RESUMO
Dietary restriction promotes resistance to surgical stress in multiple organisms. Counterintuitively, current medical protocols recommend short-term carbohydrate-rich drinks (carbohydrate loading) prior to surgery, part of a multimodal perioperative care pathway designed to enhance surgical recovery. Despite widespread clinical use, preclinical and mechanistic studies on carbohydrate loading in surgical contexts are lacking. Here we demonstrate in ad libitum-fed mice that liquid carbohydrate loading for one week drives reductions in solid food intake, while nearly doubling total caloric intake. Similarly, in humans, simple carbohydrate intake is inversely correlated with dietary protein intake. Carbohydrate loading-induced protein dilution increases expression of hepatic fibroblast growth factor 21 (FGF21) independent of caloric intake, resulting in protection in two models of surgical stress: renal and hepatic ischemia-reperfusion injury. The protection is consistent across male, female, and aged mice. In vivo, amino acid add-back or genetic FGF21 deletion blocks carbohydrate loading-mediated protection from ischemia-reperfusion injury. Finally, carbohydrate loading induction of FGF21 is associated with the induction of the canonical integrated stress response (ATF3/4, NF-kB), and oxidative metabolism (PPARγ). Together, these data support carbohydrate loading drinks prior to surgery and reveal an essential role of protein dilution via FGF21.
Assuntos
Dieta da Carga de Carboidratos , Fatores de Crescimento de Fibroblastos , Traumatismo por Reperfusão , Procedimentos Cirúrgicos Operatórios , Animais , Feminino , Humanos , Masculino , Camundongos , Carboidratos da Dieta/metabolismo , Proteínas Alimentares/metabolismo , Fatores de Crescimento de Fibroblastos/metabolismo , Fígado/cirurgia , Fígado/metabolismo , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão/metabolismoRESUMO
Superior vena cava syndrome can lead to significant morbidity and mortality, particularly in acute settings. We report a case of an acute Port-a-Cath-associated thrombosis of the superior vena cava. Percutaneous catheter-directed thrombectomy was performed using the JETi8 thrombectomy device with additional angioplasty and stenting, allowing rapid flow restoration and rapid clinical recovery. Postoperative anticoagulation was initiated and pursued lifelong. This report is unique in illustrating how JETi8 thrombectomy seems to be a safe and effective therapy, allowing rapid flow restoration, rapid clinical improvement, and persistent patency at 6 months.
RESUMO
Inhibition of the master growth regulator mTORC1 (mechanistic target of rapamycin complex 1) slows ageing across phyla, in part by reducing protein synthesis. Various stresses globally suppress protein synthesis through the integrated stress response (ISR), resulting in preferential translation of the transcription factor ATF-4. Here we show in C. elegans that inhibition of translation or mTORC1 increases ATF-4 expression, and that ATF-4 mediates longevity under these conditions independently of ISR signalling. ATF-4 promotes longevity by activating canonical anti-ageing mechanisms, but also by elevating expression of the transsulfuration enzyme CTH-2 to increase hydrogen sulfide (H2S) production. This H2S boost increases protein persulfidation, a protective modification of redox-reactive cysteines. The ATF-4/CTH-2/H2S pathway also mediates longevity and increased stress resistance from mTORC1 suppression. Increasing H2S levels, or enhancing mechanisms that H2S influences through persulfidation, may represent promising strategies for mobilising therapeutic benefits of the ISR, translation suppression, or mTORC1 inhibition.