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Pancreatic fistula is a complication that frequently occurs after pancreatic surgery. Although various attempts have been made to prevent pancreatic fistula after pancreatic surgery, no effective methods have been developed thus far. In this study, to prevent the pancreatic fistula, we attempted to prepare the hydrogels consisting of two types of polyvinyl alcohol (PVAs), Poval® and Exceval® by the freezing–thawing (F/T) method. As the concentration and the number of F/T cycles increased, it was revealed that the swelling degree tended to decrease, and tensile strength tended to increase. Especially, Exceval® formed more robust hydrogels than that of Poval® hydrogel prepared by the same conditions. Furthermore, the release behavior of tartrazine from 10% Exceval® hydrogels differed depending on the number of F/T cycles. It was also revealed that the diffusion pattern of the drug in the hydrogel differed along with the release, and the entire amount of tartrazine in the hydrogel was released by 120 min. As nafamostat mesylate was loaded, in vivo study, Pancreatic enzyme values were obtained after 48 h, which allowed comparison of the preventive effects against pancreatic fistula between the untreated group, the Exceval® hydrogel group, and nafamostat mesylate‐containing Exceval®‐applied group. Furthermore, there was a significant difference between the untreated group and the hydrogel‐applied group. Besides, PVA hydrogels prepared by the F/T method could probably absorb pancreatic enzymes. This study found that Exceval® hydrogel prepared by the F/T method was considered a novel hydrogel formulation to prevent pancreatic fistula. [ABSTRACT FROM AUTHOR]

Background and Aim: The incidence of non‐alcoholic steatohepatitis (NASH)‐related hepatocellular carcinoma (HCC) is progressively increasing. However, the pathophysiology and etiology of NASH progression to HCC are unknown. We hypothesized that steatosis was the key factor in NASH‐related hepatocarcinogenesis and aimed to evaluate the effects of long‐term liver X receptor (LXR) agonist stimulation on hepatic steatosis induced by a high‐fat diet and oxidative stress. Methods: We used an LXR agonist (T0901317) and CCl4 to induce hepatic steatosis and oxidative stress, respectively. C57BL/6 mice fed with a high‐fat diet were treated with either T0901317 + CCl4 (T09 + CCl4 group) or CCl4 alone (CCl4 group). T0901317 (2.5 mg/kg) and CCl4 (0.1 mL/kg) were intraperitoneally administered twice weekly for 24 weeks. Results: The liver‐to‐body weight ratio was significantly higher in the T09 + CCl4 group than in the CCl4 group. Mice in the T09 + CCl4 group exhibited abnormal lipid metabolism and NASH‐like histopathological features. Additionally, all mice in the T09 + CCl4 group developed liver tumors diagnosed as well‐differentiated HCC. The genes identified via microarray analysis were related to NASH and HCC development. Conclusions: By combining long‐term LXR agonist stimulation with oxidative stress and a high‐fat diet, we successfully reproduced liver conditions in mice similar to those in humans with NASH and progression to HCC. Our results provide new insight into NASH‐related HCC progression and therapy. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the efficacy of a novel hydrogel sheet in preventing postoperative pancreatic fistula (POPF). Background: Postoperative pancreatic fistula is a life‐threatening complication. As no study has reported the use of hydrogel sheets in preventing POPF, their effectiveness for that purpose remains unclear. Methods: A novel hydrogel sheet made of polyvinyl alcohol (PVA) was prepared by the freeze‐thaw method. The pancreatic ducts and surrounding pancreatic parenchyma of rats were transected to induce a pancreatic fistula. Next, the sheet was attached to the transection site. Ascitic fluid amylase and lipase concentrations were measured. Neoveil®, a nonwoven polyglycolic acid (PGA) felt, is already clinically used as an absorbable reinforcing material at pancreatic transection sites. Neoveil® was used for comparison, as was VIEWGEL®, which is marketed as a wound dressing. Results: The hydrogel sheet remained in place 48 hours postoperatively. The ascitic amylase concentrations in the control, VIEWGEL®‐treated, Neoveil®‐treated, and hydrogel‐treated rats, respectively, were 4992.4 ± 5355.7, 1068.4 ± 269.1, 730.2 ± 425.2, and 303.1 ± 240.1 IU/L; the ascitic lipase concentrations were 2279.8 ± 3395.2, 169.5 ± 100.6, 90.4 ± 71.0, and 86.8 ± 59.8 IU/L. The ascitic amylase and lipase levels were significantly lower in the hydrogel group than in the other groups (P <.05). Conclusions: This novel hydrogel sheet effectively prevents pancreatic fistulas and has promising clinical application potential. [ABSTRACT FROM AUTHOR]

The effect of omega-dipoles on the adsorbed film of fluoroalkanol at the oil/water interface is clarified. The partial molar entropy and energy changes associated with the adsorption of HDFC9OH are evaluated and compared to those of FDFC0OH in order to see the effect of omega-dipoles on the adsorption of HDFC9OH.

An efficient route to highly substituted indoles was developed. It included regioselective functionalization of tetrahydroindol-4(5 H)-ones, prepared by ring-opening cyclization of cyclohexane-1,3-dione-2-spirocyclopropanes with primary amines, and subsequent oxidation. The 6-substituted indoles were synthesized from a readily available 5-substituted cyclohexane-1,3-dione-2-spirocyclopropane. The synthesis of 5- and 7-substituted indoles was achieved by regioselective electrophilic alkylation of tetrahydroindol-4(5 H)-one, followed by oxidation. The 4-substituted indoles were synthesized by nucleophilic alkylation of the corresponding pyrrole derivative, which was prepared by partial oxidation of tetrahydroindol-4(5 H)-one, and sequential oxidation. The synthesis of 4-substituted indoles was also accomplished by palladium-catalyzed coupling of 4-hydroxyindole-derived triflates. Furthermore, the synthesis of 4,5,6,7-tetrasubstituted indoles was achieved by using these regioselective alkylations. [ABSTRACT FROM AUTHOR]

Aim Apoptosis is associated with various types of hepatic disorders. We have developed a novel cell-transfer drug delivery system (DDS) using a multifunctional envelope-type nano device that targets liver sinusoidal endothelial cells (LSECs). The purpose of this study was to determine the efficacy of the novel DDS containing siRNA at suppressing apoptosis in LSECs. Methods Bax siRNA was transfected into a sinusoidal endothelial cell line (M1) to suppress apoptosis induced by an anti-Fas antibody and staurosporine. C57BL/6J mice were divided into three groups: (i) a control group, only intravenous saline; (ii) a nonselective group, injections of siRNA sealed in the nonselective DDS; and (iii) an LSEC-transfer efficient group, injections of siRNA sealed in an LSEC-transfer efficient DDS. Hepatic cell apoptosis was induced by an anti-Fas antibody. Results Bax siRNA had an anti-apoptotic effect on M1 cells. Serum alanine aminotransferase was reduced in the LSEC-transfer efficient group, as were cleaved caspase-3 and the number of terminal deoxynucleotidyl transferase dUTP nick end labeling positive hepatocytes. Silver impregnation staining indicated that the sinusoidal space was maintained in the LSEC-transfer efficient group but not in the other groups. Electron microscopy showed that the LSECs were slightly impaired, although the sinusoidal structure was maintained in the LSEC-transfer efficient group. Conclusion Hepatocyte apoptosis was reduced by the efficient suppression of LSEC apoptosis with a novel DDS. Protecting the sinusoidal structure by suppressing LSEC damage will be an effective treatment for acute liver failure. [ABSTRACT FROM AUTHOR]