Evolution and treatment of vitamin B12 deficiency as a risk factor for (cognitive and functional) neurodegenerative diseases in institutionalized elderly = Evolución y tratamiento de la deficiencia de vitamina B12 como factor de riesgo de enfermedades neurodegenerativas (cognitivas y funcionales) en las personas mayores institucionalizadas.

Prevalence of vitamin B12 deficiency is very common in elderly people and can reach values as high as 40.5% of the population. It can be the result of the interaction among several factors. Vitamin B12 deficiencies have been associated with neurological, cognitive deterioration, haematological abnormalities and cardiovascular diseases that have an important influence on the health of the elderly and their quality of life. It is necessary to approach the problems arisen from the lack of data relative to them. The main objective of this thesis was to analyse the evolution of vitamin B12 status and related parameters, lipid and haematological profiles and their relationship to health risk factors, and to functional and cognitive status over one year and to determine the effect of an oral supplementation of 500 μg of cyanocobalamin for a short period of 28 days. An additional objective was to analyze the possible effects of medicine intakes on vitamin B status. Three studies were performed: a) a one year longitudinal follow-up with four measure points; b) an intervention study providing an oral liquid supplement of 500 μg of cyanocobalamin for a 28 days period; and c) analysis of the possible effect of medication intake on vitamin B status using the ATC classification of medicines. The participants for these studies were recruited from nursing homes for the elderly in the Region of Madrid. Sixty elders (mean age 84 _ 7y, 19 men and 41 women) were recruited for Study I and 64 elders (mean age 82 _ 7y, 24 men and 40 women) for Study II. For Study III, baseline data from the initially recruited participants of the first two studies were used. An informed consent was obtained from all participants or their mentors. The studies were approved by the Ethical Committee of the University of Granada. Blood samples were obtained at each examination date and were analyzed for serum cobalamin, holoTC, serum and RBC folate and total homocysteine according to laboratory standard procedures. The haematological parameters analyzed were haematocrit, haemoglobin and MCV. For the lipid profile TG, total cholesterol, LDL- and HDLcholesterol were analyzed. Anthropometric measures (BMI, skinfolds [triceps and subscapular], waist girth and waist to hip ratio), functional tests (hand grip, arm and leg strength tests, static balance) and MMSE were obtained or administered by trained personal. The vitamin B12 supplement of Study II was administered with breakfast and the medication intake was taken from the residents’ anamnesis. Data were analyzed by parametric and non-parametric statistics depending on the obtained data. Comparisons were done using the appropriate ANOVAs or non-parametric tests. Pearsons’ partial correlations with the variable “time” as control were used to define the association of the analyzed parameters. XIII The results showed that: A) Over one year, in relationship to vitamin B status, serum cobalamin decreased, serum folate and mean corpuscular volumen increased significantly and total homocysteine concentrations were stable. Regarding blood lipid profile, triglycerides increased and HDL-cholesterol decreased significantly. Regarding selected anthropometric measurements, waist circumference increased significantly. No significant changes were observed for the rest of parameters. B) Prevalence of hyperhomocysteinemia was high in the elderly studied, ranging from 60% to 90 % over the year depending on the cut-off used for the classification. LDL-cholesterol values were high, especially among women, and showed a tendency to increase over the year. Results of the balance test showed a deficiency and a tendency to decrease; this indicates that the population studied is at high risk for falls. Lower extremity muscular function was deficient and showed a tendency to decrease. A highly significant relationship was observed between the skinfold of the triceps and blood lipid profile. C) Low cobalamin concentrations correlated significantly with low MMSE scores in the elderly studied. No correlations were observed between vitamin B12 status and functional parameters. D) Regarding vitamin B12 status, holo-transcobalamin seems to be more sensitive for diagnosis; 5-10% of the elderly had a deficiency using serum cobalamin as a criterion, and 45-52% had a deficiency when using serum holotranscobalamin as a criterion. E) 500 μg of cyanocobalamin administered orally during 28 days significantly improved vitamin B12 status and significantly decreased total homocysteine concentrations in institutionalized elderly. No effect of the intervention was observed on functional and cognitive parameters. F) The relative change (%) of improvement of vitamin B12 status was higher when using serum holo-transcobalamin as a criterion than serum cobalamin. G) Antiaenemic drug intake normalized cobalamin, urologic drugs and corticosteroids serum folate, and psychoanaleptics holo-transcobalamin levels. Drugs treating pulmonary obstruction increased total homocysteine concentration significantly. H) The daily mean drug intake was 5.1. Fiftynine percent of the elderly took medication belonging to 5 or more different ATC groups. The most prevalent were psycholeptic (53%), antiacid (53%) and antithrombotic (47%) drugs.

Contribución al estudio de propiedades ópticas en medios heterogéneos

Como contribución del estudio de medios heterogéneos, esta tesis recoge el trabajo llevado a cabo sobre modelado teórico y simulación del estudio de las propiedades ópticas de la piel y del agua del mar, como ejemplos paradigmáticos de medios heterogéneos. Se ha tomado como punto de partida el estudio de la propagación de la radiación óptica, más concretamente de la radiación láser, en un tejido biológico. La importancia de la caracterización óptica de un tejido es fundamental para manejar la interacción radiación-tejido que permite tanto el diagnóstico como la terapéutica de enfermedades y/o de disfunciones en las Ciencias de la Salud. Sin olvidar el objetivo de ofrecer una metodología de estudio, con un «enfoque ingenieril», de las propiedades ópticas en un medio heterogéneo, que no tiene por qué ser exclusivamente el tejido biológico. Como consecuencia de lo anterior y de la importancia que tiene el agua dentro de los tejidos biológicos se decide estudiar en otro capítulo las propiedades ópticas del agua dentro de un entorno heterogéneo como es el agua del mar. La selección del agua del mar, como objeto de estudio adicional, es motivada, principalmente, porque se trata de un sistema heterogéneo fácilmente descriptible en cada uno de sus elementos y permite evaluar una amplia bibliografía. Además se considera que los avances que han tenido lugar en los últimos años en las tecnologías fotónicas van a permitir su uso en los métodos experimentales de análisis de las aguas. El conocimiento de sus propiedades ópticas permite caracterizar los diferentes tipos de aguas de acuerdo con sus compuestos, así como poder identificar su presencia. Todo ello abre un amplio abanico de aplicaciones. En esta tesis doctoral, se ha conseguido de manera general: • Realizar un estudio del estado del arte del conocimiento de las propiedades ópticas de la piel y la identificación de sus elementos dispersores de la luz. • Establecer una metodología de estudio que nos permita obtener datos sobre posibles efectos de la radiación en los tejidos biológicos. •Usar distintas herramientas informáticas para simular el transporte de la radiación laser en tejidos biológicos. • Realizar experimentos mediante simulación de láser, tejidos biológicos y detectores. • Comparar los resultados conocidos experimentalmente con los simulados. • Estudiar los instrumentos de medida de la respuesta a la propagación de radiación laser en tejidos anisotrópicos. • Obtener resultados originales para el diagnóstico y tratamiento de pieles, considerando diferente razas y como alteración posible en la piel, se ha estudiado la presencia del basalioma. • Aplicación de la metodología de estudio realizada en la piel a la simulación de agua de mar. • Obtener resultados originales de simulación y análisis de cantidad de fitoplancton en agua; con el objetivo de facilitar la caracterización de diferentes tipos de aguas. La tesis doctoral se articula en 6 capítulos y 3 anexos perfectamente diferenciados con su propia bibliografía en cada uno de ellos. El primer capítulo está centrado en la problemática del difícil estudio y caracterización de los medios heterogéneos debidos a su comportamiento no homogéneo y anisotrópico ante las radiaciones ópticas. Así pues, presentaremos una breve introducción al comportamiento tanto de los tejidos como del océano ante radiaciones ópticas y definiremos sus principales propiedades: la absorción, el scattering, la anisotropía y los coeficientes de reflexión. Como continuación, un segundo capítulo trata de acercarnos a la resolución del problema de cómo caracterizar las propiedades ópticas descritas en el primer capítulo. Para ello, primero se introducen los modelos teóricos, en segundo lugar los métodos de simulación más empleados y, por último, enumerar las principales técnicas de medida de la propagación de la luz en los tejidos vivos. El tercer capítulo, centrado en la piel y sus propiedades, intenta realizar una síntesis de lo que se conoce sobre el comportamiento de la piel frente a la propagación de las radiaciones ópticas. Se estudian sus elementos constituyentes y los distintos tipos de pieles. Por último se describe un ejemplo de aplicación más inmediata que se beneficia de este conocimiento. Sabemos que el porcentaje de agua en el cuerpo humano es muy elevado, en concreto en la piel se considera de aproximadamente un 70%. Es obvio, por tanto, que conocer cómo afecta el agua en la propagación de una radiación óptica facilitaría el disponer de patrones de referencia; para ello, se realiza el estudio del agua del mar. En el cuarto capítulo se estudian las propiedades del agua del mar como medio heterogéneo de partículas. En este capítulo presentamos una síntesis de los elementos más significativos de dispersores en el océano, un estudio de su comportamiento individual frente a radiaciones ópticas y su contribución al océano en su conjunto. Finalmente, en el quinto capítulo se describen los resultados obtenidos en los distintos tipos de simulaciones realizadas. Las herramientas de simulación empleadas han sido las mismas tanto para el caso del estudio de la piel como para el agua del mar, por ello ambos resultados son expuestos en el mismo capítulo. En el primer caso se analizan diferentes tipos de agua oceánica, mediante la variación de las concentraciones de fitoplancton. El método empleado permite comprobar las diferencias que pueden encontrarse en la caracterización y diagnóstico de aguas. El segundo caso analizado es el de la piel; donde se estudia el comportamiento de distintos tipos de piel, se analizan para validar el método y se comprueba cómo el resultado es compatible con aplicaciones, actualmente comerciales, como la de la depilación con láser. Como resultado significativo se muestra la posible metodología a aplicar para el diagnóstico del cáncer de piel conocido como basalioma. Finalmente presentamos un capítulo dedicado a los trabajos futuros basados en experimentación real y el coste asociado que implicaría el llevarlo a cabo. Los anexos que concluyen la tesis doctoral versan por un lado sobre el funcionamiento del vector común de toda la tesis: el láser, sus aplicaciones y su control en la seguridad y por otro presentamos los coeficientes de absorción y scattering que hemos utilizado en nuestras simulaciones. El primero condensa las principales características de una radiación láser desde el punto de vista de su generación, el segundo presenta la seguridad en su uso y el tercero son tablas propias, cuyos parámetros son los utilizados en el apartado de experimentación. Aunque por el tipo de tesis que defiendo no se ajusta a los modelos canónicos de tesis doctoral, el lector podrá encontrar en esta tesis de forma imbricada, el modelo común a todas las tesis o proyectos de investigación con una sección dedicada al estado del arte con ejemplos pedagógicos para facilitar la compresión y se plantean unos objetivos (capítulos 1-4), y un capítulo que se subdivide en materiales y métodos y resultados y discusiones (capítulo 5 con sus subsecciones), para finalizar con una vista al futuro y los trabajos futuros que se desprenden de la tesis (capítulo 6). ABSTRACT As contribution to the study of heterogeneous media, this thesis covers the work carried out on theoretical modelling and simulation study of the optical properties of the skin and seawater, as paradigmatic examples of heterogeneous media. It is taken as a starting point the study of the propagation of optical radiation, in particular laser radiation in a biological tissue. The importance of optical characterization of a tissue is critical for managing the interaction between radiation and tissues that allows both diagnosis and therapy of diseases and / or dysfunctions in Health Sciences. Without forgetting the aim of providing a methodology of study, with "engineering approach" of the optical properties in a heterogeneous environment, which does not have to be exclusively biological tissue. As a result of this and the importance of water in biological tissues, we have decided to study the optical properties of water in a heterogeneous environment such as seawater in another chapter. The selection of sea water as an object of further study is motivated mainly because it is considered that the advances that have taken place in recent years in photonic technologies will allow its use in experimental methods of water analysis. Knowledge of the optical properties to characterize the different types of waters according to their compounds, as well as to identify its presence. All of this opens a wide range of applications. In this thesis, it has been generally achieved: • Conduct a study of the state of the art knowledge of the optical properties of the skin and identifying its light scattering elements. • Establish a study methodology that allows us to obtain data on possible effects of radiation on biological tissues. • Use different computer tools to simulate the transport of laser radiation in biological tissues. • Conduct experiments by simulating: laser, detectors, and biological tissues. • Compare the known results with our experimentally simulation. • Study the measuring instruments and its response to the propagation of laser radiation in anisotropic tissues. • Get innovative results for diagnosis and treatment of skin, considering different races and a possible alteration in the skin that we studied: the presence of basal cell carcinoma. • Application of the methodology of the study conducted in the skin to simulate seawater. • Get innovative results of simulation and analysis of amount of phytoplankton in water; in order to facilitate the characterization of different types of water. The dissertation is divided into six chapters and three annexes clearly distinguished by their own literature in each of them. The first chapter is focused on the problem of difficult study and characterization of heterogeneous media due to their inhomogeneous and anisotropic behaviour of optical radiation. So we present a brief introduction to the behaviour of both tissues at the cellular level as the ocean, to optical radiation and define the main optical properties: absorption, scattering, anisotropy and reflection coefficients. Following from this, a second chapter is an approach to solving the problem of how to characterize the optical properties described in the first chapter. For this, first the theoretical models are introduced, secondly simulation methods more used and, finally, the main techniques for measuring the propagation of light in living tissue. The third chapter is focused on the skin and its properties, tries to make a synthesis of what is known about the behaviour of the skin and its constituents tackle the spread of optical radiation. Different skin types are studied and an example of immediate application of this knowledge benefits described. We know that the percentage of water in the human body is very high, particularly in the skin is considered about 70%. It is obvious, therefore, that knowing how the water is affected by the propagation of an optical radiation facilitate to get reference patterns; For this, the study of seawater is performed. In the fourth chapter the properties of seawater as a heterogeneous component particles are studied. This chapter presents a summary of the scattering elements in the ocean, its individual response to optical radiation and its contribution to the ocean as a whole. In the fifth chapter the results of the different types of simulations are described. Simulation tools used were the same for the study of skin and seawater, so both results are presented in the chapter. In the first case different types of ocean water is analysed by varying the concentrations of phytoplankton. The method allows to check the differences that can be found in the characterization and diagnosis of water. The second case analysed is the skin; where the behaviour of different skin types are studied and checked how the result is compatible with applications currently trade, such as laser hair removal. As a significant result of the possible methodology to be applied for the diagnosis of skin cancer known as basal cell carcinoma is shown. Finally we present a chapter on future work based on actual experimentation and the associated cost which it would involve carrying out. The annexes conclude the thesis deal with one hand on the functioning of the common vector of the whole thesis: laser, control applications and safety and secondly we present the absorption and scattering coefficients we used in our simulations. The first condenses the main characteristics of laser radiation from the point of view of their generation, the second presents the safety in use and the third are own tables, whose parameters are used in the experimental section. Although the kind of view which I advocate does not meet the standard models doctoral thesis, the reader will find in this thesis so interwoven, the common model to all theses or research projects with a section on the state of the art pedagogical examples to facilitate the understanding and objectives (Chapters 1-4), and a chapter is divided into materials and methods and results and discussions (Chapter 5 subsections) arise, finishing with a view to the future and work future arising from the thesis (Chapter 6).