Influence of a mediterranean diet supplemented in coenzyme Q10 on metabolomic profile and on the expression of antioxidante, pro-inflammatory and endoplasmis reticulum stress-related genes in an elderly population

Introduction: Accelerated aging population is a global phenomenon that is expanding over the last decades. The aging process is known to be accompanied by an increase in oxidative stress (OxS) and endoplasmic reticulum (ER) stress, which have been associated with the activation of inflammatory pathways. Nutrition and other lifestyle habits have a major impact on the risk of developing chronic diseases that appear more frequently in the elderly. Diet, particularly fat quality, may affect the reactive oxygen species (ROS) production and, in consequence, both OxS and ER stress. Due to the fact that postprandial state is the main physiological condition of the occidental society, it is crucial to study the postprandial effect induced by the long-term consumption of different dietary patterns. In this connection, the consumption of a diet with antioxidant properties such as the Mediterranean diet (Med diet) and supplementation with a natural antioxidant compound such as Coenzyme Q10 (CoQ) have been proved to decrease the postprandial OxS by reducing processes of cellular oxidation. Hypothesis: The consumption of diets with different fat quality modulates the processes related to OxS, ER stress and the inflammatory response in terms of gene expression in an elderly population, during both fasting and postprandial state. Moreover, the supplementation with a natural antioxidant such as CoQ further improves this modulation. Main objective: To evaluate whether the long-term consumption of three dietary patterns with different fat quality (Med diet with or without supplementation in CoQ and saturated fatty acid-rich diet) modulates OxS in fasting and postprandial state by modifying the gene expression of Nrf2, p22phox and p47phox NADPH oxidase subunits, SOD1, SOD2, Gpx1, TrxR and...Introducción: El envejecimiento acelerado de la población es un fenómeno mundial que se está produciendo progresivamente a lo largo de las últimas décadas. Este proceso se asocia con un incremento del estrés oxidativo (EO) y de estrés del retículo endoplásmico (RE), los cuales a su vez están relacionados con la activación de la respuesta inflamatoria. La nutrición y otros hábitos de vida ejercen un gran impacto sobre el riesgo de desarrollar enfermedades crónicas que se presentan con mayor frecuencia en personas de edad avanzada. Se ha demostrado que la dieta, particularmente la calidad de la grasa de la misma, afecta a la producción de especies reactivas de oxígeno y, en consecuencia, a los procesos de EO y de estrés del RE. Debido al hecho de que el estado postprandial constituye la situación fisiológica habitual en la que se encuentra el ser humano a lo largo del día en las sociedades occidentales, es necesario estudiar el efecto postprandial inducido por el consumo de diferentes modelos dietéticos. En este sentido, el consumo de una dieta Mediterránea (dieta Med) con propiedades antioxidantes y la suplementación con un compuesto natural antioxidante como la Coenzima Q10 (CoQ) contribuyen a reducir los procesos de oxidación celular, disminuyendo a su vez el EO postprandial. Hipótesis: El consumo de dietas con distinta calidad grasa puede modular la expresión génica de parámetros asociados con mecanismos de EO, estrés del RE y de respuesta inflamatoria en ayunas y durante el período postprandial en una población de edad avanzada. Además, la suplementación con un antioxidante natural como la CoQ podría aportar un beneficio adicional en estos parámetros..

DNA Repair Mechanisms as Drug Targets in Prokaryotes

Nowadays, a great amount of pathogenic bacteria has been identified such as Mycobacterium sp. and Helicobacter pylori and have become a serious health problem around the world. These bacteria have developed several DNA repair mechanisms as a strategy to neutralize the effect of the exposure to endogenous and exogenous agents that will lead to two different kinds of DNA damage: single strand breaks (SSBs) and double strand breaks (DSBs). For SSBs repair, bacteria use the base excision repair (BER) and nucleotide excision repair (NER) mechanisms, which fix the damaged strand replacing the damaged base or nucleotide. DSBs repair in bacteria is performed by homologous recombination repair (HRR) and non-homologous end-joining (NHEJ). HRR uses the homologous sequence to fix the two damaged strand, while NHEJ repair does not require the use of its homologous sequence. The use of unspecific antibiotics to treat bacterial infections has caused a great deal of multiple resistant strains making less effective the current therapies with antibiotics. In this review, we emphasized the mechanisms mentioned above to identify molecular targets that can be used to develop novel and more efficient drugs in future.Nowadays, a great amount of pathogenic bacteria has been identified such as Mycobacterium sp. and Helicobacter pylori and have become a serious health problem around the world. These bacteria have developed several DNA repair mechanisms as a strategy to neutralize the effect of the exposure to endogenous and exogenous agents that will lead to two different kinds of DNA damage: single strand breaks (SSBs) and double strand breaks (DSBs). For SSBs repair, bacteria use the base excision repair (BER) and nucleotide excision repair (NER) mechanisms, which fix the damaged strand replacing the damaged base or nucleotide. DSBs repair in bacteria is performed by homologous recombination repair (HRR) and non-homologous end-joining (NHEJ). HRR uses the homologous sequence to fix the two damaged strand, while NHEJ repair does not require the use of its homologous sequence. The use of unspecific antibiotics to treat bacterial infections has caused a great deal of multiple resistant strains making less effective the current therapies with antibiotics. In this review, we emphasized the mechanisms mentioned above to identify molecular targets that can be used to develop novel and more efficient drugs in future

Incorporación del estudio de ADN fetal en sangre materna al cribado de cromosomopatías

Objetivo: Evaluar la efectividad del cribado combinado de primer trimestre para la detección prenatal de aneuploidías tras 6 años de implantación en nuestro servicio y su repercusión en la disminución de pruebas diagnósticas invasivas. Se propone establecer un protocolo para incorporar el estudio de ADN fetal en sangre materna a partir de las revisiones bibliográficas publicadas. Método: Se evaluó el riesgo de anomalía cromosómica fetal en 3177 gestaciones mediante cribado combinado de primer trimestre entre enero de 2011 y diciembre de 2014. Se revisaron las amniocentesis realizadas desde que se instauró el cribado combinado en 2008 comparándolas con las de los 5 años anteriores. Resultados: La tasa de detección del cribado para trisomía 21 fue del 94,4% y la tasa de falsos positivos de 6,4%. En el año 2005 estábamos realizando 194 amniocentesis, tras 6 años de implantación del cribado, en el año 2013 se realizaron 35 amniocentesis lo que implica una disminución del 70%. Conclusiones: El cribado combinado de primer trimestre ha demostrado una mayor tasa de detección para trisomía 21 que el cribado de segundo trimestre y/o la edad materna, además de que ha llevado a una importante reducción en el número de pruebas invasivas. En los próximos años la incorporación del estudio de ADN fetal mejorará la detección de aneuploidías, con una drástica disminución de las pruebas invasivas por lo que se hace necesario la implantación de nuevos protocolos. Aims: To evaluate the effectiveness of first trimester combined screening in the prenatal detection of aneuploidy after 6 years of implantation in our service and its impact in reducing invasive diagnostic tests. It is proposed to establish a protocol to incorporate the study of fetal DNA in maternal blood from published literature reviews. Methods: The risk of fetal chromosomal anomalies was assessed in 3177 pregnancies with first trimester combined screening between January 2009 and December 2014. The amniocenteses performed were checked against those of the previous 5 years. Results: The detection rate of screening for trisomy 21 was 94.4% and the false-positive rate was 6.4%. In 2005 there were 194 amniocenteses. In 2013, 5 years after the introduction of screening, 68 amniocenteses were performed, representing a 70% reduction in invasive procedures. Conclusions: First trimester combined screening has shown a higher detection rate for trisomy 21 that the second trimester screening and/or maternal age, and has substantially reduced the use of invasive prenatal diagnostics procedures. In the coming years, the incorporation of the study of fetal DNA improve the detection of aneuploidys with a drastic reduction of invasive tests so that, the implementation of new protocols is necessary

Proteome from patients with metabolic syndrome is regulated by quantity and quality of dietary lipids

Background: Metabolic syndrome is a multi-component disorder associated to a high risk of cardiovascular disease. Its etiology is the result of a complex interaction between genetic and environmental factors, including dietary habits. We aimed to identify the target proteins modulated by the long-term consumption of four diets differing in the quality and quantity of lipids in the whole proteome of peripheral blood mononuclear cells (PBMC). Results: A randomized, controlled trial conducted within the LIPGENE study assigned 24 MetS patients for 12 weeks each to 1 of 4 diets: a) high-saturated fatty acid (HSFA), b) high-monounsaturated fatty acid (HMUFA), c) low-fat, high-complex carbohydrate diets supplemented with placebo (LFHCC) and d) low-fat, high-complex carbohydrate diets supplemented with long chain (LC) n-3 polyunsaturated fatty acids (PUFA) (LFHCC n-3). We analyzed the changes induced in the proteome of both nuclear and cytoplasmic fractions of PBMC using 2-D proteomic analysis. Sixty-seven proteins were differentially expressed after the long-term consumption of the four diets. The HSFA diet induced the expression of proteins responding to oxidative stress, degradation of ubiquitinated proteins and DNA repair. However, HMUFA, LFHCC and LFHCC n-3 diets down-regulated pro-inflammatory and oxidative stress-related proteins and DNA repairing proteins. Conclusion: The long-term consumption of HSFA, compared to HMUFA, LFHCC and LFHCC n-3, seems to increase the cardiovascular disease (CVD) risk factors associated with metabolic syndrome, such as inflammation and oxidative stress, and seem lead to DNA damage as a consequence of high oxidative stress

Actinomicosis de pared abdominal. A propósito de un caso

ResumenAntecedentesLa actinomicosis de pared abdominal es un cuadro clínico poco frecuente, asociado al uso de dispositivo intrauterino, o como complicación de cirugía abdominal. Su diagnóstico es difícil por ser poco habitual y comportarse como una neoplasia maligna.ObjetivosPresentamos el caso de una paciente portadora de DIU desde hacía cuatro años que presentaba un tumor pétreo en pared abdominal asociada a un conjunto de síntomas que, clínica y radiológicamente, simulaba una carcinomatosis peritoneal asociada a síndrome paraneoplásico, incluso en el curso de una laparotomía exploradora.Caso clínicoLa paciente acudió a nuestro hospital con un cuadro de dos meses de evolución con dolor abdominal y síntomas que simulaban un síndrome paraneoplásico. El diagnóstico de sospecha se realizó por el hallazgo del microorganismo en una citología cervical con el resto de cultivos y estudios anatomopatológicos negativos para Actinomyces, confirmándose por la curación completa con el tratamiento empírico con penicilina.ConclusionesLa actinomicosis debe ser sospechada en pacientes con tumores pélvicos o de pared abdominal que simulan procesos malignos. El tratamiento antibiótico es el de elección y hace innecesario el manejo quirúrgico más agresivo.AbstractBackgroundAbdominal wall Actinomycosis is a rare disease associated with the use of intrauterine device and as a complication of abdominal surgery. Diagnosis is difficult because it is unusual and behaves like a malignant neoplasm.AimA case report is presented of a patient who had used an intrauterine device for four years and developed a stony tumour in the abdominal wall associated with a set of symptoms that, clinically and radiologically, was simulating a peritoneal carcinomatosis associated with paraneoplastic syndrome, even in the course of an exploratory laparotomy.Clinical caseThe patient attended our hospital with a two-month history of abdominal pain and symptoms that mimic a paraneoplastic syndrome. The diagnosis of abdominal actinomycosis was suspected by the finding of the microorganism in cervical cytology together with other cultures and Actinomyces negative in pathological studies, confirming the suspicion of a complete cure with empirical treatment with penicillin.ConclusionsActinomycosis should be considered in patients with pelvic mass or abdominal wall mass that mimics a malignancy. Antibiotic therapy is the first treatment choice and makes a more invasive surgical management unnecessary

Polymorphism at the TNF

Alcance Examinar si el consumo de una dieta mediterránea (MedDiet), en comparación con una dieta baja en grasas, interactúa con dos polimorfismos de un solo nucleótido en el gen del factor de necrosis tumoral alfa (rs1800629, rs1799964) para mejorar los triglicéridos (TG), el control glucémico y marcadores de inflamación. Métodos y resultados El genotipado, las mediciones bioquímicas, la intervención dietética y la comida de prueba de carga de grasa oral se determinaron en 507 pacientes con síndrome metabólico (MetS) seleccionados de todos los sujetos incluidos en el ensayo clínico CORDIOPREV (n = 1002). Al inicio del estudio, los sujetos G/G (n = 408) en el polimorfismo rs1800629 mostraron niveles más altos de TG en ayunas y posprandiales (p = 0,003 y p = 0,025, respectivamente) y proteína C reactiva de alta sensibilidad (hsCRP) (p = 0,003) concentraciones plasmáticas que los portadores del alelo A menor (G/A + A/A) (n = 99). Después de 12 meses de MedDiet, las diferencias iniciales entre genotipos desaparecieron. La disminución de TG y hsCRP fue estadísticamente significativa en sujetos G/G (n = 203) en comparación con los portadores del alelo A menor (p = 0,005 y p = 0,034, respectivamente) (n = 48). No se observaron otras interacciones gen-dieta en ninguna de las dietas. Conclusión Estos resultados sugieren que el rs1800629 en el gen del factor de necrosis tumoral alfa interactúa con MedDiet para influir en el metabolismo de los TG y el estado de inflamación en sujetos con MetS. Comprender el papel de las interacciones gen-dieta puede ser la mejor estrategia para el tratamiento personalizado del síndrome metabólico.Scope To examine whether the consumption of a Mediterranean diet (MedDiet), compared with a low-fat diet, interacts with two single nucleotide polymorphisms at the tumor necrosis factor alpha gene (rs1800629, rs1799964) in order to improve triglycerides (TG), glycemic control, and inflammation markers. Methods and results Genotyping, biochemical measurements, dietary intervention, and oral fat load test meal were determined in 507 metabolic syndrome (MetS) patients selected from all the subjects included in CORDIOPREV clinical trial (n = 1002). At baseline, G/G subjects (n = 408) at the rs1800629 polymorphism, showed higher fasting and postprandial TG (p = 0.003 and p = 0.025, respectively), and high sensitivity C-reactive protein (hsCRP) (p = 0.003) plasma concentrations than carriers of the minor A-allele (G/A + A/A) (n = 99). After 12 months of MedDiet, baseline differences between genotypes disappeared. The decrease in TG and hsCRP was statistically significant in G/G subjects (n = 203) compared with carriers of the minor A-allele (p = 0.005 and p = 0.034, respectively) (n = 48). No other gene–diet interactions were observed in either diet. Conclusion These results suggest that the rs1800629 at the tumor necrosis factor alpha gene interacts with MedDiet to influence TG metabolism and inflammation status in MetS subjects. Understanding the role of gene–diet interactions may be the best strategy for personalized treatment of MetS