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Biomedical subjects

A G Burger

Publications and source records attributed to A G Burger.

At least 73 records · Page 4Linked to original sources

In vivo inhibition of the 5'-deiodinase type II in brain cortex and pituitary by reverse triiodothyronine.

To study the effect of rT3 on the 5'-deiodinase type II (5'D-II) of rat brain cortex and anterior pituitary, daily infusions of rT3 at rates of 0.5, 1.5, 4.5, and 13.5 nmol/day X 100 g body weight were given to a total of 87 hypothyroid rats. rT3 inhibited the 5'D-II activity in the total homogenate and in the microsomal fraction in the brain cortex, inhibition becoming significant (28-33%) with the infusion of 4.5 nmol/day X 100 g body weight, at serum levels of 2.4 pmol rT3/ml. Infusion of 13.5 nmol/day X 100 g body weight produced 71-73% inhibition. In homogenates of the anterior pituitary, inhibition was significant with infusions of 13.5 nmol/day X 100 g body weight (30%). To examine how rT3 might inhibit 5'D-II activity, labeled rT3 (137 muCi/day) was infused into 4 hypothyroid rats, and the rT3 content in the homogenate and in the cell subfractions was measured by HPLC. No rT3 was detectable in the nuclei, and less than 1% was found in the microsomal fraction. The infused rT3 was thus no longer present in the microsome preparations and homogenates. The inhibitory effect of rT3 was also compared with that of T4. Serum T4 levels of 45 pmol/ml were required in order to inhibit 5'D-II to the same extent as with 7 pmol rT3/ml. The requirement of this high serum level of T4 excludes the potential role of T4 impurities in the infused rT3 preparation. We therefore conclude that rT3 inhibits 5'D-II in brain cortex per se independently of T4.

Animals↗

Is conversion of thyroxine to triiodothyronine and reverse triiodothyronine autoregulated? Studies with short term suppression of thyroid function with 3'isopropyl 3,5-diiodothyronine.

We investigated the effect of a 6 days course of 20 micrograms of a thyromimetic thyronine analogue 3'isopropyl, 3,5-diiodothyronine (DIIP) on serum thyroid hormone and TSH levels in 10 normal male volunteers. TSH was inhibited progressively during the 6 days of DIIP treatment. By the third day after stopping the treatment this trend had already reversed. Of the serum thyroid hormones the T3 level had decreased by 32% and was the first to increase 5 days after stopping treatment. Serum T4 fell by 35% and returned later to normal. The next effect was an increase in the T3/T4 ratio which was most marked 5 days after treatment had stopped. Kinetic studies with 125I-T3 and 125I-reverse T3 were performed at this time. In comparison to pretreatment kinetics no change in MCR was obtained. It is therefore suggested that at least part of the more rapid increase of T3 than T4 after stopping the suppression therapy reflects an increased conversion.

Adult↗

Triiodothyronine (T3)-induced thermogenesis: altered T3-efficiency in tissues from fed, starved, and refed hypothyroid rats.

A microcalorimetric study of perifused tissue samples obtained from hypothyroid thyroidectomized rats killed 15 h after a single injection of T3 was conducted in order to observe at the tissue level, and in a constant environment, the T3-dependent thermogenesis induced in fed, starved, and refed states. When 9 micrograms T3/100 g BW had been administered to fed animals, tissue heat production rate (E) increased in liver, soleus muscle, and myocardium. In kidney cortex an increase in E was observed only after 90 micrograms T3. A dose-response study was performed with liver samples, in which both oxygen consumption and heat production rates were measured. Liver and soleus muscle were then further investigated. T3-dependent thermogenesis could not be demonstrated in tissues obtained from rats which had been starved for 3 days before receiving 9 micrograms T3/100 g BW. After a small carbohydrate intake corresponding to about 60 kJ/rat (refed state; 1 kJ congruent to 0.4 kcal) given over a 3-h period preceding the injection of T3, T3-dependent thermogenesis was again present. It is concluded that differences in T3 dependent thermogenesis similar to those previously observed in animals under different nutritional states continue to exist in vitro, when tissues are no longer exposed to differing levels of humoral factors.

Animals↗

Recovery of serum TSH and thyroid hormones after 3'isopropyl-3,5-diiodo-L-thyronine (DIIP) treatment: absence of inhibiting effect of bromocriptine on TSH secretion and evidence for autoregulation of serum T3 levels.

Bromocriptine, because of its dopaminergic activity, could possibly inhibit TSH secretion. This hypothesis was tested in 7 normal male volunteers. Thyroid function was suppressed with the very potent thyromimetic analogue, 3'isopropyl-3,5-diiodo-L-thyronine (DIIP). We wanted to observe, after stopping this treatment, whether the return of serum T3, T4, rT3 and TSH values was influenced by concomitant bromocriptine treatment (5 mg/day). For comparison, the DIIP study was also performed without bromocriptine treatment. In both cases, serum T4 and serum T3, which had decreased by, respectively, 34% +/- 5% and 17% +/- 5%, returned over the same time interval to their initial values. Serum TSH and TRH-mediated TSH secretion were also unaffected by the bromocriptine treatment. DIIP does not interfere in the serum determination of T3, T4 and rT3. During suppression with DIIP serum T3 fell less than serum T4 and returned more rapidly to its initial concentrations. It is concluded that dopaminergic inhibition by bromocriptine, at this dose, is insufficient to alter normal thyroid function. In addition, during suppression and shortly thereafter there is a tendency for the serum T3 levels to be maintained.

Adult↗

Plasma levels of 3-methylhistidine after ingestion of the pure amino acid or of muscular proteins measured by radioimmunoassay.

A radioimmunoassay for plasma 3-methylhistidine (3MeHis) measurements has been developed. The assay has no significant crossreactivity with 18 other amino acids including histidine, carnosine, anserine, and creatinine. In normal subjects who have eaten no meat for 36 hours, plasma levels are constant over a 24-hour period (8.78 +/- 0.48 mumol/L, mean +/- SD). The use of 3MeHis for the assessment of intestinal protein absorption and its potential use as a marker of protein degradation were evaluated by studying its plasma kinetics. The absorption of the free 3MeHis is rapid and reaches a peak after 75 minutes. The peak is delayed after meat ingestion and reaches a maximum after 180 minutes. The ratio of the 75- to 180-minute 3MeHis levels was 1.40 +/- 0.06 for pure 3MeHis and 0.78 +/- 0.06 after meat ingestion (P less than 0.001). Peak height and area under the plasma concentration versus time curve were proportional to the dose received, indicating first order kinetics for 3 MeHis. It has a half-life of 12.2 hours, a metabolic clearance rate of 0.08 L/h and volume of distribution is 11.7 +/- 1.7 L as calculated from the serum values which were obtained up to 24 hours after oral 3MeHis administration. Its endogenous production can therefore be calculated to be 116 mumols per day in young subjects. Thus, the radioimmunoassay develops the potential of this amino acid as a marker of protein degradation and absorption for physiological investigations.

Adult↗

Influence of feed on the course of tenosynovitis caused by REO virus infection in broilers.

The first outbreak of tenosynovitis caused by infection with REO virus in the Netherlands, involving 15 broiler flocks, is described. The disease could be reproduced easily by subcutaneous, oral and contact infection of susceptible broilers with the isolated virus. The 15 affected flocks all came from one broiler parent flock and were fed with feed from one mill (A). Twenty other flocks, also coming from this parent flock and reared in the same period on feed from another feed mill (B) did not suffer from tenosynovitis. The parent flock showed no disease symptoms but seroconversion to REO virus occurred after the onset of the problems in the offspring. The influences of the different feeds on the course of the synovitis could be reproduced experimentally, but with less extreme differences than observed in the field. The possible ways in which feeds may influence tenosynovitis causing REO virus infection are discussed.

Animal Feed↗

Occurrence and significance of infectious bronchitis virus variant strains in egg and broiler production in the Netherlands.

Despite vaccination against Infectious bronchitis virus (IBV) with the Massachusetts type vaccine viruses H120 and H52 in the Netherlands, an increasing number of properly vaccinated flocks have suffered from the disease since 1978. In the years 1978-1982, the virus was isolated from 162 IBV suspected flocks. Cross-virus-neutralization tests showed that the majority (67 per cent) of these isolates belonged to serotypes other than the Massachusetts type, the Connecticut-, Florida-, Iowa 97-, Iowa 609- and JMK serotype. The majority of these Dutch isolates could be divided into 4 serogroups, called D207, D212, D3128 and D3896. Only a few isolates were not related to these serotypes. A survey of 328 flocks for antibody against these serotypes demonstrated that antibody against one or more of these novel serotypes were present in most of the flocks. Experiments demonstrated that vaccination with the H120 vaccine virus was not able to protect chickens against the adverse effects of a challenge with the novel serotypes.

Animals↗

The monodeiodination of triiodothyronine and reverse triiodothyronine in man: a quantitative evaluation of the pathway by the use of turnover rate techniques.

These studies were performed to evaluate the quantitative role of monodeiodination in the peripheral metabolism of T3 and rT3 in man. As a prerequisite step, the serum concentrations of two diiodothyronines (T2s), 3,5-T2 and 3',5'-T2, were established by specific RIAs. In 20 normal subjects, mean (+/- SEM) serum concentrations of 3,5-T2 and 3',5'-T2 were 0.40 +/- 0.18 and 2.07 +/- 0.13 ng/dl, respectively. The mean concentrations of both T2s were significantly increased in hyperthyroidism. In primary hypothyroidism, the mean 3,5-T2 concentration was not significantly different from normal, but 3',5'-T2 concentrations were undetectable in the majority of subjects. In the first experiments, the MCRs of rT3 and all three T2s were derived by the constant infusion method. Seven normal subjects were infused simultaneously with the three 125I-labeled T2s for 12 h, and in four of the subjects, [131I]rT3 was also administered. The MCRs (liters/day . 70 kg; mean +/- SEM) were: rT3, 130 +/- 17; 3,5-T2, 168 +/- 15; 3,3'-T2, 621 +/- 84; and 3',5'-T2, 305 +/- 45. The daily production rates (PR; micrograms per day/70 kg; mean +/- SEM) were: rT3, 29.1 +/- 1.0; 3,5-T2, 0.6 +/- 0.1; 3,3'-T2, 20.8 +/- 4.1; and 3',5'-T2, 5.7 +/- 2.1. In the four subjects who received [131I]rT3, the serum T2 concentrations and PRs were also derived by turnover rate techniques. At equilibrium, 2.0 +/- 0.7% and 6.0 +/- 1.6% of [131I] rT3 were found as [131I]3,3'-T2 and [131I]3',5'-T2, respectively. The serum T2 concentrations were derived by the product of these percentages and the serum rT3 concentrations and compared with those obtained by T2 RIA. The serum 3',5'-T2 concentration was 1.3 +/- 0.4 ng/dl (tracer), and its PR was 3.4 +/- 1.1 micrograms/day (tracer); these values were closely correlated with those obtained by RIA. Serum 3,3'-T2 concentrations were 0.4 +/- 0.2 ng/dl (tracer) and 2.7 +/- 0.4 ng/dl (RIA), and the PRs were 3.2 +/- 1.6 micrograms/day (tracer) and 20.3 +/- 5.7 micrograms/day (RIA), indicating that rT3 5'-deiodination contributes only a small proportion of serum 3,3'-T2 and its PR. An analysis of the rT3 PR and the 3,3'-T2 and 3',5'-T2 PRs derived from the turnover of rT3 revealed that 28% of the rT3 produced was degraded by monodeiodination. Of this total, 49% of the deiodination occurred at the 5' position and 51% occurred at the 5 position.(ABSTRACT TRUNCATED AT 400 WORDS)

Chemical Precipitation↗

Rapid adaptations of serum thyrotrophin, triiodothyronine and reverse triiodothyronine levels to short-term starvation and refeeding.

Nutrition influences thyroid function at the level of TSH secretion, at the level of monodeiodination, and possibly elsewhere. In order to study the effect of starvation on TSH secretion, 8 healthy male volunteers fasted for 30 h and were then refed with 800 kcal. Refeeding was performed at 19.00 h and blood was sampled at 20 min intervals until midnight. Control experiments were performed in the same subjects both when they were normally fed and when the starvation period was prolonged a further 5 h until midnight. Starvation decreased serum TSH levels to below 1 mU/1, and without refeeding the nocturnal peak of the TSH nycthemeral rhythm was abolished. With refeeding serum TSH tended to increase towards midnight and was significantly higher than during starvation. However, the serum TSH levels remained significantly below those at the same time of the day in the absence of a preceding starvation period. Serum T3 levels were significantly lower than in the fed state. The mean values were 1.84 +/- 0.03 vs 2.30 +/- 0.06 nmol/l (120 +/- 2 vs 150 +/- 4 ng/100 ml, mean +/- SEM P less than 0.01). Refeeding did not result in a measurable change in serum T3 concentration (1.80 +/- 0.05 nmol/l; 120 +/- 3 ng/100 ml, mean +/- SEM, n.s.). The contrary was true for rT3 levels which increased in starvation and tended to fall with refeeding, but this decrease was not significant. As glucocorticoids have been implicated in the control of monodeiodination and TSH secretion, serum cortisol levels were also measured. They did not differ during the 3 experimental periods.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗

[Endocrine function in old age (70 years and over)].

Internists are frequently faced with the problem of interpreting hormonal values and the results of endocrine tests in elderly patients. In this review, endocrine changes observed in the course of the ageing process are systematically examined for each endocrine gland. The causes of the modifications observed can for the sake of simplicity be classified into three types: 1. Reduction of the hormone's metabolism with, subsequent to its prolonged half-life, a reduction of secretion due to an appropriate feedback mechanism, without modification of the secretory capacity of the glands involved (e.g. thyroid hormones and cortisol). 2. Reduction of hormonal secretion as a consequence of loss of glandular mass (e.g. the gonads). 3. Changes in the sensitivity of target cells to a hormone (e.g. insulin, ADH, catecholamines, lactotrope cells, TRH and hypothalamus to steroids) due to either loss of receptors or modifications in post-receptor events.

Aged↗

Ether link cleavage is the major pathway of iodothyronine metabolism in the phagocytosing human leukocyte and also occurs in vivo in the rat.

These studies were performed to test the hypothesis that ether link cleavage (ELC) is an important pathway for the metabolism of thyroxine (T(4)) in the phagocytosing human leukocyte. When tyrosyl ring-labeled [(125)I]T(4)([Tyr(125)I]T(4)) was incubated with phagocytosing leukocytes, 50% of the degraded label was converted into [(125)I]3,5-diiodotyrosine ([(125)I]DIT). Of the remaining [Tyr(125)I]T(4) that was degraded, two-thirds was recovered as [(125)I]-nonextractable iodine ([(125)I]NEI), and one-third as [(125)I]iodide. The production of [(125)I]DIT was not observed when phenolic ring-labeled [(125)I]T(4) ([Phen(125)I]T(4)) was used, although [(125)I]NEI and [(125)I]iodide were produced. None of these iodinated compounds were formed in leukocytes that were not carrying out phagocytosis. The fraction of T(4) degraded by ELC was decreased by the addition of unlabeled T(4) and by preheating the leukocytes, findings which suggested that the process was enzymic in nature. ELC was enhanced by the catalase inhibitor aminotriazole, and was inhibited by the peroxidase inhibitor propylthiouracil, suggesting that the enzyme is a peroxidase and that hydrogen peroxide (H(2)O(2)) is a necessary cofactor in the reaction. To test this hypothesis, studies were performed in several inherited leukocytic disorders. ELC was not observed in the leukocytes of patients with chronic granulomatous disease, in which the respiratory burst that accompanies phagocytosis is absent. ELC was normal in the leukocytes of two subjects homozygous for Swiss-type acatalasemia, and aminotriazole enhanced ELC in these cells to an extent not significantly different from that observed in normal cells. ELC was normal in the leukocytes of a patient with myeloperoxidase deficiency, but could be induced by the incubation of [Tyr(125)I]T(4) with H(2)O(2) and horseradish peroxidase in the absence of leukocytes. The in vivo occurrence of ELC in the rat was confirmed by demonstrating the appearance of [(125)I]DIT in serum from parenterally injected [(125)I]3,5-diiodothyronine, but no [(125)I]DIT was produced when [(125)I]3',5'-diiodothyronine was administered. FROM THESE FINDINGS WE CONCLUDE THE FOLLOWING: (a) ELC is the major pathway for the degradation of T(4) during leukocyte phagocytosis, and accounts for 50% of the disposal of this iodothyronine; (b) the NEI and iodide formed by phagocytosing cells are derived from the degradation of the phenolic and tyrosyl rings of T(4), although ELC per se accounts for only a small fraction of these iodinated products; (c) the process by which ELC occurs is enzymic in nature, and its occurrence requires the presence of the respiratory burst that accompanies phagocytosis; (d) the enzyme responsible for ELC is likely to be a peroxidase, although a clear role for myeloperoxidase as the candidate enzyme remains to be established; (e) iodothyronines are also degraded by ELC in vivo, and the quantitative importance of this pathway in various pathophysiological states requires further investigation.

Amitrole↗

Evidence of a thyrotropin-releasing hormone-dependent increase in plasma thyrotropin during refeeding of starved rats.

After 3 days of starvation, refeeding with carbohydrate (CHO) leads to a rapid increase in plasma T4 and T3, suggesting increased TSH secretion. The aim of the present study was to describe the time course of plasma TSH changes during refeeding with CHO and fat. Repetitive blood samples were obtained from freely moving animals by indwelling jugular venous catheters. Refeeding was performed on the fourth day of starvation at either 1100 or 1900 h, and blood was sampled during the preceding hour and during the following 3 h. In control experiments, blood was sampled over 4 h without refeeding. Refeeding with CHO and fat induced a significant increase in plasma TSH in the first hour. This increase could be abolished by a previous injection of an anti-TRH serum, while normal rabbit serum was without effect. Plasma corticosterone, measured hourly, also showed a tendency to increase with refeeding. It is concluded that refeeding of starved rats represents a reproducible stimulus for TSH secretion.

Animals↗

3'-isopropyl-3,5-diiodo-L-thyronine: a potent synthetic thyromimetic thyronine analog. Studies of its kinetics and biological potency in man and rats and its toxicology.

In order to compare phenolic and tyrosyl ring monodeiodination, we investigated 3'-isopropyl-3,5-diiodo-L-thyronine (DIIP), a potent thyronine analog which can only be monodeiodinated on the tyrosyl ring. A specific RIA was developed. The in vivo metabolism and biological potency of DIIP and T3 were compared. DIIP and T3 kinetic studies were performed in vivo using 40 male SIVZ rats who received 5 micrograms DIIP and 0.5 microCi 131I-T3. Blood samples were obtained for up to 15 h. The MCR of DIIP was 2.8 ml/h/100 g BW and the volume of distribution was 27 ml/100 g BW, corresponding values for T3 being 34 ml/h/100 g BW and 175 ml/100 g BW. Subacute toxicology studies in rats showed that DIIP was not more toxic than T3. On the basis of these results, experiments were performed in man. Five male subjects received 40 micrograms DIIP p.o. and blood samples were collected over 17 days. The MCR was 54 ml/kg . day, the volume of distribution 188 ml/kg and the fractional disappearance rate 0.0119/h. When given to an hypothyroid patient, 16-20 micrograms DIIP daily was sufficient to restore clinical and biochemical euthyroidism. These studies demonstrate that a decreased MCR can be accompanied by increased biological activity. It is suggested that the limited monodeiodination of DIIP is one of the factors explaining the differences observed in the potency and metabolism of DIIP and T3.

Adult↗

Effects of triiodothyronine and nutritional status on nuclear non-histone proteins of the rat liver.

UNLABELLED: In the hepatic nucleus of the rat at least 2 nuclear globulin bands, identified by SDS polyacrylamide gel electrophoresis, are known to be influenced by thyroid hormones. In the present article a quantitation of these bands was obtained by scanning techniques. The effects of T3 were studied in male thyroidectomized (Tx) and intact rats. After sacrifice the hepatic nuclear globulins were prepared according to published methods. In Tx rats substituted with a single dose of 50 micrograms or during one week 2 micrograms T3 the t band decreased from 5.3% to 2.7% of the total nuclear globulin content which represent a complete normalisation. The n band did not show this rapid response to T3 as 2 micrograms given for one week only partially restored this band (Tx 1.4%, Tx + T3 2.2%). However during starvation of intact rats only the n band was slightly influenced by T3 as 2 micrograms of T3 partially prevented the decrease of this band seen in untreated euthyroid starving rats. The increase of the t band in starvation was not affected by T3. IN CONCLUSION: the n and t bands are controlled by several factors, two of which are T3 and nutrition. The control of the t band seems to be dominated by the nutritional status of the animal. T3 seems to keep some activity on the n band, even in starved rats.

Animals↗

A case of Aujeszky's disease virus infection in young chicks.

On a rearing farm with 96,000 birds, 10,000 three and four days old chicks died with nervous symptoms. A virus was isolated from the brains and identified as an Aujeszky's disease virus. The isolate was very pathogenic for chickens up to about 7 days of age, causing mortality after parenteral injection (intracerebral, intraperitoneal, intramuscular) but not after oral, eye drop or spray application. An Aujeszky vaccine virus, made apathogenic by passages in chicken cells for use in swine, had the same pathogenic properties for chicks. The isolated Aujeszky's disease virus is regarded as the agent responsible for the death of the 10,000 chicks on the farm. This virus most likely had been injected in just hatched chicks instead of or together with the Marek vaccine virus. In addition to meningitis, edema, neuronophagia and cuffing of blood vessels with mononuclear cells, haemorrhages were observed in thin sections of brain and spinal cord. After injection of isolate and vaccine virus in the leg muscle intranuclear inclusion bodies were observed in the ganglion cells in the spinal cord. Inclusion bodies have not been described before in pathological conditions of the nervous tissue of chickens.

Animals↗

The interaction of free fatty acids in radioimmunoassays for reverse triiodothyronine.

We have investigated the effect of FFA on the RIA of rT3 because of our previous findings of a correlation between serum rT3 values and increased FFA concentrations during prolonged exercise and reports of interference by FFA in other thyroid hormone assays. Apparent rT3 values increased by 19% and 34% in in vivo studies of acute lipolysis in subjects 5 min post exercise or 10 min post heparin, respectively, while T3 and T4 concentrations were unchanged. Varying concentrations of palmitic acid were added in vitro to four normal sera, and the increase in FFA concentration correlated significantly with the increase in apparent rT3 values. The mean +/- SE of the regression slope was 9.3 +/- 1.8 ng/dl rT3/mM FFA (r = 0.96 +/- 0.02). The addition of linoleic acid produced a similar effect. T3 and T4 concentrations were unchanged. The interaction of FFA in the rT3 RIA was unrelated to the procedure used to separate the assay, to the concentration of 8-anilino-1-napthalene-sulfonic acid in the assay buffer, to FFA binding directly to the antisera or to use of a particular antisera. The magnitude of the effect was similar in charcoal-treated sera, and the addition of 2 mM palmitic acid to the assay standard curve decreased the y intercept but did not alter the slope, suggesting an interaction of rT3 with FFA, rather than change in affinity of the antisera.

Energy Intake↗