Transhepatic Placement of Metallic Biliary Stent for Internal Drainage of Persistent Liver Abscesses.

Transhepatic placement of a metallic biliary stent for internal drainage of persistent liver abscesses was performed in 9 patients (males; median age, 65 years; range, 57-82 years) with refractory liver abscess. The median follow-up period was 2.8 months (range, 0.4-50.3 months). Technical success was achieved in all cases without any major complications. Clinical success, defined as the removal of the drainage tube without recurrent symptoms of infection, was achieved in 8 cases. Median duration until removal of the drainage tube from stent placement was 7 days (range, 0-36).

Comprehensive analysis of the Co-structures of dipeptidyl peptidase IV and its inhibitor.

BACKGROUND: We comprehensively analyzed X-ray cocrystal structures of dipeptidyl peptidase IV (DPP-4) and its inhibitor to clarify whether DPP-4 alters its general or partial structure according to the inhibitor used and whether DPP-4 has a common rule for inhibitor binding. RESULTS: All the main and side chains in the inhibitor binding area were minimally altered, except for a few side chains, despite binding to inhibitors of various shapes. Some residues (Arg125, Glu205, Glu206, Tyr662 and Asn710) in the area had binding modes to fix a specific atom of inhibitor to a particular spatial position in DPP-4. We found two specific water molecules that were common to 92 DPP-4 structures. The two water molecules were close to many inhibitors, and seemed to play two roles: maintaining the orientation of the Glu205 and Glu206 side chains through a network via the water molecules, and arranging the inhibitor appropriately at the S2 subsite. CONCLUSIONS: Our study based on high-quality resources may provide a necessary minimum consensus to help in the discovery of a novel DPP-4 inhibitor that is commercially useful.

Pectin from Prunus domestica L. induces proliferation of IEC-6 cells through the alteration of cell-surface heparan sulfate on differentiated Caco-2 cells in co-culture.

Dietary fiber intake provides various physiological and metabolic effects for human health. Pectin, a water-soluble dietary fiber, induces morphological changes of the small intestine in vivo. However, the molecular mechanisms underlying pectin-derived morphological alterations have not been elucidated. Previously, we found that pectin purified from Prunus domestica L. altered the sulfated structure of cell-surface heparan sulfate (HS) on differentiated Caco-2 cells via fibronectin and α5ß1 integrin. In this study, we investigated the biological significance of the effect of pectin on HS in differentiated Caco-2 cells. An in vitro intestinal epithelium model was constructed by co-culture of differentiated Caco-2 cells and rat IEC-6 cells, which were used as models of intestinal epithelium and intestinal crypt cells, respectively. We found that pectin-treated differentiated Caco-2 cells promoted growth of IEC-6 cells. Real-time RT-PCR analysis and western blotting showed that relative mRNA and protein expression levels of Wnt3a were upregulated by pectin treatment in differentiated Caco-2 cells. Analysis by surface plasmon resonance spectroscopy demonstrated that pectin-induced structural alteration of HS markedly decreased the interaction with Wnt3a. However, depression in the secretion of Wnt3a from Caco-2 cells by anti-Wnt3a antibody did not affect the proliferation of IEC-6 cells in co-culture system. These observations indicated that pectin altered the sulfated structure of cell-surface HS to promote secretion of Wnt3a from differentiated Caco-2 cells and Wnt3a indirectly stimulated the proliferation of IEC-6 cells.

Selective Reduction Mechanism of Graphene Oxide Driven by the Photon Mode versus the Thermal Mode.

A two-dimensional nanocarbon, graphene, has attracted substantial interest due to its excellent properties. The reduction of graphene oxide (GO) has been investigated for the mass production of graphene used in practical applications. Different reduction processes produce different properties in graphene, affecting the performance of the final materials or devices. Therefore, an understanding of the mechanisms of GO reduction is important for controlling the properties of functional two-dimensional systems. Here, we determined the average structure of reduced GO prepared via heating and photoexcitation and clearly distinguished their reduction mechanisms using ultrafast time-resolved electron diffraction, time-resolved infrared vibrational spectroscopy, and time-dependent density functional theory calculations. The oxygen atoms of epoxy groups are selectively removed from the basal plane of GO by photoexcitation (photon mode), in stark contrast to the behavior observed for the thermal reduction of hydroxyl and epoxy groups (thermal mode). The difference originates from the selective excitation of epoxy bonds via an electronic transition due to their antibonding character. This work will enable the preparation of the optimum GO for the intended applications and expands the application scope of two-dimensional systems.

Factors affecting sensitivity to antitumor platinum derivatives of human colorectal tumor cell lines.

PURPOSE: The aim of this study is to examine the factors affecting sensitivity to cisplatin, carboplatin, and oxaliplatin in human colorectal tumor cell lines. METHODS: Caco-2, DLD-1, HCT-15, HCT116, LS180, SW620, and WiDr cells were used. Their growth inhibition by platinum derivatives was evaluated with a WST-1 assay utilizing succinate dehydrogenase activity. Cellular accumulation and DNA-binding of platinum were measured with an inductively coupled plasma mass spectrometer. The mRNA levels of copper transporters (hCtr1, ATP7A, and ATP7B) and organic cation transporters (hOCT1, hOCT2, and hOCT3) were evaluated by the real-time reverse transcription-PCR method using SYBR green. RESULTS: The cytotoxicity of platinum derivatives ranked oxaliplatin > cisplatin > carboplatin in almost all cells used. Cellular accumulation and DNA-binding of platinum varied among the types of cells, but levels were similar on treatment with cisplatin and oxaliplatin, and lower in response to carboplatin. The levels of copper and organic cation transporter mRNAs also differed with cell type. A correlation analysis revealed that sensitivity to platinum derivatives was dependent in part on the amount of platinum bound to DNA. In addition, the cellular accumulation of platinum and level of ATP7A mRNA may be factors affecting the cytotoxicity of cisplatin, while the cytotoxicity of oxaliplatin was suggested to be affected by the levels of ATP7A and hOCT1 mRNAs. CONCLUSION: Some factors affecting the sensitivity of tumor cells to platinum derivatives were proposed, and will provide useful information for cancer chemotherapy with platinum derivatives.

Comparative analysis of cell injury after exposure to antitumor platinum derivatives in kidney tubular epithelial cells.

BACKGROUND: Platinum derivatives differ in effectiveness and safety. The purpose of this study is to compare differences in the mechanism of nephrotoxicity among these derivatives. METHODS: LLC-PK(1) cells were used as a model of tubular epithelial cells. Cytotoxicity was evaluated by WST-1 assay, and cellular accumulation of platinum was examined by inductively coupled plasma mass spectrometer. As indexes of necrosis and apoptosis, lactate dehydrogenase release, DNA fragmentation and caspase 3 activation were examined. RESULTS: In terms of cytotoxicity, the derivatives ranked in the order of oxaliplatin > cisplatin > nedaplatin > carboplatin, being comparable with that for the level of platinum accumulated in LLC-PK(1) cells. Lactate dehydrogenase release and DNA fragmentation were observed following treatment with all the derivatives, but were lowest for carboplatin. In terms of activating caspase 3, the order was cisplatin > nedaplatin > oxaliplatin > carboplatin. CONCLUSION: Cytotoxicity by the derivatives was dependent on cellular accumulation of platinum and suggested to be mediated by apoptosis and necrosis; however, contributions differed among the derivatives.