Actualización clínica del síndrome metabólico

Metabolic syndrome has been defined as a global issue since it affects a lot of people. Numerous factors are involved in metabolic syndrome development. It has been described that metabolic syndrome has negative consequences on health. Consequently, a lot of treatments have been proposed to palliate it such as drugs, surgery or life style changes where nutritional habits have shown to be an important point in its management. The current study reviews the literature existing about the actual epidemiology of metabolic syndrome, the components involucrate in its appearance and progression, the clinical consequences of metabolic syndrome and the nutritional strategies reported in its remission. A bibliographic search in PubMed and Medline was performed to identify eligible studies. Authors obtained that metabolic syndrome is present in population from developed and undeveloped areas in a huge scale. Environmental and genetic elements are involucrate in metabolic syndrome development. Metabolic syndrome exponentially increased risk of cardiovascular disease, some types of cancers, diabetes mellitus type 2, sleep disturbances, etc. Nutritional treatments play a crucial role in metabolic syndrome prevention, treatment and recovery.El síndrome metabólico ha sido identificado como un problema global debido a que afecta a una gran cantidad de personas. Numerosos factores están involucrados en su aparición y desarrollo. Se ha descrito que el síndrome metabólico tiene consecuencias negativas en la salud. Consecuentemente, numerosos tratamientos han sido propuestos para paliar el síndrome metabólico como fármacos, cirugías o cambios en el estilo de vida donde los hábitos nutricionales serían un importante elemento en el control del síndrome metabólico. El presente estudio revisa la literatura existente sobre la epidemiología del síndrome metabólico, los componentes involucrados en su aparición y progresión, las consecuencias clínicas del mismo y las estrategias nutricionales utilizadas en su remisión. Se llevó a cabo una búsqueda bibliográfica en Pubmed y Medline con objeto de identificar estudios elegibles. Se obtuvo que el síndrome metabólico está presente en población tanto de países desarrollados como de países en vías de desarrollo. Factores medioambientales y genéticos están involucrados en su desarrollo. Su padecimiento incrementa de forma exponencial el riesgo de padecer enfermedad cardiovascular, determinados tipos de cánceres, diabetes mellitus tipo 2, anomalías del sueño, etc. Las estrategias nutricionales jugarían un papel esencial en la prevención, tratamiento y recuperación del síndrome metabólico

From the beginning to the end: the story of the mitochondrial disease associated with the ADCK2 gene, going through CoQ10 supplementation and caloric restriction

Programa de Doctorado en Biotecnología, Ingeniería y Tecnología QuímicaLínea de Investigación: Biotecnología, Biomedicina y Ciencias de la SaludClave Programa: DBICódigo Línea: 110Mitochondria are enclosed membrane organelles that burn nutrient molecules to produce adenosine triphosphate (ATP) by oxidative phosphorylation (OXPHOS) and are present in cells of animals, plants and fungi. Mitochondria also carry out other important processes such as urea cycle, fatty acids ß-oxidation and the Krebs cycle. A crucial element in mitochondrial function is Coenzyme Q10 (CoQ10) is a unique lipid endogenously produced, a crucial element in the mitochondrial electron transport chain (ETC) and antioxidant found in all cell membranes. The main function of CoQ is to send electrons that receive from complex I and complex II to complex III at the ETC resulting in ATP production. But, CoQ10 could be also reduced by different hydrogenases, showing the high number of pathways where CoQ10 participates. CoQ is composed of a benzoquinone ring and a polyisoprenoid chain which inserts CoQ into the phospholipid bilayer. CoQ is produced at mitochondria by a nuclear-encoded CoQ proteins cluster. The biosynthetic pathway is not clear yet and it is carried by at least 13 proteins. The ADCK2 gene has been recently associated with CoQ pool regulation and fatty acids metabolism. ADCK2 haploinsufficiency in humans is related to mitochondrial myopathy, muscle wasting, reduction of CoQ levels and impairment of fatty acids ß-oxidation. We developed a heterozygous Adck2 knockout mouse that reproduces the mutation. The four chapters of the thesis are focused on this mutant mouse model to better understand the mitochondrial syndrome associated with the ADCK2 gene. Firstly, we present a detailed study of the embryonic development of mutant mice to elucidate if damages could start during this stage. We analysed the transcriptomic profile during early and late development, finding tissue-specific deregulation during late embryonic development. Heterozygous Adck2 knockout mouse embryos presented an abnormal somatogenesis analysed with two different Myogenic Regulatory Factors. We examined a prenatal CoQ10 administration obtaining that mutant embryos under CoQ10 supplementation showed a reversion to wild type profile in the transcriptomic profile and skeletal muscle formation. Secondly, we decided to focus on postnatal myogenesis based on the results from the first chapter. For that purpose, adult muscle stem cells were isolated from wild type and mutant mice under standard conditions and under CoQ10 administration and differentiated. Mutant cells presented a defect in differentiation that leads to smaller myotubes and delayed differentiation that was associated with a reduction in oxygen consumption and fatty acids ß-oxidation. Mutant cells isolated from mutant mice supplemented with CoQ10 showed an improvement in differentiation and also on mitochondrial respiration. An in vivo analysis of satellite cells was performed to support our in vitro data inducing muscle damage and examining skeletal muscle regeneration. Mutant mice presented an impaired skeletal muscle regeneration and were more susceptible to muscle damage, CoQ10 administration improved skeletal muscle regeneration. We performed the experiments in cells from young and old mice, the differences were bigger in cells from old mice suggesting that ageing could act as a modulator in the phenotype of mutant mice. As summary of this chapter, mutant mice suffer a defect in postnatal myogenesis, particularly during myogenic differentiation. We decided to study the decline associated with the ageing process in our mutant mice in the third chapter. Old mutant mice presented a decrease in myofiber size and showed different myofiber composition while old mutant mice longitudinally supplemented with CoQ10 exhibited a myofiber size and composition more similar to wild type mice. Skeletal muscle performance was assessed through ageing, mutant mice presented a more severe decline in physical capacity compared to wild type mice. CoQ10 administration ameliorated skeletal muscle function decline in mutant mice. We developed a method to examine respiration in isolated mitochondria from skeletal muscle. Mitochondria from skeletal muscle of mutant mice presented a reduction in oxygen consumption while isolated mitochondria from mutant mice on CoQ10 administration showed an increase in respiration with both glucose and fatty acids substrates. Heterozygous Adck2 knockout mice suffer a more severe decline through ageing and CoQ10 administration could improve the phenotype of mutant mice. Finally, we studied the metabolic modulation of the phenotype of mutant mice by caloric restriction (CR). CR restored glucose and insulin homeostasis in mutant mice to wild type levels. CR modulated skeletal muscle metabolic profile, resulting in a more oxidative myofiber composition and increased oxygen consumption using glucose and fatty acids substrates in isolated mitochondria. To further explore the effect of CR on muscle stem cells, satellite cells were cultured with serum obtained from mice on ab libitum and CR. Mutant cells cultivated with CR serum showed an increase in differentiation and oxygen consumption. CR intervention improved age-associated decline and defects associated with Adck2 haploinsufficiency. The four chapters of the project are focus on the study of Adck2 mutant mice but under different conditions and methods including CoQ10 administration or under CR condition, resulting in a completed phenotype analysis of the model studied.Universidad Pablo de Olavide de Sevilla. Departamento de Fisiología, Anatomía y Biología Celula

Roll of Mrf4 gen in homeostasis of adult skeletal muscle.

Myogenesis is the process that controls skeletal muscle growth during embryonic and postnatal development, and it is orchestrated by a family of four transcription factors (TFs) known as MRFs (Myogenic Regulatory Factors)(1). Our group is working on the function of two of these genes: Mrf4 and Myf5. We and others have established a link between MRFs function and muscle atrophy/hypertrophy (2).   Mrf4 is the only MRF highly expressed in all adult skeletal muscles, but a complete understanding of its function is lacking as previous KOs models affect Myf5 expression in cis (3). Recently, our group has generated two new KO alleles using CRISPR technology (Mrf4 L1/L1 and Mrf4 L2/L2). Preliminary data shows that both alleles develop mild muscle hypertrophy, without affecting Myf5 expression in cis. Experiments in vivo indicate that the two alleles have alterations in muscle metabolism.   This project is focused on elucidating how this TF is involved in muscle growth, function, and homeostasis. Furthermore, as adult satellite cells emerge from embryonic founder cells in which Mrf4 expression was activated, we are also studying Satellite Cell biology and function in the absence of Mrf4.   Surprisingly, we have identified important phenotypic differences between the two alleles; one hypothesis is that one or both may generate a small peptide that modifies the phenotype.   Methods: We dissected the extensor digitorium longus muscle, isolated myofibers from young (3 months) and old (24 months), WT and Mrf4-/- mice, and divided these in three groups: 1- Fibers were fixed and permeabilised for immunostaining with Pax7 antibody to study the myofiber size and content in satellite cells/nuclei; 2- Fibers were plated for bioenergetic analysis using a XF24e Seahorse Analyzer that provides oxygen consumption rate as indicator of mitochondrial respiration as a proxy for metabolic function; and 3- Fibers were plated in proliferation medium to allow their associated Satellite Cells to abandon the niche, migrate and proliferate, and we studied parameters of Satellite Cell proliferation and differentiation.   In order to study the potential effect of small peptides generated by one or both alleles, we generated overexpression plasmids containing the sequences of interest. C2C12 myogenic cells were co-transfected with a GFP-expression vector using the electroporator BTX Gemini and then selected to determine if there were significant differences in proliferation and differentiatio

La suplementación con cafeína mejora el salto en contramovimiento en jugadores jóvenes de fútbol: estudio piloto

Introduction: The objective of this study was to analyze the effect of caffeine ingestion in soccer performance, particularly in the countermovement jump test (CMJ).Material and methods: A total of 17 players from a U-19 amateur Spanish team participated in this pilot study. A double-blind placebo-controlled randomized experimental design was used in 2 different sessions (1.5 hour per session) separated by 1 week. CMJ was collected at the beginning and at the end of sessions; Rating of Perceived Exertion (RPE) was recorded. Players ingested caffeine or placebo at the beginning of session (minute 0 of session), providing a total of 4 mg of caffeine or a placebo per kg of body mass. Side effects from caffeine and placebo ingestions were analyzed. The effect sizes (ES) were calculated using values for Cohen’s and Quantitative differences were assessed qualitatively (QA).Results: The jump height with caffeine supplementation at the beginning of training was 37.03 (±3.87) cm and at the end was 39.35 (±4.05) cm, obtaining significant improvements (p<0.05; ES: 0.56; QA: 99/1/0). Significant differences on CMJ at the end of the training session between caffeine and placebo groups were observed (39.35 [±4.05] cm vs. 36.85 [±3.15] cm; p<0.05; ES: 0.65; QA: 0/1/99). Significant differences on RPE between groups were observed. A non-significant tendency to suffer more side effects with caffeine ingestion was obtained.Conclusions: This study shows how the ingestion of 4 mg of caffeine per kg of body mass could be an ergogenic aid to improve soccer performance. However, further studies with bigger soccer players sample would be necessary to refute the present results.Introducción: El objetivo del presente estudio fue analizar el efecto de la ingestión de cafeína en el rendimiento en fútbol, específicamente en el test de salto en contramovimiento (CMJ).Materiales y métodos: 17 jugadores de la categoría Sub-19 de un equipo amateur español participaron en el estudio piloto. Se siguió un diseño a doble ciego, placebo-control, aleatorizado en 2 entrenamientos (1,5 horas/sesión) separados por 1 semana. El CMJ se recogió al inicio y al final de las sesiones, la tasa de esfuerzo percibido (RPE) fue recogida. Los jugadores tomaron cafeína o placebo al inicio del entrenamiento (minuto 0), proveyendo 4 mg/kg de masa corporal de cafeína o placebo. Se analizaron los efectos secundarios provenientes de la cafeína y del placebo. Los tamaños de efecto (ES) se calcularon utilizando valores para Cohen y las diferencias cuantitativas se evaluaron cualitativamente (QA).Resultados: La altura del salto media cuando se ingirió cafeína fue 37,03 (±3,87) cm al inicio y 39,35 (±4,05) cm al final del entrenamiento, obteniendo una mejora significativa (p<0,05; ES: 0,56; QA: 99/1/0). Se observaron diferencias significativas en el CMJ al final de los entrenamientos entre la ingestión con cafeína y placebo (39,35 [±4,05] cm vs. 36,85 [±3,15] cm; p<0,05; ES: 0,65; QA: +0/1/99). Se obtuvieron diferencias significativas en la RPE entre los grupos. Se observó una tendencia no significativa a sufrir más efectos secundarios cuando se ingirió cafeína.Conclusiones: Este estudio muestra como la ingestión de 4 mg/kg de cafeína podría ser una ayuda ergogénica para mejorar el rendimiento en fútbol. Se requieren más estudios con mayor tamaño muestral para confirmar los resultados

LUMBAR DISK HERNIATION: EVALUATION OF MEDICAL CARE AND PAIN MANAGEMENT AT THE SPECIALTIES HOSPITAL CREHVITAL AMBATO-ECUADOR: RETROSPECTIVE, CROSS-SECTIONAL STUDY, AND ASSESSMENT OF TWO CLINICAL CASES

Objectives: The objective of the study was to assess medical care and pain management of 237 lumbar disk herniation cases treated from 2011 to 2021 in the Specialties Hospital CREHVITAL, Ambato-Ecuador, and to provide a set of standards for appropriate management. Methods: Retrospective, cross-sectional analysis of archives, and registries of patient’s data provided by the Specialties Hospital CREHVITAL, Ambato-Ecuador. Participants: A total of 237 patients with lumbar disk herniation received medical services from 2011 to 2021; outcome measures were: Pain management, patient characteristics, surgical procedures, and medication after surgery. Results: The 40–50 age range had the highest prevalence of lumbar disk herniation and a higher percentage of the pathology in men (66%) than in women. Of the 237 patients, magnetic resonance imaging (MRI) showed the highest lumbar disk herniation of the L4–L5 (101 men and 20 women), followed by herniation of the L5–S1 (59 men and 51 women). Two types of surgeries were performed: Classical surgery on 157 patients and microsurgery on 80 patients. The average period before receiving treatment was 1.5 years of maintaining back pain, and the early post-operative management consisted of patients receiving diclofenac, ketorolac, and ceftriaxone. Analgesics were used in 73.43% of patients. All cases required strict control, follow-up, and post-operative check-ups. Conclusion: This study provides essential and conclusive evidence and information on treated cases of lumbar disk herniation and its incidence in the medical field

Pico de crecimiento y masa muscular en jugadores jóvenes de fútbol

Introduction: It has been reported that peak height velocity could be an important period in body development in athletes. The objective was to examine the peak height velocity and maturity offset in young soccer players and analyze anthropometrical measures relate with body development. Material and Methods: Fifty-eight male young soccer players were studied. They were categorized in three diverse age categories, Under-19 (post-peak height velocity), Under-16 (on peak height velocity) and Under-14 (pre-peak height velocity) years old. Height, sitting height, weight, girths and skinfolds were measured to determine peak height velocity, maturity offset and body components. Descriptive statistics means (Standard Deviation) were calculated. One-way ANOVA analyses and Pearson correlations were determined. The level of significance was set at p<0.05. Results: The mean height and weight values were 167.63 (10.52) cm and 60.12 (12.43) kg, the medium fat mass was 13.49 (3.65)%. The average muscular transverse areas for arm, thigh and calf were 41.70 (10.82) cm2, 154.87 (38.02) cm2 and 85.76 (17.67) cm2 respectably. The average PHV was 13.97 (0.53) years and the median maturity offset was 1.00 (1.92) years. Significant differences were found among the three age categories analyzed for the anthropometrical elements and for the maturity offset. Significant correlations between maturity offset and anthropometrical components were obtained. Conclusions: In agreement with previous studies, increases on anthropometrical components and muscle areas were reported after the peak velocity. Consequently, peak height velocity and maturity offset should be considered in young soccer players’ management.Introducción: Se ha observado que el pico de crecimiento podría ser un período importante en el desarrollo de deportistas. Objetivo: Determinar el pico de crecimiento y el estado madurativo en jugadores jóvenes de fútbol y analizar medidas antropométricas relacionadas con el desarrollo corporal. Material y Métodos: Cincuenta y ocho jugadores se clasificaron en 3 categorías de edad diferentes, Sub-19 (post-pico de crecimiento), Sub-16 (en el pico) y Sub-14 (pre-pico). Se midieron la altura, la altura sentado, el peso, perímetros y pliegues para determinar el pico de crecimiento, el estado madurativo y los componentes corporales. Métodos estadísticos descriptivos (Desviación Estándar), análisis ANOVA de una vía y correlaciones de Pearson fueron calculados. El nivel de significación se fijó en p<0,05. Resultados: La altura y el peso medios fueron de 167,63 (10,52) cm y 60,12 (12,43) kg, la grasa corporal media fue 13,49 (3,65)%. La masa muscular transversal del brazo, muslo y pantorrilla fueron 41,70 (10,82) cm2, 154,87 (38,02) cm2 y 85,76 (17,67) cm2. El pico de crecimiento y el estado madurativo medios fueron 13,97 (0,53) y 1,00 (1,92) años. Se encontraron diferencias significativas entre las categorías analizadas para los parámetros antropométricos y el estado madurativo. Se obtuvieron correlaciones entre el estado madurativo y los componentes antropométricos. Conclusiones: Se reportaron incrementos en componentes antropométricos y en las áreas musculares tras el pico de crecimiento. Consecuentemente, el pico de crecimiento y el estado madurativos deberían ser tenidos en cuenta en el manejo de deportistas jóvenes

Efectos del Programa de Mejoramiento Integral de Barrios sobre el valor del suelo y del área construida. Un piloto en Bosa Occidental

El propósito de este documento es evaluar el programa de Mejoramiento Integral de Barrios –PMIB-, frente al incremento en el valor del suelo y el área construida en las zonas intervenidas, en el sector de Bosa Occidental; programa que es implementado por la Secretaría Distrital del Hábitat (SDHT).Documento publicado en este sitio por autorización de la SD

Calorie restriction rescues mitochondrial dysfunction in Adck2-Deficient skeletal muscle

ADCK2 haploinsufficiency-mediated mitochondrial coenzyme Q deficiency in skeletal muscle causes mitochondrial myopathy associated with defects in beta-oxidation of fatty acids, aged-matched metabolic reprogramming, and defective physical performance. Calorie restriction has proven to increase lifespan and delay the onset of chronic diseases associated to aging. To study the possible treatment by food deprivation, heterozygous Adck2 knockout mice were fed under 40% calorie restriction (CR) and the phenotype was followed for 7 months. The overall glucose and fatty acids metabolism in muscle was restored in mutant mice to WT levels after CR. CR modulated the skeletal muscle metabolic profile of mutant mice, partially rescuing the profile of WT animals. The analysis of mitochondria isolated from skeletal muscle demonstrated that CR increased both CoQ levels and oxygen consumption rate (OCR) based on both glucose and fatty acids substrates, along with mitochondrial mass. The elevated aerobic metabolism fits with an increase of type IIa fibers, and a reduction of type IIx in mutant muscles, reaching WT levels. To further explore the effect of CR over muscle stem cells, satellite cells were isolated and induced to differentiate in culture media containing serum from animals in either ad libitum or CR diets for 72 h. Mutant cells showed slower differentiation alongside with decreased oxygen consumption. In vitro differentiation of mutant cells was increased under CR serum reaching levels of WT isolated cells, recovering respiration measured by OCR and partially beta-oxidation of fatty acids. The overall increase of skeletal muscle bioenergetics following CR intervention is paralleled with a physical activity improvement, with some increases in two and four limbs strength tests, and weights strength test. Running wheel activity was also partially improved in mutant mice under CR. These results demonstrate that CR intervention, which has been shown to improve age-associated physical and metabolic decline in WT mice, also recovers the defective aerobic metabolism and differentiation of skeletal muscle in mice caused by ADCK2 haploinsufficiency.This work was supported by Junta de Andalucía grant BIO-177, the Instituto de Salud Carlos III FIS grant FIS PI20/00541, CIBERER (U729)-ISCIII, the FEDER Funding Program from the European Union and the Spanish Ministry of Science, Innovation and Universities grant RED2018-102576-T. This work was supported by the Spanish Ministry of Education, Culture and Sports through fellowship FPU16/03264 to JH-C, and the Association Française contre les Myopathies (AFM) through fellowship grant #22450 to CV-G. This work was funded in part by the Intramural Research Program of the National Institute on Aging, NIH. This research was also supported by the Instituto de Salud Carlos III (PI19/01310) (Co-funded by the European Union) and by the Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR) (2017: SGR 1428) and the CERCA

Secondary CoQ10 deficiency, bioenergetics unbalance in disease and aging

Coenzyme Q10 (CoQ10) deficiency is a rare disease characterized by a decreased accumulation of CoQ10 in cell membranes. Considering that CoQ10 synthesis and most of its functions are carried out in mitochondria, CoQ10 deficiency cases are usually considered a mitochondrial disease. A relevant feature of CoQ10 deficiency is that it is the only mitochondrial disease with a successful therapy available, the CoQ10 supplementation. Defects in components of the synthesis machinery caused by mutations in COQ genes generate the primary deficiency of CoQ10. Mutations in genes that are not directly related to the synthesis machinery cause secondary deficiency. Cases of CoQ10 deficiency without genetic origin are also considered a secondary deficiency. Both types of deficiency can lead to similar clinical manifestations, but the knowledge about primary deficiency is deeper than secondary. However, secondary deficiency cases may be underestimated since many of their clinical manifestations are shared with other pathologies. This review shows the current state of secondary CoQ10 deficiency, which could be even more relevant than primary deficiency for clinical activity. The analysis covers the fundamental features of CoQ10 deficiency, which are necessary to understand the biological and clinical differences between primary and secondary CoQ10 deficiencies. Further, a more in-depth analysis of CoQ10 secondary deficiency was undertaken to consider its origins, introduce a new way of classification, and include aging as a form of secondary deficiency.Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía, Grant/Award Numbers: UPO-1259581, UPO-126247, UPO-1265673; Instituto de Salud Carlos III, Grant/Award Number: PI17/01286; Ministerio de Educación, Cultura y Deporte, Grant/Award Numbers: FPU14/04873, FPU16/0326

Aplicación móvil para la corrección automática de tests y encuestas con visión artificial

Memoria ID-197. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2018-2019