Hantavirus infection-induced B cell activation elevates free light chains levels in circulation.

In humans, orthohantaviruses can cause hemorrhagic fever with renal syndrome (HFRS) or hantavirus pulmonary syndrome (HPS). An earlier study reported that acute Andes virus HPS caused a massive and transient elevation in the number of circulating plasmablasts with specificity towards both viral and host antigens suggestive of polyclonal B cell activation. Immunoglobulins (Igs), produced by different B cell populations, comprise heavy and light chains; however, a certain amount of free light chains (FLCs) is constantly present in serum. Upregulation of FLCs, especially clonal species, associates with renal pathogenesis by fibril or deposit formations affecting the glomeruli, induction of epithelial cell disorders, or cast formation in the tubular network. We report that acute orthohantavirus infection increases the level of Ig FLCs in serum of both HFRS and HPS patients, and that the increase correlates with the severity of acute kidney injury in HFRS. The fact that the kappa to lambda FLC ratio in the sera of HFRS and HPS patients remained within the normal range suggests polyclonal B cell activation rather than proliferation of a single B cell clone. HFRS patients demonstrated increased urinary excretion of FLCs, and we found plasma cell infiltration in archival patient kidney biopsies that we speculate to contribute to the observed FLC excreta. Analysis of hospitalized HFRS patients' peripheral blood mononuclear cells showed elevated plasmablast levels, a fraction of which stained positive for Puumala virus antigen. Furthermore, B cells isolated from healthy donors were susceptible to Puumala virus in vitro, and the virus infection induced increased production of Igs and FLCs. The findings propose that hantaviruses directly activate B cells, and that the ensuing intense production of polyclonal Igs and FLCs may contribute to acute hantavirus infection-associated pathological findings.

Correction: Monocyte subset redistribution from blood to kidneys in patients with Puumala virus caused hemorrhagic fever with renal syndrome.

[This corrects the article DOI: 10.1371/journal.ppat.1009400.].

Monocyte subset redistribution from blood to kidneys in patients with Puumala virus caused hemorrhagic fever with renal syndrome.

Innate immune cells like monocytes patrol the vasculature and mucosal surfaces, recognize pathogens, rapidly redistribute to affected tissues and cause inflammation by secretion of cytokines. We previously showed that monocytes are reduced in blood but accumulate in the airways of patients with Puumala virus (PUUV) caused hemorrhagic fever with renal syndrome (HFRS). However, the dynamics of monocyte infiltration to the kidneys during HFRS, and its impact on disease severity are currently unknown. Here, we examined longitudinal peripheral blood samples and renal biopsies from HFRS patients and performed in vitro experiments to investigate the fate of monocytes during HFRS. During the early stages of HFRS, circulating CD14-CD16+ nonclassical monocytes (NCMs) that patrol the vasculature were reduced in most patients. Instead, CD14+CD16- classical (CMs) and CD14+CD16+ intermediate monocytes (IMs) were increased in blood, in particular in HFRS patients with more severe disease. Blood monocytes from patients with acute HFRS expressed higher levels of HLA-DR, the endothelial adhesion marker CD62L and the chemokine receptors CCR7 and CCR2, as compared to convalescence, suggesting monocyte activation and migration to peripheral tissues during acute HFRS. Supporting this hypothesis, increased numbers of HLA-DR+, CD14+, CD16+ and CD68+ cells were observed in the renal tissues of acute HFRS patients compared to controls. In vitro, blood CD16+ monocytes upregulated CD62L after direct exposure to PUUV whereas CD16- monocytes upregulated CCR7 after contact with PUUV-infected endothelial cells, suggesting differential mechanisms of activation and response between monocyte subsets. Together, our findings suggest that NCMs are reduced in blood, potentially via CD62L-mediated attachment to endothelial cells and monocytes are recruited to the kidneys during HFRS. Monocyte mobilization, activation and functional impairment together may influence the severity of disease in acute PUUV-HFRS.

Characterization of low-density granulocytes in COVID-19.

Severe COVID-19 is characterized by extensive pulmonary complications, to which host immune responses are believed to play a role. As the major arm of innate immunity, neutrophils are one of the first cells recruited to the site of infection where their excessive activation can contribute to lung pathology. Low-density granulocytes (LDGs) are circulating neutrophils, whose numbers increase in some autoimmune diseases and cancer, but are poorly characterized in acute viral infections. Using flow cytometry, we detected a significant increase of LDGs in the blood of acute COVID-19 patients, compared to healthy controls. Based on their surface marker expression, COVID-19-related LDGs exhibit four different populations, which display distinctive stages of granulocytic development and most likely reflect emergency myelopoiesis. Moreover, COVID-19 LDGs show a link with an elevated recruitment and activation of neutrophils. Functional assays demonstrated the immunosuppressive capacities of these cells, which might contribute to impaired lymphocyte responses during acute disease. Taken together, our data confirms a significant granulocyte activation during COVID-19 and suggests that granulocytes of lower density play a role in disease progression.

A comprehensive assessment of four whole blood stabilizers for flow-cytometric analysis of leukocyte populations.

Though cryopreservation of cell fractions is widely used in flow cytometry studies, whole blood cryopreservation is more challenging due to the presence of erythrocytes and effects of fixatives commonly used for preservation. Here, we evaluated and compared head-to-head the performance of four commercial whole blood cryopreservation kits; (1) Cytodelics, (2) Stable-Lyse V2 and Stable-Store V2 (SLSS-V2), (3) Proteomic stabilizer (PROT-1), and (4) Transfix. We found that PROT-1, Transfix, and Cytodelics maintained the distribution of major leukocyte subsets-granulocytes, T cells, natural killer cells, and B cells, on a comparable level to unpreserved samples, despite the attenuation of fluorescence intensities in flow cytometric assays. Moreover, these three stabilizers also maintained the activated phenotypes of neutrophils upon stimulation with N-formylmethionyl-leucyl-phenylalanine and lipopolysaccharides. The upregulation of adhesion molecules (CD11b), Fc receptors (CD16), and granule proteins (CD66b), as well as the shedding of surface L-selectin (CD62L), was conserved most efficiently in PROT-1 and Cytodelics when compared to samples only treated with erythrocyte lysing. However, none of the stabilizers provided a reliable detection of CCR7 for accurate quantification of T cell maturation stages. We also evaluated the performance of Cytodelics in longitudinal clinical samples obtained from acute COVID-19 patients, where it allowed reliable detection of lymphopenia and granulocyte expansion. These results support the feasibility of whole blood cryopreservation for immunophenotyping by flow cytometry, particularly in longitudinal studies. In conclusion, the performance of different stabilizers is variable and therefore the choice of stabilizers should depend on cell type of interest, as well as antibody clones and experimental design of each study.

Spo0M: structure and function beyond regulation of sporulation.

In this mini-review, we present a perspective on the recent findings relating Spo0M structure and function that will stimulate and guide further studies in the characterization of this interesting protein. Cell division and sporulation constitute two of the best studied processes in the model organism Bacillus subtilis; however, there are many missing pieces in the giant regulatory puzzle that governs the independent and shared networks between them. Spo0M is a little studied protein that has been related to both, cell division and sporulation, but its biochemical function and its direct interactions have not been yet defined. Structural analysis of Spo0M revealed the presence of an arrestin-like domain and an FP domain (a dimerization domain present in proteasome elements), motifs more commonly found in eukaryotic proteins. The aim of this perspective is to present open questions regarding the functional and structural features of Spo0M that make this protein a good candidate for the ancestor of arrestins in bacteria and an important element in developmental and differentiation processes of Bacillus subtilis.

Membrane remodeling and organization: Elements common to prokaryotes and eukaryotes.

Membrane remodeling processes in eukaryotes, such as those involved in endocytosis and intracellular trafficking, are mediated by a large number of structural, accessory and regulatory proteins. These processes occur in all cell types, enabling the exchange of signals and/or nutrients with the external medium and with neighboring cells; likewise, they are required for the intracellular trafficking of various cargo molecules between organelles, as well as the recycling of these structures. Recent studies have demonstrated that some elements of the molecular machinery involved in regulating and mediating endocytosis in eukaryotic cells are also present in some bacteria, where they participate in processes such as cell division, sporulation and signal transduction. However, the mechanism whereby this prokaryotic machinery carries out such functions has barely begun to be elucidated. This review summarizes recent information about the cytoskeletal and membrane-organizing proteins for which bacterial homologs have been identified; given their known functions, they may be considered to be part of an ancestral membrane organization system that first emerged in prokaryotes and which further evolved into the more complex regulatory networks operating in eukaryotes. © 2017 IUBMB Life, 69(2):55-62, 2017.

Increased Heparanase Levels in Urine during Acute Puumala Orthohantavirus Infection Are Associated with Disease Severity.

Old-world orthohantaviruses cause hemorrhagic fever with renal syndrome (HFRS), characterized by acute kidney injury (AKI) with transient proteinuria. It seems plausible that proteinuria during acute HFRS is mediated by the disruption of the glomerular filtration barrier (GFB) due to vascular leakage, a hallmark of orthohantavirus-caused diseases. However, direct infection of endothelial cells by orthohantaviruses does not result in increased endothelial permeability, and alternative explanations for vascular leakage and diminished GFB function are necessary. Vascular integrity is partly dependent on an intact endothelial glycocalyx, which is susceptible to cleavage by heparanase (HPSE). To understand the role of glycocalyx degradation in HFRS-associated proteinuria, we investigated the levels of HPSE in urine and plasma during acute, convalescent and recovery stages of HFRS caused by Puumala orthohantavirus. HPSE levels in urine during acute HFRS were significantly increased and strongly associated with the severity of AKI and other markers of disease severity. Furthermore, increased expression of HPSE was detected in vitro in orthohantavirus-infected podocytes, which line the outer surfaces of glomerular capillaries. Taken together, these findings suggest the local activation of HPSE in the kidneys of orthohantavirus-infected patients with the potential to disrupt the endothelial glycocalyx, leading to increased protein leakage through the GFB, resulting in high amounts of proteinuria.

Analysis of Spo0M function in Bacillus subtilis.

Spo0M has been previously reported as a regulator of sporulation in Bacillus subtilis; however, little is known about the mechanisms through which it participates in sporulation, and there is no information to date that relates this protein to other processes in the bacterium. In this work we present evidence from proteomic, protein-protein interaction, morphological, subcellular localization microscopy and bioinformatics studies which indicate that Spo0M function is not necessarily restricted to sporulation, and point towards its involvement in other stages of the vegetative life cycle. In the current study, we provide evidence that Spo0M interacts with cytoskeletal proteins involved in cell division, which suggest a function additional to that previously described in sporulation. Spo0M expression is not restricted to the transition phase or sporulation; rather, its expression begins during the early stages of growth and Spo0M localization in B. subtilis depends on the bacterial life cycle and could be related to an additional proposed function. This is supported by our discovery of homologs in a broad distribution of bacterial genera, even in non-sporulating species. Our work paves the way for re-evaluation of the role of Spo0M in bacterial cell.

La autorregulación: un avance hacia la autonomía de enfermería / Autorregulaçáo: um avanço em direção à autonomia da enfermagem / Self-regulation: a step towards nursing autonomy

RESUMEN La profesión de Enfermería en Chile se vio afectada por los hechos ocurridos en la sociedad chilena desde la Constitución de 1980 y la modificación del Código Sanitario en 1981, a través del Decreto Ley 3621. La construcción de la definición de Enfermería introducida al Código Sanitario chileno en el año 1997 proporcionó el respaldo legal a la función social de la enfermera, reconociendo a su vez a Enfermería como una profesión autónoma. Objetivo: Analizar cómo se gestó la construcción de la definición de Enfermería que se introdujo en el Código Sanitario chileno, en su artículo N° 113. Método: Estudio de abordaje socio-histórico, a través del testimonio de dos enfermeras que fueron actores relevantes en la construcción de la definición de Enfermería. Las entrevistas fueron analizadas a través del análisis de discurso. Resultados: Se expone una reflexión crítica realizada por enfermeras visionarias para lograr obtener una definición de Enfermería, que reconoce legalmente a la profesión en su función social, principalmente en el cuidado de la salud de las personas. Conclusión: Este hecho histórico que legitimó la función social de la enfermera significó un proceso reivindicativo al mandato social de la labor de la enfermera y constituyó un hito sociopolítico, sin embargo, a más de veinte años aparecen nuevos desafíos en el área de la salud y cuidado de las personas, cobrando valor continuar con la autorregulación para consolidar su autonomía e identidad profesional.

ABSTRACT The nursing profession in Chile was affected by events that occurred in the Chilean society since the Constitution of 1980 and the modification of the Health Code in 1981, through the DL 3621 (Executive order). The construction of the definition of nursing introduced to the Chilean Health Code in the year 1997 provided legal support to the social function of the nurse, recognizing nursing as an autonomous profession. Objective: To analyze how the construction of the definition of nursing that was introduced in the Chilean Health Code, in its article No. 113, was developed. Method: Socio-historical approach, through the testimony of two nurses who were relevant actors in the construction of the definition of nursing. The interviews were analyzed through discourse analysis. Results: We present a critical reflection made by visionary nurses to construct a definition of nursing, which legally recognizes the profession in its social function, mainly in people's health care. Conclusion: The historical event that legitimized the social function of the nurse meant a vindicating process to the social mission of the nurse's work and became a sociopolitical milestone, however, more than twenty years later new challenges arise in the area of people's health care, giving new value to self-regulation to strengthen autonomy and professional identity.

RESUMO A profissão de enfermagem no Chile foi afetada pelos acontecimentos na sociedade chilena desde a Constituição de 1980 e a modificação do Código Sanitário em 1981, através do DL 3621. A construção da definição de Enfermagem inserida no Código Sanitário chileno o ano de 1997 forneceu o suporte legal à função social da enfermeira, reconhecendo a Enfermagem como uma profissão autônoma. Objetivo: Analisar como foi construída a definição de enfermagem que foi inserida no Código Sanitário chileno, no artigo n° 113. Método: Estudo de abordagem sócio-histórica, através do depoimento de duas enfermeiras que foram atores relevantes na construção da definição de enfermagem. As entrevistas foram analisadas por meio da análise do discurso. Resultados: Apresenta-se uma reflexão crítica feita por enfermeiras visionárias para obter uma definição de Enfermagem, que legalmente reconhece a profissão em sua função social, principalmente no cuidado da saúde das pessoas. Conclusão: Este fato histórico que legitimou a função social da enfermaria significou um processo reivindicatório á missão social do trabalho do enfermeiro e significou um marco sócio-político, porém, mais de vinte anos depois existem novos desafios na saúde e no cuidado das pessoas, ganhando valor continuar com a auto-regulação para consolidar sua autonomia e identidade profissional.

La autorregulación: un avance hacia la autonomía de enfermería

La profesión de Enfermería en Chile se vio afectada por los hechos ocurridos en la sociedad chilena desde la Constitución de 1980 y la modificación del Código Sanitario en 1981, a través del Decreto Ley 3621. La construcción de la definición de Enfermería introducida al Código Sanitario chileno en el año 1997 proporcionó el respaldo legal a la función social de la enfermera, reconociendo a su vez a Enfermería como una profesión autónoma. Objetivo: Analizar cómo se gestó la construcción de la definición de Enfermería que se introdujo en el Código Sanitario chileno, en su artículo N° 113. Método: Estudio de abordaje socio-histórico, a través del testimonio de dos enfermeras que fueron actores relevantes en la construcción de la definición de Enfermería. Las entrevistas fueron analizadas a través del análisis de discurso. Resultados: Se expone una reflexión crítica realizada por enfermeras visionarias para lograr obtener una definición de Enfermería, que reconoce legalmente a la profesión en su función social, principalmente en el cuidado de la salud de las personas. Conclusión: Este hecho histórico que legitimó la función social de la enfermera significó un proceso reivindicativo al mandato social de la labor de la enfermera y constituyó un hito sociopolítico, sin embargo, a más de veinte años aparecen nuevos desafíos en el área de la salud y cuidado de las personas, cobrando valor continuar con la autorregulación para consolidar su autonomía e identidad profesional.

The nursing profession in Chile was affected by events that occurred in the Chilean society since the Constitution of 1980 and the modification of the Health Code in 1981, through the DL 3621 (Executive order). The construction of the definition of nursing introduced to the Chilean Health Code in the year 1997 provided legal support to the social function of the nurse, recognizing nursing as an autonomous profession. Objective: To analyze how the construction of the definition of nursing that was introduced in the Chilean Health Code, in its article No. 113, was developed. Method: Socio-historical approach, through the testimony of two nurses who were relevant actors in the construction of the definition of nursing. The interviews were analyzed through discourse analysis. Results: We present a critical reflection made by visionary nurses to construct a definition of nursing, which legally recognizes the profession in its social function, mainly in people's health care. Conclusion: The historical event that legitimized the social function of the nurse meant a vindicating process to the social mission of the nurse's work and became a sociopolitical milestone, however, more than twenty years later new challenges arise in the area of people's health care, giving new value to self-regulation to strengthen autonomy and professional identity.

A profissão de enfermagem no Chile foi afetada pelos acontecimentos na sociedade chilena desde a Constituição de 1980 e a modificação do Código Sanitário em 1981, através do DL 3621. A construção da definição de Enfermagem inserida no Código Sanitário chileno o ano de 1997 forneceu o suporte legal à função social da enfermeira, reconhecendo a Enfermagem como uma profissão autônoma. Objetivo: Analisar como foi construída a definição de enfermagem que foi inserida no Código Sanitário chileno, no artigo n° 113. Método: Estudo de abordagem sócio-histórica, através do depoimento de duas enfermeiras que foram atores relevantes na construção da definição de enfermagem. As entrevistas foram analisadas por meio da análise do discurso. Resultados: Apresenta-se uma reflexão crítica feita por enfermeiras visionárias para obter uma definição de Enfermagem, que legalmente reconhece a profissão em sua função social, principalmente no cuidado da saúde das pessoas. Conclusão: Este fato histórico que legitimou a função social da enfermaria significou um processo reivindicatório á missão social do trabalho do enfermeiro e significou um marco sócio-político, porém, mais de vinte anos depois existem novos desafios na saúde e no cuidado das pessoas, ganhando valor continuar com a auto-regulação para consolidar sua autonomia e identidade profissional.

Red internacional de gestión del cuidado de enfermería: alcances y desafíos en el marco de la Cobertura Universal de Salud / International network of management of nursing care: achievements and challenges in the context of Universal Health Coverage

Introducción: la Red Internacional de Gestión del Cuidado de Enfermería fue creada con el objetivo de compartir intereses, saberes y experiencias respecto a la gestión del cuidado de enfermería, mediante el desarrollo de avances que empoderen el ejercicio profesional y colaboren con la calidad y seguridad de los cuidados. Objetivo: identificar alcances y desafíos de la Red Internacional de Gestión del Cuidado de Enfermería, enmarcada en la Cobertura Universal de Salud. Métodos: se realizó estudio documental con información recogida en el período 2010 - 2015. Se siguieron pasos de definición de tópicos, selección de información, organización, redacción y estructura del informe, en el mes de marzo de 2016. Conclusiones: se lograron identificar alcances y desafíos de la red, enmarcada en la Cobertura Universal de Salud. Se destaca que el trabajo en red ha sido una fortaleza del colectivo enfermero(AU)

Introduction: The International Network Management Nursing Care was created with the objective of sharing interests, knowledge and experience regarding the management of nursing care, by developing advances that empower professional practice and collaborate with the quality and safety of the cares. Objective: To identify achievements and challenges of the International Network of Nursing Care Management, part of the Universal Health Coverage. Methods: Documentary study was conducted with data collected in the period 2010 - 2015. The steps followed were definition of topics, selection of information, organization, writing and structure of the report in March 2016. Conclusions: They were able to identify achievements and challenges of the network, part of the Universal Health Coverage. It emphasizes that networking has been strength of the nursing collective(AU)

Examen nacional de enfermería en chile: importancia y desafíos / National exam of nursing in Chile: the importance and challenges

Si bien la evaluación de la calidad de la formación de los egresados, a través de un examen nacional, es una realidad reciente en Chile, la experiencia internacional es amplia y variada. Este artículo da a conocer la necesidad y trascendencia de aplicar algún tipo de medición de competencias en egresados de carreras de enfermería, las características de las evaluaciones que realizan algunos países que las han implementado; así como las políticas y organizaciones que regulan su aplicación. También describe la experiencia de aplicación de un examen nacional en el área de la salud en Chile, como es el caso de medicina y enfermería.

Assessing the quality of education of graduates, through a national exam, is a recent activity in Chile, however, international experience is extensive and varied. This article shows the need and importance of some form of measurement of skills in graduates of nursing careers, the characteristics of the assessments made by some countries that have implemented it, as well as policies and organizations regulating its implementation. It also describes the experience of implementation of a national exam in the area of health in Chile, such as medicine and nursing.

Cirugía reconstructiva de las úlceras por presión / Reconstructive surgery of pressure sores

Las úlceras por presión son frecuentes en determinado grupo de pacientes con condiciones predisponentes. Estas en su evolución pueden necesitar tratamiento quirúrgico, pero existe una elevada incidencia de complicaciones posoperatorias en este tipo de pacientes, dada la confluencia en ellos de factores que conspiran contra el éxito de la cirugía de estas lesiones. Se realiza un estudio retrospectivo, descriptivo, de corte transversal, con el propósito de evaluar los resultados del tratamiento quirúrgico de las úlceras por presión en un período de 2 años. Teniendo en cuenta el comportamiento de las variables estudiadas, se arribó a conclusiones que permitirán trazar nuevas estrategias en la atención de estos pacientes, para minimizar la morbilidad posoperatoria y la estadía hospitalaria(AU)

Pressure sores are frequent in certain group of patients with predisposing conditions. In their evolution, this type of sores may require surgery, but the incidence of postoperative complications is high in this type of patients, given the confluence of factors that go against the sucessful surgery of these lesions in these patients. A retrospective cross-sectional descriptive study was made to evaluate the results of surgical treatment of pressure sores in a 3 years-period. Taking into account the studied variables, the drawn conclusions will allow designing new strategies for care of these patients, in order to reduce postoperative morbidity and lenght of stay at hospital(AU)

¿Por qué desarrollar competencias generales en los alumnos de enfermería? / Developing general skills in nursing students: is it necessary?

El articulo invita a la reflexión en torno a la necesidad de desarrollar competencias generales en los futuros profesionales de enfermería. entendiendo como "Competencia General", aquellas habilidades que nos ayudan a mejorar continuamente el desempeño y que son independientes de las competencias específicas de cada profesión, un ejemplo de ellas, es la habilidad de gestión, entendiendo como tal el desarrollo de una actitud proactiva, con capacidad para resolver problemas, tomar decisiones segun el nivel de influencia en el interior de las organizaciones. Hoy se hace necesario que las enfermeras desarrollen estas habilidades si queremos posicionarnos en un mundo cambiante y globalizante.

Control de proliferación de células tumorales humanas en cultivo: II células de neuroblastoma / Control of human cultured tumoral cell proliferation: II neuroblastoma cell

El control de la proliferación celular en cultivo de tejido ha sido un fenómeno ampliamente estudiado, principalmente en fibroblastos de ratón y rata, pudiéndose concluir que los mecanismos que operan son menos restrictivos para las células tumorales en cultivos hechos, esto hace suponer que la extrapolación de este fenómeno in vivo sea importante en el estudio de las formas de control de la proliferación de las neoplasias malignas

Características proliferativas de hibridomas B de ratón bajo diferentes condiciones de cultivo: su relación con el tamizaje de factores de crecimiento específicos / Proliferation characteristics of mouse B hybridomas under different culture condition: their relationship with the screening of specific growth factors

Se llevó a cabo la caracterización del crecimiento de varios hibridomas B de ratón, bajo diferentes condiciones de cultivos. Los experimentos de cultivo a alta densidad, clonaje y formación de colonias en medio gelificado con agarosa, empleando combinaciones de suero fetal bovino y sobrenadante de cultivos de células endoteliales humanas, demostraron que este último es capaz de promover el crecimiento a niveles comparables y aun superiores que el inducido por capas de células "alimentadoras". Se determinó que el hibridoma IOR-L1 es dependiente, para su proliferación, de la adición al medio de factores promotores del crecimiento no contenidos, o escasamente representados, en el suero fetal bovino. Sobre la base de estos experimentos se propone un sistema biológico para ser utilizado en el seguimiento de la marcha de purificación de actividades promotoras del crecimiento de hibridomas B

Sistema de producción del anticuerpo monoclonal IOR-T3 para uso terapéutico / Production system for the therapeutic monoclonal antibody IOR-T3

En el presente trabajo se reportan las experiencias obtenidas en la producción de 21 lotes del anticuerpo monoclonal IOR-T3 para uso terapéutico. Partiendo de líquido ascítico murino como fuente del anticuerpo monoclonal, se propone un sistema de purificación que tiene como paso principal una cromatografía de afinidad en proteína A Sefarosa. Este sistema es aplicable a la producción de anticuerpos monoclonales en la escala de los gramos con calidad adecuada para ser utilizados en forma inyectable, permitiendo obtener rendimientos de más del 70% de IgG recuperada. Los controles de actividad biológica realizados durante las diferentes etapas del proceso, permiten conocer si tanto las células a inocular como el líquido ascítico tienen una calidad adecuada para continuar la marcha. Se exponen los controles a realizar en el producto final para garantizar su calidad inyectable, entre los que se encuentran: pureza, esterilidad, ausencia de pirógenos y anticuerpos contra virus murinos. Los datos acumulados permiten apreciar la variabilidad existente en el comportamiento de los diferentes parámetros controlados durante el flujo productivo, demostrándose que existe una relación estadísticamente significativa entre la concentración de IgG en ascitis, su concentración mínima de trabajo y rendimientos de IgG monoclonal por mililitro de líquido ascítico y por miligramo de IgG procesados