Search PubMed⌕ Search

Biomedical subjects

H Meinhold

Publications and source records attributed to H Meinhold.

At least 55 records · Page 3Linked to original sources
PubMed1990

Thyrotropin (TSH) and thyroid hormone concentrations during partial sleep deprivation in patients with major depressive disorder.

Thyrotropin (TSH), thyroxine (T4), free T4, triiodothyronine (T3), and free T3 (fT3) concentrations were measured in 25 patients with major depressive disorder at 8 a.m. both before and after partial sleep deprivation (PSD) during the second half of the night. Significant increases in TSH and T3 levels and a corresponding trend in fT3 levels were seen. No convincing correlations occurred between changes in the secretion of any of the hormones and the antidepressant effect of PSD. However, this does not rule out the possibility that the two phenomena, which occur in depression at different anatomical levels with presumably different degrees of disturbance in the respective receptor systems, have common underlying neurochemical mechanisms. Comparison of the effect of the PSD on changes in hormone secretion and mood with the corresponding effects in a sample of depressed patients who underwent total sleep deprivation showed no significant differences between the effects of these two forms of sleep deprivation on either variable.

Adult↗
PubMed1989

Eicosanoid release as laboratory indicator of biocompatibility.

Biocompatibility evaluation of extracorporeal devices requires the establishment of sensitive indicators of blood cells/surface interactions. Among others, arachidonic acid derivatives, such as prostaglandins and thromboxanes, play an important role in the cell control systems. Hence, the release of eicosanoids during blood exposure to dialyzer membranes was investigated. Experiments included in vitro incubation of human blood with flat membranes (FM), as well as ex vivo perfusion of hollow fiber membranes (HFM) with blood from healthy volunteers in single-pass fashion. In both models, a significant release of prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) was detected. In addition, the amount of eicosanoid release depended on the type of membrane tested. After a 10-min FM incubation with fresh blood, plasma concentrations of TXB2 and PGE2 were pronounced by polycarbonate when compared to Cuprophan and polyacrylonitrile. During 10 min of open loop perfusion of HFM, polymethylmethacrylate was the most active biomaterial, whereas the reactivity of Cuprophan was significantly lower. Among HFM, Hemophan was by far the less active. These results indicate that the release of eicosanoids represents a sensitive parameter of blood cells/membrane reactivity. Thus, the question arises as to whether or not the extracorporeal process of cyclooxygenase activity could contribute to the clinical side effects of chronical hemodialysis.

Biocompatible Materials↗
PubMed1988

Metabolic clearance and production of diiodotyrosine in healthy man.

Metabolic clearance rate (MCR) and daily production rate (PR) of diiodotyrosine (DIT) were estimated using a constant infusion technique of trace amounts of [125-I]-DIT followed by chromatographical isolation of tracer. Median DIT MCR was in eight healthy subjects estimated to 162 l/day x 70 kg (range 135-242), whereas PR was 52 nmol/day x 70 kg (range 25-126). The median serum DIT concentration was 0.27 nmol/l (range 0.16-0.62). In five L-thyroxine substituted subjects without endogenous thyroxine (T4) production, serum DIT concentrations were below 0.02 nmol/l, suggesting that more than 94% of daily produced DIT is secreted by the thyroid gland.

Adult↗
PubMed1987

Dialyzer membranes: effect of surface area and chemical modification of cellulose on complement and platelet activation.

Using an ex vivo model, the effects of membrane composition and surface area on both the complement system (as reflected by plasma C3a levels) and platelets [as indicated by plasma concentrations of thromboxane B2 (TXB2) and platelet factor 4 (PF4)] were studied. In this model, polyacrylonitrile (PAN) was associated with less complement activation than cuprammonium cellulose (CC). A new "modified cellulose" (MC) membrane, in which a small number of the free hydroxyl groups on cellulose are substituted with a tertiary amino compound, was also associated with a low degree of complement activation, similar to that with PAN. However, the extent of hydroxyl group substitution in four MC membrane subtypes did not correlate with the reduction in complement activation. In studies using CC, the amount of generated C3a correlated with the membrane surface area, although the relationship was curvilinear. Plasma concentrations at the "dialyzer" outlet of TXB2 and PF4 were similar with CC, PAN, and MC. In studies with the MC subtypes, increasing the extent of hydroxyl group substitution paradoxically increased, albeit slightly, the amount of TXB2 generation. In studies with CC, a linear relationship between membrane surface area and TXB2 generation was found. The results suggest a dissociation between platelet and complement effects among different dialyzer membranes, and underline the importance of membrane surface area.

Acrylic Resins↗
PubMed1987

Turnover and urinary excretion of circulating diiodotyrosine.

The MCR of diiodotyrosine (DIT) was determined by measuring serum DIT concentrations by RIA after a single injection of 200 micrograms DIT and noncompartmental analysis. Comparison of the stable DIT method with the tracer DIT technique in dogs yielded good agreement of measured DIT MCRs. The mean (+/- SD) MCR and blood production rate of DIT were 122 +/- 29 L/day X 70 kg and 24.2 +/- 12.7 nmol/day X 70 kg (10.5 micrograms/day X 70 kg), respectively, in 10 normal subjects. Urinary DIT was measured by RIA after its immunoprecipitation from urine. Acid hydrolysis had no effect on measured urinary DIT concentrations, suggesting the presence of predominantly unconjugated DIT. Mean urinary DIT excretion was 1.23 +/- 0.43 (+/- SD) nmol/24 h (533 ng/24 h) or 0.108 +/- 0.048 nmol/nmol creatinine in 32 normal individuals. In patients with defective thyroidal iodine metabolism, urinary DIT was extremely elevated, ranging from 1.2-17.7 nmol/mmol creatinine. Comparison of normal production and excretion rates suggests that about 5% of the daily extrathyroidal DIT turnover is excreted in the urine unchanged or in a DIT-like form.

Adolescent↗
PubMed1987

Pharmacokinetics and urinary excretion of orally administered diiodotyrosine.

Serum levels of diiodotyrosine (DIT) and urinary excretion rates of DIT and iodine were measured in 10 normal subjects after oral administration of 1.57 mumol of DIT corresponding to 400 micrograms of iodine. Serum DIT concentrations rose promptly from a mean endogenous basal level of 0.23 nmol/l to maximum values between 6.0 and 20 nmol/l within 30 min to 1 h after DIT ingestion. Decreasing DIT levels were found in all subjects 2 h after DIT intake. Urinary excretion of intact DIT was low, being less than 1% of the administered dose of exogenous DIT within 2 days. In contrast, 52% of the iodine administered in the form of DIT was excreted in the urine in the same time interval. The rapid absorption of DIT from the gastrointestinal tract combined with rapid and almost complete metabolic degradation by deiodination make orally applied DIT seem a suitable iodine carrier compound for therapeutic purposes.

Administration, Oral↗
PubMed1987

Effects of blood-dialyser interaction on prostaglandins in uraemic patients and in healthy man.

The present study examines extracorporeal prostaglandin production during routine and simulated haemodialysis in healthy volunteers. The roles of dialyser membranes and alcohol washing procedures were investigated. The source of extracorporeal prostaglandin E2 was estimated by a specific platelet cyclo-oxygenase antagonist. Extracorporeal thromboxane production, with and without antagonist, was compared in an attempt to substantiate the role of the cyclo-oxygenase pathway by sources other than platelets. Clinical investigations show that prostaglandin liberation in the extracorporeal bloodstream is detectable. Additionally, laboratory results suggest an association between the type of dialyser membrane and extracorporeal prostaglandin release. The amount of prostaglandin E2 was reduced when dialysers were pre-washed with alcohol. Furthermore, it was experimentally possible to determine that a large part of extracorporeal prostaglandin E2 is released by sources other than platelets, suggesting a possible role of monocytes in extracorporeal prostaglandin production.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Effects of age and diagnosis on thyrotropin response to thyrotropin-releasing hormone in psychiatric patients.

The thyrotropin (thyroid-stimulating hormone; TSH) response to thyrotropin-releasing hormone (TRH) was studied in 64 age-matched healthy volunteers, 44 patients with endogenous depression, and 21 patients with schizophrenia. A significant negative correlation between delta TSH and age was found both in healthy subjects and in depressed patients. We based our comparison on normal ranges for delta TSH calculated from the delta TSH values in the healthy subjects related to age. It was then seen that blunted TSH response to TRH does not occur significantly more often in depression (13.6%) than in healthy controls (4.7%). Blunted TRH test results were also found in a considerable number of severely ill schizophrenic patients (19%). Application of an improved radioimmunoassay revealed a highly significant correlation between TSH values at baseline and after stimulation, and showed decreased baseline TSH levels in subjects with blunted TRH test results.

Adult↗
PubMed1986

Familial dysalbuminaemic hyperthyroxinaemia: studies of albumin binding and implications for hormone action.

The abnormal intermediate-affinity T4 binding to albumin which is characteristic of familial dysalbuminaemic hyperthyroxinaemia (FDH) is dependent on buffer, temperature, and ionic composition. Scatchard analysis of T4-binding to isolated albumin preparations from FDH subjects showed that half the circulating albumin showed the higher-affinity T4 binding site, assuming one site per molecule. Using dextran-charcoal separation at 4 degrees C the T4 affinity (Kd) of purified albumin from FDH subjects was 7.5 nmol/l in phosphate and 17 nmol/l in Tris-Cl- buffer. T4 binding to FDH albumin was inhibited by a range of substances in the order: 8-anilino-1-naphthalene sulphonic acid greater than merthiolate greater than propylthiouracil greater than methyl-thiouracil greater than carbimazole greater than salicylate greater than barbitone. Binding of T4 was competitively inhibited by low concentrations of dithiothreitol (DTT). The effect of DTT 0.1-0.5 nmol/l was reversed by removal of DTT by dialysis. Competition with a range of iodothyronines indicated that the 3', 5'-iodine atoms are most important for binding to this site. Serum binding of salicylate, frusemide, fenclofenac and barbituric acid, and a range of steroid hormones was similar in FDH and normal sera. Serum levels of sex hormone binding globulin (SHBG), were not significantly different from sex-matched controls. Nuclear [125I]-T3 binding sites in circulating lymphocytes from two FDH subjects showed affinities (Kd) of 59 and 79 pmol/l (normal 67 +/- 7 pmol/l, n = 6). These findings suggest that the highly specific binding anomaly of FDH is due to a disulphide-dependent structural change in albumin.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Protein Disorders↗
PubMed1986

In vivo formation of diiodotyrosine by extrathyroidal thyroxine ether-link cleavage and effects of mononitrotyrosine on this pathway in the rat.

The formation of DIT from T4 was quantitatively studied in thyroidectomized (T) rats given 16 micrograms synthetic T4 daily. Measurement of the elimination of radioiodinated DIT and T4 tracers from serum yielded MCRs of 19.0 ml/h X 100 g body weight for DIT and 0.65 ml/h X 100 g body weight for T4. Mean serum concentrations +/- SD (nanomoles per liter; n = 8) measured by RIA 24 and 48 h after the last T4 administration were as follows: DIT, 0.243 +/- 0.130 and 0.150 +/- 0.070, respectively; T4, 173 +/- 34 and 97 +/- 20, respectively. In T rats which had not received T4, DIT and iodothyronines in serum were undetectable. From the results of kinetic studies and RIA measurements, the fraction of circulating T4 converted to DIT was calculated to be 3.9-4.3%. After administration of the iodotyrosine inhibitor 3-nitro-L-tyrosine (MNT) to T4-treated T rats at a dosage of 50 mumol/day for 1 week or longer, it was possible to observe, on the one hand, the expected delay of DIT tracer elimination from serum resulting in a decreased MCR of 9.9 ml/h X 100 g body weight. On the other hand, MNT treatment led to a strong decline of DIT serum levels below the detection limit in all animal groups. This effect of MNT on the peripheral T4-to-DIT conversion requires further studies using other experimental systems for confirmation and elucidation of its mechanism. It is concluded that peripheral DIT formation in the animal model used occurs via ether-link cleavage of administered T4 and/or some of its iodothyronine metabolites. On the basis of data from recent studies, the peripheral DIT turnover resulting from iodothyronine degradation can be estimated to be about 35% in intact rats. Our data confirm the in vivo generation of extrathyroidal DIT from T4 in the rat. Although the experiments were performed at unphysiologically high T4 serum levels and our quantitative data, therefore, cannot be applied to euthyroid conditions with absolute certainty, the results suggest that ether-link cleavage of T4 yielding DIT is not an insignificant pathway of peripheral T4 metabolism in the rat.

Animals↗
PubMed1986

Response of total and 'free' thyroid hormones and diiodotyrosine to bovine TSH in subclinical hypothyroidism.

Thirty-three patients with Addison's disease were studied. Twenty-two had idiopathic Addison's disease; within this group, 14 patients had clinical or subclinical hypothyroidism, and 16 had increased titres of thyroid autoantibodies. Five patients had tuberculous, and eight had unclassifiable Addison's disease; only one patient in the latter group had evidence of thyroid autoimmunity. A stimulation test with 15 mU bTSH/kg was performed in three patients with Schmidt's syndrome (coexisting Addison's disease and manifest primary hypothyroidism), 15 patients with either subclinical hypothyroidism or increased titres of thyroid autoantibodies, 10 patients without thyroid involvement, and 10 normal controls. There was no detectable increase of 'free' and total thyroid hormones in Schmidt's syndrome. The mean increases after 3-4 h of T4, fT4, T3 and fT3 were 22, 35, 63 and 66%, respectively, in patients without thyroid involvement, and 13, 24, 46 and 45% in patients with subclinical hypothyroidism. 'Free' but not total thyroid hormones rose significantly (P less than 0.01) higher in patients without signs of thyroid involvement than in patients with subclinical hypothyroidism and/or thyroid autoantibodies. Thyroid hormone response to bTSH in Addison's disease with apparently healthy thyroid glands was not different from normal controls. Serum diiodotyrosine rose in all groups except in hypothyroidism; hypothyroid patients had, however, basal levels well within the normal range. Thus, thyroid hormone synthesis appears to be blocked at a point distal to diiodotyrosine formation in this particular situation. These results support the assumption that TSH elevation in idiopathic Addison's disease is due to coexisting thyroid autoimmunity and that it reflects incipient thyroid failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Addison Disease↗
PubMed1985

Ru-labeled ruthenocenoyl-glycine: comparison of clearance with hippuran.

Ruthenocenoyl-glycine (ruppuran) is a metallocene analog of iodo-labeled hippuran. After injection of 103Ru-labeled ruppuran and ruthenocenoyl-1,1'-diglycine in rabbits, measurement with external detectors revealed a very rapid accumulation in the kidneys followed by rapid excretion of the 103Ru activity. By measurement of the radioactivity concentration in plasma and urine samples collected 1-60 min after IV injection, the plasma clearance was calculated and compared with the clearance of 125I-labeled hippuran injected simultaneously. The clearance of ruppuran and ruthenocenoyl-diglycine in rabbits was found to be somewhat higher than that of hippuran. Extrapolating to man (1.73 m3), plasma clearance with both ruthenocene derivatives was approximately 500-600 ml/min. Biochemical data as well as the nuclear properties of 97Ru indicate the usefulness of 97Ru-labeled ruthenocenoyl-glycine as a radiopharmaceutical for kidney function studies.

Animals↗
PubMed1985

Effects of small doses of bovine TSH on serum levels of free and total thyroid hormones, their degradation products, and diiodotyrosine.

Bovine TSH was administered iv to 10 normal volunteers in doses of 2.5, 7.5, 15 and 30 mU/kg. Brisk elevations of serum diiodotyrosine occurred already after the smallest dose (mean, +183%) while larger doses had only slight additional effects. T3 rose much higher than T4 (+71% compared to +23% after 15 mU bTSH/kg), and free thyroid hormones exhibited changes similar to total T3 and total T4. The mean absolute increase in serum fT3 ranged from 2.03 to 9.04 pmol/l and proved to be an easily measurable parameter for the TSH effect. Dose-response effects were seen for the increase of fT4, fT3 and T3. TBG and rT3 did not change but the degradation product 3,3'-T2 showed large increments of serum levels. There was no correlation between the response of T3 and T4, fT3 and fT4, or diiodotyrosine and any of the other parameters of thyroid function. The interindividual differences in the magnitude of thyroid hormone response to TSH were considerable, and there was no relationship between this response and thyroid volume by ultrasound. We conclude that direct stimulation of the thyroid gland with bTSH in small doses leads to consistent increases of thyroid hormones, especially T3 and fT3, that the response varies between individuals, and that the precursor diiodotyrosine is released together with thyroid hormones.

Adult↗