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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 67 (1989), S. 1229-1235 
    ISSN: 1432-1440
    Keywords: PGE1, PGE2, PGI2, Iloprost ; cAMP ; Normal liver ; Hepatocellular cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The binding of prostaglandin (PG) E1 and Iloprost, a chemically stable PGI2-analogue, to purified plasma cell membranes (LPZM) from liver tissue samples obtained at surgery revealed heterogeneity of the binding sites identifying high and low affinity subpopulations. In contrast to these findings only high affinity binding sites were characterized for PGE2. Displacement studies exhibited the highest competition for the PGE1-sites by PGE1 and subsequently by PGE2, Iloprost, PGD2 and PGF2 α. The binding of PGE2 to the hepatic receptor could be best displaced by PGE2 and subsequently by PGE1 and Iloprost, PGD2 and PGF2 α. In addition, PGE1, PGE2 and Iloprost enhanced cAMP-production dose-dependently over baseline. Clinical studies revealed a remarkably lower binding capacity for PGE1 in hepatocellular cancer tissue than in noral liver parenchyma. The different binding behaviour of PGE1 (Iloprost) and PGE2 for the first time provides evidence that PGE1 and PGI2 like at platelet membranes occupate the same receptor also at human LPZM. Since a reasonable number of binding sites for these substances and an enhanced cAMP-production were shown in the liver, the study indicates a regulatory role of PGs in hepatic function.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 49 (1996), S. 515-520 
    ISSN: 1432-1041
    Keywords: Prostaglandin E1 (PGE1) Hypercholesterolaemia ; low-density lipoprotein (LDL) ; LDL receptor ; human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Previous in vitro radioligand binding data have shown that prostaglandin E1 (PGE1) increases the number and the binding affinity of low-density lipoprotein (LDL) receptors of the human liver. Experimental data in normo- and hypercholesterolaemic rabbits have confirmed these findings, showing a significant increase in LDL-binding to the liver in vivo after prolonged PGE1 therapy. Methods: This study aimed to confirm the experimental and animal data in human in vivo. 123I-LDL binding to the liver was quantified in vivo in patients suffering from peripheral vascular disease, seven of them with heterozygous familial hypercholesterolaemia (HC) and five with normal total plasma cholesterol, after PGE1 administration (5 ng·kg−1·min−1; 6 h daily for 5 days/week for 5 weeks). LDL uptake by the liver was quantified by single photon emission computer tomography (SPECT). Results: The amount of LDL trapped by the liver in normocholesterolaemics (45.6%) was significantly higher than in hypercholesterolaemics (22.0%). PGE1 induced an increase in liver LDL binding, which was more pronounced in HC (+38.2%) than in normocholesterolaemic patients (+8.11%).
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1041
    Keywords: Key words Prostaglandin E1; low-density lipoprotein ; cholesterol ; atherosclerosis ; lesional imaging ; arterial apo B-containing lipoprotein influx,
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: An increased apo B-containing lipoprotein influx and cholesterol ester accumulation in arteries are well-known events in human atherogenesis. In vitro and experimental animal studies have provided evidence of a beneficial effect of PGE1 on both vascular apo B-containing lipoprotein accumulation and cholesterol ester content. Methods: We examined the effect of PGE1 (administered via an intravenous portable infusion pump at a rate of 5 ng PGE1 kg−1 ·  min−1 for 5 days a week, 6 h daily, over a total of 5 weeks) in ten patients (eight males, two females) on 123I-apo B-containing lipoprotein accumulation into the large arteries in vivo. Apo B-containing lipoprotein isolation was carried out by immunoaffinity chromatography and radiolabeling with the iodine monochloride method. 123I-apo B-containing lipoprotein accumulation was imaged and quantified by means of special computer software before and after 5 weeks of PGE1 therapy Results: PGE1 led to a significant decrease in maximal arterial apo B-containing lipoprotein retention. The mean decrease in the carotid and femoral arteries in type I lesions amounted to between 16.9% and 30.4%, and in type II lesions between 22.4% and 30.7%, 20 h after injection of radiolabeled apo B-containing lipoprotein. The type of arterial apo B-containing lipoprotein kinetic curves, however, remained unchanged. Conclusion: These findings indicate that PGE1 decreases the apo B-containing lipoprotein influx in the large arteries and the vascular cholesterol content, suggesting that PGE1 may lead to regression of lipid-rich lesions in human in vivo.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 42 (1992), S. 43-46 
    ISSN: 1432-1041
    Keywords: Isradipine ; hypertension ; platelet function ; prostaglandin system ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of treatment for eight weeks with isradipine 1.25 mg twice daily for 4 weeks and thereafter 2.5 mg twice daily for 4 weeks on ex vivo platelet function was investigated in 10 male hypertensive patients, aged 51 (6.1) y. Systolic and diastolic blood pressure, platelet aggregation in response to ADP, serum thromboxane B2 and β-thromboglobulin levels were significantly decreased at rest before exercise ergometry, during exercise and at rest after exercise. The platelet count, platelet sensitivity and the plasma levels of 6-oxo-prostaglandin F1α were not affected by isradipine. It is concluded that a compound that lowers blood pressure and inhibits platelet activation may be of clinical benefit in the routine treatment of hypertension.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 49 (1996), S. 515-520 
    ISSN: 1432-1041
    Keywords: Key words Prostaglandin E1 (PGE1) Hypercholesterolaemia; low-density lipoprotein (LDL) ; LDL receptor ; human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Previous in vitro radioligand binding data have shown that prostaglandin E1 (PGE1) increases the number and the binding affinity of low-density lipoprotein (LDL) receptors of the human liver. Experimental data in normo- and hypercholesterolaemic rabbits have confirmed these findings, showing a significant increase in LDL-binding to the liver in vivo after prolonged PGE1 therapy. Methods: This study aimed to confirm the experimental and animal data in human in vivo. 123I-LDL binding to the liver was quantified in vivo in patients suffering from peripheral vascular disease, seven of them with heterozygous familial hypercholesterolaemia (HC) and five with normal total plasma cholesterol, after PGE1 administration (5 ng⋅kg−1 ⋅min−1 ; 6 h daily for 5 days/week for 5 weeks). LDL uptake by the liver was quantified by single photon emission computer tomography (SPECT). Results: The amount of LDL trapped by the liver in normocholesterolaemics (45.6%) was significantly higher than in hypercholesterolaemics (22.0%). PGE1 induced an increase in liver LDL binding, which was more pronounced in HC (+ 38.2%) than in normocholesterolaemic patients (+ 8.11%).
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1041
    Keywords: taprostene (CG 4203) ; PGI2 analogue ; platelet function ; arachidonate metabolism ; haemodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In order to assess the effect of taprostene on haemodynamics, platelet function and arachidonate metabolism in 4 healthy volunteers an intravenous infusion of 25 ng · kg−1 · min−1 was given for 6 h. During the infusion period systolic blood pressure dropped from 130 to 111 mm Hg and diastolic blood pressure from 77 to 69 mm Hg. The heart rate rose from 77 to 84 beats/min. During the taprostene infusion the slope and height of the ADP and collagen induced platelet aggregation curves were significantly inhibited and the sensitivity of platelets to PGI2 and PGE1 was increased. Plasma and serum thromboxane B2, conversion of exogenous radiolabelled arachidonic acid, WU-test, circulating endothelial cell count, concentration of platelet factor 4, β-thromboglobulin, malondialdehyde and the PGI2-synthesis stimulating plasma factor did not show any clear drug-related alteration. It is concluded that infusion of taprostene 25 ng · kg−1 · min−1 caused measurable inhibition of platelet function ex vivo.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 0090-6980
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 0090-6980
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 0090-6980
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 0090-6980
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
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