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| 1 | Plecanatide and dolcanatide, novel guanylate cyclase-C agonists, ameliorate gastrointestinal inflammation in experimental models of murine colitis显示文摘AIM: To evaluate the effect of orally administeredplecanatide or dolcanatide, analogs of uroguanylin, on amelioration of colitis in murine models.METHODS: The cyclic guanosine monophosphate(cG MP) stimulatory potency of plecanatide and dolcanatide was measured using a human colon carcinoma T84 cellbased assay. For animal studies all test agents were formulated in phosphate buffered saline. Sulfasalazine or 5-amino salicylic acid(5-ASA) served as positive controls. Effect of oral treatment with test agents on amelioration of acute colitis induced either by dextran sulfate sodium(DSS) in drinking water or by rectal instillation of trinitrobenzene sulfonic(TNBS) acid, was examined in BALB/c and/or BDF1 mice. Additionally, the effect of orally administered plecanatide on the spontaneous colitis in T-cell receptor alpha knockout(TCRα-/-) mice was also examined. Amelioration of colitis was assessed by monitoring severity of colitis, disease activity index and by histopathology. Frozen colon tissues were used to measure myeloperoxidase activity.RESULTS: Plecanatide and dolcanatide are structurally related analogs of uroguanylin, which is an endogenous ligand of guanylate cyclase-C(GC-C). As expected from the agonists of GC-C, both plecanatide and dolcanatide exhibited potent cG MP-stimulatory activity in T84 cells. Once-daily treatment by oral gavage with either of these analogs(0.05-0.5 mg/kg) ameliorated colitis in both DSS and TNBS-induced models of acute colitis, as assessed by body weight, reduction in colitis severity(P < 0.05) and disease activity index(P < 0.05). Amelioration of colitis by either of the drug candidates was comparable to that achieved by orally administered sulfasalazine or 5-ASA. Plecanatide also effectively ameliorated colitis in TCRα-/- mice, a model of spontaneous colitis. As dolcanatide exhibited higher resistance to proteolysis in simulated gastric and intestinal juices, it was selected for further studies. CONCLUSION: This is the first-ever study reporting the therapeutic utility of GC-C agonists as a new class of orally delivered and mucosally active drug candidates for the treatment of inflammatory bowel diseases. | Kunwar Shailubhai Vaseem Palejwala Krishna Priya Arjunan Sayali Saykhedkar Bradley Nefsky John A Foss Stephen Comiskey Gary S Jacob Scott E Plevy | 2015 | World Journal of Gastrointestinal Pharmacology and Therapeutics2015，6，4： | 5 |
| 2 | Village-wide effects of agricultural biotechnology: The case of Bt cotton in India显示文摘 | ARJUNAN S MATIN Q | 2009 | World De- velopment2009，37，1： | 1 |
| 3 | A three-degrees-of-freedom micromotion In-parallel actuated manipulator 显示文摘 | LEE K M ARJUNAN S | 1991 | IEEE Trans Rob Autom1991，17，5： | 1 |
| 4 | A three degree of freedom micromotion in parallel actuated manipulator显示文摘 | Lee K M Arjunan S | 1991 | IEEE Trans on Robotics and Automation Design1991，7，5： | 1 |
| 5 | Towards classification of low-level finger movements using forearm muscle activation: a comparative study based on ICA and fractal theory显示文摘 | Naik G R Kumar D K and Arjunan S P | 2011 | International Journal of Biomedical Engineering and Technology2011，6，2： | 1 |
| 6 | Applications of ICA and fractal dimension in sEMG signal processing for subtle movement analysis:a review显示文摘 | Naik GR Arjunan S Kumar D | 2011 | Australasian Physical & Engineering Sciences in Medicine2011，34，2： | 1 |
| 7 | 显示文摘 | Arjunan T V Senthil T S | 2013 | Materials Technology2013，28，2： | 1 |
| 8 | Tolerance in rice (Oryza sativa L) in relation to salt uptake and yield 显示文摘 | ARJUNAN A CHABDRASEKARAN S | 1988 | Indian J Plant Physiol1988，16，4： | 1 |
| 9 | Vibrational and electronic investigations, thermodynamic parameters, HOMO and LUMO analysis on erotonaldehyde by ab initio and DFT methods 显示文摘 | Jayaprakash A Arjunan V Jose S P Mohan S | 2011 | Spectroehimica Aeta Part A: Molecular and Biomolecular Spectroscopy2011，83，： | 1 |
| 10 | Sulfoaluminate-belite cement from low-calcium fly ash and sulfur-rich and other industrial by-products 显示文摘 | Arjunan P Michael R S Della M R | 1999 | Cement and Concrete Research1999，29，8： | 1 |
| 11 | Coronary artery caliberin normal children and patients with Kawasaki disease but without aneurysms: An echocardiographic and angiographicstudy显示文摘 | Arjunan K Daniels S R Mayer R A | 1986 | J Am Coll Cardiol1986，8，： | 1 |
| 12 | Relationship betweengrain yield and flag leaf angle in rice显示文摘 | Sadasivam R Arjunan A Mohandass S | 1989 | Intern Rice Res Newsl1989，14，4： | 1 |
| 13 | A 3 - DOF micromotion in - parallel act uated ma- nipulator显示文摘 | Lee K H Arjunan s | 1991 | Robot and Automotion1991，7，5： | 1 |
| 14 | Towards classification of low-level finger movements using forearm muscle activation: A comparative study based on ICA and Fractal theory 显示文摘 | Naik G R Kumar D K Arjunan S P | 2011 | Int J Biomed Eng Techno12011，6，2： | 1 |
| 15 | Superhydrophohic polytetrafluoroethylene thin fihns with hierarchical roughness deposited using a single step vapor phase technique 显示文摘 | Gupta S Arjunan A Deshpande S | 2009 | Thin Solid Films2009，517，16： | 1 |
| 16 | A three-degrees-of-freedom micromotion in-parallel actuated manipulator显示文摘 | LEE K M ARJUNAN S | 1991 | IEEE Transactions on Robotics and Automation1991，7，5： | 1 |
| 17 | Fractal Properties of SurfaceElectromyogram for Classification of Low Level Hand Movementsfrom Single-Channel Forearm Muscle Activity 显示文摘 | Arjunan S P Kumar D K | 2011 | Journal ofMechanics in Medicine and Biology2011，11，3： | 1 |
| 18 | Fractal properties of surface electromyo gram for classification of low level hand movements from single- channel forearm muscle activity 显示文摘 | Arjunan S P Kumar D K | 2011 | Journal of Mechanics in Medi cine and Biology2011，11，3： | 1 |
| 19 | Novel binding motif and new flexibility revealed by structural analyses of a pyruvate dehydrogenase-dihydrolipoyl acetyltransferase subcomplex from the Escherichia coli pyruvate dehydrogenase multienzyme complex显示文摘 | Arjunan P Wang J Nemeria N S | 2014 | J Biol Chem2014，289，30： | 1 |
| 20 | A dynamic loop at the active center of the Escherichia coli pyruvate dehydrogenase complex E1 component modulates substrate utilization and chemical communication with the E2 component显示文摘 | Kale S Arjunan P Furey W | 2007 | J Biol Chem2007，282，28： | 1 |
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