Aggregated low‐density lipoprotein induce impairment of the cytoskeleton dynamics through urokinase‐type plasminogen activator/urokinase‐type plasminogen activator receptor in human vascular smooth muscle cell

Summary. Background: Urokinase‐type plasminogen activator (UPA) regulates vascular smooth muscle cell (VSMC) functions relevant in vascular remodeling by facilitating proteolysis at the cell surface and inducing cell signaling pathways. Our previous results demonstrated that aggregated low‐density lipoprotein (agLDL) impair cytoskeleton dynamics, a key event contributing to VSMC behavior during progression of atherosclerotic plaques. Objectives: To investigate whether mechanisms underlying inhibition of cytoskeleton dynamics in lipid‐loaded VSMC occurs through a UPA‐mediated process. Methods: Adhesion assay was performed in lipid‐loaded human VSMC after 16‐h exposition to agLDL (100 μg mL^?1). Protein subcellular localization and actin‐fiber formation were assessed by confocal microscopy. For analysis of protein expression western blots were carried out. Co‐immunoprecipitates of UPAR were examined by one‐dimensional‐ or two‐dimensional electrophoresis (1‐DE or 2‐DE), mass spectrometry MALDI‐TOF and western blot. Results: agLDL induced UPA subcellular delocalization and significantly decreased UPA levels during attachment of VSMC. UPA (enhanced endogenous‐expression or exogenous added) acting as a urokinase‐type plasminogen activator receptor (UPAR)‐ligand restored actin‐cytoskeleton organization and adhesion capacity of lipid‐loaded cells to control levels. UPAR co‐immunoprecipitated with the unphosphorylated form of myosin regulatory light chain (MRLC) in lipid‐loaded cells. The detrimental effects of agLDL on MRLC phosphorylation were reversed by high levels of UPA. The UPA effects on VSMC exposed to agLDL involved FAK phosphorylation. Conclusions: The detrimental effects of atherogenic LDL on VSMC are mediated by a decrease and delocalization of the UPA–UPAR interaction that result in an impairment of cytoskeleton dynamics and adhesion capacity affecting cell phenotype and function.     

Rapid assessment of Hib disease burden in Vietnam

Background  

Several countries have applied the Haemophilus influenzae type b (Hib) rapid assessment tool (RAT) to estimate the burden of Hib disease where resources for hospital- or population-based surveillance are limited. In Vietnam, we used the Hib RAT to estimate the burden of Hib pneumonia and meningitis prior to Hib vaccine introduction.     

心梗后患者递增负荷运动中ST段降低与VO_2、VE、BL和RPP变化的关系

目的:探讨心梗后(PMI)患者递增负荷运动中生理反应与心电图ST段水平变化的关系,旨在根据服用和不服用β-受体阻滞剂患者的不同反应,为心脏康复中适宜运动强度的制定提供依据。方法:46名服用β-受体阻滞剂的和55名不服用β-受体阻滞剂的男性PMI患者,依据改良布鲁斯方案在活动跑台上进行递增负荷运动试验。运动中每30s测量一次摄氧量(VO2)和通气量(VE),每3min记录一次心率血压乘积(RPP)和血乳酸浓度(BL),并连续监测12导心电图。结果:(1)ST段下降水平与VO2、VE和BL的关系,两组患者间无显著差异(P>0.05)。但两组在相同RPP时,其ST段水平却存在显著差异(P<0.01);(2)ST段下降1mm时,患者的VO2、VE和BL分别约为30ml.kg-1.min-1、63L.min-1和5.3mmol.L-1;(3)ST段下降1mm时,服用和不服用β-受体阻滞剂患者的RPP分别为190beats.mmHg.100-1和230 beats.mmHg.100-1。结论:为了减少心肌缺血的发生,结果(2)和(3)中生理指标的数值,应被作为心脏康复中PMI患者运动强度的上限。     

Peripheral Triangular Fibrocartilage Complex Tears Cause Ulnocarpal Instability: A Biomechanical Pilot Study

Background  

Instability at the ulnocarpal joint has many causes, but the common thread among these causes is the presence of abnormalities in the triangular fibrocartilage complex (TFCC). However, the biomechanical consequences at the ulnocarpal joint after detachment of the TFCC from the ulnar styloid are not clearly defined. Better delineation of whether peripheral TFCC detachments cause ulnocarpal instability will help to design surgical treatments.     

Catheter Ablation for Paroxysmal Atrial Fibrillation: A Randomized Comparison between Multielectrode Catheter and Point‐by‐Point Ablation

Introduction: Catheter ablation for paroxysmal atrial fibrillation is widely used for patients with drug‐refractory paroxysms of arrhythmia. Recently, novel technologies have been introduced to the market that aim to simplify and shorten the procedure. Aim: To compare the clinical outcome of pulmonary vein (PV) isolation using a multipolar circular ablation catheter (PVAC group), with point‐by‐point PV isolation using an irrigated‐tip ablation catheter and the CARTO mapping system (CARTO group; CARTO, Biosense Webster, Diamond Bar, CA, USA). Methods: Patients with documented PAF were randomized to undergo PV isolation using PVAC or CARTO. Atrial fibrillation (AF) recurrences were documented by serial 7‐day Holter monitoring. Results: One hundred and two patients (mean age 58 ± 11 years, 68 men) were included in the study. The patients had comparable baseline clinical characteristics, including left atrial dimensions and left ventricular ejection fraction, in both study arms (PVAC: n = 51 and CARTO: n = 51). Total procedural and fluoroscopic times were significantly shorter in the PVAC group (107 ± 31 minutes vs 208 ± 46 minutes, P < 0.0001 and 16 ± 5 minutes vs 28 ± 8 minutes, P < 0.0001, respectively). The AF recurrence was documented in 23% and 29% of patients in the PVAC and CARTO groups, respectively (P = 0.8), during the mean follow‐up of 200 ± 13 days. No serious complications were noted in both study groups. Conclusions: Clinical success rates of PV isolation are similar when using multipolar circular PV ablation catheter and point‐by‐point ablation with a three‐dimensional (3D) navigation system in patients with PAF, and results in shorter procedural and fluoroscopic times with a comparable safety profile. (PACE 2010; 33:1039–1046)     

Hemodilution and intravenous perflubron emulsion as an alternative to blood transfusion: effects on tissue oxygenation during profound hemodilution in anesthetized dogs

BACKGROUND: Intravenously administered perfluorocarbon (PFC) emulsions increase oxygen solubility in plasma. PFC might therefore temporarily replace red cells (RBCs) lost during intraoperative hemorrhage. In patients who have undergone hemodilution, the return of autologous blood may be delayed by the administration of PFC, and autologous RBCs may be saved for transfusion after surgical bleeding is stopped and PFC is cleared by the reticuloendothelial system. STUDY DESIGN AND METHODS: In 22 anesthetized, hemodiluted dogs (hemoglobin [Hb] 7 g/dL) breathing 100-percent O2, an intraoperative volume-compensated blood loss was simulated. The efficacy of three therapeutic regimens in maintaining tissue oxygenation was compared: 1) RBC group (n = 7): maintenance of a Hb > 7 g per dL by transfusion of autologous RBCs; 2) PFC group (n = 7): bolus application of a second-generation PFC emulsion (60% wt/vol perflubron) and further acute normovolemic hemodilution (ANH) to a Hb of 3 g per dL; and 3) control group (n = 7): further ANH alone to a Hb of 3 g per dL. Systemic and myocardial oxygenation status and tissue oxygenation were assessed. RESULTS: Autologous RBCs transfused to maintain a Hb of 7 g per dL preserved hemodynamics and tissue oxygenation during blood loss. In the PFC and control groups, heart rate and cardiac index increased significantly in response to further ANH. Tissue oxygenation was not different in the PFC and the RBC groups. Direct comparison of the PFC and control groups revealed better tissue oxygenation in the PFC group, as reflected by significantly higher mixed venous, coronary venous, and local tissue pO2 on liver and skeletal muscle. CONCLUSION: Bolus intravenous administration of 60- percent (wt/vol) perflubron emulsion and further hemodilution from a Hb of 7 g per dL to one of 3 g per dL were as effective as autologous RBC transfusion in maintaining tissue oxygenation during volume-compensated blood loss designed to mimic surgical bleeding.