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EXPERIMENTAL STUDY OF THE EFFECTS OF AGING ON THE AUDITORY RECEIVERAuthor: MAESTRE LÓPEZ LORENA. Year: 2002. University: COMPLUTENSE DE MADRID. Place of defense: FACULTAD DE BIOLOGÍA. Place of preparation: FACULTAD DE BIOLOGÍA. Summary: The presbiacusia is progressive hearing loss, bilateral and symmetric associated with aging. The morphologic alterations associated with presbiacusia include: the loss of the sensory cells, cells of the pillars, nerve cells of spiral ganglion, as well as an alteration of structures related to the production of endolymph as in the case of vascular groove . Another possible effects of presbiacusia could be the alteration of efferent fibers that contact with the hair cells and from the complex higher olive grove. In this Doctoral Thesis has conducted a study of the degeneration of auditory receiver with age as animal model using the mouse strain C57BL / 6, due to its characteristic of presenting a sensorineural aging very early, with characteristics similar to humans, for it has encompassed the study of different cell structures that are altered during the presbiacusia, the receiver hearing itself, the afferent nerve fibers that transmit information to the central nervous system and efferent fibers that regulate such transmission. The animals were divided into 9 age groups from 1 to 24 months. For the study of auditory receiver has witnessed a pattern of distributing the galectina-1. The gelectina-1 is a glycoprotein group of lectin involved in the adhesion and cell proliferation. In the cochlea of adult animals is expressed in the epithelial cells of the internal and external spiral groove surrounding the cell and sensory cells of the organ of Corti support. During the presbiacusia, in parallel with the process of degeneration of the organ of Corti, I found an alteration in the expression of that lectina going to occupy places where not present in the receiver normal hearing. The latest status of this degeneration is the replacement of the receiver by a monolayer of cells expressing strongly galectina-1, particularly in the low and medium espiras of the cochlea which correspond to the frequencies acute. The results could indicate the important physiological function of the galectina-1 and its ligands in the process of receiving auditory degeneration associated with aging. Along with the degeneration is detected by methods described morphometric a decrease in the number of spiral ganglion neurons from occurring gradually beginning in the cochlea espira baseline and subsequently incorporated espiras averages. This shows the resilience of high espiras cochlear the degeneration caused by aging. In the case study of altering the efferent fibers with evejecimiento has been used as a marker protein sinaptofisina, protein hexamérica present in the small synaptic vesicles (SSVs), and considered as a specific marker of sinápsis efferent, in our case the system eferente lateral and medial. A morphometric study immunohistochemical and has been detected a decrease in the amount of this protein with age is more pronounced, as in the previous cases, the espira baseline. The loss of sinaptofisina at this level could involve the loss of function associated with these fibers, namely a lack of protection against intense noise and the lack of inhibition in certain messages sound. COMPARATIVE STUDY OF THE EFFECTS OF HYPERCHOLESTEROLEMIA AND MIXED DYSLIPIDAEMIA ON VASCULAR FUNCTION AND STRUCTURE. IMPLICATIONS OF LIPID-LOWERING THERAPY.Author: CEDIEL GIL EVA. Year: 2003. University: COMPLUTENSE DE MADRID. Place of defense: FACULTAD DE MEDICINA. Place of preparation: FACULTAD DE CIENCIAS BIOLÓGICAS.
Summary: Introduction: Plasma levels of total cholesterol and low-density lipoprotein (LDL) play an important role in the development of atherosclerosis and subsequent crowning of the disease, which is a leading cause of cardiovascular morbidity and mortality. Laacumulación lipids in the blood during hypercholesterolemia and mixed dyslipidaemia produces alterations in vascular function even before they are morphological changes and comoalteraciones in fibrinolysis. Objectives: 1) compare the effect of a diet high in cholesterol and a diet high in cholesterol more saturated fatty acids on the vascular structure and function, and fibrinolysis in rabbits. 2) To study the effects of chronic treatment with an HMG-CoA reductase inhibitor on the functional vascular alterations, structural and fibrinolytic, hipercolesterolémicos rabbits and mixed dyslipidaemia. Materials and Methods: The study was performed in male rabbits New Zealand (2 kg) fed durante14 weeks with a diet high in cholesterol at 1% (HC: hipercolesterolémico) with a diet rich encolesterol to 0.5% plus 14% oil coconut (MD: dislipémico), and a standard diet as control of the above (C: control). Half of the animals in each group were tratadossimultáneamente with atorvastatin (ATC: 2 mgIKgldía). At the end of the period of 14 weeks tomaronmuestras blood to measure plasma levels of total cholesterol and triglycerides, plasma activity of t-PA and PAl-l. The thoracic aorta was extracted for the study of vascular reactivity in anillosaórticos (vasorrelajación and vasoconstriction of endothelium-dependent and independent) and structural changes (area of the injury, an area of the glass, area dellúmen and area of the average) and ultrastructural. Results: Laadministraciónde a dietaenriquecidaconun 1% colesterolo witha dietaconun0.5% cholesterol more than 14% of coconut oil is associated with a similar increase in nivelesplasmáticos cholesterol. Only observed elevated levels of triglycerides in animals fed with a 0.5% cholesterol more than 14% of coconut oil, a decline in relajacióndependiente of endothelium, which is most pronounced changes in animals with mixed dyslipidaemia, unchanged for the endothelium-independent relaxation, a reduction comparable to the respuestavasoconstrictora to KCl in rabbits hipercolesterolémicos and dislipémicos unchanged in response to FE and AlI; an increase in endothelium-dependent contraction (Ach + LNAME), this being higher in rabbits with dyslipidaemia mixed, unchanged in response to ET-1 YU46619; an increase in the plasma activity of PAl-ly a decrease of the activity of plasma t-PA, an increase of the area of the lesion and a reduction in the area of light that was higher in rabbits with mixed dyslipidaemia in hipercolesterolémicos. Treatment with atorvastatin produces a decrease in plasma levels of cholesterol. Only in rabbits with mixed dyslipidaemia there is a reduction in plasma levels of triglycerides; an increase in vasorrelajación dependent endothelium, more pronounced in rabbits with mixed dyslipidaemia, and without alteration in the endothelium-independent relaxation; an increase in the response vasoconstrictor to KCl in rabbits hipercolesterolémicos and mixed dyslipidaemia unchanged in response to FAITH, a decrease of the vasoconstrictor response to IIA hipercolesterolémicos in rabbits and mixed dyslipidemia, a decline in the vasoconstrictor response of endothelium-dependent (Ach + LNAME). It modifies the response to ET-1 and U46619; improved fibrinolytic balance, a reduction in the size of the lesion and an increase in the area 8 of the l 40c uz, higher in rabbits with mixed dyslipidaemia in hipercolesterolémicos. Conclusions: R) hypertriglyceridemia power the deleterious effect of cholesterol on the endothelial function and vascular structure. However hypertriglyceridemia not power the effect of cholesterol on fibrinolysis in rabbits. 2) Treatment with atorvastatin improves endothelial function, structure and imbalance vascular fibrinolytic, similar in rabbits hipercolesterolémicos and mixed dyslipidaemia. These beneficial effects seobservaron even enpresencia high levels of cholesterol. TEMPORAL LOBE EPILEPSY DRUG-RESISTANT. CONTRIBUTIONS OF THE CLINICAL NEUROPHYSIOLOGY.Author: LLANO SAN CLAUDIO IGNACIO. Year: 2004. University: COMPLUTENSE DE MADRID. Place of defense: FACULTAD DE MEDICINA. Summary: This paper attempts to analyze the results of surgery for ELT in a series of cases from 2001-2004 in the unit of the Epilepsy Surgery (EUA) Hospital Universitario de la Princesa, comparing the results with previous studies and exoner new inputs the v-EEG with EFO for the diagnosis and prognosis of surgery for ELT. Thus what follows is a description of the sampling characteristics of the series, analysis of the surgical morbidity of surgical outcomes in terms of controlling the crisis after a minimum follow-up of 6 months (assessing the ability to control the crisis and analysis of possible prognostic factors: age of the patients at the time of surgery, age of onset of epilepsy, years of disease progression, sex, lobe involved, the frequency of crises before surgery). It also proceed to carry out a study of the diagnostic capability (lateralizadora and localizadora) of the various tests study prequirúrgico (MRI, EEG, SPECT interictal and vídeo-EEG with and without EFO, a comparison of the results with the number of prior cases (UCE patients in the greater 1990 and July 2001) and a study of the neurophysiological characteristics of the ELT with v-EEG with EFO, presented special attention to siguietnes appliances: Patterns bioeléctricos ictales obtained with v-EEG with EFO in ELTM, critical relationship between patterns and prognosis surgical and analysis of voltage sources in studies with EFO. EFFECT OF CHRONIC HORMONE TREATMENTS ON AGING BRAIN.Author: SALAZAR NUSSIO VERÓNICA. Year: 2004. University: COMPLUTENSE DE MADRID. Place of defense: FACULTAD DE MEDICINA. Place of preparation: FACULTAD DE MEDICINA. Summary: It is known that the aging process is associated with a decrease in FM synthesis and / or. Secreciónde several hormones, many of which have a recognized role neuroprotective. In order to study the process of aging brain and repercursionesde various treatments; hormonal chronic carried out a survey which consists of two phases. An initial, whose aim is to study the evolution of aging in various morphological cere1frafes-errratas-Wistar. Both sexes, and a second phase, which discusses the impact exerted by different hormone treatments chronic (WR, Melatonin, Estradiol, RI + Estradiol and Phytosoya @) on the parameters changed with age. It is also conducting a study of the effect of chronic treatment with GH and Melatonin on learning and spatial memory in male rats. For the first phase, using three different subpopulations: one male and one female aged 2 to 24 months of age (mdv) divided into different groups depending on the age at which they are being slaughtered, and a third subpopulation females castradas to 12 mdv, which are slaughtered between 14 and 24 mdv The second phase was carried out in rats of 24 mdv Males and females (castradas and intact) that are subject to different hormone treatments chronic. The last study was conducted in rats male 24 mdv Treated with GH and with Melatonin. . Parameters studied are: total number of neurons in the hilus of the hippocampus, cell proliferation in the teeth turn, levels Nucleosomas yde Bcl: 2 in homogenado cerebral expression of Mn-SOD, GPx and Sir2 in total brain and the expression of caspase -3 and -9 in the hypothalamus. For the study of learning and memory space, our animals are subjected to the Morris water maze. With age, the total number of neurons hilares disminuyede significantly from the 22 m, d; it. In rats of both sexes. ASimismo, cell proliferation in turn decreases teeth in a very sharp from 2 mdv In rats of both sexes. Aging brings with it an increase in the apoptotic process (increased nucleosomas) and a decrease in the defenses anti-apoptóticas (BcI2) en.ambos sexes. After treatment with growth hormone to old animals of both sexes there is a decrease in apoptosis and increased defenses antiapoptóticas in brain tissue, which include BcI-2, GPx and Sir2. All eHoconduce to maintaining the number of neurons, but does not alter cell proliferation. The chronic treatment with estradiol is not able to maintain the number of neurons hilares in females old castradas therefore is not able to change the expression of caspase-3 and -9 nor the Mn-SOQ, GPx and Sir2. Yes manages to increase however cell proliferation in turn teeth, treatment with growth hormone and estradiol in females castradas to maintain the total number of neurons in the hilus, but fails to increase cell proliferation in the drawing teeth. The chronic treatment with melatonin is not able to maintain the number of neurons hilaras Animal old values similar to those of young animals, but manages to increase cell proliferation in the drawing teeth. The fdoestrógenos not 'get to keep the number of neurons hilares in females castradas old, but they increase cell proliferation in the drawing teeth. The treatment produces a decrease in the process of apoptosis, as shown by lower Nucleosomas, while increasing the defenses antiapoptóticas by increasing levels of Bcl-2. The phytoestrogens are unable to reverse the expression of Mn-SOD, GPx and Sir2, drastically diminished after castration. Animals old 24 mdv Have a spatial learning poorer than that of young animals from 2 mdv, aunqu 8 and the end 26b to training both groups get the same effectiveness. In old animals, treatment with chronic hormone melatonin has succeeded in improving learning and memory space. Not so treatment with GH. STUDY OF THE EXPRESSION OF INTERMEDIATE FILAMENTS (VIMENTINA, GFAP AND DESMINA) IN THE RETINA OF ADULT VARIOUS SPECIES OF VERTEBRATES AND IN THE EMBRYONIC CHICKEN RETINAAuthor: SANTIAGO SÁNCHEZ CONCEPCIÓN. Year: 2004. University: COMPLUTENSE DE MADRID. Place of defense: FACULTAD DE CIENCIAS BIOLÓGICAS. Place of preparation: FACULTAD DE MEDICINA.
Summary: In this dissertation work we studied the expression filament type ID (vimentina, GFAP Ydesmina) in the retina of adult chicken, rat, rabbit and human and in the embryonic chicken retina. To this end, we used techniques and inmunoblot inmunohistoquímica. By inmunoblot Our results show that the expression of vimentina varies along the embryonic development of the retina chicken, speaking with high intensity stages E4-E6, after declining in E8 and again increase from the last stages of development. We have also found differences in the molecular weight and the intensity of expression vimentina between retinal adult of the species mentioned. The GFAP expression starts with low intensity in the retina of chicken in the state P5 and its expression increases in the following stages. In relation to desmina, we have found to be expressed in small amounts in the retina of adult chicken. The estudíos inmunohistoquimicos using human retinal show that is expressed by cells MÃ ¼ ller, astrocytes, some cells of the outer layer of the nuclear internal possibly horizontal cells, and cells in the wall of blood vessels and some that there is a gradíente decreasing expressing vimentina from peripheral retina central retina. Moreover, the population of astrocytes is heterogeneous with respect to the expression of vimentina and GFAP, which only exist astrocytes express GFAP GFAP And vimentina And others, and possibly -astrocitos only express vimentina. We also find that the desmina expressed in the human retina, gradíente descending from central peripheral retina, and dístribuye more aggressively for the blood vessels, astrocytes and the most internal cells MÃ ¼ ller. AGING AND ENTRENEMIENTO FORCE: NEUROMUSCULAR AND HORMONAL CHANGES.Author: GARRÚES IRISARRI MIRIAN ARÁNZAZU. Year: 2004. University: PÚBLICA DE NAVARRA. Place of defense: ESCUELA UNIVERSITARIA DE ENFERMERIA. Place of preparation: INSTITURO NACIONAL DE EDUCACIÓN FÍSICA DE CATALUÑA.LÉRIDA.. Summary: The first objective of this study was to examine the effect of aging on the neuromuscular system and the production of muscle strength in the upper and lower extremities. A second objective was to examine the effect of 16 weeks of training at the maximum strength, muscle power of the upper and lower extremities and the serum concentration of various hormones [Testosterone (T), Free Testosterone (TL) and cortisol (C )]. In the first study involved forty-seven men who were subdivided on the basis of age in middle-aged men (H.2, 35-46 ailos, n = 26) and elderly (H65, 60-74ai1os, n = 21). In the second estudjo vein6dós persons (median age, H46, n = l1 and elderly H64, n = 11), developed a training program combined force máxjma and muscle power led to the major muscle groups. The maximum bilateral concentric strength from the position of half sentadilla (lRMMs), chest banking ORMps), and unilateral extension of the knee (isometric, FMIER and dynamic lRMER) and the cross sectional area (ASTcF) were lower (P less O. OOl) H65 in H42. The values of ASTcF positively correlated (r = 0.59-0.65, P O. greater OI) with individual values of lRMMs. FMIER And lRMER in H65, whereas these correlations were lower in H.2. The value of the maximum force isometric (FMIER) standardized by the ASTcF in H.2 was higher (P greater 0.05-0.01) than in H65. The maximum output power per unit time of the extensors and flexors in H65fue lower (P greater O.Ol-O.OOl) that H.2 and the heights reached cn jump concentric and counter were 27-29% minors (P greater 0.001) than those recorded in H42. The group H65mostró lower capacity (P greater O. OOI) to develop muscle power with the upper and lower extremities in concentric muscle action that the H.2. In the action half sentadilla the maximum development of power was reached with loads of 60-70% lRM and action pectoral banking with the burdens of 30-45% lRM. In H65 activation of the muscles antagonists was higher (P greater O.OI-O.OOI) actions during isometric and dynamic extension of the knee that H.2. During the sixteen weeks of training were significant change in the relative improvement of the maximum strength and the muscle power of the upper and lower extremities in both groups (P greater 0.05-0.001) and no difference was found in the relative improvement among the groups. Increases of force expressed in absolute values were higher in H.6 (P greater 0.05-0.01) in H64, especially in the 8 final weeks of training. There were no changes in basal T, TL AND C. However, the analysis of covariance showed that during the 16 weeks of training the TL had a tendency to decline in H64 and increase in H4G (P greater 0.05). In the combined group of H46 and H64 were found relations between the average value of individual concentration Ty TL And improving the maximum force in the 16 weeks of training (r = 0.49 and r = 0.5, respectively, P increased 0.05). The results of these studies are consistent with those found in the literature on the parallel reduction of the maximum strength and muscle mass with aging. In older people it was observed that the relationship between force and AST of extensors of the lower limbs was lower than found in the group of middle-aged people dc. This possibly is related to a decrease in the age-associated activation neuromusucular. During aging loss of strength posiblement 8 and is dif 793 erente between the upper and lower extremities. The decline in the power and the explosive force is also larger than the decrease of the maximum strength in the upper extremities and in the lower. However, in both age groups, the muscle power is maximized with loads of 30-45% of MRI in the upper extremities and with loads of 60-70% lRM in the lower. In the elderly a high activation of the muscles antagonists could limit the full efficiency for developing strength net in the direction of the movement. The prolonged strength training is acompafta improvements in the maximum strength and muscle power in both age groups. The pattern for adjusting the maximum strength and muscle power was different between the upper and lower extremities. In older people increasing the maximum strength and muscle power was lower than middle-aged people. However, in both age groups increased muscle mass in a similar way. In older people limitations type neuromuscular and endocrine could hinder the ability to develop maximum strength and power with muscle strength training. The results found in this study are useful for the spoke of strength training and muscle power. Keywords: Aging, training, maximum strength, muscle power, Testosterone, Cortisol, activation agonist, antagonist. EFFECTS OF DIFFERENT LIPID EMULSIONS ON PARENTERAL FUNCTIONS OF NEUTROPHILS AND LYMPHOCYTESAuthor: BUENESTADO CANTADOR Ma. DESAMPARADOS. Year: 2004. University: VALENCIA. Place of defense: Facultad de Medicina - Universitat de València. Place of preparation: FACULTAD DE MEDICINA Y ODONTOLOGÍA. Summary: The emulsions lipídicas parenteral aim to be the primary source of energy and essential fatty acids. There is enough evidence to suggest that this kind of nutrition affects the immune function. In our study we wanted to verify experimentally the existence of differences in the effect of different immunosuppressive lipídicas emulsions used in parenteral feeding containing different lipid composition and evaluate them the functions of neutrophils and lymphocytes were affected. The emulsion Lipofundina @ presented a profile anti-inflammatory and immunosuppressive inhibiting the chemo, the release of Ca2 +, the trancripción and release of IL-8 neutrophil and the release of IL-2 in lymphocytes in vitro. Intralipid @ introduced profile immunosuppressant, inhibiting the proliferation and the release of IL-2 lymphocyte, as well as an increasing apoptosis neutrofilica in vitro. Both were able to reduce interactions leucocito-endotelio induced by LPS in an experimental animal model thereby reducing the ability of the host to defend itself against infections Clinoleic @ affected (only to the release of elastase neutrophilic being deprived of immunosuppressive effects both in vivo and in vitro. MECHANISMS FOR THE PROTECTION OF ISCHEMIC PRECONDITIONING IN LIVER TRANSPLANTATION GRAFTING ESTEATÓSICOSAuthor: CARRASCO CHAUMEL ESTHER. Year: 2004. University: BARCELONA. Place of defense: FACULTAD DE BIOLOGÍA. Place of preparation: INSTITUTO DE INVESTIGACIONES BIOMÉDICAS DE BARCELONA - CONSEJO SUPERIOR DE INVESTIGACIONES CIENTÍFICAS.
Summary: Currently, the main limitation of liver transplantation is the lack of donors. To compensate for the lack of bodies on many occasions resorted to organ transplant that are not optimal for this purpose, called livers subóptimos. These grafts highlights, for its prevalence, livers esteatósicos. Livers esteatósicos are more susceptible to injury from ischemia / reperfusion (I / R) associated with liver transplant that not fatty livers, and thus are at increased risk of dysfunction after being transplanted. Studies conducted in models of ischemia normotérmica point to a major change in the liver microcirculation, an increase in the accumulation of neutrophils, increased release of inflammatory mediators or greater injury by oxidative stress as possible causes of this increased vulnerability to injury R / R. The Precondicionamiento (CP) ischemic, a surgical strategy based on the application of brief periods of ischemia before subjecting the body to an R / S prolonged, has proved effective in protecting the fatty livers off the injury I / A model of ischemia normotérmica, which suggests that the preservation of ATP levels exerted by the PC ischemic would have a decisive role in protecting the ischemic PC in this type of livers. Several authors suggest that NO and AMPK are involved in protecting the PC front of the ischemic lesion of R / S in experimental models of ischemia normotérmica. On these bases, in this thesis raised the following objectives: 1-Studying whether the PC ischemic, modulating the mechanisms involved in the increased vulnerability of fatty livers from injury I / R, protects against lung and the liver injury associated fatty livers for transplantation. Just as the assessment of the involvement of NO in the protective effect of ischemic PC. 2-To assess the role of AMPK and NO on the effects of ischemic PC in the energy metabolism of fatty livers before transplantation. Under the conditions evaluated in this thesis alterations in the microcirculation, the accumulation of neutrophils or production of TNF-alpha did not appear to be the mechanisms responsible for the increased susceptibility of fatty livers from injury I / R, on the contrary The oxidative stress plays a fundamental role in the increased susceptibility presenting this type of livers from injury I / R associated with liver transplantation. The PC ischemic protected livers esteatósicos off the injury I / R associated with liver transplantation. The PC ischemic, modulating system xanthine / XOD, reduced lung and liver injury associated with the transplant grafts esteatósicos. NO is involved in protecting the PC on ischemic injury associated with liver and lung transplant livers esteatósicos. This mediator vasoactive the modular system xanthine / XOD and harms of genetic OFR, protected against the local and systemic disorders associated with liver transplantation. The synthesis of NO during the ischemic PC is induced activation of AMPK. Strategies based on the pharmacological management of AMPK or activators of NO donors simulate beneficial effects. While activator of AMPK are also beneficial in the case of grafts esteatósicos, NO donors were ineffective in such grafts. In these circumstances, the NO was combined with excess OFR in this type of graft generating peroxinitritro, further aggravating the vulnerability of this type of livers from injury R / R. FUNCTIONAL STUDY OF THE PROJECTION COMISURAL OF COLICULO LOWER IN THE RAT PIGMENTED.Author: HERNANDEZ GONZALEZ OLGA. Year: 2004. University: SALAMANCA. Place of defense: FACULTAD DE MEDICINA. Place of preparation: FACULTAD DE MEDICINA. Summary: The colículos lower (ICs) in both hemispheres are connected through the comisural the BOI (CoCI). Previous studies show that this projection is mainly comisural by neurons excitadoras, though there are studies that suggest the existence of a small number of neurons inhibitory GABAergicas. Although CoCI is the road that connects the most important nuclei of brain stem auditory system, its functional role is unknown. To investigate its role, we have recorded the neural activity evoked in the neurons of an IC while inyectábamos acid quinurénico (nonspecific blocker of glutamate receptors), in the contralateral CI. After blocking the projection comisural witnessing declines and increases in spectral and temporal responses. The decline in activity suggests that comisura contains fibers excitadoras and increased inhibitory fibers and therefore its effect may be mediated by circuits monosinapticos or disinapticos excitadores-inhibidores. In addition, the effects were proportionately larger at levels near the doorway. For this reason we concluded that the projection comisural modulates neuronal gain control of the BOI. Additionally, we conducted a survey of the basic physiological properties of neurons in the rat's IC pigmented to obtain a control data. This registration maps frequency (MdFs) 237 neurons after stimulation with pure tones. The MdFs were classified according to type of area as a type V (69%) and type no-V (29%), the rest of the units were unclassifiable. The MdFs no-V is a very heterogeneous group, which includes responses type narrow, closed, low and high frequencies, multiple peaks, with U-shaped mosaic and inhibitory. MEDIATORS APOPTOSIS DURING RENAL ISCHEMIA REPERFUSIONAuthor: VIÑAS MUÑOZ JOSÉ LUIS. Year: 2005. University: BARCELONA. Place of preparation: INSTITUTO DE INVESTIGACIONES BIOMÉDICAS DE BARCELONA. Summary: The injury renal ischemia reperfusion is a disease of great significance and clinical importance. During this process will develop a series of pathological phenomena including programmed cell death also called apoptosis. This is mediated by various factors such as nitric oxide (NO) and its producing enzymes. In this work, based on a model in vivo, we describe an interaction between endothelial isoform and the inducible isoform of the NOS through which the activity of endothelial isoform induces an increase in expression of the inducible isoform during the process of ischemia reperfusion renal. Also this work also describes the role of the mitochondria and more specifically the NOS presented within this orgánulo during ischemia reperfusion. This mitochondrial isoform was found sobreexpresada during the process of ischemia reperfusion, triggering the production of peroxynitrite by interaction between NO and free radicals present in the interior mitocontrial, and producing an alteration resulting in a mitochondrial release of cytochrome c and subsequent incidence of apoptosis . The third of these studies focused on the role of the cytoskeleton in the process described above. The relationship of the cytoskeleton with the incidence of apoptosis in this model is mediated by the ability of nitración by peroxynitrite, which is formed during renal ischemia reperfusion. This peroxynitrite nitra residues of the actin cytoskeleton, causing the disruption of this drift in the development of apoptosis, mostrándose in this work as the disruption of the cytoskeleton is part of the process apoptótico. THE ISCHEMIC PRECONDITIONING STRATEGY AS USEFUL IN THE SURGICAL LIVER TRANSPLANT GRAFT WITH THE TAILAuthor: FRANCO GOU ROSA. Year: 2005. University: BARCELONA. Place of defense: FACULTAD DE BIOLOGÍA DE UNIVERSIDAD DE BARCELONA. Place of preparation: INSTITUTO DE INVESTIGACIONES BIOMÉDICAS DE BARCELONA - CSIC. Summary: Liver transplantation to graft the tail was developed to increase the number of organs available and it diminish the waiting list. In addition syndrome ischemia / reperfusion associated with the transplant process, we need a process of regeneration parala viability of the graft. The syndrome ischemia / reperfusion (I / R) also has adverse systemic effects in the lung. The ischemic preconditioning (PC) is a useful strategy surgical face injury R / S models in R / S normotérmica and liver transplantation with 8 and 16 hours of ischemia, with good results in clinical, tumor resection, but unknown its effect on the model of liver transplantation with graft in the rat tail. In this thesis has shown that you PC is a useful strategy in front of the injury I / R that promotes regeneration associated with the model of liver transplantation in the rat tail, modulate growth factors, such as growth factor hepatocitario (HGF) and growth factor transformante-beta (TGF-beta) to modulate the production of free radicals (OFR) (by the Kupffer cells) and all this passes through the decline in IL-alfa and with involvement of nitric oxide (NO). However, the PC does not exercise its protective role by changes in the system producer OFR xanthine / xanthine oxidase, changes in the levels of cytokines TNF-alpha and IL-6, or through the preservation of energy metabolism. On the other path independent of NO, the PC stimulates expression of the Heat shock protein (HSP) 70 and HO-1, stimulating regeneration in the case of HSP70 and reducing injury and stimulating regeneration in the case of HO- 1. Moreover, the PC was able to confer protection for pulmonary, and the decline in IL-1alfa resulted in a decrease in plasma levels of TNF-alpha and an increase of soluble TNF-alpha receptor type 2, it is capable of inactivating the TNF-alpha free in the bloodstream, avoiding the harmful effects of lung TNF-alpha level. EFFECT OF HORMONE TREATMENTS ON CHRONIC SKIN AGINGAuthor: FERNÁNDEZ-TRESGUERRES CENTENO ANA. Year: 2005. University: COMPLUTENSE DE MADRID. Place of defense: FACULTAD DE MEDICINA. Place of preparation: DEPARTAMENTO DE FISIOLOGIA, FACULTAD DE MEDICINA. Summary: The objectives of this study were: 1-To examine the effect of aging on the various components dela skin (epidermis, dermis, and subcutaneous cellularity dermal) from the point of view histological and histomorfometrico. 2-To investigate the metabolism of primary keratinocytes in culture, originating from animals of different ages, analyzing different parameters of oxidative stress and apoptósis. 3-examine the effect of the ovariectomy on the parameters mentioned above. 4-Consider the effects exerted by different hormone treatments chronic (WR, melatonin, estrogen and phytoestrogens) on the histological and histomorphometric parameters changed with age. 5-To study the effects of various treatments chronic hormone (GH, melatonin, estrogen and phytoestrogens) on the parameters changed with the age of oxidative stress and apoptosis in cultured primary keratinocytes. The aging skin produces both histological alterations as metabolic. Histologically, there is a decrease in the epidermal thickness, a significant increase in the thickness of subcutaneous cellular tissue and a decrease in cellularity skin. The thickness of the skin does not appear to change with age, but it appears more loose and unstructured, with bundles of collagen longer and narrow. In growing keratinocytes parameters associated with oxidative stress increases with aging, resulting in an increase of LPO and CO. With regard to the levels of apoptosis occurs increased nucleosomas, caspase 3 and caspase 8, while levels of Bcls diminish with age. The females remain intact some ovarian estrogen production until old age. That is why some of these changes are most evident in male animals and ovariectomized females, suggesting a possible protective role of endogenous ovarian estrogen. Treatment for 10 weeks between 22 and 24 months produces the following changes in the skin: 1, RI - (2mg/kg/dia): histologically increases epidermal thickness, thickness increases and improves skin structure making it more compact, decreasing the thickness of subcutaneous cellular tissue and increased cellularity skin. In growing keratinocytes, producing a decline in LPO, CI, nucleosomas, caspase 3 and caspase 8, as well as increased levels of Bcl2. 2 - With melatonin (1mg/kg/dia): histologically increases epidermal thickness, improves skin structure making it more compact, decreasing the thickness of subcutaneous cellular tissue and skin slightly increased cellularity. In growing keratinocytes parameters associated with oxidative stress and apoptosis levels also improved, with effects similar to GH. 3 - With estrogen (125 ug / week) in rats old ovarictomizadas: it is capable of reversing the parameters altered with castration, both histólogicos as metabolic, in some cases more clear that treatment with GH. This treatment is able to improve the elastic fibers. 4 - With fitoestrogenos (60mg/kg/dia): induces positive effects of estradiol similar to you, but lower intensity, altered the parameters of oxidative stress and apoptósis in keratinocytes. Histologically only improve the amount of elastic fibers and the number of fibroblasts, in all other parameters altered not induce any effect. NOVEL REGULATORY MECHANISM ON T-CELL ACTIVATION MEDIATED BY DENDRITIC CELLSAuthor: PACHECO RIVERA RODRIGO ANDRÉS. Year: 2005. University: BARCELONA. Place of defense: FACULTAD DE BIOLOGIA. Place of preparation: DEPARTAMENTO DE BIOQUÍMICA Y BIOLOGÍA MOLECULAR. FACULTAD DE BIOLOGÍA, UNIVERSIDAD DE BARCELONA. ENDOCRINE DISRUPTERS IN THE MARINE ENVIRONMENT: MECHANISMS OF ACTION AND EFFECTS IN EXPOSED FISH.Author: MARTIN SKILTON REBECA-XENA. Year: 2005. University: BARCELONA. Place of defense: FACULTAD DE BIOLOGÍA. Place of preparation: FACULTAD DE BIOLOGÍA, UNIVERSIDAD DE BARCELONA. Summary: A growing number of studies show that a large number of synthetic chemicals act as endocrine disruptors (DDs) on fish and other vertebrate species. Many of these DDs have been classified as estrogen / androgenic or anti-oestrogenic / antiandrogéncios based on its ability to elicit responses to genomic level or block receptor-mediated responses. However, it is not very well known Des genetic interactions with endogenous enzymes responsible for the metabolism of xenobiotics, or the ability of these OF interfere with the metabolism of endogenous substrates such as hormones. This thesis investigates the effects of DDs on key enzymes responsible for the synthesis and metabolism of steroids and xenobiotics metabolism of compounds in different fish species, and its main aim is to investigate the interference of compounds in vivo models DDs this activity. In addition, specific responses have been studied enzyme key to the metabolism of phase I and II, and the levels of steroids, tools that have been used in field studies on how to establish the degree of exposure to DDs and the impact of pollutants on marine wild fish. ENDOTHELIAL DYSFUNCTION AND INFLAMMATION IN EXPERIMENTAL HYPERTENSION: ROLE OF ANGIOTENSIN IIAuthor: SANZ ROSA DAVID. Year: 2005. University: COMPLUTENSE DE MADRID. Place of defense: FACULTAD DE MEDICINA. Place of preparation: FACULTAD MEDICINA. Summary: The objectives of the study were: 1-To study the effects of hypertension in rats on vascular alterations structural, functional vascular abnormalities, and vascular hepatic oxidative stress, and systemic vascular inflammation, the possible participation of the system NFkB / IkB on vascular inflammatory mediators. 2-Consider the consequences of chronic treatment with a receptor antagonist AT1 angiotensin II on the above parameters associated with the experimental hypertension in rats. Role of Angiotensin II. The hypertension in SHR is characterized: * An increase in the area of the aorta, the average light and vascular, as well as the quotient media / lumen. These structural changes are accompanied by an increase in the expression of ARKNm and vascular protein factor profibótico CTGF, and the content of collagen. * A vascular dysfunction characterized by decreased endothelium-dependent relaxation to Ach, a decrease of relaxation to isoproterenol, an increase of contraction to the AI to the IIA, an increase of vasocontricción dependent endothelium to Ach + LNAME and a decline in the contraction of KCl and the FE. No change in response to NPS. * An increase in the mRNA expression of vascular for p252phox (the NADPH oxidase subunit), without changes in the vascular expression of mRNA NOSe. * A decrease in GSH and GSSG increased and consequently, a reduction ratio of GSH / GSSG. A decrease of the activity of GPx and an increase in the activity of the GRed, indicating a reduction in antioxidant defense. Moreover is associated with increased levels of liver MDA suggesting an increase in the hepatic oxidative stress. * An increase in the mRNA expression of cytokines IL-1beta, IL-6 and TNF-alpha in aorta, as well as an increase in inflammatory cytokines plastic IL-1beta and IL-6, with no changes in the levels of PCR plastics or INF-gamma. Changes in the system NFkB / IkB, due to an increase in the gene expression of p105 (precursor of the subunit p50 of NFkB) and a reduction of its inhibitor IkB. Treatment with candesartán (2mg/Kg/día) for 10 weeks in the SHR produced: * A reduction in blood pressure levels. * A decrease in the area of media, from light quotient of vascular and media / lumen. This improvement in the structural alterations were accompanied by a reduction in the expression of mRNA, as well as the production of the protein CTGF and content of collagen in the aorta. * An improvement in the vascular function due to increases vasorelajación dependent endothelium and relaxation to isorpterenol, while decreasing the contraction to the AI Ach + LNAME, and increases the contraction to KCl and FE. * An increase in the mRNA expression of vascular the NOSe and a reduction of the expression of vascular mRNA p22phox (the NADPH oxidase subunit), suggesting higher bioavailability of NO. * An increase of GSH and GSSG decreased and, consequently, an increase in the ratio GSH / GSSG, but with no effect on the activity of GPx or the Gred. A reduction of MDA suggesting a lower hepatic oxidative stress. * A reduction in the inflammatory parameters plasma IL-1beta and IL-6 and a normalization of gene expression vascular IL-1beta, IL-6 and TNF-alpha. The conclusions that have been reached with this work are as follows: In the SHR; 1-Endothelial dysfunction is characterized by a reduction in the bioavailability of NO mainly due to an increase in oxidative stress and vascular liver. 2 - The CTGF participating significantly in vascular remodeling it. 3, - The system NFkB / IkB and some cytokines such as IL-1beta, IL-6 and TNF-alpha, are involved in the inflammatory process. 4 - Angiotensin II, acting through receptor AT1, 8 is respo 1d7 nsable largely on the changes mentioned above. EFFECT OF GLP-1 ON THE TRANSPORT OF GLUCOSE AND LIPID METABOLISM IN ADIPOCYTE AND ITS CHARACTERISTICS IN OBESE AND DIABETIC STATES, WITH REGARD TO NORMAL.Author: SANCHO BÓRNEZ VERÓNICA. Year: 2005. University: COMPLUTENSE DE MADRID. Place of defense: FACULTAD DE CC. BIOLÓGICAS. Place of preparation: FACULTAD DE CC. BIOLÓGICAS, UCM. Summary: The reason for this work has been to study the action, in general, the naturally occurring peptide GLP-1, insulinotrópico and antidiabetic drug, and two of his counterparts, exendida-4 (EX4) and exendina-9 (EX9), the transport of glucose and lipid metabolism in the adipocyte, the cellular mechanisms involved, and their characteristics in normal, obese and diabetic. The study was conducted in rats, normal and experimental model of diabetes type 2, and the normal man and experimental model of diabetes type 2, and the morbidly obese and normal man. The original contributions of the study can be summarized as follows: 1 - The GLP-1 and both exendinas such as insulin stimulated glucose transport in the rat adipocyte normal, and that the cell diabetic, whose response insulin and Ex-4 is smaller, the GLP-1 is more effective and powerful. In addition, the results documented that the effect of GLP-1, such as the insulin is determinantemente mediated by PI3K and MAPKs, and possibly PCK, but not by the p70s6k, enzymes also involved in the action of both exendinas except PI3K in the E-4, whose involvement does not seem to be essential. 2 - The LPG-1 and E-4, such as insulin, but not the E-9, stimulate the uptake of glucose in the adipocyte of normal man, and the activity of PI3K, MAPKs and p70s6K, but unlike with insulin, does not make the PKB. And the well-known effect lipolítico LPG-1 is conditional upon an increase in activity PI3K, MAPKs, and possibly some isoform of PKC, but not the p70s6k. 3 - The adipocyte of morbidly obese shows a basal glucose transport normal, and retain their ability to respond to insulin, but not to LPG-1, and that both exendinas not only does not encourage, but do inhibit significantly, The basal lipolysis higher than normal, and that the action of GLP-1 and EX4, such as the glucagon, is lower. The liogénesis baseline is also stronger, but while the LPG-1 is very little cash, both exendinas as insulin, are very effective, even more than in the normal subject in the case of insulin. And these differences with the subject in the normal action of GLP-1, exendinas and adipocyte insulin in the morbidly obese, can be justified by abnormalities detected not only in the basal activity of certain enzymes signaling -PI3K, PKB and MAPKs- but in its response to these hormones / peptides. ROLE OF OXIDATIVE STRESS AND NITRIC OXIDE IN VASCULAR ALTERATIONS, SYSTEMIC AND KIDNEY, BILIARY CIRRHOSIS PILOT.Author: Alcaraz García Antonia. Year: 2006. University: MURCIA. Place of defense: Facultad de Medicina. Place of preparation: Facultad de Medicina. Summary: An overproduction of NO is one of the most important mechanisms causing the haemodynamic changes that occur in experimental animals and patients with liver cirrhosis. The increase in NO induces a systemic vasodilation, due in part to a lower response to vasoconstrictors in different vascular beds, and consequently hypotension. The renal vasoconstriction is a consequence of systemic changes to retain sodium and water and maintain blood pressure. Despite this vasoconstriction, renal NO production is also increased, and although this increase might be compensatory vasoconstriction, it is interesting to note that the inhibition of NO in animals cirrhotic improvement (rather than worsen) renal perfusion and excretion sodium and water contrary to what occurs under normal conditions. Although this beneficial effect may be partly due to an increase in blood pressure, studies in this laboratory have shown that doses of synthesis inhibitors that do not change no blood pressure, also increase natriuresis and diuresis in cirrhotic animals, intrarrenal suggesting a significant effect of NO in cirrhosis. Thus, it is possible that the excess of NO in the kidneys cirrhotic is toxic or is promoting a paradoxically vasoconstriction. Because of the low toxicity of NO in most systems, a product of the reaction of NO should be responsible for their toxicity. In the presence of high levels of superoxide anion (O2) the formation of peroxynitrite (ONOO-) is one of the most favorable chemical reactions of NO, as it is one of its routes inactivation. In this regard, there is increasing evidence that free radicals of oxygen derivatives (among the most important O2) are extraordinarily high in cirrhosis and play an important role in cardiovascular and renal manifestations. Indeed, as was discussed in the introduction, the antioxidant therapy may improve and renal hemodynamic changes in animals and patients with cirrhosis, and these beneficial effects are similar to those achieved much with the synthesis inhibitors of NO, although mechanisms to explain this similarity has not been clarified. The ONOO- is one of the most powerful oxidizers known in biological systems and has been proposed as a mediator of the majority of the cytotoxic effects associated with NO because of the multiplicity of their reactions. The ONOO- can alter vascular and renal function through several mechanisms: 1) can alter in protracted response vasoactiva to vasoconstrictors and vasodilators, 2) promoting renal vasoconstriction and retention of sodium and water; 3) can start peroxidation of the membrane lipids, and 4) can alter the expression and / or function of enzymes and other proteins important for the regulation of the levels of NO and O2 through several mechanisms. One is producing the nitración residue protein, among which the nitrosilación of tyrosine residues to form nitrotirosina, footprints left by peroxynitrite in vivo. Another is through mechanisms of intracellular signaling, acting on transcription factors and intracellular signaling proteins sensitive to oxidants. There is evidence, though rare, the existence of increased levels of peroxynitrite in cirrhosis. Of the various factors that can contribute to the deterioration of renal hemodynamic and cirrhosis, oxidative stress and NOT appear to be of particular importance. The combination of the two, excessive NO synthesis and production of free radicals (O2-), facilitates the generation of powerful oxidizing compounds such as peroxynitrite (ONOO-), which can alter the response to vasoactive substances and the expression of enzymes important in regulating systemic vascular function and excretora kidney. Consequently, decreasing the concentration of either, NO or O2, it can reduce the biological effects of peroxynitrite and improve hemodynamic changes in the kidney and liver cirrhosis. EXPRESSION OF THE ACTIVE FORM OF INTEGRINA CAD49D/CD29 IN ERITROBLASTOS OF HUMAN BONE MARROW; REGULATORY FUNCTION AND PATHOPHYSIOLOGY.Author: VILLARRUBIA MIGALLÓN NOELIA. Year: 2006. University: COMPLUTENSE DE MADRID. Place of defense: FACULTAD DE MEDICINA. Place of preparation: FACULTAD DE MEDICINA - UNIVERSIDAD COMPLUTENSE DE MADRID. Summary: Introduction The process of erythropoiesis is defined as the succession of stages madurativas allowing differentiation from a hematopoietic stem cell bone marrow (BM) until eritrocito mature. Retention in erythroid precursor MO, necessary for adequate maturation, it depends on different adhesion molecules such as integrina CD49d/CD29, whose main ligands are protein fibronectin FN and the molecule VCAM-1 or CD106. However, the fact that other hematopoietic cells whose tendency to stay at little or no MO also express the integrina CD49d/CD29 suggests that the mere expression of this integrina not justify sésil nature of the erythroid series. OBJECTIVES AND METHODS The main objective of this work has been the study by flow cytometry of the expression and regulation of the active form (competent to unite ligand) of the integrina CD49d/CD29 in eritroblastos MO human. FINDINGS AND CONCLUSIONS 1, MO-eritroblastos of human express CD49d/Cd29 activated under physiological conditions, which probably gives them a great capacity for binding to bone marrow stroma through binding to FN and CD106. 2 - The expression of CD29 activated eritroblastos MO human is dependent CD106 soluble content in the plasma core and the stabilizing effect of divalent cations (especially Mn2 +). 3 - The CD106 soluble plasma core is coupled with the integrina Cd49d/Cd29 the membrane of eritroblasto under physiological conditions, which probably constitutes a mechanism for regulating the in vivo active form of integrina. 4 - The regulation of integrina CD49d/Cd29 in eritroblastos MO by soluble factors does not require intracellular signaling or reorganization of the cytoskeleton, but the presence of an active cellular metabolism. 5, - eritroblastos MO establish human interactions homotípicas in vitro regulated by soluble factors from plasma core and mediated, at least in part, by integrina activated CD49d/CD29. The formation of aggregates could be a retention mechanism in vivo erythroid precursors in the bone marrow microenvironment. 6 - The eritroblastos MO in patients with myelodysplastic syndrome express lower CD49d/CD29 activated with respect to the normal MO, this being related to the presence of diseritropoyesis cytological and output forms immature erythroid to peripheral blood, which quite probably indicates that the integrated CD49d/CD29 activated plays a very important role in tracing the eritroblastos in the marrow microenvironment.
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