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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 40 (1991), S. 625-627 
    ISSN: 1432-1041
    Keywords: O-(β-hydroxyethyl)-rutosides ; leg oedema ; healthy subjects ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary O-(β-hydroxyethyl)-rutosides (HR) is used for the treatment of disorders of the venous and microcirculatory systems. In order to evaluate the time course of its activity, the effect of HR on a provocation model of orthostatic oedema in healthy volunteers was used. After a 2 week placebo run-in period, 16 healthy volunteers were randomized to HR (2 tablets of 500 mg/day) of placebo for a further 3 weeks, in a double-blind parallel design. Oedema was provoked by standing motionless for 1 h, with measurement of leg volume before and afterwards. The procedure was undertaken at entry to the study and then weekly during the entire 5 week period. There were no significant differences in the extent of oedema produced by the orthostatic challenge during the 2 week run-in period or in the subjects who continued on placebo (∼90 arbitrary units i.e. ∼48 ml). During the 3 week treatment with HR, however, there was a progressive reduction (−1.1, −5.9, and −7.6 arbitrary units after 1, 2, and 3 weeks, respectively) in the volume of induced oedema, which was significant after 2 and 3 weeks of treatment compared to the placebo group.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 39 (1990), S. 137-141 
    ISSN: 1432-1041
    Keywords: dimetindene maleate ; histamine provocation ; healthy subjects ; time course ; MRT ; blood level-effect correlation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In order to evaluate the time course of its effects, dimetindene maleate has been investigated in a histamine provocation model in man. Eight healthy male volunteers were treated i. v. with 4 mg dimetindene maleate or sodium chloride solution in a double blind, cross over study. Intracutaneous histamine injections were given at −1, 2, 5, 14, 17, 20, 23, 26, and 29 h following drug administration and the areas of flares and wheals were measured after 5, 10, 20, and 30 min. There was strong inhibition of the development both of flares and wheals, which was more pronounced for the former. Baseline adjusted areas under the curve differed significantly following drug and placebo treatment. The maximum effect was observed at 2 h. The mean residence time of the inhibitory effect was calculated to be ≈ 13 h compared to the mean residence time of dimetindene in blood of ≈ 5 h, which indicates a non-linear relationship between blood level and effect.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Clinica Chimica Acta 76 (1977), S. 329-338 
    ISSN: 0009-8981
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have investigated the time-course of the weal and flare inhibiting activity of dimethindene maleate in man and compared the resulting effect-kinetic data with those from pharmacokinetic investigations. The study was carried out in a double blind, placebo controlled cross-over design with randomly assigned healthy volunteers. Dimethindene maleate (4 mg) was intravenously injected, followed by intracutaneous histamine provocations (−1, 2, 5, 14, 17, 20, 23, 26, and 29 h). The two cross-over periods were separated by a wash-out phase of 17 h. Flare and weal areas were documented 5, 10, 20, and 30 min after provocation with histamine. A strong inhibition of the development of flares and weals was observed and was more pronounced in flares than in weals. With regard to the time course of the inhibiting effect, its maxima both for flares and weals were observed at a provocation time of 2 h. The mean residence time of the inhibiting effect was calculated to be ca. 13 h for flares and ca. 15 h for weals. These values are nearly 2–3 times as high as the mean residence time of 6 h calculated from blood level data. Blood- and effect-levels are thus non-linearly related.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have investigated the time-course of the flare inhibiting activity of dimethindene maleate in man and compared the resulting effect-kinetic data with those from pharmacokinetic investigations. The study was carried out in a double-blind, placebo-controlled cross-over design with randomly assigned healthy volunteers. Dimethindene maleate (4 mg) was orally applied, followed by intracutaneous histamine provocations (−1, 2, 5, 14, 17, 20, 23, 26, 29 h). The two cross-over periods were separated by a wash-out phase of 17 h. Flare areas were documented 5, 10, 20 and 30 min after provocation with histamine. A strong inhibition of the development of flares was observed. With regard to the time-course of the inhibiting effect, its maximum was observed at a provocation time of 5 h. The mean residence time of the inhibiting effect was calculated to be ca. 13 h. This is different from the mean residence time of ca. 8 h obtained from blood level data. Blood- and effect-levels are not linearly related under oral treatment conditions.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 306 (1979), S. 287-293 
    ISSN: 1432-1912
    Keywords: 2.4-diamino-6.7-dialkylpteridine ; Diuretics ; Micropuncture ; Tubular transport ; Rat kidney
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The excretion of the diuretic substance DADMP (2.4-diamino-6.7-dimethylpteridine) and of DMP (6.7-dimethylpterin) was studied on single nephrons of the rat kidney using microperfusion and microinjection techniques. In the proximal tubule only DADMP was reabsorbed to a significant degree. Fractional reabsorption rate was independent of the load applied and the permeability constant was found to be 2.2·10−4 cm·s−1. Similar results were obtained in nephrons in which the substances, with inulin, were injected from middle proximal tubular puncture sites and recovered in the urine. DMP appeared in the urine quantitatively and simultaneously with the injected inulin. DADMP recovery, however, was only 20–30% of the injected load during the injection period and after 2 h some 70% was recovered from the urine of both kidneys. The reabsorbed fractions were independent of the loads applied, which varied between 2·10−13 mol·min−1 and 10−9 mol·min−1. A comparison of the microperfusion and the microinfusion data suggests that the reabsorption of DADMP occurs predominantly in the proximal convolution, and it appears that the differences between the renal handling of DMP and DADMP are explicable by their different lipid solubilities.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Pflügers Archiv 375 (1978), S. 9-16 
    ISSN: 1432-2013
    Keywords: Pterins ; Micropuncture ; Tubular transport ; Rat kidney
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In rat kidney, the rate of urinary biopterin [biopterin (B), 7,8-dihydrobiopterin (BH2), and 5,6,7,8-tetrahydrobiopterin (BH4)] excretion as measured by Crithidia assay, was found to be at least 3 times greater than the rate at which it is filtered (GFR·PBiopt.). At a renal blood flow of 6.43±1.34 ml/min per g kidney wt., biopterin concentrations in arterial and renal venous blood and plasma were similar [art. blood: 250±50 ng/ml, ren. venous blood: 247.3±50.9 ng/ml, art. plasma: 23.1±5.8 ng/ml, ren. venous plasma: 23.4±6.9 ng/ml (means±S.D.)]. 14C-BH4 and3H-inulin, infused by means of a micropump into late proximal segments of single nephrons at concentrations of 10−4–10−6 mol, were excreted at similar fractional rates (inulin: 0.85–0.97, BH4: 0.87–0.92, total recovery 1.00–1.09 and 0.99–1.11, respectively). Similar results were obtained with 6,7-dimethylpterin, but not with 6,7-dimethyl-5,6,7,8-tetrahydropterin. The latter is reabsorbed at a fractional rate of 0.20 at concentrations of 10−7 and 10−6 mol. In microperfusion studies in isolated proximal tubular segments in vivo et situ, no reabsorption of 6,7-dimethylpterin could be detected. In case of 6,7-dimethyl-5,6,7,8-tetrahydropterin (DMPH4) at concentrations of 5·10−5 and 10−5 mol/l, however, a permeability constant of 2.39·10−5 cm/s has been measured. From the fact that more biopterin leaves the kidney with urine plus venous blood than entered it is concluded that reduced biopterin is synthesized de novo in the kidney. With the exception of DMPH4, all types of biopterin are not significantly reabsorbed, but rather, are excreted into the urine due to an anisotropic permeability characteristic of the nephron.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Inflammation research 13 (1983), S. 249-251 
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the conscious cat the histidine decarboxylase inhibitorO-methyl-3(+)catechin (Zy 15029) promoted a dose-dependent atropine-sensitive increase in basal acid output. Gastric acid secretion stimulated by food or insulin at different time intervals after pretreatment with Zy 15029 was dose and time dependently diminished up to 70% whereas acid output following pentagastrin stimulation was not reduced by doses effective against the former two stimuli. Only a high dose, which due to side effects has to be claimed as not tolerable in the cat, reduced acid output by about 40%, when application of Zy 15029 and stimulation were 90 min apart. It is suggested that in the cat gastric acid response following the three different stimuli was at least in part but to a variable extent mediated by endogenous histamine. Dose-dependent side effects of Zy 15029 might have been due to histidine decarboxylase inhibition in brain and changes in histaminergic neutrotransmission.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 3-Methoxy-5,7,3′4′-tetrahydroxyflavan (ME), a specific histidine decarboxylase inhibitor, has been shown to significantly reduce the gastric acid secretion and gastric tissue histamine levels in 6 h pylorus ligated rats. It has been found to be as effective as cimetidine in reducing the gastric acid secretion. However, cimetidine does not affect the gastric tissues histamine levels in the normal or pylorus ligated rats. These observations clearly establish that the two drugs reduce the gastric acid secretion by different mechanisms and suggest that their combination may show a potentiated gastric anti-ulcer activity.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The involvement of histamine in mediating gastric function under normal and pathological conditions has been largely established. The relationship between gastric acid production and peptic ulcer diathesis is also well known. Recently, endogenous histamine formation and its release from mast cells has been implicated in the pathogenesis of human and experimental gastric ulcers produced by restraint and pyloric ligation. It has also been implicated in the gastric mucosal damage produced by drugs like aspirin, phenylbutazone and reserpine. These observations suggest that histidine decarboxylase inhibitors may be useful in the prevention of such lesions. Our studies on the evaluation of some histidine decarboxylase inhibitors show that these compounds have a promising potential for developing an effective and safe anti-ulcer drug. This mini-review incorporates the results of our studies which have been adequately supported by other studies as well.
    Type of Medium: Electronic Resource
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