In vitro effects of glycyrrhizin on the serum enzymes in chronic hepatitis patients were studied. Forty μg and 100 μg of glycyrrhizin per one ml of reaction mixture inhibited transaminase activity by about 10% and 32-37%, respectively, in a noncompetitive manner. The former concentration was comparable to the clinical dose by intravenous administration in the treatment of liver diseases. Glycyrrhizin also had inhibitory action on the activities of serum LDH and LAP, but not on MAO activity. Furthermore, this agent exhibited activation on acid RNase, but not on alkaline RNase.

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To study in vivo effect of methylcobalamin (CH₃-B₁₂) on the peripheral nerve structures, rats with experimental diabetes induced by streptozotocin were administered with daily intramuscular injection of CH₃-B₁₂ (500μg/kg). Improved general conditions such as an increase in body weight or ameliorated glucose intolerance were observed in the diabetic rats treated continuously with CH₃-B₁₂ for 16 weeks.
There were no definite morphometrical differences between the diabetic rats treated with CH₃-B₁₂ only for 8 weeks during the latter half of this experiment, and non-treated iabetic rats. However, the diabetic rats continuously treated with CH₃-B₁₂ for 16 weeks showed low incidence of degenerated nerve fibers and less reduction of myelinated nerve fiber density than those of npn-treated diabetic rats (p<0.01 and p<0.05).
The reduction of myelinated nerve fibers predominantly of large diameter (5-8μ) were prevente in the treated diabetic rats in contrast with those of nontreated diabetic rats on the histograms of the diameter of myelinated nerve fibers.
The results suggested that an early continuous treatment with CH₃-B₁₂ inhibited the evolution of peripheral nerve lesions in rats with experimental diabetes.

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The diuretic activity of piretanide injection was compared with that of bumetanide injection in 6 patients with liver cirrhosis. Drugs were allotted according to a single-blind Latin square design. The following conclusions were obtained:
1. For each drug the diuretic effect reached a maximun within 2 hours after intravenous administration, and in 4 hours the effect largely disappeared .
2. Six mg of piretanide was found to be almost equivalent to 0.5 mg of bumetanide with respect to the effects upon urinary volume and Na⁺ excretion.
3. The electrolyte excretion pattern obtained with piretanide was similar to that of bumetanide.
4. No changes in symptoms, abnormal laboratory data, or untoward effects were noted with either drug.

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The plasmal level and urinary excretion of pirenzepine were investigated in man by radioimmunoassay after a single or multiple oral administration of pirenzepine tablets to healthy male volunteers. In a single administration (dose: 12.5, 25, 50 or 150 mg), the maximum plasma level appeared 2 hours after administration on average, the elimination half-life was about 13 hours on average, and urinary excretion rate within 96 hours was 7-12%. In multiple administration, three times a day (25 mg or 50 mg/time) for 4 days, the plasma level was observed to increase for the first 3 days of administration and to keep plateau thereafter. Also, the experimental values were in accordance with the simulation curve. These results suggested that the pharmacokinetic property of pirenzepine was not changed in different doses nor in multiple administration.

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Anthelmintic drug levamisole, clinically used as an immunopotentiator, has been shown to restore the decreased cellular immune response. In this experiment, levamisole was found to increase serum complement level either in guinea pig or in human without malignancy, investigated by hemolytic assay using sensitized sheep erythrocytes (EA) for the classical pathway activity and unsensitized rabbit erythrocytes (RaE) for the alternative pathway activity. Assay of complement components revealed a mild increase in Clq, C4, C3, C9, and C1-inhibitor, while no specific tendency was observed in C5, properdin and C3 activator. Although leva misole provided no effect upon serum complement activation in vitro, these evi dences suggested that levamisole might potentiate immune response of the host by elevating serum complement level.

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The effects of proranolol and pindolol on systemic hemodynamics at rest and during bicycle exercise with work load at 27 watts were studied in 22 outpatients. Cardiac output was measured by dye dulution method. Twelve lead electrocardiograms were taken and blood pressure was measured by cuff method. The dosages used were 20 mg of propranolol and 5 mg of pindolol. There was no significant difference in effect on heart rate between propranolol and pindolol. Propranolol significantly decreased blood pressure only on exercise, while pindolol did it at rest as well as on exercise. Propranolol decreased cardiac output on exercise to the same extent than at rest while pindolol did it only on exercise. There was no significant change in stroke index on administration of propranolol, but a significant decrease on exercise with pindolol. Propranolol decreased cardiac work index on exercise to the extent than at rest while pindolol decreased it only on exercise. There was no significant difference in effect on double products between propranolol and pindolol, both of which decreased double products at rest as well as on exercise. Although propranolol increased peripheral vascular resistance at rest as well as on exercise, pindolol did not significantly change it.
This data indicates that pindolol exerts more influence on hemodynamics on exercise than at rest except for blood pressure and double products, both of which are decreased at rest as well as on exercise.

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As a method for examining the psychological dependence potential of afloqualone, a centrally acting muscle relaxant, the subjective effects of the drug were studied in 8 healthy male volunteers under the double blind condition. The trial in each subject consisted of a 3-day afloqualone administration session and a 3-day control agent administration session with a 4-day interval between the two sessions. The subjects were hospitalized for the 3 days of each session and treated with oral daily doses of either afloqualone or control agents. In the afloqualone session, 2 capsules containing afloqualone (10 mg each) and 2 placebo capsules, 3 afloqualone capsules and 1 placebo capsule, and 4 afloqualone capsules were administered on the 1st, 2 nd, and 3 rd day respectively.
In the control agent session, one capsule containing 5 mg of diazepam and 3 placebo capsules were administered on either the 1st or 3 rd day and 4 placebo capsules were administered on each of the other 2 days. Half of the subjects had the afloqualone session first while the rest had the control agent session first, and in the control agent sessions, half of the subjects received diazepam on the 1st day while the remaining half received it on the 3 rd day. In each session the subjective feelings of the subjects were examined using 4 types of questionnaires given 1 to 11/2 hours after administration. In addition, such psychological tests as the personality, tapping, and Uchida-Kraepelin tests were conducted both prior to and after each administration. As a result, while some statistically significant subjective effects were observed with diazepam, none were found with afloqualone even though the blood levels of the drug were sufficiently high in these subjects. Thus, within the above dose regimen, afloqualone was regarded to have no pharmacological property, productive of psychological dependence in man.

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The effects of methylprednisolone sodium succinate (Solu-Medrole^®) in shock were studied by the double blind technique at 32 medical centers, using hydrocor. tisone sodium succinate (Solu-Cortef^®) as the active control drug. Either methylprednisolone sodium succinate or hydrocortisone sodium succinate was administered in an initial dose of 20-30 mg per kg of body weight to each of 135 patients. Any patients who failed to respond well to the initial doses were given additional doses. The effects of the steroids used were evaluated within 12 hours following the final doses.
The results obtained are as follows:
1. The general improvement rate was higher for the methylprednisolone sodium succinate group than for the hydrocortisone sodium succinate group.
2. The global utility rate was greater for the methylrednisolone sodium succinate group than for the hydrocortisone sodium succinate group.
3. Methylprednisolone sodium succinate group showed a greater improvement than the hydrocoritsone sodium succinate group in the post-treatment measurements of shock score, systolic blood pressure, pulse pressure, shock index, urinary output, arterial blood pH and Base Excess.

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Pharmacokinetics of amikacin (200 mg/body, im) was studied in the bedridden elderly patients, in comparison with those in normal healthy volunteers and elderly volunteers.
Elimination of amikacin from plasma was seen to follow the course of delete one compartment model system. Interindividual variations in serum concentration were observed in the bedridden elderly patients. Values for the following pharmacokinetic parameters were obtained: Elimination rate constant (Kel) =0.461±0.069 hr^-1, biological half life (T1/2) =1.53±0.24 hr, volume of distribution (Vd) =0.236±0.025 1/kg for normal healthy volunteers (n=4), Kel =0.208±0.05 hr^-1, T1/2 =3 .55±1.02 hr, Vd=0.376±0. 091 1/kg for bedridden elderly patients (n=5), Kel=0.303±0.026hr^-1, T1/2=2.30±0.19hr, Vd=0.263±0.032 1/kg for elderly volunteers (n=3).
Cumulative renal excretion of amikacin was 36.3% of total dose by 6 hrs for bedridden elderly patients, 62.5% for elderly volunteers and 79.3% for normal healthy volunteers. Decreased renal excretion of amikacin was related to decreased renal function due to aging and increased Vd.

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