Self-assembly of glycerol monooleate with the antimicrobial peptide LL-37: a molecular dynamics study.

Over the past decade, the rapid increase in the incidence of antibiotic-resistant bacteria has promoted research towards alternative therapeutics such as antimicrobial peptides (AMPs), but their biodegradability limits their application. Encapsulation into nanocarriers based on the self-assembly of surfactant-like lipids is emerging as a promising strategy for the improvement of AMPs' stability and their protection against degradation when in biological media. An in-depth understanding of the interactions between the structure-forming lipids and AMPs is required for the design of nanocarriers. This in silico study, demonstrates the self-assembly of the amphiphilic lipid glycerol monooleate (GMO) with the antimicrobial peptide LL-37 into nanocarriers on the molecular scale. Molecular dynamics (MD) simulations show the formation of direct micelles, with either one or two interacting LL-37, and vesicles in this two-component system in agreement with experimental results from small-angle X-ray scattering studies. The hydrophobic contacts between LL-37 and GMOs in water appear responsible for the formation of these nanoparticles. The results also suggest that the enhanced antimicrobial efficiency of LL-37 in these nanocarriers that was previously observed experimentally can be explained by the availability of its side chains with charged amino acids, an increase of the electrostatic interaction and a decrease of the peptide's conformational entropy upon interacting with GMO. The results of this study contribute to the fundamental understanding of lipid-AMP interactions and may guide the comprehensive design of lipid-based self-assembled nanocarriers for antimicrobial peptides.

Pancreaticoduodenectomy In Patients With Hepatic Artery, Anatomic Variants: Tailoring, Perioperative Care and Surgical Outcomes.

Introduction: Pancreaticoduodenectomy (PD) is the procedure of choice in patients with tumors of pancreatic head or periampullary region. Hepatic artery anatomic variants (HAav) are frequently encountered during PD. Aim: To evaluate the incidence of HAav in a series of PDs and their consequence on technical tailoring and outcome. Material and Methods: Forty-five patients with HAav were identified in a consecutive series of 140 PDs for periampullary and pancreatic head tumors performed between January 1, 2007 and December 31, 2015. The groups with or without HAav were compared in terms of operative approach, complications and survival. Results: All patients underwent Whipple procedure, with right posterior approach for those having HAav. HAav was spared without damage in 41 cases. Four patients in whom the HAav were either sacrificed (2) or damaged (2) required arterial reconstruction. Conclusions: HAav are frequently encountered during PD. Its safeguarding is mandatory but in malignancy it can be damaged or sacrificed, hence arterial reconstruction is required. HAav have no negative impact on surgical morbidity and outcome.