[The role of vasodilator agents in cardiac insufficiency].
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Biomedical subjects
Publications and source records attributed to S Satoh.
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Some pharmacological actions of intraperitoneally (i.p.) administered d-pseudoephedrine (d-pseudo) on the central nervous system of mice were compared with those of l-ephedrine (l-eph). Locomotor activity was increased by l-eph (50, 100 and 200 mg/kg,) but not by d-pseudo (50, 100 and 200 mg/kg). Wheel-revolving activity was reduced by a 200 mg/kg dose of both drugs. Rectal temperature was increased by l-eph at 50, 100 and 200 mg/kg. However, it was decreased by 50 and 100 mg/kg doses of d-pseudo, and the change in response to 200 mg/kg of d-pseudo was biphasic, decreasing first and increasing subsequently. Pentobarbital-induced sleeping time was shortened by l-eph (50 and 100 mg/kg), but was not influenced by any of the doses of d-pseudo. In the experiment on locomotor activity, L-3,4-dihydroxyphenylalanine (400 mg/kg, i.p.) potentiated the effects of d-pseudo and l-eph, but reserpine (1 mg/kg, day X 5 days, i.p.) and 6-hydroxydopamine (40 micrograms/mouse, intracerebroventricular injection) potentiated only the effect of l-eph. These results suggest that the effect of d-pseudo on the central nervous system of mouse is not only weaker than that of l-eph, but also the mechanisms of action of these two substances are different.
A 59-year-old woman with recurrent malignant melanoma of the vulva has well responded to a combination of immunotherapy and chemotherapy. As an immunotherapy, 10KE OK-432 were injected into the tumor twice a week. Chemotherapeutic regimen consisted of intravenous push of 1 mg vincristine on day 1,100 mg dacarbazine from day 1 through 5 and 50 mg nitrosourea (ACNU) on day 5. This treatment was repeated with 4 week intervals. Before treatment, the patient had a 3 X 3 X 5 cm subcutaneous mass on the left vaginal wall near the introitus. Fifty percent objective reduction of the tumor was achieved 6 weeks after commencement of intralegional immunotherapy and chemotherapy, and the tumor almost disappeared 8 months later. At this time, the treatment was changed to a supportive immunotherapy with intramuscular injection of 1KE OK-432 twice a week. But the tumor began to enlarge 2 months later and the patient is now being treated with the same combination therapy. Major side effects were febrile episodes on the day of intratumor injection of OK-432 and nausea, vomiting during the interval of chemotherapy. Anemia was the main hematologic side effect, but leukocytopenia and thrombocytopenia were not severe. The combination of intratumor injection of OK-432 and chemotherapy seems to be effective for the treatment of malignant melanoma.
Using dogs, we experimentally produced devascularized areas in the small intestine and colon and took quantitative measurements of the submucosal local blood flow using the hydrogen clearance method.. In the area slightly toward the ischemic side of the devascularized margin, local blood flow is less on the mesenteric side in both the ileum and the colon, and microcirculation is better maintained in the colon that in the ileum. When the anastomosis was performed in the area in which the local blood flow on the mesenteric side was 60 per cent of the control value in the ileum or 70 per cent in the colon, recovery of the control value was achieved by the seventh postoperative day. When anastomosis was performed in the area in which the local blood flow on the mesenteric side was 15 per cent of the control value in the ileum and 22 per cent of the control value in the colon, the flow on the mesenteric side did not recover to the level of the control value by the seventh postoperative day, and anastomotic leakage occurred in some dogs. All anastomotic leakage occurred on the mesenteric side. The local blood flow rate at the point at which the last signal was detected by Doppler ultrasound flowmeter after moving Doppler probe from the devascularized margin toward the ischemic side was 57 per cent of the control value in the ileum and 54 per cent of that in the colon. Such levels of blood flow are considered sufficient for successful healing of tissue after an anastomosis.
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Effects of antidepressants and other drugs on the behaviour of rats in the forced swimming test were examined. Acute and chronic administration of antidepressants reduced the duration of immobility during the first 5 or 10 min of a 30 min test by prolonging escape-directed behaviour which appeared only during this period. However, the drugs did not affect the duration of immobility during the last 20 or 25 min, when the rats were in a state of almost complete immobility. In contrast, methamphetamine, caffeine and scopolamine reduced the duration of immobility not only during the first 5 min but also the next 15 or 25 min without prolonging the escape-directed behaviour but by increasing general motor activity. The effect of antidepressants was potentiated by chronic treatment as compared to acute administration. In the chronic experiments, a significant reduction in the duration of immobility was first observed on the 6th day of the treatment. Although a single injection of diphenhydramine caused an effect similar to antidepressants, this effect disappeared after chronic treatment. These results indicate that immobility itself is not affected by antidepressants. However, it is suggested that the reduction in the duration of immobility only during the first 5 min of the test, which was caused by the prolongation of the escape-directed behaviour, and the potentiation of the effect after chronic treatment are an action specific to antidepressants.
Minced rat renal medulla was incubated for 30 min at 37 degrees C in the presence of angiotensin I, II or III (100 ng/ml) to determine the existence of a direct stimulating effect on prostaglandin (PG) production. PGE2, PGF2 alpha, 6-keto PGF1 alpha and Thromboxane B2 (TXB2) were determined by radioimmunoassay. For analysis of data variance, the results were separated according to whether the net output of PGE2 was above or below 1.5 ng PGE2 equivalent/mg tissue/30 min. Under low-output conditions, angiotensin I, II or III stimulated PGE2 production significantly (p less than 0.02) and tended to augment PGF2 alpha production, while under high-output conditions no effect on PGE2 or PGF2 alpha production was observed. Under either output condition, angiotensin I, II or III had no effect on 6-keto PGF1 alpha and TXB2.
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When prostaglandin E (PGE) contents in kidney medullary tissue were determined, we found that the PGE level was significantly higher in the male rats. The activity of PG synthetase in kidney medullary microsomes to synthesize PGE2 and the effect of treatment with sex hormones on the activity were also investigated. There was no significant difference in PG synthetase activity between male and female intact rats. Subsequently, ovariectomy and orchidectomy wee carried out and corn oil (control group), testosterone (2.0 mg/kg) or estradiol (0.2 mg/kg) were given subcutaneously every other day for 2 weeks. Testosterone treatment produced a significant increase in the activity of PG synthetase in males, but not in females, when compared with control values. In contrast, estradiol treatment produced a significant decrease in PG synthetase activity in both sexes. These results suggest that sex hormones may play an important role in the regulation of PG biosynthesis in kidney.
To study the mechanism of the potentiating effect of lithium chloride (LiCl) on methamphetamine (MA)-induced stereotypy in mice, effects of various drugs on the action of LiCl on the stereotypy and pharmacokinetics of MA in different brain regions and liver were examined. The potentiating effect of LiCl disappeared in mice pretreated with atropine or scopolamine whereas LiCl potentiated the stereotypy in mice pretreated with p-chlorophenylalanine, alpha-methyl-p-tyrosine, nialamide, physostigmine or butylscopolamine. The concentrations of MA in the striatum, brainstem and liver were increased and the half-life of MA in these tissues was prolonged by LiCl. The effect of LiCl on the kinetics of MA in the brain, but not that in the liver, was blocked by scopolamine. LiCl prolonged the half-life of MA in the brain and liver in mice treated with physostigmine or butylscopolamine. The inhibition of MA elimination from the brain and its blockade by scopolamine seem to explain the potentiating action of LiCl on the stereotypy and the antagonism by scopolamine of the behavioural action of LiCl, respectively.
Clinical evaluation of cefotiam (panspolin), a new cephem antibiotics, was performed in the infectious disease associated with hematological disorders and in the respiratory system. In hematological dis orders, 40% of good and 25% of fair results were obtained in clinical effects. In respiratory infections, however, 92% of good results were obtained. Opportunistic infection due to Gram-negative bacilli are often experienced in patients with leukemia. Since cefotiam has sufficient bacteriocidal effects in broad spectrum, it would be a good therapeutic agent against infectious diseases associated with hematological disorders.