Sepsis is a serious and life-threatening syndrome that often occurs in intensive care unit (ICU) patients. During sepsis, inflammatory cytokines and nitric oxide (NO) can be overproduced, causing tissue and cell injury. Propofol is an intravenous agent used for sedation of ICU patients. Our previous study showed that propofol has immunosuppressive effects on macrophage functions. This study was designed to evaluate the anti-inflammatory and antioxidative effects of propofol on the biosyntheses of tumor necrosis factor alpha (TNF-alpha), interleukin 1beta (IL-1beta), IL-6, and NO in lipopolysaccharide (LPS)- activated macrophages. Exposure to a therapeutic concentration of propofol (50 microM), LPS (1 ng/mL), or a combination of these two drugs for 1, 6, and 24 h was not cytotoxic to the macrophages. ELISA revealed that LPS increased macrophage TNF-alpha, IL-1beta, and IL-6 protein levels in a time-dependent manner, whereas propofol significantly reduced the levels of LPS-enhanced TNF-alpha, IL-1beta, and IL-6 proteins. Data from RT-PCR showed that LPS induced TNF-alpha, IL-1beta, and IL-6 mRNA, but propofol inhibited these effects. LPS also increased NO production and inducible nitric oxide synthase (iNOS) expression in macrophages. Exposure of macrophages to propofol significantly inhibited the LPS-induced NO biosynthesis. The present study shows that propofol, at a therapeutic concentration, has anti-inflammatory and antioxidative effects on the biosyntheses of TNF-alpha, IL-1beta, IL-6, and NO in LPS-activated macro-phages and that the suppressive effects are exerted at the pretranslational level.

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Only a limited number of psychosocial factors were associated with nausea and vomiting and fatigue in early pregnancy. Depression was related to physical symptoms, but unclear was whether depression preceded or resulted from the symptoms. Many women experienced symptoms, and better understanding of causality is needed to ameliorate the effects on women's well-being.

Crown ethers are small, cyclic polyethers that have found wide-spread use in phase-transfer catalysis and, to a certain degree, in protein chemistry. Crown ethers readily bind metallic and organic cations, including positively charged amino acid side chains. We elucidated the crystal structures of several protein-crown ether co-crystals grown in the presence of 18-crown-6. We then employed biophysical methods and molecular dynamics simulations to compare these complexes with the corresponding apoproteins and with similar complexes with ring-shaped low-molecular-weight polyethylene glycols. Our studies show that crown ethers can modify protein surface behavior dramatically by stabilizing either intra- or intermolecular interactions. Consequently, we propose that crown ethers can be used to modulate a wide variety of protein surface behaviors, such as oligomerization, domain–domain interactions, stabilization in organic solvents, and crystallization.