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Biomedical subjects

P Langer

Publications and source records attributed to P Langer.

At least 145 records · Page 8Linked to original sources

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↗

Pituitary-thyroid function during acute immobilization stress in rats.

In nine experiments a total of 394 male Wistar rats weighing about 300 g was used. In each experiment, one intact control group was used and several other groups were subjected to immobilization (IMO) for 2 to 240 min in a prone position by inserting their heads through steel wire loops fixed on a board and by fasting their limbs to four metal strips by adhesive tape. All animals were killed by decapitation and the levels of thyrotropin (TSH), thyroxine (T4), 3,5,3'-triiodothyronine (T3) and 3,3',5'-triiodothyronine (rT3) in plasma were estimated by radioimmunoassay. In one experiment, significant changes in the level of all hormones measured were found within 2 to 15 min of IMO, e.g. an increase of TSH, T4 and rT3 and a decrease of T3. Later (i.e. between 30 and 240 min) the level of TSH, T4 and T3 was repeatedly found to be significantly decreased almost in all experiments as compared to controls. In contrast, a significant increase of rT3 was found only in one out of 7 experiments, the values in other ones being unchanged. Corresponding changes of hormone levels were observed when IMO for 150 min was repeated daily for 7 or 40 days and the animals were sacrificed immediately after the last stress, while one day of rest after such procedures as well as after a single IMO for 150 min appeared to be sufficient for the levels to return to control values.

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↗

Nanosecond flash photolysis study of carbon monoxide binding to the beta chain of hemoglobin Zürich [beta 63(E7)His leads to Arg].

Binding of carbon monoxide to beta chains of hemoglobin Zürich has been studied by flash photolysis over the time range of nanoseconds to seconds at temperatures from 20 to 300 K. From 20 to 200 K a single rebinding process (process I) is seen, characterized by a distribution of barrier heights with a peak enthalpy of 2.3 kJ/mol. Above 200 K some ligands escape from the pocket into the matrix, and above 260 K recombination from the solvent sets in. Process I is visible up to 300 K, but above 200 K its rate remains essentially constant at about 4 X 10(8)s -1. Above about 250 K, process I is exponential in time, indicating rapid conformational relaxation. The results are discussed within the framework of a sequential model for ligand binding.

Arginine↗

Acute and transient activation of pituitary-thyroid axis during unforced restriction in rats: component of nonshivering thermogenesis in conscious animals?

Groups of 6-8 male Wistar Olac SPF rats weighing about 300 g were subjected to unforced restriction (UR) in small cages with a metallic bottom and a Plexiglas cover for various intervals from 2 min to 72 h. An acute activation of the pituitary-thyroid axis was found which was manifested by an increase of thyrotropin (TSH) and thyroxine (T4) levels at 2-5 min of UR. This was presumably due to the emotional effect of a rapid transfer and to the placing of the animals into restriction cages. Later, between 3 and 6 h of UR, another, and more pronounced period of activation of the pituitary-thyroid axis and of the peripheral thyroid hormone metabolism was repeatedly observed which lasted until about 36-48 h and was manifested by a highly significant increase of TSH, T4, 3,5,3'-triiodothyronine (T3) and 3,3',5'-triiodothyronine (rT3) levels. It was concluded that this phenomenon presumably may be a component of nonshivering thermogenesis resulting from a decreased muscular activity and resembling the conditions occurring under cold stress. Such a view was supported by findings of highly increased nonesterified fatty acid levels in plasma in restricted animals, by unchanged levels of TSH and thyroid hormones found in unrestricted animals kept individually in regular group cages and, finally, by a preventive effect of ambient temperature of 32 degrees C on the pituitary-thyroid activation at 6 h of UR. In some experiments, no substantial differences in hormone levels were found between the animals kept in Plexiglas or stainless wire-mesh restriction cages. Finally, a multifold increase of prolactin level in plasma was found as early as 2 min of UR, the peak being observed between 5 and 20 min and a decrease to about the initial level at about 360 min.

Animals↗

Immediate increase of thyroid hormone release during acute stress in rats: effect of biogenic amines rather than that of TSH?

An increase of thyroxine (T4; 36% in average) and 3,5,3'-triiodothyronine (T3; 9% in average) levels in plasma was found in rats after 2 min of immobilization stress (IMO), while later (from 5 to 240 min of IMO) the level of both hormones decreased sharply. This increase was prevented by ip injection of phenoxybenzamine (4 or 16 mg kg-1), prazosin (2.5 mg kg-1), yohimbin (4 or 16 mg kg-1) and fluoxetine (10 mg kg-1) at 60 min before IMO, but similar injections of phentolamine (4 or 16 mg kg-1), tolazoline (4 or 16 mg kg-1), methysergide (10 mg kg-1), cyproheptadine (10 mg kg-1) as well as of lower doses of prazosin (0.6 or 1.2 mg kg-1) did not show such an effect. The level of TSH was increased after 2 min IMO too, but this was considered to be a separate phenomenon from the increase of T4 and T3, since in several groups injected with some of the above drugs the level of TSH was decreased together with increased levels of T4 and T3. It is suggested that the acute release of thyroid hormone might be due to the effect of biogenic amines which may be blocked by some alpha-adrenergic blocking agents. Since neither adrenalectomy nor adrenal-medullectomy prevented such a release, it may be concluded that circulating catecholamines of adrenal origin did not play any role in this process.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗

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↗

A Teorell oscillator system with fine pore membranes.

A Teorell membrane oscillator system has been investigated theoretically and experimentally. Instead of the broad pore (e.g., glass sinter) membranes used by Teorell and other investigators, we used membranes of a hydrodynamic permeability lower by factor of 10(3)-10(5) and a fixed ion concentration higher by a factor of 10(2)-10(5). A system with such membranes was thought to be a more adequate analogue of excitable biological tissues (for which the Teorell oscillator had been presented as a model). Stationary state voltage-current curves were recorded, and flip-flops were only found in membranes whose hydrodynamic permeability was above a certain value. A theoretical description, agreeing closely with the experimental findings, is given in terms of the Nernst-Planck-Schlögl equations; flip-flops are predicted only if the hydrodynamic permeability is above the fixed ion concentration is below a critical value. These values depend on the hydrostatic pressure and on the ratio of the cation and anion diffusion coefficient in the membrane, and they are found to be far beyond (approximately 3 orders of magnitude) the data for membranes used by others in similar experiments. Although our theoretical analysis demonstrates that the Teorell mechanism is ineligible as a source of excitability in those biological systems for which sufficient data ate available to permit comparison, the membrane properties for which the theory predicts flip-flops are such that it cannot be excluded a priori.

Electric Conductivity↗

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↗

Changes of iodothyronine levels in plasma after acute and long term hypokinesia (unforced restriction) in rats.

Groups of 8 rats each were subjected to hypokinesia (unforced restriction) in plexiglass cages for 1, 5 and 9 days in first experiment and groups of 10 rats each were subjected to 1, 5, 14 and 60 days of hypokinesia in a second experiment. In addition, in a second experiment two groups of 10 animals were subjected first to hypokinesia for 60 days and then kept in regular group cages for 7 and 21 days, respectively. In each experiment a control group was used which was not subjected to restriction. Each animal was decapitated at the appropriate interval and the level of thyroxine (T4), 3,5,3'-triiodothyronine (T3) and 3,3',5'-triiodothyronine (rT3) was measured with the aid of radioimmunoassay. Most remarkable changes appeared on the first day of hypokinesia when significantly increased levels of TR and T3 were found in both experiments. In a second experiment the level of T4 was significantly decreased in all groups but that restricted for 1 day. No changes of T3 level were found with the exception of the above described increase in the first day, while the levels of rT3 showed irregular and inconsistent changes. A hypothesis was tested whether the increased T4 and T3 levels result from a decreased fecal excretion of these compounds due to presumably increased food intake during the first day of hypokinesia, but it was found that the intake of food and water on the first day was the same as on subsequent days. Thus, the mechanism of the observed changes remains to be further studied.

Animals↗

Effects of open-heart surgery on thyroid hormone levels.

The effect of heart surgery with and without cardiopulmonary by-pass on plasma levels of thyroxine (T4) and triiodothyronine (T3) was studied in 19 patients. It was found that even before the operation the plasma levels of T4 and of T3 were significantly lower in the by-pass group of patients in comparison with those without by-pass. This lower level of thyroid hormones could be explained by greater pre-operative stress. This presumption is supported by the finding of the greater pre-operative plasma concentrations of dopamine-beta-hydroxylase and growth hormone in patients of the by-pass group. While in patients not undergoing CPB a tendency to the decrease of plasma thyroid hormones was observed during the early postoperative phase, in patients of the by-pass group a small increase was observed. On the basis of the finding that thyroid hormones exercise powerful and specific effect on myocardial contractility, it is suggested that the low hormone level might have a role in the pathogenesis of postoperative low cardiac output syndrome.

Adult↗