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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Cysteine sulfinate decarboxylase (CSD), the putative biosynthetic enzyme for taurine, has been shown to exist in two forms in rat brain, respectively CSDI and CSDII, one of which (CSDII) is considered to be in fact glutamate decarboxylase (GAD). CSDI assay after immunotrapping was made possible by using an anti-CSD antiserum raised in sheep immunized with a partially purified CSD fraction from liver. This antiserum immunoprecipitated both liver CSD and brain CSDI activities with the same affinity but did not inhibit their enzymatic activities. The immunotrapping of CSDI was selective without any contamination by GAD/CSDII activity. The immunotrapped CSD activity, which corresponded exactly to the amount of CSD not precipitated by a GAD/CSDII antiserum, was not inhibited by a specific irreversible GAD inhibitor. A quantitative, selective and sensitive assay was thus developed by measuring CSD activity on the solid phase after immunotrapping. Kinetic parameters of the immunotrapped enzyme remained unchanged. CSDI activity represented only a fraction, around 20% with saturating concentration of substrate, of the total CSD activity in rat brain homogenate. This indicates that most studies on total CSD activity dealt essentially with CSDII activity that is indeed GAD. Regional and subcellular distributions of CSDI have been determined. CSDI activity was about threefold higher in the richest (cerebellum) compared to the poorest (striatum) region without any correlation with GAD/CSDII distribution. Subcellular distribution showed a fourfold enrichment of CSDI activity in the synaptosomal fraction. The precise role of CSDI and CSDII in the biosynthesis of taurine in vivo remains to be elucidated.
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  • 2
    ISSN: 1435-1463
    Keywords: Spiperone binding ; Parkinson's disease ; multiple system atrophy ; vascular lesions ; differential diagnosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In order to investigate the diagnostic value of3H-spiperone binding capacity to lymphocytes in the differential diagnosis of de novo Parkinson's disease (idiopathic Parkinson syndrome, PD), we performed a double blind prospective study of spiperone binding capacity of 123 patients and 23 healthy control persons, belonging to different diagnostic groups (PD, Parkinsonian syndrome due to vascular lesions, multiple system atrophy [MSA], essential tremor). Diagnoses were based on medical history, clinical examination, CT or MRI scan, acute response to dopamimetric drugs, one year follow up, and long term response to L-DOPA treatment. Spiperone binding was assayed using ten different concentrations (0.03–3 nmol) in absence or presence of 1μmol (+)-butaclamol to determine nonsepecific binding. There was no significant difference in spiperone binding between patients with PD not treated with L-DOPA, and patients with other basal ganglia disorders including parkinsonian syndrome due to vascular lesions, multiple system atrophy, or progressive supranuclear palsy, and age matched controls. Binding was significantly higher in parkinsonian patients with PD treated with L-DOPA and patients with essential tremor. It is concluded that at present3H-spiperone binding gives no further information in the differential diagnosis of de novo Parkinson's disease.
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  • 3
    ISSN: 1433-0407
    Keywords: Schlüsselwörter FSME-Endemiegebiet ; Mittelhessen ; Doppelinfektionen ; Lyme-Borreliose ; Zecken ; Liquorbefund ; Key words Tick-borne encephalitis ; Lyme disease ; Double infection ; Endemic area ; CSF-findings
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Tick-borne encephalitis (TBE) is the most severe arbovirus disease transmitted by ticks. The mortality of the central European form is 0.7–2%. Active immunisation is recommended for endemic regions. We report on 4 patients with TBE aquired in Middle-Hessen between 1994 and 1997 (2 in 1997). After repeated CSF and serum testing the TBE-specific antibodies were found in all 4 cases. In one case there was also evidence for a prior infection with borrelia burgdorferi. The results of the initial CSF-analysis were atypical in 2 cases (high cell count of 136 cells/mm3, total protein up to 1.5 g/l). The endemic region for TBE has expanded in northern direction into Middle-Hessen, a region in which Lyme borreliosis is also endemic. Thus, true double infections are possible. This and the initially frequently atypical CSF-findings make the differential diagnosis difficult. Therefore, repetitive CSF and blood examinations are recommended.
    Notes: Zusammenfassung Die FSME ist die häufigste, schwere durch Zecken übertragene Arbovirose Mitteleuropas. Die Letalität der in Teilen Deutschlands vorkommenden westlichen Variante beträgt 0,7–2%. Eine aktive Immunisierung ist möglich und für exponierte Gruppen in Endemiegebieten empfohlen. In Mittelhessen waren bisher keine Endemiegebiete bekannt. Wir berichten über 4 Patienten mit in Mittelhessen erworbenen FSME-Infektionen und typischem Krankheitsverlauf im Zeitraum von 1994–1997 (davon zwei 1997). Bei allen Patienten ließ sich die Infektion serologisch sichern, bei einem der 4 Patienten bestand zusätzlich der Hinweis auf eine abgelaufene oder möglicherweise gleichzeitige Borrelia-burgdorferi-Infektion. Der initiale Liquorbefund war in 2 Fällen atypisch, der Nachweis von spezifischen Antikörpern war im Verlauf in allen Fällen möglich. Mittelhessen ist seit 1997 als FSME-Endemiegebiet anzusehen, welches sich weiter nach Nordwesten auszubreiten scheint. Das gleichzeitige Vorkommen von Borrelia burgdorferi erschwert die Diagnostik und muß an Doppelinfektionen denken lassen.
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  • 4
    ISSN: 1433-0407
    Keywords: Schlüsselwörter M. Parkinson ; Ökonomie ; Krankheitskosten ; Motorische Komplikationen ; Key words Parkinson’s disease ; Cost of illness ; Motor fluctuations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Parkinson’s disease (PD) causes significant expense for the national health care system due to its chronic progressive course, the duration of the disease, the high prevalence and the devastating prognosis. In Germany more than DM 320 million are spent for drugs to alleviate parkinsonian symptoms. The aim of this study was to calculate the economic burden of PD by assessing direct medical costs. Forty patients suffering from idiopathic PD were interviewed at an office of neurological specialists and at an outpatient movement disorder clinic about their use of health care resources 3 months prior to the study. The total annual costs reported were DM 14,500, consisting of DM 6500 for drug therapy and DM 8000 for other medical services, including hospital inpatient care (DM 5600), outpatient care (DM 700), medical sundries (DM 1100) and physiotherapy (DM 600). The costs were positively correlated to the extent of the disease (Hoehn and Yahr stage; HY) and the occurrence of motor fluctuations/dyskinesias.We found that both drug-therapy expenses and total medical costs doubled from HYI to HYIV. The rarely employed s.c. therapy with apomorphine additionally increased the costs of drug therapy in HYV. The occurrence of fluctuations/ dyskinesias also increased medical expenses by approximately a factor of two. Indirect burden due to increased days off of work, unemployment and earlier retirement are also significant in Parkinson’s disease. This study oncludes that a treatment which could prevent or retard disease progression as well as a treatment that delays or reduces motor complications would not only ameliorate the situation of patients suffering from PD, but would also lead to significant reductions in cost for the national health care system.
    Notes: Zusammenfassung Die Parkinson-Erkrankung verursacht beträchtliche Ausgaben für das Gesundheits- und Sozialwesen. Allein in Deutschland werden Arzneimittel mit einem Volumen von ca. DM 320 Mio. für die Behandlung der Parkinson-Erkrankung verschrieben. Ziel dieser Studie mit 40 Patienten mit der Diagnose eines M. Parkinson aus Praxen niedergelassener Neurologen und einer Spezialambulanz für Bewegungsstörungen war es, die Krankheitskosten anhand eines Patientenkolletivs zu berechnen. Die direkten medizinischen Ausgaben wurden anhand retrospektiver Daten, die mittels eines Fragebogens erhoben wurden, für 3 Monate vor Studieneinschluß berechnet. Die direkten medizinischen Kosten der Erkrankung beliefen sich insgesamt auf DM 14500 pro Jahr (DM 6500 für Medikamente, DM 8000 für Leistungen, wie Krankenhausaufenthalt (DM 5600), ärztliche Leistungen (DM 700), Hilfsmittel (DM 1100) und Krankengymnastik (DM 600)). Die medikamentösen sowie die nichtmedikamentösen Kosten zeigten eine direkte Abhängigkeit vom Krankheitsstadium nach Hoehn und Yahr (HY). Die Kosten für Medikamente verdoppelten sich vom HY-Stadium I zum Hoehn-und-Yahr-Stadium IV. Insbesondere die Therapie mit Apomorphin führte in den späten Krankheitsstadien (HY V) zu einer erheblichen Verteuerung der medikamentösen Kosten. Das Auftreten von Fluktuationen und Dyskinesien hatte ebenfalls eine deutliche Zunahme der Ausgaben zur Folge; hier war die Behandlung um den Faktor 2 teurer als bei Patienten ohne Fluktuationen. Indirekte Kosten durch Arbeitsausfall und Frühverrentung sind als weitere wichtige Kostenfaktoren beim M. Parkinson anzusehen. Der Einhalt bzw. die Verlangsamung der Progression der Erkrankung oder die Verzögerung von motorischen Komplikationen würden nicht nur eine deutliche Verbesserung für die Behandlung von Parkinson-Patienten zur Folge haben, sondern wären auch von signifikanter ökonomischer Relevanz für die Gesellschaft und das Gesundheitssystem.
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  • 5
    ISSN: 1433-0407
    Keywords: Schlüsselwörter Pramipexol ; Ropinirol ; Narkolepsie ; Tagesmüdigkeit ; Keywords Pramipexole ; Ropinirole ; Narcolepsy ; Daytime sleepiness
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Recently, sudden “sleep attacks” have been described in parkinsonian patients taking the nonergoline dopamine agonists pramipexole and ropinirole. Due to this possible side effect, patients must be instructed not to drive vehicles and to refrain from other activities carrying the risk of self-injury. However, the very existence of sleep attacks remains controversial in sleep medicine, since a gradual transition from wakefulness to sleep is normally observed. Accordingly, sudden onset of sleep, e.g., in narcolepsy or sleep apnea syndrome, is usually associated with excessive daytime sleepiness. Prevalence of sleep disorders and daytime sleepiness have been shown to be increased in Parkinson's disease. Nonergoline dopamine agonists are already known to induce somnolence. Currently, it is not predictable whether sleep attacks represent a sudden transition from wakefulness to sleep or result from an increased propensity to fall asleep, with patients perceiving a sudden onset. Possible pathophysiological mechanisms and legal implications of sleep attacks are discussed.
    Notes: Zusammenfassung Im Zusammenhang mit der Einnahme der Nonergolin-Dopaminagonisten Pramipexol und Ropinirol wurde vor kurzem das Auftreten plötzlicher “Schlafattacken” bei Parkinson-Patienten postuliert. Aufgrund dieser möglichen Nebenwirkung müssen mit Pramipexol oder Ropinirol behandelte Patienten darauf hingewiesen werden, kein Kraftfahrzeug zu führen und keine anderen Aktivitäten, bei denen ein Mangel an Aufmerksamkeit zu Selbst- oder Fremdgefährdung führt, auszuüben. Aus schlafmedizinischer Sicht gilt das Auftreten von “Schlafattacken” jedoch als ungewöhnlich, da ein allmählicher Übergang aus dem Wach- in den Schlafzustand angenommen wird. So ist das z. B. bei der Narkolepsie oder dem Schlafapnoesyndrom beschriebene rasche Einschlafen in der Regel mit vorbestehender Tagesmüdigkeit assoziiert. Schlafstörungen und Tagesmüdigkeit weisen eine hohe Prävalenz bei der Parkinson-Krankheit auf. Zudem ist Schläfrigkeit als Nebenwirkung der Nonergolin-Dopaminagonisten bereits bekannt. Zum jetzigen Zeitpunkt ist nicht vorhersagbar, ob es sich bei den “Schlafattacken” um einen plötzlichen Übergang aus dem Wach- in den Schlafzustand handelt oder diese überwiegend als Folge eines subjektiv als plötzlich empfundenen Einschlafens bei vorbestehender Tagesmüdigkeit zu interpretieren sind. Mögliche pathophysiologische Mechanismen des Phänomens der “Schlafattacken” sowie rechtliche Implikationen aus der Aufklärungspflicht des Arztes werden in diesem Beitrag diskutiert.
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  • 6
    ISSN: 1432-1106
    Keywords: Neural grafting ; Neural transplantation ; Parkinson's disease ; Cryopreservation ; Fetal mesencephalon ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the present study we quantitatively assessed to what extent freeze-storage at liquid nitrogen temperature influences the survival and function of fetal mesencephalic grafts in the dopamine-depleted rat striatum. Ventral mesencephalic (VM) tissue was dissected from rat fetuses and stored overnight in a preservative medium at 4 °C (hibernation). It was grafted intrastriatally either as a fresh cell suspension or was frozen as tissue fragments or as a cell suspension after stepwise incubation in ascending concentrations of dimethyl-sulphoxide. Following a cryopreservation interval of 80 days in liquid nitrogen, the frozen samples were rapidly thawed, rinsed, and grafted. Cellular viabilities of graft cell suspensions, as assessed by ethidium bromide/acridine orange staining, were decreased from 90% in fresh tissue to 38-35% in frozen and thawed tissue. Amphetamine-induced turning behavior at 6 weeks post-grafting was significantly attenuated in hosts that had received fresh grafts or grafts that were frozen as tissue fragments. Tyrosine hydroxylase-(TH-) immunocytochemistry of recipient brains revealed significant decreases in TH-positive graft cell numbers in rats grafted with cryopreserved tissue (38–42% of fresh tissue). Moreover, the dye exclusion viability of thawed VM tissue was found to accurately predict the subsequent graft survival. There was no difference with respect to graft cell numbers between the two freezing methods employed, though block storage seems to be more simple from a practical point of view. The present study indicates that freezing in liquid nitrogen may be a feasible method for long-term storage of fetal neural tissue for grafting, although a marked decrease in graft survival and function of cryopreserved tissue must be taken into account.
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  • 7
    ISSN: 1432-1106
    Keywords: Basal ganglia ; Transmitters ; Neuropeptides ; GABA ; Enkephalin ; Striato-nigral pathways
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of striatal ibotenic acid lesions on dynorphin-, substance P- and enkephalin-like immunoreactivities in the substantia nigra has been studied with immunohistochemistry as well as biochemistry. A comparison was made with the effects produced by intranigral ibotenic acid lesion and by 6-hydroxy-dopamine injection into the medial forebrain bundle. In addition, the effect of the striatal lesions on nigral glutamic acid decarboxylase (GAD)-positive structures was analysed with immunohistochemistry. The effect of the lesions was analysed functionally in the Ungerstedt rotational model, in order to obtain a preliminary evaluation of the extent of the lesions. The striatal lesions produced a parallel depletion of dynorphin and substance P levels in the substantia nigra, pars reticulata, ipsilateral to the treated side, which was dependent upon the extent and location of the lesion. Ibotenic acid lesions into the tail and the corpus of the striatum produced stronger nigral-peptide depletion than lesions in the head and the corpus of the striatum. Comparison of placement of lesions and localization of depleted area in the substantia nigra revealed a topographical relationship. Furthermore, the nigral depletion patterns of dynorphin and substance P were similar. The immunohistochemical analysis revealed that also GAD-positive fibers in the pars reticulata to a large extent disappeared after striatal lesions, in parallel to the dynorphin- and substance P-positive fibers. However, the depletion was less pronounced for GAD than for the peptides, probably related to presence of local GABA neurons in the zona reticulata of the substantia nigra. These results indicate that with the types of lesion used in this study it is not possible to provide evidence for a differential localization within the striatum of dynorphin-, substance P- and GABA-positive cell bodies projecting to the substantia nigra. The radioimmunoassay showed that (Leu)- but not (Met)-enkephalin was affected to the same extent as the dynorphin peptides, supporting the view that (Leu)-enkephalin in the pars reticulata of the substantia nigra is derived from proenkephalin B and not from proenkephalin A. In the immunohistochemical analysis (Met)-enkephalin-like immunoreactivity could only be detected in the pars compacta of the substantia nigra and did not seem to be affected by any of the lesions. The striatal lesions produced a behavioural asymmetry, which could be disclosed by stimulating the rats with apomorphine, which produced ipsilateral rotation. The total number and intensity of the rotation were closely correlated to the extent and location of the striatal lesion as well as to the amount of dynorphin and substance P depletion found in the substantia nigra of the treated side. The results provide further evidence for the presence of a dynorphin-containing system with fibers originating mainly in the corpus and tail of the striatum and terminating in the zona reticulata of the substantia nigra and may, similarly to the previously characterized substance P and GABA containing pathways, have a role in the control of motor behaviour.
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  • 8
    ISSN: 1432-1106
    Keywords: Key words Parkinson’s disease ; Dopamine ; Substantia nigra ; Striatum ; 6-Hydroxydopamine lesion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Intrastriatal application of 6-hydroxydopamine (6-OHDA) initiates a delayed and progressive loss of nigral dopaminergic neurons and therefore may better resemble the slowly developing neuropathology of Parkinson’s disease. We investigated the anatomical, behavioural and biochemical consequences of intrastriatal 6-OHDA after prior labelling of nigral dopaminergic neurons in rats and whether the dihydropyridine L-type calcium channel blocker nimodipine protected from the induced deficits. Adult rats received bilateral intrastriatal injections of the retrograde fluorescence tracer fluorogold and nimodipine (n=12) or placebo (n=9) pellets implanted subcutaneously. One week later all rats were injected unilaterally with 6-OHDA (20 μg) at the same intrastriatal site. Placebo-treated rats displayed relatively few d-amphetamine-induced ipsilateral net rotations (R) (1.3±1.4 R/min; mean±SEM) 1 week after the lesion with a slight but non-significant decline thereafter (after 2, 3 and 4 weeks). In nimodipine-treated rats the rotation behaviour after 1 week was more prominent (3.5±0.8 R/min; mean±SEM) with a similar slight decline until week 4. Fluorescent and immunocytochemical analysis of the midbrain after 4 weeks revealed a 35% and 39% loss of tyrosine hydroxylase positive cells and a 62% and 56% (placebo and nimodipine, respectively) loss of fluorogold-labelled cells in the ipsilateral substantia nigra pars compacta. Striatal dopamine levels were reduced to 47% (placebo) and 43% (nimodipine) of the control side and the dopamine metabolites dihydroxyphenylacetic acid and homovanillic acid to about 50%. Pretreatment with nimodipine failed to antagonize or to ameliorate any of the lesion-induced deficits. We conclude that pretreatment with 80 mg nimodipine pellets does not prevent nigrostriatal damage induced by intrastriatal 6-OHDA.
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  • 9
    ISSN: 1432-1920
    Keywords: Key words Parkinson's disease ; Differential diagnosis ; Magnetic resonance imaging ; Signal intensity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A reduction in signal in the basal ganglia on T2-weighted images is said to correlate with a poor response to L-DOPA and may help to identify patients with nonidiopathic parkinsonism. Our aim in this prospective study was to use the contrast-to-noise ratio of the MRI signal on T2-weighted images in various parts of the basal ganglia in 43 patients with de novo parkinsonism. Signal intensity measurements were compared to the response to the dopamine agonist apomorphine and dopamine-D2 receptor binding obtained by 3-iodo-6-methoxybenzamine single-photon emission computed tomography (IBZM-SPECT). A reduced contrast-to-noise ratio in the putamen correlated significantly with a negative response to apomorphine and reduced striatal IBZM binding. No additional signal intensity measurement correlated with response to apomorphine or specific IBZM binding. However, there was a considerable overlap of contrast-to-noise ratios between patients with a positive or negative response to apomorphine or normal and reduced IBZM binding. We suggest that semiquantitative assessment of signal intensity in the putamen shows a significant reduction in patients with probably nonidiopathic parkinsonism compared with patients with probably idiopathic parkinsonism. However, this method does not exclude idiopathic parkinsonism in a given patient.
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  • 10
    ISSN: 1432-1106
    Keywords: Key words Brain transplantation ; MIF ; MSF ; 6-OHDA ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Activated microglia play an important role in the rejection of intracerebral grafts and the degeneration of axotomized neurones. We studied the effect of macrophage migration stimulatory factor (MSF) or macrophage migration inhibitory factor (MIF) on allogeneic foetal mesencephalic dopaminergic grafts transplanted into the striatum of 6-hydroxydopamine-lesioned rats. Rotation testing revealed a significant compensation of lesion-induced motor asymmetry 3 weeks post-grafting in animals treated with MIF and vehicle-treated controls compared with pre-graft values (Student′s t-test, P≤0.005) and MSF-treated animals (ANOVA, post hoc Fisher PLSD test, P≤0.05). The MSF group showed no significant compensation. Graft recipients with MIF application (1452.06 ± 164.32 tyrosine hydroxylase-positive ventral mesencephalic cells) and controls (1753.21 ± 165.51 tyrosine hydroxylase-positive neurones) displayed good graft survival. Animals with MSF application showed a significant reduction of tyrosine hydroxylase-positive grafted cells (MSF 570.36 ± 209.49 cells) and graft volumes compared with the MIF and the control group (ANOVA, post hoc Fisher PLSD test, P≤0.05). The propotional area of microglia was significantly reduced in MIF animals compared with control animals (ANOVA, post hoc Fisher PLSD test, P≤0.001). Activated microglia and macrophages were reduced by half in the MIF-treated group compared with MSF animals and controls. We conclude that intrastriatal injections of MSF result in impaired function and survival of allogeneic ventral mesencephalon (VM) grafts 3 weeks after transplantation. MIF can reduce the number of microglia and macrophages in allogeneic foetal VM grafts. A reduction of microglia via MIF application did not enhance graft function and survival.
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