Biomedical subjects

W Wesemann

Publications and source records attributed to W Wesemann.

At least 37 records · Page 2Linked to original sources

PubMed1995

Increased number of high sensitive platelets in hypercholesterolemia, cardiovascular diseases, and after incubation with cholesterol.

The number of low density platelets was found to be increased in patients with hypercholesterolemia, as compared with the number in controls. The percentage increase of the low density platelet subpopulation was even more pronounced in patients with hypercholesterolemia when compared with that in patients suffering from myocardial infarction or angina. In vitro studies with control platelets incubated with cholesterol rich liposomes showed also an increase in the subpopulation of low density platelets. After incubation of control platelets with cholesterol rich liposomes, a higher membrane anisotropy and a higher cholesterol to phospholipid (C/P) molar ratio of the plasma membrane were found. Furthermore, cholesterol-enriched platelets were more sensitive upon thrombin stimulation. The results suggest that a shift of platelet subpopulations to a higher number of low density platelets could be caused by either the level of plasma cholesterol or an in-vitro incubation with cholesterol rich liposomes.

Analysis of Variance↗

PubMed1995

In vivo studies on the effects of memantine on dopamine metabolism in the striatum and n. accumbens of the rat.

The action of the amantadine derivative memantine on the dopamine metabolism in the striatum and the n. accumbens of the rat was studied in vivo with different voltammetrical techniques. It was shown by differential pulse voltammetry that memantine enhanced extracellular levels of dopamine (DA) in the striatum of the anaesthetized rat, whereas an increase of 3,4 dihydroxyphenylacetic acid (DOPAC) could be observed only under freely moving conditions using square wave voltammetry. Under chloral hydrate anaesthesia the effect of memantine on extracellular DOPAC levels in the striatum and the n. accumbens was compared with MK-801, a well-known non-competitive NMDA-antagonist. Memantine did not affect striatal DOPAC concentrations under these conditions whereas MK-801 reduced the DOPAC signal. In the n. accumbens memantine enhanced the levels of extracellular DOPAC, while after MK-801 the signal was only slightly different from control. These findings suggest that in addition to its NMDA receptor antagonism, memantine affects dopaminergic transmission also by other mechanisms.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1995

Cerebral oligemic hypoxia and iron toxicity in the mesolimbic system of rats.

60 min of bilateral clamping of the carotid arteries (BCCA) in pentobarbital anaesthetized adult Wistar rats increases the lipid peroxidation in hippocampal tissue as estimated four weeks later. 1.5 micrograms FeCl3 in 2 microliters buffer injected unilaterally in the ventrolateral striatum enforced the effect when applicated one week after the BCCA treatment. During ageing, the explorative and locomotor behaviour of BCCA rats decreased earlier than the behaviour activities of the controls. These activities show no more changes 9 months after surgery but the BCCA treated rats were more sensitive to 2 mg/kg apomorphine s.c., demonstrated by the distance travelled during 1 hour of habituation in a new environment. BCCA treated rats rotate in response to apomorphine after an intrastriatal and ventrolateral injection of 0.3 microgram FeCl3 15 and 14 weeks, respectively, after BCCA and iron instead of 1.5 micrograms after iron injection alone. Transient BCCA leads to a dramatical increase of released DA. We assume, therefore, that during the autooxidation of released DA, free radicals trigger the increase of lipid peroxidation. Predamaged tissue due to increased lipid peroxidation reacts to very small amounts of iron and iron seems to be more toxic in such cerebral tissue.

Animals↗

PubMed1995

Effect of lazaroid U-74389G on iron-induced reduction of striatal dopamine metabolism.

The substantia nigra of parkinsonian brains is reported to contain increased amounts of iron as compared with age-matched controls. Since iron might be cytotoxic via radical mechanisms, we analyzed the effect of intranigral iron infusion on the dopaminergic activity in the striatum of the rat. The striatal dopamine metabolism of the rat was followed 1, 3, and 6 weeks after unilateral intranigral iron (III) (1.5 micrograms) application. A progressive decrease of extraneuronal 3,4-dihydroxyphenylacetic acid (DOPAC) levels was observed in the ipsilateral striatum by means of in vivo pulse voltammetry. The significant reduction of the DOPAC signal could be attenuated by pretreatment of the animals with the lazaroid U-74389G, applied ip 20 minutes before unilateral intranigral iron application. Our data indicate that a single iron application into the substantia nigra leads to a progressive loss of dopaminergic activity in the striatum, also observed in Parkinson patients. Furthermore, the Lazaroid U-74389G seems to be beneficial in this model of Parkinson's disease.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1995

The TaClo concept: 1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo), a new toxin for dopaminergic neurons.

Due to its structural analogy to the neurotoxin MPTP, "TaClo" (1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline), a compound readily originating in vitro from tryptamine ("Ta") and chloral ("Clo"), is discussed as a potential natural inducer of parkinsonian-like symptoms. Its spontaneous formation in man has to be taken into account after application of the drug chloral hydrate or after exposure to the solvent trichloroethylene. This first representative of chloral-derived heterocycles could now indeed be demonstrated to be formed in vivo after application of its putative precursors to rats. In vivo analysis of the nigrostriatal dopamine metabolism, behavioural studies, and histochemical findings as well as a strong inhibition of the complex I of the mitochondrial respiratory chain revealed the neurotoxic potential of TaClo on the dopaminergic system.

Animals↗

PubMed1995

Biochemical lesions of the nigrostriatal system by TaClo (1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline) and derivatives.

In vivo voltammetry with carbon fibre electrodes was used to study the effects of highly halogenated tetrahydro-beta-carbolines on the striatal dopamine (DA) metabolism of the rat. As representatives of chloral-derived heterocycles, "TaClo" (1-trichloro-1,2,3,4-tetrahydro-beta-carboline) and its N-methylated derivative. "N-methyl-TaClo", were investigated. After intranigral injection of 10 micrograms TaClo, the DA activity in the ipsilateral striatum was reduced compared with the intact side. Application of N-methyl-TaClo (10 micrograms) resulted in a nearly total reduction of the DOPAC signal. Furthermore, also "TaBro" (1-tribromomethyl-1,2,3,4-tetrahydro-beta-carboline), the bromal-derived analogue of TaClo, was tested. The impairment of the DA metabolism in rats achieved with 10 micrograms TaBro was found to be between that observed after application of TaClo and N-methyl-TaClo, respectively. The results demonstrate the toxic potential of chloral- and bromal-derived beta-carbolines towards dopaminergic neurons.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1995

Long-term behavioural effects of TaClo (1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline) after subchronic treatment in rats.

1-Trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo), which shows a great structural similarity to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), when administered to rats lead to enhanced spontaneous locomotion when they were tested 4-9 days after subchronic injection at a daily dose of 0.2 mg/kg over a seven week period. However, 9 weeks after the end of the course of injections animals walked more slowly during 12 hours of nocturnal activity, and apomorphine-induced locomotion was decreased 12 weeks later. These results suggest that the drug may exert a progressive neurotoxic effect.

Analysis of Variance↗

PubMed1994

Intranigral injected iron progressively reduces striatal dopamine metabolism.

The striatal dopamine metabolism of the rat was followed 1, 3, and 6 weeks after unilateral intranigral iron (III) (50- and 1.5 micrograms) application. For both concentrations a progredient decrease of extraneuronal 3.4-dihydroxyphenylacetic acid (DOPA) levels was observed in the ipsilateral striatum.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1994

Effect of transient reduction of cerebral blood flow on membrane anisotropy and lipid peroxidation in different rat brain areas.

Light-microscopical studies revealed that oligemic hypoxia for 24 and 60 min as produced by bilateral clamping of the carotid arteries (BCCA) in normotension does not produce neuronal cell necrosis in the vast majority of rat brain. Less than 5% of cases showed a pattern of mild selective neuronal necrosis as would be expected in ischemia. However, significant changes in both lipid peroxidation (as measured by MDA formation) and membrane anisotropy (measured by DPH or TMA-DPH, respectively, as a fluorescence probe) in cortical and striatal, but not in hippocampal, membrane fractions could be measured in ex vivo studies. Twenty-four and 60 min of BCCA without reperfusion decreased lipid peroxidation in the cerebral cortex but not in the striatum. BCCA, either for 24 or 60 min, and 60 min of reperfusion produced no changes in lipid peroxidation in either structure. However, 24 and 60 min of BCCA followed by 14 days of reperfusion led to a significant increase in MDA formation in the striatum, while lipid peroxidation in the cortex was only increased after 60 min of BCCA. Cortical as well as striatal membrane anisotropy increased significantly 14 days later in rats submitted to BCCA for 24 or 60 min. The study shows an increased lipid peroxidation 2 weeks after a transient reduction in cerebral blood flow although no neuronal necrosis could be observed in general.

Animals↗

PubMed1994

Correlation of optotypes with the Landolt ring--a fresh look at the comparability of optotypes.

The legibility of three selected sets of optotypes: (1) letters; (2) Snellen E; and (3) KOLT test have been compared to the Landolt ring in a study based on the German Standard DIN 58220, Part 2 and the International Standard ISO 8597. The letters were printed in the standard typeface used on German street signs (sans serif Linear-Antiqua, Typeface B). The main results are: 1. A set of letters can be selected in such a way that the differences in legibility displayed between different letters in the set are smaller than the ISO/DIN allowance of 0.05 logarithmic units of the visual angle, although the letters are not constructed according to the traditional 5 by 5 or 5 by 4 construction principles. 2. The eight letters C, D, E, K, N, P, U, Z are proposed for standardized visual acuity tests because of their almost equal legibility. 3. The height of the typeface used for this selected set of letters should be 5% less than the diameter of the Landolt ring in order to achieve the same legibility as the latter. 4. Both shape optotypes (Snellen E and KOLT test) must be approximately 15% smaller than the diameter of the Landolt ring in order to obtain comparable visual acuity scores.

Form Perception↗

PubMed1994

Daily variations of functional parameters and density distribution in human blood platelets.

Blood platelets play a critical role in the onset of myocardial infarction, which has been shown to have a circadian rhythmicity with a peak incidence in the morning. In an attempt to correlate platelet parameters with the outcome of cardiovascular diseases, we studied the daily (24-h) variation of the following platelet parameters: distribution pattern of functional heterogeneous platelet subpopulations; serotonin uptake; ketanserin binding; aggregation upon thrombin, serotonin, and ADP stimulation; and platelet count. Furthermore, we analyzed the tryptophan and serotonin concentrations in the blood samples. The percentage of less dense platelets, which represent the subpopulation with the highest preactivation, showed a rhythmicity period of 24 h and an acrophase at 21:18 h. The time course of intermediate and high density platelets was inverse to that of low density platelets. The serotonin uptake exhibited also a rhythmicity with a 24-h period. The acrophase was at 13:50 h. The aggregation curves were inverse to the ketanserin binding curves. The serotonin concentration exhibited a 12-h rhythmicity. The results obtained suggest that (a) changes in platelet activity are reflected by several parameters of platelet function that underlie daily variations; (b) the aggregation curves show a peak in the morning, with an additional peak in the afternoon; and (c) changes in the distribution pattern occur independently from variations in platelet functions like aggregation and serotonin binding.

Adenosine Triphosphate↗

PubMed1993

The influence of sleep deprivation on thyroid hormone metabolism in rat frontal cortex.

The effects of 24 h sleep deprivation (SD) on central thyroid hormone metabolism were investigated in rat frontal cortex. SD induced a significant rise in the activity of iodothyronine type II 5'-deiodinase (5'D-II), which catalyzes the conversion of thyroxine (T4) to triiodothyronine (T3) in the rat central nervous system (CNS). Tissue concentrations of T4 remained unchanged, whereas levels of T3 increased to more than 150% of the corresponding levels measured in control rats. Serum concentrations of T4 and T3 were also significantly enhanced by SD--an effect that has previously been described in depressed patients having undergone the same procedure. These results suggest that SD can dramatically increase T3 concentrations (and possibly function) in rat CNS. Whether or not these findings are of relevance in regard to the well-known antidepressant effect of SD in psychiatric patients with major depressive disorders remains to be established.

Animals↗

PubMed1993

Plasma membrane properties in heterogeneous human blood platelet subfractions modulate the cellular response at the second messenger level.

Three subfractions of human blood platelets differing in density and function exhibited also differences when EPR (electron paramagnetic resonance) spin label measurements and fluorescence polarization were performed. The membrane anisotropy in the plasma membranes was higher in low density platelets as compared with that of platelets of intermediate and higher densities. This higher plasma membrane anisotropy correlated with a significantly higher cholesterol-phospholipid (C:P) molar ratio in the plasma membranes of low density platelets. As compared with the other platelet subfractions the low density platelets exhibited the smallest cAMP increase after activation with the aggregation inhibitor prostaglandin (PGE1), and the highest percentage of inositol phosphate accumulation after thrombin stimulation. The results suggest a high correlation between functional parameters and the plasma membrane architecture of human blood platelets.

Adenylyl Cyclases↗

PubMed1993

Stress-induced changes of extracellular 5-hydroxyindoleacetic acid concentrations followed in the nucleus raphe dorsalis and the frontal cortex of the rat.

In the present paper, the effect of different stressors on extracellular 5-hydroxyindoleacetic acid (5-HIAA) concentrations in the frontal cortex and the N. raphe dorsalis (NRD) of the rat were studied. The following stressful procedures were used: Immobilization, 10 min, cold, 20 min, and forced exercise in a rotating wheel, 2h. These procedures were compared with a handling procedure, 10 min. The extracellular 5-HIAA concentration was followed by in vivo voltammetry with carbon multifibre electrodes in the awake animal. Handling had no significant effect on extracellular 5-HIAA concentrations neither in the frontal cortex nor the NRD, whereas immobilization and cold evoked significant increases in both brain areas. During and after forced exercise a significant increase was measurable only in the frontal cortex, while extracellular 5-HIAA concentrations were unchanged in the NRD. Since it is very likely that the modulation of the activity of the central serotoninergic system under stressful conditions is closely connected with changes in behaviour and temperature regulation, we compared our findings on extracellular 5-HIAA levels during stress with the effect of the 5-HT1A agonist (+)-8-hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT), a substance known to reduce body temperature. The i.p. injection of a low dose decrease significantly both, the extracellular 5-HIAA concentration in the NRD and body temperature. Our results suggest that the serotoninergic activation in the frontal cortex may prove to be a general response to stress which could function perhaps as a part of the central coping mechanism, whereas serotonin (5-HT) in the NRD may modulate specific regulatory responses such as body temperature.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1993

Modulation of serotonin binding sites in the brain of the Djungarian hamster, Phodopus sungorus, during adaptation to a short photoperiod.

During the physiological adaptation of the Djungarian hamster, Phodopus sungorus, to a short photoperiod in autumn the modulation of specific serotonin (5-HT) binding sites of synaptic membranes was investigated in two brain regions, i.e. cerebral cortex and basal brain (CNS without cerebral cortex, cerebellum, pineal gland, and spinal cord). The radioligands [3H]5-HT and [3H]ketanserin were used to characterize total 5-HT1 and 5-HT2 binding sites, respectively. An increase of 5-HT1 and 5-HT2 binding sites was observed in both brain regions within 14 days after reduction of the photoperiod from a 14:10 h light/dark (l/d) cycle to an 8:16 h l/d cycle. The increase was still present after 56 days of the short photoperiod. Binding kinetics assayed after 4 days of the short photoperiod show that maximal specific binding of [3H]5-HT and [3H]ketanserin was increased, while dissociation constants (KD) were not changed. The membrane anisotropy of synaptic membranes, measured by fluorescence polarization, was reduced transiently during the early part of the adaptation. Neither the phospholipids nor the mole ratio of cholesterol to phospholipids were significantly affected by adaptation to short photoperiod. The results suggest an important role of the central nervous 5-HT system in the physiological adaptation of the Djungarian hamster to a short photoperiod.

Adaptation, Physiological↗

PubMed1993

Functional studies on monoaminergic transmitter release in parkinsonism.

1. In vivo pulse voltammetry and apomorphine induced circling behaviour were used to study the effect of antiparkinsonian drugs and neurotoxins on striatal, extraneuronal dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations which are a measure of dopamine (DA) release/DA metabolism and serotonin (5-HT) release, respectively. 2. The DA precursor dihydroxyphenylalanine (DOPA, i.p.) increased extraneuronal DOPAC and reduced 5-HIAA levels whereas the opposite effect was induced by the 5-HT precursor 5-hydroxytryptophan (5-HTP, i.p.). Tryptophan, i.p., decreased the extraneuronal DOPAC levels without significant effect on 5-HT release. 3. The monoamine oxidase (MAO) inhibitors pargyline, i.p., and deprenyl, i.p., as well as the DA agonist apomorphine, i.p., decreased the catechol signal. The DA antagonist haloperidol, i.p., increased extraneuronal DOPAC. 4. In longterm studies unilateral application of the neurotoxins 6-hydroxydopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetra-hydroxypyridine (MPTP), and 1-methyl-4-phenylpyridinium cation (MPP+) into the substantia nigra pars compacta abolished the DOPAC signal in the striatum at the lesioned side. This effect can be partially or fully restored by DOPA depending on the time elapsed after neurotoxin administration. 5. In accordance with the voltammetric recorded unilateral lesion of the dopaminergic system the apomorphine stimulated circling behaviour was significantly enhanced in MPTP and MPP+ treated rats as compared with controls. 6. The results obtained indicate that antiparkisonian drugs and neurotoxins besides their effect on total catecholamine and 5-HT concentrations change specifically the extraneuronal levels of the transmitter (metabolites). Moreover the results suggest that neurotoxin-treated rats can be used as a model to study Parkinson-like effects with regard to the pathogenesis and treatment of this disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1993

Lowering of body core temperature by exposure to a cold environment and by a 5-HT1A agonist: effects on physiological and psychological variables and blood serotonin levels.

The present study was designed to compare the effects of a pharmacologically induced decrease in body core temperature to the effects observed with lowering of body temperature by exposure to a cold environment. Our special interest was the involvement of 5-HT in thermoregulatory responses. Sixty healthy male volunteers were randomly assigned to one of the following conditions: exposure to normal ambient temperature (28 degrees C) and placebo, exposure to cold ambient temperature (5 degrees C) and placebo, or normal ambient temperature and 10 mg of the partial 5-HT1A agonist ipsapirone. As indicators of physiological responses to lowering of body temperature, tympanic temperature, skin temperature, EMA, metabolic rate, and heart rate were monitored and saliva cortisol levels and peripheral 5-HT concentrations were determined. In addition, ratings on ambient temperature, thermal discomfort, and feelings of irritability were obtained. While lowering of body core temperature was associated with marked counterregulations (decrease of skin temperature, increase in EMA and metabolic rate) and feelings of discomfort, this was not observed with ipsapirone. An increase in cortisol levels was primarily observed in the ipsapirone group and was not reflected by respective changes in whole blood or platelet 5-HT indicating that brain and platelet 5-HT are not related.

Adult↗

PubMed1993

Immobilization and light-dark cycle-induced modulation of serotonin metabolism in rat brain and of lymphocyte subpopulations: in vivo voltammetric and FACS analyses.

The effect of immobilization and light-dark cycle on the serotoninergic system of the n. raphe dorsalis and on the distribution of blood lymphocyte subpopulations was studied in the rat. As was shown by in vivo voltammetry, 10 min immobilization enhanced serotonin metabolism with a maximum 15 min after immobilization. The distribution of the blood lymphocytes into subpopulations was also affected: pan-T and T helper lymphocytes were reduced during immobilization and reached minimum values after 20 min recovery. The circadian rhythms of serotonin metabolism and the distribution of pan-T and T helper cells exhibited a slight phase shift if compared with each other.

Animals↗