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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 | Rapid techniques for determination of free lime and free magnesia in cement clinker and portlandite in hydrates 显示文摘 | Arjunan P Kumar A | 1994 | Cement and Concrete Research1994，24，2： | 1 |
| 3 | Improved free-standing GaN schot- tky diode characteristics using chemical mechanical pol- ishing显示文摘 | Arjunan A C Singh D | 2008 | Applied Science2008，255，： | 1 |
| 4 | Improved free-standing GaN schottky diode characteristics using chemical mechanical polishing 显示文摘 | ARJUNAN A C SINGH D | 2008 | Applied Science2008，255，： | 1 |
| 5 | Direct and controllable nitric oxide delivery into biological media and living cells by a pin-to-hole spark discharge (PHD) plasma显示文摘 | Dobrynin D Arjunan K Fridman A | 2011 | Journal of Physics D: Applied Physics2011，44，07： | 1 |
| 6 | Existence results for an impulsive neutral functional differential equation with state-dependent delay显示文摘 | Anguraj A Arjunan M M Hernández E | 2007 | Appl Anal2007，86，7： | 1 |
| 7 | Existence results for impulsive neutral functional differential equations with infinite delay显示文摘 | Chang Y K Anguraj A Arjunan M M | 2008 | Nonlinear Anal HS2008，2，1： | 1 |
| 8 | Existence results for non-densely defined neutral differential inclusions with nonlocal conditions显示文摘 | Chang Y K Anguraj A Arjunan M M | 2008 | J Appl Math Comput2008，28，12： | 1 |
| 9 | 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 |
| 10 | Existence results for an impulsive neutral functional differential equation with state-dependent delay 显示文摘 | Anguraj A Arjunan M M Hernandez E | 2007 | Appl Anal2007，86，7： | 1 |
| 11 | Existence results for impulsive neutral functional differential equations with infinite delay 显示文摘 | Chang Y K Anguraj A Arjunan M M | 2008 | Nonlinear Anal HS2008，2，1： | 1 |
| 12 | 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 |
| 13 | Existence results for non-densely defined neutral differential inclusions with nonlocal conditions 显示文摘 | Chang Y K Anguraj A Arjunan M M | 2008 | J Appl Math Comput2008，28，： | 1 |
| 14 | 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 |
| 15 | Rapid techniques for determination of free lime and free magnesia in cement clinker and portlandite in hydrates显示文摘 | Arjunan P Kumar A | 1994 | Cement and Concrete Research1994，24，2： | 1 |
| 16 | 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 |
| 17 | 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 |
| 18 | Existence results for an impulsive neutral functional differential equation with state-dependent delay显示文摘 | Anguraj A Mallika Arjunan M E Hernández M | | 0，，： | 1 |
| 19 | Rapid techniques for determination of free lime and free magnesia in cement clinker and portlandite in hydrates 显示文摘 | Arjunan P Kumar A | 1994 | Cem Concr Res1994，24，2： | 1 |
| 20 | Survival effect of PDGF-CC rescues neurons from apoptosis in both brain and retina by regulating GSK3beta phosphorylation显示文摘 | Tang Z Arjunan P Lee C Li Y Ktmar A Hou X | | 0，，04： | 1 |
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