Refractory gastric ulcer due to undisclosed use of topical diclofenac epolamine patches

Background: Topical forms of nonsteroidal anti-inflammatory drugs (NSAIDs) have been created to lessen systemic adverse effects. In general, they are believed to be well tolerated and appropriate for use as an over-the-counter (OTC) drug. Case Presentation: A 68-year-old woman visited our clinic due to tarry stool. The patient reported multiple episodes of recurrent bleeding from a gastric ulcer for 2 months and was treated with endoscopic hemostatic clipping. The patient disclosed she had been using a large number of diclofenac patches for more than 3 months. The patient was treated conservatively by discontinuation of diclofenac patches and treatment with a proton pump inhibitor and omeprazole. Conclusion: In conclusion, inappropriate use of topical NSAID patches can be a cause of peptic ulcer bleeding. Patients reporting multiple episodes of recurrent bleeding from a gastric ulcer should be questioned, particularly about the use of OTC medications that might include topical NSAID patches

Well leg compartment syndrome after surgery for ulcerative colitis in the lithotomy position: A case report

AbstractIntroductionWell leg compartment syndrome (WLCS) is an uncommon and severe complication that occurs after colorectal surgery in the lithotomy position.Presentation of caseThe current patient was a 28-year-old male suffering from ulcerative colitis. He was underwent elective proctectomy, including ileal J pouch formation and anal anastomosis with temporary loop ileostomy. The ileoanal pouch procedure was quite difficult, and during this procedure, the high lithotomy and head down tilt positions were continued for 255min.After the operation, the patient complained of severe cramping pain, swelling and serious tenderness on palpation in both legs. On the first postoperative day, the patient's complaints gradually worsened. The intra-compartmental pressure was measured, and WLCS was diagnosed. Emergency bilateral fasciotomy was performed. Initially, the patient had a sensory deficit and analgesia, however, his sensory disturbance and pain had almost recovered two months after fasciotomy by rehabilitation.DiscussionIn the current case, the important factors associated with the development of WLCS are thought to be a prolonged operative time in which the patient is placed in the high lithotomy position during ileoanal pouch procedure.ConclusionWe would thus like to emphasize that operations for the ileoanal pouch procedure to treat ulcerative colitis have a high potential for inducing WLCS, because it usually requires a prolonged operative time in which the patient remains in the high lithotomy position

Exponentially Modified Protein Abundance Index (emPAI) for Estimation of Absolute Protein Amount in Proteomics by the Number of Sequenced Peptides per Protein

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Epigenetic regulation of the tissue-specific expression of human UDP-glucuronosyltransferase (UGT) 1A10

Human UDP-glucuronosyltransferase (UGT) 1A10 is not expressed in the liver; however, UGT1A10 is highly expressed in the intestine, contributing to presystemic first-pass metabolism. Earlier studies revealed that hepatocyte nuclear factor (HNF) 1α and Sp1, as well as an intestine-specific transcription factor, caudal type homeobox (Cdx) 2, are involved in the constitutive expression of UGT1A10. However, why UGT1A10 is not expressed in the liver, where HNF1α and Sp1 are abundantly expressed, is unknown. In this study, we sought to elucidate the mechanism, focusing on epigenetic regulation. Bisulfite sequence analysis revealed that the CpG-rich region (-264 to +117) around the UGT1A10 promoter was hypermethylated (89%) in hepatocytes, whereas the UGT1A10 promoter was hypomethylated (11%) in the epithelium of the small intestine. A luciferase assay revealed that the methylation of the UGT1A10 promoter by SssI methylase abrogated transactivity even with overexpressed Cdx2 and HNF1α. The UGT1A10 promoter was highly methylated (86%) in liver-derived HuH-7 cells, where UGT1A10 is not expressed. In contrast, the UGT1A10 promoter was hardly methylated (19%) in colon-derived LS180 cells, where UGT1A10 is expressed. Treatment with 5-aza-2′-deoxycitidine (5-Aza-dC), an inhibitor of DNA methylation, resulted in an increase in UGT1A10 expression only in HuH-7 cells. Moreover, overexpression of HNF1α and Cdx2 further increased UGT1A10 expression only in the presence of 5-Aza-dC. Collectively, we found that DNA hypermethylation would interfere with the binding of HNF1α and Cdx2, resulting in the defective expression of UGT1A10 in human liver. Thus, epigenetic regulation is one of the mechanisms that determine the tissue-specific expression of UGT1A10. © 2013

Special Section on Epigenetic Regulation of Drug Metabolizing Enzymes and Transporters Epigenetic Regulation Is a Crucial Factor in the Repression of UGT1A1 Expression in the Human Kidney

ABSTRACT Human uridine 59-diphospho-glucuronosyltransferase (UGT) 1A1 catalyzes the metabolism of numerous clinically and pharmacologically important compounds, such as bilirubin and SN-38. UGT1A1 is predominantly expressed in the liver and intestine but not in the kidney. The purpose of this study was to uncover the mechanism of the tissue-specific expression of UGT1A1, focusing on its epigenetic regulation. Bisulfite sequence analysis revealed that the CpG-rich region near the UGT1A1 promoter (285 to +40) was hypermethylated (83%) in the kidney, whereas it was hypomethylated (37%) in the liver. A chromatin immunoprecipitation assay demonstrated that histone H3 near the promoter was hypoacetylated in the kidney but hyperacetylated in the liver; this hyperacetylation was accompanied by the recruitment of hepatocyte nuclear factor (HNF) 1a to the promoter. The UGT1A1 promoter in human kidney-derived HK-2 cells that do not express UGT1A1 was fully methylated, but this promoter was relatively unmethylated in human liver-derived HuH-7 cells that express UGT1A1. Treatment with 5-aza-29-deoxycytidine (5-aza-dC), an inhibitor of DNA methylation, resulted in an increase of UGT1A1 mRNA expression in both cell types, but the increase was much larger in HK-2 cells than in HuH-7 cells. The transfection of an HNF1a expression plasmid into the HK-2 cells resulted in an increase of UGT1A1 mRNA only in the presence of 5-aza-dC. In summary, we found that DNA hypermethylation, along with histone hypoacetylation, interferes with the binding of HNF1a, resulting in the defective expression of UGT1A1 in the human kidney. Thus, epigenetic regulation is a crucial determinant of tissue-specific expression of UGT1A1

Calculation of diffusion coefficients for carbon dioxide + solute system near the critical conditions by non-equilibrium molecular dynamics simulation

金沢大学大学院自然科学研究科生産プロセスA non-equilibrium molecular dynamics simulation was adopted to calculate the diffusion coefficients for a pseudo-binary system of carbon dioxide and for a carbon dioxide + solute system at 308.2 and 318.2K. The calculated results were compared with the self- and tracer diffusion coefficients calculated by an equilibrium molecular dynamics simulation. The simulated results for the pseudo-binary system of carbon dioxide by the non-equilibrium molecular dynamics simulation are in good agreement with the results of self diffusion coefficients for pure carbon dioxide by the equilibrium molecular dynamics simulation. The simulated results of mutual diffusion coefficients for the carbon dioxide + solute system by the non-equilibrium molecular dynamics simulation are slightly lower than the results of the tracer diffusion coefficients by the equilibrium molecular dynamics simulation. The anomalous behavior of diffusion coefficients near the critical concentration was represented by the results of the non-equilibrium molecular dynamics simulation. © 2004 Elsevier B.V. All rights reserved

Concentration dependence of diffusion coefficients for supercritical carbon dioxide + naphthalene system

金沢大学大学院自然科学研究科生産プロセスThe concentration dependence of diffusion coefficients for naphthalene in supercritical carbon dioxide at 308.2K was measured by a pseudo steady-state solid dissolution method. The experimental diffusion coefficients were compared with the calculated results by the Darken equation including a thermodynamic factor and tracer diffusion coefficients of supercritical carbon dioxide and naphthalene. The thermodynamic factor in the Darken equation was determined by using several cubic equations of state. The calculated results by the Darken equation represent the concentration dependence of the experimental diffusion coefficients. © 2002 Elsevier Science B.V. All rights reserved

Characterization of human UGT2A3 expression using a prepared specific antibody against UGT2A3

UDP-Glucuronosyltransferase (UGT) 2A3 belongs to a UGT superfamily of phase II drug-metabolizing enzymes that catalyzes the glucuronidation of many endobiotics and xenobiotics. Previous studies have demonstrated that UGT2A3 is expressed in the human liver, small intestine, and kidney at the mRNA level; however, its protein expression has not been determined. Evaluation of the protein expression of UGT2A3 would be useful to determine its role at the tissue level. In this study, we prepared a specific antibody against human UGT2A3 and evaluated the relative expression of UGT2A3 in the human liver, small intestine, and kidney. Western blot analysis indicated that this antibody is specific to UGT2A3 because it did not cross-react with other human UGT isoforms or rodent UGTs. UGT2A3 expression in the human small intestine was higher than that in the liver and kidney. Via treatment with endoglycosidase, it was clearly demonstrated that UGT2A3 was N-glycosylated. UGT2A3 protein levels were significantly correlated with UGT2A3 mRNA levels in a panel of 28 human liver samples (r = 0.64, p <0.001). In conclusion, we successfully prepared a specific antibody against UGT2A3. This antibody would be useful to evaluate the physiological, pharmacological, and toxicological roles of UGT2A3 in human tissues. (C) 2019 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.Peer reviewe

Patched1 Haploinsufficiency Increases Adult Bone Mass and Modulates Gli3 Repressor Activity

SummaryHedgehog (Hh)-Patched1 (Ptch1) signaling plays essential roles in various developmental processes, but little is known about its role in postnatal homeostasis. Here, we demonstrate regulation of postnatal bone homeostasis by Hh-Ptch1 signaling. Ptch1-deficient (Ptch1+/−) mice and patients with nevoid basal cell carcinoma syndrome showed high bone mass in adults. In culture, Ptch1+/− cells showed accelerated osteoblast differentiation, enhanced responsiveness to the runt-related transcription factor 2 (Runx2), and reduced generation of the repressor form of Gli3 (Gli3rep). Gli3rep inhibited DNA binding by Runx2 in vitro, suggesting a mechanism that could contribute to the bone phenotypes seen in the Ptch1 heterozygotes. Moreover, systemic administration of the Hh signaling inhibitor cyclopamine decreased bone mass in adult mice. These data provide evidence that Hh-Ptch1 signaling plays a crucial role in postnatal bone homeostasis and point to Hh-Ptch1 signaling as a potential molecular target for the treatment of osteoporosis