Mitochondria and Energetic Depression in Cell Pathophysiology

Mitochondrial dysfunction is a hallmark of almost all diseases. Acquired or inherited mutations of the mitochondrial genome DNA may give rise to mitochondrial diseases. Another class of disorders, in which mitochondrial impairments are initiated by extramitochondrial factors, includes neurodegenerative diseases and syndromes resulting from typical pathological processes, such as hypoxia/ischemia, inflammation, intoxications, and carcinogenesis. Both classes of diseases lead to cellular energetic depression (CED), which is characterized by decreased cytosolic phosphorylation potential that suppresses the cell’s ability to do work and control the intracellular Ca2+ homeostasis and its redox state. If progressing, CED leads to cell death, whose type is linked to the functional status of the mitochondria. In the case of limited deterioration, when some amounts of ATP can still be generated due to oxidative phosphorylation (OXPHOS), mitochondria launch the apoptotic cell death program by release of cytochrome c. Following pronounced CED, cytoplasmic ATP levels fall below the thresholds required for processing the ATP-dependent apoptotic cascade and the cell dies from necrosis. Both types of death can be grouped together as a mitochondrial cell death (MCD). However, there exist multiple adaptive reactions aimed at protecting cells against CED. In this context, a metabolic shift characterized by suppression of OXPHOS combined with activation of aerobic glycolysis as the main pathway for ATP synthesis (Warburg effect) is of central importance. Whereas this type of adaptation is sufficiently effective to avoid CED and to control the cellular redox state, thereby ensuring the cell survival, it also favors the avoidance of apoptotic cell death. This scenario may underlie uncontrolled cellular proliferation and growth, eventually resulting in carcinogenesis

Crohn's disease and Sweet's syndrome: an uncommon association Enfermedad de Crohn y síndrome de Sweet: una asociación infrecuente

Sweet's syndrome or acute febrile neutrophilic dermatosis (SS) is characterized by the sudden onset of painful erythematous lesions (papules, nodules, and plaques) together with fever and neutrophilia. The lesions are typically located on hands, arms, upper trunk, neck and face, showing an asymmetric distribution. Acute phase reactants are usually elevated and dermal infiltration of neutrophils without vasculitis is seen on skin biopsies. It is considered as a marker of systemic disease in over half of the cases, and is associated with infections, inflammatory bowel disease, autoimmune connective tissue disorders and various neoplasias. Its association with Crohn's disease (CD) is unusual and it appears mainly in association with colonic involvement. Fewer than 50 cases have been published in the medical literature since its first description in 1964, some concurrent with the first episode of CD. We present two patients with Crohn's disease and Sweet's syndrome diagnosed in our department at the time of CD diagnosis, as well as their response to treatment, subsequent course of the disease, and a review of the scientific literature.El síndrome de Sweet o dermatosis neutrofílica febril aguda (SS) se caracteriza por la aparición brusca de lesiones eritematosas, (pápulas, nódulos y placas) dolorosas, junto con fiebre y neutrofilia, siendo de presentación poco frecuente. Las lesiones se localizan preferentemente en manos, brazos, parte superior del tronco, cuello y cara, con distribución asimétrica. Suele haber elevación de reactantes de fase aguda y en las biopsias cutáneas se identifica una infiltración dérmica de neutrófilos sin vasculitis. Se considera un marcador de enfermedad sistémica en más de la mitad de los casos, asociándose a infecciones, enfermedad inflamatoria intestinal, conectivopatías autoinmunes y diversas neoplasias. Su asociación con la enfermedad de Crohn (EC) es poco habitual, asociado sobre todo a afectación colónica. Se han publicado menos de 50 casos en la literatura médica desde su primera descripción en 1964, algunos de ellos simultáneos con el primer brote de la EC. Presentamos dos pacientes con enfermedad de Crohn y síndrome de Sweet diagnosticados en nuestro servicio en el momento del diagnóstico de la EC, así como su respuesta al tratamiento, evolución posterior y revisión de la literatura científica