PATHOLOGY

Author: COLOMER OFERIL JAUME.
Year: 2002.
University: BARCELONA [More theses of this university] [www.ub.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: PEDIATRIA-FACULTAD DE MEDICINA.

Summary: A-HIPOTESIS Knowledge of the level of protein expression and interaction among the various structural membrane proteins and enzymes, which are responsible for most of the muscular dystrophies, can help in the clinical diagnosis and genetic resources, while providing information on the pathogenesis the various entities. The identification of patterns of protein interactions, especially for those diseases in which the primary protein defects are part of other complex protein. (Dystrophin Associated Gluycoprotein, DAG), would be a priority in this thesis. B-OBJECTIVES OBJECTIVE 1-Studying the expression and interaction of dystrophin-associated glycoproteins and dystrophin -Dystrophin Associated Glicproteins - (DAG) in 17 patients suffering from one of Becker muscular dystrophy (DMB) and December 15 (DMD ). OBJECTIVE 2-Studying the expression and interaction of dystrophin-associated glycoproteins and dystrophin Dystrophin Associated Glicporteins- (DAG) in 11 patients suffering from muscular dystrophy for a primary deficit of sarcoglicanos. OBJECTIVE 3-Rate by Western blot expression of Calpaína 3 in 4 patients with different mutations in the gene CALPN 3. OBJECTIVE 4-phenotypic characterization and protein expression in a heterogeneous group of patients with deficits protein level of the extracellular matrix, basal lamina and nucleoproteínas. CONCLUSIONS 1 - The level of dystrophin expression correlates well with the phenotypes Duchenne muscular dystrophy / Becker, although the latter group has not been able to objectify a clear correlation between the level of protein expression and the observed phenotype. The deficit of dystrophin conditioned interact with all of the sarcoglycan complex components with a special reduced gamma-sarcoglicano and beta-distroglicano. Interaction with the merosina was very discreet and void with caveolina 3. The utrophin was sobreexpresada in all patients. 2, - The protein expression in primary deficits of any of the components of the sarcoglycan complex ranged from a deficit full and partial unrelated to the observed phenotypes. The interaction with the other components of the sarcoglycan complex and beta-distroglicano was variable. No, it was interaction with dystrophin or the merosina. All patients regardless of the mutation showed overexpression of utrophin. 3 - The expression of calpain 3 was reduced or absent with antibodies 30 and 60 kD, and its analysis therefore very useful for diagnosis. Unable to establish a correlation genotype / phenotype. 4 - The study has helped to strengthen the characterization of the various clinical phenotypes within the concept of congenital muscular dystrophy and nucleoproteínas facilitating their recognition both clinical and genetic identification.

Author: DORADO MARTÍN JUAN JOSÉ.
Year: 2002.
University: EXTREMADURA [More theses of this university] [www.unex.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA.

Summary: We conducted a study of the most common chronic diseases of the population 40 years or older (557 people) from the list of people attached to a doctor's Health Center of San Fernando in the city of Badajoz and its relationship to social classes establishing the relationship between body mass index (BMI) of the entire population, the most prevalent chronic diseases (obesity, hypertension, diabetes, Hypercholesterolemia, Hipertrigliceridemia, Ischemic cardiomyopathy, Cerebrovascular Disease, Atrial fibrillation, Nefrolitiasis, Varicosis Members Lower , Chronic Obstructive Pulmonary Disease, Osteoarthritis generally Gonartrosis, Coxartrosis, Espondiloartrosis, Osteoporosis), and the status of healthy person, with the most important social determinants (education, per capita income, social class, tabáquico habits, alcohol consumption , housing and property owned vehicle. age group is the largest population of 40-49 years, with 34% of the total. 26.9% of the study population is illiterate and 18% have secondary education or superiors. The majority of the population belongs to the working classes (68%). The 13% of the population belongs to class I and II (Managers and professionals primarily). The 43% of the population have net income per year per person between 3000 and 6000 Euros. Being a 26% who have incomes in excess of 6000 euros / year. BMI is associated in a statistically significant with the level of instruction, declining 1.16 Kg/m2 for every increase in the scale of Educational attainment (illiterate, uneducated, primary and secondary education or higher). BMI of women associates, as well as the level of instruction, the per capita income of reverse. Women have 1.41 kg/m2 more weight on average than men. illiterate women have a BMI of 31.9 and those with secondary education or higher 24.6. with BMI was associated with a p less 0001 the following conditions (Gonartrosis, hypertension, diabetes Hypercholesterolemia, Hipertrigliceridemia and varicose veins in the legs) and a p less 0.05 arthritis and espondiloartrosis dorsal and lumbar. HTA was inversely associated with the per capita income, and directly with BMI, diabetes, cholesterol and age. healthy people are directly associated with the per capita income, men are more healthy women and men who have never smoked are more healthy than those who had smoked more than 20 years . addition, osteoarthritis is associated with social class and is more common in women, Hipertrigliceridemia is associated with excessive alcohol consumption, and COPD and Ischemic heart disease with smoking, the latter also partnering with hypertension and hypercholesterolemia . atrial fibrillation is associated with hypertension and heart Ischemic and Cerebrovascular disease is associated with hypertension. The findings of our study can be highlighted: 1 - The level of instruction is the best socioeconomic variable associates with chronic morbidity of the population. 2-Raising the level of education of the population would improve the health of the same. 3-populations with low levels of education should have more health resources than those of most educated high, which has a higher morbidity. 4-Both the level of education as a BMI two parameters could be useful in assessing the needs of both social and health resources in addition to those that already exist based on the age of the population.

Author: GIMENEZ LLORT ANTONIO.
Year: 2003.
University: BARCELONA [More theses of this university] [www.ub.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: HOSPITAL SANT JOAN DE DEU.

Summary: INTRODUCCIÃâN disease SchÃÂ ¶ nlein-Henoch is a disease multisitÃÂ © mica that mainly affects vessels pequeÃÂ ± or caliber of the skin, joints, digestive system and riÃÂ ± ÃÂ ³ n. REASON AND JUSTIFICACIÃâN OF THE THESIS The estrÃÂ © s oxidative can be decisive in the apariciÃÂ charges of sÃÂndrome of SchÃÂ ¶ nlein-Henoch at its evoluciÃÂ charges or lapresentaciÃÂ charges of nefropatÃÂ. Free radicals in excess or dÃÂ © ficit of mechanisms antioxidants podrÃÂa encourage apariciÃÂ ³ n of the disease. OBJECTIVES 1-Studying the role of daÃÂ ± or oxidative in patogÃÂ © nesis and development of pÃÂ fourth rpura of SchÃÂ ¶ nlein-Henoch. 2-Consider implicaciÃÂ charges of agents antioxidants (glutathione peroxidase, glutathione reductase, superÃÂ ³ xido dismutase, catalase, ubiquinona, coenzyme Q, malondialdehyde, vitamins A, C and E) in the development of pÃÂ fourth rpura of SchÃÂ ¶ nlein-Henoch in their stages of activity and remisiÃÂ ³ n. 3-Study the implicaciÃÂ charges of antioxidant agents in nefropatÃÂa of SchÃÂ ¶ nlein-Henoch. ALL MATERIAL AND MÃâ ° are studied 23 niÃÂ ± os affections of pÃÂ fourth rpura of SchÃÂ ¶ nlein-Henoch. These are divided into two groups segÃÂ º n its afectaciÃÂ ³ n kidney. Group A includes 12 patients with complicaciÃÂ ³ n renal and group B 11 without complicaciÃÂ ³ n kidney. All of them were efectÃÂ eighth to determinaciÃÂ charges of antioxidant enzymes, antioxidants, substances marker for peroxidaciÃÂ ³ n lipÃÂdica. RESULTS In glutathione reductase were significantly lower values obtained in niÃÂ ± os that active disease compared to the control group (p less 0.05). We found no differences in the rest of antioxidant agents studied. CONCLUSIONS 1-Patients tenÃÂan to pÃÂ fourth rpura of SchÃÂ ¶ lein-Henoch in activity of glutathione reductase values were significantly mÃÂ ¡s lower than the control group. 2 - The enximas antioxidants studied: glutathione peroxidase, glutathione reductasas, catalase and superÃÂ ³ xido dismutase, no differences estadÃÂsticamente significant between the control group and patients with pÃÂ fourth rpura of SchÃÂ ¶ nlein-Henoch active in remisiÃÂ charges or presenting nefropatÃÂa. 3 - The antioxidant substances studied: ubiquinona, coenzyme Q, and vitamins A, C and E had no differences estadÃÂsticamente significant between the control group and patients with pÃÂ fourth rpura of SchÃÂ ¶ nlein-Henoch active in remisiÃÂ charges or who pesentaron nefropatÃÂa. 4 - The peroxidaciÃÂ ³ n lipÃÂdica studied by determinaciÃÂ charges of malondialdehyde has shown no significant differences between the control group and patients with pÃÂ fourth rpura of SchÃÂ ¶ nlein-Henoch active in remisiÃÂ charges or presenting nefropatÃÂa.

Author: CRESPO ASENSIO JAVIER.
Year: 2004.
University: BARCELONA [More theses of this university] [www.ub.es].
Place of defense: FACULTAD DE BIOLOGÍA.
Place of preparation: LABORATORIO DE INVESTIGACIÓN CARDIOVASCULAR (HOSPITAL DE SANT PAU).

Summary: NOR-1 (Neuron-derived orphan recetor-1) is an orphan nuclear receptor involved in the proliferation and migration of smooth muscle cells (CML) induced by serum. In atherosclerosis is a key cell activation vascular (CML and endothelial cells) for low-density lipoprotein (LDL) and mitogens. The molecular mechanisms by which this occurs activation known only partially. The objective of this thesis is to explore whether NOR-1 is vascular cell activation induced by LDL and endothelial growth factor (VEGF) vascular, and if the expression of this gene can be controlled by drugs antiateroscleróticos. Using techniques and semi-quantitative RT-PCR (real-time PCR) note that the expression of NOR-1 is induced by LDL in CML and arterial wall pig hipercolesterolémicos and that the HMG-GoA reductase inhibitors (statins) are able to inhibit this induction. The effect of statins inthe cells is reversed by the geranilgeraniel but not by the farnesol. By inhibiting RhoA with simvastatin, exotoxin C3 and toxin B or by inhibiting the activity of Rho Kinase (ROCK, an effect of RhoA) with Y-27632, it inhibits the expression of pro-NOR-1-induced LDL. In the same vein in transfection experiments of CML rat activation of the promoter of NOR-1-induced LDL is inhibited by simvastatin and also contransfectar cells with a dominant negative RhoA (RhoAT19N). exotoxin C3 and Y-27632. We also note that a promoter consisting of four elements consensus CRE is activated by LDL, which is indeed the cotrasfectar cells inhibited with RhoAT19N. In addition LDL are capable of activating Smenb, gene regulated by elements CRE and simvastatin effect of inhilbe this. On the other hand, studies with endothelial cells from human umbilical vein (HUVEC), VEGF induces the expression of NOR-1. Inhibiting the expression of NOR-1 with antisense oligonucleotides directed against the initiation of translation of NOR-1 decreases the proliferative effect and the migration of VEGF in these cells. These results show that NOR-1 is induced by LDL in CML through a mechanism dependent on the activation of CREB and the route of RhoA / ROCK. In addition NOR-1 is involved in the migration and proliferation induced by VEGF in endothelial cells. NOR-1 could be the key role played by antiaterogénico statins, and could be a potential therapeutic target to regulate angiogenesis and atherosclerosis.

Author: MOLINA CASADO M. PLÁCIDA.
Year: 2004.
University: MÁLAGA [More theses of this university] [www.uma.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: DELEGACIÓN PROVINCIAL DE SALUD/FACULTAD DE MEDICINA.

Summary: The Oral Anticoagulant Therapy involves a problem at the moment of Public Health. The incidence in the general population is estimated at 0,9-1,3%, rising around a 15% per year, linked to the inclusion in the treatment of patients with AF In the year 2001, for coordinated action in the Services Hematology, PA and the Directorate of Quality Assurance Unit of the Provincial Delegation of Health was chosen for the sake of increasing the quality of care, monitoring of these patients by their methods PA, under the supervision of the Services Hematology. The thesis assesses the results of this decision in the year 2004. Once excluded from the study centers of District Costa del Sol, except the 3 for Torremolinos-Benalmádena, having followed a different model, we find that to December 31, 2003, 63% of the health centers participating and 95% of professionals such centers. The average time of training received by the professionals was 6 hours. We are studying the methods of puncture, the consumption of strips and timing delay in obtaining the results, and their differences Sanitary District. To show the effectiveness of studying the n fifth of patients who were found in rank, as measured by the determination of INR and the time remaining. To study the Security used complications n ° and grade, major and minor. The results speak of the difficulties of implementation and good figures from effectiveness and safety, which posibilitala possible implementation of this methodology in other areas. The study is a pioneer in Spain and Europe, opening the way for better monitoring of these patients, since the quality of care.

Author: MARTÍNEZ GARRIGA BLANCA.
Year: 2004.
University: BARCELONA [More theses of this university] [www.ub.es].
Place of preparation: UNIDAD DE MICROBIOLOGÍA, CAMPUS DE BELLVITGE.

Summary: This paper examines the main mechanisms of resistance to fluroquinolonas in clinical isolates of Streptococcus pneumoniae S. Pneumoniae is a Gram positive bacterium characterized by the severity of the infections that occur in the human species. The emergence of strains of S.pneumoniae resistant to antibiotics such as penicillin and other beta-lactámicos, has led to the use of new antimicrobial agents as fluoroquinolones, which include ciprofloxacin. This work shows the possible role of other oral streptococci in the eventual transfer of resistance genes to quinolones in S.pneumoniae. Furthermore, it describes the mechanisms involved in resistance to ciprofloxacin in clinical isolates of S.pneumoniae, placing special emphasis on the mechanisms of reflux. The work shows that the resistance of the majority of clinical isolates will be mainly mutations in the major targets of the antibiotic study. However, it also shows the possible involvement of a mechanism of reflux in the outstanding resistance to ciprofloxacin two of the isolates of S.pneumoniae. The inactivation of the gene pmrA, gene coding for the protein only reflux described thus far in S.pneumoniae, appears to indicate the presence of a mechanism of reflux independent PmrA. The comparative analysis between the genome sequence of R6 and distinct proteins reflux already described in other Gram positive bacteria indicate the possible existence of at least one other bomb reflux in S.pneumoniae. Analyzed the two main mechanisms of resistance was applied a methodology based on the technique of microarrays, which showed the potential of this tool in the identification of new genes involved in resistance to fluoroquinolones in S.pneumoniae.

Author: IYÚ ESPINOSA DAVID.
Year: 2005.
University: MURCIA [More theses of this university] [www.um.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA.

Summary: Previous studies in our laboratory have shown an increase of nitric oxide (NO) in rat cirróticas by bile duct ligation (LCS), using its synthesis inhibitors (Ramirez, 1995). Along the same lines, our laboratory has many data indicate that NO is very important interferes with the mechanisms for regulating the concentration of Ca2 + intracellular in the vascular wall. Thus, in experiments in which they used the mesenteric arterial bed, and isolated perfused of rats subjected to LCS, it was found that while the entry of Ca2 +, through various channels, such as the release of this from deposits intemos was lower in rats subjected to LCS (Nadal et al., 2002). To find out more about these changes, our lab has carried out studies with smooth muscle cells, isolated from the abdominal aorta of rats subjected to LCS, confirming that the entry of Ca2 + extracellular, such as the release from the reservoirs is lower in the muscle cells in rats LCS (Atucha et al., 2003). In both cases, the use of inhibitors of NO synthase improved the response of Ca2 +, confirming the role of NO in the regulation of levels and muscle origin, in addition, endothelial production of NO. Many studies have been used cardiovascular platelets easily obtainable as a model used to analyze the comparative form some of the properties of smooth muscle cells. So, have been linked to increases of Ca2 + in platelets with hypertension (Eme et al., 1984). In our model rats LCS, as in other types of cirrhosis, there is a hyperdynamic circulation, vasodilatation widespread, and thus, it would be interesting to study the cellular signal of Ca2 + in platelets in order to check whether the same changes occur as described in the smooth muscle cells and to see the role of NO in these cells. On the other hand, is known tendency to bleed presenting patients with liver cirrhosis. Among the various causes being considered as responsible for this bleeding is a decrease in platelet function (Sosch et al., 2005). The study of the signal cellular Ca2 +, which is essential for the activation of platelets, platelets from rats subjected to LCS, can help us understand the possible role that platelets are in the haemostatic abnormalities suffered by patients with liver cirrhosis . Therefore, in this study we set out the following objectives: 1.Analizar mechanisms of entry and release of intracellular calcium in platelets from animals with cirrhosis biliar.2.Estudiar the role of nitric oxide in calcium homeostasis of platelets animals with cirrhosis biliar.3.Determinar the expression of proteins binding to the calcium in platelets from animals with biliary cirrhosis. The results were as follows: 1. Platelets of the two experimental groups with the same concentration cytosolic Ca2 + in basal conditions, both the absence and presence of Ca2 + extracelular.2. The thrombin stimulation produces an increase in concentration cytosolic Ca2 + is increased in platelets of rats cirróticas, both the absence and presence of Ca2 + extracellular. This result is not influenced by the incubation of platelets in their own plasma (activated or inactivated). 3. The total levels of Ca2 +, stored in intracellular deposits of platelets rats cirróticas s 8 on higher aa8 is that in the controls. In this line ATPase activity of SERCA is also higher in platelets rats cirróticas. 4. The entry capacitativa calcium in response to tapsigargina is significantly lower in platelets LCS rats than in the controls. 5. Platelets of the two experimental groups with the same release of NO in basal conditions, both the absence and presence of Ca2 + extracellular. 6. The stimulation with thrombin, in the presence of Ca2 + extracellular produces an increase in the release of NO, which is higher in platelets rats cirróticas. Similarly, stimulation with tapsigargina, in the presence of Ca2 + extracellular also produces an increase in the release of NO, which is also higher in platelets rats cirróticas. 7. The release of NO in the presence of Ca2 + extracellular in response to thrombin is lowered to incubate platelets with L-NAME 100 u.1M, however, the signal cellular Ca2 + remains totally unaffected by the L-NAME 100 u. 1 M, in either in the presence or absence of Ca2 + extracellular after stimulate platelets with thrombin and tapsigargina. 8. The level of expression of proteins SERCA, Calreticulina and Calpaína is the same in the two experimental groups, however, the Calmodulina and PMCA is higher in platelets rats cirróticas. The findings were as follows: 1.Las platelets animals with biliary cirrhosis presented alterations in the mobilization of calcium consistent with higher storage capacity secondary to the increased activity of reuptake mechanisms. 2. Despite the thrombin agonist produces greater release of nitric oxide in the blood platelets of rats with biliary cirrhosis, inhibition of synthesis is not accompanied by a normalization of disturbances of calcium intraplaquetario yello suggests that nitric oxide does not is responsible for these abnormalities. 3. Platelets of animals with biliary cirrhosis show a different expression of the protein binding to the calcium.

Author: TORO DE MENDEZ MORELVA.
Year: 2005.
University: VALENCIA [More theses of this university] [www.uv.es].
Place of defense: FACULTAD DE MEDICINA Y ODONTOLOGÍA.
Place of preparation: FACULTAD DE MEDICINA Y ODONTOLOGIA.

Summary: We carried out a study immunohistochemical including a panel of 18 biomarkers and molecular study in 81 biopsies of cervical cancer (59 carcinomas epidermoides and 19 adenocarcinomas neck) diagnosed in the Department of Pathology of the University Clinical Hospital in Valencia, with the purpose of the immunohistochemical characterization of this neoplasm invading and determine the presence of ADN-HPV partner. The immunohistochemical study was conducted in cervical tumors and benign cervical tissue as a control, using the technique of avidina-biotina, interpreted using a semi-quantitative scale. It was determined the presence and genotyping of ADN-HPV in neoplastic samples, the method PCR-SPF10/LiPA. The most common histologic type was epidermoid carcinoma moderately differentiated (43.5%) and adenocarcinoma endocervical (42.1%). The average age of the patients was 50.67 more or less 13.62 years. The immunohistochemical findings were as follows: cervical carcinomas showed a proliferative index (Ki-67/MIB-1) between moderate and high; presented positive immunoreactivity for cellular proteins regulatory ciclina D1, pRb, p16, p21, p27 and ciclina E Like at 32.1%, 30%, 79.5%, 52.5%, 53.2% and 7.7% respectively. Regarding the apoptotic proteins, before the antibody reactivity against p53 was 3.9%, MDM-2 (100%), Bax (67.5%) and BcI-2 (3.7%). The molecules of cell adhesion cadherina-E, CD44s and CD44v3 were sobrexpresadas with cytoplasmic localization preferably in 76.6%, 90.9% and 97.5%. The immune response to the ubicuitina was 98.7%, cytokeratins (AE1/AE3) 97.5%, CEA 89.7% and telomerase 52.6%. We found statistically significant differences in the immunoreactivity of tumors compared to controls except for the reactivity of p53, Bcl-2 and CEA; also in terms of the reactivity of p27, MDM-2, cytokeratins, cellular localization of cadherina - E CD44v3 in carcinomas of different degrees of maturation and in the case of histological subtypes for cervical adenocarcinoma Bax, telomerase and CD44v3. Correlation found in the inmunoexpresión 1) Ki-67 with p16, p21, p27, telomerase and ubicuitina. 2) pRb and ciclina D1, CEA and CD44s; p53 with ciclina D1 and AEC. 3) p16/p21, p16/p27, p21/p27, p27/Bax, p27/Bcl-2 and p16/MDM-2. 4) ciclina D1 with p21, CEA and Cadherina-E. 5) Cadherina-E with CD44s, CD44v3, MDM-2 and ubicuitina; CD44s/CD44v3; CD44v3 and p16, ubicuitina, telomerase and cytokeratins. 6) Citoqueratinas with p27, MDM-2, CD44v3 and Ki.67. As for the presence of ADN-HPV in neoplastic samples, 96.3% (78/81) were positive; of these, 59% (46/78) introduced single infection and 41% (32/78) infection multiple . The most common type specific viral was HPV16 (55.13%) followed by the HPV18, HPV58 and HPV X, the same percentage (1.28%), likewise the HPV16 was the most frequent type viral both carcinomas epidermoides (55.9%) in adenocarcinomas cervical (52.6%). We found no statistically significant difference in inmunoexpresión panel of biomarkers studied between single and multiple infections. Cervical cancer associated with oncogenic HPV infection is characterized as showing immunoreactivity altered in major ways regulators of the cell cycle, modulation of apoptotic proteins, inmunolocalización cellular abnormal cell adhesion molecules, and high sobrexpresión of EAA and cytokeratins, intense degradation of proteins and activation of telomerase. The histological types of cervical cancer share a multifactorial process of carcinogenesis in which he is involved, commonly, the presence of oncogenic HPV as a causative agent necessary for the development of this malignancy.

Author: LÓPEZ MORENO SONIA.
Year: 2005.
University: BARCELONA [More theses of this university] [www.ub.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA.

Summary: This Doctoral Thesis comprises eight scientific studies investigating the genetics and mitochondrial function in the peripheral blood mononuclear cells (CMSP) from different groups of patients infected with HIV. The objective of these studies is to determine the toxic effects that anti-retrovirals (ARVs) and the HIV infection in vivo can exert on mitochondria such cellar. The introduction reflects the destructive capacities of HIV on the immune system cells, and the ability suppressor of ARVs on HIV. Equally, we note the importance of mitochondrial biology to the viability of any cellular oxidative metabolism, the significance and clinical impact that an alteration in mitochondrial can make the human body. The interaction of these three factors (HIV, and mitochondria ARVs) can compromise mitochondrial function and magnify the susceptiblidad of these organelles power generators to suffer any disruption that, ultimately, can manifest itself clinically. Over the past 10 years, the highly active antiretroviral therapy (HAART) against HIV infection has brought great benefits to individuals infected, but chronic administration of HAART, has generated the emergence of a number of serious side effects, as example myopathy, polyneuropathy, pancreatitis, hyperlactatemia, lactic acidosis and lipodystrophy (LD), which have been associated with a pathogenic origin associated with mitochondrial dysfunction. Serious consequences q2ue can have these side effects can motivate the abandonment of ARV treatment and lead to therapeutic failure. From here stems the vital importance of determining potential pathophysiological mechanisms of these changes, which allow for the control of the side effects associated with HAART. In the studies presented derive the following conclusions: 1, in-patients who have developed ARV treatment LD presented alterations mitocontriales in CMSP, which is mainly expressed as depletion of mitochondrial DNA (ADNmt) and decreased activity of the enzyme protein complexes system oxidative phosphorylation (system OXPHOS), which are partially encoded by the ADNmt. 2 - The alterations in the mitochondrial CMSP of HIV positive patients with LD does not imply a substantial restriction of mitochondrial oxidative capacity in this cell type. 3 - The mitochondrial toxicity of ARVs is detectable in the CMSP of HIV positive patients receiving HAART at a stage asimptomática, before they are clinical manifestations of some serious side effects associated with HAART. 4 - The involvement of the mitochondrial CMSP for ARVs is manifested differently and with varying intensity depending on the combination of ARVs administered. 5-depletion ADNmt present at the CMSP patients asimptomáticos receiving HAART is not usable as a single marker for early detection of side effects, because they do not always involves alteration of the mitochondrial oxidative function. 6-cell compensatory mechanisms exist prior to the development of clinical symptoms of mitochondrial toxicity, which allow patients asimptomáticos can sustain a normal content of the protein subunits that make up the complex enximáticos system OXPHOS and retain the role mitochondrial oxidative unchanged at Although presenting some depletion of ADNmt. 7 - The HIV infection itself causes a disruption mitoconddrial widespread in CMSP, probably mediated by apoptotic mechanisms. 8, - own HIV infection induces the activation of apoptotic mechanisms to skeletal muscle, which in this fabric are not increased further by the administration of HAART or by the development of LD.

Author: CONDE GALLEGO ESTHER.
Year: 2005.
University: COMPLUTENSE DE MADRID [More theses of this university] [www.ucm.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA UNIVERSIDAD COMPLUTENSE DE MADRID.

Summary: In this thesis has been studied by parent tissue levels of expression of multiple proteins associated with major cellular processes, in a series of patients diagnosed with bronchogenic carcinoma not microcítico (CRNM) in initial studies (IA-IIBp). Through a multidisciplinary approach to data integration clinical, pathological and molecular have been identified molecular markers for diagnostic, prognostic and predictive in CBNM. With regard to the latter, has made a detailed study of the genetic and molecular context in which it takes place EGFR gene mutations in a separate series of patients diagnosed with adenocarcinoma of the lung. Among other findings, he noted the relationship between overexpression of the protein S6p and the presence of mutations in this gene, suggesting the immunohistochemical determination of the protein S6p as an indirect method to ascertain the status mutacional EGFR gene.

Author: ÁLVAREZ FLORES MARIA BETRIZ.
Year: 2005.
University: COMPLUTENSE DE MADRID [More theses of this university] [www.ucm.es].
Place of defense: FACULTAD DE BIOLOGÍA.
Place of preparation: HOSPITAL UNIVERSITARIO DE GETAFE.

Summary: The lymphatic leukemia (LLC-B) lymphoproliferative syndrome is the most common adult and is characterized by the gradual accumulation of B lymphocytes immunologically generally incompetent sobreexpresan antigen CD5. This accumulation of lymphocytes is mainly due to inhibition of apoptosis, or programmed cell death, the remaining cells in phase G0 cell cycle. The cause of the disturbance is unknown. Clinically, patients with LLC-B present behavior and response to treatment heterogeneous. Studies apoptosis applied to the LLC-B, show an increase in the expression of the protein antiapoptótica -bcl-2, with an increase in the ratio bcl-2/bax (protein proapoptótica) compared to normal B-lymphocytes and while this ratio has correlated with the clinical stage of the patients there at the moment controversy over its relationship with clinical response to treatment. It is the little-known role of other proteins involved in apoptosis in patients with LLC-B, but family members of Bcl-2 and Bax, Bcl-Xy Mcl-1 might play an important role in this process. The in vitro analysis of apoptosis in LLC-B, has offered equally controversial results on the correlation between induced apoptosis in vitro by various drugs (Fludarabina, 2-CDA, Chlorambucil, Flavopirinol, Theophylline) and clinical response to it. Also the results have been contradictory relationship between whether or not quimiosensibilidad in vitro and levels of the different proteins involved in apoptosis. In the treatment of LLC-B, there are new and different therapeutic trends following the emergence of a new class of cytotoxic agents, purine analogues, whose best-known representatives and employees as the axis of the treatment of LLC-B are Fludarbina and the Claridibina. Currently, it seems that the treatment of LLC-B is geared towards the use of three types of drugs; purine analogues, alkylating and antraciclínicos, whose best results employed either alone or in various forms of combination therapy has yet to be defined. This study has evaluated the induction of apoptosis in vitro in the populations of B lymphocytes and T normal tumor patients with LLC-B following exposure to different combination of 3 antineoplastic drugs with recognized cytotoxic activity in this entity (Fludarabina, Mafosfamida and Mitoxantrone ). Furthermore, the term has been marked ex vivo Cspasa 3 active, and the Fas protein belonging to the family of Bcl-2: Bcl-2, Bax, Bcl-Xy Mcl-1 in lymphocytes ByT of LLC-B. Similarly have been assessed changes in expression of the same after the various chemotherapy treatments in vitro.

Author: CARRILLO MOLINA JORGE.
Year: 2006.
University: AUTÓNOMA DE BARCELONA [More theses of this university] [www.uab.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: LABORATORIO DE INMUNOBIOLOGIA PARA LA INVESTIGACIÓN Y LAS APLICACIONES DIAGNÓSTICAS (LIRAD-BST).

Summary: The type 1 diabetes mellitus is a disease autoinmunitaria characterized by the destruction of beta cells, producing insulin, by the immune system itself. Although it has been ascertained that T lymphocytes are primarily responsible for the destruction of beta cells, this process is necessary to involve other types of cells, such as dendritic cells, macrophages and lymphocytes B. The B lymphocytes can be deployed for several reasons: 1 - The presence of autoantibodies in the serum of patients, even in the preclinical phase, with a distinctly prognosis. 2, - Elimination of the population of B lymphocytes in the NOD model, prevents the onset of the disease. Work performed with the model NOD have determined that the B lymphocytes could participate in the process diabetogénico as a population of antigen presenting cells, with a distinctly diabetogénico. This role would require that these cells to specifically recognize autoantígenos relevant disease (GAD65, insulin…) Another interesting fact is that B lymphocytes infiltrate the pancreas islets in the same way they do T lymphocytes, reaching constitute 50% of the infiltrated spot, and are located in close contact with the T lymphocytes Despite this, in the study of B lymphocytes has focused on periphery, not addressing the population of B lymphocytes that infiltrates the pancreatic islets. The primary goal of our research group has focused on the phenotypic characterization, functional and antigen of this cell population. This dissertation focuses on the latter point and poses as a main objective to characterize the specificity antigéncia of B lymphocytes infiltrantes in pancreatic islets in animal models that show susceptibility to the disease (NOD and 8.3-NOD) and models that show a moderate resistance to the process (F1 (NODxNOR) and 8.3-F1 (NODxNOR)). For this hybridomas were generated by merging the population of B lymphocytes infiltrantes in line with islets myeloma NS-1. The study of these hybridomas has revealed that a high percentage of these cells recognize estructures of the peripheral nervous system. The molecular analysis of immunoglobulins expressed for these cells, has shown that this reactivity can be the result of a selection process antigen positive way. These data support the hypothesis that the autoimmune attack directed against beta cells is accompanied or preceded by the destruction of the peripheral nervous system to reverse the pancreatic islets.

Author: PIJUAN ANDÚJAR LARA.
Year: 2006.
University: AUTÓNOMA DE BARCELONA [More theses of this university] [www.uab.es].
Place of defense: UNIDAD DOCENTE HOSPITAL DEL MAR.
Place of preparation: UNIVERSIDAD AUTÓNOMA DE BARCELONA.

Summary: Follicular lymphoma is the 35-45% of all non-Hodgkin's lymphomas and 75-80% of low-grade lymphomas. Many of the patients with follicular lymphoma respond to initial treatment, but most fall is the annual percentage rate of relapse of 5-10%. In a 30 to 60% of cases, over time can be transformed to a cell lymphoma diffuse large B more aggressive. From the point of view pathogenic Follicular lymphoma is a malignancy of mature B cells that has been offset normal lymphocytes germinal center of the secondary lymphoid follicles. It contains mainly 2 cell types, centrocitos and centroblastos. Morfológicamente most cases of follicular lymphoma have a predominantly follicular pattern. In terms of cytogenetics, Follicular lymphoma is characterized by the translocation t (14.18) (q32, q21). Thus the gene bcl-2 of chromosome 18 are juxtaposed with the gene coding for the immunoglobulin heavy chain (IgH) of chromosome 14 leading to the overexpression of the protein Bcl-2, whose main effect is inhibiting programmed cell death or apoptosis of cells. Despite this, not yet aware of all that other genetic alterations or host factors that are coupled with the translocation t (14.18) (q32, q21) make that a final malignant phenotype and produce an expansion clonal uncontrollable in the germinal center. It should be noted that the translocation t (14.18) (q32, q21) occurs in 85% of cases and that there are some less common variants of the same, as the t (2; 18) or t ( 18, 22) will also result in overexpression of Bcl-2. In about 15% of cases are involved translocations of other genes as bcl-6, especially in the higher-grade lymphomas. The diagnosis of follicular lymphoma is defined by the study of anatomo - patológico biopsy of a lymph node affection, supplemented with the study inmunofenotípico and molecular level. For the clinical stage of follicular lymphoma is necessary to the study of bone marrow because his condition, apart from determining the stage of the disease, is what will determine the clinical management of the patient, being useful for monitoring treatment. The bone marrow is affected between 40 and 70% of cases. In this Doctoral Thesis on the one hand we focused on the study of molecular all nodes with follicular lymphoma patients included in the study and the other part of the biopsy of the bone marrow and create the assumption that the study of morphological and immunohistochemical the bone marrow biopsies in these patients is not enough to predict whether or not there is residual affection and we believe that with the same molecular studies could detect the presence of affectation that has been observed without the presence of morphologically lymphoid infiltrates in the bone marrow . The results provided by the thesis has been able to demonstrate that through molecular techniques are showing the effect of the bone marrow by follicular lymphoma patients in the biopsy done and studied histological and inmunohistoquímicamente not objetivaban. It has also been able to demonstrate this infiltration through the study of the molecular characteristics of the lymph affections at the time of diagnosis. These data suggest a disturbing way forward as they indicate the need to incorporate the techniques of molecular diagnostics as part of the routine pathology laboratories.