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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Addiction biology 9 (2004), S. 0 
    ISSN: 1369-1600
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The appetite and weight regulating peptide leptin was associated recently with alcohol craving during withdrawal. Nevertheless, correlations were only significant with craving displayed on the visual analogue scale for maximum craving during the previous week (VAS), and not if assessed with the highly validated Obsessive Compulsive Drinking Scale (OCDS). The objective of the following study, therefore, is to elucidate further the associations between the leptin system and craving concepts during alcohol withdrawal. A sufficiently large sample size should allow multiple statistical subgroup and confounder analyses. We prospectively investigated 102 chronic alcoholic inpatients (23 females, 79 males) during withdrawal on days 0 (admission), 1, 2 and days 7 - 10. In addition to the statistical analysis of the total sample, females and males were to be analysed separately. For detecting associations between leptin levels and craving scores multiple regression analysis was performed. Plasma leptin levels were determined, and craving for ethanol was assessed by both the OCDS and the VAS. Leptin plasma levels significantly increased during alcohol withdrawal compared to day 0, while all craving scores decreased. Body mass corrected leptin plasma levels predicted craving on day 0 in the OCDS total score (R  = 0.55, F  = 7.91, df = 1.19, p  〈 0.05) and in the OCDS obsessive subscore (R  = 0.57, F 〈 = 8.48, df = 1.19, p  〈 0.05) in females. Neither in males nor in the total population did multiple regression analysis reveal any significant results. Leptin levels seem to change during inpatient alcohol withdrawal. In a multivariate model, correlations between leptin levels and the highly validated craving scores of the OCDS can only be assumed in females. Hence, gender differences have to be taken into account when searching for neurobiological models of alcohol craving.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1435-1463
    Keywords: Keywords: Potassium channel ; inwardly rectifying potassium channel ; GIRK ; flupirtine ; N-methyl-D-aspartate receptor antagonist ; patch clamp ; superior colliculus culture.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary. The spectrum of action of flupirtine includes analgesia, muscle relaxation and neuroprotection. N-methyl-D-aspartate (NMDA) receptor antagonism has been discussed as a possible mechanism of action of this compound with little direct evidence. The objective of the present study was to develop a plausible model to explain flupirtine's spectrum of action. A four-stage strategy was selected for this purpose: Firstly, the serum concentration of flupirtine under therapeutic conditions was determined on the basis of the current literature. The second stage involved assessing the known in-vitro effects in light of the therapeutic active concentration. Using whole cell patch clamp recordings from cultured rat superior colliculus neurones interactions between flupirtine and NMDA receptors were assessed. Only very high concentrations of flupirtine antagonized inward currents to NMDA (200 μM) at −70 mV with an lC50 against steady-state responses of 182.1 ± 12.1 μM. The effects of flupirtine were voltage-independent and not associated with receptor desensitization making actions within the NMDA receptor channel or at the glycine modulatory site unlikely. NMDA receptor antagonism probably has little relevance for the clinical efficacy of flupirtine as the concentrations needed were far higher than those achieved in clinical practice. However, the activation of a G-protein-regulated inwardly rectifying K+ channel was identified as an interesting molecular target site of flupirtine. In the next stage, the central nervous spectrum of action of experimental K+ channel openers (PCO) was considered. As far as they have been studied, experimental K+ channel openers display a spectrum of action comparable to that of flupirtine. In the final stage, a global model was developed in which flupirtine stabilizes the resting membrane potential by activating inwardly rectifying K+ channels, thus indirectly inhibiting the activation of NMDA receptors. The model presented here reconciles the known functional NMDA receptor antagonism of flupirtine with the activation of K+ channels that occurs at therapeutic concentrations, thus providing an understanding of flupirtine's spectrum of action. This makes flupirtine the prototype of a clinically applicable substance group with analgesic, muscle-relaxant and neuroprotective properties.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1433-0407
    Keywords: Schlüsselwörter Manganintoxikation ; Parkinsonismus ; MRT ; Verlaufskontrolle ; L-Dopa-Therapie ; Key words Manganese intoxication ; Parkinsonism ; MRI ; Follow-up study ; L-dopa treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Manganese intoxication is an unusual, severe form of intoxication. This report deals with a patient now 80 years old who accidentally ingested a solution of potassium permanganate for a period of at least 4 weeks 14 years ago. Since then, the patient suffers from a mild parkinsonian syndrome and distally accentuated polyneuropathies. Psychiatric disorders, especially demential or depressive symptoms, were not observed. Manganese analysis of his hair still shows a clear increase in manganese concentration. The MRI of his brain showed no pathological changes, in particular none of those often described with symmetric signal elevation in T1 in the area of the basal ganglia. In this study, we present clinical, laboratory, and neuroradiological findings. Unusual in this case with a short exposition is the long duration and clinical improvement without L-dopa treatment.
    Notes: Zusammenfassung Eine Manganintoxikation ist eine ungewöhnliche, schwere Intoxikationsform. Wir berichten über einen jetzt 80-jährigen Patienten, der vor 14 Jahren über die Dauer von mindestens 4 Wochen versehentlich Kaliumpermanganat eingenommen hatte. Der Patient leidet weiterhin unter einem leichten Parkinsonsyndrom und einer distal betonten Polyneuropathie. Psychiatrische St¨rungen, insbesondere ein dementielles oder depressives Symptom, fanden sich nicht mehr. Die Mangananalysen der Haare zeigen auch jetzt noch deutlich erhöhte Konzentrationen. Das MRT des Gehirns erbrachte keinen pathologischen Befund, insbesondere keine häufig bei Manganintoxikationen beschriebenen Veränderungen mit symmetrischen Signalanhebungen in T1-Wichtung im Bereich der Basalganglien (Globus pallidus). In einer aktuellen Untersuchung werden klinische, laborchemische sowie neuroradiologische Ergebnisse vorgestellt. Die Besonderheit des Falles erklärt sich aus einer kurzen Expositionsdauer mit einer langen Verlaufszeit und klinischer Befundbesserung ohne L-Dopa-Behandlung.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1436-736X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Type of Medium: Electronic Resource
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