Histopatologia de la leishmaniasis cutánea causada por Leishmania (Leishmania) mexicana en la península de Yucatán, México

Localized Cutaneous Leishmaniasis (LCL) known as "chiclero's ulcer" in southeast Mexico, was described by SEIDELIN in 1912. Since then the sylvatic region of the Yucatan peninsula has been documented as an endemic focus of LCL. This study of 73 biopsies from parasitological confirmed lesions of LCL cases of Leishmania (Leishmania) mexicana infection was undertaken: 1) to examine host response at tissue level; and 2) to relate manifestations of this response to some characteristics of clinical presentation. Based on Magalhães' classification we found that the most common pattern in our LCL cases caused by L. (L.) mexicana was predominantly characterized by the presence of unorganized granuloma without necrosis, (43.8%). Another important finding to be highlighted is the fact that in 50/73 (68.5%) parasite identification was positive. There was direct relation between the size of the lesion and time of evolution (r s = 0.3079, p = 0.03), and inverse correlation between size of the lesion and abundance of amastigotes (r s = -0.2467, p = 0.03). In view of the complexity of clinical and histopathological findings, cell-mediated immune response of the disease related to clinical and histopathological features, as so genetic background should be studied.La Leishmaniosis Cutánea Localizada (LCL) mejor conocida como "úlcera del chiclero" en el sureste de México fue descrita por SEIDELIN en 1912. Desde entonces la región selvática de la península de Yucatán ha sido identificada como un área endémica de LCL. En el presente estudio se analizaron 73 biopsias de lesiones de casos de LCL causados por Leishmania (Leishmania) mexicana con el fin de: 1) examinar la respuesta a nivel tisular; y 2) relacionar las manifestaciones de esta respuesta con ciertas características de la presentación clínica. Con base en la clasificación histopatológica de Magalhães el patrón histopatológico más frecuente se caracterizó por la presencia de granuloma desorganizado y ausencia de necrosis (43.83%). Otro hallazgo importante a señalar fue la presencia de parásito en 50/73 (68.5%) de las biopsias estudiadas. Respecto a las posibles relaciones significativas hubo una relación directa entre el tamaño de la lesión y el tiempo de evolución (r s = 0.3079, p = 0.03); una correlación inversa entre el tamaño de la lesión y la abundancia de promastigostes (r s = -0.2467, p = 0.03). Con base en la complejidad de los hallazgos clínicos e histopatológicos, consideramos necesario estudiar la respuesta inmune mediada por células relacionada con los cambios histopatológicos, así como el papel de los factores genéticos

Evaluación del daño en la vértebra lumbar L5 mediante análisis por elementos finitos

International audienceBone metastasis to the spine, pelvis, or hip in patients suffering from prostate cancer occurs in about 80% of cases. A spinal metastasis may cause pain, instability and neurological injuries. Thus, it is relevant to assess when critical conditions have been reached and bone structural integrity is compromised. Data-driven numerical methods based on the postprocessing of medical imaging provide a tool to model the material complexity of biological tissues. Computed axial tomography (CAT) together with segmentation tools allow the reconstruction of 3D models of the bone that include mechanical properties representing the anisotropic condition of the bone structures. In this work, we present the model of the L5 lumbar vertebra of a patient affected by metastasis, and evaluate biomarkers to indicate the level of damage, compared with the reference case of a healthy bone in an initial stage.La metástasis ósea a la columna vertebral, la pelvis o la cadera en pacientes con cáncer de próstata es una patología que ocurre en aproximadamente el 80% de los casos. La metástasis en la columna vertebral puede causar dolor, inestabilidad y lesiones neurológicas. Por lo tanto, es relevante evaluar cuándo se han alcanzado condiciones críticas y la integridad estructural del hueso está comprometida. Los métodos numéricos basados en datos del paciente, obtenidos mediante el postprocesamiento de imágenes médicas, proporcionan una herramienta para modelar la complejidad del material de los tejidos biológicos. La tomografía axial computarizada (TAC) junto con las herramientas de segmentación permiten la reconstrucción de modelos 3D del hueso que incluyen propiedades mecánicas, y que representan la condición anisotrópica de las estructuras óseas. En este trabajo, presentamos el modelo de la vértebra lumbar L5 de un paciente afectado por metástasis y evaluamos biomarcadores para indicar el nivel de daño, comparando con el caso de referencia del hueso sano en una etapa inicial. Palabras clave: daño óseo; segmentación ósea; vértebras; metástasis; FEA basado en imagen

Clinical Study Effect of Selective Serotonin Reuptake Inhibitors and Immunomodulator on Cytokines Levels: An Alternative Therapy for Patients with Major Depressive Disorder

Major depressive disorder (MDD) is a psychiatric illness that presents as a deficit of serotonergic neurotransmission in the central nervous system. MDD patients also experience alterations in cortisol and cytokines levels. Treatment with selective serotonin reuptake inhibitors (SSRIs) is the first-line antidepressant regimen for MDD. The aim of this study was to determine the effect of a combination of SSRIs and an immunomodulator-human dialyzable leukocyte extract (hDLE)-on cortisol and cytokines levels. Patients received SSRIs or SSRIs plus hDLE. The proinflammatory cytokines IL-1 , IL-2, and IFN-; anti-inflammatory cytokines IL-13 and IL-10; and 24-h urine cortisol were measured at weeks (W) 0, 5, 20, 36, and 52 of treatment. The reduction in cortisol levels in the SSRI-treated group was 30% until W52, in contrast, the combined treatment induced a 54% decrease at W36. The decline in cortisol in patients who were treated with SSRI plus hDLE correlated with reduction of anti-inflammatory cytokines and increases levels of proinflammatory cytokines at the study conclusion. These results suggest that the immune-stimulating activity of hDLE, in combination with SSRIs, restored the pro-and anti-inflammatory cytokine balance and cortisol levels in depressed patients versus those who were given SSRIs alone

Extracellular vesicles from Mycobacterium tuberculosis-infected neutrophils induce maturation of monocyte-derived dendritic cells and activation of antigen-specific Th1 cells

Tuberculosis remains one of the leading public health problems in the world. The mechanisms that lead to the activation of the immune response against Mycobacterium tuberculosis have been extensively studied, with a focus on the role of cytokines as the main signals for immune cell communication. However, less is known about the role of other signals, such as extracellular vesicles, in the communication between immune cells, particularly during the activation of the adaptive immune response. In this study, we determined that extracellular vesicles released by human neutrophils infected with M. tuberculosis contained several host proteins that are ectosome markers. In addition, we demonstrated that extracellular vesicles released by human neutrophils infected with M. tuberculosis released after only 30 min of infection carried mycobacterial antigens and pathogen-associated molecular patterns, and we identified 15 mycobacterial proteins that were consistently found in high concentrations in extracellular vesicles released by human neutrophils infected with M. tuberculosis; these proteins contain epitopes for CD4 T-cell activation. We found that extracellular vesicles released by human neutrophils infected with M. tuberculosis increased the expression of the costimulatory molecule CD80 and of the coinhibitory molecule PD-L1 on immature monocyte-derived dendritic cells. We also found that immature and mature dendritic cells treated with extracellular vesicles released by human neutrophils infected with M. tuberculosis were able to induce IFN-γ production by autologous M. tuberculosis antigen-specific CD4 T cells, indicating that these extracellular vesicles acted as antigen carriers and transferred mycobacterial proteins to the antigen-presenting cells. Our results provide evidence that extracellular vesicles released by human neutrophils infected with M. tuberculosis participate in the activation of the adaptive immune response against M. tuberculosis.This work was supported by Consejo Nacional de Ciencia y Tecnología (CONACYT grant A1-S-16113 to IEG) and by Secretaría de Investigación y Posgrado, Instituto Politécnico Nacional (IPN). L.V.-F., E.S.P., M.G.-M., and D.B. were recipients of CONACYT fellowships. J.S.-L., R.C.-S., S.E.-P., and I.E.-G. are fellows of Comisión de Operación y Fomento de Actividades Académicas (COFAA)–IPN. J.S.-L., R.C.-S., S.E.-P., I.E.-G., and I.W.-B. are fellows of Estímulos al Desempeño de los Investigadores (EDI)–IPN