Pharmacol Rep
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The interaction between uncompetitive NMDA receptor antagonists (memantine and ketamine), and morphine (mu-opioid receptor agonist) and pentazocine (kappa-opioid receptor agonist) was studied in the writhing test in mice. Memantine and ketamine, administered at subthreshold doses, potentiated antinociceptive effect of the threshold (1 mg/kg) dose of morphine. The effects of the threshold (6 mg/kg) dose of pentazocine were not significantly changed by ketamine, and were significantly enhanced by the higher dose of memantine (15 mg/kg). ⋯ The obtained results have shown that NMDA receptor antagonists (ketamine, memantine) are able to enhance the antinociceptive activity of opioids (morphine, pentazocine). It is necessary to underline that this effect was more apparent for morphine (mu-opioid receptor agonist) + NMDA antagonists than for pentazocine (kappa-opioid receptor agonist). These results may have some importance for clinical practice.
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Both inflammation and thrombosis can be orchestrated by the interactions between circulating cells, such as leukocytes and platelets, with vascular, endothelial and smooth muscle cells, which, during activation or apoptosis, can release circulating microparticles (MPs). Indeed, MPs are membrane vesicles with procoagulant and proinflammatory properties. MPs are present in blood from healthy individuals and in patients under several pathological states, for instance sepsis, preeclampsia, Crohn's disease and diabetes, strengthening the notion that MPs may play a role in these diseases. ⋯ On the contrary, MPs from preeclamptic women compared to those from normal pregnant women showed pro-inflammatory properties in the vascular wall inducing vascular hyporeactivity in vessels from humans and mice. These effects were associated with complex interactions between NO and cyclooxygenase systems via endothelial cell activation. Altogether, these findings suggest that MPs can be considered as vectors of biological messages for vascular homeostasis, during immunity and inflammation.
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Immunopharmacological studies of drugs used in cardiovascular diseases provide new data concerning their modulating effect on the levels of proinflammatory cytokines, chemokines and adhesion molecules. Therefore, we have made an attempt to find out whether enalapril, quinapril and losartan (drugs used in the treatment of arterial hypertension) are able to modulate lipopolysaccharide (LPS)-induced proinflammatory cytokine serum concentrations (tumor necrosis factor alpha - TNF-alpha, interleukin-1 beta _ IL-1 beta, interleukin-6 - IL-6) in spontaneously hypertensive rats (SHR). The animals were divided into four groups as follows: SHR + M (control rats receiving 1% solution of methylcellulose), SHR + E (rats receiving enalapril - 10 mg/kg), SHR + Q (rats receiving quinapril - 10 mg/kg) and SHR + L(rats receiving losartan - 20 mg/kg). 1% solution of methylcellulose and hypotensive drugs were administered by a gavage for 21 days. ⋯ Hypotensive drugs also showed no effect on lipid level. The latest data indicate additional properties of hypotensive drugs. However, further studies are necessary to elucidate precisely the role of proinflammatory cytokines in arterial hypertension.
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Cytisine, a natural plant alkaloid, has been marketed in Central and Eastern Europe for over 40 years for the clinical management of smoking cessation. Despite the fact that cytisine has been used by millions of smokers, its characteristics have not been reviewed in scientific literature in English, and presently existing clinical studies on its effectiveness and safety are insufficient to warrant licensing by modern standards. Understanding of the mechanism of cytisine action as a smoking cessation aid provides a necessary basis for conducting clinical trials to confirm its efficacy as an optimal antismoking therapy. ⋯ Our recent uncontrolled trial has shown that a 12-month carbon monoxide-verified continuous abstinence rate following a standard course of treatment with cytisine with minimal behavioral support is similar (13.8%; N = 436) to that observed following treatment with NIC replacement therapy. Since cytisine exhibits a desirable pharmacological profile which makes it an attractive smoking cessation drug, it should be advanced to randomized clinical trials. However, more detailed preclinical studies on its pharmacokinetics and safety profile are required.
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Angiotensin converting enzyme inhibitor (ACE-I) treated hypertensive patients are well known to be at risk during general anesthesia, because of hypotension that can occur. We compared hemodynamic changes in these patients during induction of general anesthesia with propofol and etomidate - two intravenous anesthetics. Hypotension after propofol that we observed in ACE-I group versus normotension after etomidate (p < 0.001) in our opinion may be the result of additive effect of similar endothelium-dependent mechanism of action of propofol and ACE-I, i.e. increase in production and release of nitric oxide (NO). This very unique observation, however, needs further investigation to precisely define the mechanism of our finding.