Rhinosinusitis is an inflammatory and obstructive process that affects the nasal cavity and sinuses. It's called chronic rhinosinusitis (CRS) when the disease lasts beyond 12 weeks. CRS can be associated with nasal polyps (CRSwNP) or not (CRSsNP). CRSwNP is a disease with high morbidity characterized by the existence of neoplastic structures that cause airways obstruction. Polyps are formed by the infiltration of inflammatory cells. Current treatments are ineffective in many of the patients having to undergo repeated surgical procedures therefore the developing of new and more effective drugs are necessary. Research in animal models is currently limited by the lack of diagnostic and disease monitoring methods without sacrificing animals. This study evaluates the effectiveness of the analysis of images carried out by computed tomography (CT) and positron emission tomography (PET) techniques in the diagnosis and monitoring of CSR-PN in an animal model. This animal model of the disease was obtained by an instillations protocol with ovalbumin as a sensitizer and Staphylococcus aureus enterotoxin B as inducing agent. CT technique is based on the ability of penetration of x-rays for detecting changes in tissue density. PET technique has the ability to calculate the glucose uptake by a homologous radiolabel. Tissue density and glucose uptake are properties that are altered in the course of a severe inflammatory process. The results obtained confirm the validity of these techniques to determine the existence of an inflammatory process and neoplastic structures in the developed disease model. The results obtained by the histological post-mortem analysis techniques corroborated this conclusion. It can be said that the use of CT and PET techniques is an effective method for determining and monitoring the evolution of CSRwPN in animal models in vivo, allowing the research into effective treatments for the disease. AgradecimientosEste trabajo es posible gracias a Xavi, quien creyó desde un primer momento que yo era la persona indicada para llevarlo a cabo y siempre sacó un momento para guiarme y aconsejarme en cada uno de los pasos de su realización.Mi agradecimiento, también, a los compañeros de la Fundación, que tanto me han ayudado a conseguir terminar un proyecto tan largo como este, en el tiempo estipulado, permitiéndome compaginarlo con el curso, así como prestándome su ayuda incondicional cuando me surgía alguna duda o me faltaba algún dato para poder seguir avanzando.A Rafa por ofrecerse a tutorizar este trabajo, permitiéndome poder desarrollarlo y defenderlo ante un tribunal.Por supuesto necesito también agradecer su apoyo a mi familia y amigos, especialmente a mi madre y a mi novia, Inma, pues sin su ayuda me hubiera sido mucho más difícil avanzar durante este largo periodo de trabajo, animándome siempre, ayudando cuando podían hacerlo y recordándome que a veces lo mejor para seguir a delante es despejarse un poco.Por último quiero dar gracias a mi padre por enseñarme, junto a mi madre, a ser lo que soy ho...
Chronic renal failure (CRF) is accompanied by adaptive changes in electrolyte reabsorption in the thick ascending limb of Henle of surviving nephrons. To study the cellular mechanism of this adaptation, we measured intracellular cAMP in micro-dissected medullary thick ascending limb (mTAL) segments in rats with CRF. mTAL exhibited in CRF an increase of basal cAMP from 25.6 +/- 10.0 in controls to 65.8 +/- 11.3 fmol mm-1 tubule in CRF (P < 0.05). Vasopressin and calcitonin stimulated mTAL adenylate-cyclase in a dose-dependent manner in controls but failed to stimulate in CRF. Likewise, maximal stimulation with 10(-3) M 3-isobutyl-1-methylxanthine (IBMX) plus 10(-5) M forskolin increased cAMP in controls to 63.0 +/- 16.0 but not in CRF, where maximal stimulated values remained at 63.1 +/- 18.8 fmol mm-1 tubule (P NS). Alpha2-adrenoreceptor activation with clonidine at concentrations ranging from 10(-8) to 10(-6) M diminished cAMP production by 37% in CRF (P < 0.05), whereas no differences were found in controls. Thus, the basal intracellular cAMP is increased in rat mTAL in CRF. The finding that neither forskolin nor vasopressin were able to further augment intracellular cAMP would suggest that stimulatory pathways of the adenylate-cyclase system are activated in the basal state. However, mTAL cells in CRF seem to retain the response of normal epithelium to inhibitory pathways such as the one mediated by alpha2-adrenoreceptors.
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