PHARMACOLOGY

Author: DANNERT ALSASUA MARҍA TERESA.
Year: 2003.
University: COMPLUTENSE DE MADRID [More theses of this university] [www.ucm.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: DPTO.DE FARMACOLOGҍA.FACULTAD DE MEDICINA.

Summary: The discovery of the cannabinoid receptor system and cannabinoid endÃÂ ³ geno has boosted investigaciÃÂ charges on the effects fisiolÃÂ ³ ments that can be involved in the modulaciÃÂ charges that sistema.Asimismo has increased sÃÂntesis of new compounds that may act as agonists and antagonists of these receptors . This work has been aimed at the caracterizaciÃÂ ³ n mechanism acciÃÂ charges through which two agnistas cannabinoids different in nature quÃÂmica, R (+) - metanandamida and WIN 55212-2, produce relajaciÃÂ charges in the aorta vascular isolation of rata.Se have studied some of the main mechanisms of vasodilataciÃÂ ³ modular No blood produced by cannabinoides.Hasta date, no habÃÂa made ningÃÂ seventh No work of this type in rat aorta artery. Our results reveal that the effect vasorrelajante of R (+) - metanandamida and WIN 55212-2 in isolated rat aorta, seems to be produced by the mediaciÃÂ ³ n several mecanismos.En relaciÃÂ ³ n a receptor involved in vasodilataciÃÂ ³ n produced by these cannabinoids, both compounds actuÃÂ ¡na travÃÂ © s cannabinoid receptors, but does not appear to be the recipients clÃÂ ¡sicos the exclusively involved, but in this vasodilatory effect tambiÃÂ © No participating receivers VR1, albeit partial, and systems effectors activated estos.Esta is the first time that this effect is described with the cannabinoid sintÃÂ © tico WIN 55212-2.

Author: MAÑÁ NIETO PAULA.
Year: 2004.
University: SANTIAGO DE COMPOSTELA [More theses of this university] [www.usc.es].
Place of defense: FACULTAD DE MEDICINA Y ODONTOLOGÍA.
Place of preparation: FACULTAD DE FARMACIA.

Summary: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. Although the cause of MS is unknown todavla, work in the animal model of experimental autoimmune encephalitis (EAE) have suggested that exogenous molecules that share sequence similarity with autoantlgenos honey / na may play an important role as causative agents of disease human. This paper has studied the molecular similarity between the domain inmunoglobullnico extracellular the protelna of milk butirofllina (BTNlgD) and the extracellular domain of the glicoprotelna mielinica of ol / godendrocitos (ED-MOG) candidate autoantígeno in MS. The data in this thesis show that as a result of the reactMdad crusade pathogenic not restricted to a region subdominante of MOG, inoculation of mice C57BLJ6 with BTNlgD, either before or after induction of disease ED-MOG not only prevents but also suppresses the demonstrations cllnicas of EAE. The protective effect of treatment with BTNlgD was associated with a marked depression of the immune response cell Th1 (IFN-, IL-2, IL-12 and GM-CSF) asl as a reduction in serum IgG2c and IgG2b. This inhibition correlated consistently with specifies an increase in production IL-10. The adoptive transfer of T cells specific for the BTNlgD before active immunization with ED-MOG resulted in a temporary reduction of clinical symptoms. These data suggest that the beneficial effects associated with treatment with BTNlgD on Immune response in the SEA include a combination of mechanisms as anergy asl generation regulatory cells that secrete high levels of IL-10. In conclusion, the results obtained in this work are opposed to the assumption that the molecular mechanism of similarity only prompts an immune response and suggests that pathological elements environmental presenting reactMdad crusade antlgenos themselves, they can also generate a source of cells that contain phenotypes protectors versus autoimmunity.

Author: CAMIÑA GARCIA M. MERCEDES.
Year: 2004.
University: SANTIAGO DE COMPOSTELA [More theses of this university] [www.usc.es].
Place of defense: FACULTAD DE FARMACIA.
Place of preparation: FACULTAD DE FARMACIA.

Summary: Recently, studies on the consumption of wine have received considerable attention, both by the scientific community and the general public. The low incidence of ischemic heart disease and other cardiovascular disease (CVD) in the southern French population, despite having a diet rich in saturated fats and some risk factors similar to those of other industrialized countries (little exercise, a large consumption of snuff , etc..) has been attributed to increased consumption and chronic moderate wine, especially red wine by the population (a phenomenon that is called the French Paradox). The trans (t-RESV, trans-3, 4 ', S-trihidroxiestilbeno), naringina (4', S ,7-tridroxiflavanona-7-ramnoglucósido) and (+-) naringenina (4 ', S, 7-tridroxiflavanona) are three natural compounds polifenólicos of Vitis vinifera L. (Vitaceae), abundant mainly in the skin of grapes while naringina and (+-)- naringenina are also so abundant in the fruits of several species of the genus Citrus] and whose therapeutic interest has grown dramatically in in recent years, primarily for their properties anticancerígenas, antioxidant and anti-inflammatory. Surprisingly, however, its pharmacological effects in vitro on the cardiovascular system have not yet been studied extensively. Against this background, and also taking into account the (+-)- naringenina is a precursor of several natural flavonoids vasoactive (in the wine) with very similar chemical structure, we thought it might be interesting to explore the potential vasodilatory effects of these three compounds polifenólicos. The t-RESV (1-10 IJM) had no effect on the phenylephrine-induced contractions (FE) and high concentrations of extracellular KCI in rat aortic rings without endothelium. However, relaxed, in a concentration-dependent manner, the contractile response produced by WITNESS (1 IJM, IC50 = 3.12 + - 0.26 IJM, n = S) or high concentrations of KCI (60 mM, IC50 = 9.60 +-0.87 IJM, n = S) rings in intact rat aorta. The corresponding values of IC50 significant differences (P greater 0.01). The vasodilatory effects of t-RESV were completely inhibited by the N-nitro-L-arginina (L-NOARG, 0.1 mM) and methylene blue (10 IJM), but were not affected by atropine (10 IJM ) Yla yohimbina (1 IJM). The inhibitory effect produced by the L-NOARG was antagonizado by L-arginine (0.1 mM) but not by the D-arginina. The t-RESV (1-10 mM) did not affect the activity of the enzyme nitric oxide synthase constitutive endothelial (NOSce) homogenados of rat aorta. In addition, the t-RESV (1-10 mM) did not manifest properties scavenger (neutralizadoras) superoxide radicals or inhibitors of xanthine oxidase (XO) because it did not alter the reduction of blue nitrotetrazolio (NBT) and the oxidation of xanthine uric acid to the system using hipoxanthine (HX) / XO. On the other hand, t-RESV (1-10 mM) was able to inhibit the synthesis of superoxide anions in resident macrophages obtained from rat peritoneal exudate activated with 12-miristato-13-acetato of forbol (WFP CISO = 7, 4 + - 0.6 mM) or foreign particles (OxyBURST @ / Kluyveromyces lactis, CISO = 5, S + - 0.4 mM n = 5). The t-RESV (1-10 mM) inhibited the enzymatic activity of NADH / NADPH oxidase vascular in homogenado of rat aorta, ie quimioluminiscencia specific signal emitted by the reaction between lucigenina and superoxide radicals generated Since oxygen and NADH (the preferred substrate for the NADH / NADPH oxidase in rat aorta). The value of the IC50 was 4.81 +-0.37 IJM (n = S). The above results indicate that the effect vasorrelajante dependent endothelium produced by the t-RESV in the rat aorta, appears to be due to inhibition of NADH / NADPH oxidase vascular and the subsequent decline in the production of superoxide anion, protecting NOT his inactivation. Assuming the t-RESV show a similar behavior in human blood vessels, our results could exp 8 licar, bc0 l least in part, the beneficial effects of long-term moderate consumption of wine in the prevention of various CVD, mainly ischemic heart disease. On the other hand, (+-)- naringenina (1 mM-0, 3 mM) did not affect the contractile response induced by ácico okadaico (AO, 1 mM). However, (+-)- naringenina (10 mM-0, 1 mM) completely relaxed, in a concentration-dependent and almost equally effective, contractions induced FE (1 mM; CISO = 71.2 + - 5.3 mM), WFP (1 mM; IC50 = 7S, 1 +-S, 2 mM) or high concentrations of KCI (60 mM; IC50 = 72 +-4.8 mM) in aortic rings intact rat (n = S, P less Or, FS). The mechanical removal of endothelium and / or pretreatment of the aortic rings with glibenclamide (10 mM) or tetraetilamonio (TEA, 2 mM) did not alter significantly the vasodilatory effects of this flavanona. In studies with Ca2 + radioactive, (+-)- naringenina (10 mM-0, 1 mM) did not alter the catchment baseline 45Ca2 + but significantly inhibited the flow inlet 45Ca2 +-induced FE (CISO = 34.5 + - 2.9 mM) and high concentrations of KCI (CISO = 34.5 + - 2.9 mM) in rat aortic rings without endothelium (n = S). The (+-)- naringenina (10 mM-0, 1 mM) did not show properties neutralizadoras of superoxide radicals generated enzymatically by the system HXlXO nor had inhibitory effect on the enzyme activity of XO. In addition, (+-)- naringenina (0.1 mM) significantly potentiated the increase in cytosolic concentrations of cGMP and cAMP diminished by the FE (1 mM) or high concentrations of KCI (60 mM) in miocitos cultured aortic rat. The (+-)- naringenina inhibited preferably phosphodiesterase type 1 (FDE1) (activated by the calmodulina), the phosphodiesterase type 4 (FDE 4) And the phosphodiesterase type-S (FDES) isolated from bovine aortas with values CISO of 45 mM, 60 mM and 68 mM, respectively. On the other hand, and surprisingly, the heterósido of (+-)- naringenina, naringina (10 mM-O, 1 mM), had no effect on any of the experiments described above. These results indicate that the effects vasorrelajantes of (+-)- naringenina appear to be due to inhibition of the activity of FDE1, FDE4 And FDES.

Author: RODRÍGUEZ SIERRA M. ANGELES.
Year: 2004.
University: COMPLUTENSE DE MADRID [More theses of this university] [www.ucm.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA. U. COMPLUTENSE.

Summary: Carcinoma urotelial bladder presents high rates of morbidity and mortality, mainly due to the frequent recurrence and progression observed in spite of the widespread aspectro therapeutic that can be enforced. For this reason it is necessary to adopt additional measures to improve the therapeutic choice. The protein p53 is a biomarcador related to the genesis, tumor progression, and control over apotosis, so we felt that the study of his speech might identify groups at risk of progression and recurrence, and the therapeutic response in the way of activation of apoptosis. We studied 225 patients with a minimum follow-up of three years, finding that the expression of p53 has been shown as an independent predictive factor of reciediva and progression in the multivariate analysis; depending on the stage in the aspect of survival. In the factor analysis of tumors that infiltrate the lamina propria, we have found high percentages of patients free of disease without overexpression in tumors with similar effectiveness for any treatment applied to three years, five years more effective radiotherapy. In overexpression tumors with the most effective treatment has been three and five years, the partial cystectomy; show laBCG as an alternative to short-term, very low percentages of patients free of disease with other therapeutic measures implemented. These results suggest to us that the valuation of the expression of p53 may be a useful tool in the management of patients with bladder carcinoma uroterial of, and should be included in the protocols of therapeutic action. KEYWORDS: treatment, prognosis, factor analysis.

Author: DÍAZ ROLDÁN JORGE.
Year: 2004.
University: SEVILLA [More theses of this university] [www.us.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA.

Summary: Introduction and Objectives: The introduction of the laparoscopic technique as a new surgical access to the abdomen has meant a revolution in the field of surgery. Laparoscopy is attributed to a number of advantages resulting mainly from a lower aggression on the abdominal wall, but also are known adverse effects, especially of pneumoperitoneum. Their impact on renal function have been little studied, finding evidence that may become very important. We raised studying the effect of laparoscopy on various parameters, since clinical, hemodynamic, respiratory, in response to aggression surgery until finally assess renal function by applying modern laboratory techniques that are not intluenciadas by aggression surgery. Materials and Methods: We designed a prospective study with random distribution of patients to two groups: Group 1: Laparoscopic surgery or Group 11: Open Surgery. We set the pressure of pneumoperitoneum in 12 mm Hg. We included patients with pathology susceptible to treatment by both techniques, and without comorbidity. We studied preoperative similarity: age, sex, weight, height, body mass index, personal history, anesthetic risk (ASA), and blood pressure, oxygen saturation and hematocrit baseline. To evaluate the intra-and postoperative stability: postoperative pain, operative time, vomiting, intra-and postoperative complications, intraoperative presence of severe hypotension, pre and postoperative hematocrit, oxygen saturation, partial pressure of CO2 end-expiratory (et CO2), heart rate (Fe), systolic blood pressure (SBP) and diastolic (DBP), as well as metabolic parameters evolutionary response to aggression in the first 24 hours: leukocytes, neutrophils, erythrocyte sedimentation rate, fibrinogen degradation products, blood glucose , creatín-fosfo-kinasa (KPC), C-reactive protein (CRP) and platelets. The parameters of renal function: urea, fractional excretion of urea, creatinine, creatinine clarification, microalbuminuria, IgG in urine, alfa-lmicroglobulina in urine, blood and urine sodium, fractional excretion of sodium, chloride, calcium and potassium in the blood, fractional excretion of potassium, creatinine in urine, cistatina Cy rate fitracación glomerular (calculated). Results: Both groups are homogeneous and no differences between them. Differences between the two groups in the FC and PAS to 15 minutes and in DBP from inception up to 15 minutes, with an increase in the open group, which refejan the largest assault operation of this group. There was an increase in the level of postoperative higher leukocytes, neutrophils, KPC, and PCR in this group. There were no significant changes in levels of plasma ions (sodium, potassium, chloride or calcium). We found an increase in the urinary excretion of albumin in open surgery which represents the effects of increased aggression in the surgical group. We found no differences between the two groups in terms of renal function measure with urea, creatinine, creatinine clarification, microalbuminuria, IgG in urine, alfa-lmicroglobinuria, cistatina C and glomerular filtration rate calculated. We found an increase in glomerular filtration (glomerular filtration rate calculated levels cistatina C clarification creatinine) in patients after surgery in the immediate postoperative period. This improvement was more prominent in the laparoscopic group, according retlejan data clarification creatinine. Therefore, and as a main conclusion, we found that laparoscopic surgery by itself does not produce a deleterious effect on renal function.

Author: HUGUET RIBA MARTA.
Year: 2004.
University: BARCELONA [More theses of this university] [www.ub.es].
Place of defense: FACULTAD DE FARMACIA.

Author: AMPUERO SÁNCHEZ ISRAEL.
Year: 2004.
University: COMPLUTENSE DE MADRID [More theses of this university] [www.ucm.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA UNIVERSIDAD COMPLUTENSE.

Summary: In recent years have been many works that have associated with the endogenous cannabinoid system with psychiatric disorders such as addiction, schizophrenia or inattention and hyperactivity in children. They have also been published numerous works that show the involvement of 'this system neurotrasmisión in controlling movement. Two important elements within this system endocannabinoide, the first charge of signaling mediated by receptor and the second by breaking down the enndocannabinoides endogenous ending this neurotrasmisión are the cannabinoid receptor type 1 (CBl) and amidohidrolasa fatty acid (FAAH). The gene coding in cannabinoid receptor type 1 (CNRl) and the gene coding for amidohidrolasa of fatty acids present polymorphisms alo throughout their sequence, which might be considered in studies of association. In this work we analyzed the polimorrismo (AAT) No located in the extreme 3 'gene cannabinoid receptor type 1 and polymorphism C385A located in exon 3 of the gene coding for amidohidrolasa fatty acid in 209 individuals alcóhólicos. Of the 209 patients Alcoholics, we could only test 107, of whom 47 suffered ADHD child. The study also included 50 patients were diagnosed línicamente of Parkinson's Disease, 133 individuals had no control history of addiction to alcohol and chosen randomly from the Spanish population and 41 individuals control osteoartiitis and well studied clinically to exclude the presence Sick of Párkinson. We found an association between the polymorphism (AAT) No situado.en the extreme 3 'gene cannabinoid receptor type 1: l) The history of attention deficit disorder and hyperactivity child alcoholics and 2) The depression comorbid in Parkinson's disease.

Author: FERNANDEZ VELASCO MARÍA.
Year: 2004.
University: COMPLUTENSE DE MADRID [More theses of this university] [www.ucm.es].
Place of defense: FACULTAD MEDICINA.
Place of preparation: FACULTAD MEDICINA.

Summary: The main objetivó the Present Doctoral Thesis was to know the pattern of distribution and electrophysiological, and molecular characteristics of the flow activated hyperpolarisation (If) miocitos isolated hearts controls 3 different areas of the ventricle of the rat: the septum (S) , the left ventricular free wall (VI), and the right ventricular free wall (VD), and compared with those obtained in miocitos isolated hearts hipertróficos.También analyze the modulation by hypertrophy of the flow of rectifying K + entry (Ik1). Findings of this study are as follows: We have proved the existence in the ventricle of a rat running hyperpolarisation active, sensitive to blockade by Cs + and activated by cyclic nucleotides (cAMP), which has been widely described in regions automatic heart and is known as If (current funny). The presence of left ventricular hypertrophy incrmenta significantly the probability of observing If your amplitude density and conductance without changing the voltage dependence of the current. The increased density and conductance of associates If development hipertrofía, it is not accompanied by changes nien density or in the expression of the Ik1 per channel so that If only it could contribute to the emergence of abnormal activity in the Automatic ventricle in a situation where there is a beta adrenergic overstimulation. The isoforms HCN forming the channel native If the rat ventricle of the heart are the HCN2 and HCN4. Our study was the first to demonstrate that the regulaciónn to the top of the If that occurs during the development of left ventricular hypertrophy in rats is associated with an overexpression of isoforms HCN2 and HCN4 encoding for the channel in native If this tissue.

Author: GALENDE DOMÍNGUEZ INÉS.
Year: 2004.
University: COMPLUTENSE DE MADRID [More theses of this university] [www.ucm.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA DE LA UCM.

Summary: The regulation of clinical research in medicine is justified from the point of view of ethics to protect the subjects involved, as well as to establish the boundaries between what is allowed and not allowed to researchers and, ultimately, contribute to development of a country or region. In Spain, is a matter of State law on pharmaceuticals, but the implementation of such legislation lies with the autonomous regions. Thus, in 1993 issued Royal Decree 561/1993, from cualla § CC. AA. Should develop those skills that teníanatribuidas, mainly relating to accreditation and performance standards of the Committees on Ethics in Clinical Research (CEIC), and monitoring of clinical trials (EE.CC.). The Community of Madrid should develop its own rules, adapted to their reality and with clear objectives. Once approved such legislation should be enforceable and, finally, evaluate the results. Therefore, the objectives of this study were: to make a policy proposal for the conduct of clinical trials in the Madrid region, and once met that first goal, check its implementation through evaluation of the results in the medium and long term. The methodology followed to achieve the first objetivo-desarrollo of normativa- was the creation of a working group, attended by people involved in, until then, called Committees Trials. Meantime, the planned training activities for prospective members of those committees and went designing a computerized database for the processing and management of all information that is generated in the implementation of the standard. Once issued Decree 39/1994, in order to be accredited as CElC were conducted according to the relevant protocols ad hoc inspections, the first temporary, and after the final, with a validity period of three years. Besides the reports were prepared, one in connection with the assurance of the participants in EE.CC. And on the economic aspects and contracts, with little impact. The results presented reflect the overall activity of 17 CEIC accredited to the CM, over 8 years of operation (1995-2002), allowing it to establish 3 groups in terms of their activity. In addition, it presents a much more detail - the total business and the particular characteristics of multi-center clinical trials - 4 or more centros- evaluated by a committee of regional level (CEIC-R), which are represented all CEIC accredited. Finally, we compare the characteristics of EE.CC. Evaluated by the CEIC-R with clinical trials evaluated at the national level, during the year 2000-by the Spanish Agency of Medicines.

Author: ZALDUEGUI ECHANIZ AMAIA.
Year: 2004.
University: PAÍS VASCO [More theses of this university] [www.ehu.es].
Place of defense: FACULTAD DE FARMACIA.
Place of preparation: FACULTAD DE MEDICINA.

Summary: The results experimetnales this dissertation, covering the extent of the activity adenilato cyclase (cAMP production), the measure of the level of expression of the total density isoforms adenilato cyclase, and the characterization of the distribution and relative expression level the different isoforms of adenilato cyclase as well as protein G heterotriméricas leading to the stimulation of these enzyme activities, in particular as subunits (long and short) and b subunits (common), in two regions as the prefrontal cortex and caudate nucleus subjects controls dead by accidental causes and no history of illness neorológica and / or psychiatric care, but also in rat cortex and striped. Following the characterization of what is a very heterogeneous pattern of expression has been studied in detail the level of expression of these proteins in a population independent (20 pairs) and control subjects with a diagnosis of deopresión deaths by suicide in the two brain regions already discussed. This population was drawn carefully in relation to variables such as sex, age and postmortem interval. And we found no statistically significant differences in the levels of expression of proteins measures between the two groups object of our study or in prefrontal cortex or in the caudate. Lastly, given the toxicological analysis of the levels of suicide and antidepressants found, has been evaluated in an animal model (rat) of chronic treatment with fluoxetine, the possibility of changes in transduction induced by the drug. It also found statistically significant differences in the levels of expression of proteins measures between the plasma membrane preparations of rat cortex and control rats chronically treated with fluoxetine.

Author: RUIZ DE AZUA LOPEZ DE VICUÑA IÑIGO.
Year: 2004.
University: PAÍS VASCO [More theses of this university] [www.ehu.es].
Place of defense: FACULTAD DE FARMACIA.
Place of preparation: FACULTAD DE MEDICINA Y ODONTOLOGIA.

Summary: This dissertation makes a comprehensive study of the functionality as well as the states of the major system components of signal transduction associated with fosfoinosítidos membrane (receivers muscarínicos-proteínas Gq/11-fosfolipasa C) in human cerebral cortex in postmortem over ontogénico development (pre - and postnatal) and aging âno patológicoâ. The study has employed various experimental techniques: testing functionality of the enzyme phospholipase C activity with [3H] - PtdIns (4,5) P2, techniques inmunodetección with specific antibodies and test fixation with radioligandos, all appropriate and valid to achieve the objectives. As a major and novel findings of this study are that the receiver muscarinic M1 is dimerizado of constitutively through the formation of covalent interactions type in the extracellular regions of membrane receptor in adult human prefrontal cortex; quantitatively determine the levels of subunits alpha proteins Gq/11 in membranes of adult human cerebral cortex by approximately 800 ng / mg of total protein membrane, these levels of expression mean that these proteins represent a 0.1% of the total protein present in membranes and help establish relations estequiométricas between components receptoriales and tranductores system signal transduction analyzed with a significant excess protein Gq/11; with regard to the study of development ontogénico, describes a severe disruption of the hydrolysis of fosfoinosítidos stimulated via muscarinic receptors and the levels of expression of effector enzymes (four isoforms of the family phospholipase C-beta) as well as muscarinic receptors (especially subtype M1, M3 and M5) over that development could be closely related morphogenesis and sinaptogénesis of the cerebral cortex, in addition, these results show that the effector enzyme appear to be the limiting factor of the response action at the expense of proteins transductoras; finally, signs that there would be a reduction in system response signal transduction associated with fosfoinosítidos as a result of a decrease specific muscarinic receptors (especially subtype M1) and the isoform phospholipase C-beta1 associated with the process of senescence that seems to be an obvious connection with the formation of deposits beta-amiloide and the neurofibrillary tangles, the two major injuries pathologic features of Alzheimer's disease hipotetizando that if all individuals live long enough eventually suffer from the disease.

Author: ABAD MERIN MARIA JOSE.
Year: 2004.
University: MIGUEL HERNÁNDEZ DE ELCHE [More theses of this university] [www.umh.es].
Place of defense: INSTITUTO DE BIOLOGÍA MOLECULAR Y CELULAR.
Place of preparation: INSTITUTO DE BIOLOGÍA MOLECULAR Y CELULAR.

Summary: To identify compounds quimiosensibilizadores designed to mitigate the appearance of phenotype multidrug resistant (MDR) associated with tumor resistance to drugs antineoplásticos classics, took place the following inputs:-were first trial screening cell cytometry using high performance flow based on the intracellular accumulation of anthracycline daunomicina. - We used the test to screen and subsequently refined by combinatorial chemistry two quimiotecas synthetic N-alquilglicinas (5120 compounds) and 2,5-dicetopiperacinas (165 compounds), as well as various fractions of a plant extract obtained by HPLC. The model cell test consisted of two lines of mouse hematopoietic (L1210) and human (HL-60) availability from both lines sublineas resistant to antineoplastic drugs classics and MDR phenotype, obtained under selective pressure (L1210R and HL60- R). - From quimioteca of N-alquilglicinas have obtained two quimiosensibilizadores assets. The quimioteca 2.5-dicetopiperacinas requires further refinement. Of the plant extracts were obtained two compounds with a high potential reversor of MDR.

Author: GARCIA JORDÀ ELVIRA.
Year: 2004.
University: BARCELONA [More theses of this university] [www.ub.es].
Place of defense: FACULTAD DE FARMACIA.

Summary: In recent years, the increase in life expectancy of the population has been increasing incidence of neurodegenerative diseases, becoming one of the main health problems in today's society. The neuronal death may cause through various cellular processes, development of diseases such as Parkinson's or Alzheimer's. A common characteristic of these diseases is the alterations in him citosqueleto neuronal. The integrity of this structure is essential to the maintenance of the functions and survival of neurons. Therefore, it is of great interest to the use of in vitro experimental models that will allow us to study the macanismos through which the desesetructuración of citosqueleto induces apoptotic death, as well as trying to discover new drugs that delay or stop the neuronal degeneration. In this paper we used colchicine, an agent disrupter of microtubules, to study the routes and intracellular signals involved in the alterations of citosqueleto that induce apoptosis in an experimental model of granular cells of rat cerebellum.

Author: PÉREZ GALINDO M. PILAR.
Year: 2004.
University: GRANADA [More theses of this university] [www.ugr.es].
Place of defense: FACULTAD DE FARMACIA.
Place of preparation: FACULTAD DE FARMACIA.

Summary: Through the comparative study, on the one hand, yields and qualitative and quantitative composition of the products obtained by extractive techniques hidrodestilación classical destilación-extracción simultaneous and supercritical fluid extraction, from plant material from the application intensities of harvesting 25%, 50% and 75% of the area of Salvia lavandulaefolia Vahl.ssp.oxyodon during three years of cultivation plots, and, for protection against erosion, in terms of runoff and loss of soil, these crops have on the same year during the years of study and according to the three intensities collection applied, it has been determined the intensity of pruning of 50% as well to combine the optimum sustainable production of biomass and extractive product with a high economic use because of its industrial uses and pharmacology, along with a highly effective protection in arid soils of the southern slope of the Sierra Nevada.

Author: GONZÁLEZ LOIS CARMEN.
Year: 2004.
University: COMPLUTENSE DE MADRID [More theses of this university] [www.ucm.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: H. DOCE DE OCTUBRE.

Summary: DEFINITION constitute a diagnostic category whose common feature is a wide array lax with abundant glicosamínglicanos, whose diagnosis was used different techniques. One of the most powerful is the electron microscopy that also allows for a rapprochement histogenético the issue. OBJECTIVES Finding patterns ultrastructural value for the differential diagnosis. Find patterns suggesting ultrastructural common assumptions histogenéticas. MATERIALS AND METHODS review the material File ultrastructural a general hospital (1976-2000) collecting information clinical, morphologic and immunohistochemical relevant. Certain variables are collected systematically ultrastructural. They are grouped into cells: * Elements of differentiation recognizable. * Cells no signs of differentiation, morphology characteristic or not. It compares with neoplastic tissue mixoide not (gelatin Wharton). RESULTS Of the 87 cases studied, grouped into: adipocíticos (13); miofibroblásticos (18); muscle smooth (3); rabdomioblásticos (10); condrobásticos (2); differentiation uncertain (18); cordomas (7); neural ( 9); indeterminate and miscellaneous (7) (classification: WHO), with tumor differentiation were recognizable: * Adiposos (Lipoma Spindle Cell; Liposarcoma mixoide). * Miofibrolásticos (Nodular Fasciitis; Fibroblastoma Desmoplastic; Miofibrolbastoma breast; Mixoma yusta-articular; Angioomixoma surface; tumor Fibromoxoide ossificans). * Leiomioblásticos (Leiomyoma:, Angriomixoma aggressive; Leiomyosarcoma). * Rabdomioblásticos (Rabdomiomas; Rabdomiosarcomas). * Condrales (Condroma: Chondrosarcoma skeletal). * Neural (Schwanomas; Neurofibroma). The groups were recognizable without differentiation: * Mixomas (Heart; neurotequeomas). * Mixofibrosarcomas (Mixofibrosarcoma: sarcoma fibromixoide). * Condrosarcoma mixoide (Condrosarcoma mixoide; Paracordoma; Cordoma). There were perivascular cells of undetermined characteristic morphology in 40 cases (48.27%) and gelatin Wharton. CONCLUSIONS Matrix is not diagnostic except tumors condrales. Note 4 cellular groups (with distinction recognizable without differentiation recognizable features but without distinctive features: perivascular cells unspecified). Ultrastructural diagnosis note patterns. At least part of the mesenchymal tumors (mixoides), oncogenic alterations occur in a perivascular cells pluripotencial identifiable ultraest4ructuralmente and which also appears in neoplastic tissue mioxide not.

Author: URIZAR ANDRIEU ENEKO.
Year: 2004.
University: PAÍS VASCO [More theses of this university] [www.ehu.es].
Place of defense: FACULTAD DE FARMACIA.
Place of preparation: FARMACIA.

Author: VIZCAÍNO JAÉN M. SONIA.
Year: 2004.
University: EXTREMADURA [More theses of this university] [www.unex.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA (UNIVERSIDAD DE EXTREMADURA).

Summary: This thesis, contains a work investigaicón, based on experimental studies in genetic and metabolic carried out on a population of healthy volunteers. It identifies a number of variables that affect the level of activity of metabolic enzymes completed, in particular CYP3A4 CYP3A5 and CYP2J2. The thesis supports previous research and complete the study with some novel findings in the field of research, in this way, leaves open the door to further research in order to determine the important role played by CYP3A4 and CYP3A5 in the body, and Specifically inside a Spanish population, providing certain ethnic differences with respect to other Caucasians, which can be of great importance in implementing certain dosage medications and in determining the causes of certain diseases or disorders in some serious cases such as certain types of cancer. It is also reflected in this work metabolic differences based on sex, and with regard to have smoking or not. Finally, it reflects the correlation between metabolism presenting certain individuals and the relationship with your genetic load individually. Note: Line 99 refers to a field of Pharmacology called Pharmacogenetics.

Author: PEREZ SAN EMETERIO M. ESTELA.
Year: 2005.
University: CANTABRIA [More theses of this university] [www.unican.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA.

Summary: The present study is an analysis of the impact of acute and chronic treatment with opioids, and the abstinence on the expression of growth factor activina and its regulatory elements in the CNS middle mouse adult. And also because it is detected apoptotic cell death in the mouse brain during these studies predominantly in treating chronic and during abstinence, we analyze the levels of expression of the factors involved in the cascade of death noting an increase in the expression factors proapoptóticos and mediators of cell death, in the case of withdrawal is accompanied by a decrease in the expression of factors aantiapoptóticos.

Author: AÑEZ SIMÓN CRISTÓBAL.
Year: 2005.
University: LAS PALMAS DE GRAN CANARIA [More theses of this university] [www.ulpgc.es].
Place of defense: CENTRO SUPERIOR DE CIENCIAS DE LA SALUD.
Place of preparation: CENTRO SUPERIOR DE CIENCIAS DE LA SALUD.

Summary: There were no differences in the evolution hermodinámica or ventilation during the 6 hours that remained in the resuscitation unit. The local side effects were detected by anamnesis bad taste in the mouth in 3 patients in group IV and 6 Group IN and itchy nose in 1 patient group IN. By rinoscopia previous rhinorrhea were detected in 2 patients in each group, dry mucous in 8 patients in group IV and 5 in the group IN, 1 case of mild hyperemia of the nasal mucosa in each group and 2 patients in the group who spoke IN others findings, pallor septal mucosa and hyperemia in the area Kiesselbach. Systemic side effects reported were nausea, vomiting, itching, sweating malaise, dry mouth and epigastralgia. DISCUSSION Tramadol is a drug attractive for use in the postoperative period, because it does not produce respiratory depression. Studies of the use routes such as sublingual or rectal demonstrate proper absorption through transmucosal. We discuss aspects of dosage, system and method of administration, as well as possibilities to improve the absorption and analgesic efficacy. It also discusses the need for a multimodal approach to the treatment of postoperative pain. We discussed the potential interactions with other drugs such as ondansetron, metocloparamida, etc.., The evaluation system of pain intensity and the importance of assessing patient satisfaction with treatment received analgesic. CONCLUSIONS Tramadol administered intranasally produces analgesia in a significant number of patients without adverse effects on the nasal mucosa. Systemic side effects were similar to those observed with intravenous administration. The degree of patient satisfaction is within the range considered high.

Author: BLANCO FERNÁNDEZ GERARDO.
Year: 2005.
University: EXTREMADURA [More theses of this university] [www.unex.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA.

Summary: INTRODUCTION The upper gastrointestinal bleeding (HDA) is a common adverse effect of NSAIDs. Most of these drugs are metabolized in the liver by cytochrome P450. The enzyme CYP2C8 and CYP2C9 have an important role in the metabolism of many NSAIDs. These enzymes can undergo change in the metabolic capacity genetically determined. Variants CYP2C8 * 3, CYP2C9 * 2 and CYP2C9 * 3, the most common in our population, have a low metabolic activity. 3 increases the risk of developing HDA related to the use of NSAIDs. PATIENTS, MATERIALS AND METHODS have been involved a group of 134 patients with HDA after use of NSAIDs, another group of 177 patients treated chronically with NSAID without family or personal history of HDA and a control group of 355 individuals without disease or toxic habits known. In all individuals investigates the presence of allelic variants Frequently deCYP2C8 and CYP2C9. RESULTS We found a significantly higher percentage of individuals carrying variants CYP2C8 * 3, CYP2C9 * 2 and to a lesser extent CYP2C9 * 3 in the group of HDA. In the case of patients who consume drugs with primary metabolism through CYP2C8 and CYP2C9 odds ratios were found: To CYP2C8 * 3 OR = 2.71 (1.23-5.95), Chi square 6186 (p = 0013) ; for CYP2C9 * 2 OR = 2.31 (1,07-5), Chi square 4494 (p = 0034) karma case association CYP2C8 * 3 + CYP2C9 * 2, OR = 2.80 (1,21-6, 47), Chi square 5823 (p = 0016). But for patients who consume drugs with partial metabolism through these enzymes are the odds ratio: For CYP2C8 * 3 OR = 1.3 (0.65-2.6), Chi square 0525 (p = 0469); for CYP2C9 * 2 OR = 1.49 (0.78-2.85), Chi square 1427 (p = 0232) and in the case of partnership CYP2C8 * 3 + CYP2C9 * 2, OR = 1.62 (0,77-3 , 42), Chi square 1598 (p = 0206). Conclusions The risk of developing HDA is associated with the presence of the alternatives CYP2C8 * 3, CYP2C9 * 2. The increased risk was observed in carrying the haplotype CYP2C8 * 3 + CYP2C9 * 2. The association of the mutated genotype and the risk of developing HDA is stronger with NSAIDs that are predominant metabolized by CYP2C8 and CYP2C9 that NSAIDs with those in which these enzymes play a secondary role.