RESUMEN
Diabetes is a chronic disease characterized by marked alterations in the metabolism of glucose and by high concentrations of glucose in the blood due to a decreased insulin production or resistance to the action of this hormone in peripheral tissues. The International Diabetes Federation estimates a global incidence of diabetes of about 10% in the adult population (20 - 79 years old), some 430 million cases reported worldwide in 2018. It is well documented that people with diabetes have a higher susceptibility to infectious diseases and therefore show higher morbidity and mortality compared to the non-diabetic population. Given that the innate immune response plays a fundamental role in protecting against invading pathogens through a myriad of humoral and cellular mechanisms, the present work makes a comprehensive review of the innate immune alterations in patients with type 2 diabetes mellitus (T2D) as well as a brief description of the molecular events leading or associated to such conditions. We show that in these patients a compromised innate immune response increases susceptibility to infections.
Asunto(s)
Diabetes Mellitus Tipo 2/complicaciones , Inmunidad Innata , Infecciones/patología , Animales , Diabetes Mellitus Tipo 2/inmunología , Humanos , Infecciones/etiologíaRESUMEN
The aim of the present work was to evaluate MTX treatment (0.1, 1 and 10 µg mL-1) in vitro in order to characterize its effects on cell proliferation alterations in cell cycle of HaCaT keratinocytes and wound healing in a Skh1 mice treated with MTX (low doses 30 mg kg-1, high doses 200 mg kg-1 and repeated doses at 1.5 mg kg-1). We analyzed the cytotoxic effect of methotrexate by a resazurin assay. The effects in the proliferation, cell cycle and apoptosis of HaCaT cells were analyzed by flow cytometry. The effects of MTX on wound healing in vivo were also analyzed. A trend toward reduction in the resazurin assay was found (p > 0.05). Reduced proliferation was also identified in a clonogenic assay and a CFSE assay (p < 0.05) due to the MTX treatment. A reduction in the G2/M and S phases was observed accompanied by apoptosis induction with increased sub G0 phase and annexin V FITC staining. Effect of MTX was evidenced in vivo on the wound closure process after day 10 (p < 0.05) with alterations in tissue architecture and remodeling. There is a marked effect of MTX on wound healing in vivo in Skh1 mice with implications for long-term therapy and surgical interventions.
Asunto(s)
Proliferación Celular/efectos de los fármacos , Queratinocitos/efectos de los fármacos , Metotrexato/farmacología , Cicatrización de Heridas/efectos de los fármacos , Análisis de Varianza , Animales , Apoptosis/efectos de los fármacos , Modelos Animales de Enfermedad , Ratones , Estadísticas no ParamétricasRESUMEN
Type 2 diabetes mellitus (DM2) is strongly associated with other comorbidities such as obesity, atherosclerosis, and hypertension. Obesity is associated with sustained low-grade inflammatory response due to the production of proinflammatory cytokines. This inflammatory process promotes the differentiation of some myeloid cells, including myeloid-derived suppressor cells (MDSCs). In this study, two groups of individuals were included: DM2 patients and non-DM2 individuals with similar characteristics. Immunolabeling of CD15+ CD14- and CD33+ HLA-DR-/low was performed from whole peripheral blood, and samples were analyzed by flow cytometry, and frequencies of MDSCs and the relationship of these with clinical variables, cytokine profile (measured by cytometric bead array), and anthropometric variables were analyzed. The frequency of CD33+ HLA-DR-/low MDSCs (that produce IL-10 and TGF-ß, according to an intracellular detection) is higher in patients with DM2 (P < 0.05), and there is a positive correlation between the frequency of CD15+ CD14- and CD33+ HLA-DR-/low MDSC phenotypes. DM2 patients have an increased concentration of serum IL-5 (P < 0.05). Also, a negative correlation between the frequency of CD15+ CD14- MDSCs and LDL cholesterol was found. Our group of DM2 patients have an increased frequency of mononuclear MDSC CD33+ HLA-DR-/low that produce TGF-ß and IL-10. These cytokines have been associated with immune modulation and reduced T cell responses. DM2 and non-DM2 subjects show a similar cytokine profile, but the DM2 patients have an increased concentration of IL-5.
Asunto(s)
Diabetes Mellitus Tipo 2/inmunología , Hipertensión/inmunología , Células Supresoras de Origen Mieloide/inmunología , Adulto , Femenino , Antígenos HLA-DR/análisis , Humanos , Interleucina-10/biosíntesis , Interleucina-5/sangre , Masculino , Persona de Mediana Edad , Lectina 3 Similar a Ig de Unión al Ácido Siálico/análisis , Factor de Crecimiento Transformador beta/biosíntesisRESUMEN
The physiopathology of rheumatoid arthritis (RA) is mediated by proinflammatory cytokines, some of which are regulated by the JAK/STAT pathway. Tofacitinib is a JAK inhibitor, but its role in the regulation of microRNAs (miRNAs) is unknown. There is also no information regarding the role of miRNAs in the clinical relapse/remission of RA. The present project aims to identify a signature profile of miRNA expression in a subgroup of RA patients who had to discontinue tofacitinib treatment (because of the ending of a 5-year open-label clinical trial) and to describe the expression of miRNAs during RA remission or flare-up. The relative expression of 61 miRNAs was determined in serum samples with the Firefly™ BioWorks assay. Statistical analysis was performed by means of Student's t-test and heatmap analysis was performed with Firefly™ Analysis Workbench software and in the software GraphPad® Prism v5.0. Target prediction and Gene Ontology analysis were carried out using bioinformatic tools. We found a distinctive signature of miRNA expression associated with relapse, featuring upregulated expression of hsamiR4325p (pâ¯<â¯0.05). We also found upregulation of hsamiR1945p (pâ¯<â¯0.05) in samples of patients with RA flare-up. Gene Ontology analysis of the target genes for hsamiR4325p was performed to identify relevant pathways associated with relapse; the implications of these pathways in the physiopathology of RA are discussed. Tofacitinib treatment does not have a direct effect on the expression of measured miRNAs. The changes in hsamiR4325p and hsamiR1945p are associated with the regulation of proinflammatory pathways and RA flare-up.
Asunto(s)
Antirreumáticos/farmacología , Artritis Reumatoide/genética , MicroARNs/sangre , Piperidinas/farmacología , Pirimidinas/farmacología , Pirroles/farmacología , Adulto , Antirreumáticos/uso terapéutico , Artritis Reumatoide/sangre , Artritis Reumatoide/tratamiento farmacológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Piperidinas/uso terapéutico , Pirimidinas/uso terapéutico , Pirroles/uso terapéutico , RecurrenciaRESUMEN
Due to many physiological and genetic characteristic similarities to humans, squirrel monkeys provide an ideal animal model specifically for studying malaria, and transmissible spongiform encephalopathies (Creutzfeldt-Jacob disease). While squirrel monkeys three years and older are generally considered adult subjects suitable for use in medical research studies, little is known about the functional properties of lymphocytes in relation to the age of these animals, which could significantly impact the quality and quantity of innate and adaptive immune responses. In this study, we investigated differences in the phenotype and function of lymphocytes subsets of young (3-4 years), adult (8-10 years) and aged (16-19 years) squirrel monkeys. In general, animals in all three age groups exhibited comparable numbers of different lymphocyte subsets except for CD20+ B cells that were significantly lower in aged relative to young animals and T cells subsets expressing both CD4 and CD8 (double positive) were significantly higher in aged relative to young animals. With increasing age, phenotypic differences in central and effector memory T cells subsets were observed, that were more pronounced for the CD8+ T cells. Despite equal proportions of CD3+ T cells among the three age groups, responses of peripheral blood mononuclear cells to T cell mitogens PHA and Con A showed lower IFN-γ producing cells in the aged group than that in the young group. Furthermore, aged animals showed significantly higher plasma levels of inflammatory cytokines IL-6, IFN-γ, TNF-α, IL-10 and IL-12. These findings suggest that while the squirrel monkeys in general share phenotypic and functional similarities of lymphocyte subsets with humans in relation to age, specific differences exist in immune function of lymphocytes between young and old animals that could potentially impact experimental outcomes for which the measurement of immunologic endpoints are critical.
Asunto(s)
Linfocitos/fisiología , Saimiri/inmunología , Inmunidad Adaptativa , Factores de Edad , Animales , Animales de Laboratorio/inmunología , Antígenos CD20/metabolismo , Bolivia , Citocinas/sangre , Ensayo de Immunospot Ligado a Enzimas , Femenino , Inmunidad Innata , Interferón gamma/metabolismo , Linfocitos/citología , Fenotipo , Saimiri/fisiologíaRESUMEN
Se informa acerca de 1,000 histerectomías realizadas por el autor en un lapso de 20 años en cuatro hospitales del ISSSTE. Se analizaron algunos parámetros clínicopatológicos, morbi-mortalidad, etc. Se informa de los resultados obtenidos utilizando simplificaciones en las técnicas quirúrgicas. Los síntomas más frecuentes fueron trastornos menstruales, y el diagnóstico más frecuente fue la miomatosis con (61.2 por ciento), la media de edad entre los 35-45 años. Todas las histerectomías fueron totales, 92.6 por ciento intrafasciales y 74.8 por ciento abdominales, Llamó la atención que 7.2 por ciento de las pacientes presentaron síndrome de congestión pélvica post oclusión tubaria y la asociación de adenomiosis. La mortalidad global fue de 12.2 por ciento predominando la del tipo urosepsis. La mortalidad se presentó en un caso por mioma intraligamentario gigante y coagulopatía por consumo. Se utilizó sangre sólo en 4.2 por ciento. Se piensa que la simplificación quirúrgica aquí enunciada, permite ofrecer mayor seguridad, menor morbilidad, mínimo sangrado y tiempo quirúrgico-anestésico breve. Además se realizó un análisis crítico del uso y abuso de este tipo de intervención quirúrgica
Asunto(s)
Humanos , Femenino , Cirugía General , Histerectomía/estadística & datos numéricosRESUMEN
It was observed the effects of captivity on the reproductive competence of monkeys, to measure the degree of adaptation to a confined situation. These observation were made on Cebus, Aotus, and Saimiri monkeys, from two different monkeys colonies, facing a project of establishment a breeding monkey colony at the IICS. It was observed the behavior of the monkeys concerning the aggressivness against the other monkeys in the cage and themselves, the organization of social groups, and its hierarchy. It was evidenced the importance of the tryning of the staff dealing with the monkeys, as factor influencing the behavior of the animals. It was observed the importance of the organization of the colony, concerning the surroundings of the cages, ventilation, room temperature, illumination, presence of personnel, location of other cages, as factors exerting a strong influence in the behavior of the monkeys