Entity

Time filter

Source Type

Ōsaka, Japan

Purpose: Quantification of vascular endothelial cell damage induced by iodinated contrast media using an in situ perfused rat vena cava model. Materials and methods: The institutional review board approved this study protocol prior to the commencement of all studies. A laparotomy was performed in 90 rats divided into 18 groups of five, and an 18G-catheter was inserted into the abdominal vena cava (mean length: ca 8 mm). After sacrificing, a thoracotomy was done and the outflow perfusate was emitted via a polyethylene tube inserted into the thoracic vena cava through the right atrium for an open system. Iopamidol (300 or 370 mg I/mL, 50 or 100 mL) was injected via the abdominal vena cava at a rate of 1, 4, or 8 mL/s. The abdominal vena cava was removed for histological analysis (n = 5). Physiological saline was injected as a negative control. The detachment percentage of endothelial cells was calculated by measuring the circumference and detachment section of the endothelium. The difference of the detachment percentage and circumference between each group was compared with Tukey's range test. Results: In contrast media groups, the severity of damage to the vascular endothelial cell was direct proportional to the increase of injection rate. The detachment percentage at 4 or 8 mL/s was significantly higher than that at 1 mL/s. As a result, the correlation between the injection rate and severity of cell damage was significant; however, the detachment percentage among contrast media groups was not significant at any injection rate. Conclusion: The in situ vena cava model was able to quantify contrast media injection related endothelial damage based on histopathological endpoints. Moreover, our results indicate that mechanical shear stress besides physico-chemical properties such as osmolality or viscosity cause endothelial damage. © 2011 Elsevier Ireland Ltd. All rights reserved. Source


Objectives: To compare the transporter expression and signal profile on Gd-EOB-DTPA-enhanced MRI between non-alcoholic steatohepatitis (NASH) and cirrhotic liver induced in rats, and investigate the correlation of the transporter expression and fibrosis rate in both diseases. Methods: Forty-eight rats were divided into four groups of 12: TAA (cirrhosis), NASH 7- and 10-week, and control groups. Each group was divided into two subgroups: Group 1 for MRI and Group 2 for transporter examinations. Results: The relative enhancement of the TAA group was significantly lower than those of other groups (p∈<∈0.01). The T max and T 1/2 of the NASH 10-week group was significantly prolonged in comparison with the TAA group (p∈<∈0.01). There was no significant difference in the oatp1 expression, whereas the mrp2 expression of the TAA group was significantly higher than those of other groups (p∈<∈0.01). There was no significant correlation between the fibrosis rate and oatp1 expression, whereas a paradoxical correlation was found between the fibrosis rate and mrp2 expression (NASH: negative correlation, r∈=∈0.91, p∈<∈0. 01; TAA: positive correlation, r∈=∈0.85, p∈<∈0.01). Conclusions: Our findings showed that the mrp2 expression in cirrhosis increases in comparison with NASH, and there was a paradoxical correlation between the fibrosis rate and mrp2 expression. © 2011 European Society of Radiology. Source


Tsuda N.,Bayer Yakuhin Ltd | Okada M.,Kinki University | Murakami T.,Kinki University
European Journal of Radiology | Year: 2010

Purpose: We investigated whether the gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI was useful for nonalcoholic steatohepatitis (NASH) staging based on the severity of liver fibrosis. Materials and methods: Twenty-one male Sprague-Dawley rats aged 7 weeks, weighing about 150 g in NASH group were fed a choline-deficient diet for 4, 7 or 10 weeks, and seven rats in the control group were fed a standard diet (n = 7). After the feeding period, the rats were subjected to contrast-enhanced MRI (2D-FLASH; TR/TE = 101/2.9 ms, flip angle 90°). Gd-DTPA (0.1 mmol Gd/kg) and Gd-EOB-DTPA (0.025 mmol Gd/kg) were injected at 24-h intervals, and the speed of contrast injection was 1 mL/s. Signal intensities of the liver were measured and the relative enhancement (RE), the time of maximum RE (Tmax) and elimination half-life of RE (T1/2) in the liver were compared. The fibrosis rate (%) was calculated with the following formula: fibrosis/whole area × 100. Results: The fibrosis rates of each group were as follows: 0.52, 0.79, 2.84, and 0.50% (4, 7, 10 weeks and control groups). The fibrosis rate of the 10 weeks group was significantly higher than the control and 4 or 7 weeks groups. Although there was no difference between the Tmax and T1/2 of each group after Gd-DTPA injection, the Tmax and T1/2 of the 10 weeks group were significantly prolonged in comparison with the control and 4 or 7 weeks groups after Gd-EOB-DTPA injection (p < 0.01). There was a significant correlation between the fibrosis rate and Tmax or T1/2 after Gd-EOB-DTPA injection (r = 0.90 or 0.97). Conclusion: It was possible to assess the progress of liver fibrosis in NASH by evaluating the signal intensity-time course on Gd-EOB-DTPA-enhanced MRI. © 2008 Elsevier Ireland Ltd. All rights reserved. Source


Naito S.,Kyushu University | Tsukamoto T.,Sapporo Medical University | Murai M.,International Goodwill Hospital | Fukino K.,Bayer Yakuhin Ltd | Akaza H.,University of Tsukuba
BJU International | Year: 2011

Study Type - Therapy (Phase II non-randomized trial) Level of Evidence 2b What's known on the subject? and What does the study add? Interim result of this study had shown promising efficacy, with response rate of 14.7% and median PFS of 7.4 months, and good tolerability of sorafenib in previously-treated Japanese patients with metastatic RCC. Final result of the study adds: (1) the median overall survival of 25.3 months, which is longer than that in the global phase III study TARGET; (2) the response rate which elevated to 19.4% because of 6 late responders achieved after 9.2 months or longer of SD period; (3) lack of either unknown adverse events nor cumulative toxicity in the long-term use of sorafenib. OBJECTIVE • To explore the long-term efficacy and safety of sorafenib in Japanese patients with metastatic renal cell carcinoma (RCC) in a phase II trial. PATIENTS AND METHODS • In all, 131 Japanese patients with metastatic RCC who had received nephrectomy and failed at least one cytokine-containing systemic therapy received continuous sorafenib 400 mg twice daily, and the efficacy and safety parameters were evaluated in these patients, including objective response rate, progression-free survival and overall survival. RESULTS • Of the total, 129 patients were valid for intention-to-treat analyses and 131 patients were valid for safety analyses. • Twenty-five patients (19.4%) had confirmed partial response and 87 patients (67.4%) had stable disease as best overall response. The 25 patients included six late-responders who achieved response after 9.2 months or longer of stable disease. The objective response rate and disease control rate were 19.4% and 73.6%, respectively. • The median overall survival and median progression-free survival were 25.3 and 7.9 months, respectively. • Safety profile was consistent with those previously reported, with hand-foot skin reaction (58.0%), lipase elevation (57.3%) and diarrhoea (42.7%) as the most frequently observed drug-related adverse events. Neither unknown adverse event nor cumulative toxicity was observed over the long-term use of sorafenib. • Despite the dose discontinuation/interruption/reduction, the mean and median relative dose intensities were 86.4% and 97.4%, respectively. CONCLUSION • The final results of this trial showed that long-term use of sorafenib after cytokine treatment was well tolerated and provided new efficacy data, including late-response events and favourable overall survival in Japanese patients with metastatic RCC. © 2011 BAYER YAKUHIN, LTD. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL. Source


Tsuda N.,Bayer Yakuhin Ltd | Harada K.,Kanazawa University | Matsui O.,Kanazawa University
Journal of Gastroenterology and Hepatology (Australia) | Year: 2011

Background and Aims: To analyze the difference in signal intensity on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) among various hepatocellular nodules during hepatocarcinogenesis as correlated with the expressions of the transporters of Gd-EOB-DTPA. Methods: We received institutional animal review board approval prior to the commencement of all studies. Forty rats were divided into three groups. The rats in the tumor groups received N-nitrosomorpholine solution (n=16), and rats in the cirrhosis group (thioacetamide [TAA] group) received thioacetamide solution (n=12). As a control, the remaining 12 rats were fed normal water. Each group was divided into two sub-groups: Group 1 for Gd-EOB-DTPA-enhanced MRI (0.025mmolGd/kg, n=7) and Group 2 for reverse transcription-polymerase chain reaction to compare transporter (oatp1 and mrp2) expressions (n=5 for control and TAA groups, n=9 for tumor groups). Results: Signal enhancement of tumors decreased according to the progress of hepatocarcinogenesis. Although the relative enhancement of each tumor group was significantly lower than that of the control group (P<0.01), and there was no significant difference between TAA, hyperplastic nodules (HPN), and HCCwell groups. The relative enhancement of the HCCmod group was significantly lower than the other groups (P<0.01). The oatp1 expression of HPN tended to be higher than those of HCCwell and HCCmod. The mrp2 expression of TAA was significantly higher than those of HCCwell, HCCmod, HPN and control (P<0.01). The mrp2 expression of HPN tended to be higher than those of HCCwelland HCCmod. Conclusion: It was suggested that the signal enhancement on Gd-EOB-DTPA-enhanced MRI would correlate with the transporter expression in various hepatocellular nodules during hepatocarcinogenesis. © 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd. Source

Discover hidden collaborations