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  • 1
    Electronic Resource
    Electronic Resource
    Differential immunocytochemical staining for glial fibrillary acidic (GFA) protein, S-100 protein and glutamine synthetase in the rat subcommissural organ, nonspecialized ventricular ependyma and adjacent neuropil (1986)
    Springer
    Cell & tissue research 245 (1986), S. 343-351 
    Details
    ISSN: 1432-0878
    Keywords: Subcommissural organ ; Ependyma ; Astrocytes ; Immunocytochemistry ; Glial fibrillary acidic (GFA) protein ; S-100 protein ; Glutamine synthetase ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Antibodies raised against glial fibrillary acidic protein (GFA), S-100 protein (S100) and glutamine synthetase (GS) are currently used as glial markers. The distribution of GFA, S100 and GS in the ependyma of the rat subcommissural organ (SCO), as well as in the adjacent nonspecialized ventricular ependyma and neuropil of the periaqueductal grey matter, was studied by use of the immunocytochemical peroxidase-antiperoxidase technique. In the neuropil, GFA, S100 and GS were found in glial elements, i.e., in fibrous (GFA, S100) and protoplasmic astrocytes (S100, GS). The presence of S100 in the majority of the ventricular ependymal cells and tanycytes, and the presence of GFA in a limited number of ventricular ependymal cells and tanycytes confirm the glial nature of these cells. The absence of S100, GFA and GS from the ependymocytes of the SCO, which are considered to be modified ependymal cells, suggests either a non-astrocytic lineage of these cells or an extreme specialization of the SCO-cells as glycoprotein-synthesizing and secreting elements, a process that may have led to the disappearance of the glial markers.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00213941
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  • 2
    Electronic Resource
    Electronic Resource
    Environmental modulation of the response to amphetamine: dissociation between changes in behavior and changes in dopamine and glutamate overflow in the rat striatal complex (2000)
    Springer
    Psychopharmacology 151 (2000), S. 166-174 
    Details
    ISSN: 1432-2072
    Keywords: Keywords Novelty ; Context ; Environment ; Stress ; 6-OHDA ; Rotational behavior ; Striatum ; Nucleus accumbens shell ; Caudate ; Amphetamine ; Dopamine ; Glutamate ; Aspartate ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: We have previously shown that environmental novelty enhances the behavioral activating effects of amphetamine and amphetamine-induced expression of the immediate early gene c-fos in the striatal complex, particularly in the most caudal portion of the caudate. In contrast, we found no effect of novelty on the ability of amphetamine to induce dopamine (DA) overflow in the rostral caudate or in the core of the nucleus accumbens. Objectives: The twofold aim of the present study was to determine the effect of environmental novelty on (1) amphetamine-induced DA overflow in the shell of the nucleus accumbens and in the caudal portions of the caudate, and (2) glutamate and aspartate overflow in the caudal portions of the caudate. Methods: Two groups of rats with a unilateral 6-hydroxydopamine lesion of the mesostriatal dopaminergic system received amphetamine (0.5 mg/kg, i.v.) in physically identical cages. For one group, the cages were also the home environment, whereas, for the other group, they were a completely novel environment. In vivo microdialysis was used to estimate DA, glutamate, and aspartate concentrations. Results: Environmental novelty enhanced amphetamine-induced rotational behavior (experiments 1–3) but did not alter amphetamine-induced DA overflow in either the shell of the nucleus accumbens (experiment 1) or the caudate (experiment 2). In addition, the ability of environmental novelty to enhance amphetamine-induced behavioral activation was not associated with changes in glutamate or aspartate efflux in the caudate (experiment 3). Conclusions: The present data indicate that the psychomotor activating effects of amphetamine can be modulated by environmental context independent of its primary neuropharmacological actions in the striatal complex.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002139900359
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  • 3
    Electronic Resource
    Electronic Resource
    Autoradiographic demonstration of gastrin binding sites in rat gastric mucosa
    Amsterdam : Elsevier
    Peptides 8 (1987), S. 391-398 
    Details
    ISSN: 0196-9781
    Keywords: Autoradiography ; Chief cell ; Fundus ; Gastrin ; Generative zone ; Parietal cell ; Rat ; Stomach
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/0196-9781(87)90116-1
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  • 4
    Electronic Resource
    Electronic Resource
    Sequential administration of temozolomide and fotemustine: Depletion of O6-alkyl guanine-DNA transferase in blood lymphocytes and in tumours (1999)
    Springer
    Annals of oncology 10 (1999), S. 831-838 
    Details
    ISSN: 1569-8041
    Keywords: melanoma ; pharmacodynamics ; pharmacokinetics ; temozolomide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: The DNA repair protein O6-alkylguanine-DNA alkyl transferase (AT) mediates resistance to chloroethylnitrosoureas. Agents depleting AT such as DTIC and its new analogue temozolomide (TMZ) can reverse resistance to chloroethylnitrosoureas. We report the results of a dose finding study of TMZ in association with fotemustine. Patients and methods: Twenty-four patients with metastatic melanoma or recurrent glioma were treated with escalating dose of oral or intravenous TMZ ranging from 300 to 700 mg/m2, divided over two days. Fotemustine 100 mg/m2 was given intravenously on day 2, 4 hours after TMZ. AT depletion was measured in peripheral blood mononuclear cells (PBMCs) and in selected cases in melanoma metastases and was compared to TMZ pharmacokinetics. Results: The maximum tolerated dose (MTD) of TMZ was 400 mg/m2 (200 mg/m2/d) when associated with fotemustine the 2nd day with myelosuppression as dose limiting toxicity. The decrease of AT level in PBMCs was progressive and reached 34% of pretreatment values on day 2. There was however wide interindividual variability. AT reduction was neither dose nor route dependent and did not appear to be related to TMZ systemic exposure (AUC). In the same patients, AT depletion in tumour did not correlate with the decrease of AT observed in PBMCs. Conclusions: PBMCs may not be used as a surrogate of tumour for AT depletion. Further study should concentrate on the pharmacokinetic pharmacodynamic relationship in tumour to provide the basis for individually tailored therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008304032421
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  • 5
    Electronic Resource
    Electronic Resource
    Spontaneous neuronal firing patterns in fetal rat cortical networks during development in vitro: a quantitative analysis (1987)
    Springer
    Experimental brain research 69 (1987), S. 43-52 
    Details
    ISSN: 1432-1106
    Keywords: Spike train analysis ; Spontaneous activity ; Primary culture ; Neuronal development ; Occipital cortex ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The development of spontaneous bioelectric activity (SBA) was studied in dissociated occipital cortex cultures prepared from 19 day old rat fetuses. All cultures, recorded one per diem from 5 to 33 days in vitro (div), showed SBA. Computer analysis of 76 extracellularly recorded single unit spike trains was carried out after selection on the basis of stationarity criteria. Statistically significant developmental trends were found in (i) interspike interval dependencies and (ii) fluctuations in mean firing rate, on the order of a minute or longer. The highly dependent firing patterns, including stereotyped bursting, were present mostly in the 9–12 div group, whereas minute-to-minute fluctuations in the intensity of firing were considerably more pronounced in the oldest group (22–33 div) than in the younger cultures. In addition, firing categories defined on the basis of factor-analysis revealed that such fluctuations were almost exclusively to be found in neurons which fired in a pronounced ‘burst’, rather than a relatively continuous fashion. Only a few mature appearing synaptic structures were observed electron microscopically prior to 12 div, but increased steadily in number thereafter. No cultures prior to 14 div, but all cultures older than this, stained positively for the presence of glutamic acid decarboxylase. An extensive immunoreactive, putative GABAergic, network was present by three weeks in vitro.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00247027
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  • 6
    Electronic Resource
    Electronic Resource
    Pharmacokinetic properties of the antimuscarinic drug [3H]-hexahydro-sila-difenidol in the rat (1990)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 342 (1990), S. 146-152 
    Details
    ISSN: 1432-1912
    Keywords: Pharmacokinetics ; [3H]-Hexahydro-siladifenidol ; Sila-drug ; Rat ; Autoradiography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The pharmacokinetics of tritiated hexahydrosila-difenidol ([3H]-HHSiD) were examined in rats. Furthermore, the distribution of radioactivity was studied by means of whole body autoradiography. After i. v. administration of 2.9 mg/kg HHSiD plus [3H]-HHSiD to anaesthetized rats bearing a catheter implanted in the ductus choledochus and receiving a mannitol infusion, HHSiD was rapidly distributed and metabolized. Only 5% of the radioactivity was recovered in blood after 23 s and 0.4% after 2.5 h. 64% of the plasma radioactivity could be extracted with hexane from the samples taken 23 s after administration. 52% of the radioactivity was eliminated within 2.5 h, 13% by urinary and 39% by biliary excretion. Following oral administration of 8.6 mg/kg HHSiD plus [3H]-HHSiD there was an absorption of approximately one fourth of the administered radioactivity within 4 h. By means of whole body autoradiography (i. v. injection) as well as by tissue distribution measurement the highest levels of radioactivity were found in bile, urine, lung, kidney, adrenals, liver and pancreas. Thus, after i. v. administration to rats HHSiD is rather quickly distributed, metabolized and excreted. This explains its low antimuscarinic potency in vivo.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00166957
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  • 7
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and tolerance of a new penem antibiotic, FCE 22101, in healthy volunteers after a single intravenous dose (1989)
    Springer
    European journal of clinical pharmacology 36 (1989), S. 633-635 
    Details
    ISSN: 1432-1041
    Keywords: FCE 22101 ; penem antibiotic ; pharmacokinetics ; single dose ; healthy volunteers ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The clinical tolerance and pharmacokinetics of FCE 22101 (sodium (5R, 6S)-6-[(1R)-hydroxyethyl]-2-carbamoyloxymethyl-2-penem-3-carboxylate), a new penem antibiotic, have been studied after giving a single i.v. dose of 4 mg·kg−1 to ten healthy male volunteers. The pharmacokinetics was estimated according to a two-compartment open model. The peak plasma concentration (Cmax) was 15.5 (1.08) µg·ml−1, mean (SEM). FCE 22101 was rapidly cleared from the systemic circulation [ $$t_{1/2\lambda _z } $$ =44.2 (4.2) min; CL=7.21 (0.47) ml·kg−1·min−1]. The mean apparent volume of distribution at steady-state was 246 (16.9) ml·kg−1. The mean residence time relative to the 10 min infusion was 39.4 (1.5)min. Urinary recovery of FCE 22101 showed wide inter-subject variation, ranging from 10.2 to 53.6% of the dose. No subject complained of adverse effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00637750
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  • 8
    Electronic Resource
    Electronic Resource
    The relationships between dose and concentration of tolbutamide and insulin and glucose responses in patients with non-insulin-dependent diabetes (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 163-168 
    Details
    ISSN: 1432-1041
    Keywords: Tolbutamide ; diabetes mellitus ; non-insulin dependent ; pharmacokinetics ; pharmacodynamics ; glucose ; insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary It is uncertain how the hypoglycaemic effect of sulphonylureas varies with drug concentration in patients with non-insulin-dependent diabetes mellitus. The interrelationship of tolbutamide dosage and concentration, and glucose and insulin concentrations were therefore examined in 54 out-patients (the observational group) and in 20 patients studied under controlled conditions (the experimental group). In the observational group, tolbutamide concentration depended significantly on the daily dose, time from dose to sampling, body weight, and age. Blood glucose and insulin concentration were related, but were independent of tolbutamide concentration. In the experimental group, peak, but not pre-dose, tolbutamide concentration, depended on dose and on body mass index. Fasting and maximum post-prandial blood glucose concentration were positively correlated with maximum tolbutamide concentration, probably because tolbutamide dosage was highest in those with the poorest response. In the subset with a fasting blood glucose concentration of less than 8 mmol·l−1, neither glucose nor insulin concentrations depended significantly on tolbutamide concentrations. Tolbutamide concentration does not directly determine hypoglycaemic response in outpatients, and therapeutic monitoring of drug concentrations would not improve the management of such patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00280071
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  • 9
    Electronic Resource
    Electronic Resource
    Distribution of oral ketoconazole to vaginal tissue (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 331-333 
    Details
    ISSN: 1432-1041
    Keywords: ketoconazole ; vaginal candidosis ; oral antimycotic ; distribution ; pharmacokinetics ; vaginal tissue concentrations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma samples and biopsies of vaginal tissue were obtained from 23 healthy women undergoing operative sterilization, 1 to 6 h after a single oral dose of ketoconazole 200 mg. Drug concentrations in plasma and tissue, were measured by a specific gas chromatographic method. The vaginal tissue concentration averaged 2.4 times less than the corresponding plasma levels. Equilibrium between tissue, and plasma was established within 1 h after dosing, when vaginal tissue levels exceeded 1 µg/g. Ketoconazole concentrations decayed monoexponentially over the time interval studied (1–6 h), with the similar half-lives of 1.2 and 1.4 h in plasma and tissue, respectively. Following an oral 200 mg dose, a tissue concentration not less than 0.01 µg/ml was maintained over a 12 h period. This concentration has been shown to prevent outgrowth of the invasive (pseudo) mycelial form ofCandida albicans. Hence, a b.i.d. or t.i.d. dosage schedule of ketoconazole in vaginal candidosis would give continuously effective levels at the site of infection. Ketoconazole concentrations in vaginal fluid are thought to be much higher than in the tissue because of ion-trapping. The present data may explain the efficacy of oral ketoconazole in the treatment of vaginal candidosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613615
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  • 10
    Electronic Resource
    Electronic Resource
    Renal excretion and pharmacokinetics of methotrexate and 7-hydroxy-methotrexate following a 24-h high dose infusion of methotrexate in children (1986)
    Springer
    European journal of clinical pharmacology 30 (1986), S. 231-238 
    Details
    ISSN: 1432-1041
    Keywords: methotrexate ; hydroxymethotrexate ; lymphoid malignancy ; renal excretion ; metabolism ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In children with lymphoid malignancies 18 courses of methotrexate (18–200 mg/kg) administered as a 24-h infusion were monitored. Plasma concentrations and renal excretion rates of methotrexate (MTX) and 7-hydroxymethotrexate (7-OHMTX) were determined. A low correlation was found between the administered dose of MTX and the body exposure to MTX or 7-OHMTX. Although 84% of the MTX eventually recovered from the urine was excreted during the 24 h of the infusion, the renal clearance of MTX was markedly lower during the time of the infusion than after it. There were courses with a low and others with a high renal clearance of MTX during the infusion, despite the same urine flow. A low MTX renal clearance was correlated with a high body exposure to MTX. As the same variations were also seen in the same patient during successive courses, pharmacokinetical characterization of patients appears questionable. The renal clearance of 7-OHMTX was significantly lower than the renal clearance of MTX, and the body exposure to 7-OHMTX ranged from 2–40% of the MTX body exposure. Treatment courses with a low or a high body exposure to 7-OHMTX were not associated with different urinary recoveries of the metabolite. Differences in MTX hydroxylation could not be substantiated. Because the concentration of 7-OHMTX is high soon after the end of an infusion, a specific method of MTX determination should be chosen for controlling treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00614310
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