Colesterol y prevención de la enfermedad cardiovascular desde la edad pediátrica

El colesterol no es el único pero si un relevante factor de riesgo en el desarrollo de enfermedad cardiovascular desde la infancia (PECVI). Las bases más importantes del interés de PECVI son: 1- la presencia demostrada de lesión histológica arterial desde el 3-5 año de vida 2- la relación de estas con la presencia de uno o más factores de riesgo y 3- que la mayoría de los factores de riesgo están presentes desde la infancia y estos se proyectan hacia la época adulta.Kolesterola arrisku faktore nabarmena da, nahiz eta ez bakarra, haurtzarotiko gaixotasun kar- diobaskularraren garapenean (PECVI). PECVI horren interes oinarri garrantzitsuenak hauek dira: 1) 3. edo 5. bizitza urtetik lesio histologiko arterialaren presentzia frogatua; 2) horiek arrisku faktore baten edo gehiagoren presentziarekin lotua izatea; 3) arrisku faktore gehienak haurtzarotik presente izatea eta horiek helduarora proiektatzea.Le cholestérol est un important facteur de risque, bien qu'il ne soit pas le seul, dans le développement d'une maladie cardiovasculaire depuis l'enfance (PECVI). Les bases les plus importantes de l'intérêt de PECVI sont: 1- la présence démontrée de lésions histologiques artérielles à partir de 3-5 ans de vie; 2- leur relation avec la présence d'un ou de plusieurs facteurs de risque et 3- que la plus grande partie des facteurs de risque sont présents depuis l'enfance et qu'ils se projettent vers l'époque adulte.Cholesterol is not the only factor, that is a relevant factor of risk in the development of cardiovascular ailments as from childhood (PECVI). The most important grounds for interest of PECVI are: 1- that demonstrated presence of artery histological injury as from the 3rd - 5th year of life 2- the relation thereof with the presence of one or more of factors of risk and 3- that the majority of risk factors are at present as from childhood and projected towards adult life

Estudios lipídico-nutricionales y genéticos para la prevención de deficiencias neurosensoriales del niño y degenerativas del adulto. Premio Reina Sofía 2002 de Prevención de Deficiencias

Se describen tres líneas de investigación: lipídico-perinatal, nutricional-metabólica y metabólico-genética desarrolladas como Investigador Principal a lo largo de los últimos 25 años en la Unidad de Metabolismo del Departamento de Pediatría del Hospital de Cruces, de Bilbao. Las tres líneas convergen en un objetivo común, la prevención de deficiencias. Estas deficiencias pueden ser tanto neurosensoriales inmediatas en el propio niño, como futuras en la época adulta: enfermedad cardiovascular, diabetes, cáncer. De cada línea de investigación se describen tres apartados definidos: a) descripción global de los estudios, b) indicios de calidad de los mismos y c) logros alcanzados

A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction

Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acid­induced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5­dihydroxybenzoic acid to a range of 2,5­substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholine­induced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF­2 and H2DCF­DA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RT­PCR and western blotting were utilized to measure Akt, eNOS, Nrf­2, NQO­1 and HO­1 expression. Results: Ex vivo endothelium­dependent relaxation was significantly improved by the glycomimetics under palmitate­induced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitate­induced oxidative stress and enhanced NO production. We demonstrate that the protective effects of pre­incubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROS­induced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease

Fatty acid composition of skeletal muscle and adipose tissue in Spanish infants and children

There is a relationship between the fatty acid profile in skeletal muscle phospholipids and peripheral resistance to insulin in adults, but similar data have not been reported in infancy and childhood. The objective of this study was to investigate the fatty acid composition of skeletal muscle and adipose tissue across the paediatric age range. The fatty acid profile of skeletal muscle phospholipids and adipose tissue triacylglycerols was analysed in ninety-three healthy Spanish infants and children distributed into four groups: group 1 (0 to < 2 years, n 10); group 2 (2 to < 5 years, n 41); group 3 (5 to < 10 years, n 24); group 4 (10 to 15 years, n 18). In skeletal muscle phospholipids, oleic acid (18: 1n-9cis) content decreased significantly whereas that of linoleic (18: 2n-6) acid increased significantly with age (P for trend < 0.01). In adipose tissue, the contents of triacylglycerol and linoleic acid increased significantly across the paediatric age range (P for trend < 0.01), whereas dihomo-gamma-linolenic (20: 3n-6) and arachidonic (20: 4n-6) showed significant differences between groups. The variations in fatty acid composition observed with age indicated an imbalance in dietary n-3/n-6 long-chain PUFA

Suggested guidelines for the diagnosis and management of urea cycle disorders

Urea cycle disorders (UCDs) are inborn errors of ammonia detoxification/arginine synthesis due to defects affecting the catalysts of the Krebs-Henseleit cycle (five core enzymes, one activating enzyme and one mitochondrial ornithine/citrulline antiporter) with an estimated incidence of 1:8.000. Patients present with hyperammonemia either shortly after birth (~50%) or, later at any age, leading to death or to severe neurological handicap in many survivors. Despite the existence of effective therapy with alternative pathway therapy and liver transplantation, outcomes remain poor. This may be related to underrecognition and delayed diagnosis due to the nonspecific clinical presentation and insufficient awareness of health care professionals because of disease rarity. These guidelines aim at providing a trans-European consensus to: guide practitioners, set standards of care and help awareness campaigns. To achieve these goals, the guidelines were developed using a Delphi methodology, by having professionals on UCDs across seven European countries to gather all the existing evidence, score it according to the SIGN evidence level system and draw a series of statements supported by an associated level of evidence. The guidelines were revised by external specialist consultants, unrelated authorities in the field of UCDs and practicing pediatricians in training. Although the evidence degree did hardly ever exceed level C (evidence from non-analytical studies like case reports and series), it was sufficient to guide practice on both acute and chronic presentations, address diagnosis, management, monitoring, outcomes, and psychosocial and ethical issues. Also, it identified knowledge voids that must be filled by future research. We believe these guidelines will help to: harmonise practice, set common standards and spread good practices with a positive impact on the outcomes of UCD patients