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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Redox changes within neurones are increasingly being implicated as an important causative agent in brain ageing and neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD) and Alzheimer's disease (AD). Cells have developed a number of defensive mechanisms to maintain intracellular redox homeostasis, including the glutathione (GSH) system and antioxidant enzymes. Here we examine the effects of N-acetyl-l-cysteine (NAC) on β-amyloid (Aβ) secretion and tau phosphorylation in SHSY5Y neuroblastoma cells after exposure to oxidative stress inducing/cytotoxic compounds (H2O2, UV light and toxic Aβ peptides). Aβ and tau protein are hallmark molecules in the pathology of AD while the stress factors are implicated in the aetiology of AD. The results show that H2O2, UV light, Aβ1–42 and toxic Aβ25–35, but not the inactive Aβ35–25, produce a significant induction of oxidative stress and cell cytotoxicity. The effects are reversed when cells are pre-treated with 30 mm NAC. Cells exposed to H2O2, UV light and Aβ25–35, but not Aβ35–25, secrete significantly higher amounts of Aβ1–40 and Aβ1–42 into the culture medium. NAC pre-treatment increased the release of Aβ1–40 compared with controls and potentiated the release of both Aβ1–40 and Aβ1–42 in Aβ25–35-treated cells. Tau phosphorylation was markedly reduced by H2O2 and UV light but increased by Aβ25–35. NAC strongly lowered phospho-tau levels in the presence or absence of stress treatment.
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  • 2
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Concentrations of heavy metals, including mercury, have been shown to be altered in the brain and body fluids of Alzheimer’s disease (AD) patients. To explore potential pathophysiological mechanisms we used an in vitro model system (SHSY5Y neuroblastoma cells) and investigated the effects of inorganic mercury (HgCl2) on oxidative stress, cell cytotoxicity, β-amyloid production, and tau phosphorylation. We demonstrated that exposure of cells to 50 μg/L (180 nM) HgCl2 for 30 min induces a 30% reduction in cellular glutathione (GSH) levels (n = 13, p 〈 0.001). Preincubation of cells for 30 min with 1 μM melatonin or premixing melatonin and HgCl2 appeared to protect cells from the mercury-induced GSH loss. Similarly, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assays revealed that 50 μg/L HgCl2 for 24 h produced a 50% inhibition of MTT reduction (n = 9, p 〈 0.001). Again, melatonin preincubation protected cells from the deleterious effects of mercury, resulting in MTT reduction equaling control levels. The release of β-amyloid peptide (Aβ) 1-40 and 1-42 into cell culture supernatants after exposure to HgCl2 was shown to be different: Aβ 1-40 showed maximal (15.3 ng/ml) release after 4 h, whereas Aβ 1-42 showed maximal (9.3 ng/ml) release after 6 h of exposure to mercury compared with untreated controls (n = 9, p 〈 0.001). Preincubation of cells with melatonin resulted in an attenuation of Aβ 1-40 and Aβ 1-42 release. Tau phosphorylation was significantly increased in the presence of mercury (n = 9, p 〈 0.001), whereas melatonin preincubation reduced the phosphorylation to control values. These results indicate that mercury may play a role in pathophysiological mechanisms of AD.
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 777 (1996), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Notes: Memory training programs for cognitively impaired patients have often been criticized for their lack of relevance to everyday activities. We therefore report our experience with four patients suffering from probable Alzheimer's disease, who were trained with a new computer based program recently developed by our research group. An everyday task of personal relevance to the patient is simulated and trained on a PC-touch-screen using personal photographs of the patient's surroundings and biography. According to the degree of cognitive impairment, training has three major aspects 1) social competence in patients with beginning deficiencies, 2) orientation in patients with moderate disease, and 3) emotional aspects in patients with advanced deficiencies. The patient's training performance improved substantially. While psychopathometric tests showed no significant effects with regard to general cognitive performance, levels of motivation were high and there was a positive acceptance of the training and signs of emotional activation.
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 777 (1996), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Notes: Near infrared spectroscopy (NIRS) is a new technique that permits noninvasive monitoring of cerebral blood and tissue oxygenation. Recently, we and others have shown that NIRS measurements are sensitive enough to follow changes in cerebral hemoglobin oxygenation due to activation of brain function. Based on these findings we have assessed the influence of aging as well as the influence of neurodegeneration on cerebral hemoglobin oxygenation during mental work. The typical NIRS pattern in young healthy subjects while performing calculation tasks measured in the frontal cortex were increases in oxygenated hemoglobin [HbO2] and total hemoglobin [HbT] while reduced hemoglobin [HbR] decreased. Elderly healthy subjects showed a significant lower mean increase in [HbO2] and [HbT] levels. Regression analysis revealed an age-dependent decline in activation-induced local increase of [HbO2] as well as [HbT]. Furthermore, we monitored changes in cerebral hemoglobin oxygenation in the frontal cortex while patients with probable Alzheimer's disease (AD) performed cognitive tasks. Whereas elderly healthy subjects (as well as patients with major depression, age-associated memory impairments or vascular dementia) again showed clear increases in the local concentrations of [HbO2] and [HbT] during brain activation, AD patients showed significant decreases compared to the baseline levels in both variables that were most pronounced in the parietal cortex. To clarify whether the different patterns in cerebral hemoglobin oxygenation during cognitive activation were due to an altered functional brain organization in AD or to alterations in the cerebrovascular response to neuronal activation, we are currently performing simultaneous NIRS and (015-H20-)PET measurements during performance of a cognitive task (Stroop test). Our finding of a regional reduced oxygen supply during activation of brain function may be of relevance to the development and the time course of neurodegeneration.
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  • 5
    ISSN: 1433-0407
    Keywords: Schlüsselwörter Schizophrenie ; Soziale Situation ; Berufstätigkeit und Partnerschaft ; Prädiktoren ; Key words Schizophrenia ; Social situation ; Employment ; Partnership ; Predictors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary In the German mutlicentre ANI study comparing continuous prophylactic treatment with intermittent medication, the social situation of a large sample of 364 schizophrenic patients was investigated and followed up over a 2-year period of outpatient aftercare. Effective therapy and prophylaxis substantially reduced relapses and rehospitalization. On the other hand, the psychosocial situation still showed considerable disadvantages. Of the patients (35 years old on average), 60% were still unmarried. Almost one-half of the patients still lived alone or with their parents, and one-third lived a very solitary life. At the end of the 2-year aftercare period, one-third was able to earn their own living. Almost one-half retired early from their occupations. Predictors and intervening variables are presented in order to stimulate early rehabilitation approaches. Schizophrenics are particularly placed at a disadvantage by tighter competition in the employment market, even though the course of illness can be improve. Social psychiatry must to be involved in helping to improve social contacts, accommodation and employment in order to prevent major distress.
    Notes: Zusammenfassung Im Rahmen der deutschen multizentrischen ANI-Studie zum Vergleich kontinuierlicher Prophylaxe mit Intervallbehandlung konnte an einer größeren Gruppe von 364 Schizophrenen die soziale Situation untersucht und über eine 2jährige ambulante Nachsorge beobachtet werden. Unter wirksamer Therapie und Prophylaxe lassen sich Rezidive und Rehospitalisierungen wirksam reduzieren. Die psychosoziale Situation hingegen zeigt weiterhin erhebliche Benachteiligungen: Im durchschnittlichen Alter von 35 Jahren sind 60% ledig geblieben, gut die Hälfte lebt allein oder noch bei den Eltern, und ein Drittel ist sozial sehr isoliert. Ein Drittel kann am Ende der 2jährigen Nachsorge den Lebensunterhalt selbst bestreiten, knapp die Hälfte ist vorzeitig aus dem Erwerbsleben ausgeschieden. Prädiktoren und intervenierende Variablen werden dargestellt, damit sich an ihnen frühzeitige Rehabilitationsansätze orientieren können. Verschärfte Konkurrenz auf dem Arbeitsmarkt und erhöhte Anforderungen benachteiligen Schizophrene besonders, trotz Verbesserung des Krankheitsverlaufs. Sozialpsychiatrische Hilfen zur Kontaktförderung, für Wohnen und Arbeit sind mehr denn je erforderlich, um stärkeres Elend zu verhindern.
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  • 6
    ISSN: 1433-0407
    Keywords: Schlüsselwörter Magnetresonanztomographie ; Demenz ; Demenz vom Alzheimer-Typ ; MR-Volumetrie ; Signalveränderungen ; Key words Magnetic resonance imaging ; Dementia ; Alzheimer’s disease ; MR-volumetry ; Signalhyperintensity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary One of the most widely used neuroimaging procedures in Psychiatry and Neurology is magnetic resonance imaging (MRI). MRI has gained the position of a standard investigation in the differential diagnosis of dementia syndromes. In the clinical diagnosis of Alzheimer’s disease (AD) MRI helps to improve the diagnostical accuracy. Recently new MRI-based techniques for performing volumetric measurement of cortical and subcortical structures have been developed. First reports indicate that MRI-based volumetric measurements can be accurate in differentiating AD patients from cognitively normal elderly individuals. These new techniques may be useful adjunct in assessing the clinical diagnosis of AD. Results could also yield insight in the fundamental pathology of the degenerative disease. It is the objective of this chapter to summarize and comment on the significance of MRI in the diagnosis and research of AD. Future directions are outlined, including the use of microscopic MRI, the differentiation of white matter signal hyperintensities and the combined evaluation of stuctural MRI and functional imaging techniques.
    Notes: Zusammenfassung Die Magnetresonanztomographie (MRT) des Gehirns kommt als strukturelles bildgebendes Verfahren in der Psychiatrie und Neurologie zur breiten Anwendung. Bei der Demenz vom Alzheimer-Typ (AD) trägt die MRT zur Verbesserung der klinischen Diagnosestellung im Rahmen der Mehrebenendiagnostik [1] und zur differentialdiagnostischen Abgrenzung anderer mit einem dementiellen Syndrom einhergehender Erkrankungen bei. Neu entwickelte Verfahren der MRT-gestützten Volumetrie kortikaler und subkortikaler Strukturen erwiesen sich als nützlich in der Differenzierung zwischen kognitiv gesunden älteren Probanden und AD-Patienten. Darüber hinaus versprechen sie neue Einsichten in den zeitlichen und strukturellen Verlauf der zerebralen Degeneration. Zusätzlich kann die systematische quantitative Erfassung von Signalveränderungen bei AD-Patienten zur Verbesserung der diagnostischen Genauigkeit beitragen. Es ist die Absicht dieser Arbeit, den Beitrag der MRT zur Diagnostik der AD und zum Verständnis ihrer Pathogenese darzustellen, aber auch die Grenzen dieser Methodik aufzuzeigen. Dabei werden die Veränderungen des gesunden Alterungsprozesses miteinbezogen, die mit Hilfe der MRT-Bildgebung faßbar sind. Zukünftige Perspektiven liegen insbesondere in der Weiterentwicklung der mikroskopischen MRT, der genauen Differenzierung und Klassifikation von Signalveränderungen der weißen Substanz und im kombinierten Einsatz der MRT mit funktionellen bildgebenden Methoden.
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  • 7
    ISSN: 1433-0407
    Keywords: Schlüsselwörter Aufnahmesituation ; Qualitätssicherung ; Strukturqualität ; Prozeßqualität ; Aufnahmestation ; Key words Patients admission ; Quality assurance ; Admission ward ; Continuity of care
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The study provides empirical data to compare different systems used for hospital admission procedures in a psychiatric clinic. The Psychiatric University Clinic Basel replaced its traditional central admission ward by direct admission to a number of different treatment settings. This change had consequences for both structural and procedural quality. More admissions occurred after prior notice had been given, and these admissions occurred more often at a time of day when more clinic staff were available. The rate of voluntary admissions increased, and the continuity of care, as measured by the number of transfers within the clinic during the first 5 days post-admission, was improved. These findings, which support an interpretation that the treatment conditions were improved, must be balanced against the drawback of delayed decision-making processes with, for example, longer waiting times for the patient. However, the continuity of therapeutic relationships can be increased through further changes in the procedural quality.
    Notes: Zusammenfassung Die Untersuchung liefert empirische Daten zum Vergleich verschiedener Systeme zur stationären Aufnahme von Patienten in das psychiatrische Krankenhaus. In der psychiatrischen Universitätsklinik Basel wurde anstatt der bisherigen Aufnahme von Patienten über eine zentrale Aufnahmestation eine dezentrale Aufnahme auf verschiedenen Behandlungsstationen eingeführt. Diese Strukturveränderung hatte verschiedene Auswirkungen auf die Struktur- und Prozeßqualität. Es erfolgten mehr angemeldete Eintritte, und diese fanden häufiger zu Tageszeiten statt, in denen die Personalbesetzung günstiger ist. Die Rate freiwilliger Aufnahmen war erhöht und die Betreuungskontinuität, gemessen an der Anzahl der Verlegungen im Haus in den ersten 5 Tagen nach der Aufnahme, verbessert. Diesen Variablen, die für eine Verbesserung der Versorgungssitutation sprechen, stehen v. a. verlängerte Entscheidungsprozesse mit z. B. verlängerten Wartezeiten als Nachteile für die Patienten entgegen. Die Beziehungskontinuität kann durch weitere Veränderungen der Prozeßqualität noch erhöht werden.
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  • 8
    ISSN: 1432-2072
    Keywords: Chronic schizophrenics ; Long-term neuroleptic therapy ; Neuroleptic withdrawal ; Growth Hormone ; Prolactin ; Psychopathology ; Tardive Dyskinesia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The sensitivity of the dopaminergic hypothalamic pituitary system, as indicated by growth hormone (GH) release after apomorphine (0.5 mg SC), was studied in 11 chronic schizophrenic in-patients under long-term neuroleptic (NL) therapy and after 12 and 30 days' drug withdrawal. GH peak levels after a 12-day drug-free period were significantly elevated (13.1±12 ng/ml) as compared to NL therapy (4.6±6.1 ng/ml). Controls showed a significant higher mean peak GH response (13.6±10 ng/ml) compared to chronic schizophrenic patients under long-term NL therapy. The GH response of patients with symptoms of tardive dyskinesia (TD) did not differ significantly from that of patients without signs of TD. The prolactin (PRL) serum levels under long-term NL treatment were within the normal range in male schizophrenics but decreased significantly after 12 days' drug withdrawal. The data presented indicate a reduced sensitivity of the hypothalamic-pituitary dopamine receptors under long-term NL therapy. The significant increase in GH response on day 12 probably corresponds to a readjustment from a mostly blunted GH response under NL therapy back to stimulated levels of normal controls. No supersensitivity of the pituitary dopamine recpetors could be detected.
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  • 9
    ISSN: 1432-2072
    Keywords: Chronic schizophrenics ; Long-term neuroleptic therapy ; Neuroleptic withdrawal ; Clonidine ; Growth hormone ; Norepinephrine ; Psychopathology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The sensitivity of the alpha-adrenergic hypothalamic pituitary system, as indicated by growth hormone (GH) release after clonidine (0.15 mg i.v.), was studied in nine chronic schizophrenic in-patients (study 1) under long-term neuroleptic (NL) therapy and after 5 days' drug withdrawal and in 17 chronic schizophrenic in-patients (study 2) under long-term NL therapy and after 12 days' drug withdrawal. GH response after 5- and 12-day drug-free periods did not differ significantly from that under NL treatment; however, it was significantly lower after 12 days' drug withdrawal (AUC: 319.9±445.5 ng/ml×min) compared to age- and sex-matched normal controls (579±611 ng/ml×min). The basal norepinephrine (NE) plasma levels under long-term NL therapy were significantly elevated in both studies (study 1:894±553 pg/ml; study 2:432±268 pg/ml) compared to controls (study 1:253±55 pg/ml, study 2:234±126 pg/ml), and were decreased significantly after 5 days' drug withdrawal compared to NL treatment. There was no significant correlation between age, duration of NL therapy, last daily dosage, psychopathology, and NE plasma levels and GH response. The data presented suggest hyposensitivity of alpha-adrenergic receptor function in the hypothalamic-pituitary axis after 12 days' drug withdrawal in chronic schizophrenics. The significantly elevated NE plasma levels under NL therapy indicate that there is no adaption mechanism, even after long-term treatment.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    European archives of psychiatry and clinical neuroscience 241 (1992), S. 291-295 
    ISSN: 1433-8491
    Keywords: Schizophrenia ; Depression ; Neuroleptics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Schizophrenic outpatients (=364) were assigned at random to three different treatment strategies: (1) continuous medication with neuroleptic drugs, (2) intermittent medication with crisis intervention and (3) intermittent medication with early intervention. Depressive syndromes were rated according to three different scales for depressive syndromes (Brief Psychiatric Rating Scale anxious depression factor, Arbeitsgemeinschaft für Methodik und Dokumentation in der Psychiatrie/depression, and the self-rating Paranoid Depression Scale) after 1 and 2 years of treatment. No differences in depression scores were found between the three treatment strategies. Comparisons between patients treated with neuroleptic drugs at the time and patients without neuroleptics revealed significantly higher depression scores in the neuroleptics group in most comparisons. No differences were found between patients treated with low versus high potency neuroleptics and between oral versus depot neuroleptics. However, depression correlated with extrapyramidal symptoms.
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