Human mesenchymal stromal cell lysates as a novel strategy to recover liver function.

AIM: It is unknown if the beneficial effects of mesenchymal stromal cells (MSC) transplantation into the liver are dependent on their anchorage and differentiation into hepatocytes or rather the result of the release of stem cell intracellular content with hepatoprotector properties. MATERIALS & METHODS: The effects of intact MSC transplantation were compared with the infusion of MSC lysates in an experimental rat model of acute liver failure. RESULTS: A more powerful hepatoprotective and antiapoptotic effect was obtained after infusion of MSC lysates than intact MSC. Changes in IL-6 levels and miRNAs might explain the beneficial effects of MSC lysates. CONCLUSION: Infusion of MSC lysates show a better hepatoprotective effect than the transplantation of intact MSC.

Cardiotrophin-1 decreases liver apoptosis through calpastatin induction.

BACKGROUND: Cardiotrophin-1 (CT1) has been used to prevent cell death in different models of liver injury in rats. D-galactosamine induces cell death in culture rat and human hepatocytes. The present study evaluated the cytoprotective effects of CT1 in an experimental model of apoptosis induced by D-galactosamine in hepatocytes. METHODS: DNA fragmentation, calpain activity and Western blots of caspase-3, calpastatin and Stat3, and Akt phosphorylation were measured. Stat3 and Akt inhibitors were used to analyze the mechanisms of action of CT1. RESULTS: CT1 caused an increase in Stat3 and Akt phosphorylation and a decrease of DNA fragmentation, calpain activity, and caspase-3 induced by D-galactosamine. The reduction of calpain activity by CT1 was associated with an increase of calpastatin (its endogenous inhibitor). The effects of CT1 were also dependent on the activation of Sta3 or Akt. CONCLUSIONS: CT1 decreases cell death through a mechanism related to Stat3 and Akt phosphorylation and activation of calpastatin in D-galactosamine-treated hepatocytes.

The effect of antidrug antibodies on the sustainable efficacy of biologic therapies in rheumatoid arthritis: practical consequences.

Biologic therapies, predominantly TNF-α inhibitors, have revolutionized the treatment of rheumatoid arthritis (RA). However, their clinical utility can be limited by the development of antidrug antibodies (ADAs). Immunogenicity is a complex phenomenon related to various drug, disease, and patient characteristics, and may be more common with the monoclonal antibodies than with etanercept, a soluble TNF receptor-Fc immunoglobulin fusion protein. Neutralizing antibodies - those that hinder bioactivity by preventing drug molecules from binding to TNF - are correlated with reduced serum drug concentrations, loss of therapeutic response, adverse events, and treatment discontinuation. Cost-effective use of these agents will depend on further research into drug and ADA assays, and how they should guide dose reduction or switching strategies.

Forced swimming test decreases chemotactic responsiveness and expression of CD11a in rat monocytes.

OBJECTIVES: Previous reports have shown that the depressive status in humans and experimental animals is associated with decreased immune response. Since monocyte chemotaxis and expression of CD11a are pivotal mechanisms in immune response, impairment of these events could explain the diminished immune response in depression. METHODS: To test this, rats were submitted to the forced swimming test (FST) for 3 and 15 days. Animals were sacrificed at days 4 (3 days' FST), 16 (15 days' FST) and 30 (15 days' FST and 15 days of recovery time). At these times, a blood sample was obtained for serum and leukocyte isolation. Mononuclear leukocytes were obtained by Histopaque gradient. Chemotaxis responsiveness was determined in Boyden chambers using zymosan-activated rat serum. Cellular CD11a expression and serum CD11a were determined by immunofluorescence and ELISA, respectively. RESULTS: Decreased chemotaxis was observed in FST animals at days 4 and 16 with total recovery at day 30. Diminished expression of cellular CD11a was observed at day 16 and remained decreased at day 30. There were no significant differences in serum CD11a content. CONCLUSION: Decreased chemotactic response and expression of CD11a found in this experimental model of depression could be important mechanisms to induce impairment immune response in experimental and clinical depression.

Diferencias en la susceptibilidad a la deltametrina en poblaciones de Aedes aegypti de Trujillo, Venezuela / Different susceptibility to deltamethrin in Aedes aegypti populations from Trujillo state, Venezuela

El dengue es un importante problema de salud pública en Venezuela, donde aedes aegypti es el principal vector. El propósito de este estudio fue determinar el estado de la susceptibilidad a la deltametrina en nueve poblaciones naturales de A. aegypti del estado Trujillo, en comparación con la cepa susceptible Rockefeller. Los bioensayos fueron llevados a cabo siguiendo la metodología de la Organización Mundial de la Salud. Las poblaciones Trujillo, Pampán, Pampanito, Flor de Patria, Motatán, Tres Esquinas y Cubita mostraron valores de mortalidades comprendidas entre 89% y 97%, y KDT50 entre 15,7 min y 24,1 min, sugiriendo la posibilidad de resistencia la cual debe ser confirmada. Las poblaciones Monay y Filo fueron susceptibles, con KDT50 de 15,5 y 20,2 min respectivamente, y mortalidades a las 24 horas de 99 y 98%. Estos resultados deben ser considerados al momento de diseñar el programa de control del vector para asegurar la efectividad del mismo.

Dengue is an important public health problem in Venezuela, where Aedes aegypti is the main vector. The purpose of this study was to determine the status of susceptibility to deltamethrin in nine natural populations of A. aegypti from Trujillo state compared with the susceptible Rockefeller strain. Bioassays were carried out following the methodology of the World Health Organization. The values of mortalities were found between 89% and 97%, allowing categorize the populations from Trujillo, Pampan, Pampanito, Flor de Patria, Motatan, Tres Esquinas and Cubita as resistant under verification, with values KDT50 between 15.7 min and 24.1 min, suggesting the possibility of resistance which must be confirmed and the populations from Monay and Filo as susceptible, with a KDT50 of 15.5 and 20.2 min, respectively, and 99 and 98% mortality at 24 hours. These results should be considered when designing programs for vector control to ensure those are effective to control A. aegytpti populations.