Encapsulating peritoneal sclerosis post liver transplant and peritoneal dialysis: case report and literature review.

Encapsulating peritoneal sclerosis (EPS) is a rare and debilitating condition. A fibrocollagenous membrane, which promotes encasement of the small intestine leaving a cocoon-like appearance, takes place. It is mainly associated with peritoneal infections, medications, peritoneal dialysis and systemic inflammatory diseases. Diagnosis is based on clinical history, intestinal obstruction and imaging exam. We report a case of EPS in a 68-year-old man with a medical history of liver transplantation and peritoneal dialysis, complaining of obstructive bowel symptoms.

Design, synthesis and biological evaluation of novel thiosemicarbazones as cruzipain inhibitors.

Based on the activity of 23 TSCs on CZ taken from the literature, we have developed a QSAR model for predicting the activity of TSCs. New TSCs were designed and then tested against CZP, resulting in inhibitors with IC50 values in the nanomolar range. The modelling of the corresponding TSC-CZ complexes by molecular docking and QM/QM ONIOM refinement indicates a binding mode compatible with what was expected for active TSCs, according to a geometry-based theoretical model previously developed by our research group. Kinetic experiments on CZP suggest that the new TSCs act by a mechanism that involves the formation of a reversible covalent adduct with slow association and dissociation kinetics. These results demonstrate the strong inhibitory effect of the new TSCs and the benefit of the combined use of QSAR and molecular modelling techniques in the design of new and potent CZ/CZP inhibitors.

Gastric adenocarcinoma in the excluded stomach 18 years after bariatric surgery: a case report.

Gastric cancer (GC) ranks fourth in overall cancer mortality. Bariatric surgical procedures, especially the gastric bypass surgery (GBS), raise a concern about the risk of GC in the excluded stomach (ES). Diagnosis of GC in the ES is challenging due to anatomical changes and impossibility of endoscopic access to the ES. There are few reports of GC after GBS, and it occurs more in the gastric stump than in the ES. We report a case of a 54-year-old female with GC in the ES 18 years after GBS. The increasing number of GBS and the aggressiveness of the GC show how relevant this case is to emphasize the need to consider this diagnosis in patients who develop upper abdominal symptoms, anemia or weight loss.

Thiosemicarbazone derivatives: Evaluation as cruzipain inhibitors and molecular modeling study of complexes with cruzain.

The development of cruzipain inhibitors represents one of the most attractive challenges in the search for drugs for the treatment of Chagas disease. A recombinant form of this enzyme, cruzain, has been crystallized with numerous inhibitors, excluding thiosemicarbazones. These compounds have been established as potent inhibitors of cruzain, although there is very little data in the literature of thiosemicarbazones tested on cruzipain. In this work, we present the results of the evaluation of eleven thiosemicarbazones on cruzipain, isolated from T. cruzi epimastigotes, six of them previously evaluated on cruzain. For these latter, we studied through computational methods, the mode of interaction with the active site of cruzain and the contribution of geometric parameters to the possible mechanism of action involved in the observed inhibition. Finally, from some geometric parameters analyzed on modeled TSC-cruzain complexes, a semi-quantitative relationship was established that could explain the inhibitory activity of thiosemicarbazones on cruzipain, the enzyme actually present in the parasite.