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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
PubMed1983

Purification and chromium-excretory function of low-molecular-weight, chromium-binding substances from dog liver.

From liver of dogs injected iv with potassium dichromate (38 mg/kg body wt), a low-molecular-weight chromium-binding substance (LMCr) was purified into two subfractions, LMCr I and LMCr II, which differ in physical and chemical properties. LMCr I was identified to be an anionic, organic chromium compound with a molecular weight of 1500. It contained glutamic acid, glycine, and cysteine as the predominant amino acids and firmly bound chromium in a ratio of one chromium(III) to one molecule of LMCr I. LMCr II was isolated in crystalline form and demonstrated to be a water-soluble, inorganic chromium(III) complex consisting of Na2HPO4 . 7H2O and Na2HPO4 . 2H2O. Although its crystallization reduced the chromium content, it had a maximum chromium-binding capacity as much as one chromium per one phosphorus in water. The mixture of LMCr I and LMCr II as approximated to be the natural composition showed a lower acute toxicity as measured by lethality in mice and had higher rates of urinary excretion and renal clearance in rabbits, accompanied by lower rates of renal tubular reabsorption and retention in kidney and liver than potassium dichromate(VI) and chromium(III) chloride. Pretreatment with chromium-free LMCr II remarkably reduced the mortality rates of mice acutely poisoned with chromium chloride. These results indicate that LMCr plays an important role in the detoxification and excretion of chromium in mammals.

Amino Acids↗
PubMed1983

[Effects of tricyclohexyltin hydroxide on carbohydrate and lipid metabolisms].

Male Japan white rabbits were given orally with two doses of tricyclohexyltin hydroxide (TCHT, 250 mg/kg body weight) at 48 hr intervals and their carbohydrate and lipid metabolisms were investigated 48 hr after the last administration. Elevated fasting blood glucose levels and a significant inhibition of insulin (IRI, immunoreactive insulin) release in response to the intravenous glucose infusion were observed. Microscopic examination of pancreatic islets did not reveal any histological alteration. Plasma triglyceride levels were elevated in the TCHT-treated rabbits. Ultracentrifugation of plasma lipoproteins revealed a marked increase in chylomicron + VLDL (very low density lipoprotein) fraction. Rates of triglyceride secretion into plasma were not different between the TCHT-treated and the control animals. These data suggest that TCHT induces hyperglycemia and hyperlipidemia in rabbits, and the disturbance of metabolism seems to be related to the inhibition of insulin release from the pancreatic islets by TCHT.

Animals↗
PubMed1983

[The effect of triphenyltin fluoride on aggregation, ATP secretion and malondialdehyde formation of rabbit platelets in vitro].

Recent studies have demonstrated that triphenyltin fluoride (TPTF), widely used as an agricultural chemical and a marine antifoulant, inhibits collagen-induced platelet aggregation and ATP secretion in rabbits ex vivo. The aim of the present investigation was to elucidate the mechanism of the inhibitory action of TPTF by investigating platelet malondialdehyde (MDA) formation, aggregation and ATP secretion following the stimulation by various stimuli of rabbit platelets treated in vitro with TPTF, other triphenyl metals and aspirin. Although no inhibitory effect of TPTF was found on sodium arachidonate-induced platelet aggregation and ATP secretion, TPTF inhibited dose-dependently both platelet aggregation and ATP secretion induced by collagen. The antiaggregating (IC50) concentration of TPTF was 6.0 X 10(-6) M against collagen. In addition, TPTF prevented the collagen-, and thrombin-induced formation of MDA, but had little inhibitory effect on the conversion of exogenous arachidonic acid to MDA in platelets. In contrast, aspirin (10(-3) M) inhibited platelet aggregation, ATP secretion and MDA formation induced by all the stimuli tested. Other triphenyl metals did not any inhibitory effect on collagen-, and sodium arachidonate-induced platelet aggregation and ATP secretion even at a final concentration at 10(-3) M. These results suggest that TPTF has a specific inhibitory effect on platelet aggregation and ATP secretion by acting at some step(s) of platelet membrane between the binding site of collagen and thrombin and the release of arachidonic acid.

Adenosine Triphosphate↗
PubMed1982

Effect of acute administration of cadmium on distribution of zinc in the hamster.

Acute administration of sc doses of Cd (1mg/kg . d, 3 or 6 d) to male golden hamsters resulted in a remarkable dose-dependent increase of Zn in the liver and kidney. In contrast, Zn contents in the heart and testes showed a significant dose-dependent decrease. No change was found in Zn contents of the bone. The correlation coefficients between contents of Cd and Zn in the liver and kidney were much higher in metallothionein fractions than in the corresponding whole organs. These results suggest that Cd induces the synthesis of metallothionein in the liver and kidney, leading to simultaneous accumulation of Cd and Zn in the organs; this in turn decreases the Zn contents in other organs, where weak or no induction of metallothionein synthesis takes place. Therefore Cd might induce Zn deficiency in humans or animals whose pool size and intake of Zn are marginal.

Animals↗
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↗