Racemic Ketamine and S(+)-Ketamine Concentrations in Cerebrospinal Fluid after Epidural and Intravenous Administration in Rabbits

The pharmacokinetic characteristic of ketamine, particularly the shift from the epidural space to the cerebrospinal fluid (CSF), is still unclear. Furthermore pharmacokinetic differences between racemic ketamine and S(+)-ketamine are not clearly described when administered into the epidural space. We measured plasma and CSF concentrations of racemic ketamine and S(+)-ketamine after 2 mg/kg intravenous or 2 mg/kg epidural injection in 32 rabbits, and calculated pharmacokinetic parameters by the moment analysis method. The elimination half time of S(+)-ketamine was significantly shorter than that of racemic ketamine and the systemic distribution volume of S(+)-ketamine was significantly smaller than that of racemic ketamine in the CSF. Pharmacokinetic parameters in the CSF after epidural injection of racemic versus S(+)-ketamines were: maximum concentration, 0.4 ± 0.1 versus 0.6 ± 0.2 ?g/mL (not significant); time to maximum concentration, 9.7 ± 2.1 versus 9.0 ± 3.4 min (not significant); elimination half time, 127.1 ± 25.2 versus 89.3 ± 19.4 min (P = 0.005); area under the curve, 56.4 ± 6.4 versus 56.6 ± 11.0 ?g?mL/min (not significant); and distribution volume, 19,463.5 ± 3266.1 versus 13,613.3 ± 4895.2 mL (P = 0.014), respectively. When injected intravenously, there was no significant difference in these parameters of the CSF between racemic and S(+)-ketamines. Racemic ketamine passed easily through the blood brain barrier when administered intravenously. It also shifted to the CSF through the systemic circulation, even when they were administered epidurally. S(+)-Ketamine had similar movement as racemic ketamine

Improved brain MRI indices in the acute brain stem infarct sites treated with hydroxyl radical scavengers, Edaravone and hydrogen, as compared to Edaravone alone. A non-controlled study

<p>Abstract</p> <p>Background</p> <p>In acute stage of cerebral infarction, MRI indices (rDWI & rADC) deteriorate during the first 3-7 days after the ictus and then gradually normalize in approximately 10 days (pseudonormalization time), although the tissue is already infarcted. Since effective treatments improve these indices significantly and in less than the natural pseudonormalization time, a combined analysis of these changes provides an opportunity for objective evaluation on the effectiveness of various treatments for cerebral infarction. Hydroxyl radicals are highly destructive to the tissue and aggravate cerebral infarction. We treated brainstem infarction patients in acute stage with hydroxyl radical scavengers (Edaravone and hydrogen) by intravenous administration and evaluated the effects of the treatment by a serial observation and analysis of these MRI indices. The effects of the treatment were evaluated and compared in two groups, an Edaravone alone group and a combined group with Edaravone and hydrogen, in order to assess beneficial effects of addition of hydrogen.</p> <p>Methods</p> <p>The patients were divided in Edaravone only group (E group. 26 patients) and combined treatment group with Edaravone and hydrogen enriched saline (EH group. 8 patients). The extent of the initial hump of rDWI, the initial dip of rADC and pseudo-normalization time were determined in each patient serially and averages of these data were compared in these two groups and also with the natural course in the literatures.</p> <p>Results</p> <p>The initial hump of rDWI reached 2.0 in the E group which was better than 2.5 of the natural course but was not as good as 1.5 of the EH group. The initial dip of rADC was 0.6 in the E group which was close to the natural course but worse than 0.8 of the EH group. Pseudonormalization time of rDWI and rADC was 9 days only in EH group but longer in other groups. Addition of hydrogen caused no side effects.</p> <p>Conclusions</p> <p>Administration of hydroxyl radical scavengers in acute stage of brainstem infarction improved MRI indices against the natural course. The effects were more obvious and significant in the EH group. These findings may imply the need for more frequent daily administration of hydroxyl scavenger, or possible additional hydrogen effects on scavenger mechanisms.</p

A basic study on molecular hydrogen (H2) inhalation in acute cerebral ischemia patients for safety check with physiological parameters and measurement of blood H2 level

BACKGROUND: In animal experiments, use of molecular hydrogen ( H(2)) has been regarded as quite safe and effective, showing benefits in multiple pathological conditions such as ischemia-reperfusion injury of the brain, heart, kidney and transplanted tissues, traumatic and surgical injury of the brain and spinal cord, inflammation of intestine and lung , degenerative striatonigral tissue and also in many other situations. However, since cerebral ischemia patients are in old age group, the safety information needs to be confirmed. For the feasibility of H(2) treatment in these patients, delivery of H(2) by inhalation method needs to be checked for consistency. METHODS: Hydrogen concentration (HC) in the arterial and venous blood was measured by gas chromatography on 3 patients, before, during and after 4% (case 1) and 3% (case2,3) H(2) gas inhalation with simultaneous monitoring of physiological parameters. For a consistency study, HC in the venous blood of 10 patients were obtained on multiple occasions at the end of 30-min H(2) inhalation treatment. RESULTS: The HC gradually reached a plateau level in 20 min after H(2) inhalation in the blood, which was equivalent to the level reported by animal experiments. The HC rapidly decreased to 10% of the plateau level in about 6 min and 18 min in arterial and venous blood, respectively after H(2) inhalation was discontinued. Physiological parameters on these 3 patients were essentially unchanged by use of hydrogen. The consistency study of 10 patients showed the HC at the end of 30-min inhalation treatment was quite variable but the inconsistency improved with more attention and encouragement. CONCLUSION: H(2) inhalation of at least 3% concentration for 30 min delivered enough HC, equivalent to the animal experiment levels, in the blood without compromising the safety. However, the consistency of H(2) delivery by inhalation needs to be improved

Hydrogen(H2) treatment for acute erythymatous skin diseases. A report of 4 patients with safety data and a non-controlled feasibility study with H2 concentration measurement on two volunteers

BACKGROUND: We have treated 4 patients of acute erythematous skin diseases with fever and/or pain by H(2) enriched intravenous fluid. We also added data from two volunteers for assessing the mode of H(2) delivery to the skin for evaluation of feasibility of H(2) treatment for this type of skin diseases. METHODS: All of the four patients received intravenous administration of 500 ml of H2 enriched fluid in 30 min for more than 3 days except in one patient for only once. From two volunteers (one for intravenous H2 administration and the other for H2 inhalation), blood samples were withdrawn serially and air samples were collected from a heavy duty plastic bag covering a leg, before, during and after H2 administration. These samples were checked for H2 concentration immediately by gas chromatography. Multiple physiological parameters and blood chemistry data were collected also. RESULTS: Erythema of these 4 patients and associated symptoms improved significantly after the H2 treatment and did not recur. Administration of H2 did not change physiological parameters and did not cause deterioration of the blood chemistry. The H2 concentration in the blood from the volunteers rapidly increased with H2 inhalation and slowly decreased with cessation of H2 particularly in the venous blood, while H2 concentration of the air from the surface of the leg showed much slower changes even after H2 inhalation was discontinued, at least during the time of sample collection. CONCLUSION: An improvement in acute erythemtous skin diseases followed the administration of H2 enriched fluid without compromising the safety. The H2 delivery study of two volunteers suggested initial direct delivery and additional prolonged delivery possibly from a slowly desaturating reservoir in the skin to the surface

Orbital ferromagnetism and anomalous Hall effect in antiferromagnets on distorted fcc lattice

The Berry phase due to the spin wavefunction gives rise to the orbital ferromagnetism and anomalous Hall effect in the non-coplanar antiferromagnetic ordered state on face centered cubic (fcc) lattice once the crystal is distorted perpendicular to (1,1,1) or (1,1,0)- plane. The relevance to the real systems $\gamma$-FeMn and NiS$_2$ is also discussed.Comment: 4 pages, 3 figure