Precisely predicting the 1H and 13C NMR chemical shifts in new types of nerve agents and building spectra database.

Following the recent terrorist attacks using Novichok agents and the subsequent decomposition operations, understanding the chemical structures of nerve agents has become important. To mitigate the ever-evolving threat of new variants, the Organization for the Prohibition of Chemical Weapons has updated the list of Schedule 1 substances defined by the Chemical Weapons Convention. However, owing to the several possible structures for each listed substance, obtaining an exhaustive dataset is almost impossible. Therefore, we propose a nuclear magnetic resonance-based prediction method for 1H and 13C NMR chemical shifts of Novichok agents based on conformational and density functional study calculations. Four organophosphorus compounds and five G- and V-type nerve agents were used to evaluate the accuracy of the proposed procedure. Moreover, 1H and 13C NMR prediction results for an additional 83 Novichok candidates were compiled as a database to aid future research and identification. Further, this is the first study to successfully predict the NMR chemical shifts of Novichok agents, with an exceptional agreement between predicted and experimental data. The conclusions enable the prediction of all possible structures of Novichok agents and can serve as a firm foundation for preparation against future terrorist attacks using new variants of nerve agents.

A superoxide anion generator, pyrogallol, inhibits the growth of HeLa cells via cell cycle arrest and apoptosis.

We investigated the in vitro effects of pyrogallol on cell growth, cell cycle regulation, and apoptosis in HeLa cells. Pyrogallol inhibited the growth of HeLa cells with an IC(50) of approximately 45 microM. Pyrogallol induced arrest during all phases of the cell cycle and also very efficiently resulted in apoptosis in HeLa cells, as evidenced by flow cytometric detection of sub-G1 DNA content, annexin V binding assay, and DAPI staining. This apoptotic process was accompanied by the loss of mitochondrial transmembrane potential (DeltaPsi(m)), Bcl-2 decrease, caspase-3 activation, and PARP cleavage. Pan-caspase inhibitor (Z-VAD) could rescue some HeLa cells from pyrogallol-induced cell death, while caspase-8 and -9 inhibitors unexpectedly enhanced the apoptosis. When we examined the changes of the ROS, H(2)O(2) or O(2)(*-) in pyrogallol-treated cells, H(2)O(2) was slightly increased and O(2)(*-) significantly was increased. In addition, we detected a decreased GSH content in pyrogallol-treated cells. Only pan-caspase inhibitor showing recovery of GSH depletion and reduced intracellular O(2)(*-) level decreased PI staining in pyrogallol-treated HeLa cells, which indicates dead cells. In summary, we have demonstrated that pyrogallol as a generator of ROS, especially O(2) (*-), potently inhibited the growth of HeLa cells through arrests during all phases of the cell cycle and apoptosis.

[A case of Non-Hodgkin's lymphoma in a patient with Crohn's disease].

Although adenocarcinoma is a well known complication of chronic inflammatory bowel disease, primary gastrointestinal lymphoma occurring in Crohn's disease is rare. A 40-year-old man with 10 year-history of Crohn's disease had multiple longitudinal ulcerative lesions on descending colon in follow-up colonoscopic examination. Microscopic examination of proximal descending colon revealed peripheral T cell lymphoma and other site of the descending colon was consistent with Crohn's disease. The patient reached complete remission of malignant lymphoma after three cycles of combined chemotherapy. He has been well for 10 months with sulfasalazine maintenance therapy but was admitted to the hospital due to spontaneous bowel perforation of ascending colon. Right hemicolectomy was done, but the patient died of post-surgical recurrent mesenteric abscess and sepsis. To the best of our knowledge, this is the first case of Non-Hodgkin's lymphoma complicating Crohn's disease in Korea which was confirmed by immunohistochemical studies.