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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 | Space in Systems Biology of Signaling Pathways-Towards Intracellular Molecular Crowding in Silico显示文摘 | Takahashi K Arjunan SNV Tomita M | 2005 | FEBS Letters2005，579，8： | 1 |
| 4 | Coronary artery caliber in normal children and patients with kawasaki disease but without aneurysms:an echocardiographic and angiographic study显示文摘 | Arjunan K Daniels SR Mayer RA | 1986 | J AM Coll Cardiol1986，8，： | 1 |
| 5 | 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 |
| 6 | Fourier transform infrared and FT-Raman spectral analysis and ab initio calculations for 4-chloro-2-methylaniline and 4-chloro-3-methylaniline显示文摘 | V. Arjunan S. Mohan | 2008 | Journal of Molecular Structure2008，，1： | 1 |
| 7 | 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 |
| 8 | Effect of silica fume, meta- kaolin and low-calcium fly ash on chemical resistance of concrete 显示文摘 | ROY D M ARJUNAN P SILSBEE M R | 2001 | Cem Coner Res2001，31，12： | 1 |
| 9 | 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 |
| 10 | 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 |
| 11 | Sulfoaluminate-belite cement from low-calcium fly ash and sulfur-rich and other industrial by-products显示文摘 | Arjunan P Silsbee M R | 1999 | Cement and Concrete Research1999，29，： | 1 |
| 12 | Sulfoaluminate-belite cement from low-calcium fly ash and sulfur-rich and other industrial by- products 显示文摘 | Arjunan P Silsbee M R Roy D M | 1999 | Cement and Concrete Research1999，29，8： | 1 |
| 13 | 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 | 2010 | J Exp Med2010，207，4： | 1 |
| 14 | Sulfoaluminate-belite cement from low-calcium fly ash and sulfur-rich and other industrial by-products显示文摘 | Arjunan P Silsbee M R Roy D M | 1999 | Cement and Concrete Research1999，29，8： | 1 |
| 15 | Role of informal care providers in home based long term care in diabetes mellitus at Kaiwara Primary Health Center area, Karnataka, India显示文摘 | Isaac Arjunan D Gopinath NS Murthy | 2011 | Asian Pacific Journal of Tropical Disease2011，，2： | 1 |
| 16 | Degradation of Phenol in Aqueous Solution by Fenton,Sono-Fenton and Sono-photo-Fenton Methods显示文摘 | Arjunan B Karuppan M | 2011 | Clean-Soil Air Water2011，39，2： | 1 |
| 17 | Islands of misfit buildings: Detecting uncharacteristic electricity use behavior using load shape clustering显示文摘Many energy performance analysis methodologies assign buildings a descriptive label that represents their main activity,often known as the primary space usage(PSU).This attribute comes from the intent of the design team based on assumptions of how the majority of the spaces in the building will be used.In reality,the way a building’s occupants use the spaces can be different than what was intended.With the recent growth of hourly electricity meter data from the built environment,there is the opportunity to create unsupervised methods to analyze electricity consumption behavior to understand whether the PSU assigned is accurate.Misclassification or oversimplification of the use of the building is possible using these labels when applied to simulation inputs or benchmarking processes.To work towards accurate characterization of a building’s utilization,we propose a modular methodology for identifying potentially mislabeled buildings using distance-based clustering analysis based on hourly electricity consumption data.This method seeks to segment buildings according to their daily behavior and predict which ones are misfits according to their assigned PSU label.This process finds potentially uncharacteristic behavior that could be an indication of mixed-use or a misclassified PSU.Our results on two public data sets,from the Building Data Genome(BDG)Project and Washington DC(DGS),with 507 and 322 buildings respectively,show that 26%and 33%of these buildings are potentially mislabelled based on their load shape behavior.Such information provides a more realistic insight into their true consumption characteristics,enabling more accurate simulation scenarios.Applications of this process and a discussion of limitations and reproducibility are included. | Matias Quintana Pandarasamy Arjunan Clayton Miller | 2021 | Building Simulation2021，14，1： | 1 |
| 18 | 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 |
| 19 | 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 |
| 20 | 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 |
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