In Vivo Serial MR Imaging of Magnetically Labeled Endothelial Progenitor Cells Homing to the Endothelium Injured Artery in Mice

Background: Emerging evidence of histopathological analyses suggests that endothelial progenitor cells (EPCs) play an important role in vascular diseases. Neointimal hyperplasia can be reduced by intravenous transfusion of EPCs after vascular injury in mice. Therefore, it would be advantageous to develop an in vivo technique that can explore the temporal and spatial migration of EPCs homing to the damaged endothelium noninvasively. Methodology/Principal Findings: The left carotid common artery (LCCA) was injured by removal of endothelium with a flexible wire in Kunming mice. EPCs were collected by in vitro culture of spleen-derived mouse mononuclear cells (MNCs). EPCs labeling was carried out in vitro using Fe2O3-poly-L-lysine (Fe2O3-PLL). In vivo serial MR imaging was performed to follow-up the injured artery at different time points after intravenous transfusion of EPCs. Vessel wall areas of injured artery were computed on T2WI. Larger MR signal voids of vessel wall on T2WI was revealed in all 6 mice of the labeled EPC transfusion group 15 days after LCCA injury, and it was found only in 1 mouse in the unlabeled EPC transfusion group (p = 0.015). Quantitative analyses of vessel wall areas on T2WI showed that the vessel wall areas of labeled EPC transfusion group were less than those of unlabeled EPC transfusion group and control group fifteen days after artery injury (p,0.05). Histopathological analyses confirmed accumulation and distribution of transfused EPCs at the injury site of LCCA. Conclusions/Significance: These data indicate that MR imaging might be used as an in vivo method for the tracking of EPC

State of progress in treating cystic fibrosis respiratory disease

<p>Abstract</p> <p>Since the discovery of the gene associated with cystic fibrosis (CF), there has been tremendous progress in the care of patients with this disease. New therapies have entered the market and are part of the standard treatment of patients with CF, and have been associated with marked improvement in survival. Now there are even more promising therapies directed at different components of the pathophysiology of this disease. In this review, our current knowledge of the pathophysiology of lung disease in patients with CF is described, along with the current treatment of CF lung disease, and the therapies in development that offer great promise to our patients.</p

Clinical Pharmacokinetics of Inhaled Antimicrobials

Administration of inhaled antimicrobials affords the ability to achieve targeted drug delivery into the respiratory tract, rapid entry into the systemic circulation, high bioavailability and minimal metabolism. These unique pharmacokinetic characteristics make inhaled antimicrobial delivery attractive for the treatment of many pulmonary diseases. This review examines recent pharmacokinetic trials with inhaled antibacterials, antivirals and antifungals, with an emphasis on the clinical implications of these studies. The majority of these studies revealed evidence of high antimicrobial concentrations in the airway with limited systemic exposure, thereby reducing the risk of toxicity. Sputum pharmacokinetics varied widely, which makes it challenging to interpret the result of sputum pharmacokinetic studies. Many no vel inhaled antimicrobial therapies are currently under investigation that will require detailed pharmacokinetic studies, including combination inhaled antimicrobial therapies, inhaled nanoparticle formulations of several antibacterials, inhaled non-antimicrobial adjuvants, inhaled antiviral recombinant protein therapies and semi-synthetic inhaled antifungal agents. Additionally, the development of new inhaled delivery devices, particularly for mechanically ventilated patients, will result in a pressing need for additional pharmacokinetic studies to identify optimal dosing regimens