[Change in intraperitoneal shunt after DAA treatment for hepatitis C].

Improvement and worsening of portal hypertension after direct acting antiviral agent (DAA) treatment for hepatitis C virus-related cirrhosis have been reported, and a consensus remains elusive. In this study, we underscored on the intraperitoneal shunt formed via portal hypertension and examined how the shunt system confirmed by computed tomography (CT) changes before and after treatment in cases in which sustained virological response (SVR) was attained with DAAs. Of the cases in which we achieved an SVR of 24 with DAA treatment for hepatitis C virus-related cirrhosis at our hospital, 83 cases in which CT images were taken before and after treatment were investigated. If the intraperitoneal shunt diameter changed by 20% or more, it was analyzed as an increase or decrease. In 29 patients, intraperitoneal shunt enlargement was noted. When examining factors related to the increase, multivariate analysis detected the FIB4 index at the end of the DAA treatment. Conversely, only four cases were observed in which the size decreased. At the end of treatment, the FIB4 index was the most important factor in increasing the intraperitoneal shunt after DAA treatment for hepatitis C virus-related cirrhosis, and fibrosis was believed to be an influencing factor.

Erratum: Attenuation of postprandial blood glucose in humans consuming isomaltodextrin: carbohydrate loading studies.

[This corrects the article DOI: 10.1080/16546628.2017.1325306.].

Hiatal Hernia with Prolapse of the Pancreas Causing Bile Duct Stricture and Liver Function Disorders: A Case Report and Literature Review.

Hiatal hernia is a common condition in elderly patients, but the additional presence of prolapse of the pancreas is extremely rare. We herein report an 89-year-old woman who presented with liver function disorders and abdominal pain. Her laboratory tests revealed cholestasis, and imaging examinations showed stenosis of the common bile duct pulled toward the hernia sac. She was diagnosed with a common bile duct stricture due to pancreatic herniation and underwent laparoscopic surgery. Our review of the literature identified three types of pancreatic herniations: asymptomatic, bile duct complication, and acute pancreatitis. Pancreatic head herniation tends to induce bile duct complications.

Bowel Obstruction due to Shiitake Mushrooms: Diagnostic Features on Computed Tomography.

Shiitake mushrooms are edible mushrooms popular in East Asian cuisine. We herein report a 69-year-old man with abdominal distension and vomiting after ingesting several pieces of sautéed Shiitake mushrooms. Abdominal computed tomography (CT) revealed ring-shaped and crescent-shaped low-density objects (-100 to -300 Hounsfield units) in the ileum. Based on the specific shapes and CT numbers of the foreign bodies, he was diagnosed with small bowel obstruction due to Shiitake mushrooms. After conservative treatment, he passed four pieces of Shiitake mushrooms. Despite the rarity, the condition can be diagnosed before exploratory surgery by careful and detailed interpretation of CT findings.

Safety and Efficacy of Early Tube Removal Following Percutaneous Transhepatic Gallbladder Drainage: an Observational Study.

BACKGROUND: There are currently no guidelines concerning the advisability and timing of tube removal following percutaneous transhepatic gallbladder drainage (PTGBD). The present study aimed to assess the feasibility and risks of early removal of the PTGBD tube under the scenario of subsiding inflammation, patent cystic and common bile ducts, and absence of intraperitoneal leakage. METHODS: Patient background and outcomes were assessed retrospectively in 701 cases of acute cholecystitis treated with PTGBD. The median times until tube removal and tube dislodgement and the cumulative rates of tube dislodgement were calculated. RESULTS: Tube removal was performed in 275 patients after a median time of 16 days (range: 6 to 213 d); biliary peritonitis was observed in 2 patients following tube removal. Tubes were removed in 8 and 35 patients within 7 and 10 days, respectively. Tube dislodgement was observed in 82 patients after a median time of 12 days (range: 1 to 125 d). CONCLUSION: The present study suggests that drainage tube removal is safe and effective when performed after a short drainage period of 7 to 10 days if the criteria for the removal of the drainage tube were met.

Atypical Clinical Presentation of Crohn's Disease with Superior Mesenteric Vein Obstruction and Protein-losing Enteropathy.

We herein report a 44-year-old man suffering from systemic edema due to protein-losing enteropathy (PLE) with superior mesenteric vein (SMV) obstruction and development of collateral veins, which subsequently proved to be a chronic result of thrombosis and a complication of Crohn's disease (CD). PLE was supposedly induced by both intestinal erosion and thrombosis-related lymphangiectasia, which was histologically proven in his surgically-resected ileal stenosis. Elemental diet and anti-TNFα agent improved his hypoalbuminemia after surgery. The rarity of the simultaneous coexistence of SMV obstruction and PLE and the precedence of these complications over typical abdominal symptoms of CD made the clinical course complex.

Attenuation of postprandial blood glucose in humans consuming isomaltodextrin: carbohydrate loading studies.

Background: Isomaltodextrin (IMD) is a novel highly branched α-glucan and its function as a soluble dietary fiber is expected. Objective: The goal of this study was to evaluate the effects of IMD on postprandial glucose excursions in healthy people and to make the mechanism clear. Design: Twenty-nine subjects ingested a solution containing maltodextrin (MD) or sucrose with or without IMD. Fourteen subjects ingested a solution containing glucose with or without IMD. Blood glucose concentrations were then compared between the groups. Furthermore, in vitro digestion, inhibition of digestive enzymes, and glucose absorption tests were conducted. Results: IMD attenuated blood glucose elevation in the subjects with blood glucose excursions at the high end of normal following the ingestion of MD or sucrose or glucose alone. This effect of 5 g IMD was most clear. IMD was digested partially only by small intestinal mucosal enzymes, and maltase and isomaltase activities were weakly inhibited. Furthermore, IMD inhibited the transport of glucose from mucosal side to serosal side. Conclusions: IMD attenuated postprandial blood glucose, after the ingestion of MD or sucrose or glucose. As one of the mechanism, it was suggested that IMD inhibited the absorption of glucose on small intestinal mucosal membrane.

An enzymatically produced novel cyclomaltopentaose cyclized from amylose by an alpha-(1-->6)-linkage, cyclo-{-->6)-alpha-D-Glcp-(1-->4)-alpha-D-Glcp-(1-->4)-alpha-D-Glcp-(1-->4)-alpha-D-Glcp-(1-->4)-alpha-D-Glcp-(1-->}.

A bacterial strain AM7, isolated from soil and identified as Bacillus circulans, produced two kinds of novel cyclic oligosaccharides. The cyclic oligosaccharides were produced from amylose using a culture supernatant of the strain as the enzyme preparation. The major product was a cyclomaltopentaose cyclized by an alpha-(1-->6)-linkage, cyclo-{-->6)-alpha-D-Glcp-(1-->4)-alpha-D-Glcp-(1-->4)-alpha-D-Glcp-(1-->4)-alpha-D-Glcp-(1-->4)-alpha-D-Glcp-(1-->}. The other minor product was cyclomaltohexaose cyclized by an alpha-(1-->6)-linkage, cyclo-{-->6)-alpha-D-Glcp-(1-->4)-alpha-D-Glcp-(1-->4)-alpha-D-Glcp-(1-->4)-alpha-D-Glcp-(1-->4)-alpha-D-Glcp-(1-->4)-alpha-D-Glcp-(1-->}. We propose the names isocyclomaltopentaose (ICG5) and isocyclomaltohexaose (ICG6) for these novel cyclic maltooligosaccharides having one alpha-(1-->6)-linkage. ICG5 was digested by alpha-amylase derived from Aspergillus oryzae, cyclomaltodextrin glucanotransferase (CGTase) from Bacillus stearothermophilus, and maltogenic alpha-amylase. On the other hand, ICG6 was digested by CGTase from B. stearothermophilus and B. circulans, and maltogenic alpha-amylase. This is the first report of enzymatically produced cyclomaltopentaose and cyclomaltohexaose, which have an alpha-(1-->6)-linkage in their molecules.

Construction and characterization of chimeric enzymes of kojibiose phosphorylase and trehalose phosphorylase from Thermoanaerobacter brockii.

Chimeric phosphorylases were constructed of the kojibiose phosphorylase (KP) gene and the trehalose phosphorylase (TP) gene from Thermoanaerobacter brockii. Four chimeric enzymes had KP activity, and another had TP activity. Chimera V-III showed not TP, but KP activity, although only 125 amino acid residues in 785 residues of chimera V-III were from that of KP. Chimera V-III had 1% of the specific activity of the wild-type KP. Furthermore, the temperature profile and kinetic parameters of chimera V-III were remarkably changed as compared to those of the wild-type KP. The results of the molecular mass of chimera V-III using GPC (76,000 Da) strongly suggested that the chimera V-III protein exists as a monomer in solution, whereas wild-type KP and TP are hexamer and dimer structures, respectively. The result of the substrate specificity for phosphorolysis was that the chimera acted on nigerose, sophorose and laminaribiose, in addition to kojibiose. Furthermore, chimera V-III was also able to act on sophorose and laminaribiose in the absence of inorganic phosphate, and produced two trisaccharides, beta-D-glucosyl-(1-->6)-laminaribiose and laminaritriose, from laminaribiose.

Acceptor specificity of trehalose phosphorylase from Thermoanaerobacter brockii: production of novel nonreducing trisaccharide, 6-O-alpha-D-galactopyranosyl trehalose.

We investigated the acceptor specificity of a thermostable trehalose phosphorylase from Thermoanaerobacter brockii ATCC 35047 (TbTP) was examined using beta-D-glucose-1-phosphate (beta-G1P) as a glucosyl donor and oligosaccharides as the acceptor. Oligosaccharides with a reducing-end glucose residue as the C-6 substituent (e.g., isomaltose, gentiobiose, melibiose, isomaltotriose, and isopanose) were found to be successful acceptors. The transfer products of isomaltose, gentiobiose, and melibiose were isolated and characterized as 6-O-alpha-D-glucopyranosyl trehalose (alpha-GlcTre), 6-O-beta-D-glucopyranosyl trehalose (beta-GlcTre), and 6-O-alpha-D-galactopyranosyl trehalose (alpha-GalTre), respectively. To produce alpha-GalTre, a novel nonreducing trisaccharide, the reaction conditions of alpha-GalTre were examined using trehalose as a glucosyl donor. As a result, the yield of alpha-GalTre reached 40.5%.

Acceptor recognition of kojibiose phosphorylase from Thermoanaerobacter brockii: syntheses of glycosyl glycerol and myo-inositol.

The glucosyl transfer reaction of kojibiose phosphorylase (KP; EC 2.4.1.230) was examined using glycerol or myo-inositol as an acceptor. In the case of glycerol, KP produced two main transfer products: saccharides A and B. The structure of saccharide A was O-alpha-D-glucopyranosyl-(1-->1)-glycerol and that of saccharide B was O-alpha-D-glucopyranosyl-(1-->2)-O-alpha-D-glucopyranosyl-(1-->1)-glycerol. These results show that KP transferred a glucose residue to the hydroxyl group at position 1 of glycerol. On the other hand, when myo-inositol was used as an acceptor, KP produced four transfer products: saccharides 1-4. The structures of saccharides 1 and 2 were O-alpha-D-glucopyranosyl-(1-->1)- and O-alpha-D-glucopyranosyl-(1-->5)-myo-inositol, respectively; those of saccharides 3 and 4 were O-alpha-D-glucopyranosyl-(1-->2)-O-alpha-D-glucopyranosyl-(1-->1)- and O-alpha-D-glucopyranosyl-(1-->2)-O-alpha-D-glucopyranosyl-(1-->5)-myo-inositol, respectively. KP transferred a glucose residue to the hydroxyl group at position 1 or 5 of myo-inositol. On the basis of the structures of their glucosyl transfer products, glycerol and myo-inositol were found to have a common structure with three hydroxyl groups corresponding to the hydroxyl group of the glucose molecule at positions 2, 3 and 4. The conformation of these three hydroxyl groups in the structure is equatorial. This structure is the substrate recognition site of KP. It has been suggested that KP strictly recognizes the structures of glycerol and myo-inositol, and catalyzes the transfer reaction of a glucose residue to the hydroxyl group at position 1 in glycerol, and at position 1 or 5 in myo-inositol, corresponding to position 2 in glucose.

Suppression of apolipoprotein B secretion from HepG2 cells by glucosyl hesperidin.

Our previous study has shown that a soluble hesperidin derivative, glucosyl hesperidin (G-hesperidin), preferentially lowers serum triglyceride (TG) level in hypertriglyceridemic subjects through the improvement of very low-density lipoprotein (VLDL) metabolic abnormality. G-Hesperidin has also been found to decrease an elevated serum apolipoprotein B (apo B) level in the hypertriglyceridemic subjects, suggesting a possibility that this compound suppresses excess VLDL secretion in the liver. In the present study, to gain a better understanding of possible mechanisms by which G-hesperidin lowers serum TG, we examined whether this derivative affects apo B secretion from HepG2 human hepatoma cells, a model of hepatic VLDL secretion. As a result, G-hesperidin significantly reduced apo B secretion from the oleate-stimulated HepG2 cells. Furthermore, G-hesperidin significantly suppressed apo B secretion only in the oleate-stimulated cells and failed to act on the cells incubated without oleate. In the oleate-stimulated cells, G-hesperidin significantly decreased cellular cholesteryl ester (CE), although it had no effect on cellular TG or free cholesterol amounts. Moreover, the oleate-stimulated cells had a decrease in cellular apo B amounts by G-hesperidin exposure. These findings indicate that G-hesperidin down-regulates the assembly of apo B-containing lipoproteins via the reduction of CE synthesis augmented with oleate and results in suppressing excess apo B secretion from the cells. This effect is speculated to be associated with the improvement of VLDL metabolic abnormality in hypertriglyceridemic subjects and considered as a mechanism of lowering serum TG.

Combined NMR and quantum chemical studies on the interaction between trehalose and dienes relevant to the antioxidant function of trehalose.

In a previous study (Oku, K.; Watanabe, H.; Kubota, M.; Fukuda, S.; Kurimoto, M.; Tujisaka, Y.; Komori, M.; Inoue, Y.; Sakurai, M. J. Am. Chem. Soc. 2003, 125, 12739), we investigated the mechanism of the antioxidant function of trehalose against unsaturated fatty acids (UFAs) and revealed that the key factor relevant to the function is the formation of OH...pi and CH...O hydrogen bonds between trehalose and the cis double bonds of the UFA. Here, we investigate whether such intriguing interactions also occur between this sugar and cis double bonds in other unsaturated compounds. For this purpose, we selected various diene compounds (1,3-butadiene, 1,3-pentadiene, 1,4-pentadiene, and 2,5-heptadiene) as interaction partners. All NMR experiments performed, including 1H-1H NOESY measurements, indicated that trehalose selectively interacts with the cis-olefin proton pair in the above diene with a 1:1 stoichiometry, and the C-3 (C-3') and C-6' (C-6) sites of the sugar are responsible for the interaction. Similar interactions were not observed for the mixtures of the diene and other saccharides (neotrehalose, kojibiose, nigerose, maltose, isomaltose, sucrose, maltitol, and sorbitol). Quantum chemical calculations revealed that the OH-3 and OH-6 groups bind to the olefin double bonds of the diene through OH...pi and CH...O types of hydrogen bonds, respectively, and the stabilization energy of the resulting complex is 5-6 kcal mol(-1). These results strongly support the above NMR results. Finally, the activation energies were calculated for the hydrogen abstraction reactions from the activated methylene group of heptadiene. In particular, when the reaction was initiated by a methyl radical, the activation energy was only 10 kcal mol(-1) for the free heptadiene, but on complexation with trehalose it drastically increased to ca. 40 kcal mol(-1). This indicates that trehalose has a significant depression effect on the oxidation of the diene compounds. These results strongly support the antioxidant mechanism deduced in the previous study and indicate that the formation of unique multiple hydrogen bonds between trehalose and cis-olefin bonds is rather a general event not confined to the case of UFA.

An enzymatically produced novel cyclic tetrasaccharide, cyclo-{-->6)-alpha-D-Glcp-(1-->4)-alpha-D-Glcp-(1-->6)-alpha-D-Glcp-(1-->4)-alpha-D-Glcp-(1-->} (cyclic maltosyl-(1-->6)-maltose), from starch.

A bacterial strain M6, isolated from soil and identified as Arthrobacter globiformis, produced a novel nonreducing oligosaccharide. The nonreducing oligosaccharide was produced from starch using a culture supernatant of the strain as enzyme preparation. The oligosaccharide was purified as a crystal preparation after alkaline treatment and deionization of the reaction mixture. The structure of the oligosaccharide was determined by methylation analysis, mass spectrometry, and (1)H and (13)C NMR spectroscopy, and it was demonstrated that the oligosaccharide had a cyclic structure consisting of four glucose residues joined by alternate alpha-(1-->4)- and alpha-(1-->6)-linkages. The cyclic tetrasaccharide, cyclo-{-->6)-alpha-D-Glcp(1-->4)-alpha-D-Glcp(1-->6)-alpha-D-Glcp(1-->4)-alpha-D-Glcp(1-->}, was found to be a novel oligosaccharide, and was tentatively called cyclic maltosyl-maltose (CMM). CMM was not hydrolyzed by various amylases, such as alpha-amylase, beta-amylase, glucoamylase, isoamylase, pullulanase, maltogenic alpha-amylase, and alpha-glucosidase, but hydrolyzed by isomalto-dextranase to give rise to isomaltose. This is the first report of the cyclic tetrasaccharide, which has alternate alpha-(1-->4)- and alpha-(1-->6)-glucosidic linkages.

Enzymatic synthesis of a novel cyclic pentasaccharide consisting of alpha-D-glucopyranose with 6-alpha-glucosyltransferase and 3-alpha-isomaltosyltransferase.

A novel cyclic pentasaccharide (CPS) and a branched cyclic pentasaccharide (6G-CPS) consisting of d-glucopyranose were synthesized with 6-alpha-glucosyltransferase (6GT) and 3-alpha-isomaltosyltransferase (IMT) from Bacillus globisporus N75. The structure of CPS was cyclo-[-->6)-alpha-D-Glcp-(1-->3)-alpha-D-Glcp-(1-->6)-alpha-D-Glcp-(1-->3)-alpha-D-Glcp-(1-->4)-alpha-D-Glcp-(1-->]. The other, 6G-CPS, had the structure cyclo-[-->6)-alpha-D-Glcp-(1-->3)-alpha-D-Glcp-(1-->6)-alpha-D-Glcp-(1-->3)-[alpha-D-Glcp-(1-->6)]-alpha-D-Glcp-(1-->4)-alpha-D-Glcp-(1-->]. The formation of CPS was presumed to occur after the following four successive reactions: a 6-glucosyltransfer reaction with 6GT, a 4-glucosyltransfer reaction with 6GT, a 3-isomaltosyltransfer reaction with IMT, and a cyclization reaction with IMT.

Enzymatic synthesis of a 2-O-alpha-D-glucopyranosyl cyclic tetrasaccharide by kojibiose phosphorylase.

The glucosyl transfer reaction of kojibiose phosphorylase (KPase) from Thermoanaerobacter brockii ATCC35047 was examined using cyclo-{-->6)-alpha-d-Glcp-(1-->3)-alpha-d-Glcp-(1-->6)-alpha-d-Glcp-(1-->3)-alpha-d-Glcp-(1-->} (CTS) as an acceptor. KPase produced four transfer products, saccharides 1-4. The structure of a major product, saccharide 4, was 2-O-alpha-d-glucopyranosyl-CTS, cyclo-{-->6)-alpha-d-Glcp-(1-->3)-alpha-d-Glcp-(1-->6)-[alpha-d-Glcp-(1-->2)]-alpha-d-Glcp-(1-->3)-alpha-d-Glcp-(1-->}. The other transfer products, saccharides 1-3, were 2-O-alpha-kojibiosyl-, 2-O-alpha-kojitriosyl-, and 2-O-alpha-kojitetraosyl-CTS, respectively. These results showed that KPase transferred a glucose residue to the C-2 position at the ring glucose residue of CTS. This enzyme also catalyzed the chain-extending reaction of the side chain of 2-O-alpha-d-glycopyranosyl-CTS.

Enhancement of thermostability of kojibiose phosphorylase from Thermoanaerobacter brockii ATCC35047 by random mutagenesis.

Random mutation by error-prone PCR was introduced into kojibiose phosphorylase from Thermoanaerobacter brockii ATCC35047. One thermostable mutant enzyme, D513N, was isolated. The D513N mutant enzyme showed an optimum temperature of 67.5-70 degrees C (the wild type, 65 degrees C), and thermostability up to 67.5 degrees C (the wild type, up to 60 degrees C). The half-lives of D513N were estimated to be 135 h at 60 degrees C, 110 min at 70 degrees C and 6 min at 75 degrees C, respectively. They were about 1.6-fold, 7-fold and 6-fold longer than those of the wild-type enzyme, respectively.

Hyper expression of kojibiose phosphorylase gene and trehalose phosphorylase gene from Thermoanaerobacter brockii ATCC35047 in Bacillus subtilis and selaginose synthesis utilizing two phosphorylases.

The kojibiose phosphorylase (KP) gene and trehalose phosphorylase (TP) gene from Thermoanaerobacter brockii ATCC35047 were intracellularly hyper-expressed under the control of the Bacillus amyloliquefaciens alpha-amylase promoter in Bacillus subtilis. The production yields were estimated to be 2.1 g of KP and 4.9 g of TP per liter of medium. Selaginose, non-reducing trisaccharide, was synthesized from trehalose utilizing the recombinant KP and TP from B. subtilis. Selaginose was not hydrolyzed by salivary amylase, artificial gastric juice, pancreatic amylase, or small intestinal enzymes.

Glucosyl hesperidin lowers serum triglyceride level in hypertriglyceridemic subjects through the improvement of very low-density lipoprotein metabolic abnormality.

To examine the serum triglyceride (TG)-lowering effect of a soluble hesperidin derivative, glucosyl hesperidin (G-hesperidin), and its mechanisms, we carried out a G-hesperidin administration test in hypertriglyceridemic subjects. G-Hesperidin was administered to the subjects at 500 mg/d for 24 wk. In this study, the subjects were classified into high-TG type (TG > 150 mg/dL), borderline-TG type (TG 110-150 mg/dL) and normal-TG type (TG < 110 mg/dL) on the basis of their initial serum TG values. Among these phenotypes, serum TG level significantly decreased in the high-TG type during the G-hesperidin administration period. It was also observed that elevated values of serum remnant-like particle cholesterol (RLP-C), apolipoprotein (apo) B, apo C-II, apo C-III and apo E occurred in the high-TG type and that these serum levels were significantly reduced by G-hesperidin administration. Moreover, polyacrylamide gel electrophoresis analysis of serum lipoproteins revealed that the very low-density lipoprotein (VLDL)/low-density lipoprotein (LDL) ratio and LDL migration index of the high-TG type were remarkably higher than those of the other phenotypes but that their high values were significantly reduced by the administration. These results indicate that G-hesperidin preferentially lowers serum TG in hypertriglyceridemic subjects and that this effect is possibly caused by the improvement of VLDL metabolic abnormality, leading to the reduction of small dense LDL.

Maintenance with pamidronate following first-line MP or VAD therapy in multiple myeloma.

We investigated the anti-tumor effect of pamidronate after obtaining a decrease of serum monoclonal immunoglobulin (Ig) level by conventional chemotherapy in patients with multiple myeloma (MM) in order to evaluate whether the drug is useful as maintenance therapy for MM. Eight patients with MM received 60 mg/d pamidronate every third week for 6-18 months without chemotherapeutic agents or corticosteroids after the treatment with melphalan and prednisolone, or vincristine, adriamycin and prednisolone. Serum Ig and beta2-microglobulin (b2MG) levels were maintained at the levels obtained after the termination of chemotherapy in six and four out of eight patients, respectively. Hemoglobin levels were maintained at, or increased to more than, the levels observed at the end of chemotherapy in six patients. Decreased plasma cells in the bone marrow after the chemotherapy were evident in five patients. Two patients were categorized as non-responders, because Ig and b2MG increased and anemia progressed after treatment with the drug. Despite the very small numbers, the results suggest that pamidronate may have anti-tumor activity and be useful for treatment after the conventional chemotherapy in some cases of MM.