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Biomedical subjects

A G Burger

Publications and source records attributed to A G Burger.

At least 19 recordsLinked to original sources
PubMed1992

Thermic effect of epinephrine: a role for endogenous insulin.

The contribution of the basal insulin concentration to the metabolic response to epinephrine was measured in eight, postabsorptive, healthy volunteers before and during epinephrine (0.05 micrograms/kg fat-free mass [FFM] x min) and somatostatin (500 micrograms/h) infusion with and without insulin (0.1 mU/kg body weight [BW] x min) replacement. At basal plasma insulin concentrations, epinephrine increased oxygen consumption, heart rate, heart work, hepatic glucose production, glycogen breakdown in liver and muscle, and glucose oxidation, and the arterial plasma concentrations of glucose, lactate, and free fatty acids. Similar effects were observed during hypoinsulinemia, but epinephrine's actions on oxygen consumption and plasma concentrations of free fatty acids were disproportionally enhanced. We conclude that epinephrine-induced thermogenesis is partially inhibited by basal plasma insulin concentrations.

Adult↗
PubMed1992

Thyroid emergencies.

Thyroid storm is a rapid decompensation of severe hyperthyroidism which can best be described by the three criteria of hyperthermia, tachycardia and altered mental state with severe agitation. There has to be a precipitating factor such as infection, iodine contamination, surgery or even I-131 treatment. Severe hyperthyroidism not fulfilling the criteria of thyroid storm can also be an indication for emergency treatment, particularly in the elderly with heart disease. Suppressed serum TSH and elevated free T4 levels are essential to confirm the diagnosis. When rapidly available, radioiodine uptake of the thyroid can be useful. Therapy aims at rapidly reducing the active circulating hormone pool, hypermetabolic state, tachycardia, and finally hormone synthesis. Thyroid secretion can be blocked by ioipanoic acid or ipodate while hypermetabolic state can be reduced with beta-blockers or calcium channel-blockers. Treatment of hyperthyroidism in patients with iodine contamination is a real therapeutic challenge. Myxoedema coma, a complication of severe hypothyroidism, is defined by hypothermia (rectal temperature less than 36 degrees C), bradycardia, slow mentation, precipitating factor such as infection or drug overdose, and increased serum creatine phosphokinase levels. Diagnosis of severe hypothyroidism should be confirmed by serum measurements of TSH and free T4. Treatment consists of general supporting measures including rewarming, correction of serum electrolyte disturbances, and adequate alimentation. Thyroid hormone treatment should initially be aggressive using either 300-400 micrograms of T4 or 20-40 micrograms of T3 intravenously. Cortisone therapy may be added. Patients should be under close monitoring as arrhythmias and myocardial infarction are frequent complications of myxoedema coma and/or its treatment with thyroid hormones.

Acute Disease↗
PubMed1992

Effects of thyroxine, triiodothyronine and reverse triiodothyronine on the neonatal hypothyroid rat cerebellum.

In order to develop a model of thyroid hormone action, we studied the effect of small doses of T3 and T4 on the development of the hypothyroid neonatal cerebellum of rat pubs. Using granulosa cell death at postnatal d15 (picnotic index) as a criterion of hypothyroidism, it was found that a single injection of 50 ng T3/10g bw or 180 ng T4/10 g bw would reduce the picnotic index to levels found in euthyroid rat cerebelli. We further tested if rT3, known to be an excellent blocker of deiodinase type 2 activity, would be able to block the effects of T4. 20 micrograms rT3/10g bw had to be given to be an effective inhibitor in vivo. This dose did not affect the potency of T4 and control experiments with rT3 alone indicated that rT3 was capable of reducing the picnotic index to euthyroid levels. It is speculated that rT3 might act at the nuclear receptor but also at the cell membrane.

Animals↗
PubMed1991

The effect of short term feeding of the antioxidant triethyleneglycol-bis-3(3-tert-butyl-4-hydroxy-5-methyl)propionate on serum thyrotropin and thyroid hormones in the male rat.

Male rats were fed triethyleneglycol-bis-3(3-tert-butyl-4-hydroxy-5-methyl)propionate (TK 12627) admixed with the food at a concentration of 1000 ppm for 3, 6, 13, and 20 days. Treatment resulted in time-dependent and marked increases in serum levels of thyrotropin (TSH) and reverse triiodothyronine (rT3). Serum levels of thyroxine (T4) were slightly and transiently decreased, whereas triiodothyronine (T3) levels decreased by 35-50% at all time periods. Treatment with 50, 150, 500, and 1000 ppm for 2 weeks resulted in dose-related increases in thyroid and liver weights, follicular hypertrophy of the thyroid, morphological changes of the pituitaries, liver hypertrophy, and similar changes in the serum parameters described above. At 50 ppm, no alterations in the weights and morphology of the liver, thyroid, or pituitary nor in the serum levels of TSH or T4 were observed. The effects of TK 12627 observed at a dose of 1000 ppm for 2 weeks were reversible after cessation of treatment. Decreases in T3, increases in rT3, and no change in T4 serum levels were also obtained when thyroidectomized T4-substituted rats were treated with 1000 ppm TK 12627 for 28 days, indicating that the effects of TK 12627 are probably due to inhibition of the 5' monodeiodination of T4 to T3 and rT3 to diiodothyronine with compensatory increases in thyroid hormone conjugation at extrathyroidal sites.

Animals↗
PubMed1991

Intracellular calcium and phospholipid turnover are not involved in the inhibition of iodothyronine 5'-deiodinase type II activity by T4.

In glial cell cultures, iodothyronine 5'-deiodinase type II is stimulated by dibutyryl cAMP. Serum-free medium increases enzyme activity and prolongs the half-life of the enzyme. T4 and rT3 specifically inhibit this activity. We tested whether enzyme inactivation by T4 was mediated by changes in cytosolic free calcium concentration and/or phospholipid turnover. Intracellular calcium concentration was decreased either by chelation of extracellular calcium or by chelation of extracellular and intracellular calcium. Neither basal hypothyroid 5'-deiodinase activity nor its inactivation by T4 were modified in such experimental conditions, compared with control cells incubated in normal calcium-containing medium. T4 by itself had no effect on the cytosolic free calcium concentration for up to 20 min. Studies on phospholipid turnover included norepinephrine in parallel to T4 as positive stimulation control. While norepinephrine clearly accelerated phosphoinositide turnover, there was no effect of T4 on any phospholipid turnover. These results suggest that neither cytosolic free calcium nor phospholipid turnover is involved in T4-dependent modulation of 5'-deiodinase type II activity in astrocytes in culture.

Animals↗
PubMed1990

[A papovavirus-like infection in parakeets].

Several potential causes of disease were detected in young as well as in full-fledged parakeets of several species in an outbreak of disease on a parakeet-breeding farm. Both papovavirus and Absidia sp. were isolated; the drinking water contained a toxic level of nitrates. The pathological findings are presented and the possible role of the various findings in the pathogenesis of the disease complex is discussed.

Animals↗
PubMed1990

Evidence that hyperglycaemia per se does not inhibit hepatic glucose production in man.

The effect of hyperglycaemia on hepatic glucose production (Ra) was investigated in nine healthy men using sequential clamp protocols during somatostatin infusion and euglycaemia (0-150 min), at plasma glucose levels of 165 mg x dl-1 (9.2 mM, 150-270 min) and during insulin infusion (1.0 mU x kg-1 x min-1, 270-360 min) in study 1 or during hypo-insulinaemia and plasma glucose levels of 220 mg x dl-1 (12.2 mM; 270-390 min) in study 2. Somatostatin decreased Ra and glucose disposal rate (Rd) but increased plasma free fatty acids (FFA) and lipid oxidation during euglycaemia. Increasing plasma glucose to 165 mg x dl-1 (9.2 mM) and hypo-insulinaemia increased Rd, but no suppressive effects on Ra, plasma FFA and lipid oxidation were observed. By contrast hyperinsulinaemia (study 1), as well as a further increase in plasma glucose (study 2), both decreased Ra. However, more pronounced hyperglycaemia increased insulin secretion despite somatostatin resulting in a fall in plasma FFA and lipid oxidation. Our data questions the accepted dogma that hyperglycaemia inhibits Ra independently of insulin action.

Adult↗
PubMed1990

Thyroid hormone action on lipid metabolism in humans: a role for endogenous insulin.

The effects of moderate hyperthyroidism on lipid metabolism were investigated in six healthy subjects before and after thyroxine treatment (300 micrograms/d). T4-treatment increased basal metabolic rate (+8%) and glucose oxidation (+87%), without affecting lipid oxidation, plasma free fatty acids, glycerol, and beta-hydroxybutyrate. During euthyroidism, a hypoinsulinaemic-euglycaemic 150-minute clamp protocol increased energy expenditure (+3%), lipid oxidation (+42%), plasma free fatty acids (+254%), glycerol (+232%), and beta-hydroxybutyrate (+343%), but decreased glucose oxidation (-20%). Similar effects were observed after T4-treatment, but hyperthyroidism induced disproportionate increases in energy expenditure (+7%), plasma glycerol (+310%), and ketone body levels (+436%). We conclude that moderate hyperthyroidism enhances hypoinsulinemia-induced increases in lipolysis, free fatty acid recycling, and ketogenesis without affecting lipid oxidation. Thus basal insulin may camouflage some of thyroid hormone action on lipid metabolism.

3-Hydroxybutyric Acid↗
PubMed1990

Thermogenic effect of thyroid hormones: interactions with epinephrine and insulin.

The interactions between thyroid hormones, epinephrine, and insulin in the regulation of energy expenditure were investigated in a group of healthy young men before and after thyroxine (T4) treatment (300 micrograms/day for 14 days) at basal plasma insulin concentrations and during hypoinsulinemia with and without epinephrine infusion (0.05 micrograms.kg fat-free mass-1.min-1). T4 treatment induced moderate hyperthyroidism and increased resting energy expenditure (RMR). The effect was more pronounced during short-term hypoinsulinemia, but hypoinsulinemia by itself did not influence RMR. Epinephrine infusion caused a significant increase in energy expenditure. The effect was most pronounced at hypoinsulinemia and with T4 treatment. Hypoinsulinemia and T4 treatment were not additive in their effects. We conclude that basal insulin concentrations mask some of the thermogenic effects of thyroid hormones and epinephrine. Thus insulin antagonism may suppress some of the thermogenic actions of thyroid hormones and epinephrine.

Adult↗
PubMed1989

The impact of nutrition on thyroid hormone physiology and action.

In summary, nutritionally directed alterations in thyroid hormone metabolism appear to be adaptive and to serve important protective roles in the overall economy of the body. These adjustments to nutrition are found at practically every level of thyroid regulation, beginning in the CNS and ending with the final action of thyroid hormones in the nucleus of cells. The cellular actions of thyroid hormones modify, and are modified by, as yet poorly understood interrelationships with substrates and other hormones. The level and composition of the energy intake, including whether the organism is in energy balance, are important signals directing these hormonal adaptations.

Energy Metabolism↗
PubMed1989

Glucoregulatory function of thyroid hormones: role of pancreatic hormones.

Glucose metabolism was investigated in humans before and 14 days after 300 micrograms L-thyroxine (T4)/day using a sequential clamp protocol during short-term somatostatin infusion (500 micrograms/h, 0-6 h) at euglycemia (0-2.5 h), at 165 mg/dl (2.5-6 h), and during insulin infusion (1.0 mU.kg-1.min-1, 4.5-6 h). T4 treatment increased plasma T4 (+96%) and 3,5,3'-triiodothyronine (T3, +50%), energy expenditure (+8%), glucose turnover (+32%), and glucose oxidation (Glucox +87%) but decreased thyroid-stimulating hormone (-96%) and nonoxidative glucose metabolism (Glucnonox, -30%) at unchanged lipid oxidation (Lipox). During somatostatin and euglycemia glucose production (Ra, -67%) and disposal (Rd, -28%) both decreased in euthyroid subjects but remained at -22% and -5%, respectively, after T4 treatment. Glucox (control, -20%; +T4, -25%) fell and Lipox increased (control, +42%; +T4, +45%) in both groups, whereas Glucnonox decreased before (-36%) but increased after T4 (+57%). During somatostatin infusion and hyperglycemia Rd (control, +144%; +T4, +84%) and Glucnonox (control, +326%; +T4, +233%) increased, whereas Glucox and Lipox remained unchanged. Insulin further increased Rd (+76%), Glucox (+155%), and Glucnonox (+50%) but decreased Ra (-43%) and Lipox (-43%). All these effects were enhanced by T4 (Rd, +38%; Glucox, +45%; Glucnonox, +35%; Ra, +40%; Lipox, +11%). Our data provide evidence that, in humans, T3 stimulates Ra and Rd, which is in part independent of pancreatic hormones.

Adult↗
PubMed1989

Pharmacokinetics of 3,5,3'-triiodothyroacetic acid and its effects on serum TSH levels.

3,5,3'-triiodothyroacetic acid is an effective inhibitor of TSH secretion in central hyperthyroidism. Serum, 3,5,3'-triiodothyroacetic acid was measured with an RIA preceded by immunoprecipitation. An anti-3,5,3'-triiodothyroacetic acid antibody was obtained in rabbits, using 3,5,3'-triiodothyroacetic acid coupled to hemocyanin and diazotized benzidine as antigen (cross-reactivity with T4, T3, tetraiodothyroacetic acid was 0.2, 1.1, and 5%, respectively). Endogenous 3,5,3'-triiodothyroacetic acid levels could not be detected in 14 euthyroid, 10 hypothyroid and 10 hyperthyroid sera (detection limit 0.055 nmol/l). Kinetic studies were performed in 6 healthy male subjects who received an oral and an iv dose of 1050 micrograms of 3,5,3'-triiodothyroacetic acid. The serum measurements were analysed according to a non-compartmental method. The half-life of 3,5,3'-triiodothyroacetic acid was 6 h 22 min +/- 29 min, the volume of distribution was 114 +/- 9 1/70 kg, and the plasma clearance rate was 298 +/- 141.(70 kg)-1.day-1. Highest 3,5,3'-triiodothyroacetic acid levels were measured after 40 min (for T3 2-3 h) and its absorption was 67 +/- 6%. The nadir of the mean TSH levels was 0.72 +/- 0.09 mU/l 6 h after 3,5,3'-triiodothyroacetic acid administration. However, the time course of serum TSH response did not differ from that obtained after administration of 37.5 micrograms T3. The dose-response effect for TSH was studied using oral doses of 350, 700, 1400 and 2800 micrograms 3,5,3'-triiodothyroacetic acid. TSH was measured 9 h after 3,5,3'-triiodothyroacetic acid administration at 17.00 h, and compared with control serum TSH levels obtained at 08.00 h (1.53 +/- 0.11) and at 17.00 h the day before the test (1.87 +/- 0.11). They were 1.05 +/- 0.15 (N = 9, mean +/- SEM), 0.83 +/- 0.08 (N = 24), 0.66 +/- 0.06 (N = 24), and 0.43 +/- 0.02 mU/l (N = 6), respectively. In conclusion, TSH inhibition by 3,5,3'-triiodothyroacetic acid is similar to T3, with a potency ratio of 1 to 18.

Administration, Oral↗
PubMed1988

Amiodarone alters thyroxine transfer and distribution in humans.

Previous studies indicate that increased serum total and free T4 levels may be secondary to a proportionally greater decrease in serum T4 clearance rates than in production rates after short-term amiodarone administration, to increased T4 production rates as well as reduced serum clearance rates in selective hyperthyroxinemia without overt hyperthyroidism following chronic amiodarone administration, and to a relatively greater increase in T4 production rates than in clearance rates in classical hyperthyroidism. To further evaluate amiodarone-induced alterations of T4 metabolism, serum T4 transfer and distribution were evaluated by compartmental analysis of T4 kinetic studies from eight normal subjects receiving short-term amiodarone or an equivalent amount of iodide, five patients with selective hyperthyroxinemia induced by chronic amiodarone therapy (n = 4) or ioxithalamic acid (n = 1), and five with classical hyperthyroidism. The model consisted of rapidly and slowly equilibrating pools exchanging with serum, with all losses occurring from the tissue pools. Short-term amiodarone administration reduced the fractional T4 transfer rates between serum and the rapidly equilibrating pool to 82% of baseline. In selective hyperthyroxinemia the fractional rates of T4 transfer between serum and both extravascular pools were increased sixfold, whereas minimal alterations were present in the hyperthyroid group. The serum equivalent volume of T4 distribution in the slow pool was significantly reduced following short-term amiodarone, whereas serum and rapid pool volumes were reduced in selective hyperthyroxinemia and slow pool volume was increased in hyperthyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Effect of thyroid hormones on oxidative and nonoxidative glucose metabolism in humans.

The glucoregulatory function of thyroid hormones was investigated in six healthy subjects before and after 14 day 3,5,3',5'-tetraiodothyronine (T4) treatment (300 micrograms/day) using a sequential clamp protocol for 5 h at euglycemia (0-2 h) and hyperglycemia (165 mg/dl, 2-5 h) and different insulin infusion rates (1.0 for 0-3.5 h and 6.5 mU.kg-1.min-1, for 3.5-5 h). T4 treatment increased basal energy expenditure (+8%), glucose disposal (+31%), and oxidation (+87%) but decreased nonoxidative glucose metabolism (-30%) and was without effect on lipid oxidation. During the euglycemic clamp, T4 treatment enhanced insulin-induced glucose disposal (+16%), glucose oxidation (+34%), and inhibition of lipid oxidation (-66 vs. -40%); nonoxidative glucose metabolism was stimulated to a similar extent before and after T4. During hyperglycemia, 3,5,3'-triiodothyronine (T3) did not affect glucose disposal but increased carbohydrate-induced lipogenesis at both insulin infusion rates. We conclude that T4 treatment promotes glucose disposal and oxidation, T3 decreases noninsulin-mediated glucose storage but does not antagonize insulin action.

Adult↗
PubMed1988

Increased plasma clearance rate of thyroxine despite decreased 5'-monodeiodination: study with a peroxisome proliferator in the rat.

In euthyroid rats a 17-day treatment with nafenopin, a hypolipidemic agent and peroxisome proliferator, decreased serum total and free T4 concentrations to 32 +/- 5% and 62 +/- 8% (mean +/- SEM; n = 10), respectively, with no change in serum T3 and TSH concentrations. In methimazole-treated rats infused with 3 nmol T4/day/100 g BW, the nafenopin inhibitory effect was not significantly different from that in euthyroid rats. Nafenopin treatment had the following effects on peripheral T4 and T3 metabolism in euthyroid rats. The plasma clearance rate of T4 (PCR), which was measured by Alzet minipump infusion of tracer, was increased 2-fold (1.58 +/- 0.09 vs. 0.82 +/- 0.06 ml/h.100 g BW; P less than 0.001; n = 5), while the PCR of T3 was decreased (37.5 +/- 1.3 vs. 53.8 +/- 1.8; P less than 0.001; n = 5). The fecal clearance rate of radioactivity derived from T4 was increased 2-fold (1.93 +/- 0.10 vs. 0.77 +/- 0.07 ml/h.100 g BW), whereas the urinary clearance rate was not significantly modified. The 5'-deiodinase (5'D) activity, measured by deiodination of labeled rT3, was strongly inhibited in liver and kidney, not modified in brown fat and anterior pituitary, and increased in cerebral cortex. In methimazole-treated rats substituted with isopropyl-diiodothyronine only hepatic 5'D activity was decreased. It is concluded that the decrease in serum total and free T4, without alteration in serum T3 and TSH concentrations, resulting from nafenopin treatment is mainly due to changes in peripheral T4 and T3 metabolism, since it is also observed in T4-substituted animals. The increased PCR of T4 cannot be explained by an increase in deiodination activity, since the major 5'D pathways are inhibited after nafenopin treatment, and the urinary clearance rate is not modified. It can partly be explained by an increase in the fecal clearance rate of T4, which could be due to an increase in glucoronoconjugation. In addition, nafenopin was found to be a weak competitor of T4 binding to serum proteins, leading to a small increase in the free T4 fraction which might also contribute to the increased T4 PCR. The decrease in T3 PCR remains to be explained.

Adipose Tissue, Brown↗