La proteína tuberina: diana terapéutica para activar autofagia y mitofagia evitando la progresión a la diabetes tipo 2 / Tuberin protein: therapeutic target to activate autophagy and mitophagy avoiding the progression to type 2 diabetes

El control de calidad citoplasmático es esencial en el mantenimiento de la viabilidad celular, y particularmente, de las células β pancreáticas, debido a su gran capacidad de síntesis proteica. En este contexto, juega un papel esencial la activación de un proceso fisiológico denominado autofagia, conduciendo a la eliminación de agregados proteicos y/o orgánulos, induciendo la atenuación del estrés de retículo celular. El complejo formado por las proteínas hamartina y tuberina (TSC1-TSC2) ha emergido como un núcleo de integración de la señalización de factores de crecimiento y del estado energético celular. Este complejo funciona como un inhibidor de la actividad de la vía del complejo mecanicístico diana de la rapamicina (mTORC1) y un activador de la autofagia. En este proyecto queremos profundizar en el estudio de nuevos mecanismos moleculares de regulación de TSC2, así como sobre dichos mecanismos de control de calidad citoplasmático, autofagia y mitofagia. Proponemos que el estado de acetilación en lisinas de TSC2, mediado por la actividad desacetilasa de la sirtuina1 (SIRT1), modula la estabilidad y actividad de la misma afectando a la homeostasis celular (AU)

Cytoplasmic quality control is essential in maintaining cell viability, and articularly, β pancreatic cells, due to its huge protein synthesis capacity. In this context, it is important the activation of a physiological process called autophagy, in order to eliminate protein aggregates and damaged organelles, resulting in a reduction in the reticulum cell stress. The complex formed by hamartin and tuberin (TSC1-TSC2) has emerged as a central signal, energy status and nutrient-integrating node within the cell. This complex negatively regulates the mechanistic target of rapamycin complex 1 (mTORC1), and activates autophagy. In this proyect we aimed to further investigate new molecular mechanisms of TSC2 regulation, aswell as cytoplasmic quality control, autophagy and mitophagy ones. We propose that the TSC2 acetylation status, mediated by the deacetylation activity of sirtuin1 (SIRT1), modulates its stability and protein activity, affecting cell homeostasis

Classic transcrural celiac plexus block simulated on 100 computed tomography images.

STUDY OBJECTIVE: To evaluate intra-abdominal needle trajectories of the classic transcrural celiac plexus block (tCPB) with a simulation technique. DESIGN: Classic tCPB technique cited from 10 latest authoritative textbooks were simulated on abdominal computed tomography images retrospectively. SETTING: University-affiliated community hospital. MEASUREMENTS: One hundred axial computed tomography images across the celiac trunk were retrieved. Three lines simulating classic tCPB were executed on each image. The organs traversed by each line were noted and analyzed. The frequencies of organ traverse were compared with the incidences described in the literature. MAIN RESULTS: All 3 lines traversed various organs with different frequencies. The right side line frequently traversed the right kidney (36%). The left side line always traversed the aorta (100%). The modified line on the right side frequently traversed the inferior vena cava (32%). The highest kidney traverse percentage on both sides and the highest aorta traverse percentage on the right side were observed in pancreatic cancer patients. CONCLUSIONS: Despite uncommon clinical complications, classic tCPB needle placement frequently traversed through several key organs in this simulation series. Organ penetrations could be avoided by needle trajectory adjustment.

Computed tomography celiac trunk topography relating to celiac plexus block.

BACKGROUND AND OBJECTIVES: The celiac plexus is a dense autonomic network surrounding the celiac trunk. To block this plexus, the celiac trunk is a landmark for needle placement. Needles inserted at a distance from the midline, "walking off" the vertebra, may penetrate surrounding organs. We reviewed 200 computed tomography images to investigate the celiac trunk topography relating to the block. METHODS: Two hundred computed tomography images across the celiac trunk were displayed. The celiac emergence level and celiac-aortic-vertebral anatomies were examined. On each image, 2 needle trajectories imitating walking-off technique were placed tangential to the vertebral body passing through the crus of the diaphragm on both sides: L-9s and L-4.5s (9 and 4.5 cm from the midline, respectively). The vital organs traversed by these lines were noted and analyzed. RESULTS: Celiac emergence levels: T11-12, 6.5%; T12, 34%; T12-L1, 31%; L1, 28.5%. Aortic locations: 70% were anterior-left to and 29% were anterior-middle to the vertebra. Celiac runoffs: 63.5% from the aorta anterolaterally on the left, 36% from the midportion. Celiac-aortic-vertebral correlations showed a various distribution in groups; 88% L-9s and 64% L-4.5s on the right side, and 96% L-9s and 88% L-4.5s on the left side traversed different vital organs with various frequencies. CONCLUSIONS: The celiac trunk anatomy varies. Blocking needles walking off the vertebra from a fixed distance frequently traverse vital organs. Previewing celiac-aortic-vertebral topography with a simulating block on individual patient's computed tomography (CT) image for accordant needle placement subsequently is warranted.

Gestión de la calidad en enfermería en un centro periférico de diálisis / No disponible

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