Analysis of whole-blood antioxidant capacity after chronic and localized irradiation using the i-STrap method

Ionizing radiation exposure affects the redox state in vivo. Recently, whole-blood antioxidant capacity (WBAC) has been reported to decrease in a dose-dependent manner after acute total body irradiation (TBI). However, changes in WBAC after localized and chronic irradiations have not been reported. This study analyzed changes to WBAC in mice after either localized irradiation (irradiation of the left hind leg only) or chronic TBI using the i-STrap method. Leg-localized irradiation exerted limited effects on WBAC, while WBAC decreased in a dose rate-dependent manner after TBI. Further, the WBAC reached the minimum value in a shorter period at a smaller dose rate. Our results suggest that changes in WBAC do not directly reflect absorbed dose, but may reflect radiation-induced biological damage at the systemic level. This study will contribute to the understanding of radiation-induced injuries and diseases, and will facilitate the establishment of biomarkers for radiation exposure.     

iTRAQ-Based Quantitative Proteomics Reveals the Energy Metabolism Alterations Induced by Chlorogenic Acid in HepG2 Cells

Epidemiological studies have suggested that coffee consumption is associated with a decrease in the risk of developing obesity and diabetes; however, the detailed mechanisms underlying these effects of coffee consumption remain poorly understood. In this study, we examined the effects of chlorogenic acid on energy metabolism in vitro. Hepatocellular carcinoma G2 (HepG2) cells were cultured in a medium containing chlorogenic acid. Chlorogenic acid increased the activity of mitochondrial enzymes, including citrate synthase, isocitrate dehydrogenase, and malate dehydrogenase (MDH), which are involved in the tricarboxylic acid (TCA) cycle. Proteome analysis using the isobaric tags for the relative and absolute quantitation (iTRAQ) method revealed the upregulation of proteins involved in the glycolytic system, electron transport system, and ATP synthesis in mitochondria. Therefore, we propose a notable mechanism whereby chlorogenic acid enhances energy metabolism, including the TCA cycle, glycolytic system, electron transport, and ATP synthesis. This mechanism provides important insights into understanding the beneficial effects of coffee consumption.     

Breast-conserving surgery: quadrantectomy

The surgical techniques and clinical results of quadrantectomy as a form of breast-conserving surgery are described. A quadrantectomy is a breast-conserving technique including wide resection and tumorectomy. A quadrantectomy is designed to remove an anatomic segment of breast tissue (duct-lobular system). It has the advantage of greater surgical curability than other conserving techniques in cases with ductal spread, because breast cancer arising in the terminal duct often spreads in the duct-lobular system. However, quadrantectomy poses some cosmetic problems due to the large volume of breast tissue excised. Additionally, quadrantectomy has failed to show better results in local recurrence rates compared with wide resection. Therefore quadrantectomy should be limited to breast cancer with segmental and wide ductal spread. It is important to determine the surgical technique that compromises between local curability and cosmetic results for each patient with breast cancer.     

Dual role of vascular endothelial growth factor in hepatic ischemia-reperfusion injury

BACKGROUND: Vascular endothelial growth factor (VEGF), a major angiogenic factor, mediates a variety of disease conditions through promotion of angiogenesis. It also plays a critical role as a potent proinflammatory cytokine in a variety of physiologic and pathologic immune responses. In the present study, we evaluated the expression of VEGF in hepatic warm ischemia-reperfusion (I/R) injury and examined the effect of recombinant human (rh)VEGF administration in an established murine model. METHOD: The expression of VEGF in the liver was assessed by quantitative real-time polymerase chain reaction and immunohistochemistry during I/R injury using 70% partial hepatic ischemia model. The effect of rhVEGF administration on I/R injury was evaluated by measuring liver function and histology. In addition, local inducible nitric oxide synthase (iNOS) and endothelial NO synthase expressions were examined to address the underlying mechanisms. RESULTS: The local expression of VEGF was significantly up-regulated at 2 hours after reperfusion after 60 minutes of ischemia compared with that in the naive liver. VEGF was expressed predominantly in CD11b+ cells infiltrating into the ischemic liver. The administration of rhVEGF had a significant protective effect on ischemic injury in the liver. This effect was associated with the up-regulation of iNOS expression in the rhVEGF-treated liver. CONCLUSION: We demonstrate a dual role of VEGF in hepatic warm I/R injury. Although endogenous VEGF is expressed and functional to initiate hepatic I/R injury, exogenous rhVEGF has a beneficial effect on the ischemic liver. These data may provide new insights into the role of VEGF as well as pathophysiology of hepatic I/R injury.     

Sonic hedgehog relates to colorectal carcinogenesis

Aim

The activation of Hedgehog signaling, which is critical to normal mammalian gastrointestinal development, is implicated in the development of various tumors, including colorectal cancer. In the pancreas, a precursor lesion overexpresses the Sonic hedgehog (Shh) when compared with normal tissue and cancer. The present study was designed to investigate Shh related protein expression in hyperplastic polyps and the adenoma-carcinoma sequence in the colon and rectum.

Methods

Seventeen hyperplastic polyps, 24 adenomas of the colon, 69 adenocarcinomas (31 well-differentiated, 38 moderately-differentiated), and 30 normal colon samples were used in the study. We checked the expression of Shh, both patched (Ptch) and smoothened (Smo), by immunohistochemistry and compared the expression rate of each group.

Results

Almost all adenomas, 22 of 23 (96%), expressed Shh. In other groups, 4 of 17 hyperplastic polyps (24%), 7 of 31 well-differentiated adenocarcinomas (23%), 13 of 38 moderately-differentiated adenocarcinomas (34%) and none of the 30 normal samples expressed Shh. The rate of expression in Ptch and Smo gradually increased in accordance with tumor progression.

Conclusion

This result indicates that Shh-related carcinogenesis and Shh expression may be a trigger for the adenoma-carcinoma sequence. This study suggests a potential therapeutic target of hedgehog blockade in carcinogenesis.     

Intravenous Immunoglobulin Therapy for Refractory Interstitial Lung Disease Associated with Polymyositis/Dermatomyositis

Interstitial lung disease (ILD) associated with polymyositis/dermatomyositis (ILD-PM/DM), including amyopathic dermatomyositis (ADM), is recognized as an important condition because it frequently causes death, despite intensive therapy with high-dose corticosteroid and immunosuppressive agents, such as cyclosporine A and cyclophosphamide. Intravenous immunoglobulin therapy (IVIG) has shown efficacy for myopathy associated with PM/DM, but its usefulness for ILD-PM/DM is unclear. This study was designed to investigate the efficacy of IVIG for refractory ILD-PM/DM. A review was made of medical charts of five patients (2 men and 3 women) who were treated with IVIG for refractory ILD-PM/DM resistant to high-dose corticosteroid and cyclosporine A and/or cyclophosphamide. One patient had acute ILD-PM and four patients had acute ILD-ADM. Of the five patients, one patient with ILD-PM and one patient with ILD-ADM survived. No adverse reactions were seen due to IVIG treatment. There were no critical differences in the clinical parameters and clinical courses between survivors and nonsurvivors. IVIG treatment is safe and could be an effective salvage therapy for refractory ILD-PM/DM in certain cases, suggesting that further controlled trials are worthwhile.     

Changes in Expression of Connexin 32, Bile Canaliculus-Like Structures,and Localization of Alkaline Phosphatase in Primary Cultures of Fetal Rat Hepatocytes

We devised an experimental design in primary cultures of fetal rat hepatocytes for studying hepatocyte differentiation over a short period. In the present study, hepatocytes were first cultured for 3 days in dexamethasone-supplemented medium and then for an additional 3 days in dexamethasone- or epidermal growth factor-supplemented medium. In hepatocytes cultured continuously in dexamethasone-supplemented medium, the expression of connexin 32 increased and bile canaliculus-like structures and localization of alkaline phosphatase in the plasma membrane around bile canaliculus-like structures were maintained. Few cells incorporated bromodeoxyuridine. On the other hand, in most of the hepatocytes cultured in epidermal growth factor-supplemented medium, the expression of connexin 32 was minimally recognized, bile canaliculus-like structures were shortened or eliminated, and alkaline phosphatase was localized as numerous fine spots throughout the cytoplasm. More than 20% of all hepatocytes incorporated bromodeoxyuridine.The present study suggests that in hepatocytes, there is a close relationship among connexin 32 expression, the maintenance of bile canaliculus-like structures, and the localization of alkaline phosphatase to the plasma membrane around the bile canaliculus-like structures, and this indicates that the present experimental model is useful for studying hepatocyte differentiation over a short period.     

Successful treatment of refractory gastric antral vascular ectasia using transcatheter arterial embolization

In January 2008, a 67-year-old woman was admitted to our hospital because of hepatitis C virus-related cirrhosis and hepatocellular carcinoma (HCC). In February 2010, she had tarry stools and anemia resulting from gastric antral vascular ectasia (GAVE). Argon plasma coagulation (APC) treatment for GAVE was performed at that time. She revisited our hospital in July 2010 because of tarry stools and anemia caused by GAVE recurrence, which required 5 APC sessions and blood transfusion to control the bleeding. In October 2010, she arrived at our hospital by ambulance because of hemorrhagic shock resulting from GAVE recurrence. Despite performing 5 APC sessions and multiple blood transfusions, the tarry stools and anemia persisted during the hospitalization period. In December 2010 and January 2011, second-stage selective transcatheter arterial embolization (TAE) of the right gastric and right gastroepiploic arteries using microcoils was performed for the treatment of the refractory GAVE. Upper gastrointestinal endoscopy performed after TAE revealed the disappearance of mucosal diffuse spotty redness. In addition, no complications such as gastric ulcer and necrosis were observed. Selective TAE, effectively resolved the GAVE and anemia, and no recurrence has been observed during the last 24 months. Therefore, TAE may be a safe and radical treatment for refractory GAVE.