Generation and characterization of a novel shoulder contracture mouse model

Frozen shoulder is a relatively common disorder that leads to severe pain and stiffness in the shoulder joint. Although this disorder is self‐limiting in nature, the symptoms often persist for years, resulting in severe disability. Recent studies using human specimens and animal models have shown distinct changes in the gene expression patterns in frozen shoulder tissue, indicating that novel therapeutic intervention could be achieved by controlling the genes that are potentially involved in the development of frozen shoulder. To achieve this goal, it is imperative to develop a reliable animal joint contracture model in which gene expression can be manipulated by gene targeting and transgenic technologies. Here, we describe a novel shoulder contracture mouse model. We found that this model mimics the clinical presentation of human frozen shoulder and recapitulates the changes in the gene expression pattern and the histology of frozen shoulder and joint contracture in humans and other larger animal models. The model is highly reproducible, without any major complications. Therefore, the present model may serve as a useful tool for investigating frozen shoulder etiology and for identifying its potential target genes. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1732–1738, 2015.     

Development of angiogenic cell and gene therapy by transplantation of umbilical cord blood with vascular endothelial growth factor gene.

Endothelial progenitor cells (EPCs) are present in the mononuclear cells (MNCs) of umbilical cord blood and peripheral blood. To establish the efficiency of angiogenic cell and gene therapies, we transfected the human vascular endothelial growth factor (hVEGF) gene into cord blood MNCs to enhance endothelialization. MNCs from cord blood and peripheral blood were isolated and transfected with pCR3 expressing hVEGF165 or GFP by the Hemagglutinating Virus of Japan (HVJ)-envelope and the cells were cultured in endothelium basal medium-2. The number of attached cells from cord blood was higher than that from peripheral blood. Attached cells expressed Flk-1, VE-cadherin, PECAM-1, CD34, and Tie-2. The increase in the number of attached cells was transient with the transfection of vascular endothelial growth factor (VEGF) gene early in the experimental period. Flt-1 mRNA was not expressed early in the culture period, but was expressed at 2 weeks after separation. VEGF gene transfer into MNCs at 12 days after separation, i.e., when Flt-1 mRNA was expressed continuously, increased the number of attached cells. We evaluated the effects of the transplantation of cord blood MNCs expressing the hVEGF gene on regional blood flow in an ischemic area in a rat model of chronic hindlimb ischemia. Blood flow was significantly improved in nude rats that received transplanted control MNCs. Transplantation of cord blood MNCs transfected with the hVEGF gene yielded greater improvements in blood flow. These results indicate that the hVEGF gene enhances endothelialization of EPCs, and that the transplantation of cord blood MNCs transfected with the VEGF gene may be feasible for the treatment of ischemic diseases as a type of angiogenic cell and gene therapy.     

Comparison of the effects of a distal embolic protection device and an aspiration catheter during percutaneous coronary intervention in patients with acute myocardial infarction.

BACKGROUND: The beneficial effect of percutaneous coronary intervention (PCI) using stents for acute myocardial infarction (AMI) has already been demonstrated, but there is the problem that mechanical microvascular occlusion can occur because of thrombus/atheroma embolization when the PCI was performed. The aim of the present study was to retrospectively test and compare the effects of an aspiration catheter or distal embolic protection with a distal occlusion balloon catheter to prevent peripheral vascular embolization. METHODS AND RESULTS: The subjects consisted of 135 patients who underwent PCI with stenting within 12 h of the onset of chest pain caused by their first AMI. They were divided into 2 groups; the aspiration group, consisted of 81 consecutively seen patients who underwent aspiration catheter treatment between January 2001 and May 2002, and the distal protection group was the next group of 54 consecutively seen patients treated with a distal protection device between June 2002 and February 2003. The results were as follows. Thrombolysis in Myocardial Infarction (TIMI) score of 3 was obtained significantly more frequently in the distal protection group (94.4%) than in the aspiration group (79.0%). Additionally, the intensity of the cardiac muscle stain (blush score) was evaluated on coronary angiography and the rate of cases showing a blush score of 3, which indicates favorable blood perfusion at the tissue level, in the distal protection group (56.6%) was significantly greater than in the aspiration group (33.3%, p<0.01). The time to peak blood concentration of creatinine kinase was also significantly shorter in the distal protection group. CONCLUSIONS: The distal embolism protection method is superior to the aspiration method for prevention of embolization after PCI with stenting for AMI, in terms of tissue level reperfusion in myocardial recanalization therapy.     

QT dispersion correlates with systolic rather than diastolic parameters in patients receiving anthracycline treatment

OBJECTIVE: The aim of this study was to investigate the relation of QT dispersion to left ventricular (LV) systolic and diastolic function in patients undergoing anthracycline therapy. METHODS: We used echocardiography to evaluate LV systolic and diastolic function and electrocardiography to evaluate QT dispersion and corrected QT dispersion (QTcD) in patients with hematological diseases, who received anthracycline therapy. PATIENTS: Seventy-two patients with hematological diseases who were receiving anthracycline treatment were enrolled in the present study. RESULTS: LV end-diastolic diameter or LV end-systolic diameter had a significant positive correlation to QTcD (r = 0.35, p < 0.01, r = 0.43, p < 0.01). Also left ventricular ejection fraction of (LVEF) or fractional shortening had a significant negative correlation to QTcD (r = -0.46, p < 0.001, r = -0.27, p = 0.02). The highest QTcD group had a significantly larger LV end-diastolic diameter or LV end-systolic diameter than the lowest QTcD [48.5 +/- 5.7 vs. 44.4 +/- 4.5 (mm), p < 0.001, 34.1 +/- 6.4 vs. 28.8 +/- 4.3 (mm), p < 0.001] and the highest QTcD group had a significantly lower LVEF than the lowest QTcD [57.5 +/- 8.0 vs. 65.5 +/- 6.4 (%), p < 0.001]. On the other hand, none of the diastolic function markers were significantly correlated with QTcD. CONCLUSION: We concluded that increased QTcD is correlated with LV dilation and systolic dysfunction induced by anthracycline therapy, and does not reflect a dispersion of ventricular repolarization or asynchronous motion.