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Biomedical subjects

R Bergmann

Publications and source records attributed to R Bergmann.

At least 19 recordsLinked to original sources
PubMed1996

High-affinity binding of [3H]paroxetine to caudate nucleus and microvessels from porcine brain.

Serotonin (5-HT) is an important signal molecule not only for neurones but also for a variety of other cell types. Targeting the brain endothelium, the constitutive element of the blood-brain barrier (BBB), it elicits permeability changes. Using the selective 5-HT uptake inhibitor [3H]paroxetine we demonstrated the presence of a 5-HT transporter-like protein at the BBB. The binding capacities (Bmax) at the BBB (382 fmol mg-1) and on caudate nucleus membranes (392 fmol mg-1) were similar. However, the binding affinities differed by a factor of 5 (membranes: Kd = 0.10 nM, BBB: 0.47 nM). The affinities of various specific uptake inhibitors were also 2- to 13-fold lower in the microvessel preparation. It is suggested that the 5-HT transporter(s) in the brain and microvessels are different or differently regulated proteins.

Animals↗
PubMed1996

Prospective study of the atopy preventive effect of maternal avoidance of milk and eggs during pregnancy and lactation.

UNLABELLED: The preventive effect of maternal avoidance of cow's milk and eggs on the development of atopic dermatitis and sensitization to food allergens was studied in a prospective trial with families at high risk for atopy, intervention included encouraging exclusive breast feeding for at least 3 months and delaying the controlled introduction of solid foods. In addition, one group received a maternal diet with the complete avoidance of milk and eggs in the last trimester of pregnancy and during the period of exclusive breast feeding, another group had the same diet starting after delivery, and mothers of the third group had no dietary restrictions. The period prevalences of atopic dermatitis as well as the rates of specific sensitization to eggs and milk at 6 and 12 months were not significantly different between groups. We were unable to demonstrate a significant preventive effect of maternal diet. CONCLUSION: While breast feeding should be promoted for children at risk for atopy, mothers can be encouraged to stay on normal diet during pregnancy and the breast feeding period.

Animals↗
PubMed1995

Specific binding of [3H]imipramine indicates the presence of a specific serotonin transport system on endothelial cells of porcine brain.

The blood-brain barrier (BBB) represents a complex epithelial interface in vertebrates that separates the blood compartment from the extracellular fluid compartment of the brain. Isolated microvessels are a tool to study the function of this interface in vitro. Here we report on attempts to demonstrate the presence of the serotonin transporter on microvessels from the porcine brain. For comparison, membrane preparations of brain tissue were used. The enrichment of the microvessel fraction determined by measurement of alkaline phosphatase activity was about 30-fold. In saturation experiments high- and low-affinity binding of [3H]imipramine could be demonstrated on brain microvessels. Different concentrations of unlabelled imipramine were used to inhibit the binding of [3H]imipramine in brain tissue and microvessels. Comparison of both preparations revealed a two-fold higher density of the high-affinity binding site, while the density of the low-affinity binding site was 28-fold higher in brain microvessels. Imipramine binding could be inhibited by potent non-tricyclic inhibitors of the serotonin transporter such as paroxetine and fluoxetine but also by the tricyclic antidepressant drugs clomipramine and desipramine. Therefore, it is concluded that [3H]imipramine labels serotonin uptake sites localized on porcine brain microvessels.

Animals↗
PubMed1995

Evaluation of radioselenium labeled selenomethionine, a potential tracer for brain protein synthesis by PET.

The blood-brain transfer, protein incorporation and metabolism of L-[75Se]selenomethionine (SeMet) of relatively high specific activity (> 400 GBq mmol) were studied in male Wistar rats. The highest uptake was found in the pancreas, followed by the tumor, kidney, liver, brain and muscle. In addition, plasma and brain samples of rats were analyzed for labeled fractions of free SeMet, metabolites, and SeMet bound to t-RNA and proteins. For example, free SeMet represented more than 80% of brain radioactivity at 1.5 min while it was less than 15% at 360 min. A concomitant increase was observed for protein bound SeMet in brain. A three-compartment model was applied to calculate the blood-brain transfer constant (K1 (0.15 +/- 0.070 mL g-1 min-1) and the rate constant of SeMet incorporation into proteins (k3 = 0.026 +/- 0.008 min-1). The apparent incorporation of methionine into proteins was estimated to be about 0.73 nmol g-1 min-1. From the studies it is concluded that the use of L-[75Se]selenomethionine may be appropriate to measure brain protein incorporation in humans with PET.

Animals↗
PubMed1995

Scintigraphic visualization of pulmonary thrombi with 123I-YPACK-TNK-tPA.

BACKGROUND: We have previously demonstrated that radiolabeled tissue-type plasminogen activation (tPA) in which the plasminogen-activating catalytic site has been inactivated binds avidly to thrombi and can be used for scintigraphic detection of pulmonary thrombi in vivo. The present study was performed to overcome identified limitations of the initially developed approach and to determine whether a tracer made with a molecular variant of tPA, TNK-tPA, would provide superior images of pulmonary thrombi and hence facilitate differential diagnosis of pulmonary embolism from acute myocardial infarction. It was thought that TNK-tPA may be superior in view of its longer biological half-life and less avid uptake by macrophages that would otherwise contribute to high background because of non-clot-selective uptake of the tracer. METHODS: 123I-tyrosylprolylarginyl chloromethyl ketone (123I-YPACK-TNK-tPA) was infused into the systemic circulation of dogs with either pulmonary or right ventricular thrombi induced with thrombogenic tips of modified guide wires. Planar and single-photon emission computed tomography (SPECT) scintigraphic data were obtained, and blood and tissue samples were acquired for analysis of the distribution of the radiotracer over time. RESULTS: Tracer cleared from blood with an alpha phase half-life of 10 +/- 1 min, paralleling the clearance of unlabeled TNK-tPA. Only minimal release of labeled fragments from liver into blood occurred during the entire time course of the imaging studies. Pulmonary thrombi were visualized with SPECT within 30-120 min in all dogs. Images were superior to those obtained after infusion of labeled wild-type tPA, primarily because of diminished background radioactivity and consequently increased scintigraphic contrast. In one dog which had a right ventricular thrombus, the thrombus was readily detectable in both planar and SPECT images. CONCLUSIONS: Radiolabeled TNK-tPA in which plasminogen-activating activity has been inhibited biochemically is an excellent radiopharmaceutical for prompt scintigraphic detection of pulmonary and ventricular thrombi in vivo, and an attractive candidate for rapid, sensitive and non-invasive diagnosis of pulmonary thromboembolic disease in patients.

Amino Acid Chloromethyl Ketones↗
PubMed1994

The influence of substituents in 3-position on the activity of chroman-type potassium channel activators.

Swern oxidation of chromanol 1 led to ketone 3 with concomitant chlorination of the adjacent 4-position. Using Leuckart conditions, chromanone 2 was converted to enamine 5.--4-Bromochromene-3-carbaldehyde 8, which was obtained by Vilsmeier-Arnold reaction from 7, turned out to be a suitable intermediate for the insertion of the pyridone residue. 3-Chloro derivatives 16 and 19 resulted on heating the mesylate or tosylate with LiCl in DMF. Bromination of chromene 20 led to 21.--All compounds were tested for oral antihypertensive activity in spontaneously hypertensive rats with a dose of 1 mg/kg.

Animals↗
PubMed1994

Developmental changes of enzymes involved in peptide degradation in isolated rat brain microvessels.

The specific activities of aminopeptidase A (APA), aminopeptidase M (APM), and dipeptidyl-aminopeptidase IV (DP IV) were determined in isolated brain microvessels and in brain homogenate of rats with different ages (between 1 and 8 weeks old). In addition, the blood-brain barrier (BBB)-specific enzymes gamma-glutamyltranspeptidase (gamma-GT) and alkaline phosphatase (ALP) were measured. As similarly described by others, gamma-GT activity increased during this time period by fourfold, whereas ALP increased between weeks 1 and 2 and declined thereafter. DP IV activity increased fivefold during the first 8 weeks after birth and APM activity increased by twofold. A decrease of APA activity was found between weeks 1 and 2 after birth followed by an increase thereafter. The development of aminopeptidase activities responsible for the processing of specific neuropeptides acting on brain microvessels may be important in the development of regulation processes for cerebral blood flow and BBB permeability in the maturing animal.

Aminopeptidases↗
PubMed1994

Hyperacute rejection in an ex vivo model of renal xenografting. Role of the mediator response and its pharmacologic manipulation by the specific platelet-activating factor antagonist WEB 2086BS.

The pharmacologic modulation of the platelet-activating factor antagonist WEB 2086BS on the release of metabolites of the arachidonic acid and the cytokine TNF alpha was investigated in an ex vivo xenograft model of hyperacute rejection. Pig kidneys were perfused for 60 min in a perfusion system with oxygenated heparinized human or autologous porcine blood, respectively. During autologous perfusion, no alterations in the mediator response could be detected, whereas xenogeneic perfusion induced progressive release of mediators. Treatment by the platelet-activating factor antagonist WEB 2086BS resulted in a significantly reduced liberation of the cytokine TNF alpha and of prostanoids. The histological findings verified that a hyperacute rejection in the xenogeneic perfused organs had occurred, which was mitigated by the treatment with WEB 2086BS. This observation confirms that inflammatory mediators play a decisive role in hyperacute xenogeneic rejection. The results suggest that suppression or manipulation of mediator-specific tissue receptors by receptor-antagonists could be an additional therapeutic mode to control hyperacute rejection in xenogeneic transplantation.

Adult↗
PubMed1992

Simultaneous study of the biodistribution of radio-yttrium complexed with EDTMP and citrate ligands in tumour-bearing rats.

The influence of the ligands ethylenediaminetetramethylene phosphonic acid (EDTMP) and citrate (CIT) on the biodistribution of radio-yttrium in rats bearing a DS-carcinosarcoma was compared. 88Y-EDTMP and 87Y-CIT were i.v. injected into the same animals. Faster blood clearance and higher renal excretion were observed for the EDTMP-ligand. Of high practical interest is the reduced liver uptake of radio-yttrium (by one order of magnitude) with the EDTMP complex. Since bone and tumour accumulation is only weakly influenced, high tumour-to-liver ratios (up to 14) were observed. We propose to use EDTMP or similar complex ligands for liver blocking when radionuclides like 90Y, 169Yb, 225Ac or other group 3 elements are to be applied in endoradionuclide therapy technique.

Animals↗
PubMed1991

Experimental and clinical main forms of hypoxic-ischaemic brain damage and their monitoring.

A short review of main pathogenetic forms of hypoxic-ischaemic brain damage and its consequences for causally orientated therapy and monitoring is given. Different pathogenetic components act in several combinations. In these processes disturbances of the cardio-vascular system, of the haemorheology mainly at the level of microvessels, and disturbances of the blood brain barrier are involved. Furthermore, there are relevant disturbances of the neuronal metabolism such as accumulation of cytosolic Ca++ or disturbances caused by the effect of radicals, lipid peroxidation and changes of protein synthesis. Nowadays, chances of a cause-related therapy are increased by improved evaluation of main pathogenetic components especially regarding secondary brain damage. To evaluate these components in detail, animal models must be more clinically related, especially regarding long-term studies. The increasing knowledge about critical thresholds of reversible and irreversible brain changes also favours effective cerebral function monitoring. The main conclusions from previous experimental as well as clinically related studies indicate the necessity of very early therapeutical interventions.

Brain↗
PubMed1991

Interaction between systemic circulation and brain injuries in newborns.

In several studies different pathogenetic mechanisms of metabolic and/or cardiovascular origin were shown depending on the type of hypoxic or hypoxic/hypercapnic stress and conditions of animals (normal developed or intrauterine growth retarded newborn piglets). Thus, in normal-weight piglets the prevention of compensatory hyperventilation owing to severe hypoxia (artificially ventilated animals) leads to critical, i.e. lethal acidosis. In intrauterine growth retarded piglets, a severe hypoxia cannot be vitally compensated because of the restricted circulatory centralization. Moreover, a limited cerebrovascular dilatation during moderate hypoxia/hypercapnia produces a critical state of the metabolic supply in those animals.

Adaptation, Physiological↗
PubMed1991

Investigations of cerebral glucose utilization into the newborn brain: a [18F]-FDG positron emission tomography study using a high resolution multiwire proportional chamber detector device.

An experimental approach is presented, where for the first time positron emission tomography (PET, the most important method for in vivo measuring the key functions of brain physiology and metabolism) was applied together with other techniques for quantitative-topological estimation of key parameters such as rCMRGlu in normal and disturbed brain function states in the newborn period.

Animals↗