A monochromatic confocal micro-x-ray fluorescence (μXRF) spectrometer for the lab.

Confocal micro-x-ray fluorescence (μXRF) is a powerful tool to analyze the spatial distribution of major, minor, and trace elements in three dimensions. Typical (confocal) μXRF measurements in the lab use polychromatic excitation, complicating quantification and fundamental parameter-based corrections and furthermore deteriorating peak-to-background ratios due to scattered bremsstrahlung. The goal for the new setup was to remedy these problems, without sacrificing spatial resolution, and keep it flexible for different excitation energies and transportation to other sources.

1-Methylnicotinamide (MNA), a primary metabolite of nicotinamide, exerts anti-thrombotic activity mediated by a cyclooxygenase-2/prostacyclin pathway.

Background And Purpose: 1-methylnicotinamide (MNA) has been considered to be an inactive metabolite of nicotinamide. Here we assessed the anti-thrombotic activity of MNA in vivo.

Experimental Approach: Antithrombotic action of MNA was studied in normotensive rats with extracorporeal thrombus formation (thrombolysis), in renovascular hypertensive rats with intraarterial thrombus formation (arterial thrombosis) and in a venous thrombosis model in rats (venous thrombosis).

In vivo endothelial interaction between ACE and COX inhibitors.

Here we studied the mechanism of thrombolytic response (THR) induced by angiotensin converting enzyme (ACE-I) in vivo in anaesthetised Wistar rats with extracorporeal circulation. Intravenous injections of ACE-Is, i.e.

Mechanisms of angiotensin-converting enzyme inhibitor induced thrombolysis in Wistar rats.

Our in vivo assay for thrombolysis consisted of recording the weight of platelet-rich thrombi adhering to a collagen strip that was superfused with arterial blood in extracorporal circulation of anaesthetised Wistar rats. Immediate thrombolysis occurred in response to intravenously administrated angiotensin-converting enzyme inhibitor (ACE-I) at non-hypotensive doses of 3-30 microg kg(-1) (captopril View Article and Find Full Text PDF

Synthesis and thrombolytic activity of new thienopyrimidinone derivatives.

It has been observed that ticlopidine and clopidogrel show, apart from their delayed antiplatelet properties, an immediate and transient thrombolytic action related to the ability of these thienopyridines to stimulate the secretory function of vascular endothelium. With the objective to construct new molecules with identical thrombolytic potency but at a higher level, we carried out different structural modifications in the thienopyridine chemical molecule to conclude that the presence of a second N atom in the pyridine cycle (yielding pyrimidine moiety) and the presence of an additional cycle fused to the thienyl ring would lead to enhanced thrombolytic effects. Here we report the six-step synthesis of a series of new benzothienopyrimidinone derivatives characterized by this searched for potent thrombolytic activity.

Comparison of endothelial pleiotropic actions of angiotensin converting enzyme inhibitors and statins.

Two in vitro and one in vivo assay were performed to study the endothelial pleiotropic actions of "tissue type" angiotensin converting enzyme inhibitors (ACE-Is) such as perindopril and quinapril, their active forms, that is, quinaprilat and peridoprilat, or of statins belonging to natural (lovastatin), semisynthetic (simvastatin), and synthetic enantiomeric (atorvastatin, cerivastatin) classes. Cytoplasmic [Ca2+]i levels in cultured bovine aortic endothelial cells and endothelium-dependent nitric oxide-mediated coronary vasodilatation in the Langendorff preparation of guinea pig heart constituted our in vitro assays. The in vivo assay consisted of study of PGI2-mediated thrombolytic response in arterial blood of rats after intravenous administration of drugs.

Thrombolysis by thienopyridines and their congeners.

We propose that anti-platelet thienopyridines, such as ticlopidine or clopidogrel, are thrombolytic owing to endothelial release of prostacyclin (PGI2) and tissue plasminogen activator (t-PA). In this study we used anaesthetised Wistar rats with extracorporal circulation in which arterial blood superfused thrombi which adhered to a strip of collagen. Weight of thrombi was continuously monitored.

Effect of ticlopidine on streptokinase-induced thrombolysis in rats.

Using our original assay system we found that ticlopidine (TP, 30 mg/kg i.v.) had produced a prompt thrombolysis of preformed clots in extracorporeal circulation of anaesthetized rats.

Thrombolytic and antiplatelet action of xanthinol nicotinate (Sadamin): possible mechanisms.

Here we report on thrombolytic and hypotensive actions of Xanthinol nicotinate (Sadamin) in rats and on its anti-platelet and fibrinolytic effects in patients with peripheral arterial obliterative disease (PAOD). Special consideration was given to a proposal of new mechanisms of anti-platelet and thrombolytic actions of Sadamin. We conclude that the mechanism of anti-platelet and thrombolytic activity of Sadamin partly consists of a simultaneous release of endogenous prostacyclin and nitric oxide by the nicotinate component of Sadamin, whereas the theophylline component is responsible for enhancement of physiological actions of these endothelial mediators at the level of cyclic nucleotides which are their second messengers.

Thrombolytic activity of beta-adrenolytic drug, sotalol.

Sotalol is a beta-adrenoreceptor blocking drug, the clinical efficacy of which has been linked up to its negative chrono- and inotropic effects and its hypotensive action. In addition, beta-adrenolytic drugs are known to inhibit platelet aggregation in vitro possibly through lowering of calcium ions level. Here, we report that in rats sotalol at a dose of 10-20 mg/kg i.

Thrombolytic action of ticlopidine: possible mechanisms.

Ticlopidine (Ticlide), an anti-platelet drug with a broad scope of clinical applications, is claimed to be an antagonist of adenosine diphosphate on platelet receptors. In vitro this antagonism cannot be demonstrated. Ex vivo it is detectable many hours after oral administration of the drug, perhaps subsequently to its biotransformation to an unknown metabolite.

Prostacyclin, nitric oxide, and atherosclerosis.

Disorders in arterial production of PGI2 and NO occur in atherosclerosis. Exogenous PGI2 and NO are capable of interacting pharmacologically. We claim that no such direct interactions occur between endogenous endothelial PGI2 and NO.

The mechanism of anti-thrombotic, thrombolytic and fibrinolytic actions of camonagrel--a new thromboxane synthase inhibitor.

So far pharmacological consequences of inhibition of thromboxane A2 (TXA2) synthase by imidazole derivatives (e.g., camonagrel or dazoxiben) were linked to suppression of platelet activity.

Permissive effect of molsidomine towards cardioprotective action of iloprost in myocardial ischemia in cats.

Molsidomine, a donor of nitric oxide, is a drug used in the treatment of ischaemic heart disease. Iloprost, a stable analogue of prostacyclin, is a cardioprotective agent in dogs, cats and rats but not in men. We have studied an interaction between molsidomine and iloprost in protecting against consequences of the "no-reperfusion" myocardial ischaemia.

Kinins and thrombolysis.

In cats with extracorporeal circulation arterial blood pressure and thrombolysis were assayed. In this model apart from their hypotensive properties kallikrein (3-10 units/kg, i.v.

Cardioprotection by molsidomine and iloprost in myocardial ischemia in anaesthetized cats.

In ten anaesthetized open chest cats the ligation of left descending coronary artery (LLDCA) resulted in 80 percent of mortality with survival time of 40.9 +/- 8.6 min.

Occlusion and reperfusion-induced arrhythmias in rats: involvement of platelets and effects of calcium antagonists.

The role of blood platelets in ischemia- and reperfusion-induced arrhythmias and the efficacy of three calcium blocking drugs (verapamil, diltiazem, and nicardipine) in preventing the arrhythmias were investigated. Using anesthetized rats, we measured platelet count (Pc) continuously in vivo with a Technicon autocounter. Thromboxane B2 (TxB2) and 6-keto-PGF1 alpha levels in blood from coronary sinus were determined by radioimmunoassay (RIA).

Kallikrein-thrombolytic and hypotensive action in cats--preliminary results.

An intravenous injection of kallikrein produced hypotensive and thrombolytic effects in anesthetized cats, using the blood superfused tendon technique. The thrombolytic action of kallikrein was mediated by an unstable substance. The generation of this substance was abolished by either acetylsalicylic acid (ASA) or aprotonin and enhanced by captopril.

Prostacyclin and the mechanism of action of defibrotide.

Defibrotide (DEF) is a product of the controlled hydrolysis of DNA from mammalian lungs. In vitro DEF (1-2000 micrograms/ml) neither inhibited the aggregation of human, rabbit and cat platelets nor released PGI2 from cultured porcine aortic endothelial cells. Preincubated with platelet preparations, DEF (10 micrograms/ml) lowered the IC50 for the anti-aggregatory action of PGI2 from 2.

On the mechanism of antiaggregatory effect of myricetin.

Myricetin at a dose of 3.6 micrograms/kg iv was found to inhibit the cat blood platelet aggregation in vivo. It disaggregated platelet thrombi in vitro at a concentration of 60 nM.

On the mechanism of thrombolytic action of thromboxane synthetase inhibitors.

Using our in vivo model for studying drugs which prevent deposition of thrombi or dissipate thrombi formed in extra-corporeal circulation over a collagen strip superfused with arterial blood of anaesthetized and heparinized cats, we have found that dazoxiben--a thromboxane synthetase inhibitor--possesses not only antithrombotic but also thrombolytic potency in vivo (ED50 = 3.8 mg/kg i.v.

Nitrendipine-stimulated release of prostacyclin-like substance in normal and atherosclerotic animals.

Nitrendipine (Bayotensin) is a dihydropyridine derivative that appears to preferentially dilate peripheral vessels by a cellular mechanism similar to those found with other calcium blocking agents. In this study nitrendipine when infused (0.2-0.