Tamotsu Fukuda

Histamine turnover in the brain of morphine-dependent mice

SummaryThe turnover of brain histamine was examined in mice implanted subcutaneously with a morphine pellet (50 mg free base). The numbers of naloxone-precipitated jumpings and body shakes were maximum 2 and 3 days after implantation, respectively. The brain tele-methylhistamine level significantly increased (50% to 115%) during 12 h3 days after implantation of a morphine pellet, whereas the histamine level remained unchanged. The accumulation of tele-methylhistamine by pargyline treatment was significantly enhanced when pargyline was administered 12 h after implantation, suggesting an enhancement of histamine turnover. However, a similar degree of the tele-methylhistamine accumulation was induced by pargyline during 1–5 days after implantation, as compared with the accumulation in the control mice implanted with a placebo pellet. In mice undergoing morphine withdrawal by either the removal of morphine pellet or the treatment with naloxone 3 days after implantation, the degree of the pargyline-induced telemethylhistamine accumulation or the (S)-α-fluoromethylhistidine (α-FMH)-induced histamine decrease was similar to that observed in the placebo pellet-control mice. The numbers of naloxone-precipitated jumpings and body shakes occurring in mice 3 days after implantation were not significantly affected by any of l-histidine, α-FMH or metoprine. These results suggest that turnover of histamine in the brain is enhanced by acute morphine treatment and returns to the normal rate in the stage of chronic treatment and remains unchanged during the state of withdrawal.

Comparison of the size of neuronal and non-neuronal histamine pools in the brain of different rat strains

The size of the neuronal and non-neuronal histamine pools in the brain of three different strains of rats was measured by assuming that the α-fluoromethylhistidine-induced maximal decrement of histamine represents the size of the neuronal pool. Although the total histamine levels in the brain showed a considerable interstrain variation, no significant interstrain difference was observed in the neuronal histamine level. These results suggest that the size of the neuronal histamine pool in the brain is relatively stable, whereas the size of the non-neuronal histamine pool is variable.

Effect of dextran sulfate on the survival time and mitochondrial function of Adriamycin (doxorubicin)-treated mice.

The effect of dextran sulfate on the survival time and mitochondrial function of adriamycin (ADM)-treated mice was studied. ADM-induced toxicity in mice was reduced by treatment with dextran sulfate (60, 100, 300, and 600 mg/kg, sc). The optimum dextran sulfate dose for protection against ADM-induced toxicity in mice was about 200 mg/kg/day (sc) and 100 mg/kg/day (po). Groups treated with dextran sulfate (300 mg/kg) had significantly improved mitochondrial function as measured by oxygen uptake of state 3 (p less than 0.01), dinitrophenol-altered respiration (p less than 0.01), and respiratory control index level (p less than 0.01). From these observations, it was concluded that ADM-induced toxicity due to reduced mitochondrial function can be ameliorated by the membrane stabilizing effect of dextran sulfate.

Lack of evidence for the involvement of catecholaminergic mechanisms in the behavioral anti-methamphetamine effect of L-histidine in the mouse

The effects of L-histidine (HIS) on the hypermotility and the changes in brain monoamine dynamics induced by methamphetamine (MAMP) were examined in mice. HIS (1000 mg/kg) completely inhibited the hypermotility induced by MAMP (1 mg/kg). MAMP (1 mg/kg) significantly increased the dopamine level and decreased the 3,4-dihydroxyphenylacetic acid level. MAMP (5 and 10 mg/kg) also produced changes in the levels of noradrenaline, serotonin and their metabolites. HIS administered alone caused no significant changes in the levels of these amines and metabolites, nor did it affect MAMP-induced alterations in monoamine dynamics. These results suggest that catecholaminergic mechanisms are not involved in the behavioral anti-MAMP action of HIS.

Stability of Ascorbic Acid in Infusion Solution. II. Effect of Some Metal Ions on the Producing Hydrogen Peroxide in Some Infusion Solutions added MV and Multamin.

In our previous report, we showed that producing hydrogen peroxide increased on standing in infusion solution to which was added multivitamins. Likewise, producing hydrogen peroxide increased on standing after mixing, increasing to 6.76 ppm with the combination of KN solution MG3 with Otsuka MV and to 6.65 ppm with the combination of Solita T®-4 with Multamin®. The Zn2+ and Mn2+ metal ions showed a little effect on the degradation of ascorbic acid (AsA) in spite of the shield, whereas Cu2+ remarkably promoted AsA degradation.

Stability of Ascorbic Acid in Infusion Solution. I. Producing Hydrogen Peroxide in M.V.I., Sohvita and Neolamin Multi-added Infusion Solutions.

Numerous reports have appeared concerning compatibility, photo-degradation and adsorption in infusion solutions. Scince no studies have been done, however, on producing hydrogen peroxide in infusion solutions to which added multi-vitamins, we formulated research to focus on this particular aspect.The production of hydrogen peroxide increased immediately after mixing infusion solutions and multi-vitamins, rising to 11.02 ppm in KN solution 4B combined with M. V. I. and 8.76 ppm or 10.58 ppm in Klinizalz® B combined with Sohvita® or Neolamin Multi® respectively. Removal of soluble oxygen and light remarkably affected the on disturbance of the hydrogen peroxide production, while degradation of ascorbic acid (AsA) was observed immediately after mixture initiation.

Permeability of artificial membranes to tegaful suppositories.

Permeability of artificial membranes to tegaful in suppositories was investigated by using the dissolution apparatus in the paddle method of JP X, Sartorius absorption simulator and a suppository release apparatus. Pemeability was evaluated on the basis of the release of tegaful from suppositories through cellophane and lipid membranes. Five products (A-1, A-2, B-1, B-2 and C) of tegaful suppositories from 3 manufacturers were used.The release of tegaful from product A-2 and B-2 in the method using the dissolution apparatus and the suppository release apparatus was significantly more rapid than that from the remaining products. The release of tegaful from product B-2 with Sartorium absorption simulator was also significantly more rapid than that from product A-1 and C. The similar results were obtained in 3 methods. Therefore, this study suggests that the dissolution apparatus in the paddle method of JP X be applicable for evaluation of the release of tegaful from suppositories.

Determination of acetone and methanol contents in chinese medicinal extract granules.

Determination of acetone and methanol contents in Chinese medicinal extract granules (CMEG) was carried out for their quality test. 14 products combining 4 kinds of CMEG (Hachimijiogan, Syosaiko-toh, Orengedoku-toh and Kamisyoyou-san) from 4 manufacturers were used in this study.No significant difference was observed in acetone contents of the 14 products, all in the range not more than 10μg/ g. However, a considerable difference in methanol contents was observed among manufacturers. Methanol in CMEG prepared by wet-molding showed high content, and in CMEG prepared by dry-molding indicated almost no content. This substance was not detected in 3 products of a manufacturer as a result of a change in granulation method from wet-molding to dry-molding. Only a trace of methanol was found in the decoctions of crude drugs for CMEG. This indicates that the high contents of methanol in CMEG are dependent upon the manufacturing process.