A new rat model for thrombus-induced ischemic pain (TIIP); development of bilateral mechanical allodynia

Patients with peripheral arterial disease (PAD) commonly suffer from ischemic pain associated with severe thrombosis. However, the pathophysiology of peripheral ischemic pain is not fully understood due to the lack of an adequate animal model. In this study, we developed a new rodent model of thrombus-induced ischemic pain (TIIP) to investigate the neuronal mechanisms underlying ischemic pain. Ischemia was induced by application of 20% FeCl(2) onto the surface of the femoral artery for 20min. Induction of peripheral ischemia was confirmed by measurement of the concentration of Evans blue and by increases in the ischemia-specific markers, hypoxia-inducible factor-1 alpha and vascular endothelial growth factor in the ipsilateral plantar muscles. Ischemic pain, as indicated by the presence of mechanical allodynia, developed bilaterally and peaked at days 3-9 post-FeCl(2) application and gradually decreased through day 31. Systemic heparin pretreatment dose dependently suppressed ischemic pain, suggesting that thrombosis-induced ischemia might be a key factor in TIIP. Intraplantar injection of BMS-182874, an ET(A) (endothelin-A) receptor antagonist, at day 3 selectively blocked ipsilateral pain, indicating that ET(A) receptor activity mediated TIIP. Spinal GFAP expression was significantly increased by FeCl(2) and intrathecal injection of carbenoxolone (an astrocyte gap junction decoupler) at day 3 significantly reduced TIIP, suggesting that spinal astrocyte activation plays an important role. However, the anti-inflammatory agent, ibuprofen, did not affect TIIP. In conclusion, we have developed a novel animal model of TIIP that should be useful in investigating the pathophysiological mechanisms that underlie human peripheral ischemic pain.     

Characteristics and outcomes of varied treatment modalities for partially thrombosed intracranial aneurysms: a review of 35 cases

Objective

The purpose of this study was to analyze the characteristics of partially thrombosed intracranial aneurysms (PTIAs) in terms of location, shape, size, and symptoms, and to assess outcome according to the type of treatment.

Methods

We reviewed the radiological and clinical findings of 35 cases of PTIAs followed in our institution between 2006 and 2011. We divided all treatment modalities into two groups. Patients in group A (n?=?15) were treated by blood flow blockage from the lesion of the pathogenic segment of the parent where the PTIAs originated, and patients in group B (n?=?20) were only treated with obliteration of the remnant perfused aneurysmal sac. Radiological and clinical outcomes of treatment were compared between the two groups.

Results

Group A showed complete occlusion in 15 cases (100 %) compared to six cases (30.0 %) in group B (p?Conclusion PTIAs should be treated by preventing blood flow from the lesion of the pathogenic segment of the parent artery where PTIAs originate. This treatment approach is associated with better clinical and radiological outcomes.     

The etiology of pectus carinatum involves overgrowth of costal cartilage and undergrowth of ribs

Purpose

We compared the length of costal cartilage and rib between patients with symmetric pectus carinatum and controls without anterior chest wall protrusion, using a 3-dimensional (3D) computed tomography (CT) to evaluate whether the overgrowth of costal cartilage exists in patients with pectus carinatum.

Subjects and methods

Twenty-six patients with symmetric pectus carinatum and matched twenty-six controls without chest wall protrusion were enrolled. We measured the full lengths of the 4th–6th ribs and costal cartilages using 3-D volume rendering CT images and the curved multiplanar reformatted (MPR) techniques. The lengths of ribs and costal cartilages, the summation of rib and costal cartilage lengths, and the costal index [length of cartilage/length of rib * 100 (%)] were compared between the patients group and the control group at 4th–6th levels.

Results

The lengths of costal cartilage in patient group were significantly longer than those of control group at 4th, 5th and 6th rib level. The lengths of ribs in patient group were significantly shorter than those of control group at 4th, 5th and 6th rib level. The summations of rib and costal cartilage lengths were not longer in patients group than in control group. The costal indices were significantly larger in patients group than in control groups at 4th, 5th and 6th rib level.

Conclusion

In patients with symmetric pectus carinatum, the lengths of costal cartilage were longer but the lengths of rib were shorter than those of controls. These findings may supports that the overgrowth of costal cartilage was not the only factor responsible for pectus carinatum.     

The expression and significance of dishevelled in human glioma

Background

The proto-oncogene dishevelled (Dvl) is a critical component of the Wnt/β-catenin signaling pathway, and its elevated expression in various tumor types is associated with malignancy. However, a role for Dvl in glioma has not been explored.

Materials and methods

To determine whether Dvl expression is elevated in human glioma, we examined the protein levels in 67 human glioma samples and 3 normal brain specimens by Western blotting and immunohistochemistry. To investigate a possible association of Dvl with the malignant phenotype in glioma, the correlation of the Dvl immunoreactivity score (IRS) with β-catenin IRS, the tumor proliferation index (PI), and tumor invasion index (II) were determined for each sample.

Results

The Dvl IRS, β-catenin IRS, PI, and II increased significantly with the pathologic grade of glioma (P <0.001) with average scores of 3.46 ± 3.45, 3.92 ± 3.28, 30.93 ± 17.92, and 20.43 ± 11.79, respectively. Furthermore, the PI and II were significantly higher for the Dvl-positive group than the Dvl-negative group (P <0.001). Correlation analysis demonstrated that β-catenin IRS, PI, and II were positively correlated with Dvl IRS.

Conclusions

Dvl overexpression may contribute to the malignant proliferation and invasion of human glioma.