Current clamp at zero level in JT-60U current hole plasmas.

It is found that no current is driven in a central region of a tokamak plasma once the central current density becomes nearly zero ("current hole"), in spite of high electric conductivity, at the current drive by a toroidal electric field and a radio-frequency wave in experiments on the JT-60U tokamak. This is a new, stiff, self-organized structure of a magnetic field in an axisymmetric toroidal plasma.

Exchange transfusion with albumin-heme as an artificial O2-infusion into anesthetized rats: physiological responses, O2-delivery, and reduction of the oxidized hemin sites by red blood cells.

Human serum albumin (HSA) incorporating synthetic hemes, the tetrakis(o-pivalamido)phenylporphinatoiron(II) derivative (FeP), is an artificial hemoprotein (HSA-FeP) which is able to reversibly bind and release dioxygen under physiological conditions (in aqueous media, pH 7.4, 37 degrees C) like hemoglobin and myoglobin. Physiological responses to exchange transfusion with HSA-FeP solution [[HSA], 5 g/dL; FeP/HSA, 4 (mol/mol)] into rats after hemodilution and hemorrhage (Hct, about 10%) has been evaluated. The declined mean arterial pressure (MAP) and blood flow after a 70% exchange with HSA and the further 40% bleeding of blood were significantly recovered up to about 90% of the baseline values by the injection of HSA-FeP. Furthermore, the renal cortical O(2)-tensions and skeletal tissue O(2)-tensions were also increased, indicating the in vivo O(2)-delivery of HSA-FeP. Autoxidation of ferrous Fe(II)P to ferric Fe(III)P was retarded in the blood stream; the half-lifetime of the dioxygenated FeP [tau(1/2)(O(2))] in vivo was 4.1 h [cf. 1.0 h (in vitro)]. It has been found that autooxidized Fe(III)P was certainly reduced in the whole blood suspension. Physiological concentrations of ascorbic acid continuously provided by red blood cells probably rereduces Fe(III)P, leading to the apparent long lifetime of the dioxygenated species of FeP.

Human serum albumin incorporating Tetrakis(o-pivalamido) phenylporphinatoiron(II) derivative as a totally synthetic O2-carrying hemoprotein.

2-[8-{N-(2-Methylimidazolyl)}octanoyloxymethyl]-5,10,15, 20-tetrakis(o-pivalamido)phenylporphinatoiron(II)s (FePs) were incorporated into hydrophobic cavities of recombinant human serum albumin (rHSA), providing a totally synthetic O(2)-carrying hemoprotein (rHSA-FeP). An rHSA host absorbs maximally eight FeP molecules. Solution properties of the obtained albumin hybrid [[rHSA] = 5 wt %; FeP/HSA = 1-8 (mol/mol)] are almost identical to those of the rHSA itself; the specific gravity is 1.013 and the viscosity is 1.1 cP. Circular dichroism spectroscopy and isoelectric focusing measurement revealed that the second-order structure and surface charge distribution of rHSA were always constant independent of the binding numbers of FeP. Hydrophobic interaction is probably a major molecular force of the incorporation of this synthetic heme. rHSA-FeP can bind and release dioxygen reversibly under physiological conditions (in aqueous media, pH 7.3, 37 degrees C) like hemoglobin and myoglobin. Its O(2)-coordination structure was evaluated by resonance Raman spectroscopy. The O(2) rebinding after the laser flash photolysis showed three-phases decay, which were analyzed by triple-exponential kinetics. The O(2)-binding affinity and O(2)-association and -dissociation rate constants of rHSA-FeP satisfy the initial clinical requirements for O(2) infusion as a red cell substitute.

Physicochemical properties and O2-coordination structure of human serum albumin incorporating tetrakis(o-pivalamido)phenylporphyrinatoiron(II) derivatives.

Incorporation of tetrakis(o-pivalamido)phenylporphyrinatoiron(II) derivatives with a covalently linked axial imidazole (FeP) into human serum albumin (HSA) provides a new type of artificial hemoprotein (HSA-FeP) that binds and releases dioxygen reversibly under physiological conditions (in aqueous media, pH 7.4, 37 degreesC) and in a fashion similar to hemoglobin and myoglobin. The HSA host adsorbs a maximal eight FeP molecules, and their stepwise equilibrium constants (K1-K8) range from 1.2 x 10(6) to 1.3 x 10(4) M-1. The major binding sites of the synthetic hemes are identical to those of hemin, bilirubin, and long-chain fatty acids. The red-colored solution of HSA-FeP was stored for three months at 4 degreesC and could be kept as a freeze-dried powder for more than six months. The solution properties [[HSA]: 5 wt %, FeP/HSA = 1-8 (mol/mol)] satisfy the physiological requirements for dioxygen infusion for potential clinical use; the specific gravity is 1.013, and the viscosity is 1.1 cP. Mixing the solution with human blood does not induce any coagulation and precipitation. On the basis of the gel permeation chromatography, CD spectroscopy, and IEF measurements, the molecular size, second-order structure, and surface charge distribution of the HSA-FeP conjugate are constant and independent of the binding numbers of heme molecules. Furthermore, the O2-coordination structure of FeP embedded into certain hydrophobic domains of the albumin was confirmed by resonance Raman spectroscopy.

Human serum albumin-bound synthetic hemes as an oxygen carrier: determination of equilibrium constants for heme binding to host albumin.

Human serum albumin (HSA) incorporating synthetic tetraphenylporphinatoiron(II) derivatives (FeP1 or FeP2) can bind and release oxygen reversibly under physiological conditions (in aqueous media, pH 7.4, 37 degrees C). The maximal binding ratio of FeP1/HSA was estimated to be eight, and the stepwise equilibrium constants for FeP1 binding to HSA (K1-K8) ranged from 1.2 x 10(6) to 1.3 x 10(4) M-1. The major binding sites of FeP1 are presumably identical to those of hemin, bilirubin and long-chain fatty acids. The O2-binding ability of the HSA-FeP can be regulated by changing the molecular structure of the incorporated hemes. The half-lifetime of the O2-coordinated FeP2 in HSA was significantly longer than that of HSA-FeP1.