Funcionalidad y recomendaciones nutricionales de ácidos grasos esenciales y sus derivados en la alimentación del lactante a partir de los 6 meses de edad

Essential fatty acids and long-chain unsaturated fatty acids are important for growth and neuronal development during the final months of gestation and the early years of life. The aim of this study is to highlight the importance of ensuring a correct intake of EFAs for nutritional requirements through the intake of foods which naturally contain these acids or which have been enriched with them. The methodology used was basee on the review of electronic databases MedLine, ScienceDirect, Scirus, Trip database and that of the scientific journal library of the University of Murcia. National and international websites such as  the Asociación Española de Pediatría (AEP), European Agency for Food Safety (EAFS) and the European Society of Pediatric, Gastroenterology, Health and Nutrition (ESPGHAN) were also consulted.   The results show how EFAs and also AGPI-CL (DHA and ARA) are essential for the correct development of breastfeeders and infants. Even though the breastfeeder is enzymatically fully equipped from the first day of life to convert EFAs into AGPI-CL and derivatives, the conversion may be insufficient  and it may be necessary to include AGPI-CL in the diet. The conclusions are that during the first 6 months of life  the provision of EFAs and AGPI-CL is assured thanks to the mother’s milk or through starter formulas; at six months the introduction of complementary foods and the adaptation to cow’s milk at  twelve months (against the recommendations of the ESPGHAN) may affect the provision of these acids. There is a legal vacuum in the issue of the provision of EFAs through complementary foods other than cereals although committees like the AEP recommend that AL in meat and fish baby foods with vegetables should suppose 3-4.5% of the energy provision, and ALN at least 0.5% in order to satisfy EFA requirements in breastfeeders ans infants.Los requerimientos de ácidos grasos esenciales (AGEs) y ácidos grasos poliinsaturados de cadena larga (AGPI-CL) durante los últimos meses de gestación y los primeros años de vida son importantes de acuerdo al crecimiento y desarrollo neuronal que está teniendo lugar durante este periodo de vida. El objetivo de este trabajo ha sido destacar la importancia de garantizar un correcta ingesta de AGEs para cubrir los requerimientos nutricionales de estos, a través de la ingesta de alimentos que contienen en su composición nutricional a estos ácidos de forma natural o han sido enriquecidos con ellos. La metodología empleada para este fin ha sido la utilización de  bases de datos electrónicas como MedLine, ScienceDirect, Scirus, Trip database y de la hemeroteca científica de la Universidad de Murcia; También han sido consultadas las páginas web de organismos nacionales e internacionales tales como la Asociación Española de Pediatría (AEP), Agencia Europea de Seguridad Alimentaria (EFSA) y European Society of Pediatric, Gastroenterology, Health and Nutrition (ESPGHAN). Los resultados obtenidos muestran como los AGEs e incluso los AGPI-CL (DHA y ARA) son esenciales para el correcto desarrollo del lactante y niño de corta edad; pues aún estando el lactante desde el primer día de vida dotado de todo el sistema enzimático necesario para la conversión de AGEs en sus correspondientes AGPI-CL y sus derivados, esta conversión podría ser insuficiente, siendo necesario y/o esencial el aporte de estos AGPI-CL a través de la dieta. Las conclusiones derivadas de este trabajo fueron que durante los seis primeros meses de vida el aporte de AGEs y AGPI-CL está asegurado a través de la leche materna o en su defecto a través de las fórmulas  de inicio; a partir de los 6 meses con la introducción de la alimentación complementaria y la introducción de la leche de vaca a partir de los 12 meses de vida (introducción en contra de las recomendaciones de ESPGHAN), podría verse comprometida la aportación de estos ácidos. Existe un vacío legal en cuanto a la aportación de AGEs a través de la alimentación complementaria distinta a los cereales; sin embargo, comités como el de la AEP recomienda que en los tarritos infantiles de carnes y pescados con verdura, el aporte de AL sea entre 3-4.5% de la energía de la dieta y al menos 0.5% desde ALN para satisfacer los requerimientos de AGEs en lactantes y niños de corta edad

Pharmacological Interactions of Nintedanib and Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis in Times of COVID-19 Pandemic

The discovery of antifibrotic agents have resulted in advances in the therapeutic management of idiopathic pulmonary fibrosis (IPF). Currently, nintedanib and pirfenidone have become the basis of IPF therapy based on the results of large randomized clinical trials showing their safety and efficacy in reducing disease advancement. However, the goal of completely halting disease progress has not been reached yet. Administering nintedanib with add-on pirfenidone is supposed to enhance the therapeutic benefit by simultaneously acting on two different pathogenic pathways. All this becomes more important in the context of the ongoing global pandemic of coronavirus disease 2019 (COVID-19) because of the fibrotic consequences following SARS-CoV-2 infection in some patients. However, little information is available about their drug-drug interaction, which is important mainly in polymedicated patients. The aim of this review is to describe the current management of progressive fibrosing interstitial lung diseases (PF-ILDs) in general and of IPF in particular, focusing on the pharmacokinetic drug-drug interactions between these two drugs and their relationship with other medications in patients with IPF

EEG Biomarkers Related With the Functional State of Stroke Patients

Recent studies explored promising new quantitative methods to analyze electroencephalography (EEG) signals. This paper analyzes the correlation of two EEG parameters, Brain Symmetry Index (BSI) and Laterality Coefficient (LC), with established functional scales for the stroke assessment. Thirty-two healthy subjects and thirty-six stroke patients with upper extremity hemiparesis were recruited for this study. The stroke patients where subdivided in three groups according to the stroke location: Cortical, Subcortical, and Cortical + Subcortical. The participants performed assessment visits to record the EEG in the resting state and perform functional tests using rehabilitation scales. Then, stroke patients performed 25 sessions using a motor-imagery based Brain Computer Interface system (BCI). BSI was calculated with the EEG data in resting state and LC was calculated with the Event-Related Synchronization maps. The results of this study demonstrated significant differences in the BSI between the healthy group and Subcortical group (P = 0.001), and also between the healthy and Cortical+Subcortical group (P = 0.019). No significant differences were found between the healthy group and the Cortical group (P = 0.505). Furthermore, the BSI analysis in the healthy group based on gender showed statistical differences (P = 0.027). In the stroke group, the correlation between the BSI and the functional state of the upper extremity assessed by Fugl-Meyer Assessment (FMA) was also significant, ρ = −0.430 and P = 0.046. The correlation between the BSI and the FMA-Lower extremity was not significant (ρ = −0.063, P = 0.852). Similarly, the LC calculated in the alpha band has significative correlation with FMA of upper extremity (ρ = −0.623 and P < 0.001) and FMA of lower extremity (ρ = −0.509 and P = 0.026). Other important significant correlations between LC and functional scales were observed. In addition, the patients showed an improvement in the FMA-upper extremity after the BCI therapy (ΔFMA = 1 median [IQR: 0-8], P = 0.002). The quantitative EEG tools used here may help support our understanding of stroke and how the brain changes during rehabilitation therapy. These tools can help identify changes in EEG biomarkers and parameters during therapy that might lead to improved therapy methods and functional prognoses

Safety and immunomodulatory effects of three probiotic strains isolated from the feces of breast-fed infants in healthy adults: SETOPROB study

We previously described the isolation and characterization of three probiotic strains from the feces of exclusively breast-fed newborn infants: Lactobacillus paracasei CNCM I-4034, Bifidobacterium breve CNCM I-4035 and Lactobacillus rhamnosus CNCM I-4036. These strains were shown to adhere to intestinal mucus in vitro, to be sensitive to antibiotics and to resist biliary salts and low pH. In the present study, a multicenter, randomized, double-blind, placebo-controlled trial with 100 healthy volunteers in three Spanish cities was carried out to evaluate the tolerance, safety, gut colonization and immunomodulatory effects of these three probiotics. Volunteers underwent a 15-day washout period, after which they were randomly divided into 5 groups that received daily a placebo, a capsule containing one of the 3 strains or a capsule containing a mixture of two strains for 30 days. The intervention was followed by another 15-day washout period. Patients did not consume fermented milk for the entire duration of the study. Gastrointestinal symptoms, defecation frequency and stool consistency were not altered by probiotic intake. No relevant changes in blood and serum, as well as no adverse events occurred during or after treatment. Probiotic administration slightly modified bacterial populations in the volunteers’ feces. Intestinal persistence occurred in volunteers who received L. rhamnosus CNCM I-4036. Administration of B. breve CNCM I-4035 resulted in a significant increase in fecal secretory IgA content. IL-4 and IL-10 increased, whereas IL-12 decreased in the serum of volunteers treated with any of the three strains. These results demonstrate that the consumption of these three bacterial strains was safe and exerted varying degrees of immunomodulatory effects.Part of the research currently in progress in the authors' laboratory is funded by the company Hero Spain, S. A. through the grant #3582 managed by the Fundacion General Empresa-Universidad de Granada

Fórmulas infantiles hipoalergénicas con alto grado de hidrólisis proteica y elevado contenido de ácidos grasos poliinsaturados de cadena larga para la prevención terciaria en lactantes con alergia a las proteínas de la leche de vaca.

OBJETIVOS: Validación e investigación aplicada de una fórmula terapéutica que, cumpliendo las exigencias de la ESPGHAN, tenga como ingredientes claves de acción funcional un elevado contenido en AGPI-CL, DHA y AA, así como una elevada hidrolización de la proteína de la leche de vaca, en la prevención terciaria de la enfermedad. METODOS: La hipoalergenicidad se determinó a partir del análisis de proteína inmunoreactiva (ELISA Test); la distribución de pesos moleculares por cromatografía líquida de alta resolución con columnas de exclusión por tamaño (Shodex KW 802.5) y detector de diodo array y prueba de anafilaxia sistémica con cobayas. La valoración nutricional se determinó mediante el método ‘AOAC 960.48, de eficiencia proteica. Además, se identificaron péptidos bioactivos en la fórmula tras ser sometida a una digestión in vitro mediante cromatografía líquida de alta resolución en fase reversa (RP-HPLC), conectado a un detector de masas, cuadrupolo de trampa iónica, Bruker Dalotnik GmbH, Bremene, Germany. Finalmente la tolerancia y valoración nutricional de la fórmula se determinó mediante la realización de un ensayo clínico abierto, multicéntrico, nacional con lactantes con alergia a la proteína de la leche de vaca (APLV); la tolerancia de la fórmula se estableció mediante la prueba de provocación con la fórmula y con el registro de síntomas durante los 3 meses de seguimiento. La valoración nutricional se lleva a cabo mediante medidas antropométricas (peso, talla y perímetro craneal) y parámetros bioquímicos. Para conocer el estatus de AGPI-CL en los lactantes con APLV tras el tratamiento, se determinó su contenido en la membrana de los eritrocitos, mediante cromatografía de gases Hewlett-Packard 5890A (USA), con una columna capilar SUPELCO PHASE SPTN2330 F.S. de 60 metros de longitud y 0.32 mm de diámetro interno, impregnada con 0.20 μm de espesor de la fase estacionaria biscianopropilfenil polisiloxano y detector de ionización de llama. Con el fin de conocer su posible efecto modulador se determinaron citocinas en plasma mediante detección simultánea de multianalitos utilizando Kits de ensayo MILLIplex y la Tecnología xMAP de Luminex; el sistema completo incluyó el Luminex 200, la plataforma XY para placas, y el sistema de suministro de fluido Luminex SD, software IS y PC. Luminex® Corporation. Todos los cálculos estadísticos se llevaron a cabo usando el programa estadístico SPSS 18.0 para Windows. Valores de p<0.05 se consideraron significativos. RESULTADOS: Desde un punto de vista nutricional, los hidrolizados utilizados en la nueva fórmula terapéutica mostraron un valor biológico superior al 70% y una proporción de eficiencia en proteína mayor a 2.5. Además en el ensayo clínico las puntuaciones Z en peso, talla y perímetro craneal fueron óptimas de acuerdo a las tablas de crecimiento de la WHO. En cuanto a la alergenicidad, la fórmula mostró un contenido reducido en proteína inmunoreactiva y una distribución de pesos moleculares < 3000 Da. La prueba de anafilaxia sistémica en cobayas apoyaron los resultados anteriores y la tolerancia de la fórmula fue de un 97.7% de los lactantes con APLV del estudio. El contenido en DHA y AA en la membrana de los eritrocitos tras los 3 meses de tratamiento tendió al aumento, situándose en niveles similares a los observados en niños amamantados. Desde un punto de vista inmunológico, la citocina IL-8 y el contenido en eosinófilos disminuyeron significativamente tras los tres meses de tratamiento (IL-8: 33.78±22.58 vs 5.66±1.40 pg/ml, U de Mann Whitney U p=0.03; eosinófilos: 1457,54 ±2570,21 vs 417,39 ±402,98 cel/mm3). IL-10 citocina inmunomoduladora tendió al aumento. Se detectaron numerosos péptidos bioactivos, entre ellos uno con un posible papel inmunomdulador. OBJETIVES: Nutritional and antigenic validation of a new therapeutic formula for the nutritional treatment of infant with cow’s milk protein allergy (CMPA) and the role of long chain polyunsaturated fatty acids (LC-PUFAs) in the third prevention of the disease and tolerance. METHODS: Hypoallergenicity was determined by analysis such as immunoreactive protein detected by ELISA test; molecular weight distribution by means of high performance liquid chromatography (HPLC) with size exclusion column (Shodex KW 802.5) and diode array detector; Active Systemic Anaphylaxis (ASA) assay in guinea pigs. Nutritional assessment was performed by AOAC 960.48, Protein Efficacy Ratio. Rat Bioassay. Indeed bioactive peptides were identified in therapeutic formula after in vitro gastrointestinal digestion, using a HPLC connected with mass spectrophotometer detector – ion trap, Bruker Dalotnik GmbH, Bremene, Germany. Finally safety, tolerance and nutritional assessment were established in an opened, multicentre, national clinical trial in infants with CMPA. Safety was established by oral challenge test; tolerance by adverse events and new episodes of allergy register for 3 months of treatments and nutritional aspects by anthropometric and biochemical parameters measured before and after 3 months of nutritional treatment. LCPUFAs status in infants before and after and the nutritional treatment with this new therapeutic formula was established by detection of these fatty acids in red blood cell membrane, using a gas chromatography HP 5890A (USA), SUPELCO PHASE SPTN2330 F.S. 60 m x 0.32 mm ID, 0.20 μm phase film, coupled with flame ionization detector. With the aim to know immunomodulatory effect, Plasma levels of IL-8, IFN-γ, IL-4, IL-10, IL-13, TGF-β and IL-17A were measured by immunoassay, with a MILLIplexTM kit using the Luminex 200 system based in the xMap technology. Differences between before and after nutritional treatment were assessed by a non-parametric U Mann Whitney test. Significance was defined as p<0,05. RESULTS: From the nutritional point of view, hydrolysates and therapeutic formula showed a biological value higher than 70% and protein efficiency ratio higher than 2.5. Indeed weight, height and head circumference z-score in the clinical trial were adequated according to WHO growth tables and biochemical parameters were also right. From allergenicity point of view, hydrolysates and therapeutic formula showed very little amount of immunoreactive protein and molecular weight distribution lower than 3000 Da. ASA assay supported the previous results and the therapeutic formula was safety and tolerated by 97.7% of infants with CMPA. Levels of LC-PUFAs (DHA and AA) in red blood cells tended to increase after 3 months of nutritional treatment and levels were closed to amounts found in breast fed infants. From immunological point of view, IL-8 and eosinophils levels in plasma significantly decrease after 3 months of treatment (IL-8: 33.78±22.58 vs 5.66±1.40 pg/ml, U de Mann Whitney U p=0.03; eosinophils: 1457,54 ±2570,21 vs 417,39 ±402,98 cell/mm3). IL-10, immunomodulatory cytokines, tended to increase and several bioactive peptides, molecular weight < 1000 Da, were identified, one of them with immunomodulatory effect

Coming across a novel copper oxide 2D framework during the oxidation of Cu(111)

Two dimensional copper oxides obtained on Cu(111) by air-enriched argon sputtering plus annealing have been measured at room temperature by means of scanning tunneling microscopy (STM) and atomic force microscopy (AFM) under ultra-high vacuum (UHV) conditions. Depending on the oxygen content different oxide frameworks and diverse stoichiometric metal/oxide interfaces exist. In particular, we report on a novel open honeycomb structure with a large unit cell which is modeled as a two dimensional network made out of Cu3O units. This lattice coexists with other oxide structures richer in oxygen and is suggested to develop towards these denser phases by oxygen incorporation

Funcionalidad y recomendaciones nutricionales de ácidos grasos esenciales y sus derivados en la alimentación del lactante a partir de los 6 meses de edad

Essential fatty acids and long-chain unsaturated fatty acids are important for growth and neuronal development during the final months of gestation and the early years of life. The aim of this study is to highlight the importance of ensuring a correct intake of EFAs for nutritional requirements through the intake of foods which naturally contain these acids or which have been enriched with them. The methodology used was basee on the review of electronic databases MedLine, ScienceDirect, Scirus, Trip database and that of the scientific journal library of the University of Murcia. National and international websites such as  the Asociación Española de Pediatría (AEP), European Agency for Food Safety (EAFS) and the European Society of Pediatric, Gastroenterology, Health and Nutrition (ESPGHAN) were also consulted.   The results show how EFAs and also AGPI-CL (DHA and ARA) are essential for the correct development of breastfeeders and infants. Even though the breastfeeder is enzymatically fully equipped from the first day of life to convert EFAs into AGPI-CL and derivatives, the conversion may be insufficient  and it may be necessary to include AGPI-CL in the diet. The conclusions are that during the first 6 months of life  the provision of EFAs and AGPI-CL is assured thanks to the mother’s milk or through starter formulas; at six months the introduction of complementary foods and the adaptation to cow’s milk at  twelve months (against the recommendations of the ESPGHAN) may affect the provision of these acids. There is a legal vacuum in the issue of the provision of EFAs through complementary foods other than cereals although committees like the AEP recommend that AL in meat and fish baby foods with vegetables should suppose 3-4.5% of the energy provision, and ALN at least 0.5% in order to satisfy EFA requirements in breastfeeders ans infants.Los requerimientos de ácidos grasos esenciales (AGEs) y ácidos grasos poliinsaturados de cadena larga (AGPI-CL) durante los últimos meses de gestación y los primeros años de vida son importantes de acuerdo al crecimiento y desarrollo neuronal que está teniendo lugar durante este periodo de vida. El objetivo de este trabajo ha sido destacar la importancia de garantizar un correcta ingesta de AGEs para cubrir los requerimientos nutricionales de estos, a través de la ingesta de alimentos que contienen en su composición nutricional a estos ácidos de forma natural o han sido enriquecidos con ellos. La metodología empleada para este fin ha sido la utilización de  bases de datos electrónicas como MedLine, ScienceDirect, Scirus, Trip database y de la hemeroteca científica de la Universidad de Murcia; También han sido consultadas las páginas web de organismos nacionales e internacionales tales como la Asociación Española de Pediatría (AEP), Agencia Europea de Seguridad Alimentaria (EFSA) y European Society of Pediatric, Gastroenterology, Health and Nutrition (ESPGHAN). Los resultados obtenidos muestran como los AGEs e incluso los AGPI-CL (DHA y ARA) son esenciales para el correcto desarrollo del lactante y niño de corta edad; pues aún estando el lactante desde el primer día de vida dotado de todo el sistema enzimático necesario para la conversión de AGEs en sus correspondientes AGPI-CL y sus derivados, esta conversión podría ser insuficiente, siendo necesario y/o esencial el aporte de estos AGPI-CL a través de la dieta. Las conclusiones derivadas de este trabajo fueron que durante los seis primeros meses de vida el aporte de AGEs y AGPI-CL está asegurado a través de la leche materna o en su defecto a través de las fórmulas  de inicio; a partir de los 6 meses con la introducción de la alimentación complementaria y la introducción de la leche de vaca a partir de los 12 meses de vida (introducción en contra de las recomendaciones de ESPGHAN), podría verse comprometida la aportación de estos ácidos. Existe un vacío legal en cuanto a la aportación de AGEs a través de la alimentación complementaria distinta a los cereales; sin embargo, comités como el de la AEP recomienda que en los tarritos infantiles de carnes y pescados con verdura, el aporte de AL sea entre 3-4.5% de la energía de la dieta y al menos 0.5% desde ALN para satisfacer los requerimientos de AGEs en lactantes y niños de corta edad

Human Intestinal Dendritic Cells Decrease Cytokine Release against Salmonella Infection in the Presence of Lactobacillus paracasei upon TLR Activation

Probiotic bacteria have been shown to modulate immune responses and could have therapeutic effects in allergic and inflammatory disorders. However, little is known about the signalling pathways that are engaged by probiotics. Dendritic cells (DCs) are antigen-presenting cells that are involved in immunity and tolerance. Monocyte-derived dendritic cells (MoDCs) and murine DCs are different from human gut DCs; therefore, in this study, we used human DCs generated from CD34+ progenitor cells (hematopoietic stem cells) harvested from umbilical cord blood; those DCs exhibited surface antigens of dendritic Langerhans cells, similar to the lamina propria DCs in the gut. We report that both a novel probiotic strain isolated from faeces of exclusively breast-fed newborn infants, Lactobacillus paracasei CNCM I-4034, and its cell-free culture supernatant (CFS) decreased pro-inflammatory cytokines and chemokines in human intestinal DCs challenged with Salmonella. Interestingly, the supernatant was as effective as the bacteria in reducing pro-inflammatory cytokine expression. In contrast, the bacterium was a potent inducer of TGF-β2 secretion, whereas the supernatant increased the secretion of TGF-β1 in response to Salmonella. We also showed that both the bacteria and its supernatant enhanced innate immunity through the activation of Toll-like receptor (TLR) signalling. These treatments strongly induced the transcription of the TLR9 gene. In addition, upregulation of the CASP8 and TOLLIP genes was observed. This work demonstrates that L. paracasei CNCM I-4034 enhanced innate immune responses, as evidenced by the activation of TLR signalling and the downregulation of a broad array of pro-inflammatory cytokines. The use of supernatants like the one described in this paper could be an effective and safe alternative to using live bacteria in functional foods.This work was funded by Hero Spain S.A. through the contract n° 3143 signed with the Fundación General Universidad de Granada Empresa and co-sponsored by the CDTI, a public entity of the Ministry of Economy and Competitiveness of the Spanish Government. Carolina Gomez-Llorente received a postdoctoral fellowship from Plan Propio of University of Granada