Immobilization-induced hypersensitivity associated with spinal cord sensitization during cast immobilization and after cast removal in rats

This study examined mechanical and thermal hypersensitivity in the rat hind paw during cast immobilization of the hind limbs for 4 or 8 weeks and following cast removal. Blood flow, skin temperature, and volume of the rat hind paw were assessed in order to determine peripheral circulation of the hind limbs. Sensitization was analyzed by measuring the expression of the calcitonin gene-related peptide (CGRP) in the spinal dorsal horn following cast immobilization. Two weeks post immobilization, mechanical and thermal sensitivities increased significantly in all rats; however, peripheral circulation was not affected by immobilization. Cast immobilization for 8 weeks induced more serious hypersensitivity compared to cast immobilization for 4 weeks. Moreover, CGRP expression in the deeper lamina layer of the spinal dorsal horn increased in the rats immobilized for 8 weeks but not in those immobilized for 4 weeks. These findings suggest that immobilization-induced hypersensitivity develops during the immobilization period without affecting peripheral circulation. Our results also highlight the possibility that prolonged immobilization induces central sensitization in the spinal cord.     

Higher Expression of Receptor Tyrosine Kinase Axl,and Differential Expression of its Ligand,Gas6, Predict Poor Survival in Lung Adenocarcinoma Patients

Background

Downstream activation through receptor tyrosine kinases (RTKs) plays important roles in carcinogenesis. In this study, we assessed the clinical involvement of Axl, an RTK, and its ligand, Gas6, in surgically treated lung adenocarcinoma.

Methods

Axl and Gas6 mRNA and protein expression levels were quantified using quantitative real-time polymerase chain reaction and immunohistochemistry, respectively, in completely resected lung adenocarcinoma tissues (n = 88) and were evaluated for correlation with clinicopathologic features and patient survival.

Results

Higher expressions of Axl mRNA/protein and Gas6 protein were significantly related to worse clinicopathological features and prognosis (5-year overall survival rates: Axl mRNA low: 72.3 %, high: 49.7 %, P = 0.047; Axl protein low: 77.5 %, high: 38.6 %, P < 0.001; and Gas6 protein low: 70.5 %, high: 48 %, P = 0.042). On the contrary, higher Gas6 mRNA expression was related to better clinicopathological features and prognosis (5-year overall survival rates: Gas6 mRNA low: 59.2 %, high: 81.8 %, P = 0.054). Multivariate analysis suggests that high Axl mRNA expression may be an independent factor for poor patient prognosis (P = 0.04).

Conclusions

In lung adenocarcinoma, Axl and Gas6 expression levels were associated with tumor advancement and patient survival, thus rendering them as reliable biomarkers and potential targets for treatment of lung adenocarcinoma.

     

Solitary mediastinal metastasis of hepatocellular carcinoma treated by video-assisted thoracic surgery: report of a case

Solitary mediastinal metastasis of hepatocellular carcinoma (HCC) is extremely rare. We report a case of solitary mediastinal metastasis arising from HCC treated by video-assisted thoracic surgery (VATS). A 75-year-old man underwent hepatic resection and transcatheter arterial embolization for HCC. The level of protein induced by vitamin K antagonist was subsequently found to be elevated. Computed tomography showed a 2-cm mediastinal tumor. ¹⁸F-fluorodeoxy-glucose positron emission tomography revealed slight uptake by the tumor. VATS was performed. The histopathological diagnosis was metastatic HCC of the lymph nodes. The postoperative course was uneventful, with a postoperative hospital stay of 6 days. There has been no recurrence at 4 months after surgery. VATS is a minimally invasive and useful treatment for solitary mediastinal metastasis of HCC.     

Comparison of new and conventional versions of model-based iterative reconstruction in reduced-dose computed tomography for diagnosis of hepatic steatosis

Purpose

To compare new and conventional versions of model-based iterative reconstruction (MBIR) in reduced-dose computed tomography (CT) in terms of diagnostic performance for hepatic steatosis.

Materials and methods

Images were reconstructed from standard-dose and aggressively reduced-dose (the dose-length product was reduced by 91 %) unenhanced abdominopelvic CT scans of 86 patients using filtered back projection (SD-FBP) and new and conventional versions of MBIR (RD-MBIRn and RD-MBIRc), respectively. The mean CT attenuation of the liver (CT[L]) and the spleen as well as the ratio of these parameters (CT[L/S]) were calculated. CT[L] <48 Hounsfield units (HU) and CT[L/S] <1.1 were applied to SD-FBP (used as the reference standard; the number of positive patients was 12 and 14, respectively), RD-MBIRn, and RD-MBIRc.

Results

CT[L]s in SD-FBP/RD-MBIRn/RD-MBIRc were 56.9/55.9/52.8 HU. The difference in CT[L] between RD-MBIRn and SD-FBP was within ±5.0 HU in most cases. The sensitivity/specificity/accuracy of CT[L] <48 HU in RD-MBIRn and RD-MBIRc were 1.00/0.97/0.98 and 1.00/0.92/0.93, respectively, showing that RD-MBIRn permits significant improvements in specificity and accuracy (P < 0.05, McNemar test). For CT[L/S] <1.1, these values were 0.79/0.97/0.94 and 0.79/0.97/0.94 in RD-MBIRn and RD-MBIRc, respectively.

Conclusion

When CT[L] <48 HU was applied, RD-MBIRn presented a significantly improved hepatic steatosis diagnostic performance compared with RD-MBIRc; indeed, it was almost equivalent to that afforded by SD-FBP.

     

High molecular weight hyaluronic acid increases the differentiation potential of the murine chondrocytic ATDC5 cell line

Osteoarthritis (OA) is a group of common, chronic, and painful inflammatory joint diseases. One important finding in OA patients is a remarkable decrease in the molecular weight of hyaluronic acid (HA) in the synovial fluid of affected joints. Therapeutic HA is available to patients in most parts of the world as a viscosupplementation product for the treatment of OA. Previous clinical reports show that high molecular weight HA (HMWHA) more effectively relieves pain than low molecular weight HA (LMWHA). However, the mechanism behind this finding remains unclear. In this study, we investigated whether a LMWHA (Low‐0.9 MDa) and two types of HMWHA (High‐1.9 MDa and 6 MDa) differentially affected chondroregulatory action. We tested this using ATDC5 cell, a murine chondrocytic cell line widely used in culture systems to study chondrogenic differentiation. We found that HMWHA, especially hylan G‐F 20 (High‐6 MDa), significantly induced aggrecan and proteoglycan accumulation, nodule formation, and mRNA expression of chondrogenic differentiation markers in a time‐ and dose‐dependent manner. In addition, we showed that HMWHA prevented TNF‐α induced inhibition of chondrogenic differentiation, with no effect on cell proliferation or viability. These results reveal that HMWHA significantly promotes chondrogenic differentiation of ATDC5 cells in vitro, and suggest that HMWHA plays a significant chondroregulatory role in vivo. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1619–1627, 2014.