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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 28 (1985), S. 585-588 
    ISSN: 1432-1041
    Keywords: isoxicam ; pharmacokinetics ; renal failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The accumulation and disposition of the non-steroidal antiinflammatory drug isoxicam were investigated following its oral administration to 6 subjects with normal renal function and 13 patients with diminished renal function. Isoxicam was given daily as a single oral dose for 14–15 consecutive days. Steady-state plasma levels were achieved after 13 days. The effect of differences in renal function on the kinetics of isoxicam appeared to be minimal. Accumulation of isoxicam was similar in both groups of subjects and there was no significant difference between the groups in the plasma clearance or terminal half-life of isoxicam. There were substantial differences between individuals in the apparent plasma clearance and half-life of the drug, and this is reflected in the 7-fold range of steady-state plasma isoxicam concentrations encountered in the subjects.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 13 (1986), S. 0 
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. Synergism between the contractile effects of platelet-derived serotonin (5HT) and thromboxane A2 (TXA2) on a human blood vessel has been investigated by incubating strips of digital arteries in subcontractile concentrations of either 5HT or the TXA2-mimetic agent U46619.2. Either agonist U46619 or 5HT, in subcontractile concentrations, significantly potentiated the contractile response to the other.3. The 5HT antagonist ketanserin (10 (μmol/1), theCa2+ antagonist drugs verapamil (3 μmol/l), or nifedipine (10 nmol/l), or a Ca2+-free bathing medium, reduced the contractile responses to 5HT, but had no effect on the potentiation mediated by U46619.4. The interaction between TXA2 and 5HT derived from platelets was studied by measuring responses to platelets 1 min after aggregation (in the absence or the presence of ketanserin 10 μmol/l), and 20 min after aggregation. The results indicated that the response to platelets mediated by TXA2 and 5HT was greater than the sum of those mediated by TXA2 or 5HT separately.5. It is concluded that synergism between the contractile effects of 5HT and U46619 occurs in human blood vessels; that this is mediated by enhanced utilization of intracellular, rather than extracellular calcium; and that synergism can also occur when 5HT and TXA2 are released from stimulated human platelets.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 14 (1987), S. 0 
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: SUMMARY1. The post-receptor mechanisms of α1 and α2-adrenoceptor subtypes in guinea-pig aorta and human digital arteries have been explored.2. Nifedipine antagonized contractile responses of human digital arteries to TL99 and methoxamine to a similar degree, thus suggesting that neither the α1 nor the α2 receptor is preferentially linked to calcium entry through voltage-operated channels of the cell membrane.3. In the guinea-pig aorta, which contains only α1-adrenoceptors, methoxamine-stimulated inositol phosphate (IP) production at similar concentrations was required to produce contractile responses.4. In the human digital artery, noradrenaline also produced a significant increase in IP formation, but preliminary experiments have suggested that both TL99 and methoxamine stimulate IP production.5. Thus, the present authors have been unable as yet to confirm, in a tissue which contains both α1-and α2-adrenoceptors, that the post-receptor mechanisms of the α subtypes are different.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 10 (1983), S. 0 
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. The supernatant solutions obtained after aggregation or sonication of washed human platelets were superfused over preparations of human isolated digital arteries using a small volume bioassay method. The agents released from the platelets caused strong contractions of the artery strips.2. Platelet aggregation induced by 10 μg/ml collagen or by 100 μg/ml heat aggregated IgG, released 31.5% and 38.5% respectively, of the contractile activity produced by sonication of the platelets.3. The quantitative contractile effect of supernatants from platelets aggregated by 50 μg/ml IgG was significantly less than that for 100 μg/ml HA IgG. Similarly, the maximum contractile effect of supernatants from platelets aggregated by 300 ng/ml collagen was significantly less than that for 1 μg/ml collagen. This suggests that the concentration of contractile agents released from platelets depends on the concentration of aggregating stimulus.4. Comparison with concentration-effect curves for exogenous serotonin suggests that if the contractility of the platelet supernatant occurring after sonication of platelets is solely due to serotonin, then it is present in a concentration of approximately 3.3 times 10-6 mol/1 (6.6 nmol per 109 platelets).5. It is suggested from this study that in certain clinical situations characterized by hypertension, and in which circulating immune complexes have been found, in vivo platelet activation by immune complexes may be releasing sufficient concentrations of serotonin to constrict peripheral blood vessels and contribute to the hypertension.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 20 (1993), S. 0 
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. The aim of these experiments was to determine if the vasorelaxation of the rat isolated aorta induced by sufentanil or alfentanil is mediated by the endothelium, and, if not, by α-adrenoceptor blockade, or a direct effect on the smooth muscle.2. Both sufentanil (from 10−7 mol/L to 10−4 mol/ L) and alfentanil (from 10−7 mol/ L to 3 × 10−4 mol/L) relaxed rings, where endothelium was intact and precontracted with 40 mmol/L KC1, in a concentration-related manner. Similarly, sufentanil and alfentanil relaxed rings, in the presence or absence of endothelium, which had been precontracted with phenylephrine.3. Naloxone (10−4 mol/L) had no significant effect on the relaxation induced by either sufentanil or alfentanil.4. In a similar manner as phentolamine, pretreatment with sufentanil protected α-adrenoceptors from blockade by phenoxybenzamine (PBZ) in both endothelium intact and denuded rings, but the estimated potency of sufentanil was approximately 100-fold less than that of phentolamine in α-adrenoceptor protection. Treatment with alfentanil did not produce any receptor protection.5. We concluded that, in the rat aorta, vascular relaxation induced by sufentanil is mediated by both α-adrenoceptor blockade and a direct effect on smooth muscle, whilst the relaxant effect of alfentanil is caused by direct effects alone. We also concluded that the endothelium has little role in relaxation produced by either drug.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 17 (1990), S. 0 
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. In order to assess whether the observed hypotensive response in some patients given human granulocyte-macrophage colony stimulating factor (GM-CSF) is caused by a direct vascular effect of the GM-CSF, the effects of mouse and human GM-CSF were examined in rat aortic rings and human saphenous veins respectively.2. No effects of GM-CSF were observed, either in the presence or absence of endothelium, on responses to the α-adrenoceptor agonist phenylephrine.3. These data suggest that GM-CSF does not have direct effects on either vascular endothelium or smooth muscle, and that a direct vascular effect of GM-CSF is not the explanation for the observed clinical response.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 10 (1983), S. 0 
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. Circulating immune complexes in excess of the equivalent of 20 m̈g/ml heat-aggregated IgG were found in fourteen out of twenty patients diagnosed as having preeclampsia.2. Only six of the nineteen controls tested had similar levels of immune complexes. Recent studies have established that concentrations of heat aggregated IgG in excess of 20 m̈g/ml activate human platelets to release sufficient concentrations of vasoactive agents to constrict a human blood vessel in vitro.3. It is therefore suggested that in vivo platelet activation by circulating immune complexes may release sufficient concentrations of vasoactive agents to contribute to the hypertension in pre-eclampsia.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 1 (1974), S. 0 
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: SUMMARY 1. The effects of caffeine, halothane, potassium chloride and procaine have been studied on normal human skeletal muscle in vitro. Particular emphasis has been given to the role played by extracellular calcium ions in producing these effects.2. Caffeine produces a concentration-dependent contracture probably by stimulating the release of calcium ions from the calcium storing membranes of the muscle cell.3. Halothane potentiates the contractures produced by caffeine and potassium chloride probably by facilitating the release of calcium from the storage membranes.4. Potassium chloride produces a contracture only in the presence of caffeine or halothane.5. Procaine inhibits all the contractures studied.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 12 (1985), S. 0 
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. Digital arteries, removed at autopsy from 12 hypertensives and 11 normotensives, have been compared in vitro for the calcium dependence of contractures produced by potassium chloride and noradrenaline, and the potency of verapamil to antagonize contractures to noradrenaline.2. No significant differences were found between the vessels from the hypertensives and normotensives for the pD2 values or the maximum response to either potassium chloride or noradrenaline in bathing solutions containing 2.5, 1.0, 0.5 or 0 mmol/l calcium chloride.3. There were also no significant differences between the vessels, from the hypertensive or normotensives, in the pD2 values for the addition of calcium chloride to arteries exposed to potassium chloride or noradrenaline in a calcium free bathing medium, in the ability of verapamil to shift the pD2 values for noradrenaline, nor in the ability of verapamil to reduce the maximum responses to noradrenaline (except at the two highest concentrations of verapamil tested).4. It is concluded that it is unlikely to be a primary abnormality of the mechanisms regulating calcium ion entry and release in vascular smooth muscle in human hypertension.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 7 (1980), S. 0 
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. The sensitivity of human metacarpal veins and digital arteries obtained post-mortem to noradrenaline and phenylephrine has been tested.2. pED50 values for noradrenaline were significantly higher in the veins (699, s.e.m. = 008) than in the arteries (6.56, s.e.m. = 009), whereas pED50 values for phenylephrine in the two tissues were not significantly different (arteries: 6.24, s.e.m. = 009; veins: 6.26, s.e.m. = 005).3. The addition of propranolol (4 × 10−6 mol/l) alone, or in combination with hydrocortisone (4 × 10−5 mol/l), did not affect the responses to either noradrenaline or phenylephrine. The further addition of cocaine (3 × 10−5 mol/l) slightly shifted the noradrenaline and phenylephrine concentration-effect curves to the left in both arteries and veins, but veins were still found to be more sensitive than arteries to noradrenaline whilst there was still no difference in the sensitivity of veins and arteries to phenylephrine.4. Cocaine also slightly potentiated responses to barium chloride, potassium chloride and serotonin.5. It is concluded that the difference in sensitivity to noradrenaline between arteries and veins cannot be explained by differences in neuronal uptake and it is possible that there may be differences in the properties of the postsynaptic α-adrenoreceptors of the two tissues. It is also concluded that the potentiation of the contractile effect of noradrenaline produced by cocaine is not solely due to inhibition of neuronal uptake of amines.
    Type of Medium: Electronic Resource
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