Spelling suggestions: "subject:"lio"" "subject:"plio""
1 |
Influencia de los ácidos grasos dietéticos y del ambiente en el desarrollo de colitis espontánea en ratones IL-10(-/-)Pedrosa Tapias, Elisabet 12 April 2008 (has links)
La Enfermedad inflamatoria intestinal engloba una serie de enfermedades, siendo las más frecuentes la Colitis Ulcerosa y la Enfermedad de Crohn. Estas enfermedades de etiología desconocida y sin tratamiento curativo cursan crónicamente con periodos de remisión. Epidemiológicamente afectan a países industrializados lo que indica la influencia del factor ambiental siendo la dieta un factor clave. La evolución epidemiológica de esta enfermedad y de los hábitos alimenticios de las poblaciones con mayores índices de incidencia muestran una relación entre el aumento del consumo de grasas, especialmente de la familia n6.Los primeros datos genéticos quedaron patentes en estudios con gemelos y con familiares de enfermos. En la actualidad algunas alteraciones genéticas se asocian a distintos fenotipos de la enfermedad.Para el correcto funcionamiento del colon la mucosa intestinal compartimentaliza sus elementos de manera que se beneficia de los elementos positivos (nutrientes y flora comensal) a la vez que se protege de los posibles agentes tóxicos o patológicos del medio extraintestinal. En primera línea de interacción una monocapa epitelial constituye una barrera selectiva. Formada por células especializadas en la secreción de factores protectores y agentes antimicrobianos, y provistas de distintos receptores, el epitelio intestinal está implicado en la adquisición de la tolerancia frente a nutrientes y flora comensal mediante la información captada por estos receptores y que es transferida al compartimiento que se encuentra por debajo de esta monocapa epitelial, la lámina propia. En la lámina propia distintos tipos celulares inmunocompetentes instauran tolerancia frente a los nutrientes y a la flora comensal y estructuran una respuesta efectora frente a patógenos. La teoría más consolidada de las causas de la enfermedad inflamatoria intestinal es el reconocimiento anómalo de la flora comensal por parte del sistema inmune de la mucosa intestinal, provocando una inflamación descontrolada y crónica en individuos con predisposición genética. Aunque los factores causantes de la enfermedad inflamatoria intestinal no se conocen, los factores implicados están bien definidos: la dotación génica del individuo y la funcionalidad de los compartimientos de la mucosa cólica (epitelio y lámina propia) todo ello modulado por el ambiente.Frente a la complejidad del estudio de los factores implicados en la enfermedad inflamatoria intestinal los modelos experimentales suponen la posibilidad de recrear situaciones ambientales controladas, de testar distintos elementos nutricionales, farmacológicos, etc. y poder estudiar los efectos sobre el órgano afectado. El modelo de ratones deficientes para IL10 es un modelo que muestra alteraciones en la función barrera y que desarrolla un patrón inflamatorio Th1 similar al de la enfermedad de Crohn. Estos animales desarrollan enterocolitis espontáneamente con distinta gravedad en función de las condiciones de estabulación. Esta tesis ha tenido dos objetivos principales, valorar el desarrollo de enterocolitis en este modelo de colitis espontaneo estabulando los animales "wild type" (WT) y IL10 (-/-) en condiciones "specific pathogen free" y en condiciones convencionales. Y por otro evaluar el efecto terapéutico de triglicéridos de cadena media (MCT) en este mismo modelo substituyendo el 50% de la fracción lipidica de la dieta (ácidos grasos familia n6) por MCT (n6/MCT). El primer estudio muestra como en un ambiente controlado se consigue contener la inflamación sin que esta revierta sobre la lámina propia regulando mecanismos celulares (apoptosis) y moleculares (vía TLR/MyD88) mientras que en un ambiente complejo antigénicamente hablando la inflamación alcanza la lámina propia.El estudio terapéutico muestra resultados alentadores sobre la substitución de parte de la fracción lipídica de la dieta con MCT aunque son necesarios estudios con otros modelos de colitis. / Inflammatory bowel disease (IBD) (Crohn's disease, ulcerative colitis and indeterminate colitis) is a chronic condition of unknown etiology with no curative treatment. It alternates periods of inflammatory activity with those of remission. This disease affects more frequently the developed countries, pointing out that there might be an environmental influence. One of the most important environmental factors that have been related to IBD is diet. There has been shown a relationship between a high fat intake (specially n6 fatty acids) with a greater IBD incidence.Another factor that is needed for this disease development is genetic susceptibility. The first associations between genetics and IBD were discovered when studies of twins and other close relatives of IBD patients were performed. Nowadays there is evidence of specific genetic alterations associated to different disease phenotypes.For a proper colonic physiology, the intestinal mucosa has developed an efficient background in order to obtain benefits from positive elements such as nutrients and commensal bacteria, and, at the same time, protecting itself from extraintestinal toxic and pathologic agents.The first line acts as a selective barrier and is constituted of an epithelial monolayer. Different specialized cells constitute the epithelial barrier. These cells secrete protective factors such as antimicrobial agents. This epithelial barrier works in tolerance acquisition to nutrients and commensal bacteria. The extraepitelial information is transferred to lamina propria situated under epithelial layer through epithelial receptors. Different immunological cells constitute the lamina propia. This compartment acts tolerating nutrients and comensal flora, and is implicated in the effector response to pathogens.Although disease causes are unknown, the implicated factors seem to be clear. The consolidated theory about causes of IBD is the abnormal recognition of commensal flora by the intestinal immunological system that causes an uncontrolled and unnecessary inflammation in genetic predisposed patients, all of these factors modulated by the patient environment. Experimental animal models represent a good tool in front of the complex pathway of factors involved in IBD. These models allow to recreate controlated environmental situations, to test different nutritional elements, drugs, etc., and to study the effect of this actions on the affected organ. IL10 deficient mice model shows barrier alterations and develop a Th1 answer similar to Crohn's disease. These animals develop spontaneous enterocolitis with different stages of severity when kept under different environmental conditions.This thesis had two major objectives, to evaluate the enterocolitis development in IL10 deficient mice, wild type and knockout, that were housed under specific pathogen free (SPF) or conventional conditions. The second objective was to evaluate the therapeutic effect of replacing 50% of fat fraction (n6) of the diet with medium chain triglycerides in IL10 deficient mice.The first study shows that in a monitored environment (SPF) inflammation is controlled without affecting lamina propria through regulating cellular (apoptosis) and molecular (TLR2 and MyD88) mechanisms, whereas a complex antigenic environment (conventional conditions) induces an inflammatory process in the lamina propria. The therapeutic study shows encouraging results in the replacement of part of the fat fraction of the diet with MCT although studies with other models are necessary.
|
2 |
Greater trochanteric pain after total hip arthroplasty : incidence, clinical outcome, associated factors, tenderness evaluation with algometer and a new surgical treatmentSayed-Noor, Arkan Sam January 2008 (has links)
Greater trochanteric pain (GTP) is a regional pain syndrome characterized by lateral hip pain and tenderness. Its incidence after total hip arthroplasty (THA) is variable. Bursal inflammation, degenerative changes of the attachment of the gluteal muscles, direct operative trauma and biomechanical disturbance of the operated hip have been discussed as being related to GTP. The diagnosis is purely clinical because radiological and laboratory investigations show no definite pathology. Although most treatment modalities are conservative, some patients may develop refractory complaints leading to surgical intervention. In study I we studied the incidence of GTP in 172 consecutive patients who underwent THA during 2002 at Sundsvall Hospital. Patients with GTP (n=21, incidence 12%) were matched with controls from the same cohort. The THA outcome was assessed using the Western Ontario and McMaster Universities Arthrosis (WOMAC) Index. Trochanteric tenderness was studied using an electronic pressure algometer. We found an association between the occurrence of GTP and postoperative uncorrected lengthening of the operated limb of ≥ one centimetre. The WOMAC index revealed a reduction of the clinical outcome in the GTP group. In Study II we tested the value of using an algometer in the diagnosis of GTP after THA. We measured the pressure-pain threshold (PPT) over the greater trochanter and ilio-tibial band in 18 patients and 18 matched controls. Both groups were evaluated using the visual analogue scale (VAS). We found the algometer to have a good predictive validity and reproducibility. However, there was large inter-individual variability across subjects. The PPT ratio of 0.8 (affected vs. unaffected side) can be used as a cutoff ratio to establish GTP. There was no correlation between PPT measurements and VAS. Because of a low positive predictive value and large inter-individual variability, the pressure algometer has a limited value as a screening tool. In study III we proposed a new surgical treatment for refractory GTP after THA consisting of distal lengthening of the ilio-tibial band (ITB) by Z-plasty under local anaesthesia. This method was used in 12 women between March 2004 and June 2006. The patients were followed up by phone interview 3-4 months postoperatively and by an EQ-5D questionnaire and clinical examination including evaluation with the algometer at 1-3 years postoperatively. We found that the patients‘ quality of life was markedly improved following the operation (EQ-5D = 0.26 preoperatively vs. 0.67 postoperatively; p <0.005). There were no postoperative complications. In study IV we evaluated the accuracy of a commonly used clinical method of LLD measurement (anterior superior iliac spine-medial malleolus) by comparing it to a reliable radiological method (tear drop-lesser trochanter) in 139 patients before and after THA. We found the correlation between the clinical and radiological methods to be weak preoperatively (r=0.21, ICC= 0.33) while the correlation was moderate postoperatively (r= 0.45, ICC=0.62). It is therefore recommended that the radiological method be used to measure leg length discrepancy in patients who undergo THA.
|
3 |
Effet de la posture sur la performance et la prévention des blessures en cyclisme. Apport de la modélisation musculo-squelettique / Effects of posture on performance and prevention of injury in cycling. Insights from a musculoskeletal modeling approachMénard, Mathieu 13 October 2016 (has links)
La performance sportive et la prévention des blessures en cyclisme sont étroitement liées à l'amélioration des capacités physiques, de la technique gestuelle ainsi qu'à l'optimisation du matériel utilisé.Dans ce contexte, nous avons étudié l'influence du recul de selle sur l'efficacité du mouvement de pédalage ainsi que sur les efforts internes au niveau du genou. Une approche de modélisation musculo-squelettique a été développée afin de quantifier indirectement les forces musculaires et articulaires exercées à partir de mesures externes cinématiques et dynamiques. Un intérêt tout particulier a été porté sur l'adéquation entre les mesures des efforts extérieurs, le modèle anthropométrique et les mesures cinématiques afin de diminuer les incohérences dynamiques associées à un système surdéterminé.A partir de ces mesures, les effets du recul de la selle sur la performance ont été évalués à travers l'indice d'efficacité de la force produite à la pédale et un nouvel indice, basé sur le travail mécanique externe. Les résultats ont montré qu'un positionnement de la selle plus reculé augmente l'efficacité du mouvement de pédalage.Concernant la prévention des blessures, notre analyse s'est portée sur l'effet du recul de selle sur deux troubles musculo-squelettiques (TMS) fréquents en cyclisme : le syndrome fémoro-patellaire et le syndrome de la bandelette ilio-tibiale. Nos résultats ont montré que le recul de selle ne modifie pas les forces fémoro-patellaires communément incriminées dans la survenue de ce syndrome. Par ailleurs, une position plus reculée augmente les forces fémoro-tibiales de compression par le biais notamment de la contraction excentrique des muscles ischio-jambiers. Bien que le syndrome de la bandelette ilia-tibiale soit classiquement décrit comme un syndrome de friction (syndrome de l'essuie-glace), le calcul de la force d'interaction entre la bandelette iliotibiale et l'épicondyle fémoral a montré que la compression est le facteur discriminant dans le pathoméchanisme. L'approche méthodologique de simulation développée dans ce cadre possède par ailleurs un fort potentiel afin de corriger les défauts techniques, d'optimiser les réglages matériels et améliorer la prise en charge thérapeutique des TMS.Plus généralement, les développements méthodologiques et implications cliniques issus de ces travaux trouvent des applications directes dans le milieu du cyclisme mais aussi dans l'étude de nombreuses activités sportives (notamment sur ergomètre) du point de vue de la performance, de la prévention des blessures et de la rééducation. / Performance and prevention of injuries in cycling are closely linked to the optimisation of individual's physical capacity and technique as weil as sport equipment.In this context, we have studied the influence of saddle setback on the effectiveness of pedalling and on knee joint loads. A musculoskeletal modelling was developed to estimate muscle and joint forces from experimental kinematic and dynamic measurements. We first focused on the adequacy between sensors data, anthropometrie model and kinematic measurements to obtain dynamically consistent input data.Then, the effect of sadd le setback on perforn1ance was evaluated through the index of pedal force effectiveness and a new index based on extemal mechanical work. Results have showed that a more backward sadd le position increases the effectiveness of pedalling.As regards to in jury prevention, our analysis focused on the effect of the saddle setback on two knee injuries commonly observed in cycling: the patellofemoral syndrome and iliotibial band syndrome. Our results showed that saddle setback do not influence patellofemoral joint forces that are usually linked to this syndrome. Moreover, a more backward saddle position increases tibiofemoral compression forces due to increasing eccentric contraction of the hamstrings.Commonly described as a friction syndrome, the computation of interaction force between iliotibial band and lateral femoral epicondyle have showed that the compression was the discriminating factor in the occurrence of the syndrome. The simulation approach developed here could be used as an additional tool to help correct potentially hartnful sport techniques, optimise equipment setup/design and improve the treatment of injuries.More generally, this thesis brings new methodological improvements and clinical implications that have broader applications on sport perfortnance, injury prevention and rehabilitation.
|
Page generated in 0.0514 seconds