Effects of ozone exposure on the ocular surface

Changes in the ocular surface induced by ozone have received limited research attention. Here, we investigate the effects of ozone exposure on the integrity of the ocular surface, the production of inflammatory cytokines in tears, and changes in mucin-secreting cells in a mouse model. In addition, ozone-induced nuclear factor-κB (NF-κB)-mediated inflammatory processes were evaluated in cultured human conjunctival epithelial cells. In vivo, ozone induced the breakdown of corneal epithelial integrity, decreased the number of mucin-secreting cells, and induced the production of inflammatory cytokines, without altering tear volume. In vitro, ozone exposure led to increases in NF-κB nuclear translocation, κB-dependent transcriptional activity, NF-κB inhibitor α (IκBα) proteolysis, and expression of phosphorylated IκBα (p-IκBα), but did not cause cytotoxicity or cellular apoptosis. In addition, ozone induced the expression of inflammatory cytokines, Toll-like receptors, and C-C chemokine receptors, but decreased the expression of mucins. Furthermore, inhibition of NF-κB with pyrrolidine dithiocarbamate before exposure of cultured human conjunctival epithelial cells to ozone prevented changes in IκBα and p-IκBα levels in association with a decrease in the levels of inflammatory cytokines. Therefore, we conclude that ozone exposure interferes with ocular surface integrity and induces inflammation involving NF-κB-mediated processes at the level (and/or upstream) of IκBα. Understanding the role of ozone in the initiation of inflammatory processes on the animal ocular surface and in cultured human conjunctival epithelial cells can help elucidate the pathogenesis of ocular surface damage and suggest protective strategies for preserving a healthy ocular surface against ozone exposure.ope

Tramadol use is associated with enhanced postoperative outcomes in breast cancer patients: a retrospective clinical study with in vitro confirmation

BACKGROUND: There is growing interest in the effect of postoperative analgesics on oncological outcomes after cancer surgery. We investigated the impact of tramadol after breast cancer surgery on recurrence and mortality and explored the mechanism by which tramadol affects cultured breast cancer cells in vitro. METHODS: Electronic medical records of patients who underwent breast cancer surgery between November 2005 and December 2010 at Severance Hospital in Korea were reviewed. Cox regression analyses were used to identify factors related to postoperative recurrence and mortality. We performed the sensitivity test with propensity score matching to adjust for selection bias. In addition, we investigated the effects of tramadol on human breast adenocarcinoma (Michigan Cancer Foundation-7 [MCF-7]) cells via assessment of cell viability, clonogenic assay, and cell cycle analysis in vitro. RESULTS: Of 2588 breast cancer patients, 36.4% had received tramadol. Those who received tramadol had a 0.71-fold decreased risk of recurrence and a 0.56-fold decrease in mortality. The MCF-7 cell viability assays showed that tramadol had an anti-proliferative effect by cell cycle arrest, suppressing colony formation, and regulation of oestrogen and progesterone receptors. Tramadol induced apoptosis of MCF-7 cells via extracellular signal-regulated kinases by decreasing of 5-hydroxytryptamine (HT)2B receptor and transient receptor potential vanilloid-1 expression. CONCLUSIONS: After breast cancer surgery, patients who received tramadol had a decreased risk of postoperative recurrence and mortality. The anti-tumour effect of tramadol appears to involve inhibition of proliferation, induction of apoptosis, and effects on 5-HT2B receptor and TRPV-1.restrictio