Donor-specific antibodies in liver transplantation / Anticuerpos específicos del donante en el trasplante de hígado

Despite unique immunoregulatory properties pointing toward tolerance, the liver allograft can be negatively impacted by humoral alloreactivity, with immediate as well as long-term harmful consequences. With regard to the unmet need of long-term outcomes improvement after liver transplantation, donor-specific antibodies have recently been the matter of intense study in this context. We review here recent advances regarding the understanding of the impact of preformed as well as de novo anti-human leukocyte antigen donor-specific antibodies in liver transplantation and discuss potential strategies to overcome this problem

A pesar de sus propiedades inmunorreguladoras únicas que apuntan a la tolerancia, el aloinjerto hepático puede verse afectado negativamente por la alorreactividad humoral, con consecuencias nocivas inmediatas y también a largo plazo. Recientemente, y en relación con la necesidad no cubierta de mejorar los resultados a largo plazo tras el trasplante de hígado, se han realizado estudios exhaustivos sobre los anticuerpos específicos del donante. En el presente artículo, revisamos los últimos avances a la hora de comprender el impacto de los anticuerpos contra el antígeno leucocitario humano específicos del donante, preformados o de novo, en el trasplante de hígado y estudiamos posibles estrategias para resolver este problema

Novel combination of docetaxel and thymoquinone induces synergistic cytotoxicity and apoptosis in DU-145 human prostate cancer cells by modulating PI3K–AKT pathway

Background. The treatment of castrate-resistant prostate cancer (CRPC) still remains as an important challenge of daily oncology practice. Docetaxel significantly prolongs overall survival in men with CRPC. Thymoquinone (TQ), one of the flavonoid compounds isolated from Nigealla sativa, has been shown to possess cytotoxic activity against a variety of cancer cell lines. Materials and Methods. The aim of the study was to investigate the possible synergistic cytotoxic/apoptotic effects of a novel combination, docetaxel and TQ in DU-145 hormone- and drug-refractory prostate cancer cells and their effects on PI3K and ERK signaling pathways. Results. We observed that the combination of docetaxel and TQ resulted in a significant synergistic cytotoxicy and apoptosis as compared to any single agent alone, in a dose-dependent manner. It was found that viability of the combination treated cells was not significantly changed in the presence of LY294002 as compared to inhibitor treated cells. However, in the presence of FR180204, viability of combination treated cells was significantly decreased as compared to inhibitor treated cells. In conclusion, cytotoxic effect of the docetaxel and TQ combination is correlated with the block of the PI3K/Akt signaling pathway in DU-145 cells. Conclusion. Therefore, this combination strategy may be an alternative approach for the challenging era of daily oncologic practice. Also, the combination of docetaxel and TQ might allow a reduction in docetaxel doses and diminish adverse effects of docetaxel while maintaining the therapeutic effect in patients with CRPC (AU)

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Ecotoxicity studies of antifungal metabolites of Bacillus sp. IBA 33 / Estudios de la ecotoxicidad de metabolitos antifúngicos de Bacillus sp. IBA 33

The increments of plant diseases caused by the proliferation of fungicide-resistant pathogens intensified the research of new active metabolites against them. The study of biological methods as an alternative to chemical control has reach relevance in recent years. It has been suggested that the use of metabolites from Bacillus, is an alternative or supplementary method to chemical plant protection, if they are not toxic for the consumers and environmentally friendly. The toxicity of different concentrations of antifungal metabolites produced by Bacillus sp. IBA 33 was evaluated. Their ability to induce cytotoxic effects was investigated by different tests as hemolysis, and Artemia salina and Allium cepa L immobilization. With 2.56 mg/ml of antifungal metabolites hemolysis reached 24.07%, to 1.28 mg/ml was 14%. HC50 was 10.41 mg/ml. A. salina nauplii exposed to 3.2, 1.6 and 0.8 mg/ml of antifungal metabolites showed 80, 20 and 10% of mortality respectively; LD50 was 2.24 mg/ml. In Allium cepa L test after 72 h of treatment, the roots lengths were 8.75, 10.35 and 23.75 mm with 3.2, 1.6 and 0.8 mg/ml of antifungal metabolites respectively. The EC50 was 0.078 mg/ml. After 144 h the EC50 was 4.11 mg/ml. Only with 3.2 mg/ml of metabolites, chromosomal aberrations, cytoplasm vacuolization and decentralization of nuclei were observed in the cells of Allium cepa L. No micronuclei were detected. Under the experimental conditions, the antifungal metabolites concentrations assayed are considered non toxic (AU)

El incremento de enfermedades de plantas causado por la proliferación de patógenos resistentes a fungicidas intensificó la investigación de nuevos metabolitos activos contra ellos. El estudio de métodos biológicos como una alternativa al control químico ha alcanzado relevancia en años recientes. Se ha sugerido que el uso de metabolitos de Bacillus, es una alternativa o un método suplementario a la protección química de las plantas, siempre y cuando ellos no sean tóxicos para los consumidores y sean amigables para el medio ambiente. Se ha evaluado la toxicidad de diferentes concentraciones de metabolitos antifúngicos producidos por Bacillus sp. IBA33. Se investigó su capacidad para inducir efectos citotóxicos mediante diferentes tests como hemólisis e inmovilización de Artemia salina y Allium cepa L. Con 2.56 mg/ml de metabolitos antifúngicos la hemólisis alcanzó 24.07%, para 1.28 mg/ml fue 14%. La HC50 fue 10.41 mg/ml. Nauplios de Artemia salina expuestos a 3.2; 1.6 y 0.8 mg/ml de metabolitos antifúngicos mostraron 80; 20 y 10% de mortalidad respectivamente después de 24 h de tratamiento; la LD50 fue 2.24 mg/ml. En el test de Allium cepaL después de 72 h de tratamiento, la longitud de las raíces fueron 8.75; 10.35 y 23.75 mm con 3.2; 1.6 y 0.8 mg/ml de metabolitos antifúngicos respectivamente, con una EC50 de 0.078 mg/ml. Después de 144 h la EC50 fue 4.11 mg/ml. Solamente con 3.2 mg/ml de metabolitos fueron observadas aberraciones cromosómicas, vacualización y descentralización de los núcleos en las células de Allium cepa L. No se observaron micronúcleos. Bajo las condiciones experimentales, las concentraciones de metabolitos antifúngicos ensayadas son consideradas no tóxicas

Meta-analysis of the cytotoxic T-lymphocyte antigen 4 gene +6230G/A polymorphism and cancer risk

OBJECTIVES: Cytotoxic T-lymphocyte antigen-4 (CTLA4, CD152) is one of the most fundamental immunosuppressive cytokines that inhibits T-cell activation and terminates the T-cell response by blocking signals stimulated via CD28. A number of studies have assessed the association between CTLA-4 +6230G/A polymorphism and cancer risk. However, the results remain controversial. METHODS: In the present study, we performed a meta-analysis to derive a more precise estimation of the relationship. A comprehensive literature search was performed using the PubMed database for relevant articles published (updated to November 21, 2013). Odds ratios (ORs) and 95 % confidence intervals (CIs) were used to assess the strength of the association. RESULTS: A total of 13 articles with 14 studies were selected for this meta-analysis, including 4,489 cases and 4,715 controls. Combined analysis revealed no associations between CTLA-4 +6230G/A polymorphism and cancer risk. However, in stratified analysis by cancer type, we found that CTLA-4 +6230G/A polymorphism was associated with the risk of breast cancer (AA vs. AG + GG: OR = 0.77, 95 % CI 0.60-0.97, P = 0.03; AA vs. GG: OR = 0.66, 95 % CI 0.46-0.95, P = 0.02) and cervical cancer (AA vs. AG + GG: OR = 0.56, 95 % CI 0.42-0.75, P < 0.01). Additionally, in subgroup analysis based on ethnicity, significant association was also found between the CTLA-4 +6230G/A polymorphism and cancer risk in the Asian population (AA vs. AG + GG: OR = 0.71, 95 % CI 0.59-0.84, P < 0.01). CONCLUSION: This meta-analysis indicates that CTLA-4 +6230G/A polymorphism may be associated with a decreased risk of breast cancer and cervical cancer in Chinese population (AU)

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Colitis severa por Clostridium difficile ribotipo 027 adquirido en la comunidad / Severe colitis due to community-acquired ribotype 027 Clostridium difficile

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Patogenia de las miopatías inflamatorias idiopáticas / Pathogenesis of the idiopathic inflammatory myopathies

Las miopatías inflamatorias idiopáticas (MII) son un grupo de enfermedades adquiridas, caracterizadas por un infiltrado inflamatorio del músculo esquelético. Con base en características clínicas e inmunopatológicas, pueden ser identificadas tres enfermedades: dermatomiositis (DM), polimiositis (PM) y miositis por cuerpos de inclusión (MCI). Los mecanismos inmunopatogénicos son cruciales para discriminar entre los tres subtipos de miopatías inflamatorias. En la DM está presente una microangiopatía mediada por complemento que afecta piel y músculo. La PM y la MCI son enfermedades en donde predomina la citotoxicidad mediada por linfocitos T, principalmente linfocitos T citotóxicos de CD8+ que invaden las fibras de músculo que sobreexpresan antígenos clase i del complejo principal de histocompatibilidad. Este artículo resume los principales mecanismos y marcadores immunopatogénicos. El impacto de este conocimiento debe ser definido en su potencial blanco terapéutico en las MII (AU)

The inflammatory myopathies, commonly described as idiopathic, are a group of acquired diseases characterized by an inflammatory infiltrate of the skeletal muscle. On the basis of clinical and immuno-pathological features, three major diseases can be identified: dermatomiositis (DM), polymyositis (PM) and inclusion body myositis (IBM). Immunopathogenesis mechanisms are crucial for discriminating between the three different subsets of inflammatory myopathies. DM is a complement-mediated microangiopathy affecting skin and muscle. PM and IBM are T cell-mediated disorders, where CD8-positive cytotoxic T cells invade muscle fibres expressing MHC class I antigens. This article summarizes the main immunopathological markers. The impact of this new knowledge must be defined in relation to potential therapeutic targets for idiopathic inflammatory myopathies (AU)

Acción del cadmio durante la lactancia sobre el periodonto de rata / Effect of cadmium on rat periodontium during lactation

El cadmio (Cd) afecta la salud de la población, principalmente si habita en regiones industrializadas. En el periodo perinatal, el organismo es particularmente susceptible a la exposición al Cd. Ya que el Cd puede ser excretado en la leche, nuestro objetivo fue estudiar el efecto sobre el periodondo del primer molar superior de rata de la exposición materna durante la lactancia a agua potable conteniendo bajos niveles de Cd (300mg/l CdCl2). Ratas lactantes (21 días de edad) fueron sacrificadas, sus cabezas separadas y fijadas. En cortes histiológicos seriados de 6 mm fueron estimados los siguientes parámetros de las fibras periodontales: volúmenes de núcleo, citoplasma y célula, relación núcleo/citoplasma y densidad numérica. El peso corporal medio fue 34,86g para el control y 18,56g para el grupo tratado. Las fibras periodontales fueron menores y más numerosas y el tejido conjuntivo más abundante. Así el Cd induce desorganización de las fibras periodontales, indicando una acción directa sobre el periodonto, junto con retardo del desarrollo en las crías

Cadmium (Cd) affects the health of people, mainly tose who live in industrialized regions. The organism is particularly susceptible to Cd exposure at perinatal period. As Cd can be excreted into milk our aims was to study the effect on rat maxillary molar periodontium after maternal exposition to drinking water containing low levels of CD (300 mg/l CDCl2) during lactation. Lactent rats (21 day-old) were sacrefied and the heads separated, fixed and serially sectioned. In 6 mm-thick sections were estimated the following periodontal fiber parameters: nucleus cytoplasm and cell volumes, nucleus/cytoplasm ratio and number density. Mean body weight was 34,86g for the control pups and 18,56g for the treated ones. The periodontal fibers were smaller and more numerous and the connective tissue was more abundant. Thus, CD induced periodontal fibers disorganization, indicating a direct action on periodontium, besides retarded debelopment in pups

Avance en la comprensión del rechazo humoral en el trasplante de riñón: implicaciones en el tratamiento de pacientes / Progress in understanding humoral rejection in kidney transplantation: implications for patient management

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