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  • 2000-2004  (72)
  • 1980-1984  (287)
  • pharmacokinetics  (176)
  • Rat  (142)
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  • 1
    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
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 23 (1982), S. 331-333 
    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
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  • 3
    ISSN: 1432-2102
    Keywords: Schlüsselwörter ; Herzvitien ; Klappenersatz ; MR-Imaging ; 31P-MR-Spektroskopie ; Energiestoffwechsel ; Key words ; Valve disease ; Valve replacement ; MR-imaging ; 31P-MR-spectroscopy ; Energy metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Purpose: Heart valve disease combined with left ventricular hypertrophy leads to derangements in cardiac energy metabolism, which can be detected non-invasively by 31P-MR-spectroscopy. The purpose of the present study was to examine whether the derangements in cardiac metabolism are reversible after surgical valve replacement. Patients and methods: 10 healthy volunteers and 10 patients with aortic stenosis (pressure gradients 〉60 mmHg) were included. For assessment of energy metabolism, 31P-MR spectra were obtained with a double oblique 3D-CSI technique (voxel size 25 cm3). In 5 of 10 patients, follow-up examination was performed 3 months after surgical valve replacement (SVR). Left ventricular (LV) function was analyzed by cine MRI. Results: Before SVR the myocardial phosphocreatine to adenosinetriphosphate (PCr-ATP) ratio was significantly (p=0.0002) reduced to 0.80±0.25 in patients compared to 1.65±0.21 in volunteers. 3 months after SVR, LV mass had significantly (p=0.04) decreased from 238±33 g to 206±47 g. At the same time a significant (p=0.04) increase of the PCr-ATP ratio from 0.80±0.25 to 1.28±0.22 was observed. A slight, but not significant, reduction of the phosphodiester ATP ratio was observed before SVR, with a trend towards normalization after SVR. Conclusions: After SVR, the deranged energy metabolism shows a trend towards normalization. Further follow-up is necessary to determine whether complete normalization of the energetic derangement can be observed over longer periods of time following SVR.
    Notes: Zusammenfassung Zielsetzung: Mit einer linksventrikulären Hypertrophie einhergehende Herzvitien führen zu Veränderungen des kardialen Energiestoffwechsels, die mit der 31P-MR-Spektroskopie nichtinvasiv erfasst werden können. Ziel der vorliegenden Studie war es, zu untersuchen, ob nach chirurgischem Klappenersatz eine Normalisierung des Energiestoffwechsels beobachtet werden kann. Patienten und Methode: 10 gesunde Probanden und 10 Patienten mit Aortenklappenstenose (Druckgradient 〉60 mmHg) wurden untersucht. Zur Erfassung des kardialen Energiestoffwechsels wurde eine doppelt angulierbare 3D-CSI-Technik verwendet (Voxelgröße 25 ccm). 3 Monate nach Aortenklappenersatz (AKE) erfolgte bei 5 Patienten eine Nachkontrolle. Bei den Patienten wurden zusätzlich linksventrikuläre (LV) Funktionsparameter mittels cine-MRI-Technik analysiert. Ergebnisse: Vor Klappenersatz war bei den Patienten das Phosphokreatin-Adenosintriphosphat(PCr-ATP)-Verhältnis mit 0,80±0,25 signifikant im Vergleich zu Gesunden (1,65±0,21; p=0,0002) erniedrigt. 3 Monate nach AKE konnte eine signifikante (p=0,04) Verringerung der LV-Masse von 238±33 g auf 206±47 g nachgewiesen werden. Die LV-Ejektionsfraktion änderte sich jedoch nicht wesentlich (von 61±11% auf 65±7%; p=0,22). Zur selben Zeit zeigte sich ein signifikanter (p=0,04) Anstieg des PCr-ATP-Verhältnis von 0,80±0,25 auf 1,28±0,22 an. Für das Phosphodiester-ATP-Verhältnis zeigte sich eine geringe, jedoch nicht signifikante Reduzierung vor AKE, mit einer Tendenz zum Wiederanstieg nach AKE. Schlussfolgerungen: Nach Klappenersatz ist eine Tendenz zur Normalisierung des pathologisch veränderten Energiestoffwechsels zu beobachten. Weitere Nachkontrollen sind notwendig, um zu klären, ob es zu einem späteren Zeitpunkt zu einer vollständigen Normalisierung des Energiestoffwechsels kommt.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Trauma und Berufskrankheit 2 (2000), S. S157 
    ISSN: 1436-6274
    Keywords: Schlüsselwörter ; Achillessehnenruptur ; Nahttechniken ; Primärstabilität ; Funktionelle Nachbehandlung ; Key words ; Achilles tendon rupture ; Suture techniques ; Primary stability ; Postoperative physical therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract The treatment of subcutaneous Achilles tendon rupture aims toward a strong, healed tendon that allows physical and athletic activities at pretrauma levels. This stability can be attained with a minimum of complications using open or minimally invasive suturing techniques, if certain technical recommendations (early operation, no use of tourniquets, simple suture techniques, degradable suture materials, early onset of physical therapy) and contraindications (diabetes mellitus, general healing problems and local risks, restriction of venous or arterial perfusion, smoking, primarily inactive patients) are kept in mind. Operative techniques require no special infrastructure. Our experimental work on human tendons demonstrates the high primary stability of applied suture techniques that allow early physical therapy. Using this concept of operative treatment and early physical therapy with an orthosis, the therapeutic goal can be reached in the shortest time and with the lowest possible rates of rerupture and functional disability.
    Notes: Zusammenfassung Ziel der Behandlung der subkutanen Ruptur der Achillessehne ist eine stabil verheilte Sehne, die körperliche und sportliche Tätigkeit der hochaktiven Patienten in uneingeschränktem Maß ermöglicht. Durch offene oder minimalinvasive Nahttechniken kann diese Stabilität standardisiert und mit einer vertretbar geringen Rate relevanter Komplikationen erreicht werden, wenn operationstechnische Empfehlungen (frühe Operation, keine Blutsperre, einfache Nahttechnik, resorbierbare Nahtmaterialien, frühfunktionelle Nachbehandlung) und Kontraindikationen (allgemeine Heilungsprobleme, lokale Risiken, Diabetes mellitus, arterielle DBS, Raucher, inaktive Patienten) berücksichtigt werden. Eine spezielle Infrastruktur ist für die operative Behandlung der Achillessehnenruptur nicht erforderlich. Experimentelle Untersuchungen an menschlichen Achillessehnen zeigen eine hohe Primärstabilität der Nahttechniken, was eine frühfunktionelle Nachbehandlung ermöglicht. Mit diesem Konzept (operative Versorgung und frühfunktionelle Behandlung mit einer Orthese) wird bei einer sehr geringen Rerupturrate in einer kurzen Behandlungsdauer das gewünschte Behandlungsziel erreicht, das die Wiedererlangung des früheren sportlichen Aktivitätsniveaus sicher ermöglicht.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-2072
    Keywords: Cyclazocine ; Acute treatment ; Dopamine ; Noradrenaline ; Serotonin ; Monoamine metabolites ; Brain regional assay ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of cyclazocine on the metabolism of dopamine (DA), noradrenaline (NA) and 5-hydroxytryptamine (5-HT) in regions of rat brain were studied by measuring changes in the levels of the monoamines and their major metabolites. Doses ranging from 4–32 mg/kg were tested. Rats were sacrificed 1 or 2 h after administration of the drug, according to the experiment. Administration of cyclazocine significantly decreased DA concentration and increased the levels of DOPAC and HVA in striatum. Cyclazocine decreased the levels of NA, and markedly increased the levels of MHPG-SO4 and 5-HIAA in cortex, hypothalamus, midbrain and pons-medulla, while little change in 5-HT concentration, except a decrease after the highest dose, was observed. These changes in the metabolism of the monoamines differed in their amplitude and temporal nature. The possible roles of dopaminergic, noradrenergic and serotoninergic neurons in different brain regions are discussed in relation to modifications of locomotor activity and the induction of bizarre behavior resulting from cyclazocine administration in rats. These investigations may add to the understanding of the mechanism of psychotomimetic effects produced in man by this drug.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 170 (1984), S. 79-85 
    ISSN: 1432-0568
    Keywords: Perineuronal net ; Astrocytes ; Fastigial nucleus ; Cerebellum ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The morphological study of the rat fastigial nucleus with the Golgi-Rio Hortega method showed the presence of glial perineuronal nets surrounding the large neurons, but not the small ones. This perineuronal net appeared as a mesh of tenuous glial processes which covers the neuronal perikarya and proximal dendrites. The small alveolate compartments in this mesh seem to correspond to the holes for the synaptic boutons. Our results also indicate that the perineuronal net is derived from interneuronal protoplasmic and velate astrocytes. Using camera lucida drawings of this perineuronal net we have made a quantitative estimation of the size and density of synaptic boutons on these large neurons. The average numerical density of synaptic boutons was about 19 per 100 μm2 of the neuronal surface, the mean area of the synaptic holes being 2.5 μm2. Furthermore, the quantitative data evidence that about 52.5% of the neuronal surface is presumably occupied by synaptic boutons whereas the remaining 47.5% is covered by the glial processes of the perineuronal net. Semithin sections prepared from thick Golgi sections were used for the cytological study of the neurons surrounded by this glial pericellular network. The possible functional significance of the perineuronal net in the regulation of synaptic transmission in the fastigial cerebellar nucleus is briefly discussed.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-1912
    Keywords: Guanfacine ; Clonidine ; Continuous infusion ; Withdrawal ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In conscious unrestrained spontaneously hypertensive and normotensive rats, prepared with permanently indwelling abdominal aortic catheters, the effects on blood pressure and heart rate of a 12-day continuous subcutaneous infusion of guanfacine (10 mg/kg/day) and clonidine (500 μg/kg/day) and sudden interruption of these treatments were studied. Both drugs significantly and consistently reduced the mean arterial pressure and heart rate throughout the infusion period in the SH rats, but not in the normotensive animals. The magnitude of the effects of both drugs in the SH rat were similar. Following withdrawal of treatment with guanfacine, a discontinuation syndrome was evoked, much less severe than that observed after suspension of the infusion with clonidine. The withdrawal syndromes were characterized by an overshoot of heart rate and a period of blood pressure lability. In spite of the ineffectiveness of guanfacine and clonidine to reduce blood pressure and heart rate consistently in the normotensive rat, similar withdrawal patterns as those found in the SH rat were observed. These findings are in general agreement with the results previously found in clinical studies in hypertensive patients. The spontaneously hypertensive rat may prove a suitable animal model for pre-clinical studies of discontinuation symptoms after cessation of treatment with antihypertensive drugs.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-1041
    Keywords: amitriptyline ; imipramine ; clomipramine ; antidepressant overdose ; clinical effects ; pharmacokinetics ; cardiotoxicity ; maprotiline ; doxepine ; nortriptyline ; opipramol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Twenty-nine cases of self-poisoning with antidepressants (amitriptyline, imipramine, clomipramine, maprotiline, doxepine, nortriptyline, opipramol) were examined by frequent observation of CNS effects, heart rate, blood pressure and standard ECG, 24 h-ECG-monitoring, measurement of systolic time intervals, EEG recordings and frequent measurement of serum levels of antidepressants and primary metabolites. None of the patients died. Maximum total serum antidepressant level (parent compound + desmethyl metabolite) ranged from 20 to 2200 µg/l, with concentrations above 500 µg/l in 11 cases. The serum amitriptyline concentration remained high for 3–4 days in some of the severely intoxicated patients and the decay curves were compatible with partly saturated elimination. A degree of unconsciousness and the occurrence of excitation and hallucinations were generally seen in cases with total serum antidepressant levels above 500 µg/l. Grand mal seizures occurred more frequently at high antidepressant levels, but could not be predicted from the EEG recordings. Increased heart rate and prolonged QRS- and QTc-intervals were significantly correlated with the total serum antidpressant level. 24 h-ECG-monitoring revealed no serious arrhythmias or instances of heart block. Hypotension was only seen initially in few patients. Systolic time interval measurements showed changes suggesting impaired myocardial performance (elevated PEP/LVET ratio) at intermediate (60–500 µg/l) but not high (〉500 µg/l) total serum antidepressant levels. Measurement of serum concentration in antidepressant intoxication is important for identification of patients with high serum levels and the corresponding risk of developing toxic reactions, and to exclude patients with a low concentration who do not require intensive observation.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-1041
    Keywords: cefoxitin ; beta-lactam antibiotics ; pharmacokinetics ; serum concentration ; pleural fluid concentration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of cefoxitin was studied in 6 healthy volunteers and in 5 patients with a pleural effusion after administration of a single dose of 30 mg/kg i.v. infusion. The serum and pleural fluid concentrations of cefoxitin were determined microbiologically. The elimination half-life of the antibiotic from pleural fluid in all cases was 2–3fold longer than from serum, which shows a difference between the kinetic elimination processes of the antibiotic from the two fluids. The slow elimination of cefoxitin from pleural fluid facilitates its accumulation in this compartment during a multiple dosage regimen.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 27 (1984), S. 105-110 
    ISSN: 1432-1041
    Keywords: phenytoin ; epileptic women ; pharmacokinetics ; bioavailability ; pregnancy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Five epileptic women needing to commence phenytoin therapy during pregnancy received a single intravenous and a single oral dose of phenytoin several days apart before starting regular intake of the drug. Plasma phenytoin concentration — time data were analysed by three different pharmacokinetic techniques. However assessed, the mean oral bioavailability of the drug proved to be about 90% of the intravenous bioavailability. This finding makes it unlikely that impaired bioavailability accounts for the increase in oral phenytoin dosage necessary in pregnancy to maintain plasma phenytoin concentrations at pre-pregnancy values. Phenytoin clearance in the pregnant subjects was approximately double the published values for phenytoin clearance in nonpregnant persons. This suggests that increased (metabolic) clearance accounts for the increased phenytoin dosage requirement of pregnancy.
    Type of Medium: Electronic Resource
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