Search

Silver salts of the higher straight-chain alkanoic acids (silver soaps) and especially silver(I) behenate and silver(I) stearate are being used as the silver source in thermographic and photothermographic materials. The silver(I) alkanoates exhibit a complicated thermal behavior, and different phase transitions can be detected between the solid, crystalline state and the onset point of thermal decomposition. The phase transitions are due to a gradual breakdown of the layerlike structure of these compounds, and some of the phases are viscous mesophases. The silver alkanoates of the homologous series between silver propionate (C3H5O2Ag) and silver tetracosanoate (C24H47O2Ag) have been prepared, as well as silver hexacosanoate (C26H51O2Ag) and silver octacosanoate (C28H55O2Ag). The light stability of the compounds increases with increasing chain length. The room-temperature X-ray diffractograms indicate that the silver alkanoates consist of a bilayer structure. The thermal properties of these silver-containing metallomesogens were investigated by high-temperature X-ray diffraction, differential scanning calorimetry, and polarizing optical microscopy. The number and the nature of the phase transitions depends on the alkyl chain length. The thermal decomposition of the silver alkanoates with long alkyl chains proceeds in a liquid-crystalline state (mesophase), and leads to the formation of silver. The thermal behavior of silver behenate is discussed in detail.

A recombinant 23-kDa protein (rBPI23) derived from human bactericidal/permeability-increasing protein (BPI) possesses potent endotoxin-neutralizing abilities in vitro and in vivo. Binding of rBPI23 to those endotoxins (lipopolysaccharides [LPSs]) encountered clinically would be a prerequisite for efficacy in decreasing mortality among patients suffering from gram-negative sepsis and shock, a disease state in which an etiological role for LPS has been implicated. rBPI23 binds well to lipid A (n = 7), to rough-mutant O-chain-deficient LPS (n = 18, Re to Ra chemotypes), to lipid A-core covalently linked to the O chain, to LPSs from clinically relevant serotypes (n = 100), and to bacterial cells (n = 88) of Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae, the species most often implicated in clinical gram-negative sepsis and shock. Significant binding of rBPI23 to these antigens took place at rBPI23 concentrations of 1 to 500 ng/ml (median, 16 to 32 ng/ml). Binding did not involve 3-deoxy-D-manno-octulosonate of the inner core. Determining the exact epitope recognized by rBPI23 would require further studies with synthetic lipid A substructures. The demonstrated ability of rBPI23 to universally bind LPS provides a sound basis for further testing of its endotoxin-neutralizing abilities, including clinical trials.

Lactoferrin (LF), a cationic 80-kDa protein present in polymorphonuclear leukocytes and in mucosal secretions, is known to have antibacterial effects on gram-negative bacteria, with a concomitant release of lipopolysaccharides (LPS, endotoxin). In addition, LF is known to decrease LPS-induced cytokine release by monocytes and LPS priming of polymorphonuclear leukocytes. Its mechanism of action is incompletely understood. We have now demonstrated by in vitro-binding studies that LF binds directly to isolated lipid A and intact LPS of clinically relevant serotypes of the species which most frequently cause bacteremia (Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa), as well as to lipid A and LPS of mucosal pathogens (among others, Neisseria meningitides and Haemophilus influenzae). Binding to LPS was inhibitable by lipid A and polymyxin B but not by KDO (3-deoxy-D-manno-octulosonate), a glycoside residue present in the inner core of LPS. Binding of LF to lipid A was saturable, and an affinity constant of 2 x 10(9) M-1 was calculated for the LF-lipid A interaction. Our data may explain, in part, the mechanism whereby LF exerts its antibacterial and anti-endotoxic effects. Further studies on the ability of LF to block the detrimental effects of LPS, both in vitro and in vivo, are warranted.