associated with an avipoxvirus of the B1 subgroup. Additionally, other lesions associated with Aspergillus sp., Macrorhabdus ornithogaster, and Isospora sp. were found, which could contribute to the high mortality. Canarypox virus should be considered a differential diagnosis in cases of dyspnea and high mortality in canary flocks.

Reporte de caso- Brote de viruela aviar sistémica en canarios (Serinus canaria domestica) asociado con el virus de la viruela aviar subgrupo B1. En este estudio se reporta un brote de viruela aviar en unos canarios importados de Europa que estaban bajo cuarentena, con una mortalidad del 30% y signos clínicos de disnea y blefaroconjuntivitis. Durante la necropsia, se observó cianosis de pico, blefaritis serosa, sinusitis caseosa, orofaringitis, traqueítis, edema pulmonar, neumonía, fibrinosa respiratoria y esplenomegalia. Microscópicamente, se encontró edema, hiperplasia epitelial, degeneración hidrópica y cuerpos de inclusión intracitoplásmicos eosinófilos vacuolados; Se observaron lesiones similares en el timo, el bazo y otros órganos. El virus se aisló en embriones de pollo, se identificó y caracterizó analizando una secuencia de 913 nucleótidos del gene de la polimerasa de ADN. Las características patológicas y la biología molecular indican la presentación sistémica de la viruela aviar asociada a un avipoxvirus del subgrupo B1. Además, se encontraron otras lesiones asociadas con Aspergillus sp., Macrorhabdus ornithogaster y Isopora sp., lo que pudo contribuir a la alta mortalidad. El virus de la viruela del canario debe considerarse un diagnóstico diferencial en casos de disnea y alta mortalidad en parvadas de canarios.

Impacto de la tuberculosis en el hospital de Puerto Montt / Impact of tuberculosis in Puerto Montt hospital, Chile

Resumen Objetivo: Dimensionar la demanda de atención y/u hospitalización de la tuberculosis (TBC) en el Hospital de Puerto Montt (HPM). Método: Revisión retrospectiva de los registros de TBC del Servicio de Salud del Reloncaví (SSDR) y del HPM entre los años 2011 y 2015. Se incluyeron todos los casos de TBC activa vistos en forma ambulatoria u hospitalizada en el HPM. Resultados: Se diagnosticaron en el SSDR 298 casos de TBC, y de ellos un 64% (192/298) fue pesquisado en el HPM. Se presentan datos socioeconómicos, epidemiológicos, clínicos, de laboratorio y forma de diagnóstico de 180 casos, que cumplieron criterios de inclusión: varones 62%, edad media 44 ± 19 años. El 72% correspondieron al estrato social de menores ingresos, 4% indigentes, solo 14% poseía enseñanza media completa, 11% analfabetos, ruralidad 19%. Las principales co-morbilidades fueron alcoholismo (17%), VIH (12%), Diabetes (10%). En aquellos con TBC pulmonar o pleural (128) el tiempo con síntomas con frecuencia era prolongado (15% > 90 días) y la radiología mostraba enfermedad avanzada: infiltrados bilaterales 73%, compromiso > 3 lóbulos 55%, una o más cavitaciones 34%. Se hospitalizó el 71% (126/180), 50% por necesidad de estudio, 48%por gravedad. El 8% necesitó Unidad de Paciente Crítico (UPC). Fallecieron 24 pacientes (13%). Se asoció significativamente a mortalidad el analfabetismo y necesidad de UPC. Conclusiones: En el SSDR la TBC es un problema sanitario que afecta principalmente a poblaciones más pobres y vulnerables.

Backgroud: Tuberculosis (TB) is still a problem that impacts on hospitals of high complexity. Aim: To assess demand for care and/or hospitalization because of TB in Puerto Montt Hospital (PMH), located in the southern of Chile. Patients and Methods: Retrospective study of all Reloncaví Health Service (RHS) and PMH clinical records, between 2011 and 2015. We include all ambulatory or hospitalized cases of active TB registered in PMH during the period of the study. Results: In RHS there were 298 cases of TB and 64% of them (192/298) was detected in HPM. We present social, economic, epidemiological, clinical, laboratory studies, and specific type of diagnosis of 180 cases that met inclusion criteria: men 62%, mean age 45 ± 19 years-old. The population with lower income was 72%, 4% homeless, 14% with complete high school, 11% illiterate and 19% lived at country side. Main co-morbidities were alcoholism 17%, HIV 12%, Diabetes Mellitus 10%. In the specific group of lung/pleural TB (128 cases) the time with symptoms was often prolonged (15% > 90 days) and imagen studies showed advanced pathology: bilateral infiltrates 73%>, affecting three or more lobes 55%, cavitations 34%. 71% (126/180) were hospitalized, because of necessity of more study (50%) or severity (48%), 8% required to enter to the Critical Care Unit (CCU). Twenty-four patients died (13%). Illiteracy and the need for CCU were associated with mortality. Conclusions: In RHS TB is a sanitary problem that affects principally the most poor and vulnerable populations.

Chemically induced hypoxia promotes differential outcomes over preadipocyte- or adipocyte-macrophage communication.

Expansion of white adipose tissue induce insufficient vascularization, driving hypoxia and low-grade inflammation. Resident preadipocytes are thought to be involved. We evaluated the effects of hypoxia over preadipocytes and adipocytes, to determine which cellular type impacts the most over macrophages activation. 3T3-L1 cells were either differentiated, or maintained undifferentiated. Each group was subjected to the presence or absence of chemical hypoxia (200 µM CoCl2) for 24 h. Conditioned media were used as treatment for murine RAW264.7 macrophages for 24 h. Gene expression of HIF-1α and TNF-α, and the release of several markers were assessed. It was observed that culture media from hypoxic preadipocytes induced greater expression of inflammatory markers and NO release than culture media from hypoxic adipocytes, by macrophages. Gene expression correlated closer with inflammatory markers release specially on macrophages treated with conditioned media from preadipocytes. Hence, the present work highlights the importance of preadipocytes on inflammatory conditions in vitro.

Brown tumour in phalanx of the ring finger due to chronic kidney failure. A case report. / Tumor pardo en falange del dedo anular por insuficiencia renal crónica. Reporte de un caso.

Brown tumours are highly vascular lytic bone lesions found in primary and secondary hyperparathyroidism. The brown term is given due to the red-brown colour of the tissue, which is due to the accumulation of hemosiderin. The case is presented of a 29 year-old male with chronic renal failure, who had a mass in the tip of the ring finger after a trauma of 4 months onset, which had increased progressively in size and pain. He was treated surgically, by amputation, with no recurrence 10 months after the surgery.

Características craneofaciales de pacientes obesos en Chile. Estudio Preliminar

Introducción: La obesidad es un problema a nivel global que enfrenta el siglo XXI y Chile no se escapa de esta realidad. Así como existen características mórbidas de pacientes con obesidad, también existen características craneofaciales similares en estos pacientes. El estado nutricional es un factor que influencia el desarrollo de una persona en general, lo que tiene implicancias en el tratamiento ortodóncico, ortopédico y quirúrgico de las alteraciones maxilo - mandibulares de los pacientes. Objetivo: Investigar si la morfología craneofacial difiere entre los adolescentes obesos y los de peso normal. Métodos: Estudio retrospectivo, se basó en la comparación de medidas craneofaciales obtenidas del análisis cefalométrico, utilizando teleradiografías laterales, de dos grupos: grupo estudio (IMC mayor a 30, obeso) y grupo control (IMC normal). Resultados: Se observaron dimensiones maxilares y mandibulares mayores en el grupo estudio comparado con los pacientes del grupo control. Las medidas para la dimensión maxilar tuvieron diferencia significativamente estadística. Conclusiones: El aumento de peso es un factor importante que puede afectar los patrones de crecimiento craneofacial y debe ser tomado en consideración durante la planificación del tratamiento ortodoncico en pacientes adolescentes.

Introduction: Obesity is a global problem in the the 21st century and Chile does not escape this reality. Just as there are morbid characteristics of patients with obesity, there also share similar craniofacial characteristics. Nutritional status is a factor that influences the a person´s general development , which has implications in the orthodontic, orthopedic and surgical treatments of maxillo-mandibular alterations. Objective: Investigate whether craniofacial morphology differs between obese and average-weight adolescents. Methods: A retrospective study based on the comparison of craniofacial measures obtained from the cephalometric analysis, using lateral cephalograms, from two groups: study group (BMI over 30, obese) and control group (normal BMI). Greater maxillary and mandibular dimensions were observed in the study group compared to the patients in the control group. The measurements for de maxillary dimension had a statistically significant difference. Conclusions: Weight gain is an important factor that can affect craniofacial growth patterns and should be taken into consideration during the planning of orthodontic treatment in adolescent patients.

Association between Chronic Pain and Frailty in Mexican Elders.

Chronic pain is defined as pain lasting longer than six weeks and is one of the main complaints in elderly subjects. Frailty is a pathological condition that increases an individual's vulnerability by diminishing their homeostatic reserve, and it is considered a mortality risk factor. We examined the association between chronic pain and frailty in subjects who were recruited from a check-up clinic in Mexico City. Chronic pain and frailty were evaluated in 131 subjects through validated questionnaires. Descriptive and analytical statistics were performed. Of the participants, 41.9% presented with chronic pain, and 12.2% were frail. The unadjusted OR for the presence of frailty in subjects with chronic pain was 14.3 (95%CI 3.0-67.8), and the phi coefficient showed a weak positive correlation between the variables (Φ=0.352, p<0.001). In conclusion, chronic pain is associated with a higher risk of frailty. Well-timed diagnosis and treatment of chronic pain can help prevent dependency in these individuals.

[Limitation of the therapeutic effort in pediatric intensive care]. / Limitación del esfuerzo terapéutico en cuidados intensivos pediátricos.

Pediatric intensive care is a relatively new medical specialty, which has experienced significant technological advances in recent years. These developments have led to a prolongation of the dying process, with additional suffering for patients and their families, creating complex situations, and often causing a painful life extension. The term, limitation of the therapeutic effort refers to the adequacy and/or proportionality of the treatment, trying to avoid obstinacy and futility. The English literature does not talk about limitation of treatments, but instead the terms, withholding or withdrawal of life-sustaining treatment, are used. The removal or the non-installation of certain life support measures and the absence of CPR are the types of limitation most used. Also, there is evidence of insufficient medical training in bioethics, which is essential, as most doctors in the PICU discuss and make decisions regarding the end of life without the opinion of bioethicists. This article attempts to review the current status of knowledge concerning the limitation of therapeutic efforts to support pediatric clinical work.

Características de las interacciones farmacológicas en una unidad de cuidados intensivos de pediatría / Characteristics of drug interactions in a pediatric intensive care unit

Introduction: The aim of this study is to calculate the theoretical frequency of potential drug interactions (PDI) and their characteristics in the therapeutic plan of hospitalized patients in a Pediatric Intensive Care Unit (PICU). Patients and Methods: An observational study was conducted which analyzed PICU prescriptions between September and November 2011. The inclusion criteria included to be hospitalized in a PICU, requirements of at least 3 drugs, except those topically applied, either gender, no age limit, no hospital stay required. The Micromedex ® 2.0 program was used to detect and classify PDI. Results: Of 223 patients, 100 met inclusion criteria, 610 prescriptions were analyzed and 815 drugs were prescribed. 1,240 PDI were detected in 44 patients; 12 patients received more than 10 drugs each, presenting 1,162 PDI (93.7% of total PDI). 8 patients were hospitalized for more than 10 days, presenting 1,035 PDI (83.5% of total PDI). According to PDI theoretical severity, 37.5% were high, 51.7% moderate, 6.7% low and 4.1% contraindicated. The therapeutic group most involved was antimicrobials (17.6%) and the most frequently involved individual drugs were chloral hydrate (15.9%), midazolam (14.1%) and vecuronium (13.4%). Conclusion: PDI were more frequent in patients associated with major polypharmacy and longer hospital stay.

Introducción: El objetivo de éste estudio fue medir la frecuencia teórica de interacciones farmacológicas probables (IF) y sus características en los esquemas terapéuticos de los pacientes hospitalizados una Unidad de Cuidados Intensivos Pediátricos (UCIP). Pacientes y Método: Estudio observacional que analizó las prescripciones médicas en UCIP entre septiembre y noviembre del año 2011. Criterios de inclusión fueron estar hospitalizados en la UCIP, tener prescripciones que incluyan a lo menos 3 medicamentos, excepto aquellos de aplicación tópica, ambos sexos, sin límite de edad, ni estadía hospitalaria. Se utilizó el programa Micromedex 2.0® para la detección y clasificación de las IF. Resultados: De 223 pacientes, 100 cumplieron criterio de inclusión, en quienes se analizaron 610 prescripciones médicas, donde se indicaron 815 fármacos. Se detectaron 1.240 IF en 44 pacientes. Doce pacientes recibieron más de 10 fármacos cada uno, registrándose en ellos 1.162 IF (93,7% de las IF). Ocho pacientes estuvieron más de 10 días hospitalizados, concentrando 1.035 IF (83,5% de las IF). Según severidad teórica de las IF, se encontró 37,5% mayores, 51,7% moderadas, 6,7% menores y 4,1% contraindicadas. El grupo terapéutico más implicado fueron los antimicrobianos (17,6%) y los fármacos individuales más frecuentemente involucrados fueron hidrato de cloral (15,9%), midazolam (14,1%) y vecuronio (13,4%). Conclusión: Las IF fueron más frecuentes en pacientes con mayor polifarmacia y estadía más prolongada.

Association of ß1 and ß3 adrenergic receptors gene polymorphisms with insulin resistance and high lipid profiles related to type 2 diabetes and metabolic syndrome.

BACKGROUND: Among the diverse genes associated to type 2 diabetes (T2D), the ß-adrenergic receptors are an excellent candidate to study in Mexican population. The objective of this work was to analyze the association of polymorphisms in ADRB1 (rs1801253) (Arg389Gly) and ADRB3 (Trp64Arg) genes with T2D and metabolic syndrome (MS). METHODS: We studied 445 MS patients, 502 with T2D and 552 healthy controls. Anthropometric features and complete biochemical profile were evaluated, and Arg389Gly and Trp64Arg SNPs were determined by TaqMan assays. Data analysis was adjusted by African, Caucasian and Amerindian ancestral percentage. RESULTS: The variant Arg389Gly of ADRB1 was statistically associated with an increase of LDL levels (P < 0.008), and the variant ADRB3 Trp64Arg was associated to larger HOMA-IR (P < 0.018) and with an increase of insulin levels (P < 0.001). A multiple logistic regression analysis was made in three grouping models: For ADRB3 in the codominant model Trp/Arg genotype, there was an OR of 1.53 (1.09-2.13, P < 0.003) which was increased up to OR 2.99 (1.44-6.22, P < 0.003) for the Arg/Arg genotype. Similar risk association was found under the dominant model Trp/Arg-Arg/Arg genotype with OR 1.67 (1.21-2.30; P < 0.002). In the recessive model (Arg/Arg genotype), there was also a high association OR 2.56 (1.24-5.26, P < 0.01). CONCLUSIONS: The ADRB3 Trp64Arg variant is a susceptibility gene polymorphism for T2D and the ADRB1 Gly389Arg for lipid metabolism disruption. These results show that these variants are potential biomarkers for predicting metabolic alterations and evolution in diabetic and metabolic syndrome patients.

Antecedentes: Entre los diversos genes asociados a la diabetes tipo 2 (DT2), los receptores ­adrenérgicos­ son excelentes candidatos para estudiar en la población mexicana dada la alta prevalencia de estas patologías. El objetivo de este trabajo fue analizar la asociación de polimorfismos en los genes ADRB1 (rs1801253) (Arg389Gly) y ADRB3 (Trp64Arg) con DT2 y SM. Métodos: Se estudiaron 445 pacientes con Síndrome Metabólico, 502 con diabetes tipo 2 y 552 controles sanos. Se evaluaron las características antropométricas, perfil bioquímico completo y los polimorfismos Arg389Gly y Trp64Arg SNPs se determinaron mediante ensayos TaqMan. El análisis de datos fue ajustado por porcentaje de ancestralidad. Resultados: Para la variante ADRB1 Arg389Gly se observó una asociación estadísticamente significativa con un aumento de los niveles de LDL (P < 0,008 ), y la variante ADRB3 Trp64Arg se asoció a mayor HOMA- IR (p < 0,018) y con un aumento de los niveles de insulina (P < 0,001). Mediante modelos de regresión logística múltiple en los tres modelos de heredabilidad se evaluó la asociación de ambos polimorfismos y DT2 y SM, observando un asociación significativa en los 3 modelos solo con DT2, ADRB3 en el modelo codominante Trp/Arg un OR de 1.53 (1.9 a 2.13 , P < 0.003) que se incrementó hasta OR 2,99 (1,44 a 6,22 , P < 0,003) para el genotipo Arg/Arg . Se encontró bajo el modelo dominante genotipo Trp/Arg- Arg/Arg con OR 1.67 (1.21 a 2.30, p < 0.002). En el modelo recesivo (Arg/Arg), también un OR 2.56 (1.24 a 5.26 , P < 0.01). Conclusiones: La variante ADRB3 Trp64Arg se asoció significativamente con DT2 y ADRB1 Gly389Arg en alteraciones en el metabolismo de lípidos. Nuestros resultados demuestran que estas variantes son posibles biomarcadores para predecir las alteraciones metabólicas y la evolución en pacientes con síndrome Metabólico y diabetes tipo 2.

Molecular Mechanism and Potential Targets for Blocking HPV-Induced Lesion Development.

Persistent infection with high-risk HPV is the etiologic agent associated with the development of cervical cancer (CC) development. However, environmental, social, epidemiological, genetic, and host factors may have a joint influence on the risk of disease progression. Cervical lesions caused by HPV infection can be removed naturally by the host immune response and only a small percentage may progress to cancer; thus, the immune response is essential for the control of precursor lesions and CC. We present a review of recent research on the molecular mechanisms that allow HPV-infected cells to evade immune surveillance and potential targets of molecular therapy to inhibit tumor immune escape.

Gran quemado experiencia en una unidad de cuidados intensivos pediatricos: evolución de la morbimortalidad / Great burned pediatric patient: experience in a pediatric intensive care unit

Introducción: En 1974 Garcés y Artigas, publican un score de índice de gravedad (IG) predictivo de evolución y mortalidad. Este índice, modificado por edad, es recomendado en las guías clínicas del Ministerio de Salud de Chile. Objetivos: Relacionar la mortalidad esperada y real según IG e identificar factores asociados entre IG elevado y mayor gravedad o evolución. Materiales y Métodos: Análisis retrospectivo de fichas clínicas de pacientes quemados ingresados a la Unidad de Paciente Crítico (UPC) del Hospital Roberto del Río entre julio de 2005 a noviembre de 2007. Resultados: En el período estudiado egresaron 1.161 pacientes, 30 eran quemados, 22 (73 por ciento) tenían IG sobre 70. El porcentaje de superficie corporal total quemada (SQC) promedio fue 32 (14-75). El IG osciló entre 71 y 205. Un total de 13 pacientes presentaron IG 70-100, 8 entre 101 y 150, 1 (4,5 por ciento) paciente ingresó con IG >150. Los pacientes con IG 100-150 presentaron más complicaciones y mayor estadía en UPC, que aquellos pacientes con IG <100 (p<0,02). Letalidad global fue de 4,5 por ciento. Conclusiones: El IG en pacientes críticos (IG 101-150) sobrestimó la mortalidad real en esta serie (p <0,05), aunque el número de casos es pequeño. La mayor gravedad según IG se asoció a estadías más prolongadas y mayor incidencia de complicaciones.

Introduction: In 1974, Garcés and Artigas published a severity index (SI), predictor of mortality trends. This index, modified by age, is recommended till now by the clinical guidelines of the Chilean Ministry of Health. Objectives: Link the real and expected mortality based on the calculated SI score in great burned pediatric patients. Identify a relation between higher SI score and outcome. Materials and Methods: Retrospective analysis of medical records of burned patients admitted to the Pediatric Intensive Care Unit(PICU) Roberto del Río Hospital between July 2005 to November2007. Results: Among 1161 PICU admissions, 30 were burned patients. The ranged total burned surface area (TBSA) was 14 to 75. 22 (73 percent) had a SI above 70. The SI averaged 115 (71-205), 13 (59 percent) between 70 and 100, 8 (36.3 percent) between 101 and 150, 1 (4.5 percent) patient was admitted with SI > 150. Patients with SI between100-150 had a higher incidence of complications and length of stay in the PICU, compared with patients with SI less than100. One patient died. Conclusions: The SI in patients categorized as critical (SI 101-150) overestimated the real mortality in this series (p <0.05), although the number of cases is small. SI associated severity was related to a higher incidence of complications and longer PICU stay.

Compromiso miocárdico en infección grave por virus influenza H1N1 / Myocardial involvement in severe H1N1 influenza infection

Introduction: During the winter of 2009, some patients infected with Influenza virus H1N1 presented a severe disease. Some isolated reports of myocarditis were described. Objective: To describe severe cases of H1N1 with myocardial involvement. Patients and Methods: Chart review of children between 0-15 y.o. diagnosed as presenting Influenza A H1N1 through Polimerase Chain Reaction, who were admitted to the PICU at Hospital Roberto del Río and Clínica Dávila between June and July of 2009. Myocardial involvement was considered positive if the clinical picture showed such signs, and/or there was an altered echocardiogram. Results: Twenty one patients were hospitalized with the diagnosis of severe Infection by Influenza A H1N1 (+), of which 8 patients (38 percent) presented myocardial involvement. All required mechanical ventilation. Echocardiogram performed in the first 24 hours post admission showed shortening of the left ventricle on average 21,8 percent, with a range of 19 to 38 percent. In 7 patients (87.5 percent) a systodyastolic dysfunction was shown. Myocardial involvement lasted from 2 to 10 days (median 4). One patient died. Conclusions: Involvement of myocardium is frequent in this series. It must be sought to treat it adequately.

Introducción: Durante el invierno 2009 algunos paciente con infección por virus Influenza A H1N1, evolucionaron en forma grave. Se han descrito reportes aislados de miocarditis secundaria a Influenza A H1N1. Objetivo: Descripción de los casos graves de H1N1 que presentaron compromiso miocárdico. Material y Métodos: Revisión de los casos diagnosticados como Influenza A H1N1 por Reacción Polimerasa en Cadena, en niños entre 0-15 años, hospitalizados en la Unidad de Paciente Crítico del Hospital Roberto del Río y de Clínica Dávila, durante el período Junio - Julio del 2009. Se consideró criterio de compromiso miocárdico el cuadro clínico y/o una ecocardiografía alterada. Resultados: : 21 pacientes fueron hospitalizados con diagnóstico de infección grave por Influenza A H1N1 (+), de éstos 8 pacientes ( 38 por ciento) presentaron compromiso miocárdico. Todos requirieron ventilación mecánica. La ecocardiografia en las primeras 24 horas postingreso, evidenció una fracción de acortamiento del ventrículo izquierdo promedio de 21,8 por ciento, con un rango de 19 a 38 por ciento. En 7 pacientes (87.5 por ciento) se constató una disfunción sistodiastólica. La duración promedio del compromiso miocárdico osciló entre 2 a 10 días ( mediana 4).Hubo 1 fallecido en esta serie. Conclusiones: La frecuencia de compromiso miocárdico en esta serie es importante, debiendo buscarse dirigidamente para adecuar plan terapéutico.

IL-10 expression is regulated by HPV E2 protein in cervical cancer cells.

It has been found that certain cytokines (IL-4, IL-10 and TGF-ß1) are highly expressed locally in biopsies from patients with premalignant lesions and cervical cancer, and may induce a local immune-suppression state. In particular, IL-10 is highly expressed in tumor cells and its expression is directly proportional to the development of HPV-positive cervical cancer, suggesting an important role of HPV proteins in the expression of IL-10. In fact, we demonstrated that E6 and E7 HPV proteins regulate TGF-ß1 gene expression in cervical cancer cells. Here, we found by band shifting analysis that the HPV E2 protein binds to the regulatory region of the human IL-10 gene (-2054 nt) and induces high promoter activity in epithelial cells. Additionally, cervical cancer cells transfected to express the HPV E2 protein induce elevated levels of IL-10 mRNA in human papillomavirus-infected cells. The elevated expression of IL-10 may allow for virus persistency, the transformation of cervical epithelial cells, and consequently cancer development.

HPV 16 E2 protein induces apoptosis in human and murine HPV 16 transformed epithelial cells and has antitumoral effects in vivo.

OBJECTIVE: Our aims were to examine the ability of the human papillomaviruse (HPV) 16 E2 protein to induce apoptosis in a murine HPV-transformed cell line, and to evaluate its antitumor properties on HPV-associated tumors in vivo in immunocompetent mice. METHODS: HPV-transformed murine BMK-16/myc cells and human SiHa cells were transfected with the HPV 16 E2 gene to examine the effects of the E2 protein on cell growth and on the E6 and E7 oncogenes as well as DNA fragmentation and activation of the extrinsic pathway of apoptosis. Finally, to test the antitumor effect of the E2 protein on an experimental mouse tumor model, we generated a recombinant adenovirus expressing the E2 protein. RESULTS: The E2 protein inhibited the growth of SiHa and BMK-16/myc cell lines, and repressed the E6 and E7 oncogenes. Moreover, the E2 protein induced DNA fragmentation and apoptosis through activation of caspases 8 and 3 in BMK-16/myc cells. On the other hand, E2 also showed antitumor effects in vivo. CONCLUSIONS: Our findings indicate that E2 exerts pro-apoptotic activity in a murine HPV-transformed cell line as well as an antitumor effect in vivo.