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Biomedical subjects

F S Keck

Publications and source records attributed to F S Keck.

At least 37 records · Page 2Linked to original sources
PubMed1991

Thyroxine and reverse T3 5'deiodination in the cells of human adipose tissue.

The intracellular 5'deiodination (5'D) of T4 and rT3 has been investigated in human adipose tissue. We studied 5'D in intact adipose tissue, its morphological components and in 3T3-L1-cells. 5'D as assessed by T3-production out of T4 and by rT3-decomposition was not inhibited by propylthiouracil (PTU), but by iopodate (IOP). The apparent Michaelis constants were kM = 3 nM for rT3 and kM = 1 microM for T4. The rT3-degradation was linear over 25 h (115 pg/h.mg (prot.)) both at 37 degrees C and at 4 degrees C. The same type of 5'D was observed in adipocytes, stromal-vascular cells and in 3T3-L1-cells regarding T4 to T3 degradation (244 +/- 30, 181 +/- 27, 227 +/- 37 pg T3/mg.min), resp.; PTU did not exert any influence upon 5'D in the cells investigated. We conclude, that i. the intracellular generation of T3 in adipose tissue does not derive from type I deiodination; ii. 5'D in adipocyte precursors and differentiated adipocytes is identical and iii. there is no difference between human cells and 3T3-L1-cells regarding 5'D.

Adipose Tissue↗
PubMed1991

Thyrotropin-releasing hormone degradation in patients with insulin dependent diabetes mellitus. Effects of metabolic control.

We investigated thyrotropin releasing hormone (TRH) degradation in terms of half-life (t1/2) and metabolic clearance rate (MCR) in eight subjects with insulin dependent diabetes mellitus (IDDM) before and after strict metabolic control. The results were compared with those of six healthy control subjects. The basal plasma TRH-IR levels (31 +/- 9 fmoles/ml) were on the lowest normal limit in the IDDM patients and were not considerably changed (24 +/- 10) after strict metabolic control. The basal and delta max rise of TSH to TRH (200 micrograms i.v.) were not significantly different before or after improved metabolic control in IDDM and as compared to controls. The TRH-degradation curves showed similar exponential decay before and after improvement of metabolic control (t1/2: 7.6 +/- 0.4 min and 7.3 +/- 0.3 respectively; 6.5 +/- 0.4 min for the controls). The MCR of exogenously administered TRH in IDDM before (65.5 +/- 8.6 l/m2/day) and after (65.0 +/- 8.9) control was not different compared to the normals (76.5 +/- 9.6). The area under the plasma concentration-time curve (AUC) in IDDM before (52.193 +/- 6.773 fmoles.ml-1.min) and after improvement of metabolic control (53.186 +/- 7.856) was slightly higher than in the healthy subjects (40.151 +/- 3.741, n.s.). These findings demonstrate that a) the degradation of exogenous TRH is not dependent on the glucose metabolic state, b) insulin deficient diabetes mellitus does not affect the enzymatic system responsible for TRH degradation and, c) the hypothalamic-pituitary axis appears to be intact in IDDM.

Adolescent↗
PubMed1991

Hepatic sulfhydryl content under adrenergic stimulation in male rats.

The influence of a series of sympathomimetic agents on the liver content of non protein bound thiol groups (NP-SH), mainly representing glutathione, has been assessed in the male rat. The rats were intravenously and/or subcutaneously infused over 6 h at different dosages either with dopamine, dobutamine, epinephrine, terbutaline, or phentolamine, or simultaneously with dopamine and phentolamine, or with epinephrine and phentolamine. Besides NP-SH, total sulfhydryl group content was measured in liver cytosol, while glucose and insulin concentrations were determined in the serum. Liver NP-SH content was significantly decreased by epinephrine. This decrease was abolished and even inverted to an increase, when appropriate doses of phentolamine were infused simultaneously. Dopamine caused a rise in NP-SH content at a dose rate of 7.5 micrograms/kg.min, while lower and higher dose rates of dopamine exerted not any influence on liver NP-SH. When phentolamine was concomitantly infused with 15 micrograms/kg.min of dopamine, NP-SH was significantly elevated. Phentolamine, when infused exclusively, increased NP-SH as well, while it was not influenced, however, by terbutaline or dobutamine at any dosage. Cytosolic total sulfhydryls were found to be unaltered across all experimental groups. When the NP-SH values are related to the corresponding serum insulin levels, a close and linear relationship becomes evident. The study demonstrates, that some sympathomimetic agents can exert a considerable influence on hepatic non protein bound thiol content. The data suggest, that the varying liver NP-SH content under adrenergic drugs is primarily related to changes in serum insulin concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Single-compartment model analysis of thyrotropin-releasing hormone kinetics in hyper- and hypothyroid patients. Kinetic studies using a combined system of RIA and FPLC.

The pharmacokinetics of thyrotropin-releasing hormone (TRH) were assessed following an i.v. injection in blood of ten hyperthyroid, ten hypothyroid, and six normal subjects. A single-compartment model was employed. After methanol extraction, TRH concentrations were analyzed using a specific radioimmunoassay technique combined with fast protein liquid chromatography (FPLC). As for the basal levels of TRH, no differences were observed in either study group. Peak concentrations were always present two min after the injection of TRH. In the euthyroid subjects, TRH blood levels had a half-life (t1/2) of 6.5 +/- 0.41 min, mean +/- SD, while t1/2 was 7.2 +/- 0.62 min in the hyperthyroid and t1/2 was 12 +/- 1.67 min (p less than 0.001) in the hypothyroid patients. The metabolic clearance rate (MCR) (82.2 +/- 15.3 liters/m2/day vs. 89.8 +/- 17.2) and the volume of distribution (Vd) (7.1 +/- 4.2 liters vs. 7.3 +/- 3.4) were approximately the same in the normal subjects and in the hyperthyroid group. MCR (66.2 +/- 15.3 liters/m2/day) and Vd (6.2 +/- 3.3 liters) were found to be lower in the hypothyroid patients. In FPLC, when TRH was added to plasma, it eluted in one peak. Blood samples taken 5 min after TRH i.v. injection had an elution profile of 9.94 ml. These data indicate that 1) TRH has a very short half-life, 2) hypothyroidism can prolong the t1/2 of exogenous TRH, and 3) when TRH should be used in clinical studies, the function of the thyroid gland has to be taken into consideration.

Chromatography, Liquid↗
PubMed1990

Differential effects of dopamine on glucoregulatory hormones in rats.

The effect of dopamine at different doses on serum concentrations of insulin, glucose and corticosterone and on plasma glucagon concentration was investigated in rats. Dopamine was given intravenously over 6 h with infusion rates of 2.5, 7.5, 15, and 60 micrograms/kg.min and in combination with phentolamine. Serum insulin concentration was unchanged at low doses of dopamine. It was significantly increased from 6.0 +/- 0.7 ng/ml to 13.7 +/- 2.3 ng/ml (P less than 0.01) when 7.5 micrograms/kg.min of dopamine were used, whereas it was significantly depressed to 3.96 +/- 0.89 and to 4.0 +/- 0.34 ng/ml (P less than 0.01), respectively, at the high doses of dopamine. This latter effect could be reversed to 6.7 +/- 1.19 ng/ml and inverted to 9.2 +/- 1.7 ng/ml (P less than 0.01) by simultaneously applied phentolamine at appropriate dosages. Serum glucose levels were markedly elevated from 154 +/- 7 to 234 +/- 42 mg/dl (P less than 0.01) by the higher doses of dopamine. A significant alteration of glucagon plasma concentrations from 18.9 +/- 2.8 to 42.3 +/- 14 pg/ml (P less than 0.01) was elicited only by 7.5 micrograms/kg.min of dopamine. The data clearly demonstrate that exogenous dopamine acts differently on glucose homeostasis according to the dosage. The study provides strong evidence that dopamine decreases insulin levels via alpha-adrenergic receptor stimulation. This effect may contribute to the deterioration of glucose homeostasis with high doses of dopamine.

Animals↗
PubMed1990

The influence of circulating thyroxine serum concentration on hepatic thyroxine deiodinating activity in rats.

The influence of varying thyroid metabolic states, induced by thyroxine (T4) application, upon type I T4 deiodinating activity has been assessed in the rat liver. A series of 18 rats was thyroidectomized and treated with T4 at various doses, ranging from 0 to 50 micrograms/kg b.w. Microsomal T4 to triiodothyronine (T3) deiodinating activity (5'DA) and T4 to reverse T3 (rT3) deiodinating activity (5DA) as well as cytosolic non protein bound thiol content (NP-SH) were determined in the liver; concentrations of T4, T3, and rT3 were measured in the serum. In the experimental rats, T4 serum concentrations ranged from 1.3 micrograms/dl to 15.6 micrograms/dl (controls, 5 +/- 0.2 micrograms/dl, mean +/- SEM), T3 varied between 33 ng/dl and 150 ng/dl (91 +/- 3 ng/dl), and rT3 between 2 ng/dl and 25 ng/dl (7 +/- 2 ng/dl). Relating T4 to T3 serum levels, a curvilinear relationship (power function, r = 0.94, p less than 0.001), as described previously in man, was confirmed in the rats, as was the linear relationship between T4 and rT3 serum levels (r = 0.75, p less than 0.001). Individual 5'DA increased by more than fourfold, from 531 pg/mg.min to 2,234 pg/mg.min (controls, 1,419 +/- 67 pg/mg.min), when passing from low to high T4 serum values. The increase in 5'DA was steeper in the low T4 range, while it was progressively flattened under T4 levels above the controls' range. The particular changes in 5'DA can be illustrated by calculating the ratio of 5'DA and T4 serum levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Effects of hypothyroidism on bronchial reactivity in non-asthmatic subjects.

The effect of hypothyroidism on non-specific bronchial reactivity was studied in 11 patients without pulmonary disease (mean age 40 (SD 13) years) who had had a total thyroidectomy and radioiodine treatment for thyroid cancer 41 (36) months before the study. All patients when mildly hyperthyroid while having long term thyroxine replacement treatment and once when hypothyroid two weeks after stopping triiodothyronine for the purpose of screening for metastases. Bronchial reactivity was assessed by measuring specific airways conductance (sGaw) after increasing doses of inhaled carbachol (45-1260 micrograms). The dose producing a 35% decrease in sGaw (PD35) was determined from the cumulative log dose-response curve by linear regression analysis. Mean baseline sGaw values were similar when the patients were hypothyroid and when they were hyperthyroid (1.35 (0.36) and 1.41 (0.56) s-1 kPa-1). The interstudy coefficients of variation of baseline sGaw were higher in the thyroid patients than in a euthyroid control group (14% versus 8%). Geometric mean PD35 was lower when the patients were hypothyroid (97 micrograms) than when they were mildly hyperthyroid (192 micrograms). It is concluded that acute hypothyroidism increases non-specific bronchial reactivity in nonasthmatic subjects.

Acute Disease↗
PubMed1990

Glucoregulation under beta-adrenergic stimulation by dobutamine and terbutaline in the male rat.

The influence of the beta-adrenoreceptor stimulating agents dobutamine and terbutaline as compared to epinephrine on insulin and glucose levels has been assessed in the male rat. All agents were infused either intravenously or subcutaneously over 6 h at varying dosages. In addition, epinephrine was given concomitantly with the alpha-adrenoreceptor blocker phentolamine. The heart frequency as an estimate of the effects of the adrenergic agents beyond the glucoregulatory system was accelerated in a dose-dependent manner. Serum insulin concentrations were significantly increased by phentolamine and significantly depressed by epinephrine, while they were virtually unchanged at any dosages of dobutamine, terbutaline, or epinephrine, when simultaneously applicated with phentolamine. As for serum glucose levels, these agents, again, did not exert any influence, while glucose levels were significantly depressed under phentolamine and significantly increased under epinephrine application. The data demonstrate, that dobutamine and terbutaline at pharmacologically common dosages do not affect glucose homoeostasis. The study does not support a major effect of beta-adrenergic stimulation on the pancreatic B cell in the male rat.

Adrenergic beta-Agonists↗
PubMed1990

Liver thiol content under varying glucoregulatory states in rats.

The influence of varying glucoregulatory states as induced by fasting, feeding and intravenous glucose infusion on liver thiol content has been assessed in the male rat. As expected, increasing the serum glucose levels from 131 +/- 7 mg/dl to 343 +/- 12 mg/dl (mean +/- S.E.) caused a corresponding increase in serum insulin responses. Rising from 3.2 +/- 0.4 mumol/g w.w. in the fasted group to a peak value of 6.3 +/- 0.4 mumol/g (P less than 0.01) in the group infused by 10% glucose solution, hepatic non protein bound sulphydryl groups (NP-SH) were closely related to serum glucose levels up to 244 +/- 11 mg/dl. When higher glucose doses were infused. NP-SH values fell steadily, they even inclined below the level of the fasted rats after infusion of 30% and 40% glucose solutions (1.3 +/- 0.4 mumol/g w.w., P less than 0.05 and 0.7 +/- 0.3, P less than 0.01, resp.), mean serum glucose levels being 291 +/- 12 and 343 +/- 13 mg/dl, resp. Hepatic protein bound thiols were not affected by any of the glucoregulatory states experimentally induced. The data demonstrate that the glucoregulatory state influences hepatic NP-SH content divergently. The study suggests that under physiological conditions liver NP-SH content covariates positively with serum insulin and glucose levels.

Animals↗
PubMed1989

Acute hypothyroidism has no effect on pulmonary vascular resistance.

The effect of acute hypothyroidism on the pulmonary circulation was studied in 9 nonobese athyreotic patients by right heart catheterization at rest and during exercise. The patients were studied while they were hypothyroid 2 weeks after ceasing triiodothyronine treatment and while they were euthyroid on replacement therapy. At rest, pulmonary blood flow [4.0 +/- 0.6 l/min vs 5.8 +/- 1.0 l/min, p less than 0.01] and systolic pulmonary artery pressure [18 +/- 3 mmHg vs 23 +/- 2 mmHg, p less than 0.01] were lower when the patients were hypothyroid than when they were euthyroid. The mean and diastolic pressures in the pulmonary artery and the pulmonary capillary pressures were not different among the groups. Likewise, thyroid hormone levels had no significant effect on pulmonary vascular resistance [100 +/- 25 dyn-s-cm-5 vs 90 +/- 23 dyn-s-cm-5]. With supine exercise, pulmonary blood flow [10.1 +/- 1.6 l/min vs. 13.2 +/- 2.0 l/min, p less than 0.01], mean pulmonary artery pressure [25 +/- 6 mmHg vs 30 +/- 6 mmHg, p less than 0.02], and systolic pulmonary artery pressure [36 +/- 6 mmHg vs 44 +/- 8 mmHg, p less than 0.01] were lower when the patients were hypothyroid. The diastolic pulmonary artery pressure and the pulmonary capillary pressure were similar in both thyroid states. Again, thyroid deficiency had no effect on pulmonary vascular resistance [81 +/- 23 dyn-s-cm-5 vs 76 +/- 24 dyn-s-cm-5]. The lower systolic pressures in the pulmonary artery seen in hypothyroidism are probably due to the decreased systolic volume load of the pulmonary circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Acute hypothyroidism slows the rate of left ventricular diastolic relaxation.

The effect of acute thyroid hormone deficiency on left ventricular diastolic filling was studied by radionuclide ventriculography with simultaneous right heart catheterization in nine athyreotic patients without cardiovascular disease. The patients were studied when they were hypothyroid and when they were euthyroid on replacement therapy. Peak filling rate and the time to peak filling were used to characterize diastolic function. The time to peak filling was defined as the interval from end-systole on the radionuclide time-volume curve to the time of occurrence of peak filling. The peak filling rate was determined in absolute terms from the normalized radionuclide peak filling rate and from the end-diastolic volume, which was derived from the radionuclide ejection fraction and from the thermodilution stroke volume. In all patients, the values for peak filling rate were lower in the hypothyroid than in the euthyroid state (287 +/- 91 mL/s vs. 400 +/- 118 mL/s, delta = 41 +/- 13%, p less than 0.01). Peak filling always occurred during the first half of the diastolic interval. The time to peak filling was not significantly affected by the thyroid state (170 +/- 10 ms vs. 159 +/- 21 ms, delta = 7 +/- 10%). Left ventricular filling pressure as reflected by the pulmonary capillary wedge pressure and end-systolic volume were similar in both thyroid states (6 +/- 2 mmHg vs. 8 +/- 2 mmHg (1 mmHg = 133.32 Pa) and 32 +/- 11 mL vs. 32 +/- 7 mL, respectively). The data suggest that the rate of active diastolic relaxation is decreased in short-duration hypothyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1989

Method for rapid separation of 3,5,3'-triiodothyroacetic acid in human serum by fast protein liquid chromatography.

The 3,5,3'-triiodothyroacetic acid (TRIAC) has been approved as a valuable agent in the management of hyperthyroidism secondary to inappropriate secretion of thyrotropin. We have developed a fast protein liquid chromatography (FPLC) method for separation and quantification of TRIAC. Serum samples charged with TRIAC were extracted with methanol/ammonium acetate, the supernatants were evaporated to dryness, reconstituted in NaOH and injected on a reversed phase column for chromatography. For separation an isocratic elution method (methanol water; 0.1% trifluoroacetic acid) was used. The area under the curve (ml%) was compared with those of the calibration curves. Recoveries were 70 +/- 10.8%. TRIAC was eluted in 2.33 ml. Conclusively, the present method shows that TRIAC can be measured by FPLC and may be applied to the measurement of TRIAC in pharmacological studies.

Chromatography, High Pressure Liquid↗
PubMed1988

[Pharmacokinetics and pharmacodynamics of protirelin (TRH) in man].

Blood concentrations of thyrotropin-releasing hormone (TRH, Protirelin) were measured by a specific radioimmunoassay in 16 euthyroid subjects after intravenous (200 micrograms), nasal (2 mg) or oral (40 mg) administration of TRH. TRH blood levels peaked 2 min after i.v. administration (13,400 +/- 1,020 fmol/ml), 10 min after nasal (5,000 +/- 1,800 fmol/ml) and 150 min after oral (2,650 +/- 1,080 fmol/ml) administration. The degradation of TRH followed an exponential curve, giving a half-life of 6.5 min. The disappearance rate gave a "half-life" of 22 min in the nasal application group and of 31 min in the oral group. Maximal concentration of stimulated thyrotropin-stimulating hormone (TSH) always occurred 30 min after the peak TRH concentration without any correlation with the TRH concentration time integrals, suggesting that TSH secretion is dependent on a continually rising TRH blood level.

Administration, Intranasal↗
PubMed1988

Peripheral autoregulation of thyromimetic activity in man.

This study describes an extrathyroidal mechanism for regulating serum concentration of triiodothyronine (T3) in thyroxine (T4) deficiency or excess. Serum levels of T3, T4, reverse T3 (rT3), and thyrotropin were determined in two series of athyreotic patients (n = 22 and n = 16, respectively) during various doses of T4 substitution therapy. The patients were followed from the severe hypothyroid state up to the modest hyperthyroid state, induced by stepwise increasing doses of administered T4. The periods of constant T4 replacement doses were 1 week (group I) and 5 weeks (group II), respectively. As serum T4 levels rose from less than 0.5 micrograms/dl to 18.9 micrograms/dl, serum T3 levels showed a curvilinear increase, which was pronounced in the very low T4 range while it was flattened at the higher end of the spectrum of T4 levels. As to rT3, an analogous course did not occur. The different character of the relationships between T4 and its conversion products was further elucidated by calculating the T3/T4 and rT3/T4 ratios. T3/T4 ratio declined fourfold from 43.3.10(-3) in the severe hypothyroid to 11.7.10(-3) in the hyperthyroid range. The results support the hypothesis of a peripheral autoregulation of T4 to T3 conversion which appears to be operative at both ends of the T4 spectrum and which serves to maintain or defend serum T3 levels.

Adult↗
PubMed1988

Left ventricular function at rest and during exercise in acute hypothyroidism.

The effect of hypothyroidism on left ventricular function at rest and during exercise was studied in nine patients without demonstrable cardiovascular disease who had had total thyroidectomy and ablative radioiodine treatment for thyroid cancer. Radionuclide ventriculography and simultaneous right heart catheterisation were performed while the patients were hypothyroid two weeks after stopping triiodothyronine treatment (to permit routine screening for metastases) and while they were euthyroid on thyroxine replacement treatment. When the patients were hypothyroid, cardiac output, stroke volume, and end diastolic volume at rest were all lower and peripheral resistance was higher than when they were euthyroid. Pulmonary capillary wedge pressure, right atrial pressure, heart rate, left ventricular ejection fraction, and the systolic pressure:volume relation of the left ventricle, which was used as an estimate of the contractile state, were not significantly different when the patients were hypothyroid or euthyroid. During exercise, heart rate, cardiac output, end diastolic volume, and stroke volume were higher when the patients were euthyroid than when they were hypothyroid. Again, pulmonary capillary wedge pressure, ejection fraction, and the systolic pressure:volume relation were similar in both thyroid states. The data suggest that the alterations in cardiac performance seen in short term hypothyroidism are primarily related to changes in loading conditions and exercise heart rate; they do not suggest that acute thyroid hormone deficiency has a major effect on the contractile properties of the myocardium.

Acute Disease↗