Hipoplasia tímica en pacientes pediátricos con enfermedad respiratoria / Thymic hypoplasia in pediatric patients with respiratory illnesses

Objetivos : Determinar las características clínicas y epidemiológicas de niños con hipoplasia del timo y enfermedad respiratoria en Cuba. Material y Métodos : Estudio descriptivo retrospectivo en niños con edades comprendidas entre 1 y 6 años, de ambos sexos, atendidos en la consulta de Inmunología Pediátrica del Programa de Proyección Comunitaria del Municipio Arroyo Naranjo de La Habana o en la consulta de Inmunología Pediátrica del Hospital Materno Infantil Ángel Arturo Aballí Arellano del Municipio Arroyo Naranjo La Habana, entre los meses de septiembre 2019 y agosto 2022. Se incluyeron los niños con hipoplasia tímica y con antecedentes personales de enfermedad respiratoria infecciosa o no infecciosa diagnosticadas durante el período de estudio. Resultados : No se encontró relación entre la hipoplasia tímica y la edad o el sexo; se encontró mayor frecuencia de la hipoplasia tímica leve y moderada en niños con desarrollo de enfermedad respiratoria grave. Los factores con mayor frecuencia descritos en la enfermedad respiratoria complicada fueron la lactancia materna inefectiva, los antecedentes patológicos personales de atopia, el embarazo de riesgo, la prematuridad, el humo de tabaco en el ambiente y la asistencia a círculo infantil o a casa de cuidado infantil. Conclusiones : El desarrollo de hipoplasia tímica no mostró relación con la edad y el sexo. Se describieron varias condiciones con mayor frecuencia en niños con hipoplasia tímica y con enfermedad respiratoria complicada. La frecuencia de la hipoplasia tímica leve y moderada fue mayor en los pacientes con enfermedad respiratoria grave.

SUMMARY Objective : To determine the clinical and epidemiologic features of children with thymic hypoplasia and respiratory illnesses in Cuba. Methods : A retrospective study was conducted among children of 1-6 years of age of both sexes attended at a Pediatric Immunology Program of Hospital Materno Infantil Ángel Arturo Aballí Arellano in Habana, Cuba from September 2019 to August 2022. Children with thymic hypoplasia with and without a history of a respiratory illness either infectious or non-infectious were included. Results : No association between age and sex with thymic hypoplasia but an association was found with children with a severe respiratory illness. Factors associated with a severe respiratory illness were ineffective breastfeeding, history of an atopic condition, pregnancy of high risk, prematurity and exposure to tobacco smoke. Conclusions : Thymic hypoplasia was not associated with age or sex. An association with mild-moderate thymic hypoplasia was found with a severe respiratory illness.

Avaliação por imagem de medidas esplênicas e tímicas como biomarcadores de resposta em pacientes com câncer tratados com imunoterapia / Imaging evaluation of thymic and splenic measurements as response biomarkers in cancer patients treated with immunotherapy

INTRODUÇÃO: Em menos de duas décadas, a imunoterapia consolidou-se como um dos pilares do tratamento do câncer. Apesar da sua potencial elevada eficácia e resposta duradoura, a proporção de pacientes que apresentam resposta objetiva é relativamente baixa e existem poucos biomarcadores para selecionar os pacientes com maior potencial de resposta. OBJETIVO: Nossa hipótese era de que era possível avaliar globalmente o sistema imune do paciente através da mensuração por imagem do timo e do baço e usar essas métricas como fator prognóstico e preditivo de resposta a bloqueadores de checkpoint. RESULTADOS: Os principais resultados foram: 1) As medidas tímicas não se correlacionam com a sobrevida em pacientes tratados com imunoterapia; 2) Há aumento do volume esplênico após o uso de imunoterapia na maior parte dos pacientes, mas o grau de aumento não se correlaciona com resposta à terapia; 3) Maior volume esplênico está associado a pior sobrevida livre de progressão em pacientes com melanoma tratados com imunoterapia, mas essa correlação não pôde ser replicada em outros tipos tumorais. CONCLUSÃO: a espessura tímica não se correlaciona com desfechos clínicos em pacientes oncológicos tratados com imunoterapia. Menor volume esplênico antes de iniciar imunoterapia está relacionada a melhor prognóstico em pacientes com melanoma, mas não em outros tipos tumorais.

INTRODUCTION: In less than two decades, immunotherapy has established itself as one of the pillars of cancer treatment. Despite its potentially high efficacy and long-lasting response, the proportion of patients who have an objective response is relatively low and there are few biomarkers to select patients with the greatest response potential. OBJECTIVE: Our hypothesis was that it was possible to assess the patient's immune system globally by measuring the thymus and spleen by imaging and using these metrics as a prognostic and predictive factor of response to immune checkpoint inhibitors. RESULTS: The main results were: 1) Thymic measurements do not correlate with survival in patients treated with immunotherapy; 2) There is an increase in splenic volume after the use of immunotherapy in most patients, but the degree of increase does not correlate with response to therapy; 3) Greater splenic volume is associated with worse progression free survival in patients with melanoma treated with immunotherapy, but this correlation could not be replicated in other tumor types. CONCLUSION: thymic thickness does not correlate with clinical outcomes in cancer patients treated with immunotherapy. Smaller splenic volume before starting immunotherapy is associated with better prognosis in patients with melanoma, but not other tumor types

Effect of dietary plants on the production of immunoglobulins A in healthy Wistar rats / Efeito de plantas dietéticas na produção de imunoglobulinas A em ratos Wistar saudáveis

Introduction: some plants such as turmeric, cinnamon, and okra are known to have therapeutic functions such as antioxidant and anti-inflammatory activity. Furthermore, an immunomodulatory role has been observed in the production of antibodies, in particular immunoglobulin A (IgA), which mediates a variety of protective functions for the organism. Objective: the aim of the present study was to investigate the effect of dietary plants on the production of IgA in healthy Wistar rats. Methods: thus, 48 male Wistar rats of 90 days of age were allocated to four groups. The animals were treated for 14 days with dried turmeric, cinnamon, or okra (50, 50, 12.5 mg/day, respectively) in phosphate buffered saline, or with only phosphate buffered saline by gavage. The animals received water and feed ad libitum. Body mass and relative weight ofperitoneal fat, adrenal gland, kidney, spleen, liver and thymus, biochemical parameters, and IgA levels were analyzed. Results: no significant changes were observed in the body mass, relative weight of organs and tissues, and biochemical parameters. An increase in serum IgA levels was observed in animals treated with turmeric or cinnamon. Conclusion: we conclude that the treatment with turmeric and cinnamon increased IgA production. Therefore, our study supports the idea that dietary supplementation with these plants may improve humoral immunity.

Introdução: algumas plantas como a cúrcuma, a canela e o quiabo são conhecidas por apresentar funções terapêuticas, como atividade antioxidante e anti-inflamatória. Além disso, tem sido observado um papel imunomodulador sobre a produção de anticorpos, em especial a imunoglobulina A (IgA), a qual medeia uma variedade de funções protetoras para o organismo. Objetivo: o objetivo do presente estudo foi investigar o efeito de plantas dietéticas na produção de IgA em ratos Wistar saudáveis. Métodos: destarte, 48 ratos machos Wistar com 90 dias de idade foram alocados em quatro grupos. Os animais foram tratados por 14 dias com cúrcuma seca, canela ou quiabo (50, 50, 12,5 mg/dia, respectivamente) em solução salina tamponada com fosfato ou apenas solução salina tamponada com fosfato, por gavagem. Os animais receberam água e ração ad libitum. Foram analisados a massa corporal e o peso relativo da gordura peritoneal, glândula adrenal, rim, baço, fígado e timo, parâmetros bioquímicos e níveis de IgA. Resultados: não foram observadas alterações significativas na massa corporal, no peso relativo dos órgãos e tecidos e nos parâmetros bioquímicos. Foi observado aumento dos níveis séricos de IgA nos animais tratados com cúrcuma ou canela. Conclusão: podemos concluir que o tratamento com cúrcuma e canela aumentou a produção de IgA. Portanto, nosso estudo suporta a ideia de que a suplementação alimentar com essas plantas pode melhorar a imunidade humoral.

La ecografía del timo en la niñez: una herramienta útil para evaluar la respuesta inmune en el crecimiento y desarrollo infantil / Echography of thymus in childhood: a useful tool to evaluate the immune response in childhood growth and development

Se presenta conceptos de la inmunocompetencia y su relación con la nutrición en niños, que describen aspectos fisiológicos integrales. También se describen los aspectos inmunológicos, que permiten interpretar los mecanismos de la respuesta inmune, destacándose conceptos y criterios fisiológicos. Un niño malnutrido presenta alteraciones inmunológicas, y las mismas se las puede identificar como deficiencias a predominio celular, y a predominio humoral. Se destaca la importancia del eje Neuroinmunoendocrinológico como integrador de respuestas fisiológicas. El propósito del presente trabajo, esta dirigido a identificar las herramientas que permiten el estudio del sistema inmune en nuestro contexto, haciendo especial hincapié en la ecografía del timo, por ser una herramienta útil para evaluar al sistema inmune en niños con estado nutricional alterado en forma leve o moderada.

Concepts of immunocompetence and its relationship with nutrition in children are presented, describing comprehensive physiological aspects. Immunological aspects are also described, which allow to interpret the mechanisms of the immune response, highlighting physiological concepts and criteria. A malnourished child presents immunological alterations, and these can be identified as deficiencies with a cellular predominance, and with a humoral predominance. The importance of the Neuro-immunoendocrinological axis as an integrator of physiological responses is highlighted. The purpose of this work is aimed at identifying the tools that allow the study of the immune system in our context, with special emphasis on ultrasound of the thymus, as it is a useful tool to evaluate the immune system in children with altered nutritional status, mild or moderate.

Asociación entre hipoplasia del timo y disminución de inmunoglobulina A / Association between thymus hypoplasia and immunoglobulin A reduction

El sistema inmune madura gradualmente durante la infancia y el nacimiento es un momento crucial para este proceso. El paso por el canal del parto es el primer estímulo que el sistema inmunitario percibe para comenzar así su maduración progresiva. El timo como órgano linfoide primario, es el primero en aparecer entre todos los órganos linfoides; en este órgano ocurre la ontogenia, diferenciación y maduración de los linfocitos T que migran a los órganos linfoides secundarios como linfocitos T inmunocompetentes. La producción de IgA por los linfocitos B es uno de los mecanismos esenciales de respuesta inmune de las mucosas a las que protege en su forma de IgA secretoria. En el Instituto de Hematología e Inmunología, se atendieron en consulta 62 pacientes pediátricos entre uno y cinco años de edad, con antecedentes de infecciones respiratorias agudas frecuentes, con dos o más episodios en un mes, a los que se les diagnosticó por ultrasonografía una disminución del área tímica (hipoplasia). De ellos, 50 por ciento presentó además disminución de la concentración de IgA en suero. Estos resultados sugieren múltiples interrogantes. Consecuentemente, este trabajo tiene como objetivo presentar la asociación hallada entre la disminución del tamaño del timo y la disminución de la concentración en suero de IgA, en un grupo de niños de uno a cinco años, con antecedentes de infecciones respiratorias frecuentes, consultados en el Instituto de Hematología e Inmunología durante un año(AU)

The immune system gradually matures during childhood, and birth is a crucial moment in this process. Transit through the birth canal is the first stimulus perceived by the immune system to start its progressive maturation. The thymus, a primary lymphoid organ as it is, is the first lymphoid organ to appear. It is the site of the ontogeny, differentiation and maturation of the T-lymphocytes migrating to secondary lymphoid organs as immunocompetent T-lymphocytes. IgA production by B-lymphocytes is one of the essential immune response actions performed by mucosas, which they protect in the form of secretory IgA. A study was conducted of 62 pediatric patients aged 1-5 years attending consultation at the Institute of Hematology and Immunology who had a history of frequent acute respiratory infection, with two or more episodes in one month. These patients were ultrasonographically diagnosed with thymus size reduction (hypoplasia). Among them, 50 percent also presented a decrease in serum IgA concentration. These results pose many questions concerning the association between thymus hypoplasia and IgA reduction. The purpose of the study was therefore to present the association found between thymus size reduction and serum IgA concentration decrease in a group of children aged 1-5 years with a history of frequent respiratory infection attending the Institute of Hematology and Immunology during one year(AU)

ALK+ Anaplastic large cell lymphoma with extensive cardiac involvement: A rare case report and review of the literature

Cardiac lymphoma is a rare entity. In this setting, the secondary involvement of the heart is far more frequent than the primary cardiac lymphoma. Herein, we present an autopsy case of a disseminated anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma with a dominant mediastinal involvement. Extensive cardiac infiltration with the near replacement of the myocardial wall by the neoplastic cells was observed. A total of nine isolated case reports of anaplastic large cell lymphoma with cardiac involvement were found in the English-language literature, and a widespread cardiac and thymic infiltration by the systemic ALK-positive anaplastic large cell lymphoma has not been documented. An incidental regenerative nodule was also identified in the liver. The patient died of pulmonary thromboembolism and cardiac arrest.

Congenital thymoma

Thymomas are a heterogeneous group of tumors arising from the epithelium of the thymus. They are categorized by the proportion of neoplastic epithelia to lymphocytes and by the degree of cytologic atypia. Thymomas constitute 0.2-1.5% of all malignancies and nearly all occur in patients over 20 years. We reviewed the available literature and found less than 50 cases of thymoma reported in children (<18 years of age), the youngest being 4 years old, and no cases in newborns. They represent less than 1% of all mediastinal tumors in children. Due to the limited number of cases in the pediatric population, the diagnosis and treatment in this population is extremely challenging. Thymomas in all age groups may be associated with paraneoplastic syndromes, being myasthenia gravis the most common, which is associated with a worse prognosis in the pediatric population. We present the first case of a newborn infant with congenital thymoma. This case demonstrates a rare tumor in an unusual age group and emphasizes the importance of multidisciplinary teamwork in the decision-making and management of this condition.

Effects of dexamethasone on the morphometry and biometry of immune organs of broiler chicken / Efectos de la dexametasona en la morfometría y biometría de los Órganos Inmunes del pollo de engorde

The study was conducted to examine the histological changes i.e. morphology and biometry of immune organs (thymus, spleen and bursa cloacalis or «Fabricius¼) of broilers in response to dietary dexamethasone (DEX). The day old chicks were obtained from the commercial hatchery and randomly divided into two groups i.e. control and experimental or treated group. The control group was reared on commercial broiler ration and the experimental group (n=25) was maintained on commercial broiler ration with corticosteroid (Dexamethasone-Decason, BP 0.5 mg, Opsonin @ 7 mg/kg feed). Samples (bursa cloacalis, spleen, and thymus) were collected from the ten control and ten experimental broilers at 14 and 28 days of experiment; then tissues were stained with Hematoxylin and Eosin. The biometric measurements of the samples were performed by the calibrated stage micrometer. Finally, the obtained data were analyzed using GraphPad Prism 8 software. In DEX treated group, the morphology of thymus, spleen and bursa cloacalis did not show any abnormal alterations. But their development rate was slower on visual inspection in DEX treated group. The length and width of bursal follicle of bursa cloacalis, thymic lobule of thymus and white pulp of spleen were statistically consisted but numerically decreased in DEX treated group than the control. The present findings suggested that DEX does not affect the histological architectures of immune organs except causing developmental arrest. Numerical decrease in the biometry of immune organs indicates that DEX causes apoptosis of immune cells in lymphoid organs of broiler.

El estudio se realizó para examinar los cambios histológicos, es decir, la morfología y la biometría de los órganos inmunes (timo, bazo y bolsa cloacal) de pollos de engorde en respuesta a la dexametasona en la dieta (DEX). Los pollitos de un día se obtuvieron de un criadero comercial y se dividieron aleatoriamente en dos grupos, control y experimental. El grupo control se crió con una ración comercial de pollos de engorde y el grupo experimental (n = 25) se mantuvo con una ración comercial de pollos de engorde con corticosteroides (DexamethasoneDecason, BP 0,5 mg, Opsonin @ 7 mg/kg). Se recogieron muestras (bolsa cloacal, bazo y timo) de los diez pollos del grupo control y diez del grupo de engorde experimental, a los 14 y 28 días de experimento. Luego, los tejidos se tiñeron con hematoxilina y eosina. Las mediciones biométricas de las muestras fueron realizadas con un micrómetro calibrado. Finalmente, los datos obtenidos se analizaron utilizando el software GraphPad Prism 8. En el grupo tratado con DEX, la morfología del timo, el bazo y la bolsa cloacal no mostraron alteraciones anormales. Pero su tasa de desarrollo fue más lenta en la inspección visual en el grupo tratado con DEX. La longitud y el ancho del folículo bursal de la bolsa cloacal, el lóbulo tímico del timo y la pulpa blanca del bazo fueron estadísticamente consistentes, pero disminuyeron numéricamente en el grupo tratado con DEX en relación al control. Los hallazgos actuales sugirieron que DEX no afecta la arquitectura histológica de los órganos inmunes, excepto que causa una detención del desarrollo. La disminución numérica en la biometría de los órganos inmunes indica que DEX provoca apoptosis de las células inmunes en los órganos linfoides de los pollos de engorde.

Utilidad de la medición del timo fetal en el diagnóstico de anomalías congénitas y enfermedades obstétricas / Utility of fetal thymus measurement in the diagnosis of congenital anomalies and obstetric diseases

RESUMEN Introducción: el interés de la visualización sonográfica del timo fetal está relacionado con su importante función inmunológica, las posibilidades de diagnóstico que ofrecen los ecógrafos de alta resolución, y el incremento de informes de posibles afecciones durante el proceso de la gestación. Objetivo: determinar la frecuencia de la hipoplasia tímica fetal en gestantes de riesgo genético y relacionarla con la presencia de defectos fetales, factores de riesgo previos y aparición de efectos obstétricos adversos. Métodos: se realizó un estudio descriptivo prospectivo consistente en la evaluación ecográfica del timo fetal mediante el índice timo-tórax a 221 gestantes que acudieron a los servicios de referencia del Centro Provincial de Genética Médica, por presentar riesgo genético incrementado para cardiopatías. Resultados: se encontraron 16 fetos con un índice timo-tórax inferior o igual a 0,30, el cual se utilizó como criterio de hipoplasia tímica en este estudio, entre ellos: 4 con cardiopatías, 4 con cromosomopatías, 1 con malformación estructural aislada, 2 con preeclampsia, 1 con crecimiento intrauterino retardado, 1 pretérmino y una muerte fetal. Los motivos de referencia con mayor proporción de positividad fueron: la traslucencia nucal aumentada y la imagen de sospecha de cardiopatía congénita en ultrasonido de pesquisaje. Conclusiones: la determinación del índice timo-tórax permitió el diagnóstico de la hipoplasia tímica, tanto en el segundo como en el tercer trimestre de la gestación. Este tipo de investigación es relevante pues contribuye a identificar: defectos congénitos, factores de riesgo y efectos obstétricos adversos.

ABSTRACT Introduction: the interest in sonographic visualization of the fetal thymus is related to its important immunological function, the diagnostic possibilities offered by high-resolution ultrasound scanners, and the increased reporting of possible conditions during the gestation process. Objective: to determine the frequency of fetal thymic hypoplasia in pregnant women with genetic risks and to relate it to the presence of fetal defects, previous risk factors and the appearance of adverse obstetric effects. Methods: we conducted a prospective descriptive study consisting of the ultrasound evaluation of the fetal thymus by means of the thymic-thoracic ratio in 221 pregnant women who come to referral services of the Provincial Center of Medical Genetics, because they presented increased genetic risk for heart disease. Results: sixteen fetuses were found with a thymic-thoracic ratio less than or equal to 0.30, which was used as the criterion for thymic hypoplasia in this study: four with heart diseases, four with chromosomal diseases, one with isolated structural malformation, two with preeclampsia, one with delayed intrauterine growth, one preterm and one fetal death. The reference reasons with the highest proportion of positivity were: increased nuchal translucency and image of suspected congenital cardiopathy in screening ultrasound. Conclusions: determination of the thymic-thoracic ratio allowed us the diagnosis of thymic hypoplasia, both in the second and third trimester of pregnancy. This type of research is relevant because it helps to identify: congenital defects, risk factors and adverse obstetric effects.

Revisando un órgano olvidado: Evaluación del timo en PET-CT / Revisiting a Forgotten Organ: Thymus Evaluation in PET-CT

Resumen La pesquisa incidental de lesiones tímicas ha aumentado. Una adecuada aproximación a esas lesiones en la tomografía computada por emisión de positrones (PET-CT) es fundamental, pues se usa como parte de la mayoría de los procedimientos de planificación oncológica. Se han seleccionado casos representativos respecto de los aspectos más importantes de las imágenes de timo en PET-CT y cómo esa técnica puede contribuir a un diagnóstico preciso o a la planificación del tratamiento. Específicamente, presentamos una descripción general de las lesiones tímicas comunes y los imitadores de enfermedad, con énfasis en los hallazgos en PET-CT, incorporando también ejemplos de resonancia magnética (RM).

Abstract Incidental thymic lesion findings have increased. An adequate characterization of these lesions in positron emission computed tomography (PET-CT) is essential, since it is used as part of most oncological planning procedures. Representative cases have been selected regarding the most important aspects of thymus imaging in PET-CT and how this technique can contribute to an accurate diagnosis or treatment planning. Specifically, we present a general description of common thymic lesions and disease mimics, with an emphasis on PET-CT findings, also incorporating examples of magnetic resonance imaging.

Timo cervical aberrante: masa cervical pediátrica inusual, revisión bibliográfica y reporte de caso / Aberrant cervical thymus: unusual type of pediatric cervical mass, bibliographic review and case report

Las masas cervicales representan un desafío habitual en pediatría, que en su mayoría son de etiología benigna. Una de las causas menos conocidas es el timo cervical aberrante, una entidad clínica resultante de anormalidades en el descenso del timo a lo largo de su ruta habitual (tracto timo-faríngeo). Este es un cuadro frecuentemente mal diagnosticado, del que se desconoce su incidencia real. Actualmente, su incidencia relativa parece ir en aumento en conjunto con la disponibilidad de la ecotomografía. En Chile no hay registro epidemiológico de este cuadro ni existen reportes de caso documentados. En este artículo se presenta una revisión bibliográfica sobre masa cervical pediátrica y un reporte de caso de un paciente chileno.

Cervical masses constitute a frequent challenge in pediatric care, mostly which are of benign nature. One of the lesser known causes is the aberrant cervical thymus, which results from embryological abnormalities during the thymus descent through its normal route (thymo-pharyngeal duct). This is a frequently misdiagnosed syndrome, for which its real incidence remains unknown. Nowadays, its relative incidence is on the rise along with ultrasound availability. There is no epidemiological record or documented case reports of this entity in Chile. In this article we present a bibliographic revision on cervical mass and a case report from a Chilean patient.

Hipoplasia de timo con trisomía del cromosoma10 / Thymus hypoplasia with chromosome 10 trisomy

INTRODUCCIÓN: La hipoplasia de timo es una entidad que puede asociarse a múltiples patologías fetales de ahí la importancia de su diagnóstico y su manejo. OBJETIVO: Utilidad y métodos de evaluación del timo en la ecografía morfológica y valor de la interpretación del análisis genético de los microarrays. CASO CLÍNICO: Se presenta el caso clínico de una gestante en la que se detecta una glándula tímica hipoplásica utilizando para su medición el índice timo-torácico en un plano de tres vasos. Ante estos hallazgos se realiza una amniocentesis para análisis genético usando la QF-PCR y un análisis ARRAY-CGH. RESULTADOS: En el análisis de ARRAY-CGH se observa una duplicación patológica en mosaico compatible con una trisomía del cromosoma 10, alteración genética infrecuente de la que se han reportado unos 50 casos en recién nacidos vivos. Esta alteración presenta un rango muy amplio de alteraciones, desde malformaciones graves a niños completamente normales. En los controles posteriores la gestación es normoevolutiva y finaliza en la semana 40 mediante un parto eutócico de inicio espontáneo naciendo un bebé fenotípicamente normal con un timo de menor tamaño del habitual siendo pronto para saber las consecuencias de esta alteración en su inmunidad. CONCLUSIONES: Por un lado, el timo es una estructura fácil de visualizar en la ecografía morfológica de la semana 20 y su medición mediante el índice timo-torácico nos aporta información útil acerca de posibles patologías fetales. Por otro, tener en cuenta que debemos ser muy cautelosos con la interpretación de resultados de pruebas genéticas cuando éstas no tienen un significado clínico claro.

INTRODUCTION : Thymus hypoplasia can associate many different pathologies so is highly important the diagnosis and the management. OBJECTIVE: Utility and methods in the evaluation of the fetal thymus in the morphological ultrasound and interpretation of microarray results. CLINICAL CASE: We present a case of fetal hypoplastic thymus gland in a pregnant woman. We measure it using the thymus-torax index in a three vessel view. A genetical analysis was made using QF-PCR and Array-CGH. RESULTS: In the ARRAY-CGH analysis it is found a pathological mosaicism that match with chromosome 10 trisomy, a very uncommon genetical alteration with only 50 reported cases. This trisomy can traduce from serious malformations to complete normal children. The parents decide to continue with the pregnancy and in week 40 it finishes with an uncomplicated delivery of a healthy child. In the newborn pediatrics remark a thymus gland smaller than expected but it is early to say if it will have or not consequences in its immunity. CONCLUSION: On one hand the thymus is a structure that we can easily display in the morphological ultrasound in the 20 week of pregnancy and its measure, using the thymus-torax index, can be very helpful in the detection of fetal pathologies. On the other hand, is important being careful when we interpret a genetical alteration without a clear clinical significance.

Efeitos de análogos da acetilcolina e noradrenalina sobre interações entre timócitos e células epiteliais tímicas / Effects of acetylcholine and norepinephrine analogs on interactions between thymocytes and thymic epithelial cells

O timo é um órgão linfoide primário responsável pelo desenvolvimento e seleção de células T. Diversos fatores podem afetar o desenvolvimento de células T, como citocinas, quimiocinas e moléculas da matriz extracelular, mas também hormônios, neuropeptídeos e neurotransmissores. O timo recebe densa inervação simpática, liberando majoritariamente noradrenalina (NA), timócitos e células tímicas não linfoides expressam receptores adrenérgicos e podem sintetizar catecolaminas, sugerindo modulação de NA por diferentes vias. Por outro lado, poucas evidências anatômicas suportam a hipótese da inervação tímica parassimpática. Entretanto, acetilcolina (ACh) parece ser endogenamente produzida no órgão, uma vez que diferentes células no timo expressam a enzima sintetizadora de ACh (ChAT) e receptores colinérgicos. Sendo assim, o objetivo deste trabalho foi determinar o papel funcional de ACh e NA sobre os componentes linfoide e microambiental do timo, e sobre as interações entre células epiteliais e timócitos. Avaliamos a expressão de receptores adrenérgicos α1A, α1D, α2C, ß2 e colinérgicos M1, M3, M5 e α7 em timócitos e TECs, através do método de PCR quantitativa. Todas as populações celulares testadas expressavam os receptores selecionados.

Além disso, buscamos caracterizar o efeito de drogas análogas aos neurotransmissores sobre a morte e a proliferação de timócitos, através da marcação com anexina-V/iodeto de propídio (IP) e CFSE respectivamente. Timócitos obtidos do timo de camundongos C57BL/6 fêmeas, foram tratados com carbacol (análogo de Ach - em concentrações variando de 10 nM a 1000 nM) ou arterenol (análogo de NA - em concentrações variando de 10 nM a 1 mM). Verificamos que apenas arterenol na concentração de 1 mM induziu a apoptose nas células tratadas. Nenhum dos análogos modulou a proliferação celular. Avaliamos ainda o efeito das drogas sobre a migração de timócitos, agindo como quimioatrente ou modulando a migração induzida por fibronectina. Nenhuma das drogas demonstrou efeito quimioatraente ou alterou a migração induzida por fibronectina. Além disso, avaliamos o efeito das drogas sobre a interação TEC/timócitos atraves de ensaios de adesão e observamos que carbacol foi capaz de diminuir a adesão de timócitos a TECs em todas as concentrações testadas. Essa diminuição é refletida no número de timócitos que aderem às TECs e parece estar associada a modulação da expressão do receptor de laminina VLA-6. Nossos dados sugerem que timócitos e as linhagens de TECs testadas expressam receptores e que neurotransmissores, em especial a ACh, podem modular a interação entre TECs e timócitos. (AU)

Enfermedades del timo por exceso y por defecto / Thymus diseases by excess and default

El timo es un órgano cervicotorácico, impar y mediano, situado en la base del cuello y parte superior del mediastino. Junto a la médula ósea es uno de los dos órganos primarios del sistema inmune y ejerce su función en los neonatos y en los niños, fundamentalmente. Entra en regresión a partir de la pubertad, aunque algunos autores plantean que la involución puede comenzar un poco antes, cuando los principales tejidos linfoides están plenamente desarrollados. Interviene sinérgicamente con otras glándulas de secreción interna: tiroides, suprarrenal, hipófisis, para elaborar substancias necesarias para el desarrollo general del organismo. Es un órgano muy sensible a todo influjo. Como todos los órganos de la economía el timo presenta enfermedades producidas tanto por crecimiento exagerado, como por hipoplasias o atrofias. Dentro de las primeras las más comunes son la hiperplasia tímica y el timoma y, entre las últimas el síndrome de DiGeorge ha sido bien caracterizado en la literatura internacional desde la segunda mitad del siglo pasado. Sin embrago, en los últimos tiempos los inmunólogos hablan de la hipoplasia tímica como entidad que puede asociarse o no a estados de inmunodeficiencia. Se describen brevemente estas afecciones(AU)

The thymus is a cervicothoracic organ, odd and medium, located at the base of the neck and upper part of the mediastinum. Next to the bone marrow is one of the two primary organs of the immune system and exerts its function in neonates and children, fundamentally. It regresses after puberty, although some authors suggest that the involution can begin a little earlier, when the main lymphoid tissues are fully developed. It intervenes synergistically with other glands of internal secretion: thyroid, adrenal, pituitary gland, to develop substances necessary for the general development of the organism. It is a very sensitive organ to all influence. Like all the organs of the economy, the thymus presents diseases caused both by exaggerated growth, as by hypoplasias or atrophies. Among the former, the most common are thymic hyperplasia and thymoma and, among the latter, DiGeorge syndrome has been well characterized in international literature since the second half of the last century. However, in recent times immunologists speak of thymic hypoplasia as an entity that may or may not be associated with immunodeficiency states. These conditions are briefly described(AU)

Análise evolutiva da morfologia e da irrigação do timo de javalis (Sus scrofa Linnaeus, 1758) / Evolutionary analysis of morphology and irrigation of the thymus of boar's (Sus scrofa Linnaeus, 1758)

Objetivou-se descrever comparativamente as artérias responsáveis pela irrigação dos lobos tímicos cervicais e torácicos dos javalis, determinando-se também as características morfológicas do referido órgão nessa espécie, a ponto de correlacioná-las evolutivamente com os demais representantes da família Suidae. Os lobos tímicos cervicais direito e esquerdo receberam ramos distribuídos pelas artérias carótidas comuns direita e esquerda e cervicais superficiais direita e esquerda e, por vezes, pelas artérias torácica externa esquerda e subclávia esquerda. Essa característica vascular foi mantida ao longo da evolução, estando presente em linhagens e raças mais recentes de suídeos. A irrigação dos lobos tímicos torácicos direito e esquerdo foi realizada predominantemente por ramos diretos e indiretos ipsilaterais e contralaterais das artérias torácicas internas direita e esquerda, e também por ramos da artéria subclávia esquerda. Ramos diretos das artérias cervicais superficiais direita e esquerda e ramos diretos da artéria torácica interna direita foram encontrados para o lobo tímico médio, sendo essa uma descrição única nessa espécie, o que demonstra uma característica evolutiva primitiva nesse ancestral.(AU)

The objective of this study was to comparatively describe the arteries responsible for the irrigation of the cervical and thoracic thymus lobes of Boars, also determining the morphological characteristics of this body in this species to the point of evolutionarily correlating them with other representatives of the Suidae family. The left and right cervical thymic lobes received branches distributed by common right and left, superficial right and left carotid arteries, and neck and, sometimes, the outer left chest and left subclavian arteries. This feature was vascular maintained throughout evolution and is present in more recent strains and breeds of swine. Irrigation of the right and left thoracic thymic lobes was performed predominantly by direct and indirect ipsilateral and contralateral branches of the right and left internal thoracic arteries and also by branches of the left subclavian artery. Direct branches of the right and left superficial cervical artery and right branches of the right internal thoracic artery were found for the average thymic lobe, this being a unique description in this species, demonstrating a primitive feature in this evolutionary ancestor.(AU)

Hematoma mediastinal tímico, complicación infrecuente del cateterismo cardíaco por abordaje radial / Mediastinal thymic hematoma: infrequent complication after transradial cardiac catheterization

Las complicaciones vasculares en los cateterismos cardíacos en general son infrecuentes y están en relación directa con el sitio específico de la punción vascular. Dado que el hematoma tímico es de rara ocurrencia, no suele considerase entre los diagnósticos diferenciales del dolor torácico poscateterismo cardíaco. Se presenta el caso de una paciente de 62 años que desarrolló un hematoma tímico luego de practicar una arteriografía coronaria.

Vascular complications in cardiac catheterizations are usually infrequent and are directly related to the specific site of vascular puncture. Since the thymic hematoma is so rare, it is not considered a differential diagnosis of chest pain after cardiac catheterization. We present the case of a 62-year-old patient who develops a thymic hematoma after having been taken to a coronary arteriography.

T cell receptor excision circles as a tool for evaluating thymic function in young children

The thymus is a primary lymphoid organ responsible for the maturation of T cells as well as the immunological central tolerance. It is in the antenatal period and infancy that it plays its major role. In clinical practice, T cell receptor excision circles (TRECs) are considered a direct and reliable measure of the thymic function. TRECs are a by-product of DNA formation in gene rearrangement of T cell receptors. They are stable and they do not duplicate during mitosis, representing the recent emigrant T cells from the thymus. Despite their importance, TRECs have been neglected by physicians and there is a lack of data regarding thymic function during infancy of healthy children. In order to evaluate thymic function in the first years of life, we propose measuring TRECs as a valuable tool. One hundred and three blood samples from children and adolescents between 3 months and 20 years of age were analyzed. The mean TRECs count was 136.77±96.7 copies of TRECs/μL of DNA. The individuals between 0 and 5 years of age had significantly higher TRECs values than those between 10 and 20 years of age. No significant difference was observed in TRECs values among age groups below 5 years of age. An inverse correlation between TRECs and age was found (r=0.3 P=0.003). These data highlight and validate the evidence of decreased thymus function with age, even during infancy. Awareness should be raised with this important albeit ignored organ.

Quiste tímico multiloculado en un paciente adulto: presentación de caso y revisión de la literatura / Multiloculated thymic cyst in an adult patient: case report and literature review

Los quistes tímicos multiloculados son lesiones generalmente adquiridas, que se diagnostican de manera incidental en la mayoría de pacientes y se asocian con condiciones de naturaleza diversa, como: inflamación, infección, trauma y radioterapia. Se presenta el caso de una mujer de 55 años con un quiste tímico multiloculado, sin antecedentes de importancia o condición clínica particular al momento del diagnóstico.

Multiloculated thymic cysts are acquired lesions, diagnosed incidentally in most patients and associated with other conditions such as inflammation, infection, trauma and radiothera. We present the case of a 55-year-old woman with a multilocular thymic cyst, with no relevant history or particular clinical condition at the time of diagnosis.

Timo ectópico cervical: Presentación de un caso / Ectopic Cervical Thymus: A Case Report

Introducción: El timo ectópico es una patología poco frecuente que se caracteriza por una masa en el cuello no dolorosa, que puede ser quística o sólida, resultado de una alteración en el proceso de migración de los primordios del timo durante la gestación. La adecuada interpretación, dentro del amplio espectro de diagnósticos diferenciales, es muy importante para evitar manejos invasivos innecesarios. Presentación de caso: Se trata de un niño de 8 meses, sin antecedentes relevantes, con abultamiento en la región submandibular derecha, no dolorosa, a quien en la exploración mediante ecografía y resonancia magnética se le encontraron características de imagen idénticas al timo ortotópico, lo que constituye un raro caso de timo ectópico sólido. Posterior a la cirugía, el resultado de patología correspondió a timo ectópico. Discusión: El timo es un órgano ubicado en el mediastino anterosuperior que tiene un papel importante en la inmunidad mediada por células. Proviene embriológicamente del tercer y cuarto arcos braquiales y migra a través del conducto timofaríngeo desde el ángulo de la mandíbula hasta la unión cérvico-mediastínica. El tejido tímico ectópico puede ocurrir en cualquier punto a lo largo del conducto timofaríngeo. La incidencia no es claramente conocida. Es más común en el cuello izquierdo, quístico, en hombres, entre los 2 y 13 años y unilateral. La apariencia normal del timo, y por ende de los timos ectópicos sólidos, es exactamente igual en las diferentes modalidades de imagen. Los diagnósticos diferenciales incluyen quistes del conducto tirogloso, quistes branquiales, tumor dermoide, hemangioma, fibromatosis colli, teratoma, linfoma y neuroblastoma, entre otros. Conclusión: El timo ectópico es una lesión cervical rara que simula patología, por lo cual es importante entender las características radiológicas que permitan un adecuado diagnóstico para prevenir intervenciones y cirugías innecesarias.

Introduction: Ectopic thymus is a rare disease characterized by a non-painful mass on the neck, which may be cystic or solid, resulting from an alteration in the process of migration of the thymus primordia during gestation. Proper interpretation, within the broad spectrum of differential diagnoses, is very important to avoid unnecessary invasive management. Case presentation: We present the case of an 8 months-old boy, with no relevant history, with bulging in the right submandibular region, not painful, that in the exploration by ultrasound and magnetic resonance imaging characteristics were found identical to the thymus orthotics, constituting a rare case of solid ectopic thymus, which was taken to surgery. The pathology corresponded to ectopic thymus. Discussion: The thymus is an organ located in the anterosuperior mediastinum that plays an important role in cell-mediated immunity. It develops embryologically from the third and fourth brachial arches and migrates through the pharyngeal thymus conduit from the angle of the mandible to the mediastinal cervical junction. Ectopic thymic tissue can occur at any point along the pharyngeal thymus conduit. The incidence is not clearly known. They are more common in the left neck, cystic, in men, between 2 and 13 years and of unilateral presentation. The normal appearance of the thymus, and therefore of the solid ectopic thymus, is exactly the same in the different imaging modalities. Differential diagnoses include thyroglossal duct cysts, gill cysts, dermoid tumor, hemangioma, fibromatosis colli, teratoma, lymphoma and neuroblastoma, among others. Conclusion: The ectopic thymus is a rare cervical lesion that simulates pathology, so it is important to understand the radiological characteristics that allow an adequate diagnosis to prevent interventions and unnecessary surgeries.

Distribution and morphology of ghrelin-immunopositive cells in the thymus of the African ostrich / Distribución y morfología de células inmunopositivas de la ghrelina en el timo de la avestruz africana

Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor, has been detected in the thymus of multiple vertebrates. However, little is known about its distribution in the thymus of the African ostrich. In this study, we evaluated the distribution and morphological characteristics of ghrelin-producing cells in the thymus of the African ostrich. Our results revealed that the thymus consists of a capsule and a parenchyma, which comprises the cortex and medulla. Compared to the cortex, the medulla had a fewer number of thymocytes and a greater number of epithelial cells. Additionally, three thymic corpuscles were identified. Ghrelin-immunopositive (ghrelin-ip) cells were detected both in the cortex and medulla of the African ostrich thymus, specifically within epithelial cells and thymic corpuscles. On the other hand, no ghrelin-ip cells were detected within thymocytes. These results clearly demonstrate the presence of ghrelin-ip cells in the thymus of the African ostrich.

La ghrelina, un ligando endógeno para el receptor secretor de la hormona del crecimiento, se ha detectado en el timo de múltiples vertebrados. Sin embargo, poco se sabe sobre su distribución en el timo de la avestruz africana. En este estudio se evaluó la distribución y características morfológicas de las células productoras de ghrelina en el timo de la avestruz africana. Nuestros resultados revelaron que el timo consiste en una cápsula y un parénquima, que comprende la corteza y la médula. En comparación con la corteza, se observó un número menor de timocitos en la médula y un mayor número de células epiteliales. Además, se identificaron tres corpúsculos tímicos. Se detectaron células inmunopositivas a la ghrelina (ghrelin-ip) tanto en la corteza como en la médula del timo de la avestruz africana, específicamente dentro de células epiteliales y corpúsculos tímicos. Por otra parte, no se detectaron células ghrelin-ip dentro de los timocitos. Estos resultados demuestran claramente la presencia de células ghrelin-ip en el timo de la avestruz africana.