The role of hyperbaric oxygen therapy in septic shock: is it time for human studies?

Sepsis is a life-threatening condition for which new therapies are needed. The objective of this literature review was to compile evidence related to the use of hyperbaric oxygen (HBO2) therapy in sepsis. The goal of this analysis was to determine whether human trials are indicated. The study was designed as a narrative review of literature for studies of HBO2 therapy in sepsis. Literature was reviewed to understand potentially beneficial and harmful clinical and physiological effects of HBO2 therapy in animals with sepsis. HBO2 has several physiologic mechanisms which may be beneficial in sepsis, including restoration of mitochondrial function, improved microvascular function and organ perfusion, decreased capillary leak, improved cytokine profile, direct antimicrobial effects, and enhanced antibiotic function. The studies reviewed suggest that HBO2 therapy may be most effective if administered early and in high doses. Animal trials also show that HBO2 may provide protection to the gut mucosa by preventing bacterial translocation in sepsis. HBO2 has a potential to reduce organ failure through novel sepsis mechanisms not used in other therapies. Further human studies should be performed to better elucidate the role of HBO2 in improving sepsis clinical outcomes.

Endocytosis of very low-density lipoproteins: an unexpected mechanism for lipid acquisition by breast cancer cells.

We previously described the expression of CD36 and LPL by breast cancer (BC) cells and tissues and the growth-promoting effect of VLDL observed only in the presence of LPL. We now report a model in which LPL is bound to a heparan sulfate proteoglycan motif on the BC cell surface and acts in concert with the VLDL receptor to internalize VLDLs via receptor-mediated endocytosis. We also demonstrate that gene-expression programs for lipid synthesis versus uptake respond robustly to triglyceride-rich lipoprotein availability. The literature emphasizes de novo FA synthesis and exogenous free FA uptake using CD36 as paramount mechanisms for lipid acquisition by cancer cells. We find that the uptake of intact lipoproteins is also an important mechanism for lipid acquisition and that the relative reliance on lipid synthesis versus uptake varies among BC cell lines and in response to VLDL availability. This metabolic plasticity has important implications for the development of therapies aimed at the lipid dependence of many types of cancer, in that the inhibition of FA synthesis may elicit compensatory upregulation of lipid uptake. Moreover, the mechanism that we have elucidated provides a direct connection between dietary fat and tumor biology.-.