Effects of N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), chlorpromazine, prenylamine and N2-dansyl-L-arginine-4-t-butylpiperidine amide on vascular smooth muscle contraction were compared by using helically cut strips of rabbit aorta. These compounds are reported to be calmodulin antagonists, in vitro. W-7 at a concentration of 1 x 10(-4) M significantly antagonized the contractile responses of aortic strips to the same extent as seen with norepinephrine, serotonin, histamine, prostaglandin F2 alpha, angiotensin II and KCl. On the other hand, the addition of 1 x 10(-4) M N-(6 aminohexyl)-1-naphthalenesulfonamide, an analog of W-7 which has no chloride molecule in the structure and possesses a lower affinity for calmodulin than W-7, did not antagonize aortic contractions. Chlorpromazine at a concentration of 1 x 10(-6) M specifically antagonized the norepinephrine-, serotonin- and histamine-induced contractions, but did not antagonize the prostaglandin F2 alpha-and angiotensin II-induced contractions. Inhibition of prenylamine of the contractile response of aortic strips to KCl was marked compared with the inhibition by this drug of the responses to other agonists. N2-dansyl-L-arginine-4-t-butylpiperidine amide selectively antagonized the serotonin- and KCl-induced contractions at a concentration of 1 x 10(-5) M, however, at this concentration, the responses to norepinephrine, histamine and prostaglandin F2 alpha were not affected by the drug. Thus, each calmodulin antagonist tested has a different spectrum of action and of these only W-7 has a specific interaction with calmodulin.

Animals↗

PubMed1982

[Microcirculation].

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Animals↗

PubMed1982

[Toxicological study of amikacin following intravenous drip infusion. 1. Acute toxicity in rats, rabbits and dogs, and subacute toxicity in rabbits].

Acute toxicity of amikacin sulfate (AMK) was studied in rats, rabbits and dogs following 1 hour drip intravenous infusion (1 hour d.i.v.), and compared with those after intravenous injection (i.v.). Subacute toxicity was studied in rabbits following 1 hour d.i.v. of AMK at doses of 400, 200, 100 and 25 mg/kg for 36 days. Acute toxicity: Acute toxicity of AMK by 1 hour d.i.v. was extremely diminished as compared with that by i.v. judging from LD50, the toxicity was approximately 1/6 in rats and approximately 1/2 in rabbits and dogs. No difference was observed between males and females. Subacute toxicity: 1. No death was found in all rabbits. 2. At the doses of 25 mg/kg and 100 mg/kg, there were no significant changes or signs recognized as toxicological effects of AMK. 3. At the dose of 200 mg/kg, very slight renal damages were observed histopathologically in all the 5 rabbits. 4. At the dose of 400 mg/kg, slight or moderate renal damages were observed in all the rabbits. Those were mainly dilatation of renal proximal tubules, hydropic swelling and degeneration of renal proximal tubular epithelium. No significant impairment effect of AMK was found in heart, lung, liver and other organs. 5. From these results, it is considered that the maximum no effect dose from a view point of safety is about 100 mg/kg in this study.

Amikacin↗

PubMed1982

[Toxicological study of amikacin following intravenous drip infusion. 2. Subacute toxicity in dogs after intravenous injection].

Subacute toxicity of amikacin sulfate (AMK) was investigated with 50 Beagle dogs (male 25, female 25). As a substitute for drip intravenous infusion (d.i.v.), AMK was administered by intravenous injection (i.v.) twice a day, 1 hour apart, for 38 days at daily doses of 400, 200, 100 mg/kg and 25 mg/kg. 1. At the doses of 25 mg/kg and 100 mg/kg, there were no significant changes or signs recognized as toxicological effects of AMK. 2. At the dose of 200 mg/kg, slight renal damages were observed in 3 of 5 males and 2 of 5 females. These were slight elevation of urea N and creatinine, and slight degeneration or regeneration of the renal proximal tubules. 3. At the dose of 400 mg/kg, renal damages were noted in all the dogs. Two males and 1 female died after 14-17 days' treatment and the remainders were sacrificed for inspection after 18-20 days' treatment. In any dogs, the adverse findings were mainly observed in the renal proximal tubules but not in the glomeruli. In the other organs, there were no significant impairments. 4. From these results, it is considered that the maximum no effect dose of AMK is 100 mg/kg.

Amikacin↗

PubMed1982

[Treatment of unresectable cancer of the gallbladder and bile duct].

The gallbladder cancer carries a grim prognosis, because the disease is advanced and surgically incurable at the laparotomy. However, palliative resection and postoperative irradiation have possible effects on the prolongation of survival period. The bile duct cancer has better prognosis, because the early appearance of obstructive jaundice often leads to curative resection. In our series, however, the curative resection rate is only 48.3%. More aggressive surgical therapy might improve survival figures. In addition, postoperative radiation therapy has possible effect as an adjuvant therapy.

Adult↗

PubMed1981

Cancer of the head and neck in atomic bomb survivors: Hiroshima and Nagasaki, 1957-1976.

A search was conducted in Hiroshima and Nagasaki for all cases of cancer of the lip, nose and nasal cavity, accessory sinuses, larynx, and the oral cavity and pharynx with their subdivisions occurring during the period 1957-1976 among a large, fixed cohort of atomic bomb survivors. A total of 232 cases were identified, of which 154 (66.4%) were histologically confirmed (definite cases). Among definite cases, cancer of the epiglottis and larynx predominated (31.2%), followed by accessory sinus (24.7%) and tongue (18.8%). Of the 154 definite cases, 141 (91.6%) were squamous-cell carcinomas. Only two sarcomas were identified, neither of which was attributable to radiation exposure. Analysis of both total and definite cases, by both total group and major anatomic site, failed to reveal definite evidence of a radiation relationship. Although a suggestive relationship to radiation dose was found for accessory sinus cancers (P = 0.06) among the definite cases, inconsistencies in the data do not permit the conclusion that the incidence of tumors in this group increased as a result of atomic bomb radiation exposure. The medical literature concerning post-irradiation head and neck tumors is briefly reviewed.

Carcinoma, Squamous Cell↗

PubMed1981

Changes in predominant energy substrate after hepatectomy.

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Adenine Nucleotides↗

PubMed1981

Changes in blood ketone body ratio: their significance after major hepatic resection.

Changes in the ratio of acetoacetate to 3-hydroxybutyrate (the ketone body ratio) in arterial blood were investigated after massive liver resection in patients and rabbits. In a patient who had had a successful hepatectomy, the blood ketone body ratio decreased rapidly after the operation and then returned to the preoperative level; whereas in a patient who had had an unsuccessful hepatectomy, the blood ketone body ratio did not decrease rapidly after the operation. In 70% hepatectomized rabbits, the blood ketone body ratio decreased maximally nine hours after hepatectomy and then returned gradually to a normal level. The blood ketone body ratio paralleled the hepatic energy charge after 70% hepatectomy in rabbits. The measurement of the blood ketone body ratio is very useful for evaluation of the energy status of the remnant liver.

Acetoacetates↗