RESUMO
O envelhecimento é um processo fisiológico que traz consigo uma série de alterações no organismo que se estendem até o nível molecular. Diante disto, este é um processo complexo que afeta diversos tecidos, sendo um deles o hematopoético, local onde, através de interações da Célula Tronco Hematopoética (CTH) com o ambiente ao seu redor, incluindo a Célula Tronco Mesenquimal (CTM), ocorre a hematopoese. Embora já sejam descritas na literatura algumas alterações na medula óssea consequentes do envelhecimento, os mecanismos por trás de tais mudanças permanecem elusivas, principalmente no âmbito das interações celulares ocorrentes na medula óssea. Portanto, este trabalho buscou investigar como o envelhecimento afeta a regulação hematopoética no contexto de sua relação com as CTM medulares. Para esta pesquisa, foram utilizados camundongos machos isogênicos da linhagem C57BL/6, dividindoos em grupos conforme sua idade: jovens (3 5 meses) e idosos (18 19 meses). Foi realizada a caracterização do modelo através de aspectos físicos como consumo proteico, variação de peso, entre outros, seguido de avaliação bioquímica e hematológica. Adicionalmente, foram coletadas células medulares e, posteriormente, realizado o isolamento das CTMs. Para estudar a relação destas células com a hematopoese, foram realizados ensaios in vitro utilizando a linhagem celular leucêmica C1498 (TIB-49™, ATCC®) mantidas em contato com o sobrenadante das CTMs isoladas. Quanto aos parâmetros bioquímicos, os animais idosos apresentaram menores níveis de albumina, aspartato alanina transferase (ALT) e de triglicerídeos quando comparados aos animais jovens. Contrariamente, os animais idosos apresentaram um maior nível de colesterol. Na avaliação hematológica, foi constatado pelo hemograma que os animais idosos apresentaram valores comparáveis aos animais jovens, todavia, o mielograma mostrou menor celularidade geral, seguido de menor número de células da linhagem eritroide e maior número de precursores granulocíticos. Através da imunofenotipagem, foi revelado um maior número de CTHs e de precursores grânulosmonocíticos na medula de animais idosos quando comparado aos jovens, e uma menor frequência de progenitores linfoides. Na imunofenotipagem de sangue periférico de animais idosos houve uma redução no número de linfócitos B e de eritrócitos, e aumento na população de células natural killers. Na imunofenotipagem de CTMs, o marcador CD73 apresentou menor expressão nos animais idosos. Avaliando o secretoma destas células estromais, foram encontrados no sobrenadante de CTMs de animais idosos aumentos significativos nas concentrações de CXCL12 e SCF e redução de IL-11. No âmbito molecular, as CTMs de animais idosos apresentaram aumento na expressão de Akt1, Nos e Ppar-γ, e redução na expressão de Csf3 e Cdh2. Adicionalmente, quando comparado a ação das CTMs de animais idosos em relação as CTMs de animais jovens, observou-se que CTMs de animais idosos foram capazes de aumentar a expressão de Sox2, Pou5f1 e Nanog e diminuir a expressão de Cdkn1a de células da linhagem C1498. O sobrenadante de CTMs de animais idosos também resultou na maior proliferação e migração de células da linhagem C1498. Portanto, levando em consideração a importância das CTMs sobre a regulação do sistema hematopoético, pode-se concluir que, no envelhecimento, as CTMs criam um ambiente propício para a proliferação celular no qual a manutenção da pluripotência é estimulada, o que pode acarretar em uma desregulação do sítio hematopoético quando habitado por células malignas
Aging is a physiological process in which occurs a series of alterations in an organism that extend to a molecular level. It is a complex process that affects various tissues, one of them being the bone marrow, wherethrough the interactions of the hematopoietic stem cell (CTH) with its surrounding environment, including with the mesenchymal stem cell (CTM), hematopoiesis takes place. Although some aging-associated alterations in the bone marrow can be found described in the literature, the mechanisms behind said changes remain elusive, especially when regarding the cellular interactions present inside the bone marrow. Therefore, this research aimed to investigate how aging affects the regulation of hematopoiesis in the context of its interactions with bone marrow-derived CTMs. For this investigation, male isogenic C57BL/6 mice were used as animal models. These were separated in two groups according to their age: young (3 5 months) and aged (18 19 months). The animal models were characterized by their physical properties such as protein intake and weight variation, followed by biochemical and hematological evaluation. Bone marrow cells were obtained and identified through immunophenotyping, thus isolating different cell populations, including the CTMs. To study the relationship between these cells and hematopoiesis, in vitro assays were conducted utilizing the leukemic cell lineage C1498 (TIB-49™, ATCC®) maintained in contact with the supernatant of isolated CTMs. By their biochemical profile, aged mice showed lower levels of albumin, alanine-aspartate transferase (ALT) and triglycerides compared to the young group. In contrast, aged mice had a higher cholesterol level. Hematological evaluation by total blood count showed similar results between the two groups, however, the myelogram revealed that the aged animals had lower cellularity, with less frequent cells from the erythroid lineage, with an increase in granulocytic precursors. Through immunophenotyping, it was also revealed that aged mice have higher numbers of hematopoietic stem cells, while also being noted a reduced population of lymphoid progenitors. An increase in the granulomonocytic progenitors was also found. Immunophenotyping peripheral blood cells of aged mice revealed reduced numbers of B lymphocytes and erythrocytes, and an increased natural killer cell population. Additionally, the cell surface marker CD73 was found to be less expressed in aged mice CTMs. The secretome of these stromal cells obtained from aged mice showed higher levels of CXCL12 and SCF, and lower levels of IL-11when compared to the young counterparts. At a molecular level, CTMs obtained from aged mice expressed more Akt1, Nos and Ppar-γ, while the expression of Csf3 and Cdh2 was reduced. Additionally, when comparing the effects of aged mice CTMs with young mice CTMs, it was observed that the first expressed were capable of increasing the expression of Sox2, Pou5f1 and Nanog, while decreasing Cdkn1a expression in the C1498 cell lineage. The supernatant obtained from aged mice also favored the proliferation and cell migration of the C1498 cell line. Thus, considering the importance that CTMs have over the hematopoietic system, we can conclude that, in aging, CTMs create a special environment which favors cell proliferation and maintenance of pluripotency, which can result in a dysregulation of the hematopoietic tissue when malignant cells are present
Assuntos
Animais , Masculino , Camundongos , Envelhecimento/metabolismo , Células-Tronco Mesenquimais/classificação , Hematopoese/genética , Células-Tronco Hematopoéticas/classificação , Sistema Hematopoético/anormalidadesRESUMO
Objetivo. Avaliar a eficácia dos protocolos de aplicação transcutânea do Intravenous Laser Irradiation of Blood 30' e 60', sobre os efeitos adversos no tecido hematopoiético por agentes quimioterápicos antineoplásicos endovenosos em adultos. Método. Ensaio clínico, randomizado e unicego, realizado em serviço ambulatorial de quimioterapia de hospital público do estado de São Paulo realizado de abril de 2018 a março de 2019. A amostra constituiu de 55 pacientes com tumores sólidos, a partir do segundo ciclo de tratamento com fármacos endovenosos citotóxicos para o tecido hematopoiético. O comprimento de onda utilizado foi de 660 nm, por via transcutânea, sob artéria radial. Resultado. Comparado ao tipo de hemocomponente, obtivemos, respectivamente aos protocolos do Intravenous Laser Irradiation of Blood 30' e 60': hemoglobina (85%; 86%), plaquetas (100%; 100%) e neutrófilos (95%; 92%). Conclusão. Considerou-se ambos os protocolos eficazes e, portanto, sugere-se implantá-los em unidades de quimioterapia(AU)
Objective: To evaluate the effectiveness of the protocols for transcutaneous application of the Intravenous Laser Irradiation of Blood 30' and 60', on the adverse effects on hematopoietic tissue by intravenous antineoplastic chemotherapeutic agents in adults. Method. Clinical, randomized and single-blind trial, carried out in an outpatient chemotherapy service of a public hospital in the state of São Paulo, carried out from April 2018 to March 2019. The sample consisted of 55 patients with solid tumors, from the second cycle of treatment with cytotoxic intravenous drugs for hematopoietic tissue. The wavelength used was 660 nm, transcutaneously, under the radial artery. Result. Compared to the type of blood component, we obtained, respectively from the Intravenous Laser Irradiation of Blood 30' and 60' protocols: hemoglobin (85%; 86%), platelets (100%; 100%) and neutrophils (95%; 92%). Conclusion. Both protocols were considered effective and, therefore, it is suggested to implant them in chemotherapy units.(AU)
Objetivo. Evaluar la efectividad de los protocolos de aplicación transcutánea de Irradiación Láser Intravenosa de Sangre 30' y 60', sobre los efectos adversos sobre el tejido hematopoyético por agentes quimioterápicos antineoplásicos intravenosos en adultos. Método. Ensayo clínico, aleatorizado y simple ciego, realizado en un servicio de quimioterapia ambulatoria de un hospital público del estado de São Paulo, realizado de abril de 2018 a marzo de 2019. La muestra estuvo compuesta por 55 pacientes con tumores sólidos, del segundo ciclo. del tratamiento con fármacos intravenosos citotóxicos para el tejido hematopoyético. La longitud de onda utilizada fue de 660 nm, por vía transcutánea, bajo la arteria radial. Resultado. En comparación con el tipo de componente sanguíneo, obtuvimos, respectivamente, de los protocolos de Irradiación Intravenosa con Láser de Sangre 30' y 60': hemoglobina (85%; 86%), plaquetas (100%; 100%) y neutrófilos (95%; 92%). %). Conclusión. Ambos os protocolos se consideraron efectivos, por lo que se sugiere implantarlos en las unidades de quimioterapia(AU)
Assuntos
Humanos , Adolescente , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Terapia a Laser/enfermagem , Sistema Hematopoético , Antineoplásicos/efeitos adversos , Protocolos Clínicos , Resultado do TratamentoRESUMO
Background: Erythroid leukemia is a myeloproliferative hematopoietic disorder considered acute when there is a predominance of blasts in the bone marrow. It is frequently reported in cats infected with feline leukemia virus, but it is unclear whether this virus is involved in the oncogenesis. The clinical signs in cats are anorexia, apathy, weight loss, with evolution from 2 weeks to 2 months, pale mucous membranes, hemorrhages, ascites, salivation, and dyspnea due to pleural effusion. This affection responds little to chemotherapy with an unfavorable prognosis. The aim of this study is to report a case of a feline leukemia virus infected cat with the onset of severe hemolytic anemia. Case: A 8-year-old male mixed breed cat was attended with a history of anorexia, oligodipsia, apathy, progressive weight loss, and yellowish color of urine for 7 days. Laboratorial exams showed anemia (with metarubricytes, acanthocytes and ghost cells), leukocytosis and FeLV reagent test. The cat underwent treatment with methylprednisolone acetate and supportive care. One day later, the animal returned with icteric mucous membranes, and emesis. A blood count was performed that found worsening anemia, increased leukocytosis, and lymphocytosis. Abdominal ultrasound showed cholangiohepatitis and lymphadenomegaly in mesenteric lymph nodes. Treatment was started with ondansetron, metronidazole, and amoxicilin with potassium clavulanate. The cat returned after 3 days and laboratorial exams revealed worsening of blood parameters, so blood transfusion was performed. After 2 days, the patient started with dyspnea and hypothermia, that evolved to cardiorespiratory arrest. The body was sent to necropsy and histopathology, where blast cells and rubricytes were found in blood vessels of various organs. The bone marrow was markedly cellular with complete disappearance of adipose tissue. Most of the cells were blasts with abundant and eosinophilic cytoplasm, central nucleus with finely dotted chromatin and a large nucleolus. There were rubricytes, which made possible to confirm acute erythroid leukemia as a morphological diagnosis. Discussion: The clinical signs observed in acute erythroid leukemia are lethargy, inappetence, fever, splenomegaly, mild lymphadenomegaly, associated with leukocytosis, severe anemia, and thrombocytopenia. The reported animal presented signs similar to those described in the literature except that there was no change in platelet counts. The diagnosis of leukemia was reached after histopathology, and it is made when is observed more than 30% of myeloblasts and monoblasts together or when the blast cells count including rubriblasts is greater than 30%. Although chemotherapy, the prognosis is usually poor. It is essential to perform the myelogram for the diagnosis of myeloid leukemias in vivo. In this report, we only achieve final diagnosis after the cat's death, due to the aggressive behavior of the disease. Clinicians must be aware of the likely development of acute erythroid leukemia whenever a feline leukemia virus infected cat presents hemolytic anemia to get an early diagnosis, since this is an extremely aggressive disease, to propose prompt chemotherapy and give the patient a longer survival period.
Assuntos
Animais , Masculino , Gatos , Leucemia/veterinária , Vírus da Leucemia Felina/isolamento & purificação , Neoplasias Hematológicas/veterinária , Sistema Hematopoético/patologia , Anemia Hemolítica/veterinária , Mielografia/veterináriaRESUMO
INTRODUCCIÓN: El trasplante de precursores hematopoyéticos (TPH) ha evolucionado durante los últimos 50 años. Implica la infusión de células progenitoras hematopoyéticas en pacientes con trastornos hematológicos malignos o no malignos con el objetivo de restablecer la función hematopoyética e inmunitaria normal. También es una opción de tratamiento potencialmente curativo en pacientes portadores de tumores sólidos (1). Los primeros trasplantes se realizaron en gemelos idénticos, pero con el advenimiento de nuevas técnicas que permitieron conocer el complejo mayor de histocompatibilidad se amplió el espectro de trasplantes a donantes relacionados y no relacionados, tanto histoidénticos como aquellos con algún grado de incompatibilidad. OBJETIVOS: Evaluar los trasplantes de precursores hematopoyéticos realizados bajo cobertura financiera del Fondo Nacional de Recursos. METODOLOGÍA: Se trata de un estudio retrospectivo, de la cohorte de pacientes en quienes se realizó un TPH bajo cobertura financiera del FNR en el periodo comprendido entre el 25 de abril 1996 al 31 de diciembre 2018. RESULTADOS: a) Unidad de análisis: Solicitudes de trasplantes. En el periodo desde el inicio cobertura de TPH del 28 de abril de 1995 al 30 de diciembre 2019, se solicitaron 3160 TPH, de los cuales se autorizaron un total de 2902, no autorizados 250 y pendientes al momento del corte 8 trámites. b) Unidad de análisis: Pacientes. Características de las cohortes, tiempos y medianas de seguimiento. En el periodo en que se analizaron efectivamente las realizaciones de TPH, del 25 de abril de 1996 al 27 de diciembre 2018 se autorizaron 2699 solicitudes, y se realizaron efectivamente 2356 TPH. DISCUSIÓN: El Trasplante de progenitores hematopoyéticos es un procedimiento terapéutico que se encuentra en expansión tal cual lo muestran los dos registros internacionales más importantes, el europeo (European Society for Blood and Marrow Transplantation, EBMT) y el americano (Center for International Blood and Marrow Transplant Research, CIBMTR). Por otra parte, con el advenimiento de nuevas terapias innovadoras, para algunas patologías ocurrió un descenso significativo del número de trasplantes realizados por año. La Leucemia Mieloide crónica y su respuesta a inhibidores de tirosina quinasa es el ejemplo más representativo. De todas formas, esta técnica continuó incrementándose. Los factores principalmente asociados a este incremento son la flexibilización de la edad de los candidatos a un trasplante, el mayor número de donantes, y la ausencia de avances significativos en algunas de sus principales indicaciones como lo son la Leucemia Aguda y los Síndromes Mielodisplásicos. Esta evaluación representa más de 20 años de experiencia adquirida en procedimientos financiados por el FNR en esta técnica. El número de autorizaciones de trasplantes por año evidencia un incremento en la última década, así como el número de trasplantes efectivamente realizados de un 12.2 % (considerando los últimos 20 años) Este incremento es a expensas de los TPH alogénicos (incremento de un 57.2 % considerando las cohortes 1999-2008 y 2009-2018), concordante con lo que también ocurre a nivel internacional. En nuestra evaluación los trasplantes autólogos muestran un ligero descenso en la última década en torno a un 8.3 %. En concordancia con esto el reporte de CIBMTR del 2018 evidenció un descenso de los TPH autólogos de un 5%, aunque se habían mantenido estables los cuatro años prévios. Se trata de una población joven, con media de edad de 39 años, mayormente proveniente del sector privado de la salud. La proporción de TPH autólogo fue de un 81.4 % y el alogénico 18.6 % en forma global. En otros registros tanto de la región como del propio registro europeo muestran mayor proporción de TPH alogénicos realizados, próximos a un 40%. En nuestra evaluación se ha mantenido en estas mismas proporciones a lo largo de los años, tanto globalmente como en los diferentes institutos de medicina altamente especializada. Destacamos en el caso del IMAE en Hospital Maciel y Asociación Española para el periodo 2014- 2018 presentaron una proporción mayor de TPH alogénicos realizados. En nuestra evaluación dentro de los TPH alogénicos, la modalidad TPH alogénico "relacionado" fue el más frecuente (67.6%). Dentro de las otras dos modalidades, el TPH Haploidentico es el segundo en proporción (20.3%), a pesar de haberse incorporado ultimo dentro de la normativa del FNR.
Assuntos
Humanos , Transplante de Células-Tronco Hematopoéticas/instrumentação , Doenças Hematológicas/cirurgia , Sistema Hematopoético/cirurgia , Recursos Financeiros em Saúde , Financiamento da Assistência à SaúdeRESUMO
Introducción: Dentro de las cinco primeras neoplasias en el mundo están las Leucemias, la misma que ha venido incrementándose en las últimas décadas. El objetivo del presente estudio fue determi-nar las características epidemiológicas de las Neoplasias del tejido Hematopoyético y linfoide en pacientes atendidos en el Instituto Oncológico Nacional-SOLCA Guayaquil durante los años 2015 al 2019. Metodología: Se efectuó un estudio de diseño observacional, descriptivo poblacional; donde el universo y la muestra fueron 891 casos nuevos de neoplasias del Tejido Hematopoyético y Linfoide, recolectándose los datos en una matriz, que fueron tomados del programa informático del registro de tumores. Resultados: se diagnosticaron Leucemias Linfoideas (69.58%) y Leucemias Mieloides (30.30%); más en hombres (53.33%) que mujeres (44.67%); siendo los casos en menores de 19 años en Gua-yaquil del 57.33% y en Otras ciudades con el 64.36%; en Guayaquil el grupo de edad de 5 9 años fue más frecuente con 20.57% seguido de los menores de 5 años con 19.02%; mientras que en Otras ciudades fueran los menores de 5 años con 20.72% seguido del grupo etario de 5 9 años con 18.33%; entre otros grupos. Su mayor frecuencia en Guayaquil fueron en parroquias Tarqui, Ximena y en Otras ciudades en Región Costa (81.47%). Conclusión: Dentro de las neoplasias del Tejido Hematopoyético y Linfoide la más común fue las Leucemias Linfoideas en la población menor de 19 años con énfasis en los niños menores de 5 años mostrando una presencia importante en los años de estudio en Guayaquil y en la región Costa del Ecuador.
Introduction: Leukemias are among the first five neoplasms in the world, the same one that has been increasing in recent decades. The aim of this study was to determine the epidemiological char-acteristics of Hematopoietic and Lymphoid Neoplasms in patients treated at the National Oncological Institute-SOLCA Guayaquil during the years 2015 to 2019. Methodology: An observational, descriptive population study was carried out; Where the universe and the sample were 891 new cases of Hematopoietic and Lymphoid neoplasms, the data was col-lected in a matrix, taken from the tumor registry computer program. Results: Lymphoid Leukemias were diagnosed in 69.58% and Myeloid Leukemias with 30.30%; more in men (53.33%) than women (44.67%); being the cases in minors of 19 years in Guayaquil 57.33% and in Other cities it had 64.36%; in Guayaquil the age group of 5 - 9 years was more frequent with 20.57% followed by those under 5 years with 19.02%; while in Other cities under 5 years old with 20.72% followed by the age group of 5 - 9 years old with 18.33%; among other groups. Its highest frequency in Guayaquil was in Tarqui and Ximena parishes and in other cities it was in the Coastal Region with 81.47%. Conclusion: Among the Hematopoietic and Lymphoid neoplasms the most common was Lym-phoid Leukemias in the population under 19 years of age, with emphasis on children under 5 years of age, showing an important presence in the years of study in Guayaquil and in the Ecuadorian Coastal region.
Assuntos
Leucemia , Neoplasias Hematológicas , Pesquisa sobre Serviços de Saúde , Epidemiologia , Sistema HematopoéticoRESUMO
Genome-wide association studies of complex diseases, including nonalcoholic fatty liver disease (NAFLD), have demonstrated that a large number of variants are implicated in the susceptibility of multiple traits - a phenomenon known as pleiotropy that is increasingly being explored through phenome-wide association studies. We focused on the analysis of pleiotropy within variants associated with hematologic traits and NAFLD. We used information retrieved from large public National Health and Nutrition Examination Surveys, Genome-wide association studies, and phenome-wide association studies based on the general population and explored whether variants associated with NAFLD also present associations with blood cell-related traits. Next, we applied systems biology approaches to assess the potential biological connection/s between genes that predispose affected individuals to NAFLD and nonalcoholic steatohepatitis, and genes that modulate hematological-related traits-specifically platelet count. We reasoned that this analysis would allow the identification of potential molecular mediators that link NAFLD with platelets. Genes associated with platelet count are most highly expressed in the liver, followed by the pancreas, heart, and muscle. Conversely, genes associated with NAFLD presented high expression levels in the brain, lung, spleen, and colon. Functional mapping, gene prioritization, and functional analysis of the most significant loci (P < 1 × 10-8) revealed that loci involved in the genetic modulation of platelet count presented significant enrichment in metabolic and energy balance pathways. In conclusion, variants in genes influencing NAFLD exhibit pleiotropic associations with hematologic traits, particularly platelet count. Likewise, significant enrichment of related genes with variants influencing platelet traits was noted in metabolic-related pathways. Hence, this approach yields novel mechanistic insights into NAFLD pathogenesis.
Assuntos
Sistema Hematopoético , Hepatopatia Gordurosa não Alcoólica , Estudo de Associação Genômica Ampla , Humanos , Hepatopatia Gordurosa não Alcoólica/genética , FenótipoRESUMO
The characterization of hematopoietic stem cells (HSC) from the canine yolk sac (cYS) can contribute to future gene therapies because it is possible to obtain information about the beginning of the development of the circulatory system through the characterization. The cYS is a likely source of HSC, which is a source of blood cell development in mammals. Studies in this field have been conducted for decades; however, interest in cellular therapy is currently at its peak with greater visibility, and these cells are a promising therapeutic tool for the treatment of diseases related to animals and humans. The aim of this study was to isolate and characterize HSC from the cYS embryos at 30 to 45 days of gestational age. Our results showed that the cYS was macroscopically located in the ventral region with a central portion and extremities. The cells in culture presented a circular morphology and cell clusters. The average cell viability was 22.55% dead cells out of 6.5 × 104 total cells. The cells were also able to form colonies on methylcellulose. Flow cytometry analysis revealed the expression of CD34, CD117, and CD45. Our results suggest that the cYS can be used as a source of hematopoietic cells, and this study is very important to understand the mechanism and development of the hematopoietic system in dogs.(AU)
Assuntos
Animais , Cães , Cães , Células-Tronco Hematopoéticas/classificação , Saco Vitelino , Sistema HematopoéticoRESUMO
A deficiência de mevalonato quinase (MVK; MIM #142680; ORPHA #343) é uma doença genética, espectral, rara, associadas a mutações ao longo do gene MVK causando distúrbios na síntese do colesterol, que culminam em: inflamação sistêmica com febre, adenopatia, sintomas abdominais e outros achados clínicos. Enquanto no polo leve da doença os achados mais comuns são febres recorrentes com linfadenopatia, no polo mais grave adiciona-se o acometimento do sistema nervoso central (meningites assépticas, vasculites e atraso do desenvolvimento neuropsicomotor) e do sistema hematopoiético (síndrome de ativação macrofágica). Apesar de inúmeras terapêuticas, os bloqueadores da interleucina-1 ainda são os únicos medicamentos capazes de controlar a doença e de impedir a evolução para amiloidose. Os estudos atuais visam tentar novos tratamentos, como o transplante de células-tronco hematopoiéticas, ou mesmo a terapia gênica.
Mevalonate kinase deficiency (MVK; MIM #142680; ORPHA #343) is a rare spectral genetic disorder linked to mutations along the MVK gene leading to impaired cholesterol synthesis, clinically observed as systemic inflammation with fever, adenopathy, abdominal manifestations, and other clinical findings. While on mild forms recurrent fever with lymphadenopathy is commonly observed, severe forms add to that neurological (aseptic meningitis, vasculitis, and neuropsychomotor developmental delay) and hematopoietic involvement (macrophage activation syndrome). Despite of several therapeutic approaches, blocking interleukin-1 is the only effective method to control the disease and prevent the development of systemic amyloidosis. Ongoing studies aim to test new treatments, such as hematopoietic stem cell transplantation and gene therapy.
Assuntos
Humanos , Imunoglobulina D , Condutas Terapêuticas Homeopáticas , Deficiência de Mevalonato Quinase , Sinais e Sintomas , Terapêutica , Vasculite , Terapia Genética , Sistema Nervoso Central , Interleucina-1 , Transplante de Células-Tronco Hematopoéticas , PubMed , Febre , Linfadenopatia , Sistema Hematopoético , Doenças Genéticas Inatas , Amiloidose , Inflamação , Meningite AssépticaAssuntos
Pele , Unhas , Mama , Sistema Musculoesquelético , Sistema Nervoso , Cabeça , Pescoço , Membrana Serosa , Tórax , Sistema Digestório , Sistema Hematopoético , Sistema Urogenital , GENITAL FEMENINOS , Sistema EndócrinoRESUMO
RESUMEN Fundamento: la educación superior efectúa transformaciones profundas que se convierten en un factor clave para la puesta en marcha de procesos necesarios en el enfrentamiento a los desafíos del mundo existente. Objetivo: elaborar un material didáctico para la enseñanza aprendizaje del sistema hemolinfopoyético, con énfasis en el extendido de sangre periférica en la carrera de Bioanálisis Clínico. Métodos: se realizó un estudio descriptivo transversal en el período septiembre 2017-febrero 2018, en la Facultad Tecnológica "Octavio de la Concepción y de la Pedraja" de la Universidad de Ciencias Médicas "Carlos J. Finlay", de Camagüey. Se emplearon métodos teóricos: analítico-sintético e inductivo-deductivo; empíricos: observación a clases, la encuesta en forma de entrevista a docentes y la prueba exploratoria a estudiantes; y matemático-estadísticos para el cálculo de las frecuencias absolutas y el porcentaje. El producto fue valorado por criterios de especialistas. Resultados: se evidenciaron insuficiencias en el proceso enseñanza aprendizaje por los profesores para trabajar de manera integrada los procesos cognitivos sobre extendidos de sangre periférica como una vía para analizar las células hematopoyéticas; entre los estudiantes primaron el uso incorrecto de técnicas y procederes en los análisis y en la elaboración de los informes a partir de la observación e interpretación de extendidos de sangre periférica como componente esencial de la Hematología. Conclusiones: se elaboró un material didáctico que fue valorado por criterios de especialistas en las categorías de muy adecuado y adecuado en todos los indicadores propuestos, por lo que se consideró factible de ser aplicado.
ABSTRACT Background: Higher education carries out profound transformations that become a key factor for the implementation of necessary processes in the face of world challenges. Objective: to develop a teaching aid for the teaching - learning of the hemolinfopoietic system, with emphasis on the spread of peripheral blood in the Clinical Bioanalysis degree. Methods: a descriptive cross-sectional study was carried out from September 2017-to February 2018, at the "Octavio de la Concepción y de la Pedraja" Technological Faculty of the "Carlos J. Finlay" Camagüey University of Medical Sciences. Theoretical methods were used: analytical-synthetic and inductive-deductive; Empirical ones: observation to classes, the survey in the form of teacher interviews and the exploratory test to students; and mathematical-statistics for the calculation of the absolute frequencies and the percentage. The product was valued by criteria of specialists. Results: inadequacies in the teaching-learning process were evidenced by teachers to work in a comprehensive way on the cognitive processes on peripheral blood as a way to analyze hematopoietic cells; Among the students, the incorrect use of techniques and procedures prevailed in the analysis and in the preparation of the reports based on the observation and interpretation of peripheral blood spreads as an essential component of Hematology. Conclusions: a teaching aid was developed that was assessed by criteria of specialists in the categories of very adequate and adequate in all the proposed indicators, so it was considered feasible to be applied.
Assuntos
Educação Médica , Hematologia , Sistema Hematopoético , LaboratóriosRESUMO
Protein malnutrition is one of the most serious nutritional problems worldwide, affecting 794 million people and costing up to $3.5 trillion annually in the global economy. Protein malnutrition primarily affects children, the elderly, and hospitalized patients. Different degrees of protein deficiency lead to a broad spectrum of signs and symptoms of protein malnutrition, especially in organs in which the hematopoietic system is characterized by a high rate of protein turnover and, consequently, a high rate of protein renewal and cellular proliferation. Here, the current scientific information about protein malnutrition and its effects on the hematopoietic process is reviewed. The production of hematopoietic cells is described, with special attention given to the hematopoietic microenvironment and the development of stem cells. Advances in the study of hematopoiesis in protein malnutrition are also summarized. Studies of protein malnutrition in vitro, in animal models, and in humans demonstrate several alterations that impair hematopoiesis, such as structural changes in the extracellular matrix, the hematopoietic stem cell niche, the spleen, the thymus, and bone marrow stromal cells; changes in mesenchymal and hematopoietic stem cells; increased autophagy; G0/G1 cell-cycle arrest of progenitor hematopoietic cells; and functional alterations in leukocytes. Structural and cellular changes of the hematopoietic microenvironment in protein malnutrition contribute to bone marrow atrophy and nonestablishment of hematopoietic stem cells, resulting in impaired homeostasis and an impaired immune response.
Assuntos
Sistema Hematopoético/fisiopatologia , Deficiência de Proteína/fisiopatologia , Animais , Medula Óssea/metabolismo , Medula Óssea/fisiopatologia , Hematopoese , Células-Tronco Hematopoéticas , Sistema Hematopoético/metabolismo , Humanos , Deficiência de Proteína/metabolismoRESUMO
El trasplante hematopoyético es una estrategia terapéutica que permite posibilidad de curación en diversas enfermedades benignas y malignas. El autotrasplante tiene demostrada utilidad en mieloma y linfomas permitiendo recuperar la hematopoyesis luego de quimioterapias de alta intensidad. El alotrasplante permite reemplazar hematopoyesis defectuosa y/o introducir un potente efecto inmunológico llamado "efecto de injerto contra tumor". En los últimos años, se han desarrollado nuevos fármacos que permiten optimizar la recolección de progenitores autólogos y se han modificado los esquemas de trasplante, permitiendo un uso más amplio. El haplo trasplante alogénico ha favorecido que los enfermos tengan mejores posibilidades de encontrar donantes. En esta revisión, se analizan brevemente estas nuevas modalidades adoptadas en nuestro programa de trasplante hematopoyético.(AU)
Hematopoietic transplantation offers cure or control in several benign or malignant diseases. Autologous transplantation has proven to be useful in myeloma and lymphoma patients allowing hematopoiesis recovery after high-intensity chemotherapies. Allogeneic transplantation can replace defective hematopoiesis and / or introduce graft-versus-tumor effect. In recent years, new strategies have been developed to optimize autologous progenitor's collection and haploidentical modalities have allowed a wider use of allotransplants. In this brief review these new modalities adopted in our program are analyzed.(AU)
Assuntos
Humanos , Masculino , Feminino , Transplante , Transplante Autólogo , Transplante Haploidêntico , Sistema HematopoéticoRESUMO
A case of sporadic multicentric lymphoma in a Nelore calf is reported. Anatomic presentation, age of affected animal, and cytology done on fine needle aspiration biopsy from lymph node supported a presumptive clinical diagnosis. At necropsy there were multiple cream or white soft to firm masses of varying sizes, affecting lymph nodes, kidneys, myocardium, liver, retrobulbar tissues, lymph nodes, bone marrow, spleen, and dura mater; with a mitotic index of 90%. A tentative classification of the neoplasm as lymphoblastic lymphoma was made based on immunohistochemistry.(AU)
Assuntos
Animais , Bovinos , Linfoma/patologia , Linfoma/veterinária , Biópsia por Agulha Fina/veterinária , Sistema Hematopoético/patologiaRESUMO
A case of sporadic multicentric lymphoma in a Nelore calf is reported. Anatomic presentation, age of affected animal, and cytology done on fine needle aspiration biopsy from lymph node supported a presumptive clinical diagnosis. At necropsy there were multiple cream or white soft to firm masses of varying sizes, affecting lymph nodes, kidneys, myocardium, liver, retrobulbar tissues, lymph nodes, bone marrow, spleen, and dura mater; with a mitotic index of 90%. A tentative classification of the neoplasm as lymphoblastic lymphoma was made based on immunohistochemistry.
Assuntos
Animais , Bovinos , Linfoma/patologia , Linfoma/veterinária , Biópsia por Agulha Fina/veterinária , Sistema Hematopoético/patologiaRESUMO
Objetivo: el estudio de la biopsia de la médula ósea tiene como objetivo el diagnosticar los problemas que existen con los diversos tipos de células sanguíneas, con el fin de realizar un tratamiento y obtener un pronóstico adecuados; en el tiempo este exámen ha ido ampliándose y junto con el aspirado ayudan a la evaluación de patologías como anemia, trombocitopenia, linfomas, leucemias, tumores metastáticos, síndromes mieloproliferativos entre otros. Materiales y métodos: estudio retrospectivo, descriptivo y con diseño transversal. Se analizaron 450 muestras obtenidas desde enero a diciembre del 2013 para evaluar las distintas patologías que se presentan frecuentemente en nuestro hospital, de acuerdo a edad y sexo. Resultados: de los 450 casos receptados, analizados y reportados en el 2013; 236 muestras fueron negativas; 27 fueron muestras insuficientes e inadecuadas y 187 fueron positivas para lesiones benignas, borderline y malignas. La mayor parte de lesiones fueron más en hombres y en edades comprendidas entre 40 y 69 años. Las lesiones benignas más frecuentes fue la Hipoplasia y dentro de las lesiones malignas la infiltración linfocitica de inmunofenotipo B, la misma que se corroboró con estudio de Inmunohistoquimica. Conclusión: se determina que de los estudios realizados, la patología que con mayor frecuencia afecta a los pacientes del Hospital Carlos Andrade Marín, sometidos a biopsia de médula ósea en el año 2013 es la Infiltración de estirpe linfoide con biopsy has become important for the treatment and prognosis of diseases. Inmunofenotipo B. De ahí que el estudio de biopsia de médula ósea se ha tornado importante para el tratamiento y pronóstico de las diferentes patologías hematológicas y metastásicas.
Objective: the study of bone marrow biopsy aims to diagnose the problems that exist with the different types of blood cells, with the aim of treatment and obtain an acertive prognosis, with time this test has become popular and together with the aspirate helps with the evaluation of diseases such as anemia, trombocitopenia, leucemias, lymphomas among others, myeloproliferative syndromes, and metastatic tumors. Materials and methods: a retrospective descriptive study with cross-sectional design was used to analyze 450 samples obtained from january to december of 2013 in order to evaluate the different pathologies that arise frequently in our hospital, profiled by age and sex. Results: of the 450 analyzed cases and reported in the 2013; 236 samples were negative; 27 were insufficient and inadequate samples, 187 were positive for benign lesions, borderline or malignant. Most of the lesions were in men aged between 40 and 69 years; Hypoplasia was amongst the most benign lesions and among the malignant lesions was the Immune B Lymphocytic Infiltration, which was corroborated with inmunohistochemical staining. Conclusion: this study determines that the disease which most often affects patients of the Hospital Carlos Andrade Marín undergoing bone marrow biopsy in the year 2013 was lineage with Immune B lymphoid infiltration. Hence the study of bone marrow biopsy has become important for the treatment and prognosis of diseases.
Assuntos
Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Idoso , Patologia , Biópsia , Medula Óssea , Imuno-Histoquímica , Células Precursoras de Linfócitos B , Hematologia , Peso Corporal , Osso e Ossos , Infiltração-Percolação , Sistema Hematopoético , ÍlioRESUMO
Bone marrow is organized in specialized microenvironments known as 'marrow niches'. These are important for the maintenance of stem cells and their hematopoietic progenitors whose homeostasis also depends on other cell types present in the tissue. Extrinsic factors, such as infection and inflammatory states, may affect this system by causing cytokine dysregulation (imbalance in cytokine production) and changes in cell proliferation and self-renewal rates, and may also induce changes in the metabolism and cell cycle. Known to relate to chronic inflammation, obesity is responsible for systemic changes that are best studied in the cardiovascular system. Little is known regarding the changes in the hematopoietic system induced by the inflammatory state carried by obesity or the cell and molecular mechanisms involved. The understanding of the biological behavior of hematopoietic stem cells under obesity-induced chronic inflammation could help elucidate the pathophysiological mechanisms involved in other inflammatory processes, such as neoplastic diseases and bone marrow failure syndromes.
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Humanos , Sistema Hematopoético , Inflamação , ObesidadeRESUMO
La recuperación temprana de linfocitos es un factor pronóstico que está relacionado con una mayor supervivencia libre de eventos y supervivencia global en pacientes trasplantados. Se realizó una revisión bibliográfica con el objetivo de determinar el valor pronóstico del recuento absoluto de linfocitos en pacientes con hemopatías malignas, tratados con trasplante. Los pacientes con trasplantes autólogos alcanzan un recuento absoluto de linfocitos el día + 15 (RAL15) e 500 x mm³, más temprano que los alogénicos. El RAL15 cuando se utiliza sangre periférica es mayor que cuando se emplea la médula ósea. Los factores pronósticos asociados a una peor supervivencia global fueron la sepsis, el RAL15 < 500x mm³ y la recaída. Varios estudios muestran una mejor supervivencia global y supervivencia libre de eventos a los cinco años, en los pacientes con RAL15 e 500 x mm³. El RAL15 e 500 x mm³ es una herramienta simple y útil para predecir un mejor resultado en pacientes sometidos a trasplante hematopoyético
Early recovery of lymphocytes is a prognostic factor that is related to a higher event-free survival and overall survival after haematopoietic stem cell transplantation. A literature review was conducted in order to determine the prognostic value of absolute lymphocyte count in patients with hematological malignancies after transplantation. Autologous transplant patients reach an absolute lymphocyte count on day + 15 (RAL15) e 500 x mm³, earlier than allogeneic. The RAL15 when peripheral blood is used is greater than when using the bone marrow. Prognostic factors associated with worse overall survival were sepsis, RAL 15 <500x mm³ and relapse. Several studies show a better overall survival and event-free survival at five years in patients with e 500 x RAL15 mm³. The RAL15 e 500 x mm³ is a simple and useful tool to predict a better outcome in patients undergoing hematopoietic transplantation
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Humanos , Ativação Linfocitária/fisiologia , Sistema Hematopoético/fisiopatologia , Prognóstico , Contagem de Linfócitos/métodosRESUMO
Based on previous data on the histamine radioprotective effect on highly radiosensitive tissues, in the present work we aimed at investigating the radioprotective potential of the H4R ligand, JNJ7777120, on ionizing radiation-induced injury and genotoxic damage in small intestine, salivary glands and hematopoietic tissue. For that purpose, rats were divided into 4 groups. JNJ7777120 and JNJ7777120-irradiated groups received a daily subcutaneous JNJ7777120 injection (10 mg/kg) starting 24 h before irradiation. Irradiated groups received a single dose of 5 Gy on whole-body using Cesium-137 source and were sacrificed 3 or 30 days after irradiation. Tissues were removed, fixed, stained with hematoxylin and eosin or PAS staining and histological characteristics were evaluated. Proliferative and apoptotic markers were studied by immunohistochemistry, while micronucleus assay was performed to evaluate DNA damage. Submandibular gland (SMG) function was evaluated by methacholine-induced salivation. Results indicate that JNJ7777120 treatment diminished mucosal atrophy and preserved villi and the number of crypts after radiation exposure (240±8 vs. 165±10, P<0.01). This effect was associated to a reduced apoptosis and DNA damage in intestinal crypts. JNJ7777120 reduced radiation-induced aplasia, preserving medullar components and reducing formation of micronucleus and also it accelerated bone marrow repopulation. Furthermore, it reduced micronucleus frequency in peripheral blood (27±8 vs. 149±22, in 1,000 erythrocytes, P<0.01). JNJ7777120 completely reversed radiation-induced reduced salivation, conserving glandular mass with normal histological appearance and reducing apoptosis and atrophy of SMG. JNJ7777120 exhibits radioprotective effects against radiation-induced cytotoxic and genotoxic damages in small intestine, SMG and hematopoietic tissues and, thus, could be of clinical value for patients undergoing radiotherapy.
Assuntos
Sistema Hematopoético/efeitos dos fármacos , Indóis/farmacologia , Intestino Delgado/efeitos dos fármacos , Piperazinas/farmacologia , Protetores contra Radiação/farmacologia , Receptores Acoplados a Proteínas G/metabolismo , Receptores Histamínicos/metabolismo , Glândulas Salivares/efeitos dos fármacos , Animais , Medula Óssea/efeitos dos fármacos , Medula Óssea/patologia , Medula Óssea/efeitos da radiação , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Sistema Hematopoético/patologia , Sistema Hematopoético/efeitos da radiação , Humanos , Intestino Delgado/patologia , Intestino Delgado/efeitos da radiação , Ligantes , Masculino , Mutagênicos/toxicidade , Ratos , Ratos Sprague-Dawley , Receptores Histamínicos H4 , Glândulas Salivares/patologia , Glândulas Salivares/efeitos da radiação , Compostos de Sulfidrila/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Irradiação Corporal TotalRESUMO
Leukemias are the most common malignancy of childhood and have the highest mortality among aging people. Leukemias are a group of blood disorders characterized by an accumulation of leukemic cells in the peripheral blood of patients as a result of disturbances in proliferation and differentiation. Refractory leukemia remains the most common therapeutic challenge. In recent years, the presence of a cancer stem cell population in leukemias has been proposed as a cause for the refractory phenomenon. Insights into the cellular and molecular features of leukemia led to a new point of view in the choice of novel therapeutic agents. New agents for the treatment of this disease should selectively target leukemia stem cells or exhibit higher cytotoxic effects in cancer cells than in normal cells. A special interest is focused on anticancer agents from biological and natural sources that can be used in the treatment of leukemia. This review discusses the characteristics of some of these potential new agents.
Assuntos
Peptídeos Catiônicos Antimicrobianos/uso terapêutico , Fatores Biológicos/uso terapêutico , Radicais Livres/metabolismo , Hematopoese/fisiologia , Sistema Hematopoético/metabolismo , Leucemia/tratamento farmacológico , Receptores Purinérgicos P2/uso terapêutico , Transdução de Sinais/fisiologia , Depsipeptídeos , Humanos , Indóis , Receptores Purinérgicos P2/metabolismo , Ácido Chiquímico/análogos & derivados , Sirolimo , Serina-Treonina Quinases TOR/metabolismoRESUMO
En el presente estudio se evaluaron 34 individuos de ambos géneros (n = 15 mujeres y n = 19 hombres) con edades promedios de 37,35 ± 10,37. De los cuales 09 trabajadores de talleres mecánicos y 25 de imprentas gráficas con exposición laboral entre 8 a 10 horas/día. Bajo su consentimiento se les tomo muestra de sangre del antebrazo derecho para evaluar hematológica y morfológicamente glóbulos rojos (punteado basófilo), glóbulos blancos (segmentados neutrofilos), plaquetas y determinar por espectroscopia de absorción atómica con atomización elec trotérmica niveles séricos de plomo. Los resultados analíticos obtenidos para niveles de plomo globales expresados en μgL-1 de 36,03 ± 23,02 evidenciaron correlación directa y positiva con los parámetros bioquímicos evaluados. Ma yo res concentraciones de plomo en sangre coincidieron con pun teados basófilos toscos y alteraciones cualitativas morfológicas tales como hipocromía moderada en glóbulos rojos, granulaciones tóxicas e hipersegmentación en segmentados neutrofilos. No se observaron diferencias estadísticamente significativas con un p = 0,002 entre los grupos expuestos y tiempo de exposición por jornada laboral, más si entre los géneros con un p = 0,087, siendo más evidente el impacto de la exposición ocupacional en hombres, asumiendo mayor masa corporal y por ende mayor densidad ósea por donde este metal tóxico tiene un 95% de afinidad, además de contar el género masculino con mayor producción hematopoyética (La cantidad considerada normal fluctúa entre 4.500.000 (en la mujer) y 5.000.000 (en el hombre) por milímetro cúbico (o microlitro) de sangre). Los resultados obtenidos constituyen una herramienta útil para un pre-diagnóstico a exposición o intoxicación por plomo cuando por infraestructura no se cuente en laboratorios bioanalíticos con un equipo de espectroscopia de ab sorción atómica con atomización electrotérmica.
This study assessed 34 individuals of both genre (n = 15 women and n = 19 men) aged averages of 37.35 ± 10.37. Of whom 09 workers of garages and 25 printing graphs with occupational exposure between 8 to 10 hours per day. Under their consent took them right forearm blood sample to evaluate haematological and morphologically (stippling Basophilic) red blood cells, white blood cells (segmented neutrophils), pla te lets and by Atomic Spectrometry atomization absorption spectroscopy to determine serum levels of lead. The analytical re sults for overall lead levels ex pressed in μgL-1 36.03 ± 23.02 demonstrate positive and direct correlation with the biochemical parameters evaluated. High concentrations of lead in blood coincided with various crude basophiles and qualitative morphological alterations such as hypochromia moderate red globules, toxic granulations and hypersegmentation in segmented neutrophils. There were no statistically significant differences with p = 0.002 among exposed groups and exposure time by working day, more if genre with a p = 0.087, being most evi dent impact of occupational exposure in men, assuming greater mass body and therefore greater bone density where this toxic metal has a 95% of affinitys well as the masculine gender with greater production hematopoietic (considered normal amount fluctuates between 4.500.000 (in women) and 5.000.000 (in humans) per cubic millimeter (microliter) of blood). The results constitute a useful tool for an prediag nostic to exposure or poisoning by lead when infrastructure dont count in laboratories bioanalytics with a team of atomic absorption spectroscopy with spectrometry atomization.