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Biomedical subjects

A Baumgartner

Publications and source records attributed to A Baumgartner.

At least 55 records · Page 3Linked to original sources
PubMed1998

Effects of acute administration of ethanol and the mu-opiate agonist etonitazene on thyroid hormone metabolism in rat brain.

The effects of acute, low-dose administration of ethanol (1 g/kg bodyweight) and the mu-opioid receptor agonist etonitazene (30 microg/kg bodyweight) on the activities of the iodothyronine deiodinase isoenzymes were investigated in nine regions of the rat brain. The experiments were performed at three different times of the 24-h cycle (1300, 2100 and 0500 hours) and the rats were decapitated 30 and 120 min after administration of the respective drugs. Interest was focused on changes in the two enzymes that catalyze 1) 5'-deiodination of thyroxine (T4) to the biologically active triiodothyronine (T3), i.e. type II 5'-deiodinase (5'D-II) and 2) 5 (or inner-ring) deiodination of T3 to the biologically inactive 3'3-T2, i.e. type III deiodinase (5D-III). 120 min after administration of ethanol and etonitazene 5D-III activity was selectively inhibited in the frontal cortex (at 1300 and 1700 hours) and the amygdala (at all three measuring times). The 5'D-II activity was significantly enhanced 30 min after administration of etonitazene in the frontal cortex, amygdala and limbic forebrain, and after administration of ethanol in the amygdala alone. These effects on 5'D-II activity were seen at 2100 hours only. In conclusion, the two different addictive drugs both reduced the inactivation of the physiologically active thyroid hormone T3 and enhanced its production. These effects occurred almost exclusively in the brain regions which were most likely to be involved in the rewarding properties of addictive drugs. As thyroid hormones have stimulating and mood-elevating properties, an involvement of these hormones in the reinforcing effects of addictive drugs seems conceivable.

Animals↗
PubMed1998

Treatment of refractory depression with high-dose thyroxine.

In an open clinical trial we investigated whether addition of supraphysiological doses of thyroxine (T4) to conventional antidepressant drugs has an antidepressant effect in therapy-resistant depressed patients. Seventeen severely ill, therapy-resistant, euthyroid patients with major depression (12 bipolar, five unipolar) were studied. The patients had been depressed for a mean of 11.5 +/- 13.8 months, despite treatment with antidepressants and, in most cases, augmentation with lithium, carbamazepine, and neuroleptics. Thyroxine was added to their antidepressant medication, and the doses were increased to a mean of 482 +/- 72 micrograms/day. The patients' scores on the Hamilton rating Scale for Depression (HRSD) declined from 26.6 +/- 4.7 prior to the addition of T4 to 11.6 +/- 6.8 at the end of week 8. Eight patients fulfilled the criteria for full remission (a 50% reduction in HRSD score and a final score of < or = 9) within 8 weeks and two others fully remitted within 12 weeks. Seven patients did not remit. The 10 remitted patients were maintained on high-dose T4 and followed up for a mean of 27.2 +/- 22.0 months. Seven of these 10 remitted patients had an excellent outcome, two had milder and shorter episodes during T4 augmentation treatment, and one failed to profit from T4 treatment during the follow-up period. Side effects were surprisingly mild, and no complications were observed at all. In conclusion, augmentation of conventional antidepressants with high-dose T4 proved to have excellent antidepressant effects in approximately 50% of severely therapy-resistant depressed patients.

Aged↗
PubMed1998

Rat brain type II 5'-iodothyronine deiodinase activity is extremely sensitive to stress.

The effects of different kinds of acute stressor on thyroid hormone concentrations and deiodinase activities were investigated in four brain regions (frontal cortex, amygdala, hypothalamus, and cerebellum) and in the pituitaries and livers of adult male rats. Five groups of rats were killed after each of the following stressors: (a) an intraperitoneal injection of saline, (b) intragastric intubation, (c) and (d) two different forms of handling, being grasped as for intraperitoneal injection and being moved from one cage to another, and (e) a 2-h period spent in a slowly rotating drum. Two other groups were placed in the rotating drums for 10 and 19 h (sleep deprivation experiment), respectively. All stressors induced significant (in some cases up to 200%) increases in the activity of type II 5'-iodothyronine deiodinase, which catalyzes the deiodination of the prohormone L-thyroxine (T4) to the active metabolite 3,3',5-triiodo-L-thyronine (T3). As a consequence, the tissue concentrations of T4 fell, and those of T3 rose (sometimes by up to 300%). However, these changes were limited to selected areas of the brain that were specific for each stressor and were not seen in all brain regions investigated in any group. No clear-cut effects of stress were seen on the activities of the type III 5-iodothyronine deiodinase isoenzyme, which catalyzes the inactivation of T3, on liver or serum thyroid hormone concentrations or on liver of brain type I 5'-iodothyronine deiodinase activities. In summary, our results show that even mild and very brief stress can induce marked increases in T3 concentrations specifically in brain but not in liver or blood. Thus, contrary to common opinion, thyroid hormones may play an important physiological role in stress reactions, at least in tissues that contain type II 5'-iodothyronine deiodinase, such as brain and pituitary.

Animals↗
PubMed1998

3,3'-Diiodothyronine concentrations in the sera of patients with nonthyroidal illnesses and brain tumors and of healthy subjects during acute stress.

In this article we describe the development of a highly sensitive, accurate, and reproducible RIA for the measurement of 3,3'-diiodothyronine (3,3'-T2) in human serum and brain tissue. The detection limits were 1.8 fmol/g and 1.5 pmol/L in human brain tissue and serum, respectively. Serum concentrations of 3,3'-T2 were measured in 4 groups of patients with nonthyroidal illnesses (NTI), i.e. brain injuries (n = 15), sepsis (n = 24), liver disease (n = 22), and brain tumors (n = 23). The mean serum concentration of 3,3'-T2 in 62 healthy controls was 46.6 +/- 20.0 pmol/L. 3,3'-T2 levels declined significantly with increasing age. They were significantly lower in patients with brain injury (34.2 +/- 19.4 pmol/L; P = 0.006), were at the upper limit of normal in patients with sepsis (57.0 +/- 36.9 pmol/L; P = 0.06), and were elevated in patients with liver disease (72.6 +/- 56.7 pmol/L; P = 0.04) and brain tumors (89.0 +/- 40.9 pmol/L; P = 0.01). The serum levels of T3 were significantly lower than those in controls in all 4 patient groups. Serum concentrations of 3,3'-T2 were significantly enhanced in 9 patients with hyperthyroidism (85.4 +/- 43.0 pmol/L; P = 0.01) and were reduced in 12 patients with hypothyroidism (14.9 +/- 9.2 pmol/L; P = 0.001). In both normal brain tissue, obtained either intraoperatively or excised postmortem, and brain tumors, the concentrations of 3,3'-T2 ranged between 50-300 fmol/g. In healthy controls, 2 different forms of acute stress (sleep deprivation and delivering a lecture) significantly increased serum levels of T4 and T3, but did not affect those of 3,3'-T2 or 3,5-T2. In conclusion, our results show that, contrary to expectation, a low T3 syndrome in NTI is not always associated with low serum concentrations of 3,3'-T2. The production of 3,3'-T2 in NTI seems to be regulated in a disease-specific manner, resulting in unchanged, reduced, or elevated hormone concentrations.

Adolescent↗
PubMed1998

Doppler color-flow imaging: screening of a patent foramen ovale in children scheduled for neurosurgery in the sitting position.

A patent foramen ovale (PFO) is the most common cause of paradoxical air embolism during neurosurgical procedures in the posterior fossa in the sitting position in both adults and children. To detect right-to-left shunting, we performed Doppler color-flow imaging preoperatively in 30 children scheduled for neurosurgical procedures in the sitting position. A PFO was diagnosed on the basis of color alterations indicating an immediate blood shunt through a PFO. Six of 30 children (20%) had a PFO; in 4 of these children the sitting position then was avoided, and 2 children were operated on in a special supine position with minimal elevation of the head. Venous air embolism occurred in 9 of 24 (37%) children operated on in the sitting position and in none of the 6 children operated on in a nonsitting position. We conclude that Doppler color-flow mapping could be a useful noninvasive technique to screen children scheduled for neurosurgery in the sitting position for the presence of a PFO.

Adolescent↗
PubMed1997

Dopamine receptor gene expression in an animal model of 'behavioral dependence' on ethanol.

The steady-state levels of messenger RNA (mRNA) of five cloned dopamine (D) receptors were measured in five brain regions in rats in a recently developed animal model of 'behavioral dependence' on ethanol. One group of rats was given the choice between ethanol and water over a 9-month period and developed 'behavioral dependence' on ethanol (group a). This group was compared with a group given the choice between ethanol and water for only 2 months (not yet behaviorally dependent, group b), a group forced to consume ethanol as sole fluid over a 9-month period (not behaviorally dependent, group c) and ethanol-naive control rats. All groups were sacrificed 1 month after ethanol withdrawal. The concentrations of mRNA of D3-receptors in the limbic forebrain (which included the nucleus accumbens) were significantly lowered in groups a and b, but unchanged in group c. D3 mRNA levels were reduced in the hippocampus of group b and unchanged in the cortex, amygdala and striatum. No significant changes in the mRNA concentrations of D1-, D2-, D4- or D5-receptors were seen in the five brain regions in any group. In conclusion, chronic consumption of ethanol under the 'free-choice condition', which may best induce the drug-rewarding effect, leads to specific changes in the D3-receptor gene expression which were not seen after forced ethanol administration. Changes in D3 mRNA levels were, however, not a specific correlate of 'behavioral dependence', as they were also detected in rats not yet 'behaviorally dependent' (group b).

Alcohol Drinking↗
PubMed1997

Thyroid hormone metabolism in the rat brain in an animal model of 'behavioral dependence' on ethanol.

Thyroid hormone metabolism was investigated in the frontal cortex and amygdala in groups of rats either 'behaviorally dependent' on ethanol or chronically exposed to ethanol, but not 'dependent'. The activities of the 5'II deiodinase isoenzyme, which catalyzes the deiodination of thyroxine (T4) to the active metabolite triiodothyronine (T3), was elevated in the frontal cortex in both the 'behaviorally dependent' and the 'non-dependent' rats. The activities of the 5-II deiodinase isoenzyme, which catalyzes the inactivation of T3 to 3,3'-T2 was, however, selectively inhibited in the amygdalas of the rats 'behaviorally dependent' on ethanol, but normal in the 'non-dependent' rats. This suggests that increases in intracellular concentrations of T3 in the amygdala may be specifically related to reward mechanisms and the development of 'behavioral dependence' on ethanol.

Alcoholism↗
PubMed1997

Biometric investigation of changes in the anterior eye segment during accommodation.

Non-invasive biometry of the anterior structures of the human eye can be performed with unprecedented precision of 8-10 microns and a resolution of approximately 9 microns by partial coherence interferometry, which has the potential to assess the effect of cycloplegia on the ocular components of the anterior eye segment, to further improve the precision to 1-2 microns by the use of these agents and to quantify the amount of residual accommodations in different states of cycloplegia. In addition, the anterior chamber depth, the thickness of the crystalline lens, their changes during accommodation, as well as the movement of the anterior and posterior lens pole during accommodation can be quantified objectively and accurately to investigate the mechanism of accommodation.

Accommodation, Ocular↗
PubMed1997

Effects of lithium and carbamazepine on thyroid hormone metabolism in rat brain.

The effects of lithium (LI) and carbamazepine (CBM) on thyroid hormone metabolism were investigated in 11 regions of the brain and three peripheral tissues in rats decapitated at three different times of day (4:00 A.M., 1:00 P.M., and 8:00 P.M.). Interest was focused on the changes in the two enzymes that catalyze: (1) the 5'deiodination of T4 to the biologically active T3, i.e., type II 5'deiodinase (5'D-II) and (2) the 5 (or inner-ring) deiodination of T3 to the biologically inactive 3'3-T2, i.e., type III 5 deiodinase (5D-III). A 14-day treatment with both LI and CBM induced significant reductions in 5D-III activity. However, 5'D-II activity was elevated by CBM and reduced by LI, both administered in concentrations leading to serum levels comparable with those seen in the prophylactic treatment of affective disorders. The effects were dose dependent, varied according to the region of the brain under investigation, and strongly depended on the time of death within the 24-hour rhythm. The consequences of these complex effects of LI and CBM on deiodinase activities for thyroid hormone function in the CNS and also their possible involvement in the mechanisms underlying the mood-stabilizing effects of both LI and CBM remain to be investigated.

Animals↗
PubMed1997

Evidence for circadian variations of thyroid hormone concentrations and type II 5'-iodothyronine deiodinase activity in the rat central nervous system.

The 24-h patterns of tissue thyroid hormone concentrations and type II 5'- and type III 5-iodothyronine deiodinase (5'D-II and 5D-III, respectively) activities were determined at 4-h intervals in different brain regions of male euthyroid rats entrained to a regular 12-h light/12-h dark cycle (lights on at 6:00 a.m.). Activity of 5'D-II, which catalyzes the intracellular conversion of thyroxine (T4) to 3,3',5-triiodo-L-thyronine (T3) in the CNS, and the tissue concentrations of both T4 and T3 exhibited significant daily variations in all brain regions examined. Periodic regression analysis revealed significant circadian rhythms with amplitudes ranging from 9 to 23% (for T3) and from 15 to 40% (for T4 and 5'D-II) of the daily mean value. 5'D-II activity showed a marked nocturnal increase (1.3-2.1-fold vs. daytime basal value), with a maximum at the end of the dark period and a minimum between noon and 4:00 p.m. 5D-III did not exhibit circadian patterns of variation in any of the brain tissues investigated. Our results disclose circadian rhythms of 5'D-II activity and thyroid hormone concentrations in discrete brain regions of rats entrained to a regular 12:12-h light-dark cycle and reveal that, in the rat CNS, T3 biosynthesis is activated during the dark phase of the photoperiod. For all parameters under investigation, the patterns of variation observed were in part regionally specific, indicating that different regulatory mechanisms may be involved in generating the observed rhythms.

Analysis of Variance↗
PubMed1997

Elevated 3,5-diiodothyronine concentrations in the sera of patients with nonthyroidal illnesses and brain tumors.

This study reports the development of a highly sensitive and reproducible RIA for the measurement of 3,5-diiodothyronine (3,5-T2) in human serum and tissue. The RIA employs 3-bromo-5-[125I]iodo-L-thyronine (3-Br-5-[125I]T1) as tracer, which was synthesized carrier free by an interhalogen exchange from 3,5-dibromo-L-thyronine (3,5-Br2T0). The detection limits were 1.0 fmol/g and 0.8 pmol/L in human brain tissue and serum, respectively. T3, diiodothyroacetic acid, and 3-monoiodothyronine cross-reacted with a 3,5-T2 antibody to the extent of 0.06%, 0.13%, and 0.65%, respectively. Serum concentrations of 3,5-T2 were measured in 62 healthy controls and 4 groups of patients with nonthyroidal illness, i.e. patients with sepsis (n = 24), liver diseases (n = 23), head and/or brain injury n = 15), and brain tumors (n = 21). The mean serum level of 3,5-T2 in the healthy subjects was 16.2 +/- 6.4 pmol/L. Concentrations of 3,5-T2 were significantly elevated in patients with sepsis (46.7 +/- 48.8 pmol/L; P < 0.01), liver diseases (24.8 +/- 14.9 pmol/L; P < 0.01), head and/or brain injury (24.1 +/- 11.3 pmol/L; P < 0.05), and brain tumors (21.6 +/- 4.8 pmol/L; P < 0.01). In all 4 patient groups, serum levels of T3 were significantly reduced, confirming the existence of a low T3 syndrome in these diseases. Serum concentrations of 3,5-T2 were significantly elevated in patients with hyperthyroidism (n = 9) and were reduced in patients with hypothyroidism (n = 8). The levels of T4, T3, and 3,5-T2 were measured in normal human tissue samples from the pituitary gland and various brain regions and in brain tumors. In normal brain tissue, the concentrations of 3,5-T2 ranged between 70-150 fmol/g, and the ratio of T3 to 3,5-T2 was approximately 20:1. In brain tumors, however, T3 levels were markedly lower, resulting in a ratio of T3 to 3,5-T2 of approximately 1:1. Recent findings suggest a physiological, thyromimetic role of 3,5-T2, possibly stimulating mitochondrial respiratory chain activity. Should this prove to be correct, then the increased availability of 3,5-T2 in nonthyroidal illness may be one factor involved in maintaining clinical euthyroidism in patients with reduced serum levels of T3 during nonthyroidal illness.

Astrocytoma↗
PubMed1997

[Laser Doppler data analysis during interstitial laser thermotherapy with magnetic resonance control within the scope of an animal experiment study].

The aim of the present study was to investigate, using laser Doppler (LD) flowmetry, the phases immediately prior to and following experimental, neurosurgical laser therapy in animals. Two statistical models obtained on the basis of discriminant analysis are described. These models should enable the user to classify the sets of parameters calculated from the LD signals. With both models which contain 3 and 5 parameters, respectively. 100% discrimination of the two phases was attained. The usefulness of the models could be validated by results obtained with other models.

Animals↗
PubMed1997

Submicrometer precision biometry of the anterior segment of the human eye.

PURPOSE: To demonstrate the feasibility of measuring the anterior structures of the human eye by partial coherence interferometry and to determine its precision for eyes under normal and cycloplegic conditions. METHODS: The dual-beam version of partial coherence interferometry, a recently developed noninvasive optical ranging technique, enables high resolution measurements of several intraocular distances with unprecedented precision. A modified, more sensitive scanning version of this technique was used to assess the central and peripheral corneal thickness, the anterior chamber depth, and the lens thickness of 20 healthy, emmetropic to moderately myopic eyes. Furthermore the anterior structures of three eyes were measured under cycloplegia (1% cyclopentolate) to investigate the influence on the precision of this technique after suppression of residual accommodations. RESULTS: The mean geometric precision (standard deviation) of the measurement of the central corneal thickness was 0.29 micron (range, 0.22 micron to 0.38 micron) and 0.43 micron (range, 0.27 micron to 0.56 micron) for the peripheral corneal thickness at a distance 2 mm from its apex. The precision for measuring the anterior chamber depth and the lens thickness for fixation at infinity was 8.7 microns (range, 3.9 microns to 16.8 microns) and 8.9 microns (rang, 2.9 microns to 14.4 microns) for noncycloplegic eyes and 1.9 microns (range, 1.7 microns to 2 microns) and 1.4 microns (range, 0.7 micron to 1.8 microns) for cycloplegic eyes, respectively. CONCLUSIONS: The dual-beam partial coherence interferometry enables fast, noninvasive, submicrometer precision biometry of the anterior segment of the eye. The precision of determining the anterior chamber depth and the lens thickness is more than one order of magnitude better than that of the currently used ultrasound and optical techniques, and it can be improved by a factor of 5 by using cycloplegia.

Adult↗
PubMed1996

Serum concentrations of thyroid hormones in patients with nonseasonal affective disorders during treatment with bright and dim light.

Serum concentrations of thyroxine (T4), triiodothyronine (T3), and thyrotropine were measured in 34 patients with nonseasonal affective disorders before and after 1 week of light treatment. Nineteen of these patients received bright white light (2500 lx) and 15 dim red light (50 lx) for 2 hours daily in the mornings over a 1-week period. Slight but significant reductions in the rating scores for the depressive symptomatology were found for both the bright-and dim-light groups, but there were no significant differences between the two groups. The improvement is thus most likely a placebo effect. Surprisingly, the small changes in the severity of the depressive symptoms in the group as a whole were significantly correlated to the changes in the serum levels of T4 during the weeks of bright- and dim-light treatment, respectively. The more a patient improved, the further his or her T4 level fell and vice versa. The fluctuations in the concentrations of T4 during light treatment were significantly greater in the depressed patients than in a group of 12 healthy controls who also received bright or dim light, whereas the changes in T3 were significantly smaller than those of the healthy controls. The pronounced fluctuations in T4 levels were probably not secondary to changes in mood. Rather, they are likely to reflect changes in tissue (intracellular) metabolism of T4, which may be involved in the mechanisms underlying the fluctuations in mood in these patients.

Adult↗
PubMed1996

Risk factors for sporadic salmonellosis in Switzerland.

A case-control study was conducted to identify determinants for the acquisition of sporadic Salmonella infection in Switzerland. Over a one-year period (1993), 223 case-control pairs were enrolled in the study and risk factors were assessed by means of self-administered questionnaires. Three-quarters of the isolates were identified as Salmonella enteritidis, most of which (80%) belonged to phage type 4. There were distinct differences in risk factors between infections with Salmonella enteritidis and those with other Salmonella serovars. In both groups recent travel abroad was positively associated with illness. This association was more pronounced for infections with non-enteritidis salmonellae [odds ratio (OR) 39.5; 95% confidence interval (CI) 6.6-236.8, compared to Salmonella enteritidis 4.0; 95% CI 1.8-9.1]. Among the presumably imported infections, Salmonella enteritidis was acquired mostly in other European countries, while other serovars were acquired mostly in countries outside of Europe. Eating food containing raw or undercooked eggs during the three days before the onset of illness increased the risk of infection with Salmonella enteritidis. Desserts made with raw eggs (OR 4.6; 95% CI 2.0-10.6) were more strongly associated with disease than consumption of soft-boiled eggs (OR 2.1; 95% CI 1.2-3.7), suggesting that the risk of infection was dependent on the extent to which eggs were cooked. Egg consumption was not associated with infections with serovars other than Salmonella enteritidis; however, the intake of medications other than antacids was found to be a risk factor (OR 3.5; 95% CI 1.1-11.4).

Adult↗
PubMed1996

Phenolic and tyrosyl ring iodothyronine deiodination and thyroid hormone concentrations in the human central nervous system.

In the present study we investigated the biochemical properties of in vitro phenolic (5'D) and tyrosyl (5D) ring deiodination and the tissue concentrations of T4, T3, and rT3 in adult human central nervous system (CNS) tissue. All samples were obtained from nontumoral tissue at autopsy (n = 6) or neurosurgical operation (n = 5). Both phenolic and tyrosyl ring deiodinase activities were demonstrable in all samples obtained intraoperatively, whereas only tyrosyl ring deiodination was evident in the tissues obtained postmortem. The phenolic ring deiodination pathway corresponded to the type II 5'-deiodinase isoenzyme with regard to its high affinity for T4 and rT3 (Km = 2.2 and 2.4 nmol/L, respectively), its insensitivity to 6-propyl-n-2-thiouracil (PTU), and the sequential reaction mechanism. No PTU-sensitive 5'-deiodination of rT3 was demonstrable. Tyrosyl ring deiodination of both T4 and T3 showed typical type III 5D kinetics (Ka, 6.5 nmol/L for T4 and 3.4 nmol/L for T3) and was PTU insensitive. Nanomolar concentrations of tissue T4, T3, and rT3 were detected in samples obtained both intraoperatively and postmortem. They were very similar to the absolute values of the apparent Km for T4, T3, and rT3 in the phenolic and tyrosyl ring deiodination pathways. In conclusion, we have demonstrated the coexistence of both phenolic and tyrosyl ring deiodinase activities in the human CNS. Their kinetic characteristics, substrate specificity, and reaction mechanisms are very similar to the corresponding type II 5'- and type III 5-iodothyronine deiodinase activities in rat brain. In contrast to the findings in the rat CNS, no PTU-sensitive phenolic ring deiodinase (i.e. type I 5'D) activity was found in the human CNS. This may explain the relatively high tissue concentrations of rT3.

Adolescent↗