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Biomedical subjects

S Manabe

Publications and source records attributed to S Manabe.

At least 163 records · Page 9Linked to original sources
PubMed1982

[Properties and mechanism of hyperlipidemia induced in rabbits by tributyltin fluoride].

Male Japanese white rabbits were given tributyltin fluoride (TBTF) by gastric intubation with a single dose of 100 mg/kg body weight and their lipid and glucose metabolisms were investigated. After administration of TBTF, a reversible, but remarkable increase of lipids in plasma, particularly of triglycerides and total cholesterol, was observed. Ultracentrifugation of plasma lipoproteins revealed a marked increase in chylomicron+VLDL (very low density lipoprotein) fraction. Lipoprotein lipase (LPL) activity in postheparin plasma reduced significantly (p less than 0.02) to the levels of about 50% of the control. Fasting blood glucose level was elevated and a significant inhibition of insulin (IRI) release in response to the intravenous glucose infusion was observed in TBTF treated rabbits, but the level of blood glucose and the degree of inhibition of IRI release were low compared with those of triphenyltin fluoride treated rabbits, in which much greater fasting hyperglycemia was observed. Microscopic examination of pancreas, kidneys and thyroid gland did not reveal histological alterations contributing to the hyperlipidemia. These results suggest that hyperlipidemia induced in rabbits by tributyltin fluoride is due to decreased LPL activity. The decrease in LPL activity seems to be related to the inhibition of insulin release from islets by TBTF.

Animals↗
PubMed1982

[Recent progress in the study of analytical methods, toxicity, metabolism and health effects of organotin compounds].

Over the years, a variety of uses has been found of organic tin compounds as fungicides, as stabilizers in plastics and for other industrial uses. The purpose of this article is to summarize and review the results so far obtained as to the analytical method for organotins in biological samples, the toxicity, metabolism, and biochemical and health effects of organotin compounds. 1) Many methods have been developed for analysis of organotin compounds by spectrophotometry, polarography, gas- or liquid-chromatography, etc. These methods, however, are mainly for analysis of organotins in standard solutions or in water, and are not suitable for organotin compounds in biological samples. Recently, we have developed several methods for analysis of various kinds of organotin compounds in biological samples. These methods are able simultaneously to separate and determine trace amounts (at nanogram order) of organotin compounds and their metabolites in the same biological samples. 2) Acute toxicity of organotin compounds which appeared on the literature are summarized. Trialkyl and triaryl compounds seem to be more toxic than the tetra-, di-, or mono-compounds of the same chain length. With an increase in the number of C atoms the toxicity of alkyl compounds decreases. Aryltin compounds are less toxic than alkyltin compounds. 3) Intestinal absorption sites for tetra-alkyltins are jejunum and duodenum, and those for trialkyltins are ileum and jejunum. A considerable amount of orally administered tetra- and trialkyltins of low molecular weights are absorbed, but only very little of the other organotin compounds seems to be absorbed from the gastrointestinal tract. Absorbed organotin compounds rapidly undergo dealkylation by the microsomal mono-oxygenase system dependent on cytochrome P-450 in the liver, brain or other organs, and the compounds and their metabolites distribute to the whole body, ultimately being excreted into urine, bile and faeces. The biological half life of organotin compounds in mammals is usually short, a half of the amount of tributyl- and triphenyl-tins deposited in the body disappearing in several days. A part of organotin compounds excreted into bile is demonstrated to have been absorbed from the intestine and to circulate in the body via enterohepatic circulation. 4) Specific effects of organotin compounds on the biological systems and health include disturbance of the structure and function of the central nervous system (interstitial edema of white matter), inhibited oxidative phosphorylation in mitochondria of cells, atrophy of the thymus and thymus dependent lymphoid tissues resulting in the dysfunction of T cells for immunity, inhibited enzyme activity, lesions in the liver and bile ducts etc., although some specificity is observed among species of animals and organotin compounds. Recently we found that a single oral administration of triphenyltin fluoride to rabbits induces transient diabetes and diabetic lipemia by inhibiting insulin secretion from morphologically normal pancreatic B-cells...

Animals↗
PubMed1982

[Pathogenesis of hyperlipidemia and fatty liver of rabbits induced by methyl iodide. Increased synthesis and secretion of triglyceride in the liver].

Male Japanese white rabbits were injected subcutaneously with methyl iodide (57 mg/kg body weight/day) on two successive days and their lipid metabolism was investigated 48 hr after the last injection. The plasma triglyceride levels increased from the preinjection average of 56.1 mg/dl to 246.0 mg/dl on an average, the individual values being greatly variable. Analysis of lipoprotein profile of plasma showed a significant increase of very low density lipoproteins (VLDL). Lipolytic activities in postheparin plasma did not change. However, rates of triglyceride secretion into plasma, measured by Triton WR 1339 injection method, were significantly higher in the animals treated with methyl iodide than in the controls. Histological investigation of the liver showed diffuse fat deposits in the hepatocytes without any destructive and inflammatory changes. The results indicate that hyperlipidemia and fatty liver of rabbits induced by methyl iodide is related to the elevation of triglyceride synthesis and its secretion in the liver.

Animals↗
PubMed1981

Goitrous hypothyroidism due to iodide-trapping defect.

A 32-yr-old man with goitrous hypothyroidism due to an iodide-trapping defect is described. He was admitted because of goiter which had been increasing in size. His parents were unrelated, and no cases of goiter were found in his family. On admission, serum T3 was 39 ng/dl, serum T4 was 1.0 micro g/dl, and serum TSH was 217 micro U/ml. His 24-h thyroidal 131 I uptake was 0.05%. Antithyroid antibodies were negative. In a tracer study, the thyroidal 131 I uptakes were 6.3% at 2 h, 4.0% at 6 h, and 0.9% at 24 h after iv injection of the radioiodide. The decline in the neck counts was linear and parallel to that in the serum 131 I. The 24-h urinary excretion of 131 I was 92%. The saliva to serum and gastric juice to serum ratios of 131 I concentrations at 2 h were very low (0.95 and 0.97, respectively). After the administration of iodine (14 mg in Lugol's solution/day for 10 days), serum T3 was 228 ng/dl, serum T4 was 6.8 micro g/dl, and serum TSH was 24 micro U/ml. Some biochemical studies were carried out using the patient's thyroid tissue. In a kinetic study on iodide trapping by thyroid slices, the thyroid to medium ratio of iodide concentration in the patient's tissue was constantly about 0.1, in contrast to 1.5-4.0 in a control subject. The microsomal peroxidase activity in the patient's thyroid, assessed by iodination of bovine serum albumin, was about 3-fold that in a control subject on the basis of DNA content. Both ouabain-sensitive and -insensitive thyroidal Na+ -K+ -ATPase activities were present. These results suggest that the iodide-trapping defect in this patient was due to an impairment in the specific iodide carrier system rather than in the Na+ -K+ -ATPase itself.

Adult↗
PubMed1981

The effect of age on cadmium retention in organs of hamsters.

Age difference of cadmium retention was investigated in hamsters after a short term cadmium exposure. Three types of organs were identified in relation to cadmium retention, i. e., the liver and testes retained an increasing amount of cadmium with increasing age, the kidney and heart showed a gradual decrease in the retention after a transient increase in young ages and the bone showed no retention. These changes seemed to be related to the de novo synthesis of metallothionein in the organ.

Aging↗
PubMed1981

Triphenyltin fluoride (TPTF) as a diabetogenic agent. TPTF induces diabetic lipemia by inhibiting insulin secretion from morphologically intact rabbit B-cell.

Recent work in our laboratory has shown that oral administration of triphenyltin fluoride (TPTF) evokes hypertriglyceridemia in rabbits. The present experiments were conducted to elucidate the mechanism of TPTF-induced hypertriglyceridemia in rabbits by a combined biochemical and ultrastructural approach. After a single TPTF administration, fasting blood glucose and plasma triglyceride levels increased significantly (P less than 0.02) for about 20 days. On the other hand, both plasma and adipose tissue lipoprotein lipase (LPL) activity was markedly decreased (P less than 0.001) during this period, and triglyceride production rates on day 2 after TPTF administration was significantly decreased (P less than 0.01). Density-gradient ultracentrifugation showed a remarkable accumulation of chylomicron and VLDL in the composition of plasma lipoproteins. Insulin injection to the hypertriglyceridemic rabbits induced a significant recovery of the decreased plasma LPL activity with a concomitant decrease of plasma triglyceride levels, while abeyance of insulin injection resulted in a decrease of LPL activity again. A significant inhibition of insulin release in response to the loading of glucose, glucagon, or arginine was observed in the TPTF rabbits (P less than 0.02). Inhibition of glucagon release was also observed in the arginine-loading test (P less than 0.01). Electron microscopic studies showed small abnormalities in the pancreatic islets of TPTF-treated rabbits. These findings suggest that TPTF inhibits insulin release from rabbit islets, subsequently inducing diabetic lipemia due to the insulin deficiency. Furthermore, it is possible to provide a new animal model for diabetes and diabetic lipemia by administration of TPTF to rabbits.

Animals↗
PubMed1975

Cytokinetic analysis of osteogenic cells in the healing process after fracture.

As the result of cytokinetic analysis of osteogenic cell at the time of reintegration after experimentally administered bone fractures in mice, the following findings were obtained: 1) Gt of mesenchymal-like cells 1 week after fracture was 23 h but that 2 weeks later was 15 h. This shortening of Gt was due to the shortening of Gt1. Gt of osteoblasts, one week after, was 20 h and that 2 weeks after was 21 h. This prolongation of Gt was due to the prolongation of St. Despite the fact that Gt of mesenchymal-like cells 2 weeks after fracture was shortened, St indicated prolongation. 2) Both mesenchymal-like cells and osteoblasts indicated a reduction of growth fractions 2 weeks later. From these facts, it is considered that in the reintegration of the fracture, these proliferative cells control their own growth fractions according to the necessity of repair of the fractured part. 3) It was argued that chondrocytes originated from mesenchymal-like cells but should not be the precursors of osteoblasts. 4) It was shown that mesenchymal-like cells must have the potential to differentiate into either osteoblasts or chondrocytes. 5) Mesenchymal-like cells are the precursors of osteoblasts and the latter are the precursors of osteocytes, but mesenchymal-like cells and osteoblasts have their own respective cell cycles. 6) It was argued that the relation between S-32 uptake by the matrix of the osteoid and chondrocytes as functional cells should be studied in relation to the role played by cartilage tissue in the mechanism of ossification.

Animals↗