A lupine (Lupinus angustifolious L.) peptide prevents non-alcoholic fatty liver disease in high-fat-diet-induced obese mice

Bioactive peptides are related to the prevention and treatment of many diseases. GPETAFLR is an octapeptide that has been isolated from lupine (Lupinus angustifolius L.) and shows anti-inflammatory properties. The aim of this study was to evaluate the potential activity of GPETAFLR to prevent non-alcoholic fatty liver disease (NAFLD) in high-fat-diet (HFD)-induced obese mice. C57BL/6J mice were fed a standard diet or HFD. Two of the groups fed the HFD diet were treated with GPETAFLR in drinking water at 0.5 mg kg-1 day-1 or 1 mg kg-1 day-1. To determine the ability of GPETAFLR to improve the onset and progression of non-alcoholic fatty liver disease, histological studies, hepatic enzyme profiles, inflammatory cytokine and lipid metabolism-related genes and proteins were analysed. Our results suggested that HFD-induced inflammatory metabolic disorders were alleviated by treatment with GPETAFLR. In conclusion, dietary lupine consumption can repair HFD-induced hepatic damage possibly via modifications of liver's lipid signalling pathways

TRATAMIENTO FARMACOLÓGICO PRENATAL EN UN MODELO EXPERIMENTAL DE HERNIA DIAFRAGMÁTICA

Facultad de Medicin

Gene Expression Profile in Persistent Pulmonary Hypertension of Newborn, Preliminary Report

Background: Persistent pulmonary hypertension of the newborn (PPHN) is a serious condition with high morbidity and mortality. The therapeutic approach, even today, represents a major challenge. There is considerable interest in the understanding of the signaling pathways that regulate vasoconstriction and pulmonary vascular remodeling. Objective: We set out to identify the expression of genes S100A9 and solutes transporter, as well as their participation in the physiopathological events of PPHN. Design and methods: This is a cross-sectional study that focuses mainly on up- and down-regulated genes involved in endothelial metabolism, hypoxia transporters, ionic and nucleotides metabolism. The total RNA was obtained from blood samples of healthy full-term newborns (negative controls) and patients with PPHN. The preparation of samples for microarray analysis was as follows: control samples were stained with fluorescent nucleotides dUTP-Cy3 and pathological samples with dUTP-Cy5; samples were co-hybridized, a microarray analysis was performed using an Array Scanner Packard. Additionally, reverse transcriptase polymerase chain reaction (RT-PCR) for the genes S100A9 and solutes transporter was done. Comparative and descriptive analyses were done using t-test for independent variables, considering a p \u3c 0.05 as significant. The elements with a z-score of more than 2 standard deviations are genes likely to be differentially expressed. Results: From the total (10,000) genes analyzed, 364 (3.64%) were differentially regulated in their expression; those that registered an up-regulation were 1.13%, while 2.51% were down-regulated. S100 proteins type A9 and A12 were the most over-expressed, as well as Rho family GTPase 3. Down-regulation in the hypoxia-inducible factor 1 (HIF-1) and HIF-1 alpha subunit inhibitor was found. S100A9 and RSC1A1 had increased mRNA expression under PPHN conditions compared to healthy newborn infants. Conclusions: The up-regulation from both genes could explain, in part, the vasoreactivity and vascular remodeling characteristic of PPHN. A deeper understanding of the pathophysiology of PPHN could have a positive impact on the development of specific therapies

Lupine (Lupinus angustifolious L.) peptide ameliorates the non‐alcoholic steatohepatitis in mice

39th Congress of the Spanish Pharmacology Society, Las Palmas, Spain, 3–5 July 2019Bioactive peptides are related to the prevention and treatment of many diseases. GPETAFLR is an octapeptide isolated from lupine (Lupinus angustifolius L.) that had shown anti‐inflammatory properties. The aim of this study was to evaluate the potential activity of GPETAFLR to prevent non‐alcoholic fatty liver disease (NAFLD) in high‐fat diet (HFD)‐induced obese mice. C57BL/6J mice were fed a standard diet or an HFD. Two of the groups fed HFD diet were treated with GPETAFLR in drinking water at 0.5 mg/kg/day or 1 mg/kg/day. To determine the ability of GPETAFLR to improve the onset and progression of NAFLD, histological studies, hepatic enzyme profile, inflammatory cytokine and lipid metabolism‐related genes and proteins were analysed. Our results suggest that HFD‐induced inflammatory metabolic disorders were alleviated by treatment with GPETAFLR. In conclusion, dietary lupine consumption could repair HFD‐induced hepatic damage, possibly via modifications in the liver lipid signalling pathways.Peer reviewe

Proinflammatory Cytokines, Enolase and S-100 as Early Biochemical Indicators of Hypoxic-Ischemic Encephalopathy Following Perinatal Asphyxia in Newborns

Estimation of the neurological prognosis of infants suffering from perinatal asphyxia and signs of hypoxic-ischemic encephalopathy is of great clinical importance; however, it remains difficult to satisfactorily assess these signs with current standard medical practices. Prognoses are typically based on data obtained from clinical examinations and neurological tests, such as electroencephalography (EEG) and neuroimaging, but their sensitivities and specificities are far from optimal, and they do not always reliably predict future neurological sequelae. In an attempt to improve prognostic estimates, neurological research envisaged various biochemical markers detectable in the umbilical cord blood of newborns (NB). Few studies examining these biochemical factors in the whole blood of newborns exist. Thus, the aim of this study was to determine the expression and concentrations of proinflammatory cytokines (TNF-α, IL-1β and IL-6) and specific CNS enzymes (S-100 and enolase) in infants with perinatal asphyxia. These data were compared between the affected infants and controls and were related to the degree of HIE to determine their utilities as biochemical markers for early diagnosis and prognosis. Methods: The levels of the proinflammatory cytokines and enzymes were measured by enzyme-linked immunosorbent assay (ELISA) and Reverse Transcription polymerase chain reaction (RT-PCR). Results: The expression and serum levels of the proinflammatory cytokines, enolase and S-100 were significantly increased in the children with asphyxia compared with the controls. Conclusion: The role of cytokines after hypoxic-ischemic insult has been determined in studies of transgenic mice that support the use of these molecules as candidate biomarkers. Similarly, S-100 and enolase are considered promising candidates because these markers have been correlated with tissue damage in different experimental models

Lupine (Lupinus angustifolius L.) peptide prevents non-alcoholic fatty liver disease in high-fat diet-induced obese mice

Trabajo presentado en la XI Reunión de Jóvenes Farmacólogos de Andalucía, celebrada en Málaga el 31 mayo de 2019

Micronucleated Erythrocytes in Peripheral Blood from Neonate Rats Exposed by Breastfeeding to Cyclophosphamide, Colchicine, or Cytosine-Arabinoside

Genotoxic exposure to chemical substances is common, and nursing mothers could transmit harmful substances or their metabolites to their offspring through breast milk. We explored the possibility of determining genotoxic effects in the erythrocytes of breastfeeding rat pups whose mothers received a genotoxic compound while nursing. Ten groups of female rats and five pups per dam were studied. The control group received sterile water, and the experimental groups received one of three different doses of cyclophosphamide, colchicine, or cytosine-arabinoside. Blood smears were prepared from samples taken from each dam and pup every 24 h for six days. There were increased numbers of micronucleated erythrocytes (MNEs) and micronucleated polychromatic erythrocytes (MNPCEs) in the samples from pups in the experimental groups (P<0.02) and increased MNPCE frequencies in the samples from the dams (P<0.05). These results demonstrate the vertical transmission of the genotoxic effect of the compounds tested. In conclusion, assessing MNEs in breastfeeding neonate rats to assess DNA damage may be a useful approach for identifying genotoxic compounds and/or cytotoxic effects. This strategy could help in screening for therapeutic approaches that are genotoxic during the lactation stage and these assessments might also be helpful for developing preventive strategies to counteract harmful effects

Consenso sobre el abordaje diagnóstico y terapéutico del dolor y el estrés en el recién nacido

El dolor y estrés en el recién nacido (RN) se ha tratado en forma insuficiente; los recién nacidos que ingresan a las unidades de cuidados intensivos neonatales (UCIN), a menudo deben someterse a procedimientos invasivos, dolorosos y estresantes y el tratamiento inadecuado incrementa la morbimortalidad. El V Consenso Clínico de la Sociedad Iberoamericana de Neonatología convocó a 32 neonatólogos de Iberoamérica para establecer las recomendaciones sobre diagnóstico y terapéutica del dolor y estrés neonatal. Se desarrollaron temas de relevancia, utilizando la mejor evidencia científica disponible en bases de datos indizadas. Todos participaron en forma activa en una reunión presencial en Santiago de Chile para consensuar las recomendaciones y conclusiones. El dolor y el estrés neonatal afectan el neurodesarrollo y la conducta a largo plazo, requieren el diagnóstico oportuno, el manejo y la terapéutica adecuada, incluso con fármacos que permitan balancear la efectividad y toxicidad. El Consenso señala la importancia de evaluar el dolor en el RN en forma multidimensional y proporciona recomendaciones de las indicaciones y limitaciones para la terapia farmacológica individualizada. El uso de los analgésicos tiene indicaciones precisas y debe limitarse por la carencia de estudios aleatorizados en RN, ya que en todos los casos existen efectos adversos a considerar. Se proponen medidas no farmacológicas para mitigar el dolor. El manejo del estrés debe comenzar en la sala de partos e incluir el contacto materno, la reducción de estímulos, la implementación de protocolos de intervención reducida, entre otros. SIBEN propone las recomendaciones para mejorar las prácticas clínicas relacionadas con el dolor y el estrés neonatal