Enfermedades raras por patología mitocondrial debidas al déficit en coenzima Q10

La disfunción en la actividad de la mitocondria está relacionada con múltiples enfermedades crónicas asociadas con la vejez y con muchas patologías metabólicas. Entre ellas algunas enfermedades raras causadas por el déficit en la síntesis de coenzima Q10, el único componente lipídico implicado en la actividad de la cadena de transporte de electrones mitocondrial. El déficit en los niveles de este lípido está asociado con enfermedades muy graves caracterizadas esencialmente por sordera, ataxia, mialgia y disfunción renal entre otros síntomas. Hasta el momento se han identificado 12 proteínas implicadas en la síntesis de coenzima Q10 en humanos de las cuales se han identificado mutaciones que producen letalidad en homocigosis y graves problemas incluso en heterocigosis. Por otro lado, también se han encontrado deficiencias secundarias en los niveles de coenzima Q10 asociadas a mutaciones de otras proteínas mitocondriales o a la disfunción mitocondrial relacionada con el envejecimiento o enfermedades metabólicas. Esta deficiencia secundaria podría entorpecer la actividad mitocondrial no solo por enlentecer la actividad de la cadena de transporte de electrones sino por bloquear la actividad de los supercomplejos mitocondriales, recientemente asociados con ciertas patologías. Como el coenzima Q10 también cumple funciones importantes en otras membranas celulares tales como actuar como antioxidante en éstas y regular la actividad de otros antioxidantes como la vitamina E o C, así como regular procesos de señalización, la deficiencia en este lípido puede causar otras múltiples disfunciones que se agravan con la edad. Si bien el tratamiento con coenzima Q10 puede aliviar de alguna manera algunas patologías debidas a la deficiencia primaria, es muy posible que en el caso de la secundaria pueda ser un buen tratamiento de futuro aunque nunca hemos de perder de vista que se trata de una deficiencia derivada de una disfunción previa de la mitocondria.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. Departamento de Biología Celular, Genética y Fisiología Máster Oficial en Biología Celular y Molecular de la Universidad de Málag

Facing Challenges in an Aging World [9th European Congress of Biogerontology]

116 p.It is clear that the amount of people reaching old age is increasing worldwide. During last decades, the percentage of population aged more than 65 has been increasing. In fact, United Nations Organization reports indicate that the percentage of population aged more than 60 years was around a 10% in 1999 in the world but this increase will reach the 20% in 2050. Part of this effect is due to the increase lifespan of humans during last decades. It has been calculated that between 2045 and 2050 the lifespan of people aged 80 years will be around 10 years. It means that the number of nonagenarians and even centenarians will increase soon (United Nations Department of Economics and Social Affairs, World Population Ageing 2013). Currently Europe has reached a 20% of population aged more than 60 years and in 2050 this proportion will be around 30%. Taken into consi-deration the needs of this population, the sustainability of social and health systems needs to be revised. Several initiatives have been proposed to increase health and independen-cy in elderly people. Increasing healthspan in aged population is one of the most important challenges in the near future. For example, the program EIP-AHA (Europa Innovation Partnership on Active and Healthy Ageing) of the European Union pursues three main objectives involved in the increase in health span in European citizens. It is widely known that life habits deeply affect the capacity of cells, organs and tissues. Sedentary life habits and the increasing consume of saturated fatty acids is severely affecting the risk to suffer cardiovascular diseases, obesity, diabetes and metabolic diseases, all of them associated to chronic treatment during ageing. All sections (8) were also accompanied by different posters that have been associated to the different sections in this book. The reader of this book will then find a picture of the different fields included in the study of the biological ageing in different models from molecular to epidemiological aspects. I hope this information will be useful to, at least, understand how complex in the Biogerontology field and how much effort we have to do to increase longevity and, more importantly, health span during ageing

Alimentos contra el cáncer oral

El cáncer oral representa el 5% de todas las neoplasias y el 30% de los cánceres de cabeza y cuello. El porcentaje de supervivencia a los 5 años es de tan sólo el 25%, por lo que el diagnóstico y tratamiento precoces pueden salvar muchas vidas. La mayoría de los cánceres se relacionan con factores externos al organismo (tabaco, alcohol, betel, dieta y radiaciones solares, principalmente), que pueden modificarse o evitarse, es decir, prevenibles. Alrededor del 35% de los casos de cáncer están relacionados con la alimentación. Por este motivo, es importante que los profesionales de la salud informen a sus pacientes acerca de las enormes posibilidades profilácticas de la dieta. El objetivo de este trabajo de actualización bibliográfica es destacar la importancia de una alimentación saludable para la prevención del cáncer oral

Facing challenges in an ageing world

Editorial.The sponsorship of the following contributors made possible the meeting: Universidad Pablo de Olavide, Centro Andaluz de Biología del Desarrollo, Springer Publishers, International Coenzyme Q10 Association, Sociedad Española de Biología Celular, Universidad Internacional de Andalucía, Junta de Andalucía, Cien por Cien Natural, Pharma Nord Denmark, C. Viral, ThermoFisher Scientific and Cultek.Peer Reviewe

High-intensity interval training combined with vibration and dietary restriction Improves body composition and blood lipids in obese adults: a randomized trial

This study aimed to compare the effect of high-intensity interval training (HIIT) with additional whole-body vibration (WBV) on body composition and lipid profile in obese/overweight adults on a hypocaloric diet. Forty adults were randomly assigned to (a) HIIT and vibration and hypocaloric diet (HIITWBV, n ¼ 13), (b) HIIT and diet (HIIT, n ¼ 14), and (c) diet only (control [CON], n ¼ 13). High-intensity interval training WBV participants trained 3 times per week for 8 weeks (6 sets 1 minute of HIIT, cycling at 90% heart rate peak followed by 1 minute of interset vibration, at a frequency of 18 Hz increasing until 25 Hz with a peak-to- peak displacement of 4 mm. Training volume increased 1 set every 2 weeks until 10 sets). The HIIT group performed HIIT training followed by 2 minutes of passive recovery, while the CON continued with their daily activities combined with calorie restriction. Body composition (body fat and fat-free mass) and biochemical indices (glucose, total cholesterol, high-density lipoprotein cholesterol, and triglycerides) were determined. Following 8 weeks, body fat was significantly reduced by 7.5% and both tri- glycerides and total cholesterol decreased in the HIITWBV group only ( 16.5% and 11.7% respectively). This study suggests that HIIT in combination with WBV and a hypocaloric diet can improve overall lipid profile in overweight/obese individual

Spanish research groups on Economy and Management: a network analysis approach

The aim of this article is to study the evolution of the Spanish research groups on Economy and Management. Due to subject headings lists are considered to be insufficient and inflexible to describe relationship between sciences, the authors develop a method to link journals from the SSCI depending on their subjects on this thematic area. The application of social network analysis to retrieval information in a multidisciplinary database has been demonstrate as very helpful to represent interdisciplinarity in a knowledge area, in particular the Social Science Citation Index. Secondly, a network is created based on co-authorship from the Spanish articles provided on this database and represented for three periods: 1992-1996, 1997-2001 and 2002-2006. The use bibliometric indicators as main attributes of nodes in the network analysis have been helpful to identify equivalent positions, actors who show the same role within each graph

Tutela resarcitoria social en el caso Spanair: Comentario a la Sentencia del Tribunal Supremo 833/2017, de 24 de octubre

El punto de partida no puede ser otro que recordar que el Estatuto de los Trabajadores (ET) genéricamente consagra la deuda de seguridad como una de las obligaciones del empresario al establecer el derecho del trabajador «a su integridad física» [art. 4.2 d)] y a «una protección eficaz en materia de seguridad e higiene» (art. 19.1). Obligación que con mayor rigor de exigencia desarrolla la Ley de Prevención de Riesgos Laborales (LPRL), cuyos rotundos mandatos (arts. 14.2, 15.4 y 17.1) determinaron que se afirmase «que el deber de protección del empresario es incondicionado y, prácticamente, ilimitado» y que «deben adoptarse las medidas de protección que sean necesarias, cualesquiera que ellas fueran» (STS de 8 de octubre de 2001 –rec. 4403/2000–). Existiendo, pues, una deuda de seguridad por parte del empleador, ello nos sitúa en el marco de la responsabilidad contractual y del artículo 1.101 del Código Civil (CC), que impone la obligación de indemnizar los daños y perjuicios causados a los que «en el cumplimiento de sus obligaciones incurrieren en dolo, negligencia o morosidad, y los que de cualquier modo contravinieren el tenor de aquellas»

Predicting the Electronic Absorption Band Shape of Azobenzene Photoswitches

Simulations based on molecular dynamics coupled to excitation energy calculations were used to generate simulated absorption spectra for a family of halide derivatives of azobenzene, a family of photoswitch molecules with a weak absorption band around 400-600 nm and potential uses in living tissue. This is a case where using the conventional approach in theoretical spectroscopy (estimation of absorption maxima based on the vertical transition from the potential energy minimum on the ground electronic state) does not provide valid results that explain how the observed band shape extends towards the low energy region of the spectrum. The method affords a reasonable description of the main features of the low-energy UV-Vis spectra of these compounds. A bathochromic trend was detected linked to the size of the halide atom. Analysis of the excitation reveals a correlation between the energy of the molecular orbital where excitation starts and the energy of the highest occupied atomic orbital of the free halide atom. This was put to the test with a new brominated compound with good results. The energy level of the highest occupied orbital on the free halide was identified as a key factor that strongly affects the energy gap in the photoswitch. This opens the way for the design of bathochromically shifted variants of the photoswitch with possible applications

On the Computational Design of Azobenzene-Based Multi-State Photoswitches

In order to theoretically design multi-state photoswitches with specific properties, an exhaustive computational study is first carried out for an azobenzene dimer that has been recently synthesized and experimentally studied. This study allows for a full comprehension of the factors that govern the photoactivated isomerization processes of these molecules so to provide a conceptual/computational protocol that can be applied to generic multi-state photoswitches. From this knowledge a new dimer with a similar chemical design is designed and also fully characterized. Our theoretical calculations predict that the new dimer proposed is one step further in the quest for a double photoswitch, where the four metastable isomers could be selectively interconverted through the use of different irradiation sequences

Unraveling the molecular details of the complete mechanism that governs the synthesis of prostaglandin G2 catalyzed by cyclooxygenase-2

This is an open access article published under an ACS AuthorChoice License. See Standard ACS AuthorChoice/Editors' Choice Usage AgreementCyclooxygenase-2 (COX-2) is the key enzyme involved in the synthesis pathway of prostaglandin G₂ (PGG₂) by transformation of arachidonic acid (AA). Although COX-₂ is one of the principal pharmacological targets by the implication of PGG₂2 in several human diseases, the classical all-radical mechanism proposed for COX-₂ catalysis has never been validated at the molecular level. Herein, molecular dynamics simulations and quantum mechanics/molecular mechanics (QM/MM) calculations were combined to analyze the six steps of the all-radical mechanism. The results show that O₂ addition on C₁₁ of AA can follow an antarafacial or suprafacial approach with respect to tyrosine 385, but only the antarafacial addition leads to the product with the correct 11R stereochemistry as established in the mechanistic proposal. Moreover, only the reaction pathway coming from the antarafacial intermediate describes a viable 8,12-cyclization to form the prostaglandin-like bicyclo endoperoxide that finally leads, by kinetic control, to PGG₂ with the 15S stereochemistry found experimentally. The formation of the more stable trans ring isomer of natural PGG₂ in an enzymatic environment is also explained. Our molecular analysis shows how COX-2 uses its relatively narrow channel in the active site to restrain certain conformational changes of AA and of the reaction intermediates, so that the PGG2 enzymatic synthesis turns out to be highly regiospecific and stereospecific. A more recent 10-step carbocation-based mechanistic proposal has been discarded