Serotoninbestimmungen an Thrombocyten und an Fraktionen von Thrombocyten

Zusammenfassung Aus Suspensionen zerstörter Thrombocyten des Menschen wurden reine Fraktionen von Hyalomer und Granulomer hergestellt. Von den Fraktionen wurde jeweils ein Teil für die elektronenmikroskopische Untersuchung, ein anderer Teil für die Bestimmung des Serotonins verwandt. Durch die elektronenmikroskopische Untersuchung jeder einzelnen Fraktion wurde die Reinheit der Fraktionen überprüft. Die Bestimmung des Serotoningehaltes erfolgte am isolierten Rattenmagen. In Kontrollversuchen wurde ferner der Serotoningehalt intakter Thrombocyten bestimmt.Intakte Thrombocyten besitzen im Mittel einen Serotonin-Gehalt von 52 ng/10⁸ Thrombocyten. In den Fraktionierungsversuchen fanden wir 95% des Serotonins in den Hyalomer-Fraktionen und nur 5% des Serotonins in den Granulomer-Fraktionen. In vivo findet sich also der hohe Serotoningehalt fast ausschließlich im Hyalomer der Thrombocyten.

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Summary Pure fractions of hyalomer and granulomer were prepared from suspensions of destroyed human thrombocytes. One portion of the fractions was used for the electron microscopic studies, and the other part for the determination of serotonin (5-hydroxytryptamine). The electron microscopic investigation allowed to check the purity of each single fraction. On the isolated rat stomach the determination of the concentration of serotonin was performed. In control preparations we studied the serotonin concentration of intact thrombocytes. These thrombocytes have a mean serotonin concentration of 52 ng/10⁸ platelets. In fractioning experiments we found 95% of the serotonin in the hyalomer fractions and only 5% of the serotonin in the granulomer fractions. In vivo therefore, the high concentration of the serotonin is found almost exclusively in the hyalomer of the thrombocytes.

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Die Ergebniss wurden vor der Medizinischen Gesellschaft Düsseldorf am 23. 1. 1963 mitgeteilt. Herrn Prof. Dr.Meessen danken wir für die Anregung und Förderung der Arbeit, Herrn Prof. Dr.Greeff für die Hilfe bei den Serotoninbestimmungen.     

Stimulation of prostacyclin synthesis by defibrotide: improved contractile recovery from myocardial "stunning".

Prostacyclin (PGI2) improves regional contractility of postischemically dysfunctional ("stunned") myocardium. We determined whether defibrotide, a fraction of mammalian DNA known to stimulate endogenous formation of PGI2, also improves contractile recovery of stunned myocardium. Anesthetized, open-chest minipigs were subjected to coronary occlusion of 5 min (left anterior descending branch, LAD) followed by 120 min of reperfusion. The animals were treated with defibrotide (32 mg x kg-1 x h-1, intravenously, i.v.) or vehicle throughout the experimental period. Defibrotide improved regional contractility in the ischemic reperfused area from 30 (vehicle) to 78% of the preischemic control without altering the contractility of nonischemic myocardium. Transcardiac PGI2 formation, determined from the difference between coronary venous and arterial plasma concentrations, was elevated from 437 (preischemic control) to 869 pmol x l-1 in defibrotide-treated animals, but was unchanged in the vehicle-treated and a sham-operated group. Thromboxane A2 (TXA2) release was not modified. Defibrotide reduced ischemia-induced formation of platelet aggregates but did not affect the activity of polymorphonuclear neutrophil granulocytes. The data demonstrate an improvement of contractile recovery from stunning by defibrotide that may be related to an inhibition of ischemia-induced platelet activation and (or) membrane protection owing to enhanced transcardiac formation of PGI2.     

Screening for impaired liver function as a risk factor for drug safety at hospital admission of surgical patients

International Journal of Clinical Pharmacy - Background Hepatic insufficiency can affect patient safety and should therefore be considered during drug therapy. Hospital admission offers an ideal...     

Nitric oxide but not prostacyclin is an autocrine endothelial mediator.

Using porcine aortic endothelial cells, the present study investigates whether stimulation of prostacyclin (PGI2) and nitric oxide also causes elevation of the respective second messengers cAMP and cGMP in the endothelial generator cells. The calcium ionophore A23187 at 0.3-3 microM increased endothelial cGMP levels up to 27-fold in an L-arginine-dependent manner as assessed through complete inhibition by NG-monomethyl-L-arginine (100 microM). The 36-fold PGI2 stimulation by 3 microM A23187 was not accompanied by an intracellular increase in cAMP or an enhanced cAMP efflux. Correspondingly, the PGI2 mimetic iloprost (10 pM-100 microM) did not change endothelial cAMP levels. However, forskolin (1-100 microM) and prostaglandin E2 (PGE2) (0.1-10 microM) produced concentration-dependent increases in cAMP with a 9-fold and 8-fold stimulation at 100 microM forskolin and 10 microM PGE2, respectively. These results demonstrate that in contrast to NO, PGI2 acts as a strictly paracrine hormone without affecting the respective second messenger cAMP in the endothelial generator cells.     

Retrospective evaluation of the impact of non-oncologic chronic drug therapy on the survival in patients with bladder cancer

International Journal of Clinical Pharmacy - Background Chronic drug therapy may impact recurrence and survival of patients with bladder cancer and thus be of concern regarding drug choice and...     

Helenalin and 11α,13-dihydrohelenalin, two constituents from Arnica montana L., inhibit human platelet function via thiol-dependent pathways

This study investigates the effect on human platelet function of two sesquiterpene lactones from Arnica montana L., helenalin (H) and 11α,13-dihydrohelenalin (DH). Both compounds inhibited collagen-induced platelet aggregation, thromboxane formation and 5-hydroxytryptamine secretion in a concentration-dependent manner at 3–300 μM. When arachidonic acid was used as stimulus, thromboxane formation remained unaffected despite of inhibition of platelet aggregation. Both H and DH reduced the number of acid-soluble sulfhydryl groups in platelets, by up to 78% at anti-aggregatory concentrations. Moreover, H- and DH-induced platelet inhibition could be prevented by the thiol containing amino acid cysteine. It is concluded that H and DH inhibit platelet function via interaction with platelet sulfhydryl groups, probably associated with reduced phospholipase A₂ activity.     

Incomplete Inhibition of Platelet Secretion by Low-dose Aspirin

This study determines the effects of low-dose oral acetylsalicylic acid (Aspirin) on platelet aggregation and dense granule secretion in relation to inhibition of thromboxane formation. In addition, possible modifications of inhibition of platelet function by iloprost and linsidomine (SIN-1) were also studied. Aspirin (40 mg/day) was administered to 15 healthy male non-smoking volunteers for 8 consecutive days. Platelet function was measured ex vivo before and 12 h after the last drug intake. At the same times urinary excretion of thromboxane B(2) (TXB(2)) and 6-oxo-PGF(1α) were determined. Asirin treatment resulted in a significant (P < 0.01), by 65%, reduction of urinary TX B(2) excretion, whereas urinary excretion of 6-oxo-PGF(1α) remained unchanged, demonstrating the expected selectivity of low-dose aspirin for the platelet cyclooxygenase. There was also a nearly complete (93-95%) inhibition of collagen (0.3-5 μg/ml)-induced thromboxane formation in platelets. However, collagen-induced ATP-and 5-HT secretion was much less inhibited by aspirin and was reduced by only 20% at 5 μg/ml collagen. Similar results were obtained with ADP while thrombin (> 1.2 IU/ml)-induced 5-HT secretion was not antagonized at all. Also aspirin did not affect the inhibition of platelet function by iloprost and linsidomine (SIN-1). It is concluded that stimulation of platelet secretion by stronger stimuli, such as collagen or thrombin, is largely cyclooxygenase-independent and may not be detected by measuring serum thromboxane levels. This may be relevant for clinical situations with shear-stress-induced platelet activation, for example at carotis stenoses or other types of atherosclerotic plaques.