Simon Chapman and Ross MacKenzie review the evidence and argue that health promotion messages should emphasize that the most successful method used by most ex-smokers is unassisted cessation.

The lipopolysaccharide (LPS)-binding protein (LBP) has a concentration-dependent dual role in the pathogenesis of gram-negative sepsis: low concentrations of LBP enhance the LPS-induced activation of mononuclear cells (MNC), whereas the acute-phase rise in LBP concentrations inhibits LPS-induced cellular stimulation. In stimulation experiments, we have found that LBP mediates the LPS-induced cytokine release from MNC even under serum-free conditions. In biophysical experiments we demonstrated that LBP binds and intercalates into lipid membranes, amplified by negative charges of the latter, and that intercalated LBP can mediate the CD14-independent intercalation of LPS into membranes in a lipid-specific and temperaturedependent manner. In contrast, prior complexation of LBP and LPS inhibited binding of these complexes to membranes due to different binding of LBP to LPS or phospholipids. This results in a neutralization of LPS and, therefore, to a reduced production of tumor necrosis factor by MNC. We propose that LBP is not only present as a soluble protein in the serum but may also be incorporated as a transmembrane protein in the cytoplasmic membrane of MNC and that the interaction of LPS with membrane-associated LBP may be an important step in LBP-mediated activation of MNC, whereas LBP-LPS complexation in the serum leads to a neutralization of LPS.Human lipopolysaccharide (LPS)-binding protein (LBP) is a serum glycoprotein belonging to a family of lipid-binding proteins which includes bactericidal/permeability-increasing protein (BPI), phospholipid ester transfer protein, and cholesterol ester transfer protein (1,18,36). It consists of 456 amino acid residues preceded by a hydrophobic signal sequence of 25 residues (31). LBP is synthesized by hepatocytes (26) and intestinal epithelial cells (42) and is present in normal serum at concentrations of 5 to 10 g/ml, rising up to 200 g/ml 24 h after induction of an acute-phase response (35). This rise in LBP levels is caused by transcriptional activation of the LBP gene mediated by interleukin-1 (IL-1) and . LBP has a concentration-dependent dual role: low concentrations of LBP enhance the LPS-induced activation of mononuclear cells (MNC), whereas the acute-phase rise in LBP concentrations inhibits LPS-induced cellular stimulation (20). LBP binds a variety of LPS (endotoxin) chemotypes from rough and smooth strains of gram-negative bacteria and even lipid A, the lipid moiety of LPS (37, 38). The LPS molecules, components of the outer membrane of gram-negative bacteria, are important mediators in the pathogenesis of gram-negative sepsis and septic shock (25). Because the lipid A moiety has been shown to be responsible for the biological activity of LPS in most in vivo and in vitro test systems, it has been termed the endotoxic principle of LPS (27).LPSs activate monocytes and macrophages to secrete inflammatory cytokines (tumor necrosis factor alpha [TNF-␣] and IL-1, etc.) and other potent mediators (32) by an intracellular signal amplification pathway. These mediato...

Clostridium difficile is a leading cause of nosocomial infection in North AmericaWith favorable characteristics such as high production yield, potent toxin neutralization, and intrinsic stability, these V H Hs are attractive systemic therapeutics but are more so as oral therapeutics in the destabilizing environment of the gastrointestinal tract.