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Biomedical subjects

T Nose

Publications and source records attributed to T Nose.

At least 325 records · Page 18Linked to original sources
PubMed1983

[Effects of cianidanol (KB-53) on experimental liver injury in mice--histopathological, histochemical and enzyme-histochemical studies].

Protective effects of KB-53 on acute liver injury induced by carbon tetrachloride (CCl4) and 1-naphtylisothiocyanate (ANIT) in mice was investigated by means of histopathological, histochemical and enzymehistochemical examinations. Diffuse centrilobular necrosis, ballooning degeneration of hepatocytes and hemorrhage were markedly observed in the livers of the mice one to three days after a subcutaneous injection of CCl4. On the other hand, in the livers of KB-53 pretreated mice, forcal necrosis was observed and inflammatory cells had already infiltrated one day after CCl4-intoxication. Three days later, remarkable development of absorbent granulation tissues with syncytium and hepatocytic mitosis was observed. Furthermore, a number of PAS positive materials such as mucopolysaccharides and mucoproteins were detected in the livers of KB-53 pretreated mice. KB-53 inhibited the disappearance of glucose-6-phosphatase (G-6-Pase) in the liver after CCl4-intoxication and the rise of alkaline phosphatase (Al-Pase) in the liver after ANIT-intoxication. In addition, KB-53 inhibited the rise of Al-Pase and total bilirubin in the serum of mice after CCl4 and ANIT-intoxication. All these findings suggest that KB-53 protects liver against the morphological and functional changes, and it potentiates the proliferative and regenerative activity of the liver impaired with CCl4 and ANIT.

1-Naphthylisothiocyanate↗
PubMed1983

[Effect of cianidanol (KB-53) on delayed skin reactions in mice compromised by carbon tetrachloride and 1-naphthylisothiocyanate].

A study was carried out to investigate the influence of 3 kinds of hepatotoxic agents on the peripheral blood leucocyte population, the splenocyte population and the delayed type hypersensitivity (DTH) in mice. These parameters were not affected by the intraperitoneal injection of D-galactosamine (Gal). The intensity of picryl chloride induced DTH (PC-DTH) in mice was significantly lowered with the administration of carbon tetrachloride (CCl4) and 1-naphtylisothiocyanate (ANIT) in a dose-dependent manner after the mice were sensitized to picryl chloride (PC) from one to three days after the subcutaneous injection of CCl4 and ANIT. However the peripheral blood leucocyte population and splenocyte population were not affected by these chemicals. The lowering effect of CCl4 and ANIT on PC-DTH was somewhat weakened when PC sensitization was performed seven days after the injection of CCl4 and ANIT. No lowering effect was observed when PC sensitization was performed fourteen days after the injection of CCl4 and ANIT. The intensity of PPD induced DTH (PPD-DTH) was also lowered by the administration of CCl4 and ANIT when the sensitization to tubercle bacilli was performed three days after the injection of CCl4 and ANIT. Cianidanol (KB-53) prevented the decrease of PC-DTH and PPD-DTH in the mice injected with CCl4 and ANIT in a dose-dependent manner, but did not affect DTH in normal mice. So it seems that KB-53 has an immunostimulating effect on decreased cellular immunity.

1-Naphthylisothiocyanate↗
PubMed1983

[Effects of cianidanol on chronic liver injury induced by carbon tetrachloride and on liver regeneration after partial hepatectomy in rats].

Effects of cianidanol on chronic liver injury induced by prolonged administration of carbon tetrachloride (CCl4) and on liver regeneration after partial hepatectomy of normal liver and CCl4 chronically injured liver were investigated by the measurement of plasma and liver biochemical parameters. Cianidanol increased the total plasma protein and 14C-Leu incorporation into plasma protein, while it reduced the contents of liver cholesterol and triglycerides. In rats with chronically injured liver or regenerating liver after partial hepatectomy of chronically injured liver, cianidanol improved the retention rate of BSP and the content of liver sugar. In rats with chronically injured liver, plasma GPT and GOT activities were reduced with the administration of cianidanol. Cianidanol had no effect on the regeneration rate after partial hepatectomy of normal liver, but it increased the regeneration rate after partial hepatectomy of chronically injured liver. These results suggest that cianidanol has the effect of improving the function of liver cells damaged by CCl4 treatment and of promoting the recovery of cell function to a normal level.

Alanine Transaminase↗
PubMed1983

[Effects of cianidanol (KB-53) on liver cirrhosis induced by CCl4 in rats: a pathological investigation].

The therapeutic effects of cianidanol on the rat liver cirrhosis induced by CCl4 were investigated by means of pathological examination. Rats were administered with CCl4 subcutaneously twice a week for a consecutive 10 weeks. From a macroscopical viewpoint, pailing grayish discoloration, granular hyperplastic nodules and the disappearance of luster on the surface of the liver, and the formation of pseudolobule on the cut surface were observed in the control group. In the histopathological findings, degenerative fatty change and ballooning degeneration of parenchymal liver cells, a formation of pseudolobule caused by septal fibrosis proliferation, an acinar arrangement caused by pericellular fibrosis, and a cholangiollar proliferation were observed. All these abnormalities were diminished by the oral administration of 200 and 400 mg/kg of cianidanol for 7 days. The therapeutic effects of cianidanol were dose-dependent on the liver cirrhosis rats. Consequently, it is suggested that cianidanol has therapeutic effects on liver cirrhosis induced by CCl4 by relieving hepatocytes disorder, improving regeneration of hepatocytes and the absorption of proliferated fibrotic tissues.

Animals↗
PubMed1982

Mutagenicity evaluation of KB-944, a new calcium antagonist, in the Ames bacterial system.

Evaluation of the mutagenic activity of diethyl 4-(benzothiazol-2-yl) benzylphosphonate (KB-944) was performed using bacteria. The method consisted of mutagens or KB-944 with and without metabolic activation, and two bacteria; Salmonella typhimurium 5 test strains, TA 1535, TA 100, TA 1537, TA 1538 and TA 98, and Escherichia coli WP 2 uvr A. Results indicated that KB-944 had no mutagenic activity against S. typhimurium and E. coli.

Benzothiazoles↗
PubMed1982

[Effects of KB-1043 and some non-steroidal anti-inflammatory drugs on prostaglandin and SRS-A synthesis].

The effects of KB-1043, a new non-steroidal anti-inflammatory agent, on prostaglandin (PG) and SRS-A synthesis were investigated and compared with those of reference drugs. KB-1043 (3 X 10(-5) approximately 3 X 10(-4)M) inhibited the PG synthesis induced by PG synthetase prepared from bovine seminal vesicles. The IC50 value was 1.33 X 10(-4)M. The activity of KB-1043 was less than that of indomethacin, but was about 8 times stronger than that of aspirin. However, KB-1043 (10(-6) and 10(-5)M) did not increase the SRS-A released from sensitized guinea pig lung. With a concentration of 10(-4), KB-1043 decreased the SRS-A release. On the other hand, indomethacin (10(-6) and 10(-5)M), mefenamic acid (10(-6) and 10(-5)M), phenylbutazone (10(-5) and 10(-4)M) and aspirin (10(-4) and 10(-3)M) distinctly increased the SRS-A release from sensitized guinea pig lung.

Animals↗
PubMed1982

Vasodilator action of KB-944, a new calcium antagonist.

Vasodilator action of diethyl 4-(benzothiazol-2-yl)benzylphosphonate (KB-944) was mainly examined in comparison with papaverine in isolated perfused heart and anesthetized or conscious dogs. In isolated perfused heart, KB-944 (1-30 micrograms/heart i.a.) and diltiazem (1-30 micrograms/heart i.a.) produced a dose-dependent increase in coronary flow, and dose-dependent decrease in the heart rate and the myocardial contractile force. On the other hand, papaverine (3-100 micrograms/heart i.a.) produced a dose-dependent increase in coronary flow and heart rate, and did not practically affect the myocardial contractile force. KB-944 was about 3 times as active as papaverine and diltiazem on the percent increase of coronary flow. In anesthetized dogs, KB-944 (0.03-0.3 mg/kg i.v. or 10 mg/kg i.d.), diltiazem (0.03-0.3 mg/kg i.v. or 10 mg/kg i.d.) and papaverine (0.1-1 mg/kg i.v.) significantly increased the coronary blood flow with hypotension. Simultaneously, KB-944 and diltiazem decreased the heart rate, whereas papaverine increased it. Furthermore, KB-944 and diltiazem selectively increased the coronary blood flow more than the carotid blood flow, though papaverine increased the carotid blood flow more than the coronary blood flow. In case of i.v. route, KB-944 and diltiazem were about 5 times as active as papaverine on the percent increase of coronary blood flow. In case of i.d. route, the effect on coronary blood flow and heart rate induced by KB-944 was quantitatively similar to that induced by diltiazem, although the decrease in blood pressure induced by diltiazem was lesser than that produced by KB-944. In conscious dogs, KB-944 (0.03-0.3 mg/kg i.v. or 10-100 mg/kg p.o.) produced a dose-dependent increase in coronary blood flow and heart rate. In case of i.v. route, this vasodilator activity of KB-944 was 10 times as potent as that of papaverine. Thus, KB-944 is a more potent coronary vasodilator. Furthermore, KB-944 is well absorbed from the intestinal tract, and produces a long-acting increase in the coronary blood flow.

Anesthesia↗
PubMed1982

Vasodilator mechanism of KB-944, a new calcium antagonist.

The vasodilator mechanism of diethyl 4-(benzothiazol-2-yl)benzylphosphonate (KB-944) was investigated in anesthetized dogs and isolated aortic and taenia caecum preparations. In anesthetized dogs, the vasodilator effect of KB-944 was not inhibited by propranolol, atropine, diphenhydramine and aminophylline, and did not potentiate the coronary vasodilator action of adenosine. In isolated dog coronary arteries, KB-944 as well as verapamil inhibited the potassium-induced contraction in a concentration-dependent manner. The inhibitory effects of KB-944 and verapamil were overcome by elevating the calcium concentration of the bath solution and a competitive antagonism was found between calcium ions and both compounds. In isolated rabbit aorta, KB-944 (10(-5)--10(-7) mol/l) inhibited potassium-induced contraction in a dose-dependent manner, though KB-944 (3 x 10(-5)--3 x 10(-4) mol/l) slightly inhibited noradrenaline(norepinephrine)-induced contractions. In isolated taenia caecum, KB-944, diltiazem and nifedipine produced a shift to the right of dose-response curves for calcium in a competitive fashion, the pA2 values being 6.84 for KB-944, 6.96 for diltiazem and 9.80 for nifedipine. From these results, it would be that interference with calcium influx contributes to the vasodilator activity of KB-944.

Adenosine↗
PubMed1982

Antihypertensive effect of KB-944, a new calcium antagonist, in conscious normotensive and hypertensive rats.

Hypotensive effect of KB-944 was examined in comparison with diltiazem and nifedipine in normotensive rats, spontaneously hypertensive rats (SHR), renal hypertensive rats and deoxycorticosterone acetate(DOCA)-NaCl hypertensive rats, all in a conscious state. KB-944, diltiazem and nifedipine showed dose-dependent antihypertensive effects in the three different types of hypertensive rats as well as normotensive rats. The relative potency of the test drugs decreased in the following order: nifedipine greater than KB-944 greater than diltiazem. The doses of KB-944 leading to a decrease in systolic blood pressure of 20% of pretreatment level were estimated to be 32.8 mg/kg in normotensive rats, 5.1 mg/kg in SHR, 6.4 mg/kg in renal hypertensive rats and 5.4 mg/kg in DOCA-NaCl hypertensive rats, respectively. The hypotensive effect of KB-944 lasted longer than those of diltiazem or nifedipine. KB-944 and diltiazem increased heart rate in normotensive rats and renal hypertensive rats, though in SHR and DOCA-NaCl hypertensive rats both drugs tended to decrease heart rate. On the other hand, nifedipine increased the heart rate in all types of rats. In SHR, tolerance of KB-944 was not observed with oral administration for 5 weeks at a daily dose of 30 mg/kg.

Animals↗
PubMed1982

Cardiac action of KB-944, a new calcium antagonist.

A comparative study was made between the cardiac action of diethyl 4-(benzothiazol-2-yl)benzylphosphonate (KB-944) and those of nifedipine, diltiazem and verapamil in anesthetized dogs and isolated right atria of guinea pigs. In anesthetized dogs, KB-944 caused a dose-dependent fall in mean blood pressure and dose-dependent increase in coronary sinus outflow. Coronary sinus outflow oxygen pressure was increased with increasing coronary sinus outflow; and consequently, the coronary arterio-venous oxygen difference was decreased. The cardiac output was slightly increased, while the myocardial oxygen consumption and myocardial work were reduced. In the isolated right atria of guinea pigs, KB-944 produced a decrease in spontaneous atria rate, and at the concentration of 10(-6) g/ml atrial standstill was seen in few preparations. The contractile force was decreased by KB-944. Especially, KB-944 exerted the weakest effect on contractile force among the tested drugs. These actions of KB-944 are very similar to those of nifedipine, diltiazem and verapamil.

Anesthesia↗
PubMed1982

Antiarrhythmic effect of KB-944, a new calcium antagonist. A comparison with verapamil and diltiazem.

Effects of diethyl 4-(benzothiazol-2-yl)benzylphosphonate (KB-944), a new chemical class of Ca-antagonist, on three types of experimentally induced arrhythmias were evaluated and compared with those of verapamil and diltiazem. KB-944 at 0.02 to 0.1 mg/kg (i.v.) effectively reversed ventricular arrhythmias induced by a continuous infusion of ouabain into guinea-pigs, and its effect was 2 times more potent than that of diltiazem and 5 times less potent than that of verapamil. Epinephrine(adrenaline)-induced arrhythmias in guinea-pigs were prevented by an i.v. injection of KB-944 in doses of 0.025 to 0.2 mg/kg. KB-944 was approximately equipotent with diltiazem and 2 times less potent than verapamil. CaCl2-induced arrhythmias in rats were inhibited by KB-944 with rather high doses (ED50 2.6 mg/kg i.v.). The antiarrhythmic effect of KB-944 was 1.7 times less potent than that of diltiazem and 5 times less potent than that of verapamil. KB-944 was found to possess antiarrhythmic activities in animals qualitatively similar to those of verapamil and diltiazem.

Animals↗