Thermodynamic interference with bile acid demicelleization reduces systemic entry and injury during cholestasis.

Bile acids (BA), with their large hydrophobic steroid nucleus and polar groups are amphipathic molecules. In bile, these exist as micelles above their critical micellar concentration (CMC). In blood at low concentrations, these exist as monomers, initiating cellular signals. This micellar to monomer transition may involve complex thermodynamic interactions between bile salts alone or with phospholipids, i.e. mixed micelles and the aqueous environment. We therefore went on to test if therapeutically relevant changes in temperature could influence micellar behavior of bile salts, and in turn whether this affected the biological responses in cells, and in vivo. Sodium taurocholate (STC) belongs to a major class of bile salts. STC has a CMC in the 5-8 mM range and its infusion into the pancreatic duct is commonly used to study pancreatitis. We thus studied micellar breakdown of STC using isothermal titration calorimetry (ITC), dynamic light scattering and cryogenic transmission electron microscopy. Under conditions relevant to the in vivo environment (pH 7.4, Na 0.15 M), ITC showed STC to have a U shaped reduction in micellar breakdown between 37 °C and 15 °C with a nadir at 25 °C approaching ≈90% inhibition. This temperature dependence paralleled pancreatic acinar injury induced by monomeric STC. Mixed micelles of STC and 1-palmitoyl, 2-oleyl phosphatidylcholine, a phospholipid present in high proportions in bile, behaved similarly, with ≈75% reduction in micellar breakdown at 25 °C compared to 37 °C. In vivo pancreatic cooling to 25 °C reduced the increase in circulating BAs after infusion of 120 mM (5%) STC into the pancreatic duct, and duct ligation. Lower BA levels were associated with improved cardiac function, reduced myocardial damage, shock, lung injury and improved survival independent of pancreatic injury. Thus micellar breakdown of bile salts is essential for their entry into the systemic circulation, and thermodynamic interference with this may reduce their systemic entry and consequent injury during cholestasis, such as from biliary pancreatitis.

Rapid Soft Tissue Approximation and Repair using Laser-activated Silk Nanosealants.

Tissue approximation and repair have been conventionally performed with sutures and staples, but these means are inherently traumatic. Tissue approximation using laser-responsive nanomaterials can lead to rapid tissue sealing and repair, and is an attractive alternative to existing clinical methods. Here, we demonstrate the use of laser-activated nanosealants (LANS) with gold nanorods (GNRs) embedded in silk fibroin polypeptide matrices. The adaptability of LANS for sealing soft tissues is demonstrated using two different modalities: insoluble thin films for internal, intestinal tissue repair, and semi-soluble pastes for external repair, shown by skin repair in live mice. Laser repaired intestinal tissue held over seven times more fluid pressure than sutured intestine and also prevented bacterial leakage. Skin incisions in mice closed using LANS' showed indication of increased mechanical strength and faster repair compared to suturing. Laser-activated silk-GNR nanosealants rapidly seal soft-tissue tears and show high promise for tissue approximation and repair in trauma and routine surgery.

Vibrational dynamics of amorphous beryllium hydride and lithium beryllium hydrides.

The vibrational density of states of amorphous beryllium hydride (a-BeH2) and lithium beryllium hydrides have been studied using inelastic neutron scattering, infrared, and Raman spectroscopies. The positions of the symmetrical (120-180 meV) and antisymmetrical (200-260 meV) Be-H stretching modes and those of the H-Be-H bending mode (50-120 meV) have been determined and the results discussed and compared with recent theoretical calculations. With the addition of lithium to the beryllium hydride network, the vibrational bands are shifted to lower energies, indicating a less rigid network.