Aziridide-based inhibitors of cathepsin L: synthesis, inhibition activity, and docking studies

A comprehensive screening of N-acylated aziridine (aziridide) based cysteine protease inhibitors containing either Boc-Leu-Caa (Caa=cyclic amino acid), Boc-Gly-Caa, or Boc-Phe-Ala attached to the aziridine nitrogen atom revealed Boc-(S)-Leu-(S)-Azy-(S,S)-Azi(OBn)(2) (18 a) as a highly potent cathepsin L (CL) inhibitor (K(i)=13 nM) (Azy=aziridine-2-carboxylate, Azi=aziridine-2,3-dicarboxylate). Docking studies, which also accounted for the unusual bonding situations (the flexibility and hybridization of the aziridides) predict that the inhibitor adopts a Y shape and spans across the entire active site cleft, binding into both the nonprimed and primed sites of CL.     

Protective effects of various preservation solutions on cultured endothelial cells

Vascular endothelium represents the first target in organ preservation and plays an important role in reperfusion injury. Bovine aortic endothelial cells were cultivated and the most commonly used preservation solutions, such as University of Wisconsin HTK (Brettschneider's histidine-tryptophane-ketoglutarate), and Euro-Collins solutions were tested on the endothelial monolayer. In addition, one group of cultivated cells was preserved with cold saline solution, and endothelial monolayers grown in culture medium were used as controls. The quality of preservation was assessed after 24, 48, and 72 hours of cold storage. Reperfusion was simulated and its effects were observed by reincubation in culture medium at 37 degrees C for 6 hours. The total number of cells, cell viability (determined using trypan blue exclusion), and morphologic alterations were determined. Prostacyclin release was evaluated as a biochemical marker. University of Wisconsin solution maintains more than 99% cell viability after rewarming after both 24 and 48 hours of cold storage. After 72 hours, 86.7% of cells were still viable. Preservation with HTK and Euro-Collins solution allowed cell survival for only 24 hours (96.7%, HTK; 49.9%, Euro-Collins), with no viable cells seen after 48 hours. The cold saline-preserved sample showed 57.8% viable cells after 24 hours and 29.7% after 48 hours. No viable cells were detectable after 72 hours. Light microscopy revealed several patterns of both structural damage and intracellular change (nucleus and cytoplasm) in the endothelial monolayer after preservation with HTK, Euro-Collins solution, and cold saline solution. No morphologic alterations were seen in the University of Wisconsin solution group for as long as 72 hours.(ABSTRACT TRUNCATED AT 250 WORDS)     

Noise peaks influence communication in the operating room. An observational study

Noise peaks are powerful distractors. This study focuses on the impact of noise peaks on surgical teams’ communication during 109 long abdominal surgeries. We related measured noise peaks during 5-min intervals to the amount of observed communication during the same interval. Results show that noise peaks are associated with less case-relevant communication; this effect is moderated by the level of surgical experience; case-relevant communications decrease under high noise peak conditions among junior, but not among senior surgeons. However, case-irrelevant communication did not decrease under high noise level conditions, rather there was a trend to more case-irrelevant communication under high noise peaks. The results support the hypothesis that noise peaks impair communication because they draw on attentional resources rather than impairing understanding of communication. As case-relevant communication is important for surgical performance, exposure to high noise peaks in the OR should be minimised especially for less experienced surgeons.

Practitioner Summary: This study investigated whether noise during surgeries influenced the communication within surgical teams. During abdominal surgeries, noise levels were measured and communication was observed. Results showed that high noise peaks reduced the frequency of patient-related communication, but did not reduce patient-irrelevant communication. Noise may negatively affect team coordination in surgeries.