Mechanism of substance P-induced salivary secretion in rats.
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Biomedical subjects
Publications and source records attributed to Y Kotani.
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The effects of the sympathetic nerve stimulation and the administrations of sympathomimetics on the secretion of salivary kallikrein induced by the chorda tympani stimulation were examined quantitatively and qualitatively in the submandibular gland of the dog. The secretion of salivary kallikrein may be mediated through both adrenergic alpha- and beta-receptors. The activities of salivary kallikrein secreted by either the chorda tympani stimulation or isoproterenol were not inhibited by soy bean trypsin inhibitor in vitro, but those secreted by the sympathetic nerve stimulation and noradrenaline or adrenaline were markedly inhibited in vitro. These results suggested that secretion of glandular kallikrein was induced by the chorda tympani stimulation and the sympathetic beta-stimulation, and secretion of plasma kallikrein was induced by the sympathetic alpha-stimulation.
A rat uterine smooth muscle contracting substance was released into the superfusate of the dog's exposed canine pulp after noxious stimulation of the pulp by pricking, heat and electrical stimulation. This active substance was acid- and heat-resistant and was decomposed by carboxypeptidase B and alpha-chymotrypsin, but not by carboxypeptidase A and trypsin. This substance was also tested on several types of smooth muscle. Electrical activity of nerve cells in the reticular formation, which were sensitive to stimulation of the instep of the foot by pinching, was activated by the intrafemoral administration of the active substance. The algesic activity of this substance was examined in cantharidin blister base in man. This study conclusively demonstrated that the active substance of the pulp released by noxious stimulation produced pain and it was identified as bradykinin.
The authors have carried out the laboratory and clinical studies of cefamandole (CMD). The results are as follows: The sensitivity was measured by plate dilution method on 26 strains of Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae and 14 strains of Salmonella typhimurium isolated from patients. The distribution of sensitivity of S. aureus was 0.39 approximately 3.13 micrograms/ml and the peak of distribution was 1.56 micrograms/ml. The distribution of sensitivity of E. coli was 0.78 approximately greater than 100 micrograms/ml, and K. pneumoniae, 1.56 approximately greater than 100 micrograms/ml. The distribution of sensitivity of Salmonella typhimurium was 6.25 approximately greater than 100 micrograms/ml and its peak was 6.25 micrograms/ml. CMD were given intravenously for 30 and 60 minutes at a single dose of 25 mg/kg body weight to 6 children. The serum mean levels of CMD were 105.3 micrograms/ml at 30 minutes, 15.1 micrograms/ml at 1.5 hours, 1.6 micrograms/ml at 2.5 hours after drip infusion for 30 minutes, respectively, and 34.7, 5.2, 0.6 micrograms/ml at 1, 2, 3 hours after drip infusion for 60 minutes, respectively. And the serum level at 4 hours after administration was not detected. The mean urinary excretion rates were 73.3% in the drip infusion for 30 minutes and 60.7% in its for 60 minutes, up to 8 hours after administration. Half life was 26 minutes. CMD was effective in 18 of 21 cases of bacterial infections. No side effects were observed except for 2 cases with elevation of serum transaminase.
The authors have carried out the laboratory and clinical studies of cefuroxime (CXM). The results were as follows: The sensitivity was measured by plate dilution method on 26 strains of S. aureus, 22 strains of E. coli and 24 strains of K. pneumoniae isolated from patients. The distribution of sensitivity of S. aureus was 0.78 approximately 3.13 micrograms/ml and the peak of distribution was 1.56 micrograms/ml. The distribution of sensitivity of E. coli was 1.56 approximately 50 micrograms/ml and the peak was 6.25 micrograms/ml. The growth of 79.2% K. pneumoniae was inhibited in concentration of less than 3.13 micrograms/ml. CXM was given intravenously for 30 minutes at a single dose of 20 mg/kg to 3 children. The serum mean levels of CXM were 99.0 +/- 10.6 micrograms/ml at 30 minutes, 18.0 +/- 10.7 micrograms/ml at 1 hour, 7.0 +/- 2.0, 2.2 +/- 0.6, 0.79 +/- 0.2 microgram/ml at 2, 4 and 6 hours after drip infusion for 30 minutes, respectively. Mean half life was 48 minutes. The mean urinary recovery rate was 96.2% up to 8 hours after administration. CXM was effective in 9 of 10 cases of bacterial infections. No side effect was observed except for 1 case with elevation of serum transaminase.
The authors have carried out the pharmacokinetics and clinical studies of CS-1170. The results were as follows; CS-1170 was given by drip infusion for 1 hour dose of 20 mg per kg body weight to 3 children. The maximum blood level was reached at one hour after drip infusion. This blood levels were 38 micrograms/ml, 68 micrograms/ml and 86 micrograms/ml, respectively, (mean 64 micrograms/ml), and level at 2 hours, 11.5 micrograms/ml, 9.4 micrograms/ml, 16 micrograms/ml respectively, (mean 12.3 micrograms/ml), the blood level at 6 hours was not determined. The urinary excretion rates were 94.8 approximately 96.8% up to 6 hours after drip infusion dose of 20 mg per kg body weight. CS-1170 was effective in 7 of 8 cases with pediatric bacterial infections. An ineffective case was a pneumonia due to Serratia marcescens. No side effect was observed except for 2 cases with diarrhea and one case with elevation of GOT and GPT.
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Peak blood level of cephalexin was obtained at 4 hours after the administration of S-6437 as opposed to 2 hours after regular cephalexin. Peak blood level with regular cephalexin was higher than that with S-6437. Blood levels with S-6437, however, stayed for longer period than those with regular cephalexin. Mean urinary recovery within 12 hours after the administration of S-6437 after meal and during meal were 57.1 and 69.3%, respectively. S-6437 was studied in 23 pediatric patients, 7 with acute tonsillitis, 15 with acute cystitis and 1 with cellulitis. They were orally given 400 to 1,200 mg/day of S-6437 in two divided doses at 30 minutes after meal for 4 approximately 12 days. Of the 23 patients, 18 responded to the drug but 5 did not respond. As for side effects, eruption and diarrhea were observed in 1 and 2 patients, respectively. No other side effects were found.
Coaxial perfusion was carried out in the rat paw; pinching the instep of the foot and electrical stimulation of the sciatic nerve caused an increase in the release of a bradykinin-like substance and kinin forming enzyme into the perfusate. Release of the latter was noted with pinching even independently of the release of the bradykinin-like substance. Acetylsalicylic acid (200 mg/kg i.p.) inhibited the release of kinin forming enzyme due to pinching or to sciatic nerve stimulation, while morphine (5 mg/kg i.m.) inhibited only the release of the enzyme due to sciatic nerve stimulation. Our results suggest that production of localized pain may be largely due to the activity of the released kinin forming enzyme and the bradykinin-like substance. In addition, the mechanism of inhibition by morphine on release of kinin forming enzyme appears to differ from that of acetylsalicylic acid.
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