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  • 1
    ISSN: 1432-2072
    Keywords: Amitriptyline ; Nortriptyline ; 10-Hydroxy-nortriptyline ; Plasma drug levels ; Plasma protein binding ; Drug response ; 3-Methoxy-4-hydroxyphenylglycol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In 27 inpatients with primary affective disorder the urinary excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG) was measured prior to a 4-week treatment with 150 mg amitriptyline (AT)/day. Ratings according to the Hamilton depression scale were performed before therapy and repeated after 2 and 4 weeks. Plasma levels of AT, nortriptyline (NT), and E-10-hydroxynortriptyline (OHNT) were assayed weekly, and binding of AT to plasma proteins was determined in one sample. Better therapeutic results were obtained at intermediate, as compared to low and high concentrations of AT or AT plus NT. Independent evaluation of AT and metabolite levels revealed that patients with AT of 50–125 mg/ml responded particularly well when NT did not exceed 95 ng/ml or when NT plus OHNT was below 150 ng/ml. Outside this ‘therapeutic window’ the outcome was markedly poorer. Interindividual variation of AT binding was much smaller than variation of total concentrations. Evaluation of free, instead of total levels did not help to clarify the relationship between clinical and pharmacokinetic variables. Plasma levels within the optimal ranges were found in more patients with high than with low MHPG excretion. The frec fraction of OHNT in plasma of healthy subjects was about 35%.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2013
    Keywords: Respiratory neurons ; Procion yellow ; Morphology ; Membrane properties ; Electrotonic characteristics ; Synaptic inputs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The activity of 32 respiratory neurons located within the retroambigual region of the lower brain stem was recorded intracellulary and the neurons were stained using Procion Yellow. Inspiratory and expiratory bulbospinal (BS), vagal (V) neurons were identified by stimulation within the ventrolateral portions of the cervical spinal cord and the vagal nerves. Another group of inspiratory and expiratory neurons was not antidromically activated by such stimulations (NAA-neurons). A general feature of the retroambigual region seemed to be that neurons were clustered with rich overlapping of the dendritic trees. Dendritic overlapping was also seen at neighbouring respiratory neurons which had been stained by Procion Yellow. These clusters of cells were surrounded by a mass of myelinated axons, which ran predominantly in a longitudinal direction. The morphology of the cell somata, axons, and the dendritic trees was reconstructed from histological sections. The shapes of individual respiratory neurons of the different types were then investigated. The mean surface area of the somata was 5900 μm2 in V-neurons, 3800 μm2 in BS-neurons and 1800 μm2 in NAA-neurons. The dendritic tree extended over a length of up to 400 μm in BS- and V-neurons and over a length of up to 200 μm in NAA-neurons. The dendrites of respiratory neurons spread mainly in dorsomedial and ventrolateral directions. The axons of BS- and V-neurons coursed dorsomedially and acquired a myelin sheath some 30–50 μm away from the cell body. The input resistance of the neurons and the time constants for passive voltage decay transients produced by current pulse injection were estimated during the different periods of the respiratory cycle. The length and diameter of the dendritic segments were measured and the combined dendritic trunk parameter (Σd 3/2) was calculated. This parameter decreased with increasing electrotonic length of the dendrites. These results, in combination with the morphological data, indicate that respiratory neurons receive a tonic synaptic input. Additionally, these measurements have revealed cyclic changes of synaptic input to remote portions of the dendritic tree which seem to exert a significant influence on neuronal activity.
    Type of Medium: Electronic Resource
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