Determination of drugs used in combined cardiovascular therapy

Cardiovascular diseases are nowadays the first cause of mortality worldwide, causing around the 30% of global deaths each year. The risk of suffering from cardiovascular illnesses is strongly related to some factors such as hypertension, high cholesterol levels, diabetes, obesity The combination of these different risk factors is known as metabolic syndrome and it is considered a pandemic due to the high prevalence worldwide. The pathology of the disorders implies a combined cardiovascular therapy with drugs which have different targets and mechanisms of action, to regulate each factor separately. The simultaneous analysis of these drugs turns interesting but it is a complex task since the determination of multiple substances with different physicochemical properties and physiological behavior is always a challenge for the analytical chemist. The complexity of the biological matrices and the difference in the expected concentrations of some analytes require the development of extremely sensitive and selective determination methods. The aim of this work is to fill the gap existing in this field of the drug analysis, developing analytical methods capable of quantifying the different drugs prescribed in combined cardiovascular therapy simultaneously. Liquid chromatography andem mass spectrometry (LCMS/MS) has been the technique of choice throughout the main part of this work, due to the high sensitivity and selectivity requirements.

Computing abuse related damages in the case of new entry: An illustration for the Directory Enquiry Services market

A number of European countries, among which the UK and Spain, have opened up their Directory Enquiry Services (DQs, or 118AB) market to competition. We analyse the Spanish case, where both local and foreign firms challenged the incumbent as of April 2003. We argue that the incumbent had the ability to abuse its dominant position, and that it was a perfectly rational strategy. In short,the incumbent raised its rivals' costs directly by providing an inferior quality version of the (essential) input, namely the incumbent's subscribers' database. We illustrate how it is possible to quantify the effect of abuse in situation were the entrant has no previous history in the market. To do this, we use the UK experience to construct the relevant counterfactual, that is the "but for abuse" scenario. After controlling for relative prices and advertising intensity, we find that one of the foreign entrants achieved a Spanish market share of only half of what it would have been in the absence of abuse.

Impact of fertlizers and pesticides on soil and water quality

[ES]En la presente tesis se ha estudiado el impacto de diferentes fertilizantes y pesticidas utilizados en la Zona Vulnerable de Vitoria-Gasteiz en la calidad del suelo y las aguas de dicha zona. Se ha podido constatar que hoy en día siguen lixiviándose cantidades significativas de nitratos y pesticidas (e.g., etofumesato y difenoconazol) a las aguas de la Zona Vulnerable, durante el cultivo de remolacha azucarera (Beta vulgaris L.), muy característico de la zona de estudio. Se comprobó que el alto contenido en nitratos de las aguas subterráneas en la Zona Vulnerable es mitigado, al menos en parte, por la acción de la actividad microbiana desnitrificante que alberga la zona riparia del humedal de Salburua. Dicho proceso, sin embargo, supone la emisión a la atmósfera de importantes cantidades de gases de efecto invernadero (CO2 y N2O), y puede verse afectado negativamente por la presencia de pesticidas (e.g., deltametrina) en el medio.Por otra parte, hemos observado que diversos pesticidas (deltametrina, etofumesato, difenoconazol) aplicados en concentraciones similares a las dosis de aplicación en campo inducen cambios, de carácter limitado y transitorio, en las comunidades microbianas edáficas, siendo más significativos en el caso del fungicida difenoconazol. El efecto de los pesticidas fue más acusado a medida que aumentaba su concentración en el medio. Finalmente, encontramos que la aplicación de abonos orgánicos (avicompost), en lugar de los fertilizantes sintéticos tradicionales (NPK), además de mejorar la degradación de los pesticidas y disminuir el impacto de éstos sobre la calidad del suelo, podría ayudar a reducir las pérdidas de nitratos por lixiviación.

Role of G protein coupled inwardly rectifier K+ channels (GIRK) on the neurobiology depression

353 págs.

Biofunctionalization of alginate microcapsules: advances in cell-based drug delivery systems

172 p.

Subclinical Depressive Symptoms and Continued Cannabis Use: Predictors of Negative Outcomes in First Episode Psychosis

Background Although depressive symptoms in first episode psychosis have been associated with cannabis abuse, their influence on the long-term functional course of FEP patients who abuse cannabis is unknown. The aims of the study were to examine the influence of subclinical depressive symptoms on the long-term outcome in first episode-psychosis patients who were cannabis users and to assess the influence of these subclinical depressive symptoms on the ability to quit cannabis use. Methods 64 FEP patients who were cannabis users at baseline were followed-up for 5 years. Two groups were defined: (a) patients with subclinical depressive symptoms at least once during follow-up (DPG), and (b) patients without subclinical depressive symptoms during follow-up (NDPG). Psychotic symptoms were measured using the Positive and Negative Syndrome Scale (PANSS), depressive symptoms using the Hamilton Depression Rating Scale (HDRS)-17, and psychosocial functioning was assessed using the Global Assessment of Functioning (GAF). A linear mixed-effects model was used to analyze the combined influence of cannabis use and subclinical depressive symptomatology on the clinical outcome. Results Subclinical depressive symptoms were associated with continued abuse of cannabis during follow-up (beta=4.45; 95% confidence interval [CI]: 1.78 to 11.17; P=.001) and with worse functioning (beta=-5.50; 95% CI: -9.02 to -0.33; P=.009). Conclusions Subclinical depressive symptoms and continued cannabis abuse during follow-up could be predictors of negative outcomes in FEP patients.

Efficacy of a cognitive and behavioural psychotherapy applied by primary care psychologists in patients with mixed anxiety-depressive disorder: a research protocol

Background: In contrast with the recommendations of clinical practice guidelines, the most common treatment for anxiety and depressive disorders in primary care is pharmacological. The aim of this study is to assess the efficacy of a cognitive-behavioural psychological intervention, delivered by primary care psychologists in patients with mixed anxiety-depressive disorder compared to usual care. Methods/Design: This is an open-label, multicentre, randomized, and controlled study with two parallel groups. A random sample of 246 patients will be recruited with mild-to-moderate mixed anxiety-depressive disorder, from the target population on the lists of 41 primary care doctors. Patients will be randomly assigned to the intervention group, who will receive standardised cognitive-behavioural therapy delivered by psychologists together with usual care, or to a control group, who will receive usual care alone. The cognitive-behavioural therapy intervention is composed of eight individual 60-minute face-to face sessions conducted in eight consecutive weeks. A follow-up session will be conducted over the telephone, for reinforcement or referral as appropriate, 6 months after the intervention, as required. The primary outcome variable will be the change in scores on the Short Form-36 General Health Survey. We will also measure the change in the frequency and intensity of anxiety symptoms (State-Trait Anxiety Inventory) and depression (Beck Depression Inventory) at baseline, and 3, 6 and 12 months later. Additionally, we will collect information on the use of drugs and health care services. Discussion: The aim of this study is to assess the efficacy of a primary care-based cognitive-behavioural psychological intervention in patients with mixed anxiety-depressive disorder. The international scientific evidence has demonstrated the need for psychologists in primary care. However, given the differences between health policies and health services, it is important to test the effect of these psychological interventions in our geographical setting.

El plasma rico en factores de crecimiento como alternativa terapéutica en el ojo seco y en defectos epiteliales persistentes

184 p.

Evaluación de la posible capacidad genotóxica de fármacos antihipertensivos: losartán e irbesartán

[es] La hipertensión arterial (AHT), estado patológico definido como la elevación persistente de la presión arterial, es considerada uno de los principales problemas de salud pública. El tratamiento de la patología se realiza preferentemente con fármacos antihipertensivos. Los pacientes se encuentran sometidos a una exposición larga e ininterrumpida a estos fármacos. Los fármacos antihipertensivos se clasifican en función del mecanismo de acción por el que logran su efecto. Una de las clases son los antagonistas de los receptores de angiotensina II (ARB). Los ARB son la última clase terapéutica incluida en la terapia antihipertensiva. En este Trabajo Fin de Grado, se ha evaluado la posible capacidad genotóxica in vitro, de dos tipos de fármacos ARB (losartán e irbesartán) mediante el empleo de uno de los métodos citogenéticos más utilizados, el ensayo de micronúcleos (MN). El índice de división nuclear (NDI) fue usado también como medida de genotoxicidad. El análisis se ha realizado en linfocitos de sangre periférica (PBL) de 10 individuos control mediante dos tipos de cultivo uno sin fármaco y otro añadiendo los fármacos a los cultivos en una concentración igual a la que se encuentra en el plasma de pacientes. Los resultados muestran un aumento estadísticamente significativo de la frecuencia de células binucleadas con micronúcleos (BNMN) pero no se observan diferencias estadísticamente significativas en el índice de división nuclear. Estos resultados sugieren un posible efecto genotóxico de los fármacos pero sería necesario llevar a cabo estudios en una población más amplia e in vivo con los mismos fármacos para confirmarlo.