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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 18 (1980), S. 391-394 
    ISSN: 1432-0428
    Keywords: Prostaglandins ; prostacyclin ; PGE2 ; perfused rat heart ; prostaglandin endoperoxides ; coronary flow ; platelet aggregation ; streptozotocin diabetes ; bioassay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The release of prostacyclin and PGE2 from the isolated perfused hearts of acutely diabetic (streptozotocin 100 mg/kg) rats was studied and compared with hearts from control animals. Prostacyclin and PGE2 were measured by a differential bioassay technique. No basal release of either prostaglandin was detected. However, after addition of arachidonic acid, a dose dependent release of prostacyclin and PGE2 was noted. Prostacyclin was identified as the major prostaglandin. Release of prostacyclin and PGE2 from acutely diabetic rat hearts was increased 2–3 times compared to control hearts. No release of prostaglandin endoperoxides was observed in either group of hearts.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1440
    Keywords: Prostacyclin infusion ; Peripheral vascular disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Twelve patients (age 33–77 years, mean age 68.4 years) with peripheral vascular disease (PVD) stage III–IV received continuous intravenous infusions of 5 ng prostacyclin (PGI2)/kg/min and physiological saline for 7 days. The administration was randomized and double-blind with an interval of 7 days between the infusions. During PGI2 infusion systolic blood pressure fell significantly from 147.8±4.8 mm Hg to 140.6±4.0 mm Hg (P〈0.01) and returned to 144.5±4.9 mm Hg post infusion. Transcutaneous p 2 O (tcp 2 O ) measured on the instep of the affected limb increased significantly by 8.9±3.8 Torr during PGI2 infusion and remained elevated during the subsequent week. A significant reduction of pain was observed from the 5th day of PGI2 infusion, lasting for at least the following observation period. Platelet cAMP increased from 18.8±1.5 pmol/108 platelets to 24.7±1.6 pmol/108 platelets on the 3rd day of PGI2 infusion (P〈0.01). Spontaneous platelet aggregation was also significantly reduced during PGI2 infusion. However, 7 days after the infusion thromboxane B2 (TXB2) in plasma and spontaneous platelet aggregation significantly increased in comparison with the preinfusion values, indicating a rebound phenomenon. The clinical outcome was favorable in 9 of 12 patients, was unchanged in two patients, while progressing to limb amputation in one patient.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1440
    Keywords: Nisoldipine ; Thromboxane B2 ; 6-Oxo-prostaglandin F1α ; Platelet aggregation ; Blood pressure ; Placebo-controlled study ; Human volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The influence of the calcium antagonist nisoldipine on collagen-induced platelet aggregation and platelet thromboxane formation was studied ex vivo in healthy male volunteers in a double-blind, placebo-controlled crossover design. Measurements of general haemodynamics, immunoreactive 6-oxo-prostaglandin F1α and thromboxane B2 ex vivo and collagen-induced (0.6 and 2.5 µg/ml) platelet aggregation were performed immediately before (time 0), 0.5 h, 1 h and 2 h after ingestion of 10 mg nisoldipine or an identical placebo tablet. Compared with the control response at time 0, administration of nisoldipine resulted in a significant inhibition of both low-collagen-induced platelet aggregation and formation of immunoreactive thromboxane B2 at time 0.5 h. There were no changes in heart rate or systolic blood pressure but a significant decrease in diastolic blood pressure by nisoldipine at 1 h. No such change was obtained with placebo and there were also no alterations with nisoldipine in platelet aggregation and thromboxane formation after stimulation by high-dose collagen at this or any other time of the study. The data demonstrate a platelet-in-hibitory potential of nisoldipine in healthy men which is probably related to an increased resistance of the platelet membrane against foreign stimuli.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1440
    Keywords: Plasmapheresis ; Hemolytic-uremic syndrome ; Prostacyclin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Three children with hemolytic-uremic syndrome (HUS) were successfully treated with plasmapheresis (PP) combined with early hemodialysis and administration of Aspirin and dipyridamole. Stimulation of vascular prostacyclin release with patients' plasma was measured before and after PP. It was reduced before and increased after plasma exchange. The data indicate that PP might be a useful tool in treatment of (HUS) in children.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 64 (1986), S. 545-551 
    ISSN: 1432-1440
    Keywords: Iloprost ; Antiplatelet actions ; Blood pressure ; Regional perfusion ; Peripheral arterial obliterative disease (PAOD) ; Dose-response study ; Controlled trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The dose-dependent inhibition of platelet aggregation by the chemically stable, prostacyclin-mimetic, iloprost, was studied in patients suffering from stage II–III peripheral arterial obliterative disease (PAOD). The study was designed as a randomized placebo-controlled cross-over trial. Iloprost was administered i.v. to six patients at doses of 0.5, 1.0, 2.0 or 3.0 ng/kg×min for 4 h, with an interval of 2–3 days between the infusions. During iloprost infusion, systolic and diastolic arterial blood pressure, heart rate and blood flow in the affected limb remained unchanged. In contrast, there was a considerable, dose-dependent inhibition of ADP- and thrombin-induced platelet aggregation and secretion ex vivo at doses of 0.5–2.0 ng/kg×min iloprost, indicating that iloprost reduced platelet stimulation by 50%–70%. The antiplatelet action of iloprost remained unchanged during infusion but ceased with 2 h after administration had ended. The agent was tolerated by the patients without unacceptable side-effects at doses up to 2 ng/kg × min. It is concluded that iloprost administered i.v. at doses of 1–2 ng/kg×min in patients with stage II–III PAOD does not involve haemodynamic side-effects and might be considered an effective antiplatelet agent.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 45 (1993), S. 451-457 
    ISSN: 1432-1041
    Keywords: Hypercholesterolaemia ; Lovastatin ; platelet function ; prostacyclin receptors ; thromboxane receptors ; HMG CoA reductase inhibitor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the effects of 12 weeks of lovastatin (20 mg per day) on platelet function and thromboxane formation in 18 patients with type II hypercholesterolaemia in a double-blind, placebo-controlled, prospective study. Lovastatin significantly reduced total serum and LDL-cholesterol by 20% and 25% respectively. Washed platelets of lovastatin-treated patients had significantly reduced collagen-induced aggregation and thromboxane formation ex vivo. There was no change in ADP-induced platelet aggregation, but a significant increase in prostacyclin (iloprost)-stimulated platelet cyclic AMP concentrations in lovastatin-treated patients. This was associated with a significant increase in the number of prostacyclin receptors in platelet membranes prepared from lovastatin-treated patients. There was also an increase in platelet thromboxane receptors. There were no such changes in the placebo group. These data confirm our original observation of normalization of platelet function in hypercholesterolaemia by HMGCoA reductase inhibitors and suggest changes in platelet membrane composition at the megakaryocyte level as a possible site of action.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Copenhagen : International Union of Crystallography (IUCr)
    Acta crystallographica 51 (1995), S. 1099-1102 
    ISSN: 1399-0047
    Source: Crystallography Journals Online : IUCR Backfile Archive 1948-2001
    Topics: Chemistry and Pharmacology , Geosciences , Physics
    Notes: Microgravity offers an environment for protein crystallization where there is an absence of convection and sedimentation. We have investigated the effect of microgravity conditions on the perfection of protein crystals. The quality of crystals for X-ray diffraction studies is characterized by a number of factors, namely size, mosaicity and the resolution limit. By using tetragonal lysozyme crystals as a test case we show, with crystal growth in two separate Space Shuttle missions, that the mosaicity is improved by a factor of three to four over earth-grown ground control values. These microgravity-grown protein crystals are then essentially perfect diffraction gratings. As a result the peak to background of individual X-ray diffraction reflections is enhanced by a similar factor to the reduction in the mosaicity. This then offers a particularly important opportunity for improving the measurement of weak reflections such as occur at high diffraction resolution. These microgravity results set a benchmark for all future microgravity and earth-based protein crystallography procedures.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Copenhagen : International Union of Crystallography (IUCr)
    Acta crystallographica 53 (1997), S. 231-239 
    ISSN: 1399-0047
    Source: Crystallography Journals Online : IUCR Backfile Archive 1948-2001
    Topics: Chemistry and Pharmacology , Geosciences , Physics
    Notes: The protein apocrustacyanin C1 has been crystallized by vapour diffusion in both microgravity (the NASA space shuttle USML-2 mission) and on the ground. Rocking width measurements were made on the crystals at the ESRF Swiss-Norwegian beamline using a high-resolution ψ-circle diffractometer from the University of Karlsruhe. Crystal perfection was then evaluated, from comparison of the reflection rocking curves from a total of five crystals (three grown in microgravity and two earth controls), and by plotting mosaicity versus reflection signal/noise. Comparison was then made with previous measurements of almost `perfect' lysozyme crystals grown aboard IML-2 and Spacehab-I and reported by Snell et al. [Snell, Weisgerber, Helliwell, Weckert, Hölzer & Schroer (1995). Acta Cryst. D51, 1099–1102]. Overall, the best diffraction-quality apocrustacyanin C1 crystal was microgravity grown, but one earth-grown crystal was as good as one of the other microgravity-grown crystals. The remaining two crystals (one from microgravity and one from earth) were poorer than the other three and of fairly equal quality. Crystal movement during growth in microgravity, resulting from the use of vapour-diffusion geometry, may be the cause of not realising the `theoretical' limit of perfect protein crystal quality.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1435-1803
    Keywords: Key words Smooth muscle cells – proliferation – cyclooxygenase-2 – PGI2– PGE1– iloprost – prostacyclin receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Vasodilatory prostaglandins (PGI2, PGE2, PGE1) are known inhibitors of proliferation of vascular smooth muscle cells (SMC) after stimulation with mitogenic factors. However, endogenous prostaglandins do not prevent SMC proliferation subsequent to vessel injury in vivo. Since vascular cells produce large amounts of antiproliferative prostaglandins, especially subsequent to COX-2 expression, insufficient vascular PGI2 formation is not likely to explain the failure of endogenous prostaglandins to prevent excessive SMC growth. In this paper we demonstrate a rapid development of tolerance to PGI2 in SMC, resulting in diminished antiproliferative activity. These findings may not only be relevant for the control of SMC growth by endogenously synthesized prostaglandins but also for clinical use of PGI2 mimetics.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-1238
    Keywords: Sepsis syndrome ; Fat infusion ; Medium chain triglycerides ; Prostaglandin ; Ventilation/perfusion distributions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Fat emulsions containing medium chain triglycerides (MCT) have recently been introduced into clinical practice as a component of total parenteral nutrition. Since several authors reported increased pulmonary artery pressure and impaired gas exchange during intravenous (i.v.) fat use, in particular in septic patients, we studied the pulmonary hemodynamic and gas exchange effects of i.v. fat containg MCT and long chain triglycerides (LCT) in patients with sepsis syndrome. As the effects of fat emulsions have been attributed to increased formation of prostanoids, the production of thromboxane A2 and prostacyclin was investigated by the determination of urinary thromboxane B2 and 6-keto-prostaglandin F2α, respectively. The i.v. fat use did not induce any alterations in pulmonary hemodynamics and gas exchange, the distribution of ventilation and perfusion nor urinary probably content. We conclude that fat emulsions containing MCT induce little alterations in pulmonary hemodynamics and gas exchange. This result is probably due to reduced prostaglandin formation because fat emulsions containing MCT provide less prostaglandin precursors than pure LCT emulsions.
    Type of Medium: Electronic Resource
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