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Biomedical subjects

K Gschwendtová

Publications and source records attributed to K Gschwendtová.

At least 19 recordsLinked to original sources

Acute changes in biliary excretion of reverse triiodothyronine in rats after insulin-induced hypoglycemia: effect of glucose, verapamil, cycloheximide and actinomycin D.

Biliary excretion of reverse triiodothyronine (rT3) was estimated in rats during hypoglycemia induced by a 10-min infusion of 1 U of insulin (INS) and for the following 5 h. During that period an increase in biliary rT3 was found. This was seen also during the infusion of exogenous glucagon (10 micrograms in 1.2 ml of saline per 1 h for 5 h) given independently of INS. The infusion of glucose (1 g/kg per 50 min or 2 g/kg per 110 min) following INS infusion delayed the increase in rT3. The increase in rT3 was prevented by actinomycin D (1 mg/kg) when injected before (90 min), but not after (30 min) INS, and also by cycloheximide (2.5 mg/kg) injected immediately before INS. The same dose of cycloheximide also prevented a similar increase of rT3 during the infusion of exogenous glucagon. Verapamil (5 mg/kg divided into five doses per 4 h) blunted the increase of rT3. These data indicate that following INS injection counter-regulatory hormones may be responsible for the increased production of rT3; this altered metabolic activity apparently is dependent on protein synthesis.

Animals↗

Biliary excretion of iodothyronines (T4, T3 and rT3) after administration of exogenous thyroxine: effect of glucose and insulin.

Thin polyethylene tubings were inserted into the bile duct and femoral vein to 5 groups of 6-12 rats each under pentobarbital anesthesia. The bile was collected into glass vials which were changed every 2 h for a total of 8 h. The individual groups were infused for 8 h with following solutions in a rate of 1.2 ml/h: 1. saline; 2. saline after fasting for 48 h before the experiment which was also the case in all following groups; 3.30% glucose in saline; 4. the same glucose with 1 U insulin per h; 5. 1 U insulin only in saline. After the first control interval each animal was injected 2 micrograms L-thyroxine in 0.5 ml alkaline saline into a venous cannula. In each bile sample total thyroxine (T4), triiodothyronine (T3) and reverse triiodothyronine (rT3) were measured with the aid of specific radioimmunoassay and the results were expressed as ng/2 h. After the injection of exogenous T4 the excretion of this substance in bile significantly increased. In the case of T3 a significant decrease of biliary excretion was found in all fasted groups as compared with fed control (group 1). However, during the prolonged infusion of insulin resulting in severe hypoglycemia (group 5) the excretion of T3 stepwise significantly decreased, while at the same time that of rT3 significantly increased as compared with the other fasted groups including control, that infused with glucose or that infused glucose with insulin. It was suggested that this might result from the effect of counterregulatory hormones.

Animals↗

Immediate and dose-response related increase of biliary excretion of reverse triiodothyronine after propylthiouracil administration.

In a group of rats infused with L-thyroxine (0.13 micrograms T4 in 0.6 ml alkaline saline per hour) for 6 h to which an infusion of propylthiouracil (PTU) was added beginning from the 3rd hour (2 mg PTU in 0.6 ml saline per hour) a significant increase of biliary excretion of reverse triiodothyronine (rT3) was found. In another experiment a dose-response related rT3 excretion by bile was observed in groups of rats infused with 0.05, 0.10, 0.20 or 0.40 mg PTU in 1.2 ml alkaline saline per 2 h, all animals receiving a pulse dose of 1 micrograms rT3 at the beginning of PTU infusion. It was concluded that the increase of rT3 excretion results from the inhibition of 5'-deiodinase type I activity in the liver caused by PTU. It thus appears that such phenomenon may be used as in vivo marker of that enzyme activity.

Animals↗

Increase of biliary excretion of reverse triiodothyronine in rats during the infusion of neurotensin possibly resulting from the inhibition of iodothyronine 5'-monodeiodination.

Male rats weighing about 350 g were inserted polyethylene tubes into the bile duct and femoral vein under pentobarbital anaesthesia. After taking the first (control) 2-h bile sample the control group (n = 24) was infused saline for 4 h and the other group (n = 14) was infused neurotensin in a dose of 27 micrograms per animal per 4 h. The concentration of thyroxine (T4), triiodothyronine (T3) and reverse triiodothyronine (rT3) in the bile was estimated by radioimmunoassay. No significant differences between groups were found in the biliary excretion of T4 and T3, while the excretion of rT3 after the infusion of neurotensin was significantly increased which was not the case in controls. Since neurotensin is known to increase glycemia which effect might be or might not be mediated by glucagon, it may be suggested that these results bring an additional support for the previously reported coincidence between a prevailing effect of gluconeogenetic hormones and inhibition of iodothyronine 5'-deiodination in the liver.

Animals↗

Effect of the glycogenolytic gluconeogenetic hormones, glucagon, vasopressin and angiotensin II, on biliary excretion of iodothyronines in rats is possibly related to the inhibition of 5'-monodeiodination in the liver.

Polyethylene tubes were inserted into the bile duct and femoral vein of rats under pentobarbital anaesthesia and bile was collected for three 2-h periods. After the first (control) period the animals were infused intravenously at a rate of 1.2 ml/h with the following compounds: (1) 0.9% (w/v) NaCl (control group), (2) glucagon (1200 ng/h), (3) vasopressin (1200 ng/h) or (4) angiotensin II (600 ng/h). The concentrations of thyroxine (T4), tri-iodothyronine (T3) and reverse tri-iodothyronine (rT3) in the bile were estimated by radioimmunoassay. No significant differences between groups were found in the biliary excretion of T4 and T3, while the excretion of rT3 after the infusion of all the hormones used was significantly (P less than 0.001 at 2 to 4 h of the infusion) increased, no such increase being found in the controls. It may be concluded therefore that the administration of the above hormones resulted in some changes in iodothyronine metabolism in the liver. These may be explained by an inhibition of iodothyronine 5'-monodeiodination related to the glycogenolytic and gluconeogenetic effects of these hormones.

Angiotensin II↗

Studies and reevaluations of some aspects on thyroid function after superior cervical sympathetic gangliectomy in rats.

The results of 11 experiments in a total of 571 rats (initial body weight of 150-250 g) are reported and some findings differing from those by others are discussed. It was repeatedly found that the animals after bilateral or even unilateral superior cervical sympathetic gangliectomy (GX) did not gain body weight during the first week after surgery. Though they started to grow later, for several weeks their body weight remained significantly less than that of sham operated controls (SH). Though such phenomenon has not yet been described, it may well explain the increase of thyroid weight (as expressed per body weight) after gangliectomy alone or combined with antithyroid drug treatment or hypophysectomy as described by others. It was suggested that such changes may depend on general metabolic changes resulting in a striking inhibition of body weight gain rather than on some specific effect of GX on the thyroid. This view was supported by evaluating the data on absolute and relative thyroid weight from 4 experiments in a total of 265 animals. The level of thyroxine (T4) and thyrotropic hormone (TSG) was repeatedly found to be significantly decreased after GX for until about 72 h and 24 h after surgery, respectively, which was in agreement with the data reported by others. However, the onset of such decrease was repeatedly found to appear at 6 or 8 h after surgery (in one experiment even at 3 h after surgery) which is also contrasting to the onset of T4 decrease at 14 h after surgery as found by others who suggested a correlation of such thyroid depression with a depletion of noradrenaline from the thyroid and may be even from median eminence. In these experiments, however, a decrease of T4 level was found several hours before the depletion of noradrenaline from the thyroid which appeared at 12 h after surgery and remained at similar level until 40 days, while no remarkable changes of that were found in SH animals (with the excretion of slight increase after 24 h). Between about 4 and 40 days after surgery no significant changes in T4 and TSH levels after GX were found as compared with SH animals is in agreement with others.4+n one experiment the increase of T4 at 2 h after TRH injection, resulting apparently from the effect of endogenous TSH, was significantly inhibited in GX animals at 8 days after surgery, while in other experiments (at 8 and 40 days after surgery) no difference in T4 level increase was found in GX animals as compared with SH ones. In general, it may be suggested that superior cervical sympathetic gangliectomy may result in some temporary and perhaps transient changes in pituitary-thyroid function in rats.

Animals↗

Delayed changes of plasma level and biliary excretion of several iodothyronines after a single administration of low doses of thyroxine in rats.

Male Wistar rats were injected i.p. 2.5 or 5.0 micrograms thyroxine (T4) and the level of several iodothyronines and TSH in plasma or biliary excretion of iodothyronines were estimated by radioimmunoassay in groups of animals in various intervals up to 144 hr after the administration. In general, two peaks in the plasma level and biliary excretion of iodothyronines were found: first one within 24 hr and a delayed second one between about 48 and 72 hr after the administration. It was concluded that the first peak may correspond to the metabolic changes in fast tissue pools, while a second one might reflect some delayed iodothyronine metabolic steps in slow tissue pools after a bolus injection of T4.

Animals↗

Studies on in-vivo capacity of thyroxine deiodinating system in rat liver: biliary excretion of several iodothyronines after increasing loading doses of thyroxine.

Eighteen male rats were inserted with polyethylene tubings into bile duct and femoral vein and two rats each were injected a series of doses from 5 to 1280 micrograms L-thyroxine into a venous cannula. The bile was collected for three subsequent 2-hr periods and the excretion of total thyroxine (T4), triiodothyronines (T3 and rT3) and all diiodothyronines (3,3'-T2, 3,5-T2 and 3',5'-T2) was estimated as well as that of conjugated T4 and T3. The excretion of all compounds was considerably increased as early as within the first 2-hr period. Almost linear dose-response relationship was found between the dose of T4 and its biliary excretion up to the dose of 640 micrograms, only smaller increase being observed after 1280 micrograms T4. Similar relationship was found also in the excretion of diiodothyronines, while that of triiodothyronines after 1280 micrograms T4 was slightly less than after 640 micrograms T4. The excretion of rT3 was consistently about twice as high as that of T3. The data on diiodothyronine excretion suggested a preferential conversion of rT3 to 3',5'-T2 and that of T3 to 3,5-T2 over that to 3,3'-T2. The ratio of 3,5-T2/T3 after different doses of T4 was about 2--4 times higher than that of 3',5'-T2/rT3 suggesting the higher deiodination rate of T3 than that of rT3.

Animals↗

Dual dose-related action of peripherally administered morphine on cold-stimulated thyrotropin secretion in male rats.

Cold-induced increase of thyrotropin (TSH) release was found to be inhibited after 10 or 20 mg/kg morphine sulfate (MO) injected intraperitoneally 30 min before the transfer of adult male rats from 30 to 4 degrees C for 60 min (i.e. 90 min before sacrifice). In contrast, lower doses of MO such as 2.5 and 5 mg/kg were found to stimulate the cold-induced TSH release under the same conditions. Such a cold-induced TSH release stimulated by lower doses of MO was found to be inhibited by intraperitoneal injection of 2 or 4 mg/kg naloxone (NX) 30 min before MO injection (i.e. 120 min before sacrifice) in a dose-dependent manner, while the same doses of NX were without effect on the levels of TSH after higher doses of MO. It is suggested that these effects may depend on different sensitivities of various hypothalamic loci involved in mediating either a stimulation or inhibition of TSH release.

Animals↗

Acute changes of iodothyronine excretion by bile after a single and repeated administration of dexamethasone in rats.

Bile was collected from cannulated bile duct under pentobarbiturate anesthesia and the excretion of several iodothyronines was estimated with the aid of radioimmunoassay as described previously. The excretion of triiodothyronine (T3) was significantly decreased between 4 and 6 h after a single injection of 20 and 40 mg kg-1 dexamethasone (DEX), while no changes in the excretion of thyroxine (T4) and reverse triiodothyronine (rT3) were found. In another experiment a decrease of T3 excretion was observed together with an increase of rT3 excretion and of T4/T3 and rT3/T3 ratio between 9 and 11 h after a single injection of 0.75, 1.5 and 3.0 mg kg-1 DEX, the differences being in most cases significant as compared to controls. In the same experiments a dose related increase of excretion of 3,3'-diiodothyronine (3,3'-T2) and 3,5-diiodothyronine (3,5-T2) was found, while the excretion of 3',5'-diiodothyronine (3',5'-T2) decreased with dose of DEX. Similar results were observed even after the administration of 1.5 and 3.0 mg kg-1 DEX for 5 days. In addition, the level of rT3 in serum was significantly increased at 9 h after a single dose of 3.0 mg kg-1 DEX and after 5 days administration of 1.5 and 3.0 mg kg-1 DEX. The data support a previous view that the changes in biliary excretion of iodothyronines are closely related to deiodinating metabolism of T4 in the liver and are expressed earlier and more remarkably than these in their plasma level.

Animals↗

Studies on the inhibitory effect of apomorphine and bromocryptine on basal and TRH induced level of TSH and PRL in hypothyroid rats under pentobarbiturate anesthesia.

Groups of male rats were inserted with polyethylene tubings into femoral artery and vein under pentobarbiturate anesthesia and small blood samples were frequently taken for the estimation of TSH and PRL under maintaining isovolemia. After a single injection of apomorphine (12 mg kg-1) or bromocryptine (20 mg kg-1) much more expressed effect of these drugs on a decrease of PRL level in plasma was found than that on a decrease of TSH level and similar observation was made with the use of continuous i.v. infusion of apomorphine (50 micrograms in 20 microliter per min for 180 min). Finally, under the above dose of infused apomorphine, the effect of TRH on the increase of TSH level was depressed at the 30th min as compared to that 0 and 120th min of infusion. In addition, at 120 min of infusion the effect of TRH was significantly higher than that at 0 min. These results suggest that the effect of apomorphine may take place at the pituitary level.

Anesthesia↗

In vivo effect of amiodarone, thiocyanate, perchlorate and goitrin on thyroxine deiodination in rat liver.

The bile duct of male Wistar rats weighing 350 g was cannulated with polyethylene tubing under pentobarbiturate anesthesia and biliary excretion of thyroxine (T4), triiodothyronine (T3), reverse triiodothyronine (rT3) and 3,3'-,3,5- and 3',5'-diiodothyronine (3,3'-T2, 3,5-T2 and 3',5'-T2, respectively) was estimated in 2 h samples of bile with the aid of specific radioimmunoassay. In each animal the excretion of appropriate compounds for 2 h after intravenous injection of various drugs was expressed as per cent of that during 2 h control period before the injection. The results obtained in individual groups of animals were compared to control group which was injected saline before the second bile collection period. The injection of amiodarone (15 mg kg-1) resulted in significant decrease of T3, rT3, 3,3'-T2 and 3,5-T2 excretion and that of thiocyanate (SCN-; 50 mg kg-1) resulted in significantly increased excretion of T4, while that of T3 and 3,5-T2 was significantly decreased. Goitrin (L-5-vinyl-2-oxazolidinethione; 6 mg kg-1) and perchlorate (ClO4-; 50 mg kg-1) showed only slight effects. It was concluded that amiodarone and thiocyanate in the doses used inhibited the conversion of T4 to T3 in vivo immediately after the administration.

Amiodarone↗

Comparison of biliary excretion of iodothyronines after intravenous and intraduodenal administration of various doses of T4 and T3.

Intraduodenal 10 or 40 micrograms thyroxine (T4) and 5 or 10 micrograms triiodothyronine (T3) or i.v. bolus of 2, 4 or 8 micrograms T4 or infusion of 10 micrograms T4 within 2 h were administered to groups of 3 to 5 rats. All experiments were made under pentobarbiturate anesthesia and administration of heparin and changes of several iodothyronine levels in plasma and of their biliary excretion were measured with the aid of specific radioimmunoassay. About 1 to 4 per cent of administered T4 were found in bile within 4 h. From this it was concluded that hepatic clearance of T4 does not increase significantly under nearly physiological levels of this hormone in plasma and that, under such conditions, a majority of absorbed or administered T4 is distributed and utilized within the whole body rather than excreted by bile. In addition, several changes of the level of various iodothyronines in plasma and of their excretion by bile as related to the administered doses of T4 and T3 were described.

Animals↗

In vivo study of iodothyronine deiodination in rat liver: effect of salicylate on biliary excretion of several iodothyronines.

Biliary excretion of total (i.e. conjugated plus unconjugated) thyroxine (T4), 3,5,3'-triiodothyronine (T3), 3,3',5'-triiodothyronine (rT3), 3,5-diiodothyronine (3,5-T2), 3,3'-diiodothyronine (3,3'-T2) and 3',5'-diiodothyronine (3',5'-T2) was measured with the aid of specific radioimmunoassay in 17 control rats and in 31 rats injected sodium salicylate i.v. (200 mg kg-1). The animals were anesthetized with pentobarbiturate and the samples of bile were taken in subsequent 2 h periods from a drained bile duct. In controls a gradual decrease of excretion of all compounds measured was found during 10 h observation period. In contrast, after salicylate injection a transient increase of total bile volume and of T4, T3 and 3,5-T2 excretion was observed followed by a remarkable decrease, while a multifold and prolonged increase of the excretion of rT3, 3,3'-T2 and 3',5'-T2 was found. These data suggest an acute and remarkable effect of salicylate on T4 deiodinating pathway in the liver.

Animals↗

Direct quantitative estimation of several iodothyronines in rat bile by radioimmunoassay and basal data on their biliary excretion.

A method was developed for the hydrolysis of conjugated iodothyronines in bile with the aid of beta-glucuronidase/arylsulfatase and for subsequent direct estimation of total and free iodothyronines with the aid of specific radioimmunoassay. The amount of conjugated fraction could then be calculated from the difference. Thus, basal biliary excretion of several iodothyronines was measured in 31 normal, fed rats in which the bile duct was drained with polyethylene tubing under pentobarbiturate anesthesia and the bile was collected for 2 h. The free fraction of thyroxine, 3,5,3'-triiodothyronine and 3,3'-diiodothyronine was approx. 30% of total content, while that of 3,3',5'-triiodothyronine and 3,5-diiodothyronine was approx. 20% and that of 3',5'-diiodothyronine was less than 10%. This suggests some considerable differences in the conjugation of individual iodothyronines in the liver. The concentration of T4 in bile was about the same as in plasma, while that of other iodothyronines was about 3-8 times higher than in plasma. This shows close interrelations between the iodothyronine deiodinating pathway in liver cells in vivo and the spectrum of iodothyronine in bile. The average ratio of T3/rT3 as found in bile was about 4.

Animals↗

Preliminary observations on the absorption of biliary iodothyronines from the intestine in vivo in rats.

From a drained bile duct of the rats injected i. v. with various doses of L-thyroxine (50 to 200 microgram per animal) bile was obtained which was then injected to various parts of intestine in recipient rats. The recipient animals were anesthetized with pentobarbiturate and their bile duct as well as femoral artery and vein were cannulated with polyethylene tubings. The level of thyroxine (T4), 3,5,3'-triiodothyronine (T3) and 3,3',5'-triiodothyronine (rT3) in plasma and biliary excretion of these compounds was estimated by specific radioimmunoassay, the samples of plasma and bile being taken up to 4 h after the administration of donor bile. In one experiment also concentration of three different diiodothyronines (e.e. 3,5-T2, 3,3'T2 and 3',5'T2) in recipient bile was measured. A dose dependent increase of T4 excretion was fond in recipient bile. In some experiments also an increase of 3,3'-T2 and 3',5'-T2 excretion was observed and a higher ratio between the excreted and administered amount of rT3 was found than that of T3. An increase of T4 level in plasma was also directly related to the administered dose of this compound, while the increase of T3 and rT3 under the conditions used was observed only in some experiments where relatively higher doses of these substances were administered. It was also observed that the absorption of T4 from the administered bile was higher in fed than in fasted animals.

Animals↗

Immediate opposite effect of salicylate on thyroxine and 3,5,3'-triiodothyronine versus 3,3',5'-triiodothyronine level in plasma in rats.

In a total of 46 male rats polyethylene tubings were introduced into femoral artery and vein under pentobarbiturate anesthesia. Then heparin (300 U kg-1) was injected at 60-90 min after pentobarbiturate and two control blood samples were subsequently taken. After that sodium salicylate (200 mg kg-1) was injected i.v. and blood samples were taken at 30-420 min later. An immediate decrease of the thyroxine (T4) level in plasma to about 20% of original level and that of 3,5,3'-triiodothyronine (T3) to about 60% of that was found, while the level of 3,3',5'-triiodothyronine (rT3) was increased 20%. It was concluded that the administration of salicylate results in an immediate displacement of T4 and T3 from plasma protein binding and possibly inhibits the conversion of T4 to T3 and of rT3 to 3,3'-diiodothyronine which results in an increase of rT3 level in plasma. This might by partially prevented by an inhibiting effect of salicylate on the binding of rT3 to plasma proteins.

Animals↗