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Previous studies indicate that adenosine supplementation or nitric oxide synthase (NOS) inhibition during reperfusion exert protective effects against myocardial ischemia-reperfusion (I/R) injury. We wanted to test the hypothesis that NOS inhibition before I/R also protects the myocardium against further injury and aimed to determine the involvement of adenosine receptors in a perfused rat heart model. Rats were injected with 10 mg/kg of L-NAME (N(omega)-nitro-L-arginine methyl ester) or L-NAME + SPT (8-(p-sulfophenyl)-theophylline)--an adenosine antagonist - at 2 x 25 mg/kg or with a saline buffer, 24 hrs prior to heart excision. The hearts, perfused retrogradely were subjected to 60 min of global ischemia followed by 120 min reperfusion. L-NAME decreased NOx (nitrite and nitrate) production (16.2 +/- 3.2 vs. 7.0 +/- 1.8 micromol/L; P<0.05) in vivo and increased the release of troponin I (0.04 +/- 0.01 vs. 0.02 +/- 0.01 microg/L; P<0.05) in the plasma, compared to controls. After 120 min of reperfusion, there was a higher release of adenosine (26.1 +/- 2.2 vs. 2.4 +/- 1.2 nmol/min; P<0.01) and a decrease in troponin I levels (0.19 +/-0.07 vs. 0.59 +/- 0.16 ng/min; P<0.05) in the L-NAME group compared to controls. These results were accompanied by a higher proportion of recovery of left ventricular developed pressure (72.0 +/- 4.0 vs. 60.0 +/- 4.0%; P<0.05) and coronary flow (72.0 +/- 5.0 vs. 51.0 +/- 4.0%; P<0.05) in the L-NAME group. These beneficial effects were not blocked by the adenosine receptor antagonist. The present study reveals that L-NAME protects against I/R injury when the inhibitor is administered 24 hrs before ischemia. The beneficial effects observed in this model appear to be independent of adenosine receptor stimulation.

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Bone marrow (BM) from human and rodent species contains a population of multipotential cells referred to as mesenchymal stem cells (MSCs). Currently, MSCs are isolated indirectly by using a culture step and then the generation of fibroblast colony-forming units (CFU-fs). Unprocessed or native BM MSCs have not yet been fully characterised. We have previously developed a direct enrichment method for the isolation of MSCs from human BM by using the CD49a protein (alpha1-integrin subunit). As the CD49a gene is highly conserved in mammals, we have evaluated whether this direct enrichment can be employed for BM cells from rodent strains (rat and mouse). We have also studied the native phenotype by using both immunodetection and immunomagnetic methods and have compared MSCs from mouse, rat and human BM. As is the case for human BM, we have demonstrated that all rodent multipotential CFU-fs are contained within the CD49a-positive cell population. However, in the mouse, the number of CFU-fs is strain-dependent. Interestingly, all rat and mouse Sca-1-positive cells are concentrated within the CD49a-positive fraction and also contain all CFU-fs. In human, the colonies have been detected in the CD49a/CD133 double-positive population. Thus, the CD49a protein is a conserved marker that permits the direct enrichment of BM MSCs from various mammalian species; these cells have been phenotyped as true BM stem cells.

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The evolutions in treatments and clinical practices in organ transplantations led to modifications in the therapeutic drug monitoring (TDM) of immunosuppressive drugs. A focus is made regarding the C2 sampling of cyclosporin, as well as the TDM of mycophenolate mofetil and sirolimus. A review of literature about the evolution of drug monitoring, technical methods and sampling strategies is described. Arguments in favour of TDM are thus a decrease in the frequency of both graft rejection and adverse drug reactions, however, new strategies or new targets are needed in new associations or indications.

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The microdialysis expanded mainly in the field of the neuro- and the dermopharmacology with the study of the transmitters released in the central nervous system and derm. Since ten years, this tool gained other disciplines such as cardiology and cardiovascular surgery. Indeed, the collection and the study of the molecules released in the myocardic interstitial fluid without deteriorating it functioning made microdialysis a powerful tool in the study of the extracellular environment of the cardiomyocyte. The purpose of this study is to point out the principle of the microdialysis and to show its various uses in the field of cardiovascular pharmacology.

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The therapeutic drug monitoring aims at optimising the prescribed dosages to improve efficacy and prevent toxicity. The aim of this study were to review the main pharmacodynamic and pharmacokinetic properties of aminoglycosides, glycopeptides and ceftazidime. Then, the therapeutic drug monitoring of these antibiotics and their methods of analysis is reviewed.

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This study aimed at evaluating the role of nitric oxide (NO) when generated 24 h prior to ischemia-reperfusion. Three groups were studied in an isolated buffer-perfused heart model: Control (saline = 3.3 mL/kg, n = 10), the precursor of NO, L-arginine, (500 mg/kg, n = 10) and an inhibitor of NO synthase, L-NAME, (10 mg/kg, n = 9). All groups were injected intraperitoneally 24 h before heart extraction. Nitrites, nitrates (an index of nitric oxide release) and cardiac troponine I were assayed. During the reperfusion period, there was a low release of nitric oxide and cardiac troponine I associated with improved recovery of post-ischemic myocardial function. These results indicate that in this model, the pre-treatment improved myocardial function and thus, NO could play a role as a trigger and not as a mediator of cardioprotection.

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BACKGROUND: Administration of L-arginine during reperfusion or its addition to cardioplegic solution has been shown to protect myocardium against ischemia-reperfusion injury. This study aimed at evaluating the role of L-arginine in ischemia-reperfusion injury when administered intraperitoneally 24 hours before cardioplegic arrest. METHODS: Two groups of Sprague-Dawley rats (control, n = 10; and L-arginine, n = 10) were studied in an isolated buffer-perfused heart model. Both groups were injected intraperitoneally 24 hours before ischemia. Before experimentation blood samples were collected for cardiac troponin I and cGMP analysis. In the coronary effluents, cardiac troponin I, adenosine, cyclic guanosine monophosphate, and nitric oxide metabolites were assayed. RESULTS: Before heart excision, serum cardiac troponin I concentrations were higher in the L-arginine than in the control group (0.037 +/- 0.01 versus 0.02 +/- 0.05 microg x L(-1); p < 0.05). During reperfusion, cardiac troponin I release was lower in the L-arginine than in the control group (0.04 +/- 0.01 versus 0.19 +/- 0.03 ng x min(-1); p < 0.05). The coronary flow as well as the left ventricular developed pressure were higher in the L-arginine than in the control group before ischemia and remained so throughout the experimentation. CONCLUSIONS: These results indicate that L-arginine administered intraperitoneally 24 hours before cardioplegic arrest reduced myocardial cell injury and seems to protect myocardium against ischemia-reperfusion injury.

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Right abnormal pulmonary venous return into the inferior vena cava associated with abnormal fissure, dextrocardia, and systemic arterial supply of a variable degree, are the characteristics of the scimitar syndrome. We report on a patient in whom this rare syndrome was associated with pulmonary arteriovenous fistulas within the involved lung.

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