Evaluation of liver fibrosis by investigation of hepatic parenchymal perfusion using contrast-enhanced ultrasound: an animal study.

PURPOSE: To investigate the value of assessing the hepatic parenchymal perfusion in contrast-enhanced ultrasound (CEUS) for evaluating liver fibrosis, using an animal model. METHODS: Seventy Sprague-Dawley rats were divided into experimental (n = 35) and control (n = 35) groups. In the experimental group, liver fibrosis was induced by intraperitoneal injection of carbon tetrachloride. CEUS of the liver was performed at a 2-week interval for 14 weeks. Signal intensity of liver parenchyma was analyzed with time-intensity curves. Histologic examination of liver specimens of the animals was performed to assess the fibrosis stage. RESULTS: The peak signal intensity of hepatic parenchymal perfusion in stage 2-3 fibrosis was significantly lower than that in stage 0-1. The time to peak intensity of hepatic parenchymal perfusion was significantly longer in the experimental group than the control group, and in the stage 3 fibrosis than in stages 0-2 fibrosis. Using time to peak intensity of hepatic parenchymal perfusion to distinguish stage 3 fibrosis and stages 0-2 fibrosis, the optimum cutoff was 75,000 milliseconds with the sensitivity and specificity of 67% and 78%, respectively. CONCLUSIONS: This animal study showed that CEUS has the potential to be a complementary imaging tool in the evaluation of liver fibrosis.

The in vivo Therapeutic Effect of Free Wanderer Powder ( xiao yáo sǎn, Xiaoyaosan) on Mice with 4T1 Cell Induced Breast Cancer Model.

In the present study, we investigated the therapeutic effect of a classical TCM formula, Free Wanderer Powder ( xiao yáo sǎn), in a breast cancer mouse model induced with estrogen-insensitive breast cancer 4T1 cells. Ovariectomized Balb/c mice (6-8 weeks) or sham mice were injected into the fourth mammary fat pad with 4T1 cells in which tumors were palpable 7 days after injection. On the eighth day, the mice were divided into 4 groups and tubefed daily with vehicle, Free Wanderer Powder ( xiao yáo sǎn) formula or tamoxifen for 28 days. Tumor growth inhibition and the decrease of the average tumor mass were most evident in mice treated with Free Wanderer Powder ( xiao yáo sǎn). Free Wanderer Powder ( xiao yáo sǎn) treatment significantly reduced Bcl-2 and elevated Bax and p53 protein expressions in breast cancer tumor. These results were further confirmed by immunohistochemisty. Tamoxifen could decrease spleen mass and Bcl-2 protein expression, increase the Bax protein expression as well as exert uterotrophic effects by increasing uterus index and inducing the gene expressions in the uterus. Taken together, these results show that Free Wanderer Powder ( xiao yáo sǎn) treatment induced apoptosis at protein level and inhibited the tumor growth in 4T1-induced ovariectomized Balb/c female mice, indicating the possibility of its future use for treatment of estrogen-insensitive breast caner.

Real-time ultrasonic assessment of progressive proteoglycan depletion in articular cartilage.

The loss of proteoglycan (PG) is regarded as one of the early signs of osteoarthritis (OA), thus observing the progress of PG loss would be useful for the early detection of OA. In this study, high-frequency ultrasound was used to monitor and analyze the trypsin-induced progressive degeneration in articular cartilage. Full thickness cartilage-bone specimens (n = 10) prepared from normal bovine patellae were digested using 0.25% trypsin solution for different periods of time to evaluate the dynamics of the digestion process. The trypsin penetration front was observed in M-mode image, which was acquired using a nominal 50 MHz focused transducer. The transient speed of the digestion process was estimated from the image. The digestion fraction, which represents the ratio of the digestion depth to the total cartilage thickness, was estimated from ultrasound data and histology sections. With ultrasound, the digestion fraction observed in the 10 specimens ranged from 64% to 99% and was correlated to that measured by histology (R(2) > or = 0.63, p < 0.05). It was found that the digestion speed decreased nonlinearly with depth from 0.61 +/- 0.16 microm/s (mean +/- SD) in the superficial zone to 0.04 +/- 0.02 microm/s in a region located at 70% of the cartilage thickness in depth. The relationship between the digestion depth and the exposure duration in trypsin could be described using a third order polynomial function. The full thickness of digested and undigested tissues was also measured using caliper, estimated from ultrasound data and histology sections, and compared. These findings indicate that ultrasound could provide useful information about the trypsin-induced progressive PG depletion in articular cartilage. Therefore, ultrasound represents a useful tool to evaluate the dynamics of models of OA in vitro in cartilage specimens in a research environment and this would ultimately help the in vitro examination of articular cartilage for research related to model of OA from the early stages of tissue degradation.

Expression of ferroportin1, hephaestin and ceruloplasmin in rat heart.

Iron-mediated injury plays an important role in a number of heart disorders. Studies on heart iron are therefore crucial for understanding the causes of excessive heart iron. Heart cells have the ability to accumulate transferrin-bound-iron via the transferrin receptor and non-transferrin-bound-iron probably via the L-type Ca2+ channel and the divalent metal transporter1. However, little is known about the mechanisms of iron export in the heart cells. Here, we investigated expression of iron exporters including ferroportin 1 (Fpn1), ceruloplasmin (CP) and hephaestin (Heph) and provided evidence for their existence in the heart. We demonstrated that iron has a significant effect on expression of Fpn1 and CP, but not Heph. Treatment of a high-iron diet induced a significant increase in Fpn1, a decrease in CP but no change in Heph mRNA and protein. The control of Fpn1 and CP protein expression by iron was parallel to that of their mRNA expression, suggesting a transcriptional regulation of Fpn1 and CP by iron. The existence of these proteins in the heart implies that they might have a role in heart iron homeostasis.