Glutathione (GSH; L-gamma-glutamyl-L-cysteineglycine) is found in almost all mammalian cells, and liver has very high intracellular levels of GSH. It has many cellular functions, such as being a coenzyme, maintaining thiol/disulfide status, protection against toxic compounds and oxidative stress. GSH levels have been reported to be low in a number of pathological conditions; thus methods for increasing GSH levels are desirable. GSH may be increased by supplying its amino acid precursor cysteine, in the form of prodrugs, such as N-acetylcysteine (NAC) and 2-oxothiazolidine-4-carboxylate (OTC). It may also be increased by giving gamma-glutamylcysteine, a dipeptide precursor GSH monoester and GSH diester are effective GSH delivery drugs. Such compounds may be therapeutically useful. Gene therapy may be useful for longer term therapy of GSH deficiency.

Critical illness is associated with alterations in muscle glutathione metabolism. The muscle-reduced glutathione concentrations decrease and, in addition, the ratio between reduced and total glutathione decreases, indicating a situation of oxidative stress in this tissue. This decrease may impair the defense of muscle against oxygen free radicals and influence amino acid transport, thus contributing to the loss of balance between protein synthesis and protein degradation that is characteristic of protein catabolism.

Therapy is typically delayed by several years in these patients due to erroneous diagnosis and failed treatment of hemorrhoids and inflammatory bowel disease. Relative to hemangiomas, lymphangiomas of the rectosigmoid are even more rare and when symptomatic, present with rectal bleeding and pelvic pain.

Glutathione synthetase is an enzyme that belongs to the glutathione synthetase ATP-binding domain-like superfamily. It catalyzes the second step in the biosynthesis of glutathione from ␥-glutamylcysteine and glycine in an ATP-dependent manner. Glutathione synthetase has been purified and sequenced from a variety of biological sources; still, its exact mechanism is not fully understood. A variety of structural alignment methods were applied and four highly conserved residues of human glutathione synthetase (Glu-144, Asn-146, Lys-305, and Lys-364) were identified in the binding site. The function of these was studied by experimental and computational site-directed mutagenesis. The three-dimensional coordinates for several human glutathione synthetase mutant enzymes were obtained using molecular mechanics and molecular dynamics simulation techniques, starting from the reported crystal structure of human glutathione synthetase. Consistent with circular dichroism spectroscopy, our results showed no major changes to overall enzyme structure upon residue mutation. However, semiempirical calculations revealed that ligand binding is affected by these mutations. The key interactions between conserved residues and ligands were detected and found to be essential for enzymatic activity. Particularly, the negatively charged Glu-144 residue plays a major role in catalysis.

Objective: To explore the impact of workplace violence on job performance and quality of life of community healthcare workers in China, especially the relationship of these three variables. Methods: From December 2013 to April 2014, a total of 1404 healthcare workers were recruited by using the random cluster sampling method from Community Health Centers in Guangzhou and Shenzhen. The workplace violence scale, the job performance scale and the quality of life scale (SF-36) were self-administered. The structural equation model constructed by Amos 17.0 was employed to assess the relationship among these variables. Results: Our study found that 51.64% of the respondents had an experience of workplace violence. It was found that both job performance and quality of life had a negative correlation with workplace violence. A positive association was identified between job performance and quality of life. The path analysis showed the total effect (β = −0.243) of workplace violence on job performance consisted of a direct effect (β = −0.113) and an indirect effect (β = −0.130), which was mediated by quality of life. Conclusions: Workplace violence among community healthcare workers is prevalent in China. The workplace violence had negative effects on the job performance and quality of life of CHCs’ workers. The study suggests that improvement in the quality of life may lead to an effective reduction of the damages in job performance caused by workplace violence.

To gain insight into cellular metabolism underlying the glutathione (GSH) alterations induced by surgical trauma, we assessed postoperative skeletal muscle GSH metabolism and its redox status in 10 patients undergoing elective abdominal surgery. Muscle biopsy specimens were taken from the quadriceps femoris muscle before and at 24 and 72 h after surgery. GSH concentrations decreased by 40% at 24 h postoperatively compared with the paired preoperative values ( P < 0.001) and remained low at 72 h ( P < 0.01). The concentration of GSH disulfide (GSSG) did not significantly change throughout the study period, whereas the total GSH (as GSH equivalent) concentration decreased after surgery. Of the GSH constituent amino acids, the concentration of cysteine remained unchanged throughout the study period (from 28.2 ± 10.1 preoperatively to 29.4 ± 13.9 at 24 h postoperatively and to 28.3 ± 15.6 μmol/kg wet wt at 72 h postoperatively). Despite a reduction in glutamate concentration by 40% 24 h after surgery, no correlation was established between GSH and glutamate concentrations postoperatively. Activity of γ-glutamylcysteine synthetase did not change significantly after surgery, whereas GSH synthetase activity decreased postoperatively (from 66.4 ± 19.1 preoperatively to 41.0 ± 10.5 24 h postoperatively, P < 0.01, and to 46.0 ± 11.7 μU/mg protein 72 h postoperatively, P < 0.05). The decrease of GSH was correlated to the reduced GSH synthetase activity seen at 24 h postoperatively. These results indicate that the skeletal muscle GSH pool is diminished in patients after surgical trauma. The depletion of the GSH pool is associated with a decreased activity of GSH synthetase, indicating a decreased GSH synthetic capacity in skeletal muscle tissue.

ObjectiveThe authors investigate the effect of surgical trauma on skeletal muscle concentrations of glutathione in patients undergoing selective abdominal surgery. Summary Background DataThe posttraumatic state is accompanied by characteristic changes in the pattern of free amino acids and a decline of protein synthesis in human skeletal muscle. Glutathione has multiple metabolic functions that are involved in cellular homeostasis. It is unknown how surgical trauma affects the glutathione metabolism of skeletal muscle in surgical patients. MethodsEight patients undergoing elective abdominal surgery were investigated. Percutaneous muscle biopsies and blood samples were taken before operation and at 6, 24, and 48 hours after operation. The concentrations of glutathione were determined in muscle tissue, plasma, and whole blood, as well as the concentrations of the related amino acids in muscle and plasma. ResultsIn skeletal muscle, the levels of both reduced and total glutathione decreased by 40% (p < 0.01) at 24 hours and remained low at 48 hours after operation compared with the preoperative values. The glutathione concentration in plasma was 20% lower after operation compared with the concentration before operation (p < 0.05). There were no changes at the whole blood levels of glutathione. Tissue glutamate and glutamine decreased significantly after operation (p < 0.001), whereas intracellular cysteine and glycine remained unchanged. ConclusionsSkeletal muscle glutathione deficiency occurs after surgical trauma. This may lead to an increase in the susceptibility to intracellular oxidative injury. 420

Key Points Question Is the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to primary cytoreductive surgery (PCS) associated with better outcomes for patients with stage III epithelial ovarian cancer? Findings In this multicenter retrospective cohort study of 584 patients with stage III epithelial ovarian cancer, for patients undergoing PCS with HIPEC and those undergoing PCS alone, the median overall survival was 49.8 and 34.0 months, respectively, and the 3-year overall survival rates were 60.3% and 49.5%, respectively. Complete PCS with HIPEC was associated with the best survival outcomes, with a median overall survival of 53.9 months and a 3-year overall survival rate of 65.9%. Meaning In this study, the addition of HIPEC to PCS was associated with better survival outcomes for patients with stage III epithelial ovarian cancer.