Hatfield Best (arrowlinda2)
Therefore, this review aims to highlight major metabolic similarities between cancer cells and embryonic stem cells demonstrating that they have similar strategies in both signaling pathways regulation as well as metabolic profiles while focusing on key metabolites. Dihydroorotate dehydrogenase (DHODH) is an enzyme of the de novo pyrimidine synthesis pathway that provides nucleotides for RNA/DNA synthesis essential for proliferation. In mammalian cells, DHODH is localized in mitochondria, linked to the respiratory chain via the coenzyme Q pool. Here we discuss the role of DHODH in the oxidative phosphorylation system and in the initiation and progression of cancer. We summarize recent findings on DHODH biology, the progress made in the development of new, specific inhibitors of DHODH intended for cancer therapy, and the mechanistic insights into the consequences of DHODH inhibition. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening conditions with high morbidity and mortality. Supportive care management of SJS/TEN is highly variable. A systematic review of the literature was performed by dermatologists, ophthalmologists, intensivists and gynecologists with expertise in SJS/TEN to generate statements for supportive care guideline development. Members of the Society of Dermatology Hospitalists (SDH) with expertise in SJS/TEN were invited to participate in a modified, online Delphi-consensus. 9-point Likert scale questionnaires regarding 135 statements were administered. The RAND/UCLA appropriateness method was employed to evaluate and select proposed statements for guideline inclusion; statements with median ratings of 6.5-9 and disagreement index ≤1 were included in the guideline. For the final round, the guidelines were appraised by all the participants. An evidence-based discussion and recommendations for hospital setting and care team, wound care, ocular care, oral care, urogenital care, pain management, infection surveillance, fluid and electrolyte management, nutrition and stress ulcer prophylaxis, airway management, and anticoagulation in adult patients with SJS/TEN are included. BACKGROUND Acute generalized exanthematous pustulosis (AGEP) is a severe cutaneous adverse reaction, typically to a medication, that is characterized by fever, neutrophilia, and a disseminated non-follicular pustular eruption. AGEP is typically self-resolving upon withdrawal of the offending agent, however it is not without complications and distributive shock due to systemic inflammatory response can lead to hemodynamic instability and organ failure1-2. These patients have been successfully treated with systemic corticosteroids3. Cyclosporine use in patients with AGEP has been limited to only a few case reports4, 5. To date, no studies have evaluated the utility of cyclosporine in the management of AGEP. We report the largest cohort of patients with AGEP treated with cyclosporine and compare them to patients treated with systemic glucocorticoids. METHODS This was a retrospective study of adults admitted to Massachusetts General Hospital or Brigham and Women's Hospital with a diagnosis of AGEP from 2009-2019.rences in the setting of the aforementioned comorbidities, some selection bias was unavoidable in this cohort. The small sample size and retrospective nature also limit this study. Nevertheless, cyclosporine appears to be a non-inferior therapeutic alternative to glucocorticoids in the appropriate patient who presents with AGEP, and future prospective studies are needed to further examine its utility in AGEP. Celastrol is a natural pentacyclic triterpene extracted from the roots of Tripterygium wilfordi (thunder god vine). Celastrol was reported as a powerful anti-obesity drug with leptin sensitizing properties that decreases food consumption and mediates body weight loss when administered to diet-induced obese mice at 100 μg/kg body weight. The weight lowering properties of celastrol are likely m
