University of Louisville

About: University of Louisville is a education organization based out in Louisville, Kentucky, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 24600 authors who have published 49248 publications receiving 1573346 citations. The organization is also known as: UofL.

Adenosine 5′-Monophosphate-Activated Protein Kinase Promotes Macrophage Polarization to an Anti-Inflammatory Functional Phenotype

Abstract: Herein, we demonstrate a role of AMP-activated protein kinase (AMPK) as a potent counterregulator of inflammatory signaling pathways in macrophages. Stimulation of macrophages with anti-inflammatory cytokines (i.e., IL-10 and TGFβ) resulted in the rapid phosphorylation/activation of AMPK, whereas stimulation of macrophages with a proinflammatory stimulus (LPS) resulted in AMPK dephosphorylation/inactivation. Inhibition of AMPKα expression by RNA interference dramatically increased the mRNA levels of LPS-induced TNF-α, IL-6, and cyclooxygenase-2. Likewise, expression of a dominant negative AMPKα1 in macrophages enhanced TNF-α and IL-6 protein synthesis in response to LPS stimulation, while diminishing the production of IL-10. In contrast, transfection of macrophages with a constitutively active form of AMPKα1 resulted in decreased LPS-induced TNF-α and IL-6 production, and heightened production of IL-10. In addition, we found that AMPK negatively regulated LPS-induced IκB-α degradation and positively regulated Akt activation, accompanied by inhibition of glycogen synthase kinase β and activation of CREB. Thus, AMPK directs signaling pathways in macrophages in a manner that suppresses proinflammatory responses and promotes macrophage polarization to an anti-inflammatory functional phenotype.

Putative contributors to the secular increase in obesity: exploring the roads less traveled

Abstract: Putative contributors to the secular increase in obesity: exploring the roads less traveled

Efficacy and safety of a topical gel formulation of recombinant human platelet-derived growth factor-BB (becaplermin) in patients with chronic neuropathic diabetic ulcers: A phase III randomized placebo-controlled double-blind study

Abstract: OBJECTIVE To compare the efficacy and safety of topically applied recombinant human platelet-derived growth factor-BB (rhPDGF-BB) (becaplermin) with placebo gel in patients with chronic diabetic neuropathic ulcers of the lower extremities. RESEARCH DESIGN AND METHODS This multicenter double-blind placebo-controlled phase 111 trial included 382 patients with type 1 or type 2 diabetes and chronic ulcers of at least 8 weeks9 duration. After sharp debridement of the ulcer, patients were randomized to receive becaplermin gel 30 μg/g, becaplermin gel 100 μg/g, or placebo gel, in conjunction with a standardized regimen of good wound care until complete wound closure was achieved or for a maximum of 20 weeks. Moist saline-soaked gauze dressings were changed twice daily with study medication applied by patients or caregivers at the evening dressing change. Safety was assessed by monitoring adverse events (AEs) and by clinical laboratory evaluations. RESULTS Compared with placebo gel, becaplermin gel 100 μg/g significantly increased the incidence of complete wound closure by 43% (50 vs. 35%, P = 0.007) and decreased the time to achieve complete wound closure by 32% (86 vs. 127 days; estimated 35th percentile, P = 0.013). AEs reported during treatment or during a 3-month follow-up period were similar in nature and incidence across all treatment groups. CONCLUSIONS Becaplermin gel 100 μg/g, in conjunction with good wound care, significantly increased the incidence of complete wound closure and significantly reduced the time to complete closure of chronic diabetic neuropathic ulcers. The safety profile of becaplermin gel was similar to that of placebo gel.