Introduction: Early randomized clinical trials of autologous bone marrow cardiac stem cell therapy have reported contradictory results highlighting the need for a better evaluation of protocol designs. This study was designed to quantify and compare whole body and heart cell distribution after intracoronary or peripheral intravenous injection of autologous bone marrow mononuclear cells in a porcine acute myocardial infarction model with late reperfusion. Methods: Myocardial infarction was induced using balloon inflation in the left coronary artery in domestic pigs. At seven days post-myocardial infarction, 1 × 10(8) autologous bone marrow mononuclear cells were labeled with fluorescent marker and/or 99mTc radiotracer, and delivered using intracoronary or peripheral intravenous injection (leg vein). Results: Scintigraphic analyses and Υ-emission radioactivity counting of harvested organs showed a significant cell fraction retained within the heart after intracoronary injection (6 ± 1.7% of injected radioactivity at 24 hours), whereas following peripheral intravenous cell injection, no cardiac homing was observed at 24 hours and cells were mainly detected within the lungs. Importantly, no difference was observed in the percentage of retained cells within the myocardium in the presence or absence of myocardial infarction. Histological evaluation did not show arterial occlusion in both animal groups and confirmed the presence of bone marrow mononuclear cells within the injected myocardium area. Conclusions: Intravenous bone marrow mononuclear cell injection was ineffective to target myocardium. Myocardial cell distribution following intracoronary injection did not depend on myocardial infarction presence, a factor that could be useful for cardiac cell therapy in patients with chronic heart failure of non-ischemic origin or with ischemic myocardium without myocardial infarction.
1 October 2005 in European Journal of Pharmaceutics and Biopharmaceutics
Objective—To investigate renal function in clinically normal dogs when awake and during anesthesia with medetomidine; xylazine, ketamine, and halothane (XKH) combination; or propofol. Animals—10 adult female Beagles. Procedures—At intervals of 15 days, dogs were administered medetomidine (0.05 mg/kg, IV); XKH combination (xylazine [1 mg/kg, IV], ketamine [5 mg/kg, IV], and halothane [1% end-tidal concentration]); or propofol (6 mg/kg, IV) to induce anesthesia or no treatment. Glomerular filtration rate was assessed on the basis of renal uptake (RU; determined via renal scintigraphy) and plasma clearance (CL) of technetium 99m-labeled diethylenetriamine peentaacetic acid (99mTc-DTPA). Results—In awake dogs, mean ± SEM RU was 9.7 ± 0.4% and CL was 3.86 ± 0.23 mL/min/ kg. Renal uptake and CL of 99mTc-DTPA were not significantly modified by administration of XKH (RU, 11.4 ± 0.9%; CL, 4.6 ± 0.32 mL/min/kg) or propofol (RU, 9.7 ± 0.3%; CL, 3.78 ± 0.37 mL/min/kg). Half-life elimination time of plasma 99mTc-DTPA decreased significantly in XKH-anesthetized dogs, compared with the value in awake dogs (14.4 minutes and 28.9 minutes, respectively). However, glomerular filtration rate was significantly decreased by administration of medetomidine (RU, 3.9 ± 0.1%), and the time to maximum kidney activity was significantly increased (867 ± 56 seconds vs 181 ± 11 seconds without anesthesia). Conclusions and Clinical Relevance—Results indicated that anesthesia with propofol or an XKH combination did not alter renal function in healthy Beagles, but anesthesia with medetomidine decreased early RU of 99mTc-DTPA.
1 November 2004 in British Journal of Pharmacology
Viperidae snakes venoms represent a source of efficient bioactive components that have already led to the development of several new drugs. In this work, we analyzed the protein content of the Montivipera bornmuelleri crude venom using LC-ESI-MS, sephadex G-75 gel filtration and SDS-PAGE and demonstrated the presence of proteins with molecular masses corresponding to metalloprotease III, serine-protease and PLA2 in three fractions collected after gel filtration. Equally, we examined the antimicrobial effect of the venom that showed an important potency, as bactericidal agent, based on MBC and MIC values obtained, against Staphylococcus aureus and Morganella morganii bacteria. However, no activity was registered against Enterococcus faecalis, being the most resistant bacteria, neither against Aspergillus flavus and Penicillium digitatum fungal. Furthermore, on eleven other bacterial strains and the Candida albicans fungus, the venom has shown an intermediate efficacy by slightly reducing the growth. Our data concerning the Montivipera bornmuelleri venom give evidence of a rich and complex content aiding the exploration of new bioactive molecules for biopharmaceuticals purposes.