Development of a scalable single process for producing SARS-CoV-2 RBD monomer and dimer vaccine antigens.

We have developed a single process for producing two key COVID-19 vaccine antigens: SARS-CoV-2 receptor binding domain (RBD) monomer and dimer. These antigens are featured in various COVID-19 vaccine formats, including SOBERANA 01 and the licensed SOBERANA 02, and SOBERANA Plus. Our approach involves expressing RBD (319-541)-His6 in Chinese hamster ovary (CHO)-K1 cells, generating and characterizing oligoclones, and selecting the best RBD-producing clones. Critical parameters such as copper supplementation in the culture medium and cell viability influenced the yield of RBD dimer. The purification of RBD involved standard immobilized metal ion affinity chromatography (IMAC), ion exchange chromatography, and size exclusion chromatography. Our findings suggest that copper can improve IMAC performance. Efficient RBD production was achieved using small-scale bioreactor cell culture (2 L). The two RBD forms - monomeric and dimeric RBD - were also produced on a large scale (500 L). This study represents the first large-scale application of perfusion culture for the production of RBD antigens. We conducted a thorough analysis of the purified RBD antigens, which encompassed primary structure, protein integrity, N-glycosylation, size, purity, secondary and tertiary structures, isoform composition, hydrophobicity, and long-term stability. Additionally, we investigated RBD-ACE2 interactions, in vitro ACE2 recognition of RBD, and the immunogenicity of RBD antigens in mice. We have determined that both the monomeric and dimeric RBD antigens possess the necessary quality attributes for vaccine production. By enabling the customizable production of both RBD forms, this unified manufacturing process provides the required flexibility to adapt rapidly to the ever-changing demands of emerging SARS-CoV-2 variants and different COVID-19 vaccine platforms.

Molecular reshaping of phage-displayed Interleukin-2 at beta chain receptor interface to obtain potent super-agonists with improved developability profiles.

Interleukin-2 (IL-2) engineered versions, with biased immunological functions, have emerged from yeast display and rational design. Here we reshaped the human IL-2 interface with the IL-2 receptor beta chain through the screening of phage-displayed libraries. Multiple beta super-binders were obtained, having increased receptor binding ability and improved developability profiles. Selected variants exhibit an accumulation of negatively charged residues at the interface, which provides a better electrostatic complementarity to the beta chain, and faster association kinetics. These findings point to mechanistic differences with the already reported superkines, characterized by a conformational switch due to the rearrangement of the hydrophobic core. The molecular bases of the favourable developability profile were tracked to a single residue: L92. Recombinant Fc-fusion proteins including our variants are superior to those based on H9 superkine in terms of expression levels in mammalian cells, aggregation resistance, stability, in vivo enhancement of immune effector responses, and anti-tumour effect.

Potent immunomodulatory and antitumor effect of anti-CD20-IL2no-alpha tri-functional immunocytokine for cancer therapy.

Introduction: The anti-CD20 antibody rituximab (RTX) has substantially improved outcomes of patients with B-cell lymphomas, although more efficient therapies are needed for refractory or relapsing lymphomas. An approach to increase the clinical effectiveness of anti-tumor therapy is the use of antibody-cytokine fusion proteins (immunocytokines (ICKs)) to deliver at the tumor site the antibody effector functions and cytokines that trigger anti-tumor activities. In particular, IL-2-based ICKs have shown significant results in preclinical studies but not in clinical trials due to the toxicity profile associated to high doses IL-2 and the undesired expansion of Tregs. Methods: To improve the efficacy of RTX therapy, we fused a murine (mIgG2a) or a human (hIgG1) version of RTX to a mutated IL-2 (no-alpha mutein), which has a disrupted affinity for the high affinity IL-2 receptor (IL-2R) to prevent the stimulation of Tregs and reduce the binding to endothelial cells expressing CD25, the α chain of high affinity IL-2R. Characterization of anti-CD20-IL2no-alpha ICKs was performed by SDS-PAGE, Western-blotting and SEC-HPLC and also by several functional in vitro techniques like T-cell proliferation assays, apoptosis, CDC and ADCC assays. The in vivo activity was assessed by using murine tumor cells expressing huCD20 in C57/Bl6 mice. Results: Both ICKs exhibited similar in vitro specific activity of their IL2no-alpha mutein moieties and kept CD20-binding capacity. Anti-CD20-IL2no-alpha (hIgG1) retained antibody effector functions as complement-dependent cytotoxicity and enhanced direct apoptosis, NK cell activation and antibody-dependent cellular cytotoxicity relative to RTX. In addition, both ICKs demonstrated a higher antitumor efficacy than parental molecules or their combination in an EL4-huCD20 tumor model in immunocompetent mice. Anti-CD20-IL2no-alpha (hIgG1) strongly expanded NK and CD8+ T cells but not Tregs in tumor-bearing mice. Discussion: These findings suggest that anti-CD20-IL2no-alpha could represent an alternative treatment for B cell lymphoma patients, mainly those refractory to RTX therapy.

La terapia familiar como vía de la resignificación en la enfermedad / Family therapy as a way to redefine disease

Se realizó un rastreo bibliográfico sobre la reacomodación de las dinámicas internas en familias que tienen un infante en cuidados paliativos, haciendo hincapié en la importancia de la terapia familiar para entender la enfermedad y resignificarla mediante la técnica narrativa de la metáfora. Teniendo en cuenta lo anterior, cuando llega una crisis significativa al núcleo familiar, como una enfermedad, esta cambia la dinámica familiar, puesto que obliga a movilizarse de manera inesperada para buscar posibles soluciones a la situación que aqueja. En muchos casos, la familia recurre a la terapia familiar como estrategia para fortalecer sus recursos, y la metáfora como herramienta narrativa, es uno de los recursos que se usa para ayudar a resignificar la enfermedad. Ahora bien, en cuanto al rastreo bibliográfico, fue la base del texto reflexivo construido, ya que en el rastreo se evidenció que en la terapia familiar no se encuentra un abordaje específico en los procesos de salud que requieren acompañamiento paliativo, por lo que se hace necesario visibilizar la utilidad de la terapia familiar en estos procesos. Como conclusión, se presenta el uso de la metáfora como posible vía de trabajo con las familias que están pasando por una situación de enfermedad, puesto que facilita la externalización del problema y logran así nuevas narrativas orientadas a la resignificación.

A literature review was carried out on the rearrangement of inner dynamics in families with an infant in palliative care, emphasizing the importance of family therapy to understand the disease and resignify it through the narrative technique of metaphor. Considering the above, when a significant crisis, such as a disease, reaches the family core, family dynamics change since it forces unexpected mobilization to find possible solutions to the situation. In many cases, the family uses family therapy as a strategy to strengthen their resources, and the metaphor, as a narrative tool, is one of the resources used to help resignify the disease. Bibliographic review was the basis of the reflexive text constructed, since the review showed that in family therapy there is no specific approach in health processes that require palliative accompaniment, reason why it is necessary to draw attention to the usefulness of family therapy in this type of processes. In conclusion, the use of metaphor is presented as a possible way of addressing families who are going through a situation of disease, since it facilitates the externalization of the problem and the achievement of new narratives aimed at redefinition of the disease.

Logros y desafíos de la red universitaria REDMA: por la sostenibilidad ambiental de la educación superior en Cuba / Achievements and challenges of the REDMA university network: for the environmental sustainability of higher education in Cuba

Entre los temas más citados que hacen parte de las preocupaciones del mundo actual están la sostenibilidad ambiental y el desarrollo, no solo desde la reflexión de teóricos, humanistas, políticos y otros, sino también desde las agendas y agencias internacionales que los han posicionado como prioridad básica a ser atendida como salvaguarda de la vida en el planeta, en este sentido, la internacionalización de la economía y de los problemas socioculturales como la crisis ambiental y de valores, se tornan en asuntos medulares a considerar en la formación de profesionales. Desde la Educación Superior cubana, el logro de los fines mencionados está estrechamente relacionado con la capacidad de movilización colectiva y de proyección responsable de acciones que ofrece el trabajo en redes, de ahí que el objetivo de la presente disertación sea exponer los principales avances y resultados que ofrece hoy la Red de Medio Ambiente del MES (REDMA), en sus más de 20 años de conformada donde, desde la investigación y el intercambio científico, se integran procesos y políticas en la gestión del conocimiento y la innovación en favor del medioambiente, la prevención de riesgos y peligros, y la adaptación al cambio climático; las vías utilizadas para la compilación y selección de las mejores experiencias fueron el registro de información y la sistematización; los resultados expuestos evidencian sus contribuciones a la formación integral y multifacética de profesionales comprometidos con el desarrollo económico-social y sostenible del país.

Among the most cited issues that are part of the concerns of today's world are environmental sustainability and development, not only from the reflection of theorists, humanists, politicians and others, but also from international agendas and agencies which have positioned them as a basic priority to be addressed as a safeguard of life on the planet. In this sense, the internationalization of the economy and socio-cultural problems, such as the environmental and values crises, become core issues to be considered in the training of professionals. From the Cuban Higher Education, the achievement of the aforementioned purposes is closely related to the capacity of collective mobilization and responsible projection of actions offered by networking. Hence, the objective of this reflection is to present the main advances and results offered today by the Environment Network of the MES (REDMA), in its more than twenty years of formation where, from research and scientific exchange, processes and policies are integrated into knowledge management and innovation in favor of the environment, the prevention of risks and dangers, and the adaptation to climate change. The routes used for the compilation and selection of the best experiences were the registration of information and systematization. The exposed results show their contributions to the comprehensive and multifaceted training of professionals committed to the economic-social sustainable development of the country.

Novel HLA class I associations with HIV-1 control in a unique genetically admixed population.

Associations between HLA class I alleles and HIV progression in populations exhibiting Amerindian and Caucasian genetic admixture remain understudied. Using univariable and multivariable analyses we evaluated HLA associations with five HIV clinical parameters in 3,213 HIV clade B-infected, ART-naïve individuals from Mexico and Central America (MEX/CAM cohort). A Canadian cohort (HOMER, n = 1622) was used for comparison. As expected, HLA allele frequencies in MEX/CAM and HOMER differed markedly. In MEX/CAM, 13 HLA-A, 24 HLA-B, and 14 HLA-C alleles were significantly associated with at least one clinical parameter. These included previously described protective (e.g. B*27:05, B*57:01/02/03 and B*58:01) and risk (e.g. B*35:02) alleles, as well as novel ones (e.g. A*03:01, B*15:39 and B*39:02 identified as protective, and A*68:03/05, B*15:30, B*35:12/14, B*39:01/06, B*39:05~C*07:02, and B*40:01~C*03:04 identified as risk). Interestingly, both protective (e.g. B*39:02) and risk (e.g. B*39:01/05/06) subtypes were identified within the common and genetically diverse HLA-B*39 allele group, characteristic to Amerindian populations. While HLA-HIV associations identified in MEX and CAM separately were similar overall (Spearman's rho = 0.33, p = 0.03), region-specific associations were also noted. The identification of both canonical and novel HLA/HIV associations provides a first step towards improved understanding of HIV immune control among unique and understudied Mestizo populations.

Expression of the Sox9, Foxl2, Vasa, and TRPV4 genes in the ovaries and testes of the Morelet's crocodile, Crocodylus moreletii.

The Sox9 gene is important for determining sex in vertebrates, as well as for maintaining testis morphology and fertility during adult life. In the same way, Vasa is an important gene for the maintenance of the germinal lineage and has been highly conserved throughout evolution, as it is expressed in germ cells of both vertebrates and invertebrates. In the particular case of crocodiles, the expression of Sox9 during gonadal morphogenesis and in the testes of 3-month-old Alligator mississippiensis has been studied. However, it is interesting to carry out studies on other species of crocodiles in relation to their particular mechanism for sex determination influenced by temperature. In this work, we investigated the expression of the Sox9, Vasa, Foxl2, and TRPV4 genes in the ovaries and testes of 5-year-old juvenile crocodiles from Crocodylus moreletii. As expected, Sox9 expression was found in males, but surprisingly, it was also found in females. For the first time, the expression of Vasa was reported in spermatogonia, oogonia, and oocytes of 5-year-old crocodiles. Foxl2 is important for the development and maintenance of the ovary during adult life in vertebrates; moreover, Foxl2 protein and transcripts are both highly expressed in the ovaries compared to the testes. A possible upstream regulator of the Sox9 gene in reptiles has not yet been discovered; as such, the expression of the TRPV4 ion channel was evaluated. The TRPV4 ion channel was expressed in the cytoplasm of Sertoli and follicular cells and was therefore proposed as a possible regulator of SOX9.

Gonadal morphogenesis and establishment of the germline in the phyllostomid bat Sturnira lilium.

In vertebrates such as the mouse and the human, primordial germ cells (PGCs) arise at the base of the allantois and are carried to the epithelium of the posterior intestine, to later migrate to the primordial gonads. In the case of bats, almost nothing is known about this process. To clarify the dynamics of PGCs during gonadal morphogenesis in the phyllostomid bat Sturnira lilium, the proteins for the Ddx4, Sox9 and Mis genes were detected in the gonads of embryos at different stages of development. We identified 15 stages (St) of embryonic development in Sturnira lilium. We found that the formation of the genital ridge and the establishment of the undifferentiated gonad take place between stages 11 and 14. The onset of morphological differentiation in the gonad is first detected in the male gonads at St17. The first PGCs in meiosis are detected in the ovary at St19, whereas in the testicles, the PGCs were in mitotic arrest. Structural changes leading to testicular and ovarian development in Sturnira lilium are observed to be similar to those described for the mouse; however, differences will be established concerning the time taken for these processes to occur.

3D point cloud in the evaluation of processes that generate instability of the lumbar spine / Nuvem de pontos tridimensional na avaliação de processos que geram instabilidade da coluna lombar / Nube de puntos tridimensional en la evaluación de procesos que generan inestabilidad de la columna lumbar

OBJECTIVE: To integrate patients with lumbar instability in a multisensor platform in the process of assessment and diagnosis, assigning quantitative parameters for the sagittal balance (SB) and muscle function. METHODS: Experimental study involving adult patients diagnosed with diseases that cause alterations in the SB, that were or were not submitted to surgery with posterior instrumentation and fusion. Each patient underwent anthropometric measurements in body composition scale; a kinesiological analysis using a multisensor platform consisting of depth camera to static/dynamic analysis for the quantitative measurement of SB, and surface electromyography to capture the level of abdominal and lumbar muscles activation and through flexion and extension. RESULTS: Seven adult patients: five females (62.5%)and two men (37.5%) with a mean age 48 years. Images with depth cameras resulted in a SB of from -6.4 to +5.3cm (average -5.7cm). In individuals with positive sagittal balance the percentage of activation (PA) of the abdominal muscles was 58.5% and the lower back lumbar was 75.25%; patients with negative SB integrated the PA of the abdominal muscles of 70.25% and lumbar of 65%; the patient with neutral SB exhibited activation of the abdominal muscles of 87.75% and lumbar muscles of 78.25%. CONCLUSIONS: We observed a trend towards positive SB in patients with overweight and obesity by BMI, as well as increased activation of the abdominal muscles. The multi sensor platform is a useful tool for the diagnosis and prognosis of diseases involving sagittal imbalance. .

OBJETIVO: Integrar os pacientes com instabilidade lombar em uma plataforma multissensor no processo de avaliação e diagnóstico, atribuindo parâmetros quantitativos para o equilíbrio sagital (ES) e função muscular. MÉTODOS: Estudo experimental com pacientes adultos diagnosticados com doenças que causam alterações no ES, submetidos ou não à cirurgia com instrumentação e fusão por via posterior. Em cada paciente realizaram-se medidas antropométricas em balança de composição corporal, análise cinesiológica utilizando uma plataforma multissensor constituída por câmera profundidade para análise estática/dinâmica para medição quantitativa do ES e eletromiografia de superfície para capturar o nível de ativação da musculatura abdominal e lombar por meio de flexão e extensão. RESULTADOS: Sete pacientes adultos: cinco mulheres (62,5%) e dois homens (37,5%) com média de idade de 48 anos. As imagens com câmeras de profundidade resultaram em ES de -6,4+5,3cm (média -5,7cm). Nos indivíduos com equilíbrio sagital positivo, o percentual de ativação (PA) dos músculos abdominais foi 58,5% e dos músculos lombares foi 75,25%; nos pacientes com ES negativo integrado, a PA dos músculos abdominais foi de 70,25% e lombar 65%; o paciente com ES neutro apresentou ativação dos músculos abdominais de 87,75% e dos músculos lombares, de 78,25%. CONCLUSÃO: Observamos uma tendência ao ES positivo em pacientes com sobrepeso e obesidade pelo IMC, bem como ao aumento da ativação dos músculos abdominais. A plataforma multissensor constitui uma ferramenta útil para o diagnóstico e prognóstico de doenças com desequilíbrio sagital. .

OBJETIVO: Integrar a pacientes con inestabilidad lumbar a una plataforma multisensor en su proceso de evaluación y diagnóstico, dando parámetros cuantitativos para el balance sagital (BS) y la función muscular. MÉTODOS: Estudio de tipo experimental con pacientes adultos diagnosticados con patologías que causan alteraciones en el BS, unos no operados, y otros operados con instrumentación y fusión posteriores. Cada paciente fue sometido a mediciones antropométricas en báscula de composición corporal; un análisis kinesiólogo utilizando una plataforma multisensor constituida por cámara de profundidad para el análisis estático/dinámico para la medición cuantitativa del BS, y un electromiógrafo de superficie captó el grado de activación muscular en región abdominal y lumbar, mediante movimientos de flexión y extensión. RESULTADOS: Siete pacientes adultos: cinco mujeres (62.5%), dos hombres (37.5%); media de edad de 48 años. Las imágenes con cámaras de profundidad resultaron en un BS de -6.4 a+5.3cm (promedio-5.7cm). Aquellos con BS positivo el porcentaje de activación (PA) de los músculos abdominales fue de 58.5% y la de los lumbares fue de 75.25%; pacientes con BS negativo integraron un PA de los músculos abdominales de 70.25% y de lumbares de 65%; el paciente con balance sagital neutro tuvo activación de la musculatura abdominal de 87.75% y lumbar de 78.25%. CONCLUSIONES: Observamos tendencia al BS positivo en pacientes con sobrepeso y obesidad por IMC, así como mayor activación de músculos abdominales. La plataforma multisensor constituida es una herramienta útil para el diagnóstico y pronóstico de enfermedades con desbalance sagital. .

Presencia curricular de la Psicología de la Actividad Física y del Deporte en los planes de estudio de pregrado y posgrado de Educación Física versus Psicología, en México / A presença da disciplina psicologia da atividade física e do esporte nos currículos de graduação e de pós-graduação em Educação Física e em Psicologia, em universidades mexicanas / Curriculum presence of physical activity and sport psychology in undergrade and graduate Physycal Education versus Psychology curriculum, in Mexican universities

El objetivo del estudio fue comparar la presencia curricular de las unidades de aprendizaje de Psicología de la Actividad Física en los planes de estudio de las licenciaturas (pregrado) y posgrado de Educación Física versus Psicología en las universidades que se ofertan en la República Mexicana. Estudio descriptivo y transversal que tuvo de universo 144 programas de estudio de psicología y 68 de educación física; encontrando que en los Posgrados de Psicología el peso porcentual es un poco mayor (16.36) que en los Posgrados de Educación Física (14. 33). Pero al unir pregrado y posgrado se triplica el peso porcentual de las unidades de aprendizaje en las disciplinas de Educación Física (3.13) a diferencia que en psicología (0.93). Estos resultados permiten concluir que, como eje de formación curricular, la psicología de la actividad física y del deporte tiene mayor presencia en Educación Física que en Psicología, lo que significa la necesidad interdisciplinar y transdisicplinar de nuestro objeto de estudio; la unión e interconexión de la psicología y la actividad física y el deporte. Un problema y necesidad enfrentada fue la distinta nomenclatura de los programas de formación curricular tanto de los planes de estudio como de la unidad de aprendizaje, que pueden llevar a la necesidad nacional e internacional de acordar nombres, niveles, carga horaria y competencias (u objetivos) profesionales que pueden facilitar este tipo de análisis, pero sobretodo que faciliten el intercambio académico de estudiantes y profesores.

O presente estudo teve como objetivo comparar o peso percentual das unidades de aprendizagem de psicologia da atividade física na estrutura curricular para a formação profissional inicial e de pós-graduação nos currículos de Educação Física versus Psicologia, em universidades mexicanas. De caráter descritivo e transversal, e tendo como universo 144 currículos de Psicologia e 68 de Educação Física, o estudo mostrou que nos Programas de pós-graduação em Psicologia o peso percentual é um pouco maior (16.36) que nos Programas de Pós-graduação em Educação Física (14.33). Entretanto, ao considerarmos graduação e pós-graduação conjuntamente, o peso percentual das unidades de aprendizagem é três vezes superior nas disicplinas de Educação Física (3.13) em relação às de Psicologia (0.93).

The aim of this study was to compare the percentage of Learning Units in Psychology of Physical Activity in the curriculum structure for the training of the degree (undergraduate) and graduate curricula in Physical Education versus Psychology offered in universities in Mexico. This study was descriptive and cross-sectional, it had an universe of 144 programs of study in Psychology and 68 in Physical Education. We found that percentage in graduate programs of Psychology is slightly higher (16.36) than Graduate programs of Physical Education (14.33). But by combining Undergraduate and Graduate, the percentage of Learning Units in the disciplines of Physical Education (3.13) triples the percentaje weight in Psychology (0.93).These results allow the conclusion that, as the axis of training curriculum, Psychology of Physical Activity and Sport has a greater presence in Physical Education than in Psychology, which means the need interdisciplinary and transdisciplinary of our object of study; the connection and interconnection of the Psychology and the study of Physical Activity and Sport. A problem found during this study which needs to be faced was the nomenclature of the different training programs from both the curriculum plans of study and the learning units, which can lead to national and international agreements on names, levels, load time and professional competences (or targets) to provide this type of analysis, but especially to facilitate academic exchange programs of students and teachers.

Identification of cortical germ cells in adult ovaries from three phyllostomid bats: Artibeus jamaicensis, Glossophaga soricina and Sturnira lilium.

It is generally considered that, in mammals, the ovary is endowed with a finite number of oocytes at the time of birth. However, studies concerning rodents, lemurs and humans suggest the existence of stem cells from the germline that may be involved in germ-cell renewal, maintaining postnatal follicle development. This type of work on wild species is scarce; therefore the objective of this study was to determine ovarian morphology and the presence of progenitor cells from the germline of three species of phyllostomid bats (Artibeus jamaicensis, Glossophaga soricina and Sturnira lilium). The morphological characteristics of the ovaries and the expression of specific markers of germline cells, stem cells and proliferation cells were analysed. The morphology of the ovaries of the three bat species was similar. A polarised ovary with follicles at different stages of development and groups of cortical cells similar to primordial germ cells were observed. Immunofluorescent analysis showed that these cortical cells express germline, stem-cell and proliferative markers, indicating the identification of germ cells that could maintain pluripotency, as well as being mitotically active. This suggests that in the adult ovary of phyllostomid bats there may be a mechanism for the self-renewal of the germline.

Condiciones de valoración del capital petrolero: el caso de Chaco y Andina

El presente documento de investigación, que lleva por tìtulo Condiciones de Valorización del Capital Petrolero: El caso de Chaco y Andina en Bolivia, constituye un producto del trabajo desarrollado en el marco del Programa de Investigación La Empresa Boliviana y las Reformas Estructurales, en el esfuerso de valorar del excedente petrolero, las condiciones de producción y circulación del capital invertido en las Compañias Chaco y Andina. En los dos primeros capítulos se presentan una relación acerca de las Corporaciones de las que forman parte Chaco y Andina, estableciendo principales indicadores económicos y sociales y se realiza el análisis de posicionamiento de Chaco y Andina como Compañias Petroleras dentro de Bolivia

Monopolios petroleros en bolivia : la formación de sus ganancias extraordinarias

Este trabajo transita por los senderos de valorización de las corporaciones petroleras en Bolivia, en el periodo neoliberal del capitalismo tardío, desde un enfoque teórico y epistemológico marxista. El análisis se detiene no sólo en las determinaciones de la esfera económica que conforman la reproducción del capital petrolero, sino también en el papel del Estado, como momento político de esta reproducción. La reflexión se sustenta en información empírica recogida a lo largo de más de 3 años en compañías petroleras.

Monopolios petroleros en Bolivia: la información de sus ganancias extraordinarias

Este trabajo transita por los senderos de valorización de las corporaciones petroleras en Bolivia, en el periódo neoliberal del capitalismo tardío, desde un enfoque teórico y epistemológico maxista.

Control del dolor posoperatorio con chorhidrato de nalbufina / Control of postoperative pain with nalbuphine hydrochloric acid

Se realizó un análisis del clorhidrato de nalbufina, para control del dolor postoperatorio, en 36 pacientes sometidos a cirugía cardiovascular con circulación extracorpórea, por diversos padecimientos cardiovasculares. El estudio se realizó en el servicio de terapia postquirúrgica del Hospital de Cardiología y Neumología, utilizando nalbufina a razón de 200 microgramos por kilogramo de peso, por vía intravenosa cada 6 horas, aplicando la primera dosis en el momento en que el paciente manifestó dolor. Diez y ocho pacientes estaban intubados y diez y ocho pacientes habían sido extubados. Se observó adecuada analgesia. Hubo sedación sin llegar a depresión respiratoria, no se presentaron cambios hemodinámicos significativos y los gases arteriales mostraron acidosis compensada. No se presentaron alteraciones psicomotoras colaterales