Role of xanthine oxidoreductase in the anti-thrombotic effects of nitrite in rats in vivo.

The mechanisms underlying nitrite-induced effects on thrombosis and hemostasis in vivo are not clear. The goal of the work described here was to investigate the role of xanthine oxidoreductase (XOR) in the anti-platelet and anti-thrombotic activities of nitrite in rats in vivo. Arterial thrombosis was induced electrically in rats with renovascular hypertension by partial ligation of the left renal artery.

Pharmacological modulation of fibrinolytic response - In vivo and in vitro studies.

Fibrinolysis is an action of converting plasminogen by its activators, like tissue- or urokinase-type plasminogen activators (t-PA, u-PA), to plasmin, which in turn cleaves fibrin, thereby causing clot dissolution and restoration of blood flow. Endothelial cells release t-PA, prostacyclin (PGI2) and nitric oxide (NO), the potent factors playing a crucial role in regulation of the fibrinolytic system. Since blood platelets can release not only prothrombotic, but also antifibrinolytic factors, like plasminogen activator inhibitor type-1 (PAI-1), they are involved in fibrynolysis regulation.

Impact of aliskiren on some hemostatic parameters in experimental arterial thrombosis in rats.

Background: Aliskiren is the first orally active inhibitor of renin to be approved for clinical use as an antihypertensive agent. A number of studies show a link between aliskiren and intravascular thrombosis.

Materials And Methods: The goal of the present study was to investigate the impact of aliskiren on arterial thrombosis in normotensive and renovascular hypertensive rats.

Antithrombotic effects of pyridinium compounds formed from trigonelline upon coffee roasting.

Coffee may exert a preventive effect on arterial thrombosis. Trigonelline is one of the most abundant compounds in coffee that undergoes pyrolysis upon roasting of coffee beans. The aim of the present study was to identify pyridinium compounds formed upon trigonelline pyrolysis and coffee roasting and to investigate the effect of three of them, i.

Angiotensin-(1-9) enhances stasis-induced venous thrombosis in the rat because of the impairment of fibrinolysis.

Introduction: ACE2 alternatively converts angiotensin (Ang) II into Ang-(1-7) and Ang I into Ang-(1-9). There is little information in the literature with respect to Ang-(1-9) properties. A number of studies show a link between peptides of the renin-angiotensin system and thrombosis.

Aliskiren inhibits experimental venous thrombosis in two-kidney one- clip hypertensive rats.

A substantial amount of evidence links the renin-angiotensin system with thrombosis. For example, ACE inhibitors and angiotensin receptor blockers possess independent of the hemodynamic changes, antithrombotic activity. Aliskiren direct renin inhibitor belongs to a new very promising antihypertensive drug that effectively inhibits the renin-angiotensin system.

Antithrombotic properties of water-soluble carbon monoxide-releasing molecules.

Objective: We compared the antithrombotic effects in vivo of 2 chemically different carbon monoxide-releasing molecules (CORM-A1 and CORM-3) on arterial and venous thrombus formation and on hemostatic parameters such as platelet activation, coagulation, and fibrinolysis. The hypotensive response to CORMs and their effects on whole blood gas analysis and blood cell count were also examined.

Methods And Results: CORM-A1 (10-30 µmol/kg, i.

Cationic derivative of dextran reverses anticoagulant activity of unfractionated heparin in animal models of arterial and venous thrombosis.

Heparin is a natural polymer widely used in medicine especially during the treatment of cardiovascular diseases since it is a potent blood anticoagulant. In case of emergency, e.g.

Inhibition of platelet aggregation by carbon monoxide-releasing molecules (CO-RMs): comparison with NO donors.

Carbon monoxide (CO) and CO-releasing molecules (CO-RMs) inhibit platelet aggregation in vitro. Herein, we compare the anti-platelet action of CORM-3, which releases CO rapidly (t (½) 1 min), and CORM-A1, which slowly releases CO (t(½) = 21 min). The anti-platelet effects of NO donors with various kinetics of NO release were studied for comparison.

Periodontal pharmacotherapy - an updated review.

Periodontal disease is mainly associated with the activity of bacteria which adhere to the tooth surface and form specific structure of bacterial biofilm. Periodontal bacteria cause inflammation of the gums and aggressive immune response, affecting the periodontium. The first phase of initial therapy - mechanical removal of dental plaque and calculus - is necessary.

Effect of erythropoietin, 5-fluorouracil and SN-38 on the growth of DLD-1 cells.

Supplementation of recombinant human erythropoietin (rHuEpo) is one of the methods for the treatment of anemia. The influence of rHuEpo on proliferation or clonogenic growth of cancer cells is not clear and some of the published results are conflicting. The aim of this work was to study the effect of rHuEpo on colon cancer cells when given alone or in combination with cytostatics.

Angiotensin-(1-9), the product of angiotensin I conversion in platelets, enhances arterial thrombosis in rats.

Angiotensin (Ang) (1-9) is the renin-angiotensin-system peptide found in the plasma of healthy volunteers and after angiotensin-converting-enzyme inhibitors therapy. In vitro experiments proved that Ang-(1-9) may be produced from Ang I. In our study, we tried to expand the poor data about the in vivo properties of Ang-(1-9).

Ventilator-associated pneumonia among elderly Medicare beneficiaries in long-term care hospitals.

Ventilator-associated pneumonia (VAP) is a complication of ventilator care that produces excess, avoidable resource use and treatment costs. Control of VAP is an important aspect of quality of care improvement for long-term care hospitals (LTCHs) since they provide post-acute ventilator care for many Medicare beneficiaries. Data for Medicare patients discharged from LTCHs during CY 2004 who received continuous mechanical ventilation are examined (N=13,759).

[Tryptophan and its metabolites in renal allograft recipients].

Aim: Disturbances in amino acids metabolism are common in chronic renal failure and subside partially after renal tranplantation. Tryptophan (TRP) is one of the most important exogenous amino acids. Its main derivative is L-kynurenine (KYN).

Tissue plasminogen activator in the amygdala: a new role for an old protease.

Evidence has accumulated that point to the tissue plasminogen activator (tPA), a serine protease historically associated with blood physiology, as an important regulator of the central nervous system functioning. tPA is highly expressed in the limbic system where it regulates neuronal viability and experience-induced plasticity. In the amygdala tPA is a critical mediator of stress-induced structural and functional rearrangements that ultimately shape up behavioral responses to stressful stimuli.

N-methylnicotinamide failed to induce endothelial prostacyclin release in perfused rat hindquarters.

N-methylnicotinamide, a nicotinamide derivative, possesses anti-thrombotic activity, although the mechanism of its action is unclear. Using a rat model of isolated perfused hindlimb, we tested whether this metabolite of nicotinamide is able to inhibit the vasoconstrictive effects of epinephrine, norepinephrine, and angiotensin II, thereby releasing prostacyclin from the endothelium. We found that N-methylnicotinamide administration by infusion or bolus injection did not change the course of perfusion pressure and did not inhibit the vasoconstrictive action of epinephrine, norepinephrine, or angiotensin II.

Experimental asthma in rats.

Animal models of asthma have been used for over 100 years. The accuracy of extrapolations from animal models to human asthmatics is highly dependent on the species of animal selected. The rat, in comparison with other animals, demonstrates many features of airway allergy and allergic asthma that are similar to the human conditions.

Nicotinamide and its metabolite N-methylnicotinamide increase skin vascular permeability in rats.

Background: It has been suggested that topically applied nicotinamide and its metabolite N-methylnicotinamide (NMN(+)) might be useful agents for treatment of dermatological disorders such as acne vulgaris and rosacea.

Aim: This study aimed to find out if the mechanism of these therapeutic effects depends on their vascular effects, by investigating if nicotinamide and NMN(+) are able to influence vascular permeability of the vessels in the skin on the back of Wistar rats.

Methods And Results: A dose-dependent increase in vascular permeability was seen in rats treated intradermally with nicotinamide and NMN(+).

Pharmacokinetics and pharmacodynamics of aliskiren, an oral direct renin inhibitor.

Intensive efforts have been spent to discover therapeutic, non-peptide and orally effective hypertensive drugs. One drug that emerged from this effort is aliskiren, a direct human renin inhibitor that blocks the conversion of angiotensinogen to angiotensin I (Ang I). In contrast to other antihypertensive agents, aliskiren decreases plasma renin activity (PRA).

Plasmin system regulation in an ovalbumin-induced rat model of asthma.

Background: So far studies showing the role of the plasmin system in airway remodelling have been conducted using in vitro models. The aim of the present study was to determine plasmin system regulation in an in vivo rat model of asthma.

Methods: Asthma in Wistar rats was induced by ovalbumin (OVA) sensitization followed by an OVA challenge (OVA/OVA, n = 6).

The concentration of kynurenine in rat model of asthma.

Asthma is a chronic inflammatory disease that involves the immune system activation. Evidence is accumulating about the role of kynurenine pathway in the immune system regulation. The kynurenine pathway includes several metabolites of tryptophan, among others kynurenine (KYN).

N-methylnicotinamide inhibits arterial thrombosis in hypertensive rats.

There are few findings indicating that nicotinamide may potentially influence intravascular thrombosis. Interestingly, N-methylnicotinamide, one of the metabolites of nicotinamide - could be more potent than its parent compound. In the present study we have investigated the influence of N-methylnicotinamide on arterial thrombosis in normotensive and renovascular hypertensive rats.

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).

A new recombinant thrombolytic and antithrombotic agent with higher fibrin affinity - a staphylokinase variant. An in-vivo study.

The recombinant protein SAK-RGD-K2-Hir is characterized by its fibrin-specific properties of plasminogen activation combined with antithrombin and antiplatelet activities. It was previously shown in our in-vitro studies to be a more potent and faster-acting thrombolytic agent compared with standard r-SAK. In order to document the effects of the thrombolytic potential of SAK-RGD-K2-Hir we examined this protein in an electrically induced carotid artery thrombosis model and stasis-induced venous model in rats.

Are the endothelial mechanisms of ACE-Is already established?

The endothelial mechanism of ACE-Is action is multifaceted. On the one hand, by inhibiting ACE, ACE-Is diminish Ang II synthesis, one of the best known active peptides. On the other hand, they modify synthesis and release of PGI(2) and NO via increasing production of other biologically important peptides like bradykinin, Ang-(1-7) or Ang-(1-9).