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Biomedical subjects

J Kawada

Publications and source records attributed to J Kawada.

At least 55 records · Page 3Linked to original sources
PubMed1990

Effect of 2,4-dihydro-3H-1,2,4-triazole-3-thiones and thiosemicarbazones on iodide uptake by the mouse thyroid: the relationship between their structure and anti-thyroid activity.

Antithyroid activity of 2,4-dihydro-3H-1,2,4-triazole-3-thiones and thiosemicarbazones was tested by measuring the uptake ratio of thyroid: serum (T/S) of 125I through the mouse thyroid. Substitution with an alkyl group at the 5-position of the triazole nucleus remarkably increased the activity but substitution at the N-2 and/or N-4 positions caused a significant decrease in the activity, indicating the necessity of unsubstituted thioureylene moiety for the antithyroid activity. Thiosemicarbazone derivatives which are an open ring structure of triazoles showed comparable antithyroid activities to those in a ring form, but one thiosemicarbazone showed a much higher toxicity than the corresponding ring form compound. This suggests that the ring structure is not essential for the activity but is necessary to reduce toxic effect. Of fourteen compounds tested, 5-methyl-2,4-dihydro-3H-1,2,4-triazole-3-thione was the most potent antithyroid compound with low toxicity, with a potency tenfold that of propylthiouracil, a drug currently used.

Animals↗
PubMed1990

Insulin-like effect of vanadyl ion on streptozotocin-induced diabetic rats.

Recent studies have indicated that the blood glucose level of rats with streptozotocin (STZ)-induced diabetes (type 1) is normalized without an increase in the plasma insulin level by administration of sodium orthovanadate in the drinking water. The mechanism of this insulin-like effect of vanadate is unknown. In this study, we investigated whether vanadyl ion, which is less toxic than vanadate to rats, also has an insulin-like effect in rats with STZ-induced diabetes. When rats with STZ-induced diabetes were given a daily i.p. injection of vanadyl sulphate (9.3 and 4.6 mg vanadium/kg body weight), their blood glucose level decreased from about 22.2 to about 7.2 mmol glucose/l within 2 days and remained low for at least 12 weeks. This treatment did not affect their low plasma insulin level. Quantitative electron spin resonance (ESR) spectrometry showed that most of the vanadium (about 90%) in their tissues was present as a vanadyl form (VO2+). ESR analysis also showed that the vanadyl ion in tissues was bound endogenously with four oxygen ligands from either water or oxyamino acid residues in proteins. Vanadyl sulphate accelerated glucose incorporation into adipocytes of rats, suggesting that the action of vanadyl ion is peripheral. Interestingly, vanadyl sulphate at a high concentration (about 10 mmol/l) was more effective than insulin in enhancing glucose uptake. This study demonstrated that: (1) vanadyl sulphate (+4 oxidation state), like vanadate ion, normalizes the blood glucose levels of rats with STZ-induced diabetes; (2) the action of vanadyl ion is peripheral; and (3) the active form of vanadium for an insulin-like effect may be a vanadyl form, not vanadate.

Adipose Tissue↗
PubMed1990

Importance of the concentration of ATP in rat pancreatic beta cells in the mechanism of streptozotocin-induced cytotoxicity.

The effects of streptozotocin (STZ) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) on monolayer cultures of rat pancreatic beta cells were compared. The intracellular NAD concentration was markedly decreased by both 2 mmol STZ/l and 13.6 mumol MNNG/l, but insulin secretion was decreased significantly only by STZ. The intracellular ATP level decreased rapidly and in a time-dependent manner with STZ, but decreased less on treatment with MNNG: 80% decrease with STZ but only 35% decrease with MNNG in 12 h in the cells exposed to the chemicals for 1 h and then washed thoroughly. STZ decreased oxygen consumption of rat liver mitochondria in a time- and dose-dependent manner and enhanced the generation of hydroxyl radicals (DMPO-adducts). This enhancement was doubled on the addition of succinate as a substrate. Mitochondrial ATP production was also decreased significantly by STZ, but not by MNNG. Thus the marked depletion of intracellular ATP in beta cells by STZ seems to be due mainly to a direct effect on mitochondrial production. From these results, we suggest that the cytotoxic effect of STZ in pancreatic beta cells is due to a reduction in the intracellular level of ATP, rather than of NAD.

Adenosine Triphosphate↗
PubMed1990

Differential effects of methylmercuric chloride and mercuric chloride on oxidation and iodination reactions catalyzed by thyroid peroxidase.

Thyroid peroxidase (TPO), the major enzyme in the thyroid hormone synthesis, multifunctionally catalyzes (1) iodide oxidation, (2) iodination of the precursor protein, and (3) a coupling reaction of iodotyrosyl residues. The present study was carried out to examine the mercurial effects on the iodination, the second step of TPO. Purified porcine thyroglobulin or bovine serum albumin as acceptor protein was iodinated with [125I]NaI and H2O2 by purified porcine TPO. Iodinated protein was separated by acid precipitation on membrane filter or paper chromatography. Both CH3HgCl and HgCl2 dose-dependently inhibited the iodination, but HgCl2 was more potent to inhibit the iodination than CH3HgCl. These mercurial effects on the second step resemble the effects on the third step which were already reported; but are in marked contrast to the effects on the first step, where TPO was inhibited by HgCl2 but never by CH3HgCl.

Animals↗
PubMed1990

Phosphate and pepsin adsorptions by a new boehmite compound and aluminum hydroxide.

A new microcrystalline compound of aluminum oxide hydroxide (tentatively named PT-A) was synthesized in the hope of providing a better phosphate adsorbent for future clinical use than the currently marketed aluminum hydroxide gels (ALG). An X-ray diffraction study demonstrated a boehmite structure in PT-A but an amorphous structure in ALG. PT-A was more stable in pH change than ALG; in elution tests in artificial gastric and intestinal solutions, aluminum ion eluted from PT-A was maximally 10% of the amount from ALG at pH 1.2; and was undetectable at pH 6.8, at which point ALG still showed some aluminum elution. Phosphate-adsorbing efficacy of PT-A and ALG in vitro was about the same at pH 1.2; however, it was four times greater in PT-A than in ALG at pH 6.8, indicating that PT-A will be effective in the intestine. PT-A also adsorbed pepsin but the amount was at most the same or much less than that adsorbed by ALG, which depended on pH in solution.

Adsorption↗
PubMed1990

Variations in intrathyroidal lithium content and their effect on the iodide uptake in mouse thyroid.

Lithium (Li) is accumulated in the thyroid but the mechanism of Li accumulation is not known. In the present study, the causes of variation in Li concentration in the thyroid and the relation between cellular Li and iodide were examined. This was done by using mice treated with Li (0.01% as Li2CO3) for 4 weeks, co-administered with propylthiouracil (PTU, 0.5 mg/ml daily p.o.) or thyroxine (T4, 0.5 micrograms per day i.p.) for last 10 days. The total content of Li in a whole thyroid (ng/thyroid) was not changed through treatment with PTU or T4. But the Li concentration in terms of mg/kg of the gland was reduced with PTU and was unchanged or slightly increased with T4, due to the change in the mass of thyroid. Furthermore, short-term (3 h) Li uptake in the thyroid was not affected by pre-treatment with PTU or T4. These results indicate that the variation in thyroidal Li concentration was not due to a direct effect of PTU or T4 on Li transport, but to a thyroidal condition caused by the secondary influence of drugs. A measurement of the thyroid: serum iodide concentration ratio (T/S) of 125I showed that the iodide uptake was reduced when intracellular Li concentration was high, and that PTU alone elevated the T/S, but Li + PTU brought it back to a normal level; whereas, T4 alone diminished the T/S, Li + T4 made it rise significantly more than did T4 alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Direct evidence for ATP consumption due to iodide uptake by isolated, uncultured, pig thyroid epithelial cells.

The concept that iodide uptake by thyroid requires a supply of ATP is currently accepted. However, there is little direct evidence that the extents of iodide uptake and ATP consumption are correlated. To demonstrate this correlation, we used isolated, uncultured pig thyroid epithelial cells in basal media containing only glucose and the cations necessary for Na+,K(+)-ATPase, which prevented other possible cellular activities requiring ATP. The isolated cells were sensitive to various metabolic inhibitors of ATP-generating systems, confirming that they were intact. The extents of increase in iodide uptake and decrease in ATP content of the cells were entirely dependent on the presence of the cations, and were closely correlated with each other. Furthermore, the ATP content was not reduced in the absence of NaI, even when all necessary cations for the ATPase were present. These findings provide direct evidence for a correlation between the extents of iodide uptake and ATP consumption. Cells in medium with Mg alone did not show iodide incorporation or ATP consumption, confirming that Mg2(+)-dependent ATPase does not contribute to iodide uptake by the thyroid.

Adenosine Triphosphate↗
PubMed1990

Variations in manganese effect on 6-phosphogluconate dehydrogenases from the thyroid and liver of the mouse and an evidence for non-interchangeability of manganese and magnesium.

Both manganese (Mn) and magnesium (Mg) are known to activate 6-phosphogluconate dehydrogenase (6-PGDH). Yet in the present study none of the metal ions stimulated 6-PGDH from the thyroid of mice, but Mn alone stimulated the enzyme from the liver. Such a stimulatory effect of Mn on the liver enzyme was seen regardless of the presence of Mg, This suggests that the reaction sites for the two ions must be apart from one another or that the affinity of Mn is stronger than that of Mg. The enzyme preparations from livers of those mice which had been administered intraperitoneally with excess of Mn for 1 - 14 days were greatly stimulated by further in vitro addition of Mn, whereas the enzyme sources from the thyroids thus treated were almost insensitive to Mn in vitro. The results indicate that cellular Mn hardly reaches the levels for maximal stimulation of the enzyme in the liver. In addition, some sex difference was observed in the Mn effect on 6-PGDH from the liver.

Animals↗
PubMed1990

[A case of unilateral VIIIth, IXth and Xth cranial nerve involvement with herpes zoster].

A 46-year-old healthy man suffered from sore throat, fever and right otalgia. On the next day, he developed hoarseness and difficulty in swallowing. On the 6th day, he suffered from vertigo, nausea and vomiting associated with unsteady gait. He was admitted to the otorhinolaryngology department in our hospital and pointed out to have vesicles at his right ear. On the 13th day, he was referred to our service. On admission, no vesicles were noted at the right ear or pharynx. Neurological examination revealed mild nuchal rigidity and marked hoarseness, associated with poor elevation of soft palate and loss of pharyngeal reflex on the right side. He also had horizontal-clockwise rotatory nystagmus in primary gaze and ataxic gait. There was no hearing loss nor facial palsy. No other abnormal neurological findings were noted. The cerebrospinal fluid showed pleocytosis associated with increased protein. The viral antibody titre for herpes zoster was significantly elevated on 18th day in serum as well as in cerebrospinal fluid. Vertigo, nausea, vomiting, ataxia and difficulty in swallowing were all disappeared by the 25th day, whereas hoarseness was improved but still noted 6 months later. Among cranial nerves, trigeminal and facial nerves are the most commonly affected in patients with herpes zoster, but there have been a few reported cases of the 9th and 10th cranial nerve involvement in the literature. In these previously reported cases, all were written before the era of serological diagnosis, and herpes zoster was diagnosed by the vesicles at the ear or pharynx.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Viral↗
PubMed1989

Generation of alloxan free radicals in chemical and biological systems: implication in the diabetogenic action of alloxan.

Electron spin resonance (ESR) studies that on reaction with NADPH, alloxan was reduced forming labile anion radicals giving a 7-line signal with g = 2.005. These radicals were also produced on incubation of alloxan with rat liver subcellular fractions and their production was greatly enhanced by NADPH. Alloxan effectively scavenged superoxide anion generated by a xanthine-xanthine oxidase (XOD) system in association with its reduction to these anion radicals. These radicals were also formed during incubation of alloxan with rat pancreatic beta-cells. These results suggest that the cytotoxicity of alloxan is related to the formation of alloxan anion radicals.

Alloxan↗
PubMed1989

Ethylidene glucose-substituted new analogue of streptozotocin cannot induce diabetes: study on the basis of structure and activity relationship.

4,6-O-Ethylidene glucose (ethylidene glucose), a specific inhibitor at the outer surface of a glucose transporter in the cell membranes, substituted analogue of streptozotocin was newly synthesized. This compound did not induce diabetes in rats and also did not show cytotoxic effect on pancreatic beta cells of neonatal rats in a monolayer culture system. The reasons why such a molecule was designed and why it showed no biological effects are discussed on the basis of a structure-activity relationship. Our results afford positive evidence for the presence of a glucose transport system or a glucose transporter on pancreatic beta cells and its involvement in the action of streptozotocin on beta cells.

Animals↗
PubMed1989

Differential effects of methylmercuric chloride and mercuric chloride on the histochemistry of rat thyroid peroxidase and the thyroid peroxidase activity of isolated pig thyroid cells.

This study was designed to characterize the interaction of CH3HgCl or HgCl2 with thyroid peroxidase (TPO). Two types of experiments were performed. First, the thyroids from rats that were given 5.6 mg/kg/day of either CH3HgCl or HgCl2 for 2 weeks by intubation were subjected to histochemical treatment and then to electron microscopy. TPO activities in all cell compartments were inhibited by HgCl2 but not by CH3HgCl. Morphological observation showed that taller epithelia were induced by HgCl2, whereas flattened epithelia forming large follicles were induced by CH3HgCl. The serum thyrotropin level was substantially lowered by CH3HgCl but was unchanged by HgCl2. Second, the guaiacol oxidation by TPO in isolated and ruptured pig thyroid cells was spectrophotometrically monitored in the presence of either CH3HgCl or HgCl2. The TPO was not inhibited by CH3HgCl but was inhibited by HgCl2. These results indicated that CH3HgCl induced a hypothyroid state without affecting TPO, whereas HgCl2 inhibited TPO and induced a hypertropic state owing to compensation for loss of enzyme activity, and that the lack of inhibitory activity of CH3HgCl was not due to the inability to penetrate the cells. Therefore, there appeared to be a differential interaction of organic and inorganic forms of mercurials with the thyroid.

3,3'-Diaminobenzidine↗
PubMed1989

Effect of lithium carbonate administration singly or in combination with some psychotropic drugs on the radioiodide uptake by mouse thyroid.

The present study dealt with two objects; the first object was to examine whether or not lithium uptake in thyroid is modified by the thyroid state and how the intrathyroidal Li affects iodide uptake by the thyroid. Male and female mice were given lithium carbonate (Li) with propylthiouracil (PTU) or thyroxine (T4). Li was measured by a flameless atomic absorption spectrometry. The total Li content in thyroid was unaffected with PTU or T4, however, Li concentration per unit mass was reduced by PTU but unaffected by T4. The thyroid: serum ratio (T/S) of 125I resulted that the T/S became higher when Li concentration per unit mass was lower and vice versa, suggesting that Li uptake is controlled by thyroid states and Li in the gland interferes with the iodide uptake. Serum triiodothyronine (T3) and T4 by radioimmunoassay showed that PTU alone and in combination with Li lowered serum T4, while a high level of T4 by its supplement was suppressed by co-administration of Li. T3 level was lowered by Li alone, but not severely affected by other drugs. The results suggest that Li enhances T4 clearance without T4-T3 conversion. The second object was to examine the effect of combined psychotropic drugs on thyroid function. Carbamazepine (CBZ), haloperidol (HLP) and imipramine (IPA) were given singly or in combination with Li to examine their effects on the T/S of 125I. Only CBZ reduced the T/S but CBZ plus Li had no summative effect. Neither HLP nor IPA affected the T/S, singly or in combination with Li, suggesting that HLP or IPA does not interfere with an iodide pumping machinery. No distinct sex difference was observed in drug effects.

Animals↗
PubMed1988

Enhancement by streptozotocin of O2- radical generation by the xanthine oxidase system of pancreatic beta-cells.

Spin-trapping techniques and electron spin resonance (ESR) spectroscopy were used to study the relationship between the effect of streptozotocin (STZ) on pancreatic beta-cells and free radical formation by these cells. Results showed that STZ enhanced generation of the DMPO-OH radical adduct, which is a degradation product of the superoxide anion (O2-) in the presence of cellular components, in a hypoxanthine-xanthine oxidase (XOD) system with a homogenate of beta-cells. This enhancing effect was also observed in a system without cellular components; STZ increased the signal height due to the O2- radical in a concentration-dependent manner and caused a maximum of 150% enhancement at a concentration of 1.5 mM. Thus, STZ seemed to enhance the generation of the O2- radical in the XOD system, probably by some mechanism of its interaction with XOD. Pancreatic beta-cells exhibited a high XOD activity and a very low superoxide dismutase activity. Therefore, the present result supports the possibility that the cytotoxic effect of STZ is closely related to free radical generation in pancreatic beta-cells.

Animals↗
PubMed1988

A sigmoidal relationship between liver stearoyl CoA desaturase activity and serum hormone concentrations caused by streptozocin and its antagonists.

Stearoyl CoA desaturase activity in liver microsomes, and insulin, thyroxine, and triiodothyronine levels in serum were measured after administration of streptozocin (STZ) and its antagonists to rats. The effect of STZ, which caused hyperglycemia and inhibited the desaturase activity, was antagonized by 2-desoxyglucose and 3-O-methyl-glucose; 1-O-methyl-3-desoxyglucose and 1-O-methyl-3-O-methylglucose were without any effect. The enzyme activity plotted against insulin levels showed a broad sigmoidal curve, whereas the activities versus thyroid hormone levels showed steeper sigmoidal curves.

Animals↗
PubMed1988

An appropriate model for congenital hypothyroidism in the rat induced by neonatal treatment with propylthiouracil and surgical thyroidectomy: studies on learning ability and biochemical parameters.

Hypothyroidism was induced in rats by treatment with propylthiouracil through the mother's milk throughout the suckling period followed by surgical thyroidectomy without use of radioiodine. The growth of these animals was considerably retarded and their light-dark discriminative operant learning ability was also significantly decreased. Replacement therapy with thyroxine to maintain its normal serum concentration was effective for continuing normal growth and development of learning ability. Therefore, these hypothyroid rats are a useful model of congenital hypothyroidism. Biochemical studies showed that the inhibition of cerebral Na,K-ATPase and succinic dehydrogenase activities detected in early postnatal life in these hypothyroid rats was transient and that normal activities of these enzymes were later regained in adult rats. However, the activity of 2',3'-cyclic nucleotide 3'-phosphohydrolase and the brain myelin remained low throughout life unless thyroxine was administered. Though a critical correlation between biochemical parameters and learning ability is still uncertain, these results suggest that the formation of myelin in the neonatal period is at least dependent on thyroid hormone and would play an important role in mental development.

Animals↗