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Covalent peptidomimetic protease inhibitors have gained a lot of attention in drug development in recent years. They are designed to covalently bind the catalytically active amino acids through electrophilic groups called warheads. Covalent inhibition has an advantage in terms of pharmacodynamic properties but can also bear toxicity risks due to non-selective off-target protein binding. Therefore, the right combination of a reactive warhead with a well-suited peptidomimetic sequence is of great importance. Herein, the selectivities of well-known warheads combined with peptidomimetic sequences suited for five different proteases were investigated, highlighting the impact of both structure parts (warhead and peptidomimetic sequence) for affinity and selectivity. Molecular docking gave insights into the predicted binding modes of the inhibitors inside the binding pockets of the different enzymes. Moreover, the warheads were investigated by NMR and LC-MS reactivity assays against serine/threonine and cysteine nucleophile models, as well as by quantum mechanics simulations.
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Peptidomiméticos , Inhibidores de Proteasas , Inhibidores de Proteasas/farmacología , Inhibidores de Proteasas/química , Peptidomiméticos/farmacología , Simulación del Acoplamiento Molecular , Aminoácidos/química , Cisteína/metabolismoRESUMEN
Since the outbreak of COVID-19, one of the strategies used to search for new drugs has been to find inhibitors of the main protease (Mpro) of the virus SARS-CoV-2. Initially, previously reported inhibitors of related proteases such as the main proteases of SARS-CoV and MERS-CoV were tested. A huge effort was then carried out by the scientific community to design, synthesize and test new small molecules acting as inactivators of SARS-CoV-2 Mpro. From the chemical structure view, these compounds can be classified into two main groups: one corresponds to modified peptides displaying an adequate sequence for high affinity and a reactive warhead; and the second is a diverse group including chemical compounds that do not have a peptide framework. Although a drug including a SARS-CoV-2 main protease inhibitor has already been commercialized, denoting the importance of this field, more compounds have been demonstrated to be promising potent inhibitors as potential antiviral drugs.
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Tratamiento Farmacológico de COVID-19 , SARS-CoV-2 , Antivirales/farmacología , Proteasas 3C de Coronavirus , Humanos , Simulación del Acoplamiento Molecular , Péptido Hidrolasas , Inhibidores de Proteasas/farmacologíaRESUMEN
The upper limb is involved in burns in a high percentage of cases and its reconstruction is extremely important, given the functional impact of this anatomical region. Among the reconstruction choices for severe and large structural defects, the pedicled anterolateral thigh flap is an available option. This case study discusses the utilization of the pedicled anterolateral thigh flap for reconstruction of a complex full-thickness hand burn, when adequate arterial perforators were not available. Complex hand burns can often present challenges for reconstructive coverage, because of the complex anatomy of the upper extremity and the need to preserve as much function as possible. The use the anterolateral thigh free flap is one option that can be utilized for coverage of these large hand defects, in the face of poor local tissue advancement options. The finding of inadequate or lack of perforator vessels necessitates intraoperative changes in the surgical approach. In these cases, different alternatives exist depending on the dimensions and characteristics of the required coverage, the dissection of a pedicled flap being one of them. The pedicled anterolateral thigh flap represents an alternative for the coverage of large hand defects in the absence of valid perforators during free-flap dissection.
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Quemaduras/cirugía , Traumatismos del Antebrazo/cirugía , Colgajos Tisulares Libres/trasplante , Traumatismos de la Mano/cirugía , Adulto , Burkina Faso , Quemaduras/clasificación , Humanos , Puntaje de Gravedad del Traumatismo , Masculino , Resultado del TratamientoRESUMEN
Lysosomal storage diseases (LSDs) are caused by accumulation of partially degraded substrates within the lysosome, as a result of a function loss of a lysosomal protein. Recombinant lysosomal proteins are usually produced in mammalian cells, based on their capacity to carry out post-translational modifications similar to those observed in human native proteins. However, during the last years, a growing number of studies have shown the possibility to produce active forms of lysosomal proteins in other expression systems, such as plants and microorganisms. In this paper, we review the production and characterization of human lysosomal proteins, deficient in several LSDs, which have been produced in microorganisms. For this purpose, Escherichia coli, Saccharomyces cerevisiae, Pichia pastoris, Yarrowia lipolytica, and Ogataea minuta have been used as expression systems. The recombinant lysosomal proteins expressed in these hosts have shown similar substrate specificities, and temperature and pH stability profiles to those produced in mammalian cells. In addition, pre-clinical results have shown that recombinant lysosomal enzymes produced in microorganisms can be taken-up by cells and reduce the substrate accumulated within the lysosome. Recently, metabolic engineering in yeasts has allowed the production of lysosomal enzymes with tailored N-glycosylations, while progresses in E. coli N-glycosylations offer a potential platform to improve the production of these recombinant lysosomal enzymes. In summary, microorganisms represent convenient platform for the production of recombinant lysosomal proteins for biochemical and physicochemical characterization, as well as for the development of ERT for LSD.
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Enfermedades por Almacenamiento Lisosomal/tratamiento farmacológico , Lisosomas/enzimología , Proteínas/aislamiento & purificación , Proteínas Recombinantes/biosíntesis , Animales , Escherichia coli/metabolismo , Vectores Genéticos/metabolismo , Humanos , Plantas/genética , Proteínas/uso terapéutico , Proteínas Recombinantes/uso terapéutico , Saccharomycetales/metabolismoRESUMEN
Nutrient limitation has been proposed as a biofouling control strategy for membrane systems. However, the impact of permeation on biofilm development under phosphorus-limited and enriched conditions is poorly understood. This study analyzed biofilm development in membrane fouling simulators (MFSs) with and without permeation supplied with water varying dosed phosphorus concentrations (0 and 25 µg P·L-1). The MFSs operated under permeation conditions were run at a constant flux of 15.6 L·m2·h-1 for 4.7 days. Feed channel pressure drop, transmembrane pressure, and flux were used as performance indicators. Optical coherence tomography (OCT) images and biomass quantification were used to analyze the developed biofilms. The total phosphorus concentration that accumulated on the membrane and spacer was quantified by using microwave digestion and inductively coupled plasma atomic emission spectroscopy (ICP-OES). Results show that permeation impacts biofilm development depending on nutrient condition with a stronger impact at low P concentration (pressure drop increase: 282%; flux decline: 11%) compared to a higher P condition (pressure drop increase: 206%; flux decline: 2%). The biofilm that developed at 0 µg P·L-1 under permeation conditions resulted in a higher performance decline due to biofilm localization and spread in the MFS. A thicker biofilm developed on the membrane for biofilms grown at 0 µg P·L-1 under permeation conditions, causing a stronger effect on flux decline (11%) compared to non-permeation conditions (5%). The difference in the biofilm thickness on the membrane was attributed to a higher phosphorus concentration in the membrane biofilm under permeation conditions. Permeation has an impact on biofilm development and, therefore, should not be excluded in biofouling studies.
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Fructo-oligosaccharides (FOS) are one of the most well-studied and commercialized prebiotics. FOS can be obtained either by controlled hydrolysis of inulin or by sucrose transfructosylation. FOS produced from sucrose are typically classified as short-chain FOS (scFOS), of which the best known are 1-kestotriose (GF2), 1,1-kestotetraose (GF3), and 1,1,1-kestopentaose (GF4), produced by fructosyltransferases (FTases) or ß-fructofuranosidases. In previous work, FOS production was studied using the Aspergillus oryzae N74 strain, its ftase gene was heterologously expressed in Komagataella phaffii (Pichia pastoris), and the enzyme's tertiary structure modeled. More recently, residues that may be involved in protein-substrate interactions were predicted. In this study, the aim was to experimentally validate previous in silico results by independently producing recombinant wild-type A. oryzae N74 FTase and three single-point mutations in Komagataella phaffii (Pichia pastoris). The R163A mutation virtually abolished the transfructosylating activity, indicating a requirement for the positively charged arginine residue in the catalytic domain D. In contrast, transfructosylating activity was improved by introducing the mutations V242E or F254H, with V242E resulting in higher production of GF2 without affecting that of GF3. Interestingly, initial sucrose concentration, reaction temperature and the presence of metal cofactors did not affect the enhanced activity of mutant V242E. Overall, these results shed light on the mechanism of transfructosylation of the FTase from A. oryzae and expand considerations regarding the design of biotechnological processes for specific FOS production.
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Aspergillus oryzae , Aspergillus oryzae/genética , Hexosiltransferasas , Oligosacáridos , Pichia/genética , Saccharomycetales , SacarosaRESUMEN
Biofouling is a problem that hinders sustainable membrane-based desalination and the stratification of bacterial populations over the biofilm's height is suggested to compromise the efficiency of cleaning strategies. Some studies reported a base biofilm layer attached to the membrane that is harder to remove. Previous research suggested limiting the concentration of phosphorus in the feed water as a biofouling control strategy. However, the existence of bacterial communities growing under phosphorus-limiting conditions and communities remaining after cleaning is unknown. This study analyzes the bacterial communities developed in biofilms grown in membrane fouling simulators (MFSs) supplied with water with three dosed phosphorus conditions at a constant biodegradable carbon concentration. After biofilm development, biofilm was removed using forward flushing (an easy-to-implement and environmentally friendly method) by increasing the crossflow velocity for one hour. We demonstrate that small changes in phosphorus concentration in the feed water led to (i) different microbial compositions and (ii) different bacterial-cells-to-EPS ratios, while (iii) similar bacterial biofilm populations remained after forward flushing, suggesting a homogenous bacterial community composition along the biofilm height. This study represents an exciting advance towards greener desalination by applying non-expensive physical cleaning methods while manipulating feed water nutrient conditions to prolong membrane system performance and enhance membrane cleanability.
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PURPOSE: Bevacizumab is a monoclonal antibody that binds to vascular endothelial growth factor A. It is currently used in combination with chemotherapy to treat metastatic colorectal cancer. This therapy is not equally effective in every patient; in some, mechanisms of resistance arise that remain poorly understood. The aim of the present work was to determine whether the expression of 26 miRNAs could be associated with the effectiveness of bevacizumab plus chemotherapy, with progression-free survival (PFS), and with overall survival (OS) in metastatic colorectal cancer. PATIENTS AND METHODS: Paraffin-embedded biopsies from 76 patients with metastatic colorectal cancer were collected to isolate miRNAs. The expression of 26 miRNAs was analyzed by quantitative RT-PCR. For the purpose of analysis, patients were classified as either "responders" (PFS ≥6 months since beginning treatment) or "non-responders" (PFS <6 months). For the analysis of PFS and OS, patients were classified into two groups using the median gene expression value as the cut-off point ("high" [≥50% percentile] or "low" [<50% percentile]). Time-to-event data were analyzed using the Kaplan-Meier method and compared by the log rank test. Cox regression was used to estimate hazard ratios (HR) and their 95% confidence intervals. RESULTS: miR-7-5p and miR-10a-5p were more strongly expressed in non-responders than responders (p=0.049 and p=0.043, respectively), and OS was poorer in patients showing these higher expression levels (HR=2.54, 95% CI 1.42-4.55, p=0. 001, and HR=1.81, 95% CI 1.02-3.20, p=0.039, respectively). The overexpression of miR-143-3p, however, was associated with a better prognosis and significantly better PFS (HR=0.57; 95% CI: 0.33-0.96; p=0.033). CONCLUSION: High expression values for miR-7-5p and miR-10a-5p might be considered markers of a poorer prognosis in patients with metastatic colorectal cancer treated with bevacizumab plus chemotherapy, while the same for miR-143-3p might be a marker of better outcomes.
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In one of every four or five cases of breast cancer, the human epidermal growth factor receptor-2 (HER2) gene is overexpressed. These carcinomas are known as HER2-positive. HER2 overexpression is linked to an aggressive phenotype and a lower rate of disease-free and overall survival. Drugs such as trastuzumab, pertuzumab, lapatinib, neratinib, and the more recent afatinib target the deregulation of HER2 expression. Some authors have attributed somatic mutations in HER2, a role in resistance to anti-HER2 therapy as differential regulation of HER2 has been observed among patients. Recently, studies in metastatic ER + tumors suggest that some HER2 mutations emerge as a mechanism of acquired resistance to endocrine therapy. In an effort to identify possible biomarkers of the efficacy of anti-HER2 therapy, we here review the known single-nucleotide polymorphisms (SNPs) of the HER2 gene found in HER2-positive breast cancer patients and their relationship with clinical outcomes. Information was recompiled on 11 somatic HER2 SNPs. Seven polymorphisms are located in the tyrosine kinase domain region of the gene contrasting with the low number of mutations found in extracellular and transmembrane areas. HER2-positive patients carrying S310F, S310Y, R678Q, D769H, or I767M mutations seem good candidates for anti-HER2 therapy as they show favorable outcomes and a good response to current pharmacological treatments. Carrying the L755S or D769Y mutation could also confer benefits when receiving neratinib or afatinib. By contrast, patients with mutations L755S, V842I, K753I, or D769Y do not seem to benefit from trastuzumab. Resistance to lapatinib has been reported in patients with L755S, V842I, and K753I. These data suggest that exploring HER2 SNPs in each patient could help individualize anti-HER2 therapies. Advances in our understanding of the genetics of the HER2 gene and its relations with the efficacy of anti-HER2 treatments are needed to improve the outcomes of patients with this aggressive breast cancer.
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BACKGROUND: In metastatic colorectal cancer (mCRC), the anti-vascular endothelial growth factor drug bevacizumab (BVZ) plus chemotherapy significantly improves progression-free survival compared to chemotherapy (CT) alone. This benefit is not, however, observed in all patients. While increased chemokine CXCL5 gene expression promoting angiogenesis has been proposed as a prognostic mCRC biomarker, few studies have examined its relationship with drug efficacy. This study sought to analyze tumor CXCL5 gene expression in six patients with different efficacy of BVZ-containing CT in terms of the tumor response to treatment. CASE SUMMARY: We report six cases of stage IV KRAS-mutated mCRC. Patients were given first line treatment with BVZ-containing chemotherapy in University Hospital of Fuenlabrada. The six patients differed in terms of primary tumor location (right/left side), tumor burden (mostly hepatic and peritoneal disease) and clinical disease course. Before treatment onset, total RNA was isolated from paraffinated tumor biopsy specimens and CXCL5 gene expression quantified through conventional RT-qPCR procedures. Our main finding was that CXCL5 expression levels were several times higher in three patients with lower progression free survival (under 6 mo) from the start of treatment. CONCLUSION: A higher expression of CXCL5 was observed in the three patients showing worse tumor response to treatment.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bevacizumab/uso terapéutico , Quimiocina CXCL5/metabolismo , Neoplasias Colorrectales/terapia , Metástasis de la Neoplasia/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Bevacizumab/farmacología , Biopsia , Quimiocina CXCL5/análisis , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Resistencia a Antineoplásicos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Supervivencia sin Progresión , Proteínas Proto-Oncogénicas p21(ras)/genéticaRESUMEN
Phenylketonuria (PKU) is an autosomal recessive disorder caused by a defective phenylalanine hydroxylase (PAH), which catalyzes the hydroxylation of l-phenylalanine (l-Phe) to l-tyrosine (l-Tyr) in presence of the cofactor tetrahydrobiopterin (BH4). Defective PAH causes accumulation of phenylalanine, which has neurotoxic effects and leads to dermatological, behavioral, and neurocognitive problems. Treatments for this disease consist in life-long diets that are hard for patients to keep, or supplementation with BH4. In this study, we propose a system where a probiotic lactic acid bacteria (LAB) can be used as vehicle to express in situ an engineered human PAH. Engineered PAHs contain a secretion peptide, a gastrointestinal signal (GI), the human PAH, and a flexible glycine linker followed by the fluorescence protein mEGFP. Engineered constructs were successfully transformed, expressed, and secreted in Lactobacillus plantarum CM_PUJ411. PAH construct containing either the signal peptide GI1 or GI2 were transported through a Caco-2 cell monolayer. Nevertheless, the one containing GI1 allowed the highest transport through the cell monolayer. Co-culture of L. plantarum and Caco-2 cells showed that engineered PAH is produced in-situ and transported through the cell monolayer. Finally, the activity test showed that the engineered PAH secreted by L. plantarum CM_PUJ411 is active, leading to a reduction in l-Phe and an increase in l-Tyr levels, respectively. These results show the potential of this system as a new therapeutic alternative for the treatment of PKU patients.
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Sistemas de Liberación de Medicamentos , Lactobacillus plantarum/metabolismo , Fenilalanina Hidroxilasa/biosíntesis , Probióticos/administración & dosificación , Células CACO-2 , Tracto Gastrointestinal/metabolismo , Humanos , Lactobacillus plantarum/genética , Fenilalanina Hidroxilasa/genética , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/genéticaRESUMEN
RESUMEN La amiloidosis laríngea es un desorden infrecuente con síntomas inespecíficos que dificultan su diagnóstico. A través de la descripción y análisis de tres casos valorados en el Hospital Universitario San Ignacio, Bogotá buscamos ampliar el conocimiento en esta patología y comparar nuestros hallazgos con los descritos en la literatura. Se realizó una búsqueda retrospectiva de pacientes con diagnóstico de amiloidosis laríngea en los últimos cinco años en nuestra institución, obteniendo un total de 3 pacientes que cumplieron con nuestros criterios de selección. El síntoma más frecuente en estos pacientes fue la disfonía. La principal presentación encontrada fue de tipo sistémica, contrario a lo reportado en la literatura. Se realizó una remodelación de la vía aérea mediante microcirugía laríngea con láser de dióxido de carbono, obteniendo resultados clínicos satisfactorios. Es importante realizar más estudios del tema en nuestro país, teniendo en consideración el número reducido de casos debido a su baja prevalencia.
SUMMARY Laryngeal amyloidosis in an infrequent disorder, with nonspecific symptoms that difficult the diagnosis and without a consensus for its treatment. Through the description, analysis and comparison of three cases of laryngeal amyloidosis at the Hospital Universitario San Ignacio Bogotá, we seek to expand the knowledge in this pathology and compare it with what is described in the literature. We made a retrospective research of patients with a diagnosis of laryngeal amyloidosis in the last five years in our institution, obtaining a final sample of 3 cases that met the inclusion criteria. The most frequent symptom was dysphonia, the most frequent presentation was systemic, contrary to what was reported in the literature. Airway remodeling was performed using laryngeal microsurgery with carbon dioxide laser, obtaining good clinical results. We con-sider important to carry out more studies on the subject in our country.
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Humanos , Amiloidosis , DiagnósticoRESUMEN
Objetivo: la parotiditis recurrente benigna de la infancia (PRBI) es una enfermedad de importancia clínica. Sin embargo, su diagnóstico puede no realizarse correctamente debido al desconocimiento de esta entidad. El propósito de este estudio es describir los aspectos clínicos fundamentales de esta condición y proponer un enfoque terapéutico simple. Materiales y métodos: se realizó un análisis descriptivo de pacientes pediátricos con diagnóstico de parotiditis viral y PRBI entre los años 2008 y 2018, en el Hospital Universitario San Ignacio de Bogotá, Colombia. Resultados: se encontraron 41 pacientes con diagnóstico de PRBI; de estos, el 51,2 % fueron de sexo femenino, con una edad media de 7,1 años. A 32 pacientes (78 %) con diagnóstico de PRBI se les realizaron imágenes diagnósticas, a pesar de que la tasa de complicaciones fue baja (19,5 %). El diagnóstico fue hecho por los servicios de pediatría y otorrinolaringología en el 80 % de los casos. Conclusiones: hasta donde sabemos, este es el estudio con mayor número de pacientes con diagnóstico de PRBI en Latinoamérica. Es indispensable conocer esta enfermedad y tener en cuenta su curso benigno y pocas complicaciones, con el fin de destinar menos recursos en el uso de imágenes innecesarias y evitar el sobrediagnóstico de parotiditis por paramixovirus.
SUMMARY Objectives: Benign recurrent parotitis of childhood (BRPC) is a clinically relevant disease in childhood. Its diagnosis, however, is usually not made due to the lack of knowledge regarding such a condition. The aim of this study is to describe the most relevant aspects of this condition and propose a simple therapeutic approach. Materials and Methods: We did a descriptive analysis of pediatric patients diagnosed with viral parotitis and BRPC between 2008 and 2018, at the Hospital Universitario San Ignacio in Bogotá, Colombia. Results: 41 patients with BRPC where included; 51.2% were female, with a mean age of 7.1 years. Thirty-two patients (78%) with diagnosis of BRPC underwent diagnostic imaging, despite the low rate of complications (19,5%). The diagnosis was made by otolaryngologists or pediatricians in 80% of the cases. Conclusions: To our knowledge, this is the study with the largest number of BRPC cases in Latin America. It is essential to know about this disease and take into account its benign course and few complication rates, in order to avoid both wasting of resources in the use of unnecessary imaging and the overdiagnosis of mumps.
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Mucopolysaccharidosis IV A (MPS IV A, Morquio A disease) is a lysosomal storage disease (LSD) produced by mutations on N-acetylgalactosamine-6-sulfate sulfatase (GALNS). Recently an enzyme replacement therapy (ERT) for this disease was approved using a recombinant enzyme produced in CHO cells. Previously, we reported the production of an active GALNS enzyme in Escherichia coli that showed similar stability properties to that of a recombinant mammalian enzyme though it was not taken-up by culture cells. In this study, we showed the production of the human recombinant GALNS in the methylotrophic yeast Pichia pastoris GS115 (prGALNS). We observed that removal of native signal peptide and co-expression with human formylglycine-generating enzyme (SUMF1) allowed an improvement of 4.5-fold in the specific GALNS activity. prGALNS enzyme showed a high stability at 4 °C, while the activity was markedly reduced at 37 and 45 °C. It was noteworthy that prGALNS was taken-up by HEK293 cells and human skin fibroblasts in a dose-dependent manner through a process potentially mediated by an endocytic pathway, without any additional protein or host modification. The results show the potential of P. pastoris in the production of a human recombinant GALNS for the development of an ERT for Morquio A.
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Condroitinsulfatasas/metabolismo , Pichia/metabolismo , Proteínas Recombinantes/metabolismo , Células Cultivadas , Condroitinsulfatasas/química , Condroitinsulfatasas/genética , Condroitinsulfatasas/aislamiento & purificación , Endocitosis , Estabilidad de Enzimas , Células Epiteliales/metabolismo , Fibroblastos/metabolismo , Expresión Génica , Humanos , Oxidorreductasas actuantes sobre Donantes de Grupos Sulfuro , Pichia/genética , Transporte de Proteínas , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/aislamiento & purificación , Sulfatasas/genética , Sulfatasas/metabolismo , TemperaturaAsunto(s)
Bronquiolitis Obliterante/terapia , Quistes , Enfermedades Renales Poliquísticas , Bronquiolitis Obliterante/diagnóstico , Niño , Quistes/cirugía , Humanos , Hiperesplenismo/cirugía , Trasplante de Riñón , Hepatopatías/cirugía , Trasplante de Hígado , Masculino , Pancitopenia/etiología , Pancitopenia/cirugía , Enfermedades Renales Poliquísticas/cirugía , Insuficiencia Renal Crónica/complicaciones , Esplenectomía , Listas de EsperaRESUMEN
No disponible
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Humanos , Masculino , Niño , Bronquiolitis Obliterante/diagnóstico por imagen , Bronquiolitis Obliterante/tratamiento farmacológico , Esplenectomía/métodos , Pancitopenia/complicaciones , Radiografía Torácica , Sepsis/tratamiento farmacológico , Espirometría , Budesonida/administración & dosificación , Hiperesplenismo/complicaciones , Cirrosis Hepática/psicologíaRESUMEN
No disponible
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Humanos , Masculino , Femenino , Recién Nacido , Malformaciones de la Vena de Galeno/diagnóstico , Malformaciones Arteriovenosas , Malformaciones de la Vena de Galeno/patología , Malformaciones de la Vena de Galeno/terapia , Estudios RetrospectivosRESUMEN
Se muestra el caso de un paciente con 56 años de edad, con un síndrome adenomegálico generalizado que presentó un linfoma de Hodgkin de celularidad mixta, asociado al virus de Epstein-Barr. El paciente previo al inicio del linfoma presentó episodios prolongados de estrés emocional, lo que posiblemente contribuyó a la disminución de la vigilancia inmunológica. El caso fue abordado por los estudiantes de quinto semestre en la asignatura Acto médico, una estrategia didáctica interdisciplinaria. Este artículo presenta los aspectos a tener en cuenta en el enfoque clínico de los pacientes con adenopatías desde una perspectiva integradora de la inmunología, la clínica y los diagnósticos diferenciales. Se resalta el valor del estudio de los casos clínicos con varios métodos diagnósticos como estrategia didáctica. Finalmente, se realiza una revisión de la literatura sobre el linfoma Hodgkin orientada al papel en el que participa la infección por el virus de Epstein-Barr, relacionada con la inmunosupresión por estrés.
SUMMARY We present the case of a 56-year-old patient with a generalized adenomegalic syndrome who presented a mixed cellular Hodgkin's lymphoma associated with Epstein Barr Virus. The patient had had great emotional stress prior to the onset of lymphoma, which possibly contributed to the decrease in immunological surveillance. The case was addressed by the students of the fifth semester in the subject "Medical Act", an interdisciplinary didactic strategy. We present the aspects to be taken into account in the approach of the clinician of patients with adenopathies from an integrative perspective of immunology, clinical and differential diagnoses; and the value of the study of clinical cases with several diagnostic approaches as a didactic strategy is highlighted. Finally, we present a literature review about Hodgkin lymphoma and the role which plays stress related Epstein Barr Virus infection.