Rigid and flexible docking studies on PPAR-γ agonists: key interactions for a better antihyperglycemic activity and in silico pharmacodynamic activity versus experimental in vivo activity

We report both automated rigid and flexible ligand docking simulations performed on fifty peroxisome proliferator-activated receptor (PPAR-γ) agonists, namely, glitazones. The binding conformations and binding affinities of these agonists were obtained by the use of the Autodock 4.1 with Lamarckian genetic algorithm (LGA). All the 50 flexible docks are considered as well-docked as all of them were bound to the ligand binding domain of PPAR-γ. The predicted binding affinity values (pKa) were found to have some degree of correlation with their experimental in vivo activity values. The head group hydrogen bond interactions via H323 and H449 histidine residues were found to play a significant role. The results obtained will be valuable in designing newer selective PPAR-γ agonists.     

Perforative Peritonitis—Gastrointestinal Tract May Not Always Be the Source

Perforative peritonitis is the most common surgical emergency in general surgical practice. Gastrointestinal perforation is the etiology in the vast majority of the patients. However, occasionally, other rare causes may be encountered. One such cause of peritonitis is spontaneous perforation of non-gravid uterus. Uterine perforation is a potential complication of any intrauterine procedure and may be associated with injury to surrounding blood vessels or viscera such as the urinary bladder or intestine. Spontaneous uterine perforation is rare and less than 50 cases have been reported in the English literature. We are presenting two such cases of spontaneous perforation of the uterus in elderly postmenopausal women which presented with generalized peritonitis and were clinically indistinguishable from gastrointestinal perforation.