A Phase I clinical trial was carried out to evaluate the effects of endotoxin elimination by direct hemoperfusion using a cartridge containing chemically immobilized polymyxin B fibers (PMX-F). Thirty-seven endotoxemic patients with multiple organ failure (MOF) were treated. Direct hemoperfusion for 2 h using a PMX-F column was performed (PMX). PMX could remove circulating endotoxin from severely endotoxemic patients. Plasma endotoxin level was significantly decreased between its inlet and outlet level of PMX-F column ( P < 0.01). The mean plasma endotoxin concentration of all PMX ( n = 51) was 83.7 ± 26.7 pg/ml before PMX, and significantly decreased to 56.4 ± 27.9 after ( P < 0.01). Plasma endotoxin was significantly decreased in survivors, but that of non-survivors did not change with PMX ( P < 0.05). Body temperature, blood pressure, cardiac index, systemic vascular resistance and the oxygen consumption index improved significantly after PMX. Inotropic and vasopressive drugs were discontinued or reduced with PMX. PMX treatment showed a correlation between reduction of plasma endotoxin level and the improvement of septic syndrome, especially cardiovascular impairments. Also, this new therapy seemed to influence the outcome of severe sepsis or septic MOF patients with endotoxemia.

The binding effect of divalent cation Cu(2+) on the gelation process with a coil-helix transition in Cu(2+)/gellan aqueous solutions has been successfully elucidated by EPR, CD, and viscoelasticity measurements. Generally, Na-type gellan gum in aqueous solution can make gel when accompanied by an intrinsic coil-helix formation induced by hydrogen bonding between chains without any additional cations at T(ch)(-)(in) ( approximately 29 degrees C) with cooling temperature. An extrinsic coil-helix transition, induced by additional divalent cations in advance of the intrinsic sol-gel transition of gellan gum, is separately detected by CD measurement. The extrinsic coil-helix transition temperatures T(ch)(-)(ex) (>47 degrees C), which increased with the Cu(2+) concentration added, were nearly identical to the sol-gel transition temperature, T(sg), determined by the viscoelasticity measurement. Judging from the molar ellipticity by CD measurement and quantitative analysis of EPR spectra, it was elucidated that the helix forming process via divalent cations is composed of two steps ascribed to the different origins, i.e., a chemical binding effect via Cu(2+) ions in the initial stage and hydrogen bonds subsequently. Finally, we propose the coil-helix and the sol-gel transition mechanism initiated by the binding effect with the divalent cation, in which the partial chelate formation can cause local formation of helices and junction zones in the vicinity of the chelates at the initial stage of the process and stabilize the helices and the junction zones. On the other hand, the stabilized helices and junction zones can induce further formation and further stabilization of the Cu(2+)-gellan chelates. The mutual stabilization promotes the formation of three-dimensional network structure at the higher temperature than the intrinsic temperature for network formation.

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In this lecture the measurements and analyses of the isotropic and anisotropic diffusion coefficients(D) of rod‐like polypeptide such as poly(γ‐L‐glutamate)(PLG) with n‐alkyl side chains, of which the main chain takes the α‐helical conformation, as a function of the main chain length in the thermotropic and lyotropic liquid crystalline phases over a wide range of temperatures from 30 to 80°C by means of pulse high field‐gradient spin echo 1H NMR method have been introduced. In the anisotropic diffusion, the D∥ value in direction parallel to the α‐helical chain axis is found to be much larger than the D⊥ value in direction perpendicular to the α‐helical chain axis. The diffusion process is followed by the Kirkwood theory. Further, it is described that the diffusion in the nematic liquid crystalline phase is much slower than that in the isotropic phase.