Falciform ligament flap for the protection of the gastroduodenal artery stump after pancreaticoduodenectomy: A single center experience.

AIM OF THE STUDY: Delayed hemorrhage, though rare, remains a significant source of morbidity and mortality after pancreaticoduodenectomy (PD). An important cause of this delayed hemorrhage is erosion or pseudoaneurysm formation of the gastroduodenal artery (GDA) by pancreatic enzymes and adjacent intra-abdominal sepsis. So protection of the GDA stump may avoid this devastating complication. PATIENTS AND METHODS: This is a retrospective observational study. All patients, who underwent a PD between August 2007 and December 2014, were included in the study. We used pedicled falciform ligament flap to protect the GDA stump. After PD, pedicled falciform ligament flap was spread widely over the skeletonized hepatic artery including the GDA stump and was fixed to the surrounding retroperitoneal connective tissue. This procedure allowed complete separation of the GDA stump from the pancreatic stump. RESULTS: We performed 182 cases of PD during the study period. Although, 27 (15%) patients developed pancreatic fistula and six patients developed intra-abdominal abscess, no one experienced hemorrhage due to erosion or pseudoaneurysm formation of the GDA. CONCLUSION: The present surgical option seems to be an effective measure for the prevention of erosion and pseudoaneurysm formation of the GDA after PD.

Preparation and characterization of Simvastatin solid dispersion using skimmed milk.

Simvastatin has low aqueous solubility resulting in low oral bioavailability (5%) and thus presents a challenge in formulating a suitable dosage form. To improve the aqueous solubility, a solid dispersion formulation of Simvastatin was prepared by lyophilization utilizing skimmed milk as a carrier. Six different formulations were prepared with varying ratios of drug and carrier and the corresponding physical mixtures were also prepared. The improvement of amorphous state through solid dispersion was confirmed by differential scanning calorimetry and X-ray diffraction studies. The optimum drug-to-carrier ratio of 1:9 enhanced solubility nearly 30-fold as compared to pure drug. In-vitro drug release studies exhibited a cumulative release of 86.69% as compared to 25.19% for the pure drug. Additionally, scanning electron microscopy studies suggested the conversion of crystalline Simvastatin to an amorphous form. In a Triton-induced hyperlipidemia model, a 3-fold increase in the lipid lowering potential was obtained with the reformulated drug as compared to pure drug. These results suggest that solid dispersion of Simvastatin using skimmed milk as carrier is a promising approach for oral delivery of Simvastatin.

The complex folding behavior of HIV-1-protease monomer revealed by optical-tweezer single-molecule experiments and molecular dynamics simulations.

We have used optical tweezers and molecular dynamics simulations to investigate the unfolding and refolding process of a stable monomeric form of HIV-1-protease (PR). We have characterized the behavior under tension of the native state (N), and that of the ensemble of partially folded (PF) conformations the protein visits en route to N, which collectively act as a long-lived state controlling the slow kinetic phase of the folding process. Our results reveal a rich network of unfolding events, where the native state unfolds either in a two-state manner or by populating an intermediate state I, while the PF state unravels through a multitude of pathways, underscoring its structural heterogeneity. Refolding of mechanically denatured HIV-1-PR monomers is also a multiple-pathway process. Molecular dynamics simulations allowed us to gain insight into possible conformations the protein adopts along the unfolding pathways, and provide information regarding possible structural features of the PF state.