[Regulations. MDS Expert Forum: Evidence and value of early detection measures need to be proven].
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Evaluation Studies as Topic↗
Biomedical subjects
C Grote
Publications and source records attributed to C Grote.
Effect of lazaroid pretreatment on dopamine-induced impairment of the rat nigrostriatal system.
Oxidative stress induced by enhanced catecholamine metabolism may subsequently cause damages to the nervous system. We used in vivo-pulse voltammetry to study an enhanced brain dopamine (metabolism) induced either by intranigral dopamine (DA) injection or reduction of cerebral blood flow. One week after intranigral injection of 10 microg DA or unilateral occlusion of one carotid the DA activity in the ipsilateral striatum was decreased as compared to the contralateral side. Three weeks after DA application and carotid clamping the DA activity was restored to normal. The significant reduction of 3,4-dihydroxyphenylacetic acid (DOPAC) after one week was attenuated by pretreatment with the lazaroid U-74389G, injected 20 min before surgery. The results are in accordance with the view that radical mechanisms play a crucial role in the impairment of the nigrostriatal system induced by oligemia.
3,4-Dihydroxyphenylacetic Acid↗
Excitatory stimulation of neurons in the arcuate nucleus inhibits gastric acid secretion via vagal pathways in anesthetized rats.
It is well established that autonomic control of gastrointestinal function is modulated by central autonomic neurotransmission. In this context it has been shown that gastrointestinal motility and secretion can be modulated by exogenous neuropeptides microinjected into the paraventricular nucleus of the hypothalamus (PVN). Furthermore, there is considerable evidence suggesting that neurons projecting from the arcuate nucleus (Arc) to the PVN may be the source of endogenous neuropeptide release in the PVN. This poses the question whether stimulation of neurons in the arcuate nucleus, e.g. by an excitatory amino acid, alters gastrointestinal function. In the present study, we investigated the effect of an excitatory amino acid, kainate, microinjected into the arcuate nucleus on gastric acid secretion in urethane-anesthetized rats. Kainate (140 pmol/rat) bilaterally microinjected into the Arc induced an significant inhibition of pentagastrin (PG) stimulated (16 mg/kg per h) gastric acid secretion throughout an observation period of 120 min after microinjection. Microinjection of kainate into hypothalamic areas outside the arcuate nucleus did not modify gastric secretion. Bilateral cervical vagotomy blocked the effect of kainate injected into the Arc on PG-stimulated gastric acid secretion. These data show that gastric secretory function can be modulated by stimulation of neuronal activity in the Arc via efferent vagal pathways. The results suggest that the arcuate nucleus is a forebrain area involved in the CNS regulation of gastrointestinal function.
Anesthetics, Intravenous↗
Brain injury in amateur soccer players.
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Brain Injuries↗
Bromal-derived tetrahydro-beta-carbolines as neurotoxic agents: chemistry, impairment of the dopamine metabolism, and inhibitory effects on mitochondrial respiration.
The mammalian alkaloids tryptoline (1) and eleagnine (2) as well as the highly halogenated (X = F, Cl, Br) tetrahydro-beta-carbolines (THbetaCs) 3-5, structurally similar to the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 6), were found to have a common feature of inducing a severe impairment of the nigrostriatal dopamine metabolism and inhibiting complex I of the mitochondrial respiratory chain highly selectively. Within the series of compounds tested, 1-tribromomethyl-1,2,3,4-tetrahydro-beta-carboline ('TaBro', 5), which was prepared in high yields from the biogenic amine tryptamine ('Ta', 7) and the unnatural aldehyde bromal ('Bro', 8) by a Pictet-Spengler cyclization reaction, turned out to be the most potent toxin in vitro and in vivo. As demonstrated by voltammetric measurements on rats, for all the THbetaCs 1-5 investigated, intranigral application of a single dose of 10 microg resulted in a significant reduction of the dopaminergic activity in the striatum, with the strongest effect being observed for TaBro (5). Using rat brain homogenates, again 5 (IC50 = 200 microM) as well as its dehydrohalogenation product 11 (IC50 = 150 microM) exhibited the most pronounced inhibitory potential on mitochondrial respiration. The halogen-free THbetaCs 1 and 2 as well as the MPTP metabolite 1-methyl-4-phenylpyridinium ion (MPP+), by contrast, showed only a moderate inhibition at concentrations in the millimolar range (e.g. for MPP+: IC50 = 3.5 mM). For an elucidation of the role of hydrophobic portion in the inhibitory action against complex I activity, several N-acyl derivatives (15-21) of 5 were synthesized and tested. An X-ray diffraction study on the 3-dimensional structure of trifluoroacetylated highly halogenated THbetaCs (12-14) revealed the tetrahydropyrido part to adopt a nearly planarized half-chair conformation. Because of the steric demand of the trihalogenmethyl moiety (CF3 < CCl3 < CBr3), the N-substituent is dramatically pushed out of that ring 'plane'.
Animals↗
Neuropeptide Y in the paraventricular nucleus of the hypothalamus stimulates colonic transit by peripheral cholinergic and central CRF pathways.
There is evidence suggesting that neuropeptide Y (NPY) as well as corticotropin-releasing factor (CRF) in the paraventricular nucleus of the hypothalamus (PVN) are involved in the CNS regulation of gastrointestinal (GI) function. We studied the effects of NPY or Y1-and Y2-receptor agonists microinjected into the PVN on colonic transit. Microinjection of NPY into the PVN at doses of 0.15-1.5 microg decreased the colonic transit time of conscious rats up to 49%. Pretreatment with the peripherally acting cholinergic antagonist atropine methyl nitrate (0.1 mg kg-1 i.p.) blocked the NPY into PVN-induced effect on colonic motor function.The agonist of the Y1-receptor, NPY(Leu31, Pro34), as well as the Y2-receptor agonist, NPY(13-36), dose-dependently decreased colonic transit time when microinjected into the PVN (0.05, 0.15 and 0.5 microg). However, the Y1-receptor agonist was more effective. Intracerebroventricular (ICV) application of the CRF-receptor antagonist, alpha-helical-CRF9-41 (50 microg/rat), blocked the NPY effect in the PVN on colonic motor function. In conclusion, stimulation of colonic transit by NPY acting in the PVN was observed. The PVN is more sensitive to agonists acting on the Y1- than on the Y2-receptor to mediate stimulation of propulsive colonic motility. The effect of NPY in the PVN on colonic motor function depends on central CRF and peripheral cholinergic pathways.
Animals↗
Involvement of CCK in the paraventricular nucleus of the hypothalamus in the CNS regulation of colonic motility.
The effects of cholecystokinin octapeptide (CCK(8)), the CCK-A receptor antagonist, MK-329, and the CCK-B receptor antagonist, L-365, 260, microinfused into the paraventricular nucleus of hypothalamus (PVN) on colonic motor function was investigated in awake rats, chronically implanted with a microinjection cannula into the PVN and a catheter into the proximal colon. In fasted rats, bilateral microinfusion of CCK(8) at doses of 1.5 and 3.0 microg/rat into the PVN stimulated colonic transit, as shown by a significant increase in the geometric center by 47 and 54%, respectively. This effect of CCK(8) was site-specific to the PVN, since microinjection of the peptide into sites outside of but adjacent to PVN had no effect. In non-fasted rats, L-365,260 bilaterally microinjected into the PVN at a dose of 1.5 microg/rat inhibited propulsive colonic motor function; colonic transit time significantly increased by 73% in comparison to the control condition. Microinfusion of the CCK-A antagonist into in the PVN did not affect colonic transit. These results show that the PVN is a responsive site for the central CCK(8)-induced modulation of colonic motility. The data suggest, that endogenous CCK in the paraventricular nucleus of the hypothalamus unfolds a stimulatory effect on colonic transit through action on CCK-B receptors.
Animals↗
Iron accumulation in the substantia nigra in rats visualized by ultrasound.
In recent studies, we have found a marked increase in substantia nigra (SN) echogenicity in patients with Parkinson's disease (PD) using transcranial ultrasound. Because a substantial body of evidence has accumulated indicating a selective elevation of iron in the SN from patients with PD, we set out to test the hypothesis that trace metals like iron could lead to the observed increase of SN echogenicity in PD. Rat brains were scanned after stereotactic injection of iron in different concentrations into the SN and after injecting ferritin, zinc and 6-OHDA alone, and after the addition of desferrioxamine. The amount of iron in the SN was measured spectroscopically. For iron, and partly for 6-OHDA, in different concentrations, a dose-dependent increase of SN echogenicity could be visualized, corresponding to an increase of iron measured by spectroscopy. No increase of echogenicity was visualized after the injection of ferritin and the addition of desferrioxamine to 6-OHDA, though an increase of iron was measured by spectroscopy. Therefore, we conclude that iron not bound to these proteins may lead to an increase of echogenicity of the SN.
Animals↗
Inter-laboratory validation of solid-phase microextraction for the determination of triazine herbicides and their degradation products at ng/l level in water samples.
The accuracy and precision of solid-phase microextraction (SPME) were validated in an inter-laboratory study including ten laboratories for the analysis of triazine herbicides and their metabolites at ng/l level in aqueous samples. The SPME conditions were optimised in order to obtain maximum sensitivity. Especially, salt addition and choice of the SPME fibre coated with Carbowax-divinylbenzene increased the sensitivity. The average detection limits were in the range from 4 to 24 ng/l for the triazine herbicides, and 20 and 40 ng/l for desisopropylatrazine and desethylatrazine, respectively. The average r2 values of the calibration curves were above 0.99 for all of the analytes. The statistical data treatment was performed in accordance with the International Standardisation Organisation (ISO) standard 5725. Relative repeatability standard deviations between 6 and 14% and relative reproducibility standard deviations between 10 and 17% were found. The determined concentrations of the reference sample compared well to the "true" values, thus proving the good accuracy of the method. It is concluded that SPME is a reliable technique for the quantitative analysis of water samples containing triazine herbicides in concentrations around the European limit of 100 ng/l for individual pesticides in drinking water.
Calibration↗
Solid-phase microextraction for the analysis of human breath.
Solid-phase microextraction (SPME) has been applied to the quantitative determination of ethanol, acetone, and isoprene in human breath. The method involves extraction and preconcentration with a fused silica fiber coated with a polymeric stationary phase, desorption at 200 degrees C, and assay by gas chromatography/mass spectrometry. Three different fiber coatings have been evaluated with regard to sensitivity, linear range, precision, and detection limits. Typical RSD values in the range 2%-6% could be obtained, depending on the fiber coating and the compound investigated. The calibration curves for the compounds are reproducible and linear over the concentration ranges found in human breath samples. The method is capable of detecting concentrations of acetone and isoprene reported for healthy subjects. The influence of temperature and humidity on the extraction process has been studied in detail. A linear relationship between log K versus 1/T allows the calibration of the method for any given temperature. The device is portable, economical, and easy to use in patient sampling.
Acetone↗
Effects of interferon-gamma, interleukin-1 beta, and tumor necrosis factor-alpha on the serotonin metabolism in the nucleus raphe dorsalis of the rat.
The effects of the cytokines interferon (IFN)-gamma, interleukin (IL)-1, and tumor necrosis factor (TNF)-alpha on the serotoninergic transmission in the nucleus raphe dorsalis (NRD) were studied after peripheral and central application. The studies were performed in the freely moving rat using differential pulse voltammetry with multicarbon fibre electrodes to study the extracellular levels of the serotonin (5-HT) metabolite 5-hydroxyindoleacetic acid (5-HIAA). The extracellular 5-HIAA levels were not changed in the NRD after peripheral application of rat recombinant IFN-gamma, but elevated by the cytokines IL-1 beta and TNF-alpha. After intracerebroventricular (i.c.v.) application the cytokines IFN-gamma, IL-1 beta and TNF-alpha stimulated the serotoninergic transmission in the NRD. Our data suggest that the effect of peripherally elevated cytokine concentrations on the serotonin metabolism in the NRD of the rat is cytokine-dependent. In this respect the T-cell and NK-cell cytokine IFN-gamma acts clearly different when compared to the mainly macrophage-derived cytokines IL-1 beta and TNF-alpha, and plays a different role in the communication between immune and central nervous system.
Animals↗
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↗
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↗
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↗
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↗
The Dichotic Word Listening Test: preliminary observations in American and Canadian samples.
The present article describes observations of 670 American and Canadian child and adult control subjects on the recently developed Dichotic Word Listening Test (DWLT). The task was also administered to a sample of American children with traumatic brain injuries (n=21) of varying severity and a sample of American adults with mild traumatic injuries (n=36). The conceptual focus in this line of research was on using normative observations to identify clinically defective channels of auditory processing among patients. The principal findings were as follow: 1) the DWLT was sensitive to the effects of cerebral dysfunction following traumatic brain injury; 2) differences among normal samples with different demographic backgrounds were frequently observed, arguing for the development of local norms; 3) a shorter form of the DWLT task (DWLT30) can be used for screening purposes with relatively little reduction in sensitivity to cerebral dysfunction; 4) there appeared to be considerable improvement of DWLT performance between the ages of five and seven, due largely to higher scores from the left auditory channel; and 5) there were indications that use of French (rather than English) as one's native language before age six can negatively influence performance in adulthood on an English version of the DWLT. In general, the present findings suggest that the DWLT is likely to have relatively broad applicability for neuropsychological assessment across the life-span.
Journal Article↗