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EFFECT OF ISQUEMIA-REPERFUSION INTERSTINAL IN THE ABSORPTION AND METABOLISM OF ALBENDAZOLE AND DILTIAZEMAuthor: MOLINA DE LA TORRE ANTONIO JOSE. Year: 2005. University: LEÓN [ www.unileon.es]. Place of defense: FACULTAD DE VETERINARIA. Place of preparation: FACULTAD DE VETERINARIA. Summary: The ischemia (R / S) gut is considered a clinical problem with high mortality and an increase in its incidence in recent years. Damage included the formation of free radicals, the release of cytokines and severe alterations in the intestinal mucosa. Because the intestine has great influence on the bioavailability of orally administered drugs, both processes absortivos as by the action of the present systems of detoxification, assessed the effect of ischemia is the absorption and metabolism of albendazole (ABZ) and diltiazem (DTZ), two drugs that are administered orally and presents a major intestinal metabolism. The process I / R was generated by the occlusion of the superior mesenteric artery and subsequent reperfusion in rats, conducted studies on the spot, with microsomes and intestinal rings flared in jejunum and ileum. The results of the studies show that spot attracting ABZ from the lumen and its appearance in blood were increased by R / S bowel, reducing further the metabolite formation of albendazole sulfoxide (ABZSO). Studies ring flared and intestinal microsomes confirmed a lower activity albendazole sulfoxidasa, revealing are affected systems FMO and CYP3A responsible for this activity. Studies on the spot with DTZ, showed that after the R / S increases the appearance of the drug in blood on what observed in the control group, reducing the total formation of metabolites, which desacetildiltiazem (M1) generated by esterases was metabolite majority. Studies with microsomes showed a decline in the formation of M1, after I / R, observing that such activity is inhibited by paraoxon and bis-nitrofenilfosfato. In studies ring flared also observed a decrease in the formation of metabolites after I / R, also detected a regional differentiation both in control and in R / S, presenting an increased metabolism in the jejunum in the ileum. It also established a model in vitro intestinal cells Caco2 TC7 in conditions of hypoxia in nitrogen atmosphere. Observándose alterations but smaller than those observed in rats by I / R. We extracted microsomes this cell type and observed that the activity albendazole sulfoxidasa was carried out mainly by the FMO (~ 60%), and CYP3A (~ 40%). The activity of both systems was reduced in the state of hypoxia, on the other hand, activity diltiazem desacetilasa these microsomes were not affected in these experimental conditions.
EFFECT OF BULLFIGHTING ON STEROIDOGENESIS OF ANDRÓGENOS AND ESTROGEN IN THE SHAFT ADRENOGONADAL OF BOS TAURUS I.Author: HERNÁNDEZ MERÁS ANA MARÍA. Year: 2005. University: COMPLUTENSE DE MADRID [ www.ucm.es]. Place of defense: FACULTAD DE VETERINARIA. Place of preparation: FACULTAD DE VETERINARIA. Summary: El toro bravo belong to a variety zoological archaic, maintained only in Spanish territory, French, Portuguese and Latin America, which is reflected in society, culture and economy. We wanted to study various hormonal parameters after bullfighting to appreciate the response adrenogonadal that these animals face stress and intense exercise that involves the practice. The animals classified by age (erales, utreros and bulls) as a control group and take those animals that are returned for not collecting enough qualities to fight. The samples we took these animal groups are: blood, testes and adrenal, from where we get the blood and organs of macerated. To determine concentrations of steroid hormones (cortisol, corticosterona, testosterone, androstenodiona and 17 beta estradiol), the method of ELISA immunoassay competition. In view of the results obtained, it is noted that bullfighting cause significant tissue and plasma concentrations of cortisol, especially in younger animals. The both plasma and tissue concentrations of coritcosterona fall within the ranges physiological given by various authors for cattle, finding the lowest levels in the control group. In the case of hormones gonadales bullfighting complete causes an increase in the concentration of testosterone and 17beta estradiol both plasma and tissue, introducing the lower the control group. As for the androstenodiona, we found no significant difference between the groups studied. EFFECTS OF INGESTION OF A DIET ENRICHED IN ANTIOXIDANTS ON THE FUNCTIONAL STATUS AND OXIDATIVE STRESS OF MOUSE PERITONEAL LEUKOCYTES. CHANGES WITH AGE AND IN RESPONSE TO AN INFECTIOUS PROCESSSummary: In this thesis have been addressed three general objectives for the purpose of determining the mechanisms that underlie the process of inmunosenescencia, and their relationship with longevity, and the development of infectious processes, both closely related to a situation of oxidative stress. To do so, we supported the use of a model of premature aging, listing the animals in PAM (prematurely aging mice) and NPAM (mon-prematurely aging mice) on the basis of their performance in the T-maze test, and a model of endotoxic shock lethal, both in female mice of the strain ICR/CD-1. Furthermore, we evaluated the effect on certain parameters and the function of leukocytes peritoneal redox state of ingesting a mixture of antioxidants, such as vitamin E, vitamin C, zinc, selenium and beta-carotenos, as usual the diet, in both situations oxidative stress, to determine their possible use as a strategy to achieve a healthy aging and increased longevity, as well as strengthening our defenses to deal successfully with potential pathogens that could trigger the death prematurely. Overall, it has been shown that occurs during aging deterioration of the functionality of the immune system due at least in part to the increased oxidative stress in these cells. Also, along the endotoxic shock reproduce the observed changes during aging in the various parameters inguinarios analyzed in the peritoneal leukocytes, but so acute and prominent, leading to the premature death of the mice. Supplementation of the diet with antioxidants reverts to some extent oxidative stress behind aging and endotoxic shock improving the functionality of leukocytes from the peritoneum. Moreover, the effect of these compounds on these cells varies according to age, the dose and time of administration of antioxidants. Thus, we can say that the maintenance of homeostasis redox of immune cells appears to play a key role in its functionality, a positive impact on the longevity of mice, as well as in the evolution of infectious processes. THE SUPPLEMENTATION IN THE DIET WITH ANTIOXIDANT COMPOUNDS IMPROVES FUNCTION AND NEUTRALIZES OXIDATIVE STRESS OF MOUSE PERITONEAL LEUKOCYTES. ROLE IN AGING AND THE SCHOK ENDOTOXICAuthor: ÁLVAREZ CIFUENTES PEDRO. Year: 2005. University: COMPLUTENSE DE MADRID [ www.ucm.es]. Place of defense: FACULTAD DE CIENCIAS BIOLÓGICAS. Place of preparation: DEPARTAMENTO DE FISIOLOGÍA ANIMAL, FACULTAD DE BIOLOGÍA. Summary: In this thesis has found the existence of changes in functional status and redox of the main immune cells in two show a process that oxidative basis, as are aging and endotoxic shock. On the one hand, has been used in a mouse model of premature aging through a test of spontaneous exploration in a T-maze, which differentiates mice PAM (prematurely aging mice) NPAM (non prematurely aging mice), so the first they are "biologically more aged" the seconds. The GPA have a clear deterioration of nerve function and the function of the immune system, their leukocyte redox state, as well as a lower life expectancy in relation to NPAM. Moreover, it has found a parallelism of aging to what happens when the animals were generated by intraperitoneal injection of LPS from E. coli (25 mg / kg), a "endotoxic shock," a process that takes place an acute oxidative stress, produced from septicemia. The supplementation in the diet with antioxidants tiólicos N-acetylcysteine (NAC) and tioprolina (TP) or cereals naturally rich antixodiantes polifenólicos, improves function imunitaria and neutralizes oxidative stress, which seemed mainly in animals prematurely aged ( MAP) and in animals show a endotoxemia. Therefore, these suplementaciones have a role "preventive" and / or "therapeutic" to increase the likelihood of successful aging and healthy and to prevent the promotion of certain diseases. These results also seem to confirm the theory oxidativa-inflamatoria behind aging and a range of pathophysiological states, as the endotoxic shock.
PAPER INSULIN I CREIXEMENT TIPUS FACTORS OF INSULIN IN CREIXEMENT I METABOLISME OF TRUITA IL'ORADAAuthor: MONTSERRAT PULIDO NÚRIA. Year: 2005. University: BARCELONA [ www.ub.es]. Place of defense: FACULTAD DE BIOLOGÍA. Place of preparation: FACULTAD DE BIOLOGÍA, UNIVERSIDAD DE BARCELONA. Summary: It has studied the role of insulin and insulin-like growth factors (IGFs) on the growth and metabolism in rainbow trout (Oncohrynchus mykiss) and golden (Sparus aurata). To meet this objective, there have been experiments in vivo both species, which has caused a situation of compensatory growth. Through real-time RT-PCR has analyzed the expression of key regulators miogénicos (miogenia, myoD), as well as that of the FGFs, miostatinta, IGF-Ie IGF-II during compensatory growth in rainbow trout, the same how has studied the role of insulin and IGF-I receptors in white muscle during this phenomenon. In the golden, has studied the role of insulin and IGF-I receptors in white muscle, as well as for plasma insulin and IGF-I during different periods pilot also has analyzed the mobilization of the various reserves energy (lipid, protein and glycogen) in white muscle and liver. To complete our in vivo studies, has analyzed the expression of the receptors of growth hormone (GH) in white muscle and liver, as well as the expression of the IGFs in both tissues during regulation in rainbow trout. In light of the results in vivo proceeded to the development of a crop of muscle cells of gold. In this system in vitro has been studied the role of insulin and the IGFs in the stimulation of different routes of signal transduction in the course of cultivation. In the same way has studied the role of these peptides metabolic conducting studies on glucose uptake and alanine in different days of cultivation. To confirm that the effects of these peptides were mediated by the presence of specific receptor binding studies were conducted for the IGF-I receptor in different days of cultivation and studied the effect of different inhibitors of the transduction pathways of the a sign along the crop. USING PROTEIN DIETS REPLACEMENT IN RAINBOW TROUT (ONCORHYNCHUS MYKISS) AND GOLDEN (SPARUS AURATA). STUDY WITH STABLE ISOTOPES.Author: BELTRAN ARCAS MARTA. Year: 2005. University: BARCELONA [ www.ub.es]. Place of defense: FACULTAD DE BIOLOGÍA. Place of preparation: FACULTAD DE BIOLOGÍA. Summary: The limitation of fishmeal has stimulated research of plant resources as alternative sources for the cultivation of carnivorous species. In general, high percentages of plant sources typically involve a decrease in growth. This decrease is associated, among other reasons, to the lower quality of vegetable protein compared to animal protein. From a physiological point of view, there is a close connection between the content of amino acids in the diet (especially essential amino acids), amino acid-free tissues, metabolism in these tissues and utilization of amino acids you to synthesize proteins. The overall objective of this thesis was to study the effect of substitution on the usability of the protein in the diet. For this study, diets with different percentage of replacement were marked with stable isotopes (13C and 15N), and followed up post (11 and 24 hours) of the protein in the diet. It discussed the incorporation of marking in the main components of tissues (muscle, liver, offal), as well as plasma free amino acid and muscle. The incorporation of markers from the protein diet in the tissues and its major components, as well as the free amino acid and muscle plasma shows that golden trout and can be replaced by 50% of fishmeal unaltered the use of the diet. The allowance of 75% substitution resulted in trout greater oxidation of the protein in the diet, having an impact on growth. However, the distribution pattern of markers in the main components of the tissue was similar to the control of the situation. In contrast, 100% substitution caused an increase in this kind of recycling of the amino acids from muscle, a decrease of the relationship essential amino acids / non-essential amino acids in plasma and muscle, as well as the activation of hepatic gluconeogenesis. Moreover, the monitoring of carbohydrates in the diet 100% vegetable (by marking with almidón-13C) revealed the low availability of the latter. In gold, a 75% substitution caused, as in trout, increased oxidation of the protein in the diet. In this species, the availability of the amino acids in the diet decreased when their home was 100% vegetable, echo, producing an increase recycling protein in muscle, as evidenced by the higher isotopic enrichment of alanine, aspartate and proline, and declining the relationship essential or non-essential. However, the golden showed no problems of digestion and absorption of carbohydrates in the diet 100% vegetable. The technique of marking with stable isotopes has allowed not only do these studies without problems of environmental pollution and staff, but also the study of the isotopic fractionation of 15N has proved a useful tool for determining protein recycling. Moreover, our studies show that it 15N may be a good marker of origin of the protein in the diet. SHARES OF INSULIN ON GLUCOSE GLUT4 EXPRESSED TRANSPORTER IN THE SKELETAL MUSCLE OF THE FISH TELEÓSTEOSAuthor: DÍA FERRER MÓNICA. Year: 2005. University: BARCELONA [ www.ub.es]. Place of defense: FACULTAD DE BIOLOGÍA. Place of preparation: FACULTAD DE BIOLOGÍA. Summary: The glucose transporters outreach provided (GLUTs) proteins are essential to allow the entry of glucose into the cell. In mammalian isoforms have been identified fourteen (GLUT1-14). Specifically, the GLUT4 has been described as the isoform most important for the maintenance of normal glucose, as is the mediator of the action of insulin to increase the rate of glucose uptake. So far only in fish have identified four isoforms of GLUTs, including highlights the GLUT4, which was cloned for the first time in brown trout (Salmo trutta). At the beginning of this thesis and there was some evidence on the regulation of insulin on the expression of this transporter in vivo, specifically in the muscle of red trout. However, it is unknown whether the action of insulin was a direct effect on muscle tissue or acting through other mediators. On the other hand, nor does it meet the action of insulin on protein GLUT4 trout, an important fact considering that the protein is what ultimately holds the role of glucose transport. Therefore, in this thesis we attempted to resolve these issues in order to contribute to a better understanding of one of the important elements involved in the metabolism of carbohydrates in fish teleósteos. This survey showed that the levels of circulating insulin are able to modulate the protein content GLUT4 in vivo in skeletal muscle of trout and that this regulation is specific to the type of muscle fiber. It also showed that the effects of insulin on the expression of GLUT4 in the skeletal muscle of trout are due to the direct action of the latter on the muscle cells. The basal expression of GLUT4 increases along the differentiation of muscle cells trout. Insulin and IGF-I stimulate the expression of GUT4 and its effects are more pronounced in myo-tubes in myoblasts. Also, the expression of GLUT1 also increases during the process of muscle differentiation but slightly more than the expression of GLUT4. Insulin, in general, promotes accumulation of messenger RNA of GLUT1 in the muscle cells of trout. For his part, the IGF-I also increases the expression of GLUT1 but only does so in a remarkable way in myoblasts. This thesis also studied the regulation of traffic of GLUT4 trout by insulin in muscle cells L6. This was a line generated stable cell L6 expressing the GLUT4 trout with a epítopo myc in its extracellular portion (btGLUT4myc). Insulin was able to stimulate the appearance of btGLT4myc in the plasma membrane, thereby increasing the uptake of glucose in these cells. This effect was quantitatively less than had insulin on GLUT4myc rat because, at baseline, a higher percentage of btGLUT4myc was already present on the cell surface compared with GLUT4myc rat. In addition, btGLUT4myc responded more slowly than GLUT4myc is slower than the GLUT4myc rat. These results suggest to us that the differences observed between traffic GLUT4 trout and GLUT4 rat may be due to differences in some grounds aminoacídicos which in mammals has been shown to participate in the internalization and intracellular retention transporter at baseline. It has also been seen that insulin stimulates translocation of BtGLUT4 in the muscle cells of trout and as a result increases glucose transport in these muscle cells trout and concentrated in the perinuclear region, as has been described previously for the GLUT4 of mammal. Together, we can conclude that the mechanisms of regulation of insulin on GLUT4 in the skeletal muscle already exist in the lower vertebrates, although there are some differences with regard to mammals. Thus, we can see that over the evolution has perfected the system of regulation of doorstep gl 8 ucosa has 2e4 sta become an efficient mechanism that enables rapid recovery of blood glucose. CONTRIBUTION OF ACINAR CELLS IN THE INFLAMMATORY PROCESS ACUTE PANCREATITIS INDUCED OBSTRUCCION BILIO-PANCREATICA IN RATS. EFFECT OF N-ACETILCISTEINAAuthor: RAMUDO GONZALEZ LAURA. Year: 2005. University: SALAMANCA [ www.usal.es]. Place of defense: FACULTAD DE BIOLOGIA. Place of preparation: EDIFICIO DEPARTAMENTAL. ROLE OF PROSTAGLANDIN E2 AND NITRIC OXIDE IN THE CONTRACTILITY OF THE SMALL INTESTINE OF RABBIT.Author: GRASA LÓPEZ LAURA. Year: 2005. University: ZARAGOZA [ www.unizar.es]. Place of defense: FACULTAD DE VETERINARIA. Place of preparation: FACULTAD DE MEDICINA Y FACULTAD DE VETERINARIA. Summary: Many digestive diseases that affect animals and humans are caused by infectious agents such as bacteria E. Coli, salmonella, Sighella ... These infectious agents may induce an inflammatory response and produce trastomos in intestinal motility. In this thesis we studied the role of calcium, as well as prostaglandin E2 and NO, as mediators of inflammation in contractility of the small intestine of rabbit. Both the intestinal smooth muscle longitudinal like circular showed spontaneous rhythmic contractions and fásicas. These spontaneous contractions were affected by the release of excitatory neuromodulators muscarinic cholinergic and adrenergic. Besides these spontaneous contractions are regulated by extracellular calcium by the intracellular calcium. By contrast, the contractions produced by acetylcholine and KC1 were affected primarily by extracellular calcium. Prostaglandin E2 and several receptor agonists prostaglandin E2 (receivers EP1-4) produced smooth muscle contractions in the bowel lengthwise. This contractile response of PGE2 appear to be involved receptor EP1 and EP3, which are located in neurons plexus mientérico and submucoso and intestinal muscle layers. The PGE2 act through different mechanisms intracellular among those who would be involved calcium, protein kinase C and cAMP on the path of tirosinas cinasas. The sodium nitroprusside, a donor of NO produced relaxation of the longitudinal and circular smooth muscle of the gut. This relaxation seems to be mediated via a neuronal excitatory tone, voltage-dependent calcium channel, and the cGMP-dependent potassium channels of large conductance calcium. The spontaneous contractions of longitudinal and circular muscle of the gut were reduced in the presence of lipopolysaccharide (LPS) E. Coli. This effect of LPS seems to be mediated by NO and prostaglandins. EFFECTS OF THE ADMINISTRATION OF CANNABIONOIDES IN YOUNG RATS ON PHYSIOLOGICAL AND BEHAVIORAL VARIABLES IN ADULTHOODAuthor: BISCAIA FERNÁNDEZ JOSÉ MIGUEL. Year: 2005. University: COMPLUTENSE DE MADRID [ www.ucm.es]. Place of defense: FACULTAD DE CIENCIAS BIOLÓGICAS (UCM). Place of preparation: FACULTAD DE CIENCIAS BIOLÓGICAS (UCM) Y FACULTAD DE PSICOLOGÍA (UNED). Summary: Whereas derivatives cannabionoides are one of the most commonly used illicit drugs consumed in western countries and also taking into account that such consumption often begins during adolescence, has increased in recent years, the social alarm at the impact that this future may entail habit . Therefore, the objective of this dissertation is to study the effect of treatment on chronic age periadolescente with agonist cannabionoide PA 55940 on different psychobiological registered in adult rats of both sexes. Specifically, we are interested in studying the effects of such exposure on different cannabinoid spontaneous behavior, sexual behavior, the levels of some hormones and interaction with the opioid system. To accomplish these objectives, we have divided our investigation with three different experimental designs:-In the first experimental design, we studied the effect of treatment with CP55, 940 on the spontaneous behavior of rats in adulthood. We conducted a battery of behavioral tests (the board with holes, the open field and cross maze high), we measure the intake of animals and the evolution of their body weight and value levels corticosterona. - In the second experimental design was studied as cannabinoid exposure affects sexual behavior of rats and were valued some sex hormones: estradiol, testosterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH). - In the third experimental design, we studied the interaction between systems and cannabinoid opioid. We saw how exposure continuad of cannabionoides alter the behavior of self-administration of intravenous morphine and how they affected the level of union and functionality of the receivers as well as the expression of pro-encefálica. The results found in the first design showed that treatment with the agonist cannabionoide affected locomotor activity, Emotions, the exploratory activity as well as the intake and the development of body weight. Furthermore, we were able to find a marked effect sexodimórfico in many of the parameters studied. On the second experimental design, it could be concluded that it CP55, 940 alter the onset of sexual activity but did not change the levels of sex hormones valued. In the last experiment was that exposure to the cannabinoid agonist affects the acquisition of the behavior of intravenous self-administration of morphine and altered the union and functionality of the receivers u-opioides in certain brain regions. Again, were found some differences sexodimórifvas. There was, however, any effect of CP55, 940 on the expression of proencefalina. In conclusion, one can say that the thesis presented here provides data on the effects of cannabinoids youth consumption can have on different aspects neurobiological long term. THE SEROTONIN PERIPHERAL CONTRIBUTION TO GLUCOSE HOMEOSTASIS IN RAINBOW TROUT, ONCORHYNCHUS MYKISSAuthor: CAAMAÑO TUBÍO ROSA ISABEL. Year: 2006. University: SANTIAGO DE COMPOSTELA [ www.usc.es]. Place of defense: FACULTAD DE BIOLOGÍA. Place of preparation: FACULTAD DE BIOLOGÍA-UNIVERSIDAD DE SANTIAGO DE COMPOSTELA.
Summary: Most of the fish, unlike mammals, are metabolically ill-equipped to cope with significant amounts of carbohydrates in their diet. However, the requirements of glucose in fish are important because there are tissues that use it as a vital energy substrate, hence the need to maintain controlled glucose levels in the blood. The regulation of blood sugar is closely linked to the actions of various hormones, such as catecholamines (epinephrine, norepinephrine Oh, NA), and while control of their liberation is largely cholinergic, there is also a non-cholinergic en el que se ha speculated that can be involved serotonin (5-HT). In fish, the 5-HT is very little known, especially at the peripheral level. The basic objectives raised in this study were: i) identify major deposits peripheral 5-HT in rainbow trout, Oncorhynchus mykiss and its importance in the homeostasis of the 5-HT blood, and ii) investigate whether there was a control ( the central and / or peripheral) of the 5-HT on the release of catecholamines and blood sugar, as well as potential recipients 5-HT involved. The results revealed for the first time in fish, that: i) the principal deposits peripheral 5-HT are intestine and gills, followed by the kidney, liver, heart and spleen. The gut releases the 5-HT from the plexuses nervous 5-HT in the muscular layers of the intestinal wall and immediately recapta for metabolizarla. The low 5-HT not metabolized in the intestine reaches other tissues (liver and gills) through blood, to be grasped and metabolized. Acid indolacético (5-HIAA) that reaches the plasma from the degradation of the 5-HT, is rapidly eliminated via urine by an effective system of renal excretion, and ii) in the rainbow trout there is no central control of the 5-HT on the sympathetic nervous system, the 5-HT acts on peripheral on the system interrenal producing a hyperglycaemic effect by controlling the secretion of the A through activation of receptor type 5-HT1-like, although this does not rule out participation (minor) receptor 5-HT2 through modulation of the secretion of the NF. ELECTROPHYSIOLOGY AND MORPHOLOGY OF MOTONEURONAS KERNEL ENGINE COMMON EYE DURING POSTNATAL DEVELOPMENTAuthor: Carrascal Moreno María Livia. Year: 2006. University: SEVILLA [ www.us.es]. Place of defense: Facultad de Biología. Place of preparation: Facultad de Biología. Summary: The overall objective of this Doctoral Thesis is the electrophysiological and morphological characterization of motoneuronas (Mns) kernel engine eye (nMOC) during postnatal development. Or Second stage or intermediate stage (6-20 days) in the ending of the characteristics of the mature action potential. Or Third stage or final stage (> 20 days) in which Mns show electrophysiological characteristics typical adult. The Mns of nMOC the rat had enormous changes in major morphometric characteristics during development can make out two major stages: First stage or that elapses from birth until approximately the first 10 days postnatal in which there is an increase in the complexity and length of dendrites accompanied by an increase in surface somato-dendrítica. Moreover, at this early stage some cells show coupling. Second stage or from the 10 days postnatal in which there are no more growth in surface membrane because it is a regression in the complex, accompanied by an increase in the length of the segments, as well as an increase in Maximum distance from the soma to the terminal and the dendritic diameter. All these data show that during the postnatal development will produce significant changes in the characteristics morfo-funcionales of Mns of nMOC, which lead in the adult animal to make the bindings and eye movements in the right way .. ROLE OF ENDOGLIN AND ALK-1 ON THE ROAD SIGNALING TGF-BETAAuthor: BLANCO LÓPEZ FRANCISCO JAVIER. Year: 2006. University: COMPLUTENSE DE MADRID [ www.ucm.es]. Place of defense: FACULTAD DE MEDICINA. Place of preparation: FACULTAD DE BIOLOGÍA. Summary: The vascular endothelium is a single cell that tapiza inside the blood vessels that are in direct contact with the bloodstream. The process of formation of new blood vessels from preexisting other is called angiogenesis. In this process, the growth factor transformante-beta (TFG-beta) is a cytokine that plays a dual role, exercising functions both pro-angiogénicas as anti angiogénicas. In this thesis has shown that endoglin, receiver assistant TGF-beta highly expressed on endothelial cells is capable of promoting the activation phase of angiogenesis in response to TGF-beta. It has been obtained that is able to interact with ALK-1, receptor type I TGF-beta expressed predominantly in endothelial cells. This partnership physical takes place at both extracellular and cytoplasmic and results in a functional cooperation on their path signaling, that is, through SAmd1. It phenomena as well induce cell proliferation and induction of specific genes as ld1. By contrast, endoglin is able to block the path of signaling TFG-beta through the widely expressed type I receptor, called ALK-5 through Smad3. Moreover, it has been observed that when endothelial cells entering senescence, there is a change in the expression of endoglin isoform, generating a protein shorter called endoglina-S. This isoform is able to interact with both receptors type I TGF-beta but with a much higher affinity for ALK-5. The result of the expression of endoglina-L. Endoglina-S favors via signaling ALK-5/Smad3 the detriment of the ALK-1/Smad, reflecting an increase in the transcriptional activity of the promoter of PAI - 1 and decreased from ld1 respectively. Furthermore, it has been shown that ALK-1 is located in approximately microdominios specialized plasma membrane called caveolas, where it is able to interact with caveolina-1, its major protein component. This direct association depends on the mastery of scaffold caveolina-1 which recognizes a ground consensus in the region Trp339-Trp406 of the primary structure of ALK-1. This interaction results in activation of angiogenesis, representing one of the few cases so far in which caveolina-1 exerts a positive functional cooperation. Both the majority isoform endoglin as caveolina-1 has a role pro-angiogénica in endothelial cells, promoting the cellular response to this multifunctional cytokine. AGING FAT. INFLUENCE OF A FATTY DIET AND HORMONE THERAPY DEHYDROEPIANDROSTERONEAuthor: PÉREZ DE HEREDIA BENEDICTE FÁTIMA. Year: 2006. University: MURCIA [ www.um.es]. Place of defense: FACULTAD DE BIOLOGIA. Place of preparation: FACULTAD DE BIOLOGÍA. Summary: The adipose tissue is not homogeneous mass and passive believed, but communicates with the rest of the body. The adipocitos have receptors for neuroendocrine signals and secrete more than 50 bioactive substances, such as leptin, adiponectina, resistina, or cytokines, involved in the regulation of many functions. The adipose tissue also aging, and increases with age, the percentage of body fat. The lifestyle of our society (sedentary and high consumption of energy and fat), favors the accumulation of tissue, which, along with the increase in average life expectancy, leading to populations with a growing number of individuals overweight. Aging and obesity are related to diseases like diabetes, hiperlipidemias, cancer and cardiovascular risk, making it essential to find a therapy to slow down the progression of obesity and its complications. One candidate is Dehydroepiandrosterone (DHEA), a hormone, to which was attached slimming and rejuvenating properties. In this paper we study what physiological and biochemical changes occur with aging in the adipose tissue of Sprague-Dawley rats fed a fatty diet; determine how they influence the evolution of other parameters, such as sensitivity to insulin or plasma lipids, and hormones ; analyze whether DHEA reverses these changes, and compare the reaction of various fatty deposits to different stimuli. Some of the rats were fed with feed standard (control group), and part with a fatty diet. At different times (6 and 14 months of age) were killed subgroups of rats. At 16 months of age, animals were divided into two groups, one of which received a supplement DHEA to 0.5% in the diet for 13 weeks. We extracted brown adipose tissues, subcutaneous, periovárico, perirrenal and mesenteric to study size adipocitos, fatty acid profile and gene expression of adipoquinas. In the old animals were analyzed lipolisis to see if altered by treatment with DHEA. In measured plasma glucose, lipids, insulin, SDHEA, leptin, adiponectina, resistina, TNF, SHBG and fatty acid profile. The rats with fatty diet ate more energy, but did not elaborate on obesity in the first few months. Over time, it noted a significant increase adiposity in these animals. This highlights a synergy of age and diet changes in body composition. With age increased concentrations of plasma lipids, increasing the risk metabolic. The concentration of insulin, for its part, did not change with age or with either diet. Animals with diet had lower concentrations of fatty adiponectina and resistina that their controls. With age decreased SDHEA and adiponectina and increased leptin and resistina. These changes show a hormonal profile prone to a higher risk with metabolic aging. The expression of leptin and adiponectina decreased with age, while the resistina increased. The changes were significant deposits visceral, but not in the subcutaneous. The fatty acid profile of adipose tissue was typical of the region: the brown was the most congested, the subcutaneous the most unsaturated and mesenteric the most trans acids accumulated. Age and diet influenced this profile, with the fatty diet increased the AGS and oleic, at the expense of the PGA, reaching out the differences between initial deposits. With age, rose AGM and the PGA and fell AGS. In rats with DHEA decreased intake, weight and body fat, reversing the increase occurred during aging. The subcutaneous tissue was the most declined. In addition, increased exp 8 resión d 5a5 and adiponectina, suggesting a new mechanism of action in the beneficial effects of DHEA, and decreased concentrations of insulin, confirming its protective effect against the risk metabolic. Treatment modified fatty acid profile of adipose tissue, increasing the stearic and oleic and linoleic decreasing. The brown fabric rose the n-3, suggesting a possible link between DHEA composition of tissue and termogénesis. The factor analysis revealed that the most influential variable in the adipose tissue were age and fatty acids, especially AGS and AGM, followed by adiposity, leptin and insulin. Both the dietary treatment like hormone emerged as agents capable of altering the values of the parameters studied and the relationships between them. INFLUENCE OF THE CONTRIBUTION OF CAROTENOIDS IN THE DIET ON THE PIGMENTACIÓN, LIPID COMPOSITION AND PHYSICAL DEVELOPMENT OF JUVENILE BOCINEGRO OR SNAPPER (PAGRUS PAGRUS)Author: TEJERA HERNANDEZ NOEMI. Year: 2006. University: LA LAGUNA [ www.ull.es]. Place of defense: FACULTAD DE FISICA. Place of preparation: FACULTAD DE BIOLOGIA. Summary: The incorporation of new species of marine fish aquaculture is a challenge for the future development of this activity. The progress made in establishing techniques for growing bocinegro (Pagrus pagrus) allow regarded as a kind with a strong potential for aquaculture, and the difficulty in obtaining copies properly pigmented captive, the main obstacle to the commercialization of this species. In other espáridos, as the golden Japanese, who also have a reddish appearance in the external environment, the pigmentation of the skin results from the deposition of carotenoid pigments from the diet and, especially in the carotenoide astaxantina. The present report describes the results of four experiments fattening fingerlings of this kind, conducted in collaboration with the Ocean Institute of the Canary Islands, which has attempted to comprehensively assess the role exercised by carotenoids in the diet. To this end, have been used diets supplemented with different sources and levels of carotene, controlling how affected the growth and survival, coloring, level carotenoide total, and the level and form of the chemical astaxantina deposited on the skin of the copies submitted to study. Also, because the important requirement of highly unsaturated fatty acids that have marine fish species, has analyzed the lipid composition of the skin and lipid peroxide levels, in order to establish the role of carotenoids in protecting against oxidation of these essential fatty acids. In an initial experiment for fattening tested a diet supplemented with 12% of frozen shrimp (Plesionika sp.) To feed juvenile bocinegro, obtaining good results in terms of pigmentation is concerned. In the second experiment included different sources and levels of astaxantina, most economically viable shrimp, in the diet of bocinegro. To this end were tested levels of 25 and 50 mg / kg astaxantina Carophyll Pink and algae Haematococcus PLUVIALIS to supplement diets. In the third fattening experience lower levels were tested, 8 and 16 mg / kg sources astaxantina employed on past experience. It was also tested two levels, 25 and 50 mg / kg of carotenoide canthaxanthin. In experiments that were extracted independently of the chemical form of astaxantina supplied in the diet, free (Carophyll Pink), or esterified (Haematococcus PLUVIALIS and Plesionika sp), it was deposited on the skin of fish mostly as diéster. It was also identified certain levels of tunaxantina diéster, carotenoide described in the skin of the golden Japanese. The levels of employees in the third astaxantina experience proved insufficient to promote a reddish pigment in the skin of bocinegro, showing that the level of astaxantina more appropriate to obtain a coloring acceptable from the commercial point of view should be placed around the 20 mg / kg of feed (dry weight), being the esterified form of this carotenoide more efficient than the free time to achieve that goal. Also in this experiment were found to canthaxanthin is not effective in conferring a reddish pigmentation of the skin of copies of cultivation. As for the analysis of the composition and lipid peroxides lipídicos, the results showed that while there were no significant differences in the fatty acid composition among fish fed carotenoids and fed only with the basal diet, the level of peroxides in the skin of the latter is higher. This suggests that the inclusion of carotenoids in the diet resulted in greater protection from autooxidaciones lipid. Teni 8 endo in a4c account the results obtained in the experiments, which were conducted in tanks, and given that the system of fish farming more suited to the specific conditions of our shores is the floating sea cages were designed a fourth fattening experience to establish the suitability of these systems in the growing bocinegro. In this experiment, which tested a diet supplemented with commercial astaxantina, assistance was provided by the company Canary CEDRA, SLL, an entity which is dedicated to fattening golden bass in this type of floating structures. As a result most prominent in this experience see a darker in pigmentation copies cage respect to the tank. This fact is reflected in greater deposition astaxantina on the skin of bocinegros kept in marine cages, which can be placed higher levels of this carotenoide as protection against high intensities lumínicas to which they were exposed. So from the point of view and applied to reduce the production costs of feed supplemented with astaxantina to fatten bocinegros in cages floating marine, it is suggested not using doses above 20 mg / kg feed (dry weight) and esterified astaxantina cover the cage structures unable to reduce the light intensity on the surface of the same. Under these assumptions is currently the Project Transfer Research Results (PETRI, ref. PTR1995-0933-OP-02-01) entitled feed supplementation with astaxantina for the proper coloring of snapper (Pagrus pagrus), growing conditions commercial, coordinated by the University of La Laguna and in which the Spanish Institute of Oceanography and the company culture CEDRA, SLL This has been possible thanks to the preliminary results that have been obtained and presented in this report STUDIES INTO THE EFFECTS OF ENVIRONMENTAL SIGNALS ON EEL REPRODUCTION AND QUEMICAL COMMUNICATION.Author: HUERTAS PAU M. DEL MAR. Year: 2006. University: BARCELONA [ www.ub.es]. Place of defense: FACULTAD DE BIOLOGÍA. Place of preparation: FACULTAD DE BIOLOGÍA. Summary: The biology of eels, along with a puzzling cycle of reproduction and current stock near extinction of this species makes a very interesting subject of study. This thesis can help develop strategies for conserving for this important group teleósteos by improving understanding of their reproductive cycle, and may well have a socio-economic impact secondary. It also studied the role of environmental factors in the growth and reproduction, as it was a key factor for the artificial cultivation of the species. The importance of communication in vertebrates chemistry has been the subject of growing interest in recent years, proof of this is an increase in high-impact publications in prestigious journals. The study consists of five chapters. The first concerns the effect of density on crop growth and sexual differentiation of eel, introducing the concept of use of chemical signals in social interaction, which is dealt with in chapter two. In Chapter 3 discusses the systems involved in the transport of chemical signals from the external environment. Finally in chapter fourth and five, is studying the possible source of chemical signals that could be detected by the smell of fish and their use among and within species. DIFFERENTIATING THE DIGESTIVE PROCESSES IN RESPONSE TO THE COMPOSITION OF THE DIET IN GOLD (SPARUS AURATA) AND RAINBOW TROUT (ONCORHYNCUS MYKISS)Author: SANTIGOSA I CULÍ ESTER. Year: 2006. University: BARCELONA [ www.ub.es]. Place of defense: UNIVERSIDAD DE BARCELONA. Place of preparation: UNIVERSIDAD DE BARCELONA. Summary: The growing importance of aquaculture has prompted research aimed at improving diets for fish and reduced manufacturing costs thereof, in order to optimize the sustainable development of the sector. It is necessary to search for alternative ingredients for the meal and fish oil, traditionally used in the formulation of feed for carnivorous fish, and raw materials that are increasingly limiting. For gold (Sparus aurata) and trout (Oncorhynchus mykiss) have been experimental diets with varying percentages replacement of fishmeal by vegetable protein sources, reaching full replacement. In order to adjust the amino acid composition of the feed to the profile required by the species were used in the diets of substitution of ingredients mixed vegetables and free amino acid supplementation. In experiences of twelve weeks of growth, the replacement of fishmeal decreased the total activity of the digestive proteases, suggesting the presence of anti-nutritional factors in the diet. But in both species were presented compensatory mechanisms, such as increasing the length bowel on the increase in some activities specific proteases, or displacement of absorptive capacity from the proximal to the distal intestine. These compensatory mechanisms helped obtain good growth rates up to 75% replacement of fishmeal. Animals fed diets substitute filed a total digestive function badly damaged and a growth of about 20% lower than that of animals fed with the feed based on fishmeal. In gold was testó the simultaneous replacement of fishmeal 75% and various percentages of fish oil 33, 66 i 100%. The administration of the experimental diets with a 66% and 100% of vegetable oils during ten weeks decreased digestive enzyme activity, not hampered the capacity for absorption of amino acids. Only diet double substitution with a total replacement of fish oil negatively affected growth. We studied the effect of gold in the full inclusion of vegetable oil in diets with varying percentages 50% i 75% and origins of the plant protein sources. The animals showed different patterns of regionalization of the absorptive capacity of nutrients along the intestinal tract, according to digestibildiad of the protein sources used. The group fed diet of smaller replacement of fishmeal introduced an upper gastrointestinal proteolytic activity, and a growth rate significantly higher. The winter syndrome is a disease that affects the gold on the north shore of the Mediterranean. It has a multifactorial origin, which may cause significant economic losses during the coldest months. Have been tested in golden commercial feed with different percentages of fat 14 and 22% fees for preparation for the winter. The fattening during 75 days with the selected feed did not affect the absorption of nutrients at intestinal nor growth rates. The moderate exercise also affected the parameters studied. It ruled that at low temperatures the animals refuse the alimetno due to a disability in the absorption of nutrients, and that all groups of golden responded to a similar situation to a lasting cold. ADAPTATIONS OF THE COLON OF RATS TO SODIUM CONTENT OF THE DIET: ROLE OF THE RENIN AND VASOPRESSIN.Author: CRISTIÀ CIVIT ESTHER. Year: 2006. University: BARCELONA [ www.ub.es]. Place of defense: FACULTAD DE FARMACIA. Place of preparation: FACULTAD DE FARMACIA, UNVIERSIDAD DE BARCELONA. Summary: The dissertation includes the study of functional and structural changes occurring in the distal colon of rats due to changes in sodium intake. Specifically has studied the role of three hormone, angiotensin II, aldosterone and vasopressin, in the transport of Na + permeability in epithelial and growth miofibroblástico the area pericriptal. Through an animal model for activation of the renin (RAAS) in the rat, have reproduced the functional and structural changes in the lining of the distal colon in adapting a diet high in sodium (HS) to a diet low sodium (LS). In just 3 days of dietary LS addition to the increase in transport electrogénico sodium, there is a decrease in the permeability of the tissue, which is confirmed by an increase in the density of close associations, namely the expression of claudina 4, and an increase in resistance transepitelial. There is also the proliferation of myofibroblasts layer present in the area pericriptal, as it increases the expression of alfa-actina smooth muscle and synthesis of collagen IV and increases the expression of the union members, namely E and OB-caderina. These changes cause the accumulation of sodium in the area pericriptal, creating a tension hydraulic facilitates entry of water into an area where it is gut with a strong opposition because of the high osmolality of the faeces. The treatment with inhibitors of the enzyme chain of RAAS, captopril, losartan, and esprionolactona, reverses these effects, confirming the involvement of angiotensin II and aldosterone. To determine the specific role of each of these hormones in these adaptations of the distal colon, it has developed an animal model for activation of RAAS minimizing aldosterone synthesis through an operation adrenalectomía and controlling the plasma concentration of both hormones through exogenous infusion. The aldosterone, without the presence of angiostensina II gets reproduce the effects of diet LS increased transportation electrogénico sodium, decreasing the permeability of the tissue, increasing resistance transepitelial and encouraging growth miofibroblástico and accumulation of sodium in the area pericriptal. Angiotensin II, however, by itself does not reproduce these effects. The results are contained in two publications (Moretó et al., 2005). They also have studied the effects of the degree of dehydration on the functions of the distal colon, checking the direct involvement of the vasospresina and identifying receptors involved. Both dehydration and high concentrations of vasopressin lead to a decrease in the permeability of the tissue, an increase in the accumulation of sodium in the area pericriptal and an increase in the growth miofibroblástico. Both types of receptors V1 i V2, are involved in these effects. Moreover, it has confirmed the expression of acuaporina-2 (AQP-2) in the lining of the distal colon and increased expression in states of dehydration and because of the administration basopresina. Expression of AQP-2 is mediated by the recipient V2, and that only treatment with tolvaptan, an antagonist específcio of these receptors, inhibiting. This study highlights the hormone aldosterone as key adaptations of distal colon to reduce sodium intake in the diet, snapping a direct role of angiotensin II in these effects. In terms of dehydration, vasopressin also decreases the permeability epithelium and induces growth miofibrolástico, in addition to regulating the movement of water through acupaporinas through its receptors V2 in the distal colon of rats. EFFECT OF DIETARY SUPPLEMENTATION WITH ESPERMINA AND ESPERMIDINA ON POSTNATAL MATURATION OF THE IMMUNE SYSTEM IN RAT INTESTINAL AND SYSTEMIC.Author: GONZÁLEZ CASTRO ANA MARÍA. Year: 2006. University: BARCELONA [ www.ub.es]. Place of defense: FACULTAD DE FARMACIA. Place of preparation: FACULTAD DE FARMACIA - UNIVERSIDAD DE BARCELONA. Summary: The lymphoid tissue associated with the small intestine or GALT constitutes him component defensive majority of the mucous membranes and has anatomical and functional characteristics different from the systemic immune system. Most structures that form the GALT are formed during fetal life, but its functionality is not fully developed until after birth. The immunologic maturation process is influenced by exogenous factors from the diet, the introduction of commensal flora and contacts with potential pathogens. Previous studies conducted in our laboratory have established the progressive phenotypic maturation of linfoctios epithelium and lamina propria of the gut during the lactation in rats. The importance of breastfeeding in the maturation of the immune system along with its protective role in front of infections and allergies today is unquestionable. Among the agents of bioactive milk are the polyamines, amines biógenas policatiónicas necessary for the growth and cell proliferation. In this regard, it has been observed that the administration of polyamines, so additional lactation in experimental animals leads to the early ripening of the structure intestinal and digestive function. Therefore have addressed the following objectives and have drawn the following conclusions for each of them. * To determine the effect of dietary supplement with polyamines espermina and espermidina during lactation on the phenotypic maturation of epithelial cells and the intestinal lamina propria, and on the ability of antibody secretion of the intestinal lamina propria. Both polyamines accelerate the gradual reduction in the proportion of linfoctios intraepiteliales CD8 + occurring under physiological conditions during breastfeeding. In proximal intestine, the administration of espermina increases the proportion of cells with phenotype CD8alfaalfa + NKR-P1A +, and CD2-. Phenotype characteristic of NK cells involved in the innate immune response. However, in the distal intestine, espermina induces a greater proportion of IEL CD8 + with phenotype TCRalfabeta + CD8alfabeta + and CD2, characteristic of cytotoxic T lymphocytes involved in the adaptive immune response. The effects of espermidina are located primarily in the distal region of the small intestine, where, in a manner similar to espermina increases the relative share of the lymphocyte TCRalfabeta + subpopulation, CD8alfabeta + and CD2. * To determine the influence of dietary supplement with espermina and espermidina on the maturation of the immune system systemic during lactation, specifically on phenotypic changes of splenic lymphocytes and their ability secreting immunoglobulins. Both polyamines accelerate the increase in the proportion of CD4 + lamina propria, which occurs on a physiological during lactation. Also favoring the presence of CD4 + phenotype with mature CD90-. The administration of espermina accelerates reduction in the proportion of lymphocytes CD8 + lamina propria observed under physiological conditions during lactation. * To evaluate the possible protective effect of daily administration of polyamines from birth cope with the development of inflammation of the small intestine. Both polyamines are not capable of protecting against the development of inflammation induced by indomethacin in young rats. Therefore, as final conclusion can be established that espermina and espermidina conducive to the development and maturation of the intestinal immune system in rats during lactation, but they are not capable of protecting against the development of inflammation induc 8 first leg by 1ad indomethacin in young rats. IMPLICATION OF METABOLITES ACID ARQUIDÓNICO PRODUCED BY LIPOXIGENASAS AND CYTOCHROMES P-450 ON THE PROLIFERATION OF FIBROBLASTS 3T6.Author: CALATRAVA DIANA NIEVES. Year: 2006. University: BARCELONA [ www.ub.es]. Place of defense: FACULTAD DE FARMACIA. Place of preparation: FACULTAD DE FARMACIA - UNIVERSIDAD DE BARCELONA. Summary: Previous studies showed that the decline in the release of arachidonic acid (AA) by inhibiting the activity phospholipase (PL) A2, reduced the proliferation of fibroblasts 3T6 induced fetal serum. At the same time, it demonstrated the role of prostaglandins (PGs) in controlling the growth of fibroblast 3T6 induced by serum. It noted that the inhibition of cyclooxygenase (COXs) resulted in a partial reduction of cell proliferation, whereas antagonists receptoriales of PGE2 blocked almost entirely the growth of fibroblast 3T6. These results suggested the involvement of the AA metabolites produced through other channels on the growth of fibroblast 3T6, as the route of lipoxigenasas (LOXs) or route of cytochromes P -450 (CYPs) that produce leukotriene (LTs ), acids hidroxiecosatetraenoicos (HETEs) and acid epoxieicosatrienoicos (EETs). Thus, in this paper we study raises the involvement of these pathways on controlling the proliferation of fibroblasts 3T6. These results suggest that growth factors such as serum induce the synthesis of PGE2 and 12 (S) -HETE in cultured fibroblasts 3T6, while levels of LTB4 are at the limit of detection. On the other hand, specific inhibitors of the 5-LOX (zileuton) and the 12/5-LOXs (Baicaleína), and receptor antagonists of LTs (U-75302, REV - 5901, LY - 171883) not of significantly inhibited the growth of fibroblast 3T6 or thymidine incorporation. However, the macrophages RAW 264.7, a cell line where it has been shown that expression of 5-, 12-and 15-LOXs and where AA is metabolized mainly by COXs and LOXs, these treatments were able to inhibit the cell proliferation and mainstreaming timidan. In addition, the zileuton resulted in a delay in the cell cycle by increasing the number of cells at the stage G0/G1. In addition, we found that inhibition of growth by inhibitors of 5-LOX and antagonists receptoriales of LTs is not due to the induction of apoptosis, or cytotoxicity in macrophages RAV 264.7. These results suggest the involvement of the 5-LOX and recipients of LTs in controlling the proliferation of macrophages RAW 264.7. On the other hand, our results show that the exogenous addition of LTB4 and LTD4, in the absence of serum, induces an increase in the number of cells and the incorporation of thymidine of macrophages RAW 264.7, and this effect is mediated by the activation of MAPK pathways and PL3K/Akt. EPA competes with the AA to be matabolizado by COX-2, forming the PGs in the series-3, and the 5-LOX, leading to LTB5. Our results show that the PG3 stimulated proliferation of genetic macrophages with a similar power wing of the PGE2, while the LTB5 had less effect than LTB4. Because the path of sLOXs did not seem involved in controlling the proliferation of fibroblasts 3T6, focused interest in studying the involvement of metabolistos of AA produced by the CYPs. The CYPs may have activity * / *- 1 hydroxylase and tipo-lipoxigenasa forming HETEs or epoxigenasa producing EETs. Our results showed that serum induces the synthesis of 12 (S) -HETE in fibroblasts 3T6. Furthermore, the use of inhibitors of CYPs as sKF-525A, 17-ODYA, ABT or PPOH inhibited the synthesis of 12 (S) -HETE, cell growth and DNA synthesis. The SKF-525A resulted in a delay in the cell cycle, which might explain the inhibitory effect of these treatments on the growth and thymidine incorporation. In addition, the 5-HETE, 12 (S) -HETE, 15 (S) -HETE and 20-HETE reversal of cell growth inhibition induced by SKF-525A, while the 11,12-EET not the foundation, 5-HETE, 12 (S) -HETE and 15 (S) -HETE induce the growth of fibroblast 3T6 and the synthesis of DNA, and 8 this Efe 6aa ct came through the activation of the path Pl3K/Akt. In addition, these metabolites increased levels P-Akt. On the other hand, the thesis shows that the exogenous addition of 5,6-EET, 8,9-EET, 11,12-EET, 14,15-EET, 5,6-DHETE or 11,12-DHETE inhibited proliferation the fibroblast 3T6 and thymidine incorporation induced PDGG. In addition, it is suggested that these metabolites are pro-apoptóticos and increasing outsourcing of fosfatidilserina, caspase activity and total fragmentation of the nuclear chromatin. The 11,12-EET and 14,15-EET increased activity caspase-3 in fibroblasts 3T6, and this effect was the result of a prior activation of the caspasa-12. However, these metabolites were not able to significantly induce caspase-9 or activity caspase-8 under the experimental conditions used. Therefore, the results suggest that the path mediated stress in the endoplasmic reticulum might be involved in the action pro-apoptótica of 11,12-EET and 14,15-EET. In short, the proliferation of fibroblasts 3T6 would be governed by the AA metabolites produced by the path of COXs and by way of CYPs. In the latter case, involving the HETEs with proliferative effect, and EETs with effect anti-proliferativo and pro-apoptótico.
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