Utilidad del lavado broncoalveolar para la detección microbiológica, y factores asociados, en receptores de trasplante de precursores hematopoyéticos: estudio de cohorte retrospectivo

Introducción: Las opacidades pulmonares en receptores de trasplante de precursores hematopoyéticos (TPH) representan un desafío diagnóstico y son una causa de morbimortalidad. Existen grandes discrepancias con respecto a la sensibilidad diagnóstica del lavado broncoalveolar (LBA), sus complicaciones, y los factores asociados a la identificación microbiológica. Objetivo: Conocer la utilidad del estudio microbiológico del LBA en el diagnóstico, modificación de la conducta médica y estimar las complicaciones y mortalidad asociada al procedimiento, en receptores de TPH con opacidades pulmonares. Pacientes y Métodos: Estudio de cohorte, retrospectivo, en adultos receptores de TPH a los que se les realizó una broncoscopía con LBA por presentar opacidades pulmonares, en el Hospital Italiano de Buenos Aires entre el 01/01/2011 y el 31/12/2020. Resultados: De los 189 procedimientos analizados, en 79 se logró un hallazgo microbiológico (41,8%) y 122 permitieron modificar la conducta médica (64,6%). En 11 casos se observaron complicaciones graves dentro de las 12 horas (5,8%) de efectuado el LBA. La mortalidad intrahospitalaria fue de 16,8% (N = 21/125). El valor de neutrófilos en sangre previo al LBA (p = 0,037) y la presencia de nódulos pulmonares como lesión tomográfica predominante (p = 0,029) se asociaron independientemente al hallazgo microbiològico global. Conclusiones: Nuestra investigación apoya la realización del LBA como herramienta diagnóstica en pacientes que reciben un TPH y presentan opacidades pulmonares.

Background: Lung opacities are a cause of morbimortality in bone marrow transplant patients, and represent a diagnostic challenge. There are large discrepancies regarding the diagnostic sensitivity of bronchoalveolar lavage (BAL), its complications, and the factors associated with microbiological detection. Aim: To know the usefulness of the microbiological study of BAL in the diagnosis, in the modification in medical behavior and to estimate the complications and associated mortality of this diagnostic procedure in patients transplanted with hematopoietic progenitor cells with pulmonary opacities. Methods: Retrospective cohort study in bone marrow transplant adult patients who underwent bronchoscopy with BAL due to lung opacities at Hospital Italiano de Buenos Aires between 01/01/2011 and 12/31/2020. Results: Of the 189 BAL analyzed, 79 presented a microbiological detection (41.8%) and 122 allowed to modify the medical behavior (64.6%). Severe complications were observed within 12 hours after the procedure in11 cases (5.8%). In-hospital mortality was 16,8% (N = 21/125). The value of blood neutrophils prior to bronchoalveolar lavage (p = 0.037) and the presence of pulmonary nodules as the predominant tomographic lesion (p = 0.029) were independently associated with global microbiological detection. Conclusion: Our research supports the performance of BAL as a diagnostic tool in bone marrow transplant patients with lung opacities.

Retinoic acid induces differentiation of cochlear neural progenitor cells into hair cells / O ácido retinoico induz a diferenciação das células progenitoras neurais cocleares em células ciliadas

Abstract Introduction: Inner ear progenitor cells have the potential for multi-directional differentiation. Retinoic acid is an important requirement for the development of the inner ear. Blocking the Curtyr's retinoic acid signaling pathway can significantly reduce the number of hair cells. Therefore, we believe that retinoic acid may induce the regeneration of inner ear hair cells. Objective: To investigate whether the cochlear neural progenitor cells maintain the characteristics of stem cells during recovery and subculture, whether retinoic acid can induce cochlear neural progenitor cells into hair cells in vitro, and whether retinoic acid promotes or inhibits the proliferation of cochlear neural progenitor cells during differentiation. Methods: Cochlear neural progenitor cells were cultured and induced in DMEM/F12 + RA (10−6M) and then detected the expressions of hair cell markers (Math1 and MyosinVIIa) by immunofluorescence cytochemistry and realtime-polymerase chain reaction, and the proliferation of cochlear neural progenitor cells was detected by Brdu. Results: The nestin of cochlear neural progenitor cells was positively expressed. The ratios of Math1-positive cells in the control group and experimental group were 1.5% and 63%, respectively; the ratios of MyosinVIIa-positive cells in the control group and experimental group were 0.96% and 56%, respectively (p <0.05). The ratios of Brdu+-labeled cells in retinoic acid group, group PBS, and group FBS were 20.6%, 29.9%, and 54.3%, respectively; however, the proliferation rate in the experimental group decreased. Conclusion: Retinoic acid can promote cochlear neural progenitor cells to differentiate into the hair cells.

Resumo Introdução: As células progenitoras da orelha interna têm potencial para diferenciação multidirecional. O ácido retinoico é uma condição importante para o desenvolvimento da orelha interna. O bloqueio da via de sinalização do ácido retinoico no órgão de Corti pode reduzir significativamente o número de células ciliadas. Portanto, acreditamos que o ácido retinoico pode induzir a regeneração das células ciliadas do ouvido interno. Objetivo: Investigar se as células progenitoras neurais cocleares mantêm as características das células-tronco durante a recuperação e subcultura, se o ácido retinoico pode induzir a transformação de células progenitoras neurais cocleares em células ciliadas in vitro e se o ácido retinoico promove ou inibe a proliferação das células progenitoras durante a diferenciação. Método: As células progenitoras neurais cocleares foram cultivadas e induzidas em DMEM/F12+AR (106M) e, então, foram detectadas as expressões de marcadores das células ciliadas (Math1 e Myosin?a) com o uso de citoquímica por imunofluorescência e real time -polymerase chain reaction e a proliferação de células progenitoras neurais cocleares foi detectada pelo teste Brdu. Resultados: A nestina das células progenitoras neurais cocleares foi expressa positivamente. As proporções de células positivas para Math1 no grupo controle e no grupo experimental foram 1,5% e 63%, respectivamente; as proporções de células positivas para Myosin?a no grupo controle e no grupo experimental foram de 0,96% e 56%, respectivamente (p <0,05). As proporções de células marcadas com Brdu+ no grupo ácido retinoico, grupo PBS e grupo FBS foram de 20,6%, 29,9% e 54,3%, respectivamente; no entanto, a taxa de proliferação no grupo experimental diminuiu. Conclusões: O ácido retinoico pode promover a diferenciação das células progenitoras neurais cocleares em células ciliadas.

Study on the serum level of CoQ10B in patients with Moyamoya disease and its mechanism of affecting disease progression / Estudo sobre o nível sérico de CoQ10B em pacientes com doença de Moyamoya e seu mecanismo de afetar a progressão da doença

ABSTRACT Background: At present, the etiology and pathogenesis of Moyamoya disease (MMD) are not completely clear. Patients are usually diagnosed after cerebrovascular events. Therefore, it is of great clinical significance to explore the predictive factors of MMD. Objective: This study aimed to investigate the serum level of CoQ10B, the amount of endothelial progenitor cells (EPCs), and mitochondrial function of EPCs in MMD patients. Methods: Forty-one MMD patients and 20 healthy controls were recruited in this study. Patients with MMD were divided into two groups: Ischemic type (n=23) and hemorrhagic type (n=18). Blood samples were collected from the antecubital vein and analyzed by CoQ10B ELISA and flow cytometry. Measures of mitochondrial function of EPCs include oxygen consumption rate (OCR), mitochondrial membrane potential, Ca2+ concentration, adenosine triphosphatases activity and ROS level. Results: The serum CoQ10B level in MMD patients was significantly lower than that in healthy controls (p<0.001). The relative number of EPCs in MMD patients was significantly higher than that in healthy controls (p<0.001). Moreover, the OCR, mitochondrial membrane potential and ATPase activity were decreased and the Ca2+ and reactive oxygen species levels were increased in MMD patients (p<0.001). Conclusions: Our results showed obviously decreased serum CoQ10B level and increased EPCs number in patients with MMD compared with healthy patients, and the mitochondria function of EPCs in MMD patients was abnormal.

RESUMO Antecedentes: No momento, a etiologia e a patogênese da doença de Moyamoya (DMM) não são completamente claras. Os pacientes geralmente são diagnosticados após eventos cerebrovasculares. Sendo assim, é de grande importância clínica explorar os fatores preditivos de DMM. Objetivo: Este estudo teve como objetivo investigar o nível sérico de CoQ10B, a quantidade de células progenitoras endoteliais (CPE) e a função mitocondrial de CPE em pacientes com DMM. Métodos: Quarenta e um pacientes com DMM e 20 controles saudáveis foram recrutados neste estudo. Aqueles com DMM foram divididos em dois grupos: tipo isquêmico (n=23) e tipo hemorrágico (n=18). Amostras de sangue foram coletadas da veia antecubital e analisadas por CoQ10B Ensaio de Imunoadsorção Enzimática (ELISA) e citometria de fluxo. As medidas da função mitocondrial de CPE incluem taxa de consumo de oxigênio (TCO), potencial de membrana mitocondrial, concentração de Ca2+, atividade de adenosina trifosfatases (ATPase) e nível de espécies reativas de oxigênio (ROS). Resultados: O nível sérico de CoQ10B em pacientes com DMM foi significativamente menor do que em controles saudáveis (p<0,001). O número relativo de CPE em pacientes com MMD foi significativamente maior do que em controles saudáveis (p<0,001). Além disso, a TCO, o potencial de membrana mitocondrial e a atividade ATPase diminuíram e os níveis de Ca2+e ROS aumentaram em pacientes com MMD (p<0,001). Conclusões: Nossos resultados mostraram obviamente diminuição do nível sérico de CoQ10B e aumento do número de CPE em pacientes com DMM em comparação com pacientes saudáveis, e a função mitocondrial de CPE em pacientes com DMM estava anormal.

Avaliação comparativa entre analisadores hematológicos Mindray BC-6800 e URIT 5500, com ênfase na capacidade de detecção de blastos em pacientes portadores de leucemia aguda / Comparative evaluation between Mindray BC-6800 and URIT 5500 hematology analyzers, with emphasis on the ability to detect blasts in patients with acute leukemia

Comparar a capacidade dos analisadores hematológicos BC-6800 (Mindray) e URIT 5500 em sinalizar a presença de blastos em pacientes portadores de leucemia aguda. Foram analisadas 13 amostras de sangue periférico contendo blastos mielóide ou linfóide, provenientes de um hospital oncológico de Belém ­ Pará, previamente imunofenotipados por citometria de fluxo para verificar a capacidade dos equipamentos Mindray BC-6800 e URIT 5500 em sinalizar a presença dessas células no scatter leucocitário ou por emissão de ÀDJV. Para avaliação da existência de diferença estatística entre os resultados de hemácias, hemoglobina, leucócitos e plaquetas obtidos pelos equipamentos BC 6800 (Mindray) e URIT 5500 foi aplicado o teste não paramétrico ANOVA para análise de variância das amostras, o qual mostrou que não havia diferença estatística entre esses analitos. Não foi aplicado método estatístico para as contagens da diferencial leucocitária, pois o equipamento URIT 5500 não gerou dados numéricos para as amostras patológicas. Os dois equipamentos foram capazes de gerar ÀDJV e mudanças espacial do scatter leucocitário para amostras patológicas, contudo, o analisador BC 6800 (Mindray) foi o único a mudar a cor da população de blastos no scatter leucocitário. Os analisadores BC-6800 (Mindray) e URIT 5500 mostraram boa capacidade em sinalizar, através ÀDJV e do scatter leucocitário, para a presença de blastos mielóides ou linfóides em amostras patológicas. [au]

Compare the ability of the BC-600 (Mindray) and URIT 5500 hematological analyzers to signal the presence of blasts in patients with acute leukemia. Thirteen samples of peripheral blood containing myeloid or lymphoid blasts, from a cancer hospital in Belém - Pará, previously immunophenotyped by flow cytometry were analyzed to determine the capacity of the Mindray BC-6800 and URIT 5500 equipment in signaling the presence of these cells in the leukocyte scatter or by emitting flags. To assess the existence of statistical difference between the results of red blood cells, hemoglobin, leucocytes and platelets obtained by the BC 6800 (Mindray) and URIT 5500 equipments, the non-parametric ANOVA test was applied for analysis of variance of the samples, which showed that there was no statistical difference between these analytes. Statistical method was not applied for leukocyte differential counts, as the URIT 5500 equipment did not generate numerical data for the pathological samples. Both were able to generate flags and spatial changes from the leukocyte scatter to pathological samples, however the BC 6800 (Mindray) analyzer was the only one to change the color of the blast population in the leukocyte scatter BC-6800 (Mindray) and URIT 5500 analyzers showed good ability to signal, through flags and leukocyte scatter, for the presence of myeloid or lymphoid blasts in patholical samples. [au]

Exercício Físico Melhora as Funções das Células Progenitoras Endoteliais em Pacientes com Síndrome Metabólica / Exercise Training Improves Functions of Endothelial Progenitor Cells in Patients with Metabolic Syndrome

Resumo Fundamento As células progenitoras endoteliais (CPEs) desempenham um papel importante na manutenção da função endotelial. A síndrome metabólica (SM) está associada à disfunção das CPEs. Embora o exercício físico tenha um impacto benéfico na atividade das CPEs, seu mecanismo ainda não está completamente esclarecido. Objetivo O objetivo deste estudo é investigar os efeitos do exercício físico nas funções das CPEs e os mecanismos subjacentes em pacientes com SM. Métodos Os voluntários com SM foram divididos em grupo exercício (n=15) e grupo controle (n=15). Antes e após 8 semanas de treinamento físico, as CPEs foram isoladas do sangue periférico. Foram feitos o ensaio de unidades formadoras de colônias (UFC), o ensaio de formação de tubos, a expressão proteica do óxido nítrico sintase endotelial (eNOS), da fosfatidilinositol-3-quinase (PI3-K) e da proteína quinase B (AKT). Considerou-se um valor de probabilidade <0,05 para indicar significância estatística. Resultados Após 8 semanas, o número de UFCs aumentou significativamente no grupo exercício em comparação com o grupo controle (p<0,05). Além disso, observamos uma diminuição significativa do modelo de avaliação da homeostase da resistência à insulina (HOMA-IR), endotelina-1, proteína C reativa de alta sensibilidade e dos níveis de homocisteína no grupo exercício. A intervenção com exercícios também pode aumentar a capacidade de formação de tubos de CPEs e aumentar o nível de fosforilação de eNOS, PI3-K e AKT. Conclusão O exercício físico aprimorou as funções das CPEs. O mecanismo pode estar relacionado ao exercício, ativando a via PI3-K/AKT/eNOS.

Abstract Background Endothelial progenitor cells (EPCs) play an important role in maintaining endothelial function. Metabolic syndrome (MetS) is associated with EPC dysfunction. Although physical exercise has a beneficial impact on EPC activity, its mechanism is not completely clear yet. Objective The purpose of this study is to investigate the effects of physical exercise on the functions of EPCs and the underlying mechanisms in patients with MetS. Methods Volunteers with MetS were divided into exercise group (n=15) and control group (n=15). Before and after 8 weeks exercise training, EPCs were isolated from peripheral blood. Colony forming unit (CFU) assay, tube-formation assay, the protein expression of endothelial nitric oxide synthase (eNOS), phosphatidylinositol-3-kinase (PI3-K) and protein kinase B (AKT) were determined. A probability value <0.05 was considered to indicate statistical significance. Results After 8 weeks, the number of CFUs was significantly increased in the exercise group compared to the control group (p<0.05). In addition, we observed a significant decrease of homeostasis model assessment for insulin resistance (HOMA-IR), endothelin-1, high-sensitive C-reactive protein, and homocysteine levels in the exercise group. Exercise intervention could also enhance tube-formation capacity of EPCs and increase phosphorylation level of eNOS, PI3-K and AKT. Conclusion Physical exercise enhanced the functions of EPCs. The mechanism may be related to exercise, activating the PI3-K/AKT/eNOS pathway.

Profilaxis antifúngica primaria en pacientes oncohematológicos: ¿a quiénes, cuándo y con qué? / Primary antifungal prophylaxis in oncohematological patients: who, when, and with what?

Resumen Las infecciones fúngicas invasoras (IFI) constituyen una de las principales complicaciones infecciosas en pacientes oncohematológicos y con trasplante de células progenitoras hematopoyéticas (TCPH), ocasionando alta morbimortalidad e incrementando significativamente los costos de atención y la estadía hos pitalaria. La epidemiología de las IFI ha cambiado en las últimas décadas, siendo los hongos filamentosos, particularmente Aspergillus spp., los principales agentes etiológicos. Existen múltiples factores de riesgo para una IFI; pero la neutropenia profunda y prolongada, y la inmunodeficiencia celular severa siguen siendo los más importantes. Por este motivo, la población de mayor riesgo la constituyen los pacientes con leucemias agudas, mielodisplasias y TCPH alogénicos con enfermedad injerto contra huésped (EICH), en tratamiento con corticoides. Numerosos ensayos clínicos aleatorizados y metaanálisis han demostrado que la profilaxis antifúngica primaria (PAF) reduce significativamente la incidencia de IFI, tanto de aquellas causadas por Candida spp. como por Aspergillus spp., la mortalidad relacionada a IFI y la mortalidad global en algunos grupos de pacientes. Asimismo, en enfermos de alto riesgo, en donde se espera una incidencia de IFI elevada, es una estrategia costo-efectiva. Varios antifúngicos han demostrado beneficio clínico y pueden utilizarse como estrategia de PAF en diferentes escenarios, presentando ventajas y desventajas que deben ser tenidas en cuenta al momento de indicar una PAF. Para esto, sociedades científicas nacionales e internacionales, han emitido recomendaciones de indicación de PAF. Se analizan los aspectos relacionados con la eficacia clínica de los diferentes antifúngicos según la población de riesgo, las potenciales desventajas, momento y forma de administración.

Abstract Invasive fungal infections (IFI) are among the main infectious complications in patients with hema tological malignancies and with hematopoietic stem cell transplant (HSCT), causing high morbidity and mortality and significantly increasing the healthcare cost and hospital stay. The epidemiology of IFIs has changed in recent decades, with filamentous fungi, particularly Aspergillus spp., being the main etiological agents. There are multiple risk factors for having an IFI; however, the most important are profound and prolonged neutropenia and severe cellular immunodeficiency. For this reason, the population at greatest risk is made up of patients with acute leukemias, myelodysplasias and allogeneic HSCT with graft-versus-host disease (GVHD) treated with cortico steroids. Numerous randomized clinical trials and meta-analyses have shown that primary antifungal prophylaxis (AFP) significantly reduces the incidence of IFI, particularly those caused by Candida spp. and Aspergillus spp., IFI-related mortality, and overall mortality in some group of patients. Likewise, in high-risk patients, where a high incidence of IFI is expected, it is a cost-effective strategy. Several antifungals have demonstrated clinical benefit. They can be used as a AFP strategy in different settings, presenting advantages and disadvantages that must be taken into account in each case. For this, national and international scientific societies have issued recom mendations for the indication of AFP. Aspects related to the different antifungals' clinical efficacy are analyzed considering the population at risk, the potential disadvantages, timing, and form of administration.

Hematopoietic stem cell transplantation in a patient with osteopetrosis and mutation in CLCN7: long-term follow-up / Trasplante de células progenitoras hematopoyéticas en un paciente con osteopetrosis y mutación en CLCN7: seguimiento a largo plazo

Abstract Background: Osteopetrosis is a rare hereditary bone dysplasia characterized by insufficient osteoclast activity that results in increased bone mineral density. Hematopoietic stem cell transplantation (HSCT) can reverse skeletal abnormalities and restore hematopoiesis. Case report: We present the case of a 3-year and 2-month-old male patient with the diagnosis of osteopetrosis. The patient underwent allogeneic HSCT (Allo-HSCT) using 100% compatible bone marrow from a related donor and received a myeloablative conditioning regimen and a CD34 cell dose (4.7 × 107/kg). In the early post-transplant, frequent complications such as pneumonitis, hypercalcemia, and hyperphosphatemia ocurred. With a suitable granulocytic graft and chimerism of 100%, it was considered a successful transplant. However, the patient showed a delayed platelet graft treated with a platelet-stimulating factor for 6 months. The patient is currently disease-free, outpatient follow-up, with no data on graft-versus-host disease, and no progressive neurological damage. Conclusions: Osteopetrosis is a childhood disease that requires clinical suspicion and early diagnosis. HSCT is necessary at an early age to prevent disease progression and sensorineural, hematological, and endocrinological functions damage that can lead to death.

Resumen Introducción: La osteopetrosis es una displasia ósea hereditaria poco común, caracterizada por una actividad osteoclástica deficiente que aumenta la densidad mineral ósea. Se considera que el trasplante de células progenitoras hematopoyéticas (TCPH) puede revertir las anormalidades esqueléticas y restaurar la hematopoyesis. Caso clínico: Se presenta el caso de un paciente de sexo masculino, de 3 años y 2 meses de edad, con diagnóstico tardío de osteopetrosis. Se realizó un TCPH alogénico de donador relacionado 100% compatible con médula ósea. Se utilizaron un régimen de acondicionamiento mieloablativo y una dosis celular de CD34 de 4.7 × 107/kg de peso. En el postrasplante temprano, el paciente desarrolló complicaciones como neumonitis, hipercalcemia e hiperfosfatemia. Con un injerto granulocítico adecuado y quimerismo del 100% se consideró un trasplante exitoso. Sin embargo, el paciente presentó retraso en el injerto plaquetario, por lo que se administró factor estimulante de plaquetas por 6 meses. Actualmente el paciente se encuentra libre de enfermedad, en seguimiento ambulatorio, sin datos de enfermedad del injerto contra el hospedero y con pruebas de neurodesarrollo sin deterioro neurológico progresivo. Conclusiones: La osteopetrosis es una enfermedad infantil que requiere una sospecha clínica y un diagnóstico temprano, ya que es necesario un TCPH a corta edad como tratamiento para evitar la progresión de la enfermedad y el deterioro de las funciones neurosensoriales, hematológicas y endocrinológicas que puede derivar en la defunción del paciente.

Hematopoietic stem cell transplantation (HSCT) in the COVID-19 pandemic era / Trasplante de células progenitoras hematopoyéticas (TCPH)en la era del COVID-19

Abstract The pandemic of coronavirus infectious disease-2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a threat to global health. This has become an obstacle for the practice of hematology, mostly in low-middle income countries. For those hematologist and oncologists who perform hematopoietic stem cell transplantation HSCT the usual challenges of this kind of medical procedures have increased because of the COVID-19 pandemic. The importance of find the best route for performing HSCT avoiding excessive COVID-19 risk is of great importance. By doing so, we have been able to conduct 170 hematopoieic stem cell transplants during the COVID-19 pandemia.

Resumen La pandemia de COVID-19 ha causado daños graves a la práctica de la medicina y se ha convertido en un obstáculo para la práctica de algunas especialidades. Los trasplantes de células hematopoyéticas han sufrido las consecuencias de la pandemia y muchos centros de trasplante hematopoyético en todo el mundo suspendieron sus labores. Gracias a la implementación de medidas de escrutinio y aislamiento de los pacientes sometidos a trasplante hematopoyético, hemos podido trasplantar a 170 pacientes en la época del COVID-19.

Oral follicular lymphoid hyperplasia: clinicopathologic of a case series / Hiperplasia linfoide folicular oral: clinicopatológico de uma série de casos

RESUMEN La hiperplasia folicular linfoide (HFL) es una proliferación linfoide reactiva que puede simular linfomas, tanto clínica como histológicamente. El objetivo de este estudio fue investigar las características clínicas, morfológicas e inmunohistoquímicas de una serie de casos de HFL en la cavidad oral y discutir importantes aspectos diagnósticos y diagnósticos diferenciales en relación con los linfomas foliculares. Un análisis retrospectivo de los registros de una base de datos de 38 años reveló nueve casos diagnosticados como HFL de la cavidad oral. La edad de los pacientes osciló entre 8 y 44 años. La mayoría de las lesiones se localizaron en la mucosa oral y la presencia de un nódulo indoloro fue el hallazgo clínico más común. El análisis histopatológico reveló proliferación de células linfoides dispuestas en patrón folicular, presentando folículos primarios y secundarios con centro germinal y zona del manto, con evidencia de macrófagos que contenían cuerpos apoptóticos en su interior, así como evidencia de figuras de mitosis típicas. Observamos el área interfolicular, los linfocitos, los macrófagos e las islas epimioepiteliales. El análisis inmunohistoquímico reveló positividad de folículos linfoides para CD20, CD68, CD3 y linfoma de células B2 (Bcl-2). La presentación clínica de HFL y las evidencias histopatológicas de folículos linfáticos que muestran centros germinales indistintos con una zona del manto mal definida pueden ser un problema debido a la similitud con el linfoma folicular.

Intervenciones psicológicas en cuidadores primarios de pacientes con trasplante de células hematopoyéticas: Revisión descriptiva / Psychological interventions on primary care healthcare providers of patients with hematopoietic cells transplantation: Descriptive revision / Intervenções psicológicas em cuidadores primários de pacientes com transplante de células hematopoiéticas: Revisão descritiva

Resumen Introducción: El ser cuidador primario informal de un paciente con indicación médica de trasplante de células progenitoras hematopoyéticas puede tener consecuencias negativas en su salud mental y calidad de vida. Objetivo: Describir las intervenciones psicológicas disponibles para el cuidador primario de pacientes sometidos a trasplante de células hematopoyéticas. Metodología: Se realizó una búsqueda sistematizada de los últimos 10 años con los términos MeSH: psychotherapy AND caregive AND stem cell transplantation en las principales bases de datos médicas y de psicología, para su análisis se empleó la estrategia: Problema, Intervención, Comparación y Outcomes (PICO). Resultados: Se identificaron 122 artículos, de ellos diez cumplieron los criterios de inclusión. Las intervenciones provenían de profesionales de enfermería o trabajo social; el 50% incluyó diadas (paciente y cuidador primario), mostraron una tendencia de duración corta, enfocada al periodo posterior al trasplante. Se basan en el entrenamiento en solución de problemas, manejo de estrés, atención plena y expresión emocional. Las intervenciones lograron la disminución de la depresión, ansiedad y estrés en el cuidador; pero no alcanzaron permanencia en la significancia estadística de dichos restablecimientos. Discusión: De acuerdo con lo observado en las publicaciones y por su impacto positivo en la salud mental, se recomienda la implementación de intervenciones psicológicas en cuidadores de pacientes con trasplante de células progenitoras hematopoyéticas. Conclusión: El apoyo psicológico brindado al cuidador generalmente es de profesionales de la salud que no pertenecen al área de la psicología, con resultados clínicos favorables en las etapas más críticas de su estado mental.

Abstract Introduction: Being an informal primary healthcare provider of a patient who undergoes hematopoietic progeny cells transplantation can have adverse consequences on mental health and the quality of life. Objective: To describe the available psychological interventions for the primary healthcare provider of patients undergoing hematopoietic cells transplantations. Methodology: A systematized search of the last 10 years using the MeSH terms psychotherapy AND caregiver AND stem cell transplantation was conducted on the main medical and psychological databases. The analysis strategy followed the PICO scheme (Problem, Intervention, Comparison, Outcomes). Results: 122 articles were identified, and 10 of them fulfilled the inclusion criteria. The interventions were related to nursing or social work professionals. 50% described patient-healthcare provider dyads with short interventions focused on the post-transplantation period. Discussion: According to what has been observed in the publications and due to its positive impact on mental health, the implementation of psychological interventions is recommended in caregivers of patients who underwent hematopoietic stem cell transplantation. Conclusion: The psychological support provided to the caregiver comes mainly from health professionals who do not belong to the area of psychology, with favorable clinical results in the most critical periods for their mental state.

Resumo Introdução: Ser cuidador primário informal de um paciente sometido a transplante de células progenitoras hematopoiéticas pode ter consequências negativas na saúde mental e na qualidade de vida. Objetivo: Descrever as intervenções psicológicas disponíveis para o cuidador primário de pacientes sometidos a transplante de células hematopoiéticas. Metodologia: Realizou-se uma busca sistematizada dos últimos 10 anos com os termos MeSH: psychotherapy AND caregive AND stem cell transplantation nas principais bases de dados médicas e de psicologia, para sua análise realizou-se a estratégia: Problema, Intervenção, Comparação e Outcomes (PICO). Resultados: Identificaram-se 122 artigos, dos quais, dez cumpriram os critérios de inclusão. As intervenções provinham de profissionais em enfermagem ou trabalho social; o 50% incluiu díades (paciente e cuidador primário), mostraram uma tendência de duração curta, focalizada no período posterior ao transplante. Baseiam-se no treinamento em solução de problemas, manejo de estresse, atenção plena e expressão emocional. As intervenções conseguiram melhoras clínicas na diminuição da depressão, ansiedade e estresse no cuidador; mas não alcançaram permanência na significância estatística destes restabelecimentos. Discussão: Conforme o observado nas publicações e por seu impacto positivo na saúde mental, recomenda-se a implementação de intervenções psicológicas em cuidadores de pacientes para quem se indicou transplante de células progenitoras hematopoiéticas. Conclusão: O apoio psicológico oferecido ao cuidador vem de principalmente profissionais da saúde que não pertencem à área da psicologia, com resultados clínicos favoráveis nos períodos mais críticos para seu estado mental.

Donación dirigida de sangre de Cordón Umbilical de Hermano Compatible en el Sistema de Salud Público de Chile / Directed sibling donor cord blood donation in the Chilean Public Health System

Resumen: Introducción: La sangre de cordón umbilical (SCU) como fuente para trasplante de células proge- nitoras hematopoyéticas (TPH) está bien establecida. Internacionalmente, menos del 10% de los TPH de SCU corresponde a donantes hermanos compatibles. Dentro de la red del Programa Infantil Nacional de Drogas Antineoplásicas (PINDA), existe desde enero 2004 un programa de donación dirigida de SCU para TPH. Pacientes y Método: Se diseñó un estudio observacional, retrospectivo, descriptivo, se revisaron el número y características de las unidades de SCU recolectadas en el PINDA y el número, características y evolución de los pacientes trasplantados con esas unidades entre enero de 2004 y octubre de 2018. Resultados: Sesenta unidades de SCU han sido recolectadas, de ellas 55 con registro completo. La mediana de volumen de las unidades almacenadas fue 74,8 ml (30,0-170,8), la mediana de células nucleadas totales 7,6 x 10e8 (2,0-21,1), mediana de células CD34+ 1,6 x 10e6 (0,2-11,6). Cuatro pacientes con leucemias de alto riesgo fueron trasplantados; mediana de segui miento es de 8 años. Todos desarrollaron complicaciones severas post TPH, uno de ellos falleció de recaída y los tres actualmente vivos presentan un Karnofsky/Lansky 100%. Conclusión: El programa ha permitido el trasplante de 4 pacientes que de otro modo no habrían tenido acceso a un donante. Este programa de donación dirigida puede ser considerado una primera etapa para el desarrollo de un banco público de sangre de cordón umbilical en Chile.

Abstract: Introduction: Cord blood (CB) as a source of Hematopoietic Stem Cells for Transplantation (HSCT) is well established. Worldwide, nonetheless, less than 10% of the CB HSCTs are performed with a match sibling donor. Since 2004, the Chilean National Childhood Cancer Program (PINDA) net work, has established a CB directed donation program for HSCT. Patients and Method: An obser vational, descriptive and retrospective study was designed to assess the number and characteristics of the CB units collected in the program as well as the number, clinical characteristics and follow-up of the patients who received an HSCT from those CB units between January 2004 and October 2018. Results: Sixty CB units have been collected; 55 of them with full records and stored. The median volume collected was 74.8 ml (30.0-170.8), the median number of total nucleated cells was 7.6 x 10e8 (2.0-21.1), and the median of CD34+ cells was 1.6 x 10e6 (0.2-11.6). Four high-risk leukemia patients received HSCT, all of them developed severe complications after transplantation and one patient died due to relapse. Those patients currently alive have a 100% Karnofsky/Lansky score. The median follow-up time was 8 years. Conclusion: The PINDA program has allowed 4 patients to be transplan ted who otherwise would not have had access to a donor. This directed donation program could be seen as a model for the development of a public cord blood bank in Chile.

Clinical studies using stem cells for treatment of retinal diseases: state of the art / Estudos clínicos com uso de células-tronco para tratamento de doenças da retina: estado da arte

ABSTRACT Degenerative retinal diseases such as retinitis pigmentosa, Stargardt's macular dystrophy, and age-related macular degeneration are characterized by irreversible loss of vision due to direct or indirect photoreceptor damage. No effective treatments exist, but stem cell studies have shown promising results. Our aim with this review was to describe the types of stem cells that are under study, their effects, and the main clinical trials involving them.

RESUMO As doenças degenerativas da retina, como retinose pigmentar, distrofia macular de Stargardt e degeneração macular relaciona à idade, são caracterizadas por perda irre versível da visão devido a danos diretos ou indiretos aos fotorreceptores. Não existem tratamentos eficazes, porém os estudos com células-tronco mostraram resultados promissores. Nosso objetivo com esta revisão foi descrever os tipos de células-tronco em estudo, seus efeitos e os principais ensaios clínicos que as envolvem.

Evaluación De Quimerismo En Pacientes Con Injerto De Células Progenitoras Hematopoyéticas En Panamá Del 2000­20 / Evaluation of Chimerism in Patients with Graft Hematopoietic Progenitor Cells in Panama from 2000­2018

Introducción: El Injerto de células progenitoras hematopoy éticas (ICPH) es actualmente un trata­miento para diferentes desórdenes hematológicos malignos y no malignos. El análisis del quimeris­mo post ICPH, y la cuantificación de cada población celular, deben ser monitoreados. El presente trabajo tiene como objetivo: el evaluar los res ultados de quimerismo completo y mixto en sangre periférica del receptor pos trasplante obtenidos por método cualitativo y cuantitativo del año 2000 al 2018. Material y método: El presente es un estudio descriptivo, observacional, transversal de dos mé­ todos de quimerismo efectuados a receptores y donantes de ICPH alogénico. Resultados: De los 79 pacientes estudiados por el método cualitativo: 65 (82.2%) resultaron con qui­ merismo completo y 14 (17.7%) con quimerismo mixto. No fue posible cuantificar por este método el % de células del donante y del receptor.Conclusión: El método cuantitativo es un método exacto, que determina el % de células del receptor y del donante presentes en la muestra. Con este método se evalúan un mayor número de marcadores genéticos que con el método cualitativo, y se obtienen un mayor número de loci informativos del quimerismo al compararlo con el método cualitativo.

Introduction: Hematopoietic progenitor cell grafting (ICPH) is currently a treatment for different ma­ lignant and non­malignant hematological disorders. The analy sis of post­ICPH chimerism, and the quantification of each cell population, should be monitored. The present work has as objective: to evaluate the results of complete and mixed chimerism in peripheral blood of the post­trans plant reci­pient obtained by qualitative and quantitative method from the year 2000 to 2018. Material and method: The present is a descriptive, observational, cross­sectional study of two met­ hods of chimerism performed on allogeneic ICPH recipients and donors . Results: Of the 79 patients studied by the qualitative method: 65 (82.2%) resulted with complete chi­ merism and 14 (17.7%) with mixed chimerism. It was not possible to quantify by this method the% of donor and recipient cells. Conclusion: The quantitative method is an exact method, which determi­nes the% of recipient and donor cells present in the sample. With this method, a greater number of genetic markers are evaluated than in the qualitative method, and a greater number of information loci of chimerism are obtained than with the qualitative method.

Infecciones virales en receptores de trasplante alogénico de células progenitoras hematopoyéticas / Viral infections in allogeneic hematopoietic stem cell transplantation recipients

Introducción: El Trasplante alogénico de células progenitoras hematopoyéticas (TCPH) se asocia a una lenta recuperación de sistema inmune, lo que predispone a sus receptores a presentar múltiples complicaciones infecciosas. En este trabajo se analizan las infecciones virales de una cohorte retrospectiva. Material y métodos: se revisó la base de datos del servicio y se registraron las infecciones virales del periodo 2012-2016. Resultados: n 215. El 91% de los receptores y el 70% de los donantes eran CMV positivos antes del trasplante, el 47% de os receptores presentó reactivación de CMV y el 10% enfermedad, con una mortalidad directa del 3,1%. El 87% de los receptores y el 70% de los donantes tenían serología para EBV y el 13% tuvieron una reactivación con una carga viral > 20.000 copias/ml. El 11% de los pac tuvieron enfermedad por Herpes zoster, el 6% por Herpes 6 y el 5% por Herpes simple. Se detectó infección por adenovirus en el 25% de los pacientes, siendo el compromiso más frecuente el digestivo, seguido de la infección respiratoria baja. La mortalidad directa por adenovirus fue 5,1%. Se registraron 41 episodios de infección respiratoria aguda baja por virus respiratorios, con una mortalidad directa del 4%. El 18% de los pac tuvo cistitis hemorrágica por virus BK, con viremia asociada en el 41% de los casos. El 6% de los pacientes presentó falla hematológica asociada a Parvovirus, que un caso fue causa de la pérdida del injerto. Conclusión: las enfermedades virales son una complicación muy frecuente del TCPH y con gran peso en la mortalidad relacionada al trasplante. Los avances terapéuticos han sido menores que los alcanzados en los métodos diagnósticos (AU)

Introduction: Allogeneic hematopietic stem cell transplantation (HSCT) is associated with a slow recovery of the immune system leading to multiple infectious complications. In this study viral infections are evaluated in a retrospective cohort. Material and methods: The data base of the department was reviewed recording viral infections that occurred between 2012-2016. Results: n 215; 91% of the recipients and 70% of the donors were CMV prior to the transplant; 47% of the recipients had a CMV reactivation and 10% developed the disease with a related mortality of 3.1%. Overall, 87% of the recipients and 70% of the donor had a positive serology for EBV and 13% had a reactivation with a viral load of > 20,000 copies/ml. Of the patients, 11% had Herpes zoster, 6% Herpes 6, and 5% Herpes simplex. Adenovirus infection was detected in 25% of the patients, most commonly involving the digestive tract followed by lower respiratory tract infection. Adenovirusrelated mortality was 5.1%. Forty-one acute lower respiratory tract infections due to respiratory viruses were recorded leading to a mortality of 4%. Of all the patients, 18% had BK virus-related hemorrhagic cystitis with associated viremia in 41% of the cases. Six percent of the patients had parvovirusassociated hemotologic failure leading to graft loss in one case. Conclusion: Viral diseases are a very frequent complication in HSCT with a high transplant-related mortality. Advances in therapy have lagged behind advances in diagnostic methods (AU)

Haplotipo HLA infrecuente en un estudio familiar de histocompatibilidad para trasplante de células progenitoras hematopoyéticas / Non frequent HLA haplotype in a family-based histocompatibility study for hematopoietic stem cell transplantation

Ante una indicación de trasplante de células progenitoras hematopoyéticas se realiza la tipificación de los antígenos HLA de clase I y clase II al receptor y sus posibles donantes. En el departamento de Histocompatibilidad del Instituto de Hematología e Inmunología de La Habana se realizó un estudio familiar de histocompatibilidad a una paciente diagnosticada de leucemia linfoide aguda Ph+. La paciente y el padre presentaron el haplotipo HLA-A*03:01 B*39:10 C*12:03 DRB1*15:03 DQB1*06:02, que se identificó en el abuelo paterno, aunque por técnicas de baja resolución. A su vez, en el hermano y la madre también se tipificó un haplotipo compuesto por estos mismos alelos HLA-A, B, C, DRB1 y DQB1; y que se detectó en baja resolución en el abuelo materno. Sorprendentemente la paciente era HLA idéntica a la madre, cuando se esperaría que solo compartieran la mitad de los genes HLA. El hecho de que el haplotipo objeto de estudio apareciera en ambos padres de la paciente, quienes provenían de familias sin vínculos de parentesco conocido en al menos dos generaciones pasadas, puede considerarse un evento poco probable. Las investigaciones inmunogenéticas que están basadas en la tipificación HLA, no solo contribuyen a la selección de la mejor pareja donante receptor, sino que permiten a caracterizar el patrimonio genético del país(AU)

When a hematopoietic stem cell transplantation is indicated, the HLA class I and class II antigens are typed in the recipient and its possible donors. In the Histocompatibility department of the Institute of Hematology and Immunology of Havana, a family-based histocompatibility study was performed to a patient diagnosed with Ph+ acute lymphoid leukemia. The patient and the father presented the haplotype HLA-A*03:01 B*39:10 C*12:03 DRB1*15:03 DQB1*06:02, which was also identified in the paternal grandfather by low resolution techniques. In turn, a haplotype, composed of the same HLA-A, B, C, DRB1 and DQB1 alleles, was typed in the mother and the sibling and it was detected in low resolution in the maternal grandfather. Surprisingly, the patient was HLA identical to the mother, when they would be expected to share only half of the HLA genes. The fact that the haplotype under study appeared in both parents of the patient, who came from families without known ties of kinship in at least two past generations, can be considered an unlikely event. Immunogenetic investigations based on HLA typing, not only contribute to the selection of the best recipient donor pair, but also allow characterizing the nation's genetic heritage(AU)

Effects of Chronic Exercise on Endothelial Progenitor Cells and Microparticles in Professional Runners / Efeitos de Exercício Crônico Sobre Células Progenitoras Endoteliais e Micropartículas em Corredores Profissionais

Abstract Background: The effects of chronic exposure to exercise training on vascular biomarkers have been poorly explored. Objective: Our study aimed to compare the amounts of endothelial progenitor cells (EPCs), and endothelial (EMP) and platelet (PMP) microparticles between professional runners and healthy controls. Methods: Twenty-five half-marathon runners and 24 age- and gender-matched healthy controls were included in the study. EPCs (CD34+/KDR+, CD133+/KDR+, and CD34+/CD133+), EMP (CD51+) and PMP (CD42+/CD31+) were quantified by flow-cytometry. All blood samples were obtained after 12 h of fasting and the athletes were encouraged to perform their routine exercises on the day before. Results: As compared with controls, the CD34+/KDR+ EPCs (p=0.038) and CD133+/KDR+ EPCs (p=0.018) were increased, whereas CD34+/CD133+ EPCs were not different (p=0.51) in athletes. In addition, there was no difference in MPs levels between the groups. Conclusion: Chronic exposure to exercise in professional runners was associated with higher percentage of EPCs. Taking into account the similar number of MPs in athletes and controls, the study suggests a favorable effect of exercise on these vascular biomarkers.

Resumo Fundamento: Os efeitos da exposição crônica ao exercício sobre biomarcadores vasculares foram pouco estudados. Objetivo: Nosso estudo teve como objetivo comparar as quantidades de células progenitoras endoteliais (CPEs), e de micropartículas endoteliais (MPEs) e plequetárias (MPPs) de corredores profissionais com controles sadios. Métodos: Vinte e cinco corredores de meia maratona e 24 controles pareados quanto à idade e ao sexo foram incluídos no estudo. CPEs (CD34+/KDR+, CD133+/KDR+ e CD34+/CD133+), MPE (CD51+) e MPPs (CD42+/CD31+) foram quantificadas por citometria de fluxo. Todas as amostras de sangue foram obtidas após 12 horas de jejum, e os atletas foram incentivados a realizar seus exercícios de rotina no dia anterior à coleta. Resultados: Em comparação aos controles, CPEs CD34+/KDR+ (p=0,038) e CD133+/KDR+ (p=0,018) estavam aumentados, e CPEs CD34+/CD133+ não foram diferentes (p=0,51) nos atletas. As concentrações de MP não diferiram entre os grupos. Conclusão: A exposição crônica ao exercício em corredores profissionais associou-se a uma maior porcentagem de CPEs. Considerando o número similar de MPs entre atletas e controles, o estudo sugere um efeito favorável do exercício sobre esses biomarcadores vasculares.

Lamellar keratoplasty in rabbits using an allogeneic free omental graft and omentum-derived mesenchymal cells associated with the canine amniotic membrane / Ceratoplastia lamelar em coelhos usando enxerto de omento alógeno livre e células mesenquimais omentais associadas com membrana amniótica canina

ABSTRACT: The objective of this research was to evaluate the clinical and microscopic effects in rabbits of lamellar keratoplasty using allogeneic omentum associated with canine amniotic membrane (AM). Rabbits were divided into two groups: one received the allogeneic free omental graft covered with the AM (OM-graft group), while the other received the AM graft containing omental mesenchymal cells (OM-cell group). Clinical signs were evaluated on different postoperative days. After the clinical assessments, the rabbits were euthanized and their corneas were obtained for histopathology and immunohistochemistry (Ki-67, marker for proliferation). Both groups showed chemosis, blepharospasm, eye discharge, hyperemia, and corneal opacity/edema. Neovascularization was observed in the OM-cell group. Histopathological evaluation revealed epithelial islands within the stroma of OM-cell samples. Thirty days after surgery, complete corneal re-epithelialization had occurred in both groups. The OM-cell group showed more Ki-67 positive cells. The free omentum and its cells, combined with the AM, contributed to corneal repair, a process that was completed 30 days after lamellar keratoplasty.

RESUMO: Objetivou-se, com a pesquisa, avaliar os efeitos clínicos e microscópicos da associação do omento de coelho com a membrana amniótica (AM) canina, na ceratoplastia lamelar em coelhos. Dois grupos foram constituídos: um recebeu enxerto de omento alógeno livre, recoberto por AM (grupo OM- graft); o outro recebeu enxerto de AM contendo células mesenquimais derivadas do omento (grupo OM-cell). Manifestações clínicas foram avaliadas em diferentes tempos de pós-operatórios. Após as avaliações clínicas, coelhos foram submetidos à eutanásia e córneas foram colhidas para histopatologia e imunohistoquímica (Ki-67, marcador de proliferação). Relativamente às manifestações clínicas, ambos os grupos apresentaram sinais de quemose, blefarospasmo, secreção ocular, hiperemia e opacidade/edema. Neovascularização foi observada no grupo OM-cell. Avaliações à histopatologia mostraram que uma amostra de OM-cell apresentou ilhas de epitélio dentro do estroma. Aos 30 dias de pós-operatório, observou-se reepitelização corneal completa, em OM-graft e OM-cell. O grupo OM-cell apresentou mais células positivas para Ki-67. O omento livre e suas células, associados à AM, contribuíram para a reparação corneal, que se completou após 30 dias de ceratoplastia lamelar.

Complicaciones neurológica no infecciosas luego de trasplante de células progenitoras hematopoyéticas en pacientes pediátricos / Neurological complications after hematopoietic stem cell transplantation in pediatric patients

Objetivo: Analizar las complicaciones neurológicas no infecciosas en una cohorte de pacientes pediátricos receptores de trasplante de células progenitoras hematopoyéticas (CPH). Material y métodos: Estudio retrospectivo. Se analizaron todos los trasplantes realizados entre 1995 y 2015. Se efectuó un análisis uni-variable de la asociación de toxicidad en SNC y de encefalopatía posterior reversible (EPR) con enfermedad de injerto contra huésped (EICH), tipo de trasplante, enfermedad de base y mortalidad relacionada al trasplante, utilizando la prueba de Fisher. Se consideró como significativa una p <0.05. Resultados: Se analizaron un total de 479 trasplantes (171 niñas y 308 varones), edad m: 8 años (rango 1 m- 21 años). En 391 casos la fuente de CPH fueron donantes familiares y en 88 no familiares. Treinta y cuatro pacientes (7.10%) presentaron compromiso neurológico de origen no infeccioso. Seis presentaron (EPR) y el resto manifestaciones variadas (convulsiones, excitación psicomotriz, alucinaciones). Las manifestaciones de toxicidad neurológica fueron más frecuentes en los pacientes con EICH aguda (9,16% vs 4,63% p 0,039). Todos los pacientes con EPR presentaron EICH (p 0,04) y en el 67% de los casos esta fue grado 3-4 (p < 0,001). Al analizar la relación temporal encontramos que en el 78% de los casos la EICH precedió a la EPR. La mortalidad relacionada al trasplante fue algo superior a la de los pacientes sin complicaciones neurológicas no infecciosas (29% vs 22% NS) pero no se observaron muertes de causa neurológica (AU)

Aim: To analyze non-infectious neurological complications in a cohort of pediatric patients who underwent hematopoietic stem cell (HPSCT) transplantation. Material and methods: Retrospective study. All transplantations performed between 1995 and 2015 were analyzed. In univariate analysis the association between neurotoxicity and posterior reversible encephalopathy (PRE) and graft-versus-host disease (GVHD), type of transplant, underlying disease, and transplant-related mortality was assessed using Fisher's test. A p <0.05 was considered significant. Results: Overall, 479 transplantations (171 in girls and 308 in boys) were evaluated; mean age was 8 years (range, 1 m-21 years). In 391 cases the source of the HPSC were related and in 88 unrelated donors. Thirty-four patients (7.10%) presented with non-infectious neurological involvement. Six patients had PRE and the remaining children had variable manifestations (seizures, psychomotor agitation, hallucinations). Manifestations of neurotoxicity were more common in patients with acute GVHD (9.16% vs 4.63%; p 0.039). All patients with PRE had GVHD (p 0.04) and 67% of the children had grade 3-4 GVHD (p < 0.001). When analyzing time, we found that in 78% of the cases GVHD preceded PRE. Transplant-related mortality was slightly higher in patients without non-infectious neurological complications (29% vs 22%; NS) but no deaths due to neurological causes were observed (AU)

Efectos in vivo del ranelato de estroncio sobre células progenitoras de médula ósea de ratas diabéticas / In vivo effects of strontium ranelate on bone marrow progenitor cells of diabetic rats

La diabetes mellitus (DM) crónica se asocia con reducción en el contenido mineral óseo (osteopenia y osteoporosis). El objetivo de este trabajo fue evaluar la acción del ranelato de estroncio (RaSr) administrado por vía oral a animales control y diabéticos, sobre el potencial osteogénico de células progenitoras de médula ósea (CPMO). Dieciséis ratas Wistar macho jóvenes se dividieron en dos grupos: controles (C) y diabéticas (D) con destrucción parcial de células b-pancreáticas mediante inyecciones intraperitoneales consecutivas de nicotinamida y estreptozotocina. Siete días después de la inyección, cada grupo se subdividió: sin tratamiento, o tratadas oralmente con RaSr (625 mg/kg/día) durante seis semanas, luego de lo cual los animales fueron sacrificados. Las CPMO se obtuvieron de ratas de los cuatro grupos, por lavados del canal diafisario medular (húmero o fémur o ambos) y cultivo hasta confluencia en DMEM-10% FBS. La proliferación celular se evaluó mediante el ensayo de MTT. Luego las CPMO se replaquearon e incubaron en un medio osteogénico durante 14 días (fosfatasa alcalina [FAL] y colágeno tipo 1) o 21 días (mineralización). Las CPMO del grupo C+RaSr mostraron un aumento significativo versus control en la proliferación (133%) y en la diferenciación osteogénica (colágeno 143%, FAL 168%, mineralización 117%). La DM (grupo D) disminuyó significativamente la proliferación y diferenciación osteoblástica de las CPMO. El tratamiento con RaSr (grupo D+RaSr) previno completamente estos efectos antiosteogénicos de la DM. Así, en nuestro modelo experimental in vivo, la DM disminuye el potencial osteogénico de CPMO, efecto que puede ser prevenido por un tratamiento oral con RaSr. (AU)

Chronic diabetes mellitus (DM) is associated with a reduction in bone mineral content (osteopenia and osteoporosis). The object of this study was to evaluate the in vivo effect of he anti-osteoporotic drug strontium ranelate (SrRa) administered orally to control and diabetic animals, on the osteogenic potential of bone marrow progenitor cells (BMPC). Sixteen young male Wistar rats were divided into two groups: control (C) and diabetic with partial beta-cell destruction via consecutive intra-peritoneal injections of nicotinamide and streptozotocin (D). Seven days postinjection, each group was sub-divided: without treatment, or oral treatment with SrRa (625 mg/kg/day) for six weeks, after which the animals were euthanised (groups C, C+SrRa, D, D+SrRa). BMPC were obtained from rats of all four groups by flushing of the diaphysary canal (humerus and/or femur). Adherent cells were then cultured until confluence in DMEM10% FBS. Cell proliferation was evaluated with the MTT mitogenic bioassay. BMPC were replated and incubated in an osteogenic medium for 14 days (determination of alkaline phosphatase [ALP] and type-1 collagen) or 21 days (evaluation of mineralisation). BMPC from C+SrRa rats showed a significant increase versus control in proliferation (133%) and in osteogenic differentiation (collagen 143%, ALP 168%, mineralisation 117%). Induction of diabetes (group D) significantly decreased the proliferation and osteoblastic differentiation of BMPC. Treatment of diabetic animals with SrRa (group D+SrRa) completely prevented these anti-osteogenic effects of Diabetes. Thus, in our experimental in vivo model, Diabetes decreases the osteogenic potential of BMPC, an effect that can be prevented by oral treatment with strontium ranelate. (AU)

Trombosis y trasplante de progenitores hematopoyéticos: patogénesis y complicaciones trombóticas más frecuentes / Thrombosis and hematopoetic progenitor cells transplant: pathogenesis and most frequent thrombotic complications

Las complicaciones trombóticas son comunes en el contexto del trasplante de células progenitoras hematopoyéticas. El daño al endotelio vascular aparece como el factor desencadenante en la cascada de evento que conlleva a la trombosis en el paciente trasplantado. Estas complicaciones son diversas y aparecen en las fases inmediatas o tardías. El síndrome de obstrucción sinusoidal hepático, caracterizado por trombosis en los pequeños vasos de la microcirculación, constituye la complicación más frecuente y mejor estudiada. En este trabajo se revisa la patogénesis de las complicaciones trombóticas en el paciente con trasplante de células progenitoras hematopoyéticas y se describen las más frecuentes.

Thrombotic complications are very common during hematopoietic stem cell transplantation. The damage to vascular endothelium appears like the triggering factor leading to thrombosis in the transplanted patient. There are several thrombotic complications after hematopoietic stem cell transplantation and they can occur in the early or late phases. The sinusoidal obstruction syndrome is the most frequent and well studied of these complications and is characterized by thrombosis of small vases of microcirculation. We hereby review the pathogenesis of thrombotic complications and describe the more frequent ones.