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  • 1
    Electronic Resource
    Electronic Resource
    The anti-inflammatory activity of Ebselen but not thiols in experimental alveolitis and bronchiolitis (1988)
    Springer
    Inflammation research 24 (1988), S. 313-319 
    Details
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This paper describes the effects of the thiol compounds glutathione and N-acetylcysteine and the seleno-organic agent Ebselen on the development of Sephadex-induced lung edema and cell infiltration in the rat. Neither thiol had any effect upon the development of the edema when administered in large, repeated doses. In contrast, when Ebselen was co-administered with the thiols, there was a dose-dependent inhibition of the development of the edema, but lung weights could not be returned to normal values. However, when the thiols were omitted and Ebselen was administered alone, the development of the edema was totally blocked. In addition, in Ebselen-only treated animals there was a selective inhibition of the infiltration of lymphocytes, basophils and eosinophils into the lung lumen without affecting the populations of macrophages and neutrophils. Again, the Ebselen-induced effect was reduced by coadministration of either thiol. These findings are discussed in terms of the potential mechanism of action of Ebselenin vivo and of the possibility of Ebselen being of therapeutic potential in cases of diffuse pulmonary inflammation in humans.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02028288
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  • 2
    Electronic Resource
    Electronic Resource
    Effect of controlled-release metoprolol on blood pressure and exercise heart rate in hypertension: A comparison with conventional tablets (1988)
    Springer
    European journal of clinical pharmacology 33 (1988), S. S33 
    Details
    ISSN: 1432-1041
    Keywords: metoprolol ; hypertension ; tolerability ; exercise ; once-daily dosing ; controlled-release formulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a double-blind study with parallel groups a new controlled-release (CR) formulation of metoprolol1, 100 mg once daily, was compared with conventional metoprolol tablets, 100 mg once daily, in 27 patients with primary hypertension. Exercise tests on a bicycle ergometer were undertaken 24 h after intake of the last dose of the drug following a four-week placebo run-in period and after four weeks of active treatment. Heart rate, measured in the supine position and during exercise at the highest comparable workload, was reduced significantly more by metoprolol CR (p〈0.05), thus indicating a higher degree of β1-blockade at the end of the dose interval with metoprolol CR. There was a greater reduction in supine systolic pressure (p〈0.05) but not in supine diastolic pressure after metoprolol CR than after conventional tablets at 24 h. There was no significant difference between the two groups with respect to reduction in systolic blood pressure during exercise. The 24-h plasma concentrations of metoprolol CR and conventional tablets correlated with the effects on heart rate, but not with blood pressure. The tolerability of metoprolol CR was comparable with that of metoprolol administered as conventional tablets. In conclusion, there was significantly greater β1-blockade 24 h after the intake of drug after metoprolol CR compared with conventional tablets.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00578410
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  • 3
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and pharmacodynamics of controlled-release metoprolol: A comparison with atenolol (1988)
    Springer
    European journal of clinical pharmacology 33 (1988), S. S19 
    Details
    ISSN: 1432-1041
    Keywords: atenolol ; controlled-release metoprolol ; pharmacokinetics ; exercise heart rate ; exercise systolic blood pressure ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Pharmacokinetic and pharmacodynamic properties of a new controlled-release (CR) formulation of metoprolol1 have been compared with those of atenolol2. Metoprolol CR (100 mg and 200 mg), atenolol (50 mg and 100 mg) and placebo were each given once daily for four days in a double-blind, cross-over study to ten healthy men. The plasma concentration-time profiles were more even with metoprolol CR than with atenolol over the 24-h dose interval, shown by the lower fluctuation ratio and the longer time period during which the plasma concentration exceeded 50% of the maximum concentration. All four active treatment regimens reduced exercise heart rate over the 24-h period compared with placebo. However, the reduction in both exercise heart rate and systolic blood pressure (SBP) was more even with metoprolol CR than with atenolol. The remaining β1-blockade after 24 h, expressed as the percentage reduction in exercise heart rate in relation to placebo, was significantly greater after the administration of metoprolol CR, 200 mg, than after either dose of atenolol. At this time the β1-blockade with metoprolol CR, 100 mg, was similar to that with atenolol, 100 mg. At peak plasma concentrations, 4 h after the dose, the subjects experienced less fatigue during exercise with metoprolol CR than with atenolol.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00578408
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  • 4
    Electronic Resource
    Electronic Resource
    Controlled-release metoprolol compared with atenolol in asthmatic patients: Interaction with terbutaline (1988)
    Springer
    European journal of clinical pharmacology 33 (1988), S. S25 
    Details
    ISSN: 1432-1041
    Keywords: controlled-release metoprolol ; atenolol ; terbutaline ; ventilatory capacity ; heart rate ; skeletal muscle tremor ; asthmatic patients
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The β2-adrenoceptor mediated effects on ventilatory capacity, forced expiratory volume in one second (FEV1), forced ventilatory capacity (FVC), heart rate, and skeletal muscle tremor of a new controlled-release (CR) formulation of metoprolol1, 100 mg and 200 mg, and of atenolol2 tablets, 100 mg, were studied in eight asthmatic patients. The effects of single-dose treatment, including placebo as reference, were studied in a randomized, double-blind, cross-over design. Starting 2 h after drug intake, four intravenous infusions containing increasing doses of terbutaline were given at 30-min intervals, followed by three doses of terbutaline inhalations. Maximum plasma concentrations for both metoprolol and atenolol were achieved within the study period. The FEV1 measurements after terbutaline infusions and inhalations were significantly lower after atenolol than after either dose of metoprolol CR. This indicates less blockade of β2-adrenoceptors with metoprolol CR than with atenolol at maximum plasma concentrations. The terbutaline-induced skeletal muscle tremor and increase in heart rate were less after atenolol than after either dose of metoprolol CR, also suggesting less interaction of metoprolol CR with β2-receptors. Thus, the new CR formulation of metoprolol caused fewer adverse effects on β2-adrenoceptor mediated bronchodilatation than a clinically equivalent dose of atenolol.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00578409
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  • 5
    Electronic Resource
    Electronic Resource
    Efficacy and tolerability of a new controlled-release formulation of metoprolol: A comparison with conventional metoprolol tablets in mild to moderate hypertension (1988)
    Springer
    European journal of clinical pharmacology 33 (1988), S. S39 
    Details
    ISSN: 1432-1041
    Keywords: metoprolol ; hypertension ; controlled-release metoprolol ; systolic and diastolic blood pressure ; heart rate ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a double-blind study with parallel groups 195 hypertensive patients were randomly allocated to treatment with either conventional tablets of metoprolol, 100 mg once daily, or a new controlled-release (CR) formulation of metoprolol1, 100 mg once daily. The dose was doubled if the patient's diastolic blood pressure remained ≥95 mmHg after six weeks on 100 mg, whereas well-controlled patients continued on 100 mg once daily for a further six-week period. In the metoprolol tablet group the 200 mg dose was administered in the form of Durules. There was a significant reduction from the placebo baseline in systolic and diastolic blood pressure and heart rate at 24 h after both six weeks and 12 weeks of active treatment; no significant difference in the mean reduction from baseline between the two groups was demonstrated. However, significantly more patients responded to treatment with metoprolol CR when compared with those patients taking metoprolol tablets. After six weeks of active treatment 61% of the metoprolol CR group and 56% of the conventional metoprolol tablet group had a diastolic blood pressure 〈95 mmHg. After another six weeks the corresponding figures were 83% and 69% respectively. Between week 6 and 12, 36% of patients in the metoprolol CR group and 42% of patients in the conventional metoprolol tablet group were receiving a 200 mg dose. All formulations of metoprolol were well-tolerated. Fewer subjective symptoms were reported during active treatment than during the placebo phase. There were no differences between the groups with regard to changes in laboratory variables from baseline, changes in all combined symptoms, or changes in any one symptom.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00578411
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  • 6
    Electronic Resource
    Electronic Resource
    Subjective symptoms and pharmacokinetics/dynamics of metoprolol CR in elderly subjects — a comparison with atenolol (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 571-578 
    Details
    ISSN: 1432-1041
    Keywords: Atenolol ; metoprolol CR ; elderly subjects ; subjective symptoms ; pharmacokinetics ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a double-blind, randomised, cross-over study, the pharmacokinetic/dynamic effects and subjective symptoms of a new controlled-release (CR) formulation of metoprolol (50 and 100 mg) have been compared with atenolol (50 mg) and placebo in 20 elderly healthy subjects. The metoprolol CR formulation displayed an even plasma concentration-time profile over the dosage interval while atenolol produced a peak at 2–4 h. All three active treatments produced significant β1-blockade at 24 h compared to placebo. Four hours after dose intake, the degree of β1-blockade was significantly greater with conventional atenolol 50 mg than with either dose of metoprolol CR. Subjective well-being was examined with a self-administered questionnaire (MSE-profile), including three dimensions: Contentment, Vitality and Sleep. No significant differences were detected between placebo and either dose of metoprolol CR. At 2 h, following atenolol, a deterioration in Vitality was observed compared to placebo and metoprolol CR 100 mg. At the end of the dosage interval there was no longer any significant difference between the treatments. Perceived leg fatigue during exercise, evaluated 4 h after dosing, was more pronounced during treatment with atenolol than metoprolol CR 50 mg. The results suggest that the metoprolol CR formulation was not associated with significant effects on subjective well-being, whereas atenolol caused a deterioration at the time of the peak plasma concentration of the drug.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00278584
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  • 7
    Electronic Resource
    Electronic Resource
    Effects of pH on the stability of the indium-113m blood protein complex and the selective binding of indium-113m to transferrin (1987)
    Springer
    Research in experimental medicine 187 (1987), S. 131-137 
    Details
    ISSN: 1433-8580
    Keywords: Indium-113m ; Transferrin ; pH stability ; Vascular permeability ; Microcirculation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Indium-113m (t 1/2 = 100min; gamma-emission of 393keV) in trace amounts was injected i.v. in rats. Blood was collected by heart puncture 15 min after the injection, and blood plasma was separated by centrifugation. Gel filtration of plasma on Sephadex G-25M equilibrated with glycine/HCl (pH 2.2–3.6), NaHCO3/CO2 (pH 4.0–11.0) glycine/NaOH (pH 8.6–10.6) or sodium acetate/acetic acid (pH 3.0–5.0) was used to separate free indium from indium bound to macromolecular proteins. Determination of radioactivity in eluted fractions showed that more than 85% of the plasma indium was bound to macromolecules at pH values between 5.0 and pH 10.6. However, dissociation of the indium plasma protein complexes occurred at pH values below 5.5, and more than 90% of the indium radioactivity was found in the low molecular weight fraction at pH 2.2. Affinity chromatography using immobilized antibodies to rat transferrin was used to isolate transferrin at pH 7.4 and 5.5. Immunodiffusion and electrophoresis were used to identify the proteins in fractions obtained by affinity chromatography. It was found that the indium-113m activity was correlated with the content of transferrin and that 80%–90% of this activity was found in fractions that had affinity to antitransferrin. These fractions contained transferrin exclusively at pH 7.4, but additional protein fractions of albumin and alpha1-globulin mobility at pH 5.5. At pH 7.4 and 5.5, 10%–20% of the indium activity was detected in molecular fractions that had no affinity to antitransferrin. Immunologic analyses showed that these fractions contained transferrin. Why this transferrin did not bind to the antitransferrin remains unclear. In conclusion, In-113m can be used as an indicator of plasma proteins between pH 5.0 and 10.6.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01851974
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  • 8
    Electronic Resource
    Electronic Resource
    Some applications of the Indium-113m-transferrin technique for gamma-radiation detection of microvascular effects of serotonin and ischemia (1987)
    Springer
    Research in experimental medicine 187 (1987), S. 49-54 
    Details
    ISSN: 1433-8580
    Keywords: Indium-113m-transferrin ; Scintillation camera ; Rat organs ; Microcirculation ; Tumor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The distribution of systematically injected In-113m (t 1/2 = 100 min) in organs of the rat was analyzed, and the use of the isotope for in vivo and in vitro gamma-radiation detection studies of blood plasma protein extravasation was demonstrated in skin, muscle, and tumor. In-113m was slowly excreted from rats. One to 6h after injection the blood held 3% and 2%, respectively, of injected radioactivity/g tissue wet weight; skin and muscle held 0.1%–0.2%/g; liver, colon, and spleen held approximately 1%/g; lungs 1.5%–1.3%/g and kidneys 2.8%–3.3%/g. Scintillation camera technique revealed 40%–80% extraaccumulation of In-113m in a control extremity upon local administration of serotonin and 20%–40% in an extremity with a transplanted tumor, thus indicating a lower effect of serotonin in tumor microvascular circulation than in muscle and skin. In vitro detection of In-113m radiation by a well-counter in dissected tissues showed no effects of serotonin in the tumor and a four- to five-fold increase of radioactivity in muscle and skin, thus confirming blood protein extravasation upon serotonin treatment in these tissues. External analyses of In-113m in the vascular system using one miniaturized probe directed toward an area of interest showed that the method was too sensitive to movements of the animal, and a second probe directed toward a control area is needed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01854968
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