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Biomedical subjects

K Sakamoto

Publications and source records attributed to K Sakamoto.

At least 937 records · Page 52Linked to original sources
PubMed1985

Membrane effects of various drugs on isolated rat hepatocytes and erythrocytes.

The relationship between hepatotoxicity and membrane effects of clinically used drugs on erythrocytes was investigated. The cytotoxicity of various drugs to isolated rat hepatocytes was determined by the leakage of glutamic oxalacetic transaminase (GOT) and ornithine carbamyl transferase (OCT) into the surrounding medium. Inhibition of hypotonic hemolysis of rat erythrocytes was measured as the hemoglobin concentration in the supernatant solution. Drugs such as tricyclic antidepressants, local anesthetics (dibucaine), and bile acids (chenodeoxycholic acid), which have both a membrane stabilizing effect on erythrocytes at low concentrations and a hemolytic effect at higher concentrations, induced enzyme leakage from hepatocytes. The concentration at which hemolysis occurred corresponded to the concentration which caused a marked enzyme leakage from hepatocytes. These phenomena were observed for alkyltrimethylammonium salts (C10 to C16), the order of cytotoxicity to hepatocytes and erythrocytes was C16 greater than C14 greater than C12 greater than C10. Marked enzyme leakage was observed for chenodeoxycholic acid at 1 X 10(-3) M but not for ursodeoxycholic acid. The order of membrane stabilizing and lytic potency of tricyclic antidepressants was chlorimipramine greater than amitriptyline greater than desipramine greater than imipramine. These results suggest that these membrane effects of various drugs on erythrocytes may be useful for screening for hepatocytotoxicity in vitro.

Anesthetics, Local↗
PubMed1985

Lichen planus pemphigoides-like lesions induced by cinnarizine.

A 72-year-old woman developed a lichen planus pemphigoides-like eruption following the administration of cinnarizine. The eruption recurred on challenge with the drug. Direct immunofluorescence studies of the lesions demonstrated deposition of IgG, IgM and C3 on colloid bodies and fibrin at the epidermal basement membrane zone. Circulating IgG antibasement membrane zone antibodies were detected at high titres, with no complement-fixing activities. To our knowledge, this is the first report of immunologically defined lichen planus pemphigoides induced by a drug.

Aged↗
PubMed1985

[Effects of antiarrhythmic drugs on rat erythrocytes, isolated hepatocytes and dipalmitoyl phosphatidyl choline (DPPC)-liposomes].

The effects of antiarrhythmic drugs, aprindine, mexiletine and lidocaine, on rat erythrocytes, isolated rat hepatocytes and DPPC-liposomes were studied at various concentrations. Maximal inhibition of aprindine on the hypotonic hemolysis was observed at a concentration of 2 X 10(-4) M. In isolated rat hepatocytes, aprindine caused an increase in GOT leakage above 4 X 10(-4) M. Mexiletine and lidocaine caused a slight decrease in GOT. Only aprindine caused an increase in LDH leakage above 2 X 10(-4) M. In the relationship between the surface tension and pH conditions (pH 5.7, 7.4 and 8.0), aprindine and mexiletine indicated a depression of surface tension at a dose of 10(-4) M to 10(-3) M under all pH conditions. Lidocaine indicated a depression of surface tension at a dose of 10(-4) M at pH 8.0 only. Aprindine and mexiletine depressed the phase transition temperature (Tc) of DPPC-liposomes. The depression of Tc by aprindine was greater than that by mexiletine. The rank by order of surface activity was the same as that of enzyme leakage from hepatocytes, hemolysis of erythrocytes and depression of Tc in DPPC-liposomes in vitro. These results suggest that differences in membrane damage produced by antiarrhythmic drugs may by related to surface activity, which in turn may determine the extent of adsorption onto cell membranes.

Animals↗
PubMed1985

[Effect of nicardipine on cholesterol-fed S.H.R].

The effect of nicardipine on experimental hyperlipemia induced by a 1% cholesterol diet in spontaneously hypertensive rats (SHR) was investigated by the change of hemodynamics and the determination of lipid contents of the serum, liver, heart and aorta. Nicardipine increased liver weight and liver weight per body weight ratio, and it decreased heart and kidney weight significantly. Nicardipine inhibited the increase in blood pressure with cholesterol and normal diets. Nicardipine decreased heart rate in SHR fed the normal diet, and it inhibited the increase in heart rate in SHR fed the cholesterol diet. Serum lipid levels significantly increased with the cholesterol diet. Nicardipine significantly increased cholesterol in high density lipoprotein (HDL-C) and phospholipid in HDL (HDL-PL) with cholesterol and normal diets, and it decreased triglyceride and improved the atherogenic index "(total cholesterol-HDL-C)/HDL-C" with the normal diet. Serum GOT and GPT significantly increased with the cholesterol diet. Nicardipine significantly enhanced an increase in GOT and GPT levels with the cholesterol diet. Nicardipine increased phospholipid content in the liver, triglyceride in the heart, and it decreased total cholesterol in the aorta. A morphologic study showed a fatty liver in SHR fed the cholesterol diet, but nicardipine had no effect on the morphological changes in the liver, heart and aorta. These results suggest that nicardipine may prevent atherosclerotic degeneration by the inhibition of hypertension, increase in serum HDL and decrease in total cholesterol in the aorta.

Animals↗
PubMed1985

Effect of chronic treatment of propranolol on lipid metabolism in spontaneously hypertensive rats (SHR).

The effects of propranolol on lipid metabolism were studied in spontaneously hypertensive rats (SHR). Male SHR and corresponding Wistar Kyoto rats (WKY) were used at 5 weeks of age. The SHR were given 10 mg/kg/day of dl-propranolol . HCl by gavage for 10 weeks. Body weight gain in untreated SHR and propranolol-treated SHR (SHR-P) groups were low, as compared with those of the WKY group. Total cholesterol, phospholipid and total lipid of the serum and liver in the SHR-P group were higher than in the SHR group. In the early weeks of treatment, serum triglyceride and non-esterified fatty acid levels in the SHR-P group were slightly lower than those in the SHR group. Aortic lipid levels in the SHR-P group were lower than those in the SHR group. During the later weeks of treatment, blood glucose level in the SHR-P group was higher than in the SHR group. The serum immunoreactive insulin value in the SHR-P group was slightly lower than in the SHR group. These results may suggest that propranolol inhibits hormone-sensitive lipase activity in the early weeks of treatment and influences cholesterol biosynthesis and/or catabolism.

Aging↗
PubMed1985

Function of reticuloendothelial system on CCl4 induced liver injury in mice.

Phagocytic activity as a function of the reticuloendothelial system (RES) has been studied in CCl4-induced liver injury by using the carbon clearance test. Liver damage in mice was induced by administration of 20% CCl4 in olive oil (p.o.). After a single administration of CCl4, significant increases in liver/body weight ratio, serum GOT and GPT levels, alpha, beta and gamma-globulins and BSP retention, and decreases in serum albumin, an activity of the hepaplastintest and the correct phagocytic activity, alpha value, were found. After 15 administrations of CCl4 (3 times a week), mild increases in serum GPT level and BSP retention and decreases in the activity of the hepaplastintest and both phagocytic indices, K and alpha values, were observed. However, zymosan treatment 3 days before sacrifice induced an increase in K value depressed by multiple administrations of CCl4. The depression of carbon uptake by Kupffer cells can be seen by light microscopy after multiple administrations of CCl4 compared with that of saline and olive oil. These findings indicate that the RES phagocytosis is suppressed more strongly in chronic liver injury by 15 CCl4 administrations than in acute injury by a single one, although the biochemical parameters indicating liver injury are shown to have an opposite tendency. A clear correlation between the alteration of RES activity and the degree of liver injury was not noted.

Alanine Transaminase↗
PubMed1985

[Effect of p-tert-butylphenyl trans-4-guanidinomethyl cyclohexane carboxylate hydrochloride (NCO-650) on drug-metabolizing enzymes and fine structure in rat liver].

The effects of p-tert-butylphenyl trans-4-guanidinomethyl cyclohexane carboxylate hydrochloride (NCO-650) on drug-metabolizing enzymes and fine structure in rat liver were investigated. Aminopyrine demethylase, cytochrome b5 and cytochrome P-450 contents increased by a single administration of NCO-650 (10, 100 and 1000 mg/kg, p. o.). NCO-650 caused the morphological changes of liver fine structure such as disarrangement of rough endoplasmic reticulum (rER), detachment of ribosome from the rER and increase in smooth endoplasmic reticulum. The increases in drug-metabolizing enzyme activities and morphological changes in rat liver by NCO-650 were not dose-dependently. Trimethadione metabolism was not accelerated by the administration of NCO-650. In those results, the morphological changes in liver by a single administration of NCO-650 seem to be a direct action on the membrane of hepatocytes and its organelle. The induction of drug-metabolizing enzyme contents by NCO-650 was suggested a transitory response with the morphological changes in the liver.

Aminopyrine N-Demethylase↗
PubMed1985

Leukocyte migration inhibition in relation to nuclear pleomorphism and lymphoid infiltration in breast cancer.

Leukocyte migration inhibition (LMI) in patients with breast cancer was examined by using 3 M-KCl tissue extracts of breast tumors. Tumor extracts were obtained from 12 breast carcinomas of various histological types. In 20 of 65 (30.8%) leukocyte preparations from 25 patients with breast cancer migration was inhibited by breast cancer tissue extracts. In 26 leukocyte preparations from eight healthy persons and 22 preparations from eight patients with benign diseases of the breast migration was not inhibited by the breast cancer extracts. In only two of 47 (4.3%) leukocyte preparations from 12 patients with other cancers migration was inhibited by the extracts. The occurrence of LMI was the highest in leukocytes from the patients with breast cancer showing marked nuclear pleomorphism (10/19, 52.6%) or showing marked mononuclear cell infiltration (6/12, 50.0%). These results suggest that 3 M-KCl tissue extracts of breast cancer may contain tumor-associated antigens in solubilized form and that there may be a correlation between LMI and nuclear pleomorphism of cancer cells of the leukocyte donor as well as mononuclear cell infiltration in the tumor of the leukocyte donor.

Adenofibroma↗