Potent Analgesic Action of 2-acetoxy-5-(2-4 (trifluoromethyl)-phenethylamino)-benzoic Acid (Flusalazine) in Experimental Mice.

Purpose: Nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase (COX)-2 selective inhibitors are the most widely used drugs to treat pain. Conventional NSAIDs and COX-2 selective inhibitors, however, cause several side effects such as gastric damage, kidney damage, and cardiovascular problems. Our previous study showed that 2-acetoxy-5-(2-4-(trifluoromethyl)-phenethylamino)-benzoic acid ie, flusalazine (also known as ND-07), which exerts dual actions by serving both as an anti-inflammatory agent and a free radical scavenger, is an effective and safe treatment for severe inflammatory diseases in mice. The goal of the present study was to examine the potential analgesic action and safety of flusalazine in mice models of pain. Methods and Results: Flusalazine showed a significant analgesic effect in an acetic acid-induced abdominal constriction model. Likewise, total paw licking was reduced significantly in neurogenic (early stage) and inflammatory (late stage) pain induced by formalin in flusalazine-treated mice. In the tail immersion test, flusalazine significantly increased tail withdrawal time at 2 h after its administration. Also, the formation of paw edema in the flusalazine-treated group was significantly inhibited in a carrageenan-induced inflammatory pain model. Gastric damage was not induced by flusalazine even up to 1000 mg/kg, while aspirin and indomethacin caused critical gastric bleeding. Conclusion: These findings suggest that flusalazine's safety profile and analgesic effects have high translational potential for the clinical treatment of patients experiencing pain.

Tumor heterogeneity of pancreas head cancer assessed by CT texture analysis: association with survival outcomes after curative resection.

The value of image based texture features as a powerful method to predict prognosis and assist clinical management in cancer patients has been established recently. However, texture analysis using histograms and grey-level co-occurrence matrix in pancreas cancer patients has rarely been reported. We aimed to analyze the association of survival outcomes with texture features in pancreas head cancer patients. Eighty-eight pancreas head cancer patients who underwent preoperative CT images followed by curative resection were included. Texture features using different filter values were obtained. The texture features of average, contrast, correlation, and standard deviation with no filter, and fine to medium filter values as well as the presence of nodal metastasis were significantly different between the recurred (n = 70, 79.5%) and non-recurred group (n = 18, 20.5%). In the multivariate Cox regression analysis, lower standard deviation and contrast and higher correlation with lower average value representing homogenous texture were significantly associated with poorer DFS (disease free survival), along with the presence of lymph node metastasis. Texture parameters from routinely performed pre-operative CT images could be used as an independent imaging tool for predicting the prognosis in pancreas head cancer patients who underwent curative resection.

CRISPR-Cas9-mediated generation of obese and diabetic mouse models.

Mouse models of obesity (ob/ob) and diabetes (db/db) in which the leptin (Lep) and leptin receptor (Lepr) genes have been mutated, respectively, have contributed to a better understanding of human obesity and type 2 diabetes and to the prevention, diagnosis, and treatment of these metabolic diseases. In this study, we report the first CRISPR-Cas9-induced Lep and Lepr knockout (KO) mouse models by co-microinjection of Cas9 mRNA and sgRNAs that specifically targeted Lep or Lepr in C57BL/6J embryos. Our newly established Lep and Lepr KO mouse models showed phenotypic disorders nearly identical to those found in ob/ob and db/db mice, such as an increase in body weight, hyperglycemia, and hepatic steatosis. Thus, Cas9-generated Lep and Lepr KO mouse lines will be easier for genotyping, to maintain the lines, and to use for future obesity and diabetes research.

Endoscopic reduction of medial orbital wall fractures using the rolled silastic sheet technique.

BACKGROUND: Endoscopic reduction has become common for reducing medial orbital wall fractures because of its various advantages. Nevertheless, there is no standard method of nasal packing to support the orbital contents to maintain the reduction. We evaluated the outcomes of endoscopic reduction of medial orbital wall fractures using the rolled Silastic sheet technique. METHODS: Seventeen patients who underwent endoscopic reduction of medial orbital wall fractures were analyzed. They were diagnosed using 3-mm facial computed tomography and treated surgically under general anesthesia in our department between February 2006 and March 2008. Postoperatively, they were followed for at least 3 months. RESULTS: The 17 patients comprised 13 men and 4 women ranging in age from 18 to 71 years (mean, 40.8 years). There were no significant intraoperative or postoperative complications. All 17 patients showed complete resolution of their symptoms after surgery. CONCLUSION: The technique using the rolled Silastic sheet for medial orbital wall fractures supports the safety and efficacy of endoscopic reduction.