Complementos alimenticios funcionales: péptidos antihipertensivos procedentes de la leche

Los complementos alimenticios representan una importante fuente de nutrientes esenciales y otros elementos. Últimamente, se está produciendo un aumento de su consumo relacionado con la importancia que está adquiriendo el autocuidado de la salud, donde el farmacéutico juega un importante papel. Dentro de esta categoría de sustancias han aparecido recientemente los péptidos bioactivos. Estos péptidos son secuencias de aminoácidos de pequeño tamaño, inactivas dentro de la proteína intacta, pero que pueden ser liberados durante la digestión del alimento en el organismo o por un procesado previo del mismo. Tienen efectos beneficiosos en diversos casos y pueden influir positivamente en la salud de la población. Algunas actividades que han demostrado tener son: antihipertensiva, opiácea, antioxidante, quelante de minerales o inmunomoduladora. De entre los diferentes grupos de péptidos bioactivos, los péptidos antihipertensivos están recibiendo una especial atención debido a la frecuencia de la hipertensión arterial en la población mundial. Estos péptidos obtenidos por fermentación o hidrólisis enzimática han demostrado su actividad antihipertensiva como inhibidores de la enzima convertidora de angiotensina, mediante ensayos in vitro e in vivo en animales de experimentación en pruebas agudas, crónicas y toxicológicas, así como en ensayos clínicos en humanos. Son unos productos de probada seguridad y eficacia. Su aparición como complementos alimenticios permite al farmacéutico tener un recurso terapéutico, que no es de prescripción, para su indicación en aquellos casos en los que se detecten valores de presión arterial que sin llegar a la hipertensión sean susceptibles de una intervención farmacéutica

Bacteriocin Gene-Trait matching across the complete Lactobacillus Pan-genome.

peer-reviewedLactobacilli constitute a large genus of Gram-positive lactic acid bacteria which have widespread roles ranging from gut commensals to starters in fermented foods. A combination of in silico and laboratory-based screening allowed us to determine the overall bacteriocin producing potential of representative strains of each species of the genus. The genomes of 175 lactobacilli and 38 associated species were screened for the presence of antimicrobial producing genes and combined with screening for antimicrobial activity against a range of indicators. There also appears to be a link between the strains’ environment and bacteriocin production, with those from the animal and human microbiota encoding over twice as many bacteriocins as those from other sources. Five novel bacteriocins were identified belonging to differing bacteriocin classes, including two-peptide bacteriocins (muricidin and acidocin X) and circular bacteriocins (paracyclicin). In addition, there was a clear clustering of helveticin type bacteriolysins in the Lactobacillus acidophilus group of species. This combined in silico and in vitro approach to screening has demonstrated the true diversity and complexity of bacteriocins across the genus. It also highlights their biological importance in terms of communication and competition between closely related strains in diverse complex microbial environments

Detoxifying enzymes at the cross-roads of inflammation, oxidative stress, and drug hypersensitivity: role of glutathione transferase P1-1 and aldose reductase

9 p.-2 figPhase I and II enzymes are involved in the metabolism of endogenous reactive compounds as well as xenobiotics, including toxicants and drugs. Genotyping studies have established several drug metabolizing enzymes as markers for risk of drug hypersensitivity. However, other candidates are emerging that are involved in drug metabolism but also in the generation of danger or costimulatory signals. Enzymes such as aldo-keto reductases (AKR) and glutathione transferases (GST) metabolize prostaglandins and reactive aldehydes with proinflammatory activity, as well as drugs and/or their reactive metabolites. In addition, their metabolic activity can have important consequences for the cellular redox status, and impacts the inflammatory response as well as the balance of inflammatory mediators, which can modulate epigenetic factors and cooperate or interfere with drug-adduct formation. These enzymes are, in turn, targets for covalent modification and regulation by oxidative stress, inflammatory mediators, and drugs. Therefore, they constitute a platform for a complex set of interactions involving drug metabolism, protein haptenation, modulation of the inflammatory response, and/or generation of danger signals with implications in drug hypersensitivity reactions. Moreover, increasing evidence supports their involvement in allergic processes. Here, we will focus on GSTP1-1 and aldose reductase (AKR1B1) and provide a perspective for their involvement in drug hypersensitivityThis work has been supported by grants SAF2012-36519 from MINECO and SAF-2015-68590-R from MINECO/FEDER and ISCIII RETIC RIRAAF RD12/0013/0008 to DP,and RD12/0013/0002 to J A.Peer reviewe

Design of Lactococcus lactis Strains Producing Garvicin A and/or Garvicin Q, Either Alone or Together with Nisin A or Nisin Z and High Antimicrobial Activity against Lactococcus garvieae

Lactococcus garvieae is a main ichthyopathogen in rainbow trout (Oncorhynchus mykiss, Walbaum) farming, although bacteriocinogenic L. garvieae with antimicrobial activity against virulent strains of this species have also been identified. Some of the bacteriocins characterized, such as garvicin A (GarA) and garvicin Q (GarQ), may show potential for the control of the virulent L. garvieae in food, feed and other biotechnological applications. In this study, we report on the design of Lactococcus lactis strains that produce the bacteriocins GarA and/or GarQ, either alone or together with nisin A (NisA) or nisin Z (NisZ). Synthetic genes encoding the signal peptide of the lactococcal protein Usp45 (SPusp45), fused to mature GarA (lgnA) and/or mature GarQ (garQ) and their associated immunity genes (lgnI and garI, respectively), were cloned into the protein expression vectors pMG36c, which contains the P32 constitutive promoter, and pNZ8048c, which contains the inducible PnisA promoter. The transformation of recombinant vectors into lactococcal cells allowed for the production of GarA and/or GarQ by L. lactis subsp. cremoris NZ9000 and their co-production with NisA by Lactococcus lactis subsp. lactis DPC5598 and L. lactis subsp. lactis BB24. The strains L. lactis subsp. cremoris WA2-67 (pJFQI), a producer of GarQ and NisZ, and L. lactis subsp. cremoris WA2-67 (pJFQIAI), a producer of GarA, GarQ and NisZ, demonstrated the highest antimicrobial activity (5.1- to 10.7-fold and 17.3- to 68.2-fold, respectively) against virulent L. garvieae strains.Sección Dptal. de Nutrición y Ciencia de los Alimentos (Veterinaria)Fac. de VeterinariaTRUEMinisterio de Ciencia, Innovación y Universidades (MCIU)Universidad Complutense de Madrid and Banco de SantanderUniversidad Complutense de Madridpu

Evolving brain functional abnormalities in PSEN1 mutation carriers: A resting and visual encoding fMRI study

PSEN1 mutations are the most frequent cause of familial Alzheimer's disease and show nearly full penetrance. Here we studied alterations in brain function in a cohort of 19 PSEN1 mutation carriers: 8 symptomatic (SMC) and 11 asymptomatic (AMC). Asymptomatic carriers were, on average, 12 years younger than the predicted age of disease onset. Thirteen healthy subjects were used as a control group (CTR). Subjects underwent a 10-min resting-state functional magnetic resonance imaging (fMRI) scan and also performed a visual encoding task. The analysis of resting-state fMRI data revealed alterations in the default mode network, with increased frontal connectivity and reduced posterior connectivity in AMC and decreased frontal and increased posterior connectivity in SMC. During task-related fMRI, SMC showed reduced activity in regions of the left occipital and left prefrontal cortices, while both AMC and SMC showed increased activity in a region within the precuneus/posterior cingulate, all as compared to CTR. Our findings suggest that fMRI can detect evolving changes in brain mechanisms in PSEN1 mutation carriers and support the use of this technique as a biomarker in Alzheimer's disease, even before the appearance of clinical symptoms

Differences in breast cancer-risk factors between screen-detected and non-screen-detected cases (MCC-Spain study)

Purpose: The variation in breast cancer (BC)-risk factor associations between screen-detected (SD) and non-screen-detected (NSD) tumors has been poorly studied, despite the interest of this aspect in risk assessment and prevention. This study analyzes the differences in breast cancer-risk factor associations according to detection method and tumor phenotype in Spanish women aged between 50 and 69. Methods: We examined 900 BC cases and 896 controls aged between 50 and 69, recruited in the multicase-control MCC-Spain study. With regard to the cases, 460 were detected by screening mammography, whereas 144 were diagnosed by other means. By tumor phenotype, 591 were HR+, 153 were HER2+, and 58 were TN. Lifestyle, reproductive factors, family history of BC, and tumor characteristics were analyzed. Logistic regression models were used to compare cases vs. controls and SD vs. NSD cases. Multinomial regression models (controls used as a reference) were adjusted for case analysis according to phenotype and detection method. Results: TN was associated with a lower risk of SD BC (OR 0.30 IC 0.10-0.89), as were intermediate (OR 0.18 IC 0.07-0.44) and advanced stages at diagnosis (OR 0.11 IC 0.03-0.34). Nulliparity in postmenopausal women and age at menopause were related to an increased risk of SD BC (OR 1.60 IC 1.08-2.36; OR 1.48 IC 1.09-2.00, respectively). Nulliparity in postmenopausal women was associated with a higher risk of HR+ (OR 1.66 IC 1.15-2.40). Age at menopause was related to a greater risk of HR+ (OR 1.60 IC 1.22-2.11) and HER2+ (OR 1.59 IC 1.03-2.45) tumors. Conclusion: Reproductive risk factors are associated with SD BC, as are HR+ tumors. Differences in BC-risk factor associations according to detection method may be related to prevailing phenotypes among categories

Distinct functional activity of the precuneus and posterior cingulate cortex during encoding in the preclinical stage of Alzheimer's Disease

In this study functional magnetic resonance imaging (fMRI) is used to investigate the functional brain activation pattern in the preclinical stage of AD (pre-AD) subjects during a visual encoding memory task. Thirty subjects, eleven in the pre-AD stage, with decreased cerebrospinal fluid levels of Aβ42 (<500 pg/ml), and 19 controls with normal Aβ42 levels (CTR) were included. fMRI was acquired during a visual encoding task. Data were analyzed through an Independent Component Analysis (ICA) and region-of-interest-based univariate analysis of task-related BOLD signal change. From the ICA decomposition, we identified the main task-related component, which included the activation of visual associative areas and prefrontal executive regions, and the deactivation of the default-mode network. The activation was positively correlated with task performance in the CTR group (p < 0.0054). Within this pattern, subjects in the pre-AD stage had significantly greater activation of the precuneus and posterior cingulate cortex during encoding. Subjects in the pre-AD stage present distinct functional neural activity before the appearance of clinical symptomatology. These findings may represent that subtle changes in functional brain activity precede clinical and cognitive symptoms in the AD continuum. Present findings provide evidence suggesting that fMRI may be a suitable biomarker of preclinical AD

The Genome-wide Methylation Profile of CD4+ T Cells From Individuals With Human Immunodeficiency Virus (HIV) Identifies Distinct Patterns Associated With Disease Progression

Background: Human genetic variation-mostly in the HLA and CCR5 regions-explains 25% of the variability in progression of HIV infection. However, it is also known that viral infections can modify cellular DNA methylation patterns. Therefore, changes in the methylation of CpG islands might modulate progression of HIV infection. Methods: 85 samples were analyzed: 21 elite controllers (EC), 21 HIV-infected subjects before combination antiretroviral therapy (cART) (viremic, 93,325 HIV-1 RNA copies/ml) and under suppressive cART (cART, median of 17 months, <50 HIV-1 RNA copies/ml), and 22 HIV-negative donors (HIVneg). We analyzed the methylation pattern of 485,577 CpG in DNA from peripheral CD4+ T lymphocytes. We selected the most differentially methylated gene (TNF) and analyzed its specific methylation, mRNA expression, and plasma protein levels in 5 individuals before and after initiation of cART. Results: We observed 129 methylated CpG sites (associated with 43 gene promoters) for which statistically significant differences were recorded in viremic vs HIVneg, 162 CpG sites (55 gene promoters) in viremic vs cART, 441 CpG sites (163 gene promoters) in viremic vs EC, but none in EC vs HIVneg. The TNF promoter region was hypermethylated in viremic vs HIVneg, cART, and EC. Moreover, we observed greater plasma levels of TNF in viremic individuals than in EC, cART, and HIVneg. Conclusions: Our study shows that genome methylation patterns vary depending on HIV infection status and progression profile and that these variations might have an impact on controlling HIV infection in the absence of cART

Variability of paternal lineages in two populations from the Argentinian Northwest: Santiago del Estero and Tucumán

Se analiza el origen continental de los haplogrupos del cromosoma Y en poblaciones de Santiago del Estero y San Miguel de Tucumán con el fin de ampliar el mapa filogeográfico de los linajes paternos argentinos. Se recolectaron 283 muestras de sangre con encuestas genealógicas a donantes voluntarios de sexo masculino en centros de salud públicos y privados de ambas localidades. Mediante PCR alelo-específica se tipificaron 18 marcadores bialélicos de la región no recombinante del cromosoma Y de presencia ampliamente confirmada en Argentina. El 89% de los linajes fueron de origen euroasiático, el 7% americano y el 4% fueron dentificados como de posible ascendencia africana y/o del sudoeste asiático, debido a su asignación al linaje E1b1a1. Las frecuencias de haplogrupos de las poblaciones muestreadas fueron semejantes a las de poblaciones de las regiones Pampeana, Cuyo y Noreste. La muestra procedente del centro privado de Tucumán presentó en sus haplogrupos alóctonos frecuencias similares a las reportadas para Europa y Medio Oriente, corroborando que los tres contingentes migratorios que han aportado mayor número de inmigrantes en San Miguel de Tucumán: españoles, italianos y árabes, han dejado su huella en el acervo genético de sus poblaciones actuales. El patrón de distribución de los haplogrupos nativo americanos del cromosoma Y no difiere sustancialmente del detectado en el noroeste y en otras poblaciones argentinas y el mismo es congruente con la información arqueológica, etnohistórica y censal de Santiago del Estero y San Miguel de TucumánContinental origin as inferred from Y chromosome haplogroups is analyzed in populations from Santiago del Estero and San Miguel de Tucumán with the purpose of expanding the phylogeographic map of Argentinian paternal lineages. Two hundred and eighty-three blood samples were collected with familial information from male volunteer donors at public and private health centers. By means of allele-specific PCR, 18 biallelic markers commonly found in contemporary Argentina were typed from the non-recombinant region of the Y chromosome. Eightynine percent of the lineages were from Eurasian origin, 7% American and 4% were identified as African and/or Southwest Asian descent, owing to their assignment to the E1b1a1 lineage. Haplogroup frequencies of current populations were similar to the populations from Pampa, Cuyo and Northwest regions. Samples from the private health center of Tucumán demonstrated allochthonous haplogroup in similar frequencies to those reported in Europe and the Middle East, confirming that the migratory contingents with the greatest number of immigrants —Spaniards, Italians and Arabs— have left their mark on the gene pool of current populations. The pattern of distribution of continental Y-chromosomal haplogroups is indistinguishable from that found among Argentine populations in the northwest or in other regions, and it is consistent with archaeological, ethnohistorical and census information from Santiago del Estero and San Miguel de TucumánFil: Schwab, Marisol Elisabet. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Jurado Medina, Laura Smeldy. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Beltramo, Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Sala, Camila. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Paz Sepúlveda, Paula Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Alfaro Gómez, Emma Laura. Universidad Nacional de Jujuy. Instituto de Ecorregiones Andinas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Ecorregiones Andinas; ArgentinaFil: Dipierri, Jose Edgardo. Universidad Nacional de Jujuy. Instituto de Ecorregiones Andinas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Ecorregiones Andinas; ArgentinaFil: Bravi, Claudio Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Bailliet, Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentin