The integrated stress response in metabolic adaptation.

The integrated stress response (ISR) refers to signaling pathways initiated by stress-activated eIF2α kinases. Distinct eIF2α kinases respond to different stress signals, including amino acid deprivation and mitochondrial stress. Such stress-induced eIF2α phosphorylation attenuates general mRNA translation and, at the same time, stimulates the preferential translation of specific downstream factors to orchestrate an adaptive gene expression program. In recent years, there have been significant new advances in our understanding of ISR during metabolic stress adaptation. Here, I discuss those advances, reviewing among others the ISR activation mechanisms in response to amino acid deprivation and mitochondrial stress. In addition, I review how ISR regulates the amino acid metabolic pathways and how changes in the ISR impact the physiology and pathology of various disease models.

Oxidative stress in mouse liver caused by dietary amino acid deprivation: protective effect of methionine

No disponible

The aim of this work was to evaluate the effects of a diet depleted of amino acids (protein-free diet, or PFD), as well as the supplementation with methionine (PFD+Met), on the antioxidant status of the female mouse liver. With this purpose, cytosolic protein spots from two-dimensional non-equilibrium pH gel electrophoresis were identified by several procedures, such as mass spectrometry, Western blot, gel matching and enzymatic activity. PFD decreased the contents of catalase (CAT),peroxiredoxin I (Prx-I), and glutathione peroxidase (GPx) by 67%, 37% and 45%, respectively. Gene expression analyses showed that PFD caused a decrease in CAT (−20%) and GPx (−30%) mRNAlevels but did not change that of Prx-I. It was also found that, when compared to a normal diet, PFD increased the liver contents of both reactive oxygen species (+50%) and oxidized protein (+88%) and decreased that of glutathione (−45%). Supplementation of PFD with Met prevented these latter effects to varying degrees, whereas CAT, Prx-I and GPx mRNA levels resulted unmodified. Present results suggest that dietary amino acid deprivation deranges the liver antioxidant defences, and this can be, in part, overcome by supplementation with Met (AU)

Detection of metabolic disorders in high-risk patients: a pilot study in Salvador, Bahia

The purpose of this pilot-study was to evaluate the applicability of a screening protocol for the detection of inborn errors of metabolism (IEM) in high-risk patients. The protocol was applied in 65 patients referred to the Medical Genetics Laboratory of the University Hospital Professor Edgard Santos due to the suspicion of an IEM. Eight of these patients (12.3 percent) displayed an abnormal result in the screening protocol. These patients, along with 22 who displayed normal results in the screening protocol but who presented clinical symptoms or signs suggestive of an IEM not detectable by the tests applied, were selected for a further diagnostic investigation. In 5 of these 30 patients (7.7 percent of the total sample) it was possible to establish the diagnosis of an specific IEM. The results indicate that the designed screening protocol was sucessfully applied, allowing the detection of affected patients in a frequency comparable to that observed in larger studies performed elsewhere. The continuation of this study and the enlargement of the sample will help to delineate the profile of IEM in northeast of Brazil and will allow the identification of a significative number of patients and families. who could benefit from the therapeutic and preventive measures available for these diseases.

Aspectos nutricionales en el trastorno por déficit de atención/hiperactividad / Nutritional aspects of attention-deficit/hyperactive disorder

Introducción. El trastorno por déficit de atención/hiperactividad (TDAH) ha recibido en los últimos años gran atenciónpor parte de las especialidades pediátricas. A pesar de los avances en el conocimiento de su etiopatogenia, fundamentalmenterelacionados con la genética y la neuroimagen, su causa última todavía se desconoce. Desarrollo. El TDAH se ha relacionadocon multitud de factores, algunos concernientes a la dieta, como algunas alergias a aditivos, la toxicidad a metales pesadosy otros tóxicos ambientales, dietas bajas en proteínas con alto contenido en carbohidratos, desequilibrios minerales, déficitde ácidos grasos esenciales y fosfolípidos, déficit de aminoácidos, trastornos de tiroides y déficit del complejo vitamínico B y fitonutrientes.Los cambios en el estilo de vida en general y en la dieta se barajan como hipótesis de numerosos trastornos y problemasde salud, pero, ¿y para el TDAH? Uno de los cambios más destacables se da en las grasas vegetales y los aceites que hoydía dominan el consumo humano, ya que están desprovistos de lípidos de la familia de los ácidos grasos esenciales omega-3, comoácido alfa-linoleico, ácido eicosapentanoico y ácido docosahexanoico. Esto se ha podido agravar al aumentar las cantidadesde omega-6 y alterar la ratio entre ambos. Conclusiones. Está bien documentado que este tipo de nutrientes desempeña unpapel importante en el desarrollo, principalmente del sistema nervioso. Este trabajo revisa el papel de los ácidos grasos esencialesen los trastornos neuropsiquiátricos en general y en el TDAH en particular(AU)

Introduction. Attention-deficit/hyperactive disorder (ADHD) has received in the past years a lot of attention fromthe paediatrician’s specialties. Even though the studies of its etiopathology have advanced, mainly the ones related withgenetics and neuroimaging, the final cause today is still unclear. Development. It has been related to many factors such asdiet, like some allergies to additives, toxicity to heavy metals and other toxic substances from the environment, due to lowprotein diets with a high carbohydrate content, unbalanced minerals, essential fatty acids and phospholipid deficit, aminoacid deficits, thyroid disorders, and vitamin B complex disorders and phytochemicals. The way our lifestyle has changed ingeneral and the diet in particular nowadays is being considered as a hypothesis for many disorders and health problems, butwhat about ADHD? One of the changes that we want to emphasize is related to vegetable fat and oils that dominate humanconsumption and the reduction income of fatty acids from the omega-3 family, including alpha-linolenic acid,eicosapentaenoic acid and docosapentaenoic acid. The fact is even worse when the amount of omega-6 increases and the ratiobetween both changes. Conclusions. It is a fact that these kinds of nutrients play an important role in the nervous systemdevelopment. In this paper the essential fatty acids in neuropsychiatric disorders in general, ADHD in particular, is reviewed(AU)

Nutrición en el paciente grave: el talón de aquiles de la terapéutica en el intensivismo / Nutrition in the critically ill: Achilles' heel in the therapeutic at the intensive care

La insuficiencia nutricional que sigue a estados de hipercatabolismo, inanición, infecciones severas y enfermedades consuntivas crónicas, entre otras, puede afectar a pacientes graves con ingesta insuficiente de nutrientes y reservas nutricionales inadecuadas. Por lo general el paciente debilitado desde el punto de vista nutricional muere por sepsis y fallo multiorgánico asociados con deficiencias de aminoácidos y nitrógeno, síntesis inadecuada de proteínas y fracaso de los mecanismos inmunes. Se realizó una revisión de la nutrición en el paciente crítico, para confeccionar una guía práctica de alimentación donde se expusieron todos los elementos a tener en cuenta en un paciente que se necesite nutrir

Dietas vegetarianas / Vegetarians diets

El vegetarianismo como estilo de vida y forma de alimentación tiene en nuestra sociedad una importante presencia. Actualmente en Europa se sitúa entre el 3 y el 8% de la población, con una tendencia ascendente. Las dietas vegetarianas se relacionan con una menor incidencia de enfermedades crónicas propias del mundo desarrollado (problemas cardiovasculares, hipertensión arterial, hipercolesterolemia, diabetes, cáncer), pero excluir alimentos de origen animal conlleva riesgos nutricionales (déficit energético, proteico, de vitamina B12 y minerales), sobre todo en períodos críticos de la vida como la infancia y la adolescencia. Se revisan los principios de esta forma de alimentación, sus beneficios y riesgos, y se establecen algunas consideraciones y recomendaciones prácticas para el pediatra de Atención Primaria con familias vegetarianas entre sus pacientes (AU)

Vegetarianism as a way of life and nourishing style has an important presence in our society. Currently in Europe they are 3 to 8 % of the population, with an increasing tendency. Vegetarian diets are related to less incidence of developed world’s chronic diseases (cardiovascular impairment, arterial hypertension, hypercholesterolemia, diabetes, cancer), but excluding animal origin foods carry some nutritional risks (energy, proteins, B12 vitamin and minerals deficit), specially in critical periods of life such as childhood and adolescence. The principles of this style of nutrition are revised, its benefits and risks, and some considerations and recommendations are established for Primary Care paediatricians counting with vegetarian families among their patients (AU)

Problemática nutricional del vegetarianismo en el embarazo, la lactancia y la edad infantil / Nutritional concerns regarding vegetarianism during pregnancy, breast-feeding and chilhood

La dieta vegetariana está siendo adoptada por un porcentaje creciente de población. En sus variedades lacto u ovolactovegetariana, el riesgo nutricional puede ser minimizado mediante una buena combinación de alimentos. Sin embargo, una dieta vegetariana estricta puede tener repercusiones negativas sobre todo en periodos de rápido crecimiento, y afectar el desarrollo físico y psicomotor. Deben controlarse de forma especial los requerimientos mínimos de ácidos grasos polinsaturados de larga cadena (PLC), hie-o, cinc y vitamina B 12 (AU)

Effects of corn feeding and protein restriction on free amino acid concentration in the rat cerebellum

To determine the effect of low protein and cornbased diets on the maturation of cerebellum, three groups of young rats were fed during a period of 6 weeks with different diets; 23 and 8 percent of protein (purina-Chow base) and a corn-based diest (8 percent protein). At the end of that period, the concentrations of free amino acids in the cerebellum was measured. Glutamic acid, glucine, glutamine and serine showed the highest values in all groups studied. Corn-based diet group showed the lowest free amino acid concentration compared to that of the control group, with a significant diminutions in the concentration of glutamic acid, lysine, tyrosine and histidine. Differences between essential and nonessential amino acids were not observed in all groups studied. Although corn-based diet did not induce specific changes as those reported in severe malnutrition, its effects on the concentration of some amino acids other than tryptophan could have some physiological correlations which need to be further studied