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Biomedical subjects

G Hennemann

Publications and source records attributed to G Hennemann.

At least 19 recordsLinked to original sources
PubMed1992

Transport of 3,5,3'-triiodothyronine into the perfused rat liver and subsequent metabolism are inhibited by fasting.

The effects of 48-h fasting on transport of T3 and subsequent metabolism in the isolated perfused rat liver were investigated. Tracer T3 disappearance curves from the recirculating medium consisted of a fast component (FC) and a slow component (SC). Using a two-compartment model, both transport [expressed as the fractional transport rate constant from medium to liver (k21)] and disposal of T3 were calculated. After fasting, k21, total metabolism, and metabolism corrected for differences in mass transfer were diminished, pointing to both decreased transport and metabolism, presumably caused by depletion of liver ATP. Concerning transport, it was shown that only transport into the intracellular liver compartment and not transport to the extracellular liver compartment was decreased after fasting. As for metabolism, T3 glucuronidation was diminished; T3 sulfation and subsequent deiodination were not affected. All mentioned decreased parameters normalized after the addition of a combination of insulin, cortisol, and/or glucose to the medium, possibly by (partially) restoration of cellular energy stores.

Adenosine Triphosphate↗
PubMed1991

Euro-Collins solution versus UW-solution for long-term liver preservation in the isolated rat-liver perfusion model.

To compare UW-solution (UW) and Euro-Collins (EC) for long-term liver preservation we investigated the morphology and metabolic capacity of rat liver after 18 and 42-hours cold-storage in either UW or EC. After harvesting the rat liver was transferred to a perfusion chamber where it was perfused for 10 min with UW or EC at 4 degrees C. Thereafter livers were stored at 4 degrees C in UW or EC for 18 hours (both groups n = 6) or for 42 hours (both groups n = 8). After 18-hr or 42-hr cold-storage a 2-hr warm perfusion (37 degrees C) was started with Krebs-Ringer solution with carbogen to which 125Iodine-triiodothyronine (T3) was added. Control livers (n = 8) were immediately perfused with Krebs-Ringer without cold-storage. The following parameters were assessed: ASAT-levels in the perfusate, T3-metabolites in the bile and the perfusate, the perfusion pressure, the volume of bile secreted and light-microscopical morphology at the end of the warm perfusion period. After cold storage in UW-solution the ASAT-levels in the perfusate were lower than after storage in EC as well as the perfusion pressures. These livers demonstrated a better T3-metabolism and secreted more bile than EC-stored livers. Histological examination showed more tissue damage in the EC-stored livers than in the UW stored livers. We conclude that cold-storage of rat liver in UW-solution resulted in a better morphology and metabolic capacity as compared with EC-solution.

Adenosine↗
PubMed1991

Thyroxine and 3,3',5-triiodothyronine are glucuronidated in rat liver by different uridine diphosphate-glucuronyltransferases.

Male Wistar rats were treated with 50 mg 3,3',4,4'-tetrachlorobiphenyl (TCB)/kg BW or vehicle. After 4 days, the livers were isolated and perfused for 90 min with 2 nM [125I]T3 or 10 nM [125I]T4 in Krebs-Ringer medium containing 1% albumin. Deiodination and conjugation products and remaining substrates were determined in bile and medium samples by Sephadex LH-20 chromatography and HPLC. TCB treatment did not affect hepatic uptake and metabolism of T3. However, biliary excretion of T4 glucuronide was strongly increased by TCB, resulting in an augmented T4 disappearance from the medium, although initial hepatic uptake of T4 was not altered. Measurement of the microsomal UDP-glucuronyltransferase (UDPGT) activities confirmed that T4 UDPGT was induced by TCB, whereas T3 glucuronidation was unaffected. T3 UDPGT activity showed a discontinuous variation, which completely matched the genetic heterogeneity in androsterone glucuronidation in Wistar rats. These results indicate that different isozymes catalyze the glucuronidation of T3 and T4.

Animals↗
PubMed1990

Development and use of a mathematical two-pool model of distribution and metabolism of 3,3',5-triiodothyronine in a recirculating rat liver perfusion system: albumin does not play a role in cellular transport.

To describe the T3 kinetics in a recirculating rat liver perfusion system, we have developed a mathematical two-pool model consisting of medium and liver. It appeared that all parameters of the model could be fully resolved by using the time-dependent disappearance of radioactive T3 (2 nM) from the medium only. The model calculates the T3 medium pool, the T3 liver pool, and the amount of hormone metabolized at different times after the start of the perfusion. To check the validity of the model, metabolism was also estimated from the appearance of labeled metabolites (glucuronides, sulfates, and I-) in the medium and the cumulative excretion of T3 and metabolites into the bile. The medium pool was also estimated by the product of medium volume and remaining T3 concentration, and the liver pool as the amount of T3 at time zero minus medium pool minus T3 metabolized). These results were in excellent agreement with the predicted values from the model. Taking the metabolites appearing in medium and bile together, about 38% of the total amount of T3 metabolized during 60 min was converted into T3 glucuronide, 12% into T3 sulfate, and 48% into I-, respectively, while about 3% was excreted in the bile unaltered. The results show that not all T3 transported to the liver is being metabolized, but part is bound outside the cellular compartment. This latter pool of T3 is dependent on the albumin concentration in the medium. The amount of T3 metabolized is solely determined by the free T3 concentration and is independent of total T3 or albumin concentration in the medium.

Animals↗
PubMed1989

Congenital hypothyroidism and partial thyroid hormone unresponsiveness of the pituitary in a patient with congenital thyroxine binding albumin elevation.

We describe a girl who presented at the age of 6 weeks with cardiogenic shock due to congenital hypothyroidism (serum thyroxine (T4) less than 12 nmol/l). Thyroxine replacement therapy was instituted. In spite of high total serum T4 levels, thyroid stimulating hormone (TSH) serum values remained elevated. The raised serum T4 levels were the result of congenital elevation of thyroid binding albumin (TBA). Toxic doses of both T4 and triiodothyronine (T3) normalized the elevated TSH levels indicating that the pituitary is responsive to thyroid hormone, albeit at a higher threshold. In patients with congenital TBA elevation and an altered T4 pituitary response requiring thyroid replacement therapy, the measurement of serum free T4 levels is the parameter of choice to monitor treatment.

Congenital Hypothyroidism↗
PubMed1988

Three-compartmental analysis of effects of D-propranolol on thyroid hormone kinetics.

Tracer thyroxine (T4), 3.3',5-triiodothyronine (T3), and 3,3',5'-triiodothyronine (rT3) kinetic studies were performed in normal T4 substituted subjects before and during oral D-propranolol treatment to determine whether changes in thyroid hormone metabolism in a propranolol-induced low-T3 syndrome result from inhibition of 5'-deiodination or inhibition of transport of iodothyronines into tissues. Data were analyzed according to a three-compartmental model of distribution and metabolism. T4 plasma appearance rate decreased by 16% (P less than 0.01), reflecting a decreased intestinal absorption of orally administered T4 during propranolol. Serum T4 and free T4 levels increased significantly by 14%, whereas T4 metabolic clearance rate (MCR) was lowered by 26% (P less than 0.001). No changes were observed in size of the three T4 compartments or in fractional and mass transfer rates of T4 from plasma to the rapidly (REP) and slowly (SEP) equilibrating pools. Serum T3, free T3, T3 plasma pool, T3 mass transfer rate to REP and SEP, and the T3 pool masses were all significantly decreased during propranolol to a similar extent as the T3 plasma production rate (PR). T3 MCR decreased by 14% (P less than 0.05). Serum total and free rT3 increased, whereas the rT3 MCR was substantially lowered during propranolol (P less than 0.001). The rT3 plasma pool, rT3 REP and SEP, and the mass transfer rates to REP and SEP increased, whereas no alterations were observed in rT3 PR and fractional transfer rates of rT3 to REP and SEP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Inhibition of uptake of thyroid hormone into rat hepatocytes by preincubation with N-bromoacetyl-3,3',5-triiodothyronine.

To investigate whether affinity coupling of N-bromoacetyl-T3 (BrAcT3) to the T3 membrane carrier results in an inhibition of transport of T3 into the cell, rat hepatocytes in monolayer were incubated for 2 h at 21 C with 1.3 mumol/liter BrAcT3 in medium without protein. After extensive washing, cells were incubated during 20 h at 37 C with [125I]T3 in medium with 0.5% BSA, and products in supernatants were analyzed by LH-20 column chromatography. In addition the apparent affinity constant (Km) and maximal uptake velocity (Vmax) of the high affinity uptake process were estimated using 1 min incubations of hepatocytes with various concentrations of T3. In control experiments (i.e. without BrAcT3 affinity coupling) about 57% of the added T3 was cleared from the medium and further metabolized, 85% of the cleared T3 reappeared in the medium as I-, 15% as conjugates. Addition of propylthiouracil during the 20 h incubation with T3 strongly inhibited deiodination, without a change in T3 clearance. Because T3 is sulfated before deiodination, a concomitant rise in conjugates was observed. Addition of ouabain to control cells during the 20 h incubation with T3 strongly inhibited uptake, with a parallel decrease in I- and conjugate formation. After affinity coupling of BrAcT3, T3 clearance was inhibited (by 30% P less than 0.001). Since I- production was more depressed (by 73%) than T3 clearance, with some rise in conjugate formation (P less than 0.001), inhibition of deiodinase by BrAcT3 also took place. The effects of BrAcT3 and ouabain on uptake of T3 appeared to be additive as were the effects of propylthiouracil and BrAcT3 on deiodination. After affinity coupling of BrAcT3, the Km of T3 uptake did not change significantly; however Vmax was 54% lower (P less than 0.025) indicating a noncompetitive inhibition of the transport system. Preincubation of the cells with N-acetyl-T3 does not alter the characteristics of uptake of T3 by rat hepatocytes as compared to controls, indicating that no binding of this compound occurs. It is concluded that preincubation of hepatocytes with BrAcT3 diminished I- formation from T3; 50% of this inhibition is due to decreased membrane transport and 50% by reduction of deiodination. Inhibition of membrane transport by BrAcT3 is substantiated by a 54% lower Vmax without a significant change in Km as compared to control. The effect of transport of thyroid hormone on metabolism stresses the importance of the membrane carrier in the translocation process.

Affinity Labels↗
PubMed1988

Causes and effects of the low T3 syndrome during caloric deprivation and non-thyroidal illness: an overview.

The increased serum reverse T3 and decreased T3 during caloric deprivation and non-thyroidal illness is caused by decreased T3 production (with intact degradation) and reversed T3 degradation (with intact production) respectively. These changes can ensue from two mechanisms i.e. decreased 5'D of T4 and of reverse T3 (possibly caused by a decrease in naturally occurring reducing agents) or by decreased transport of T4 and reverse T3 into the liver (possibly caused by decreased ATP concentrations in the liver). The effects of the low T3 syndrome at the tissue level are in many instances comparable to those seen in hypothyroidism. The effects lead to conservation of energy and decrease of protein breakdown. These effects are considered to constitute a beneficial adaptative mechanism in situations in which the organism is endangered. There is no evidence that treatment of patients with the low T3 syndrome with thyroid hormones is of any benefit. Knowledge at the present moment suggests that administration of thyroid hormones during caloric deprivation or non-thyroidal illness should be avoided.

Food Deprivation↗
PubMed1987

Cellular and humoral immunity in patients with hyperthyroid Graves' disease before, during and after antithyroid drug treatment.

Many reports of thyroid stimulating immunoglobulins (TSI) in relation to treatment of Graves' disease have been published and with variable results concerning prediction of permanent remission or relapse after therapy. A range of methods has been used and little has been published measuring TSI by using their ability to stimulate cyclic AMP production in human thyroid cells in monolayer culture. We therefore conducted a prospective study of the predictive value of such an assay in patients with hyperthyroid Graves' disease before, during and after treatment of one year with methimazole and thyroid hormone substitution. Furthermore, the possible relationship between activated suppressor T lymphocytes and TSI in patients followed before, during and after medical therapy has been studied. Patients were divided into two groups; group I, 15 patients, who stayed in remission and group II, 14, who relapsed during the first year after discontinuation of therapy. Mean TSI activity did not differ between the two groups before and during the first half year of medication. In the second half year of treatment, however, mean TSI activity was significantly lower in group I. TSI activity at the end of treatment appeared to have no value in predicting final outcome. Increased TSI activity in group II during treatment was reflected in an increased pertechnetate thyroidal uptake as compared to that in group I. There was no relationship between changes in TSI activity and T cell subsets (Leu 1, 2a, 3a). We found no difference in T lymphocytes between the two groups at any time during observation. Subsets of T lymphocytes in both patient groups did not differ from normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1987

Pitfalls in the interpretation of thyroid function tests in old age and non-thyroidal illness.

In hyperthyroidism, measurement of the serum thyroxine (T4) index or free concentration often suffices to establish the diagnosis. In hyperthyroidism, including 3,3',5-triiodothyronine (T3) toxicosis, thyrotrophin (TSH) response to thyrotrophin-releasing hormone (TRH) is blunted. Sensitive measurement of serum TSH may in the future be the first-line screening test not only for primary hypothyroidism but also for hyperthyroidism. In non-thyroidal illness serum T4, reverse T3 and T3 levels change in relation to severity of disease. In mild disease, T4 is initially increases as the severity of the non-thyroidal illness increases. Reverse T3 increases and serum T3 decreases when the patients become more ill. Serum TSH response to TRH is often blunted. In old age similar changes in serum iodothyronine concentrations may take place, probably related to existing non-thyroidal illness. Also many drugs may have different effects on serum parameters of thyroid function. In acute psychiatric diseases increased serum total and free T4 levels and a blunted TRH test may be encountered.

Aged↗
PubMed1987

Active transport of iodothyronines into human cultured fibroblasts.

Thyroid hormone uptake into human cultured fibroblasts was studied using 2-min incubations with labeled iodothyronines. The results indicate the presence of an active T4 uptake process with two saturable sites with apparent Km values of 1.9 and 141 nM, respectively, and an active T3 uptake process with two saturable sites with Km values of 29 and 650 nM. The uptake of both hormones was energy dependent, i.e. inhibited by KCN or by incubation of the cells in the absence of glucose. By analogy with similar findings in rat hepatocytes we postulate that the high affinity systems represent active transport of thyroid hormone into the cell. Preincubation of the cells with 2 mM ouabain resulted in a decrease in the uptake of both T3 and T4, suggesting that a sodium gradient is necessary for transport. Similar to that in rat hepatocytes, uptake of T3 was inhibited by high concentrations of T4, and uptake of T4 was inhibited by high concentrations of T3. These data indicate that regulation of thyroid hormone uptake at the level of the plasma membrane may be operative in humans.

Biological Transport, Active↗
PubMed1987

Handling of iodothyronines by the liver and kidney in patients with chronic liver disease.

Possible arterio-venous gradients of T4, T3, rT3 and 3,3'-diiodothyronine (3,3'-T2) across the liver and the kidneys were measured in 9 patients with varying degrees of liver failure undergoing diagnostic catheterization. Plasma iodothyronine levels were measured in peripheral, hepatic and renal veins before and at 10-min intervals until 60 min after iv injection of 400 micrograms of TRH. In 2 patients estimated hepatic plasma flow and effective renal plasma flow were determined as well. In these 2 patients, no significant differences between iodothyronine levels in arterial and peripheral venous plasma were found. T4 and T3 levels were not significantly different between peripheral, renal and hepatic veins. Hepatic vein rT3 and 3,3'-T2 concentrations were 10.7 +/- 8.3% (mean +/- SD, P less than 0.005) and 36 +/- 18% (P less than 0.001) lower than those in the peripheral vein (N = 9). Renal vein rT3 was just (6.2 +/- 7.5%, P less than 0.05) lower than rT3 in peripheral vein, whereas 3,3'-T2 was not different between the two veins. Estimates of hepatic and renal plasma flow were in agreement with values from the literature. On the basis of these data approximate hepatic clearance rates of 110 and 380 1/day for rT3 and 3,3'-T2 and a renal clearance rate of about 35 1/day for rT3 were calculated. Sixty min after TRH, plasma T3 was increased to 147 +/- 56% (P less than 0.05) and 3,3'-T2 in peripheral plasma was increased to 142 +/- 36% (P less than 0.025), whereas plasma T4 and rT3 did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗