Ebselen enhances insulin sensitivity and decreases oxidative stress by inhibiting SHIP2 and protects from inflammation in diabetic mice

Ebselen, a multifunctional organoselenium compound, has been recognized as a potential treatment for diabetes-related disorders. However, the underlying mechanisms whereby ebselen regulates metabolic pathways remain elusive. We discovered that ebselen inhibits lipid phosphatase SHIP2 (Src homology 2 domain-containing inositol-5-phosphatase 2), an emerging drug target to ameliorate insulin resistance in diabetes. We found that ebselen directly binds to and inhibits the catalytic activity of the recombinant SHIP2 phosphatase domain and SHIP2 in cultured cells, the skeletal muscle and liver of the diabetic db/db mice, and the liver of the SHIP2 overexpressing (SHIP2-Tg) mice. Ebselen increased insulin-induced Akt phosphorylation in cultured myotubes, enhanced insulin sensitivity and protected liver tissue from lipid peroxidation and inflammation in the db/db mice, and improved glucose tolerance more efficiently than metformin in the SHIP2-Tg mice. SHIP2 overexpression abrogated the ability of ebselen to induce glucose uptake and reduce ROS production in myotubes and blunted the effect of ebselen to inhibit SHIP2 in the skeletal muscle of the SHIP2-Tg mice. Our data reveal ebselen as a potent SHIP2 inhibitor and demonstrate that the ability of ebselen to ameliorate insulin resistance and act as an antioxidant is at least in part mediated by the reduction of SHIP2 activity.Peer reviewe

Endometriosis of the ileum treated by laparoscopic ileocecal resection

A ２９-year-old female was admitted due to abdominal pain. Abdominal computed tomography showed a tumor in terminal ileum and expanded jejunum, and colonoscopy showed a collection of lymph follicles. Biopsy finding showed a lymphoid tissue hyperplasia and no malignant finding. Therefore, we performed a laparoscopic ileocecal resection for diagnosis and treatment. Histopathological findings showed endometrial tissue in the muscular layer, and we diagnosed endometriosis of ileum. We performed a laparoscopic ileocecal resection with lymph node dissection, because the possibility of malignant tumor could not be ruled out. Laparoscopic operation is useful for the diagnosis and treatment of intestinal endometriosis, because it prevents the adhesion and abdominal wall destruction possibly

A autopsy case of biliary fistula to the retroperitoneal space

A seventies age man was admitted complaining of epigastric pain. Computed tomography of the abdomen showed the fluid collection and inflammation in the retroperitoneal space besides pancreas. We suspected acute pancreatitis, and started the treatment by the medications. However, the treatment was not effective. Because we suspected of perforation, we underwent the operation. In the operation, there was a large amount of bile in the retroperitoneal space. We performed intraperitoneal drainage because of uncertain cause. After the operation, he got worse, and died on the ５５th day. The autopsy showed the biliary fistula at right hepatic duct to the retroperitoneal space. The biliary fistula to the retroperitoneal space was very rare case, therefore we must understand the pathological condition due to save the life

Total Synthesis of Decahydroquinoline Poison Frog Alkaloids ent-cis-195A and cis-211A

The total synthesis of two decahydroquinoline poison frog alkaloids ent-cis-195A and cis-211A were achieved in 16 steps (38% overall yield) and 19 steps (31% overall yield), respectively, starting from known compound 1. Both alkaloids were synthesized from the common key intermediate 11 in a divergent fashion, and the absolute stereochemistry of natural cis-211A was determined to be 2R, 4aR, 5R, 6S, and 8aS. Interestingly, the absolute configuration of the parent decahydroquinoline nuclei of cis-211A was the mirror image of that of cis-195A, although both alkaloids were isolated from the same poison frog species, Oophaga (Dendrobates) pumilio, from Panama

Total Synthesis of Decahydroquinoline Poison Frog Alkaloids ent-\u3ci\u3ecis\u3c/i\u3e-195A and \u3ci\u3ecis\u3c/i\u3e-211A

The total synthesis of two decahydroquinoline poison frog alkaloids ent-cis-195A and cis-211A were achieved in 16 steps (38% overall yield) and 19 steps (31% overall yield), respectively, starting from known compound 1. Both alkaloids were synthesized from the common key intermediate 11 in a divergent fashion, and the absolute stereochemistry of natural cis-211A was determined to be 2R, 4aR, 5R, 6S, and 8aS. Interestingly, the absolute configuration of the parent decahydroquinoline nuclei of cis-211A was the mirror image of that of cis-195A, although both alkaloids were isolated from the same poison frog species, Oophaga (Dendrobates) pumilio, from Panama

Theoretical pharmacological effects in single herb and polyherbal therapies : influences of processing on the constituents, and their synergistic/modulatory interactions

漢方方剤やアユルベーダ薬の薬理作用における, 修治, 相乗作用, 組み合わせの科学的根拠を明らかにするため, 著者らによる公表論文の実験データを用いて, 数式による理論化を試みた。The formulations of traditional medicines used in China, India and Japan have been constructed to expect desirable treatment of diseases. The principles are based on the interaction of several crude drugs or several ingredients even in a single crude drug. Therefore, the apparent combined effects are equivalent to the sum of effects of those components which underwent addition, potentiation, subtraction and modulation. Here we provide hypothetical mathematical formulas to explain the theory of combinatorics, which successfully proved the pharmacological effects of processed single herbs and the basis of polyherbal therapies. The constructed formulas will contribute to designing new formulations together with seeking novel patterns of pharmacological actions of traditional medicines or with understanding of the mechanisms behind them