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10.1111/bph.13388 http://scihub22266oqcxt.onion/10.1111/bph.13388 C4728428!4728428 !26565566     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 300.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 300.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 300.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 300.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\26565566 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Br+J+Pharmacol 2016 ; 173 (3 ): 575-87 Nephropedia Template TP {{tp|p=26565566 |t=2016. APT070 (mirococept), a membrane-localizing C3 convertase inhibitor, attenuates early human islet allograft damage in vitro and in vivo in a humanized mouse model |pdf=|usr=}}{{26565566 }} gab.com Text APT070 (mirococept), a membrane-localizing C3 convertase inhibitor, attenuates early human islet allograft damage in vitro and in vivo in a humanized mouse model JO: Br J Pharmacol http://www.kidney.de/pget.php?&tw=1&pmid=26565566 #FOAvip BACKGROUND AND PURPOSE: A major obstacle to islet cell transplantation is the early loss of transplanted islets resulting from the instant blood-mediated inflammation reaction (IBMIR). The activation of complement pathways plays a central role in IBMIR. The aim of this study was to test the inhibitory effect of "painting" human islets with APT070, a membrane-localizing C3 convertase inhibitor, on inflammation evoked by exposure to human serum in vitro and by transplantation in vivo in a humanized diabetic mouse model. EXPERIMENTAL APPROACH: In vitro, human islets pre-incubated with APT070 were exposed to allogeneic whole blood. In vivo, similarly treated islets were transplanted underneath the kidney capsule of streptozotocin-induced diabetic NOD-SCID IL2r?(-/-) mice that had been reconstituted with human CD34(+) stem cells. Complement activation and islet hormone content were assayed using enzyme-linked immunosorbent assays. Supernatants and sera were assayed for cytokines using cytometric beads array. Morphology of the islets incubated with human serum in vitro and in graft-bearing kidney were evaluated using immunofluorescence staining. KEY RESULTS: Pre-incubation with APT070 decreased C-peptide release and iC3b production in vitro, with diminished deposition of C4d and C5b-9 in islets embedded in blood clots. In vivo, the APT070-treated islets maintained intact structure and showed less infiltration of inflammatory cells than untreated islets. The pretreatments also significantly reduced pro-inflammatory cytokines in supernatants and sera. CONCLUSIONS AND IMPLICATIONS: Pre-treatment of islets with APT070 could reduce intra-islet inflammation with accompanying preservation of insulin secretion by beta cells. APT070 could be as a potential therapeutic tool in islet transplantation. Twit Text FOAVip APT070 (mirococept), a membrane-localizing C3 convertase inhibitor, attenuates early human islet allograft damage in vitro and in vivo in a humanized mouse model ????Br J Pharmacol http://www.kidney.de/pget.php?&tw=1&pmid=26565566 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=26565566 #FOAvip English Wikipedia <ref>{{Cite pmid|26565566 }}</ref> APT070 (mirococept), a membrane-localizing C3 convertase inhibitor, attenuates early human islet allograft damage in vitro and in vivo in a humanized mouse model #MMPMID26565566 Xiao F ; Ma L ; Zhao M ; Smith RA ; Huang G ; Jones PM ; Persaud S ; Pingitore A ; Dorling A ; Lechler R ; Lombardi G Br J Pharmacol 2016[Feb]; 173 (3 ): 575-87 PMID26565566 show ga BACKGROUND AND PURPOSE: A major obstacle to islet cell transplantation is the early loss of transplanted islets resulting from the instant blood-mediated inflammation reaction (IBMIR). The activation of complement pathways plays a central role in IBMIR. The aim of this study was to test the inhibitory effect of "painting" human islets with APT070, a membrane-localizing C3 convertase inhibitor, on inflammation evoked by exposure to human serum in vitro and by transplantation in vivo in a humanized diabetic mouse model. EXPERIMENTAL APPROACH: In vitro, human islets pre-incubated with APT070 were exposed to allogeneic whole blood. In vivo, similarly treated islets were transplanted underneath the kidney capsule of streptozotocin-induced diabetic NOD-SCID IL2r?(-/-) mice that had been reconstituted with human CD34(+) stem cells. Complement activation and islet hormone content were assayed using enzyme-linked immunosorbent assays. Supernatants and sera were assayed for cytokines using cytometric beads array. Morphology of the islets incubated with human serum in vitro and in graft-bearing kidney were evaluated using immunofluorescence staining. KEY RESULTS: Pre-incubation with APT070 decreased C-peptide release and iC3b production in vitro, with diminished deposition of C4d and C5b-9 in islets embedded in blood clots. In vivo, the APT070-treated islets maintained intact structure and showed less infiltration of inflammatory cells than untreated islets. The pretreatments also significantly reduced pro-inflammatory cytokines in supernatants and sera. CONCLUSIONS AND IMPLICATIONS: Pre-treatment of islets with APT070 could reduce intra-islet inflammation with accompanying preservation of insulin secretion by beta cells. APT070 could be as a potential therapeutic tool in islet transplantation. |*Islets of Langerhans Transplantation [MESH] |Animals [MESH] |Cells, Cultured [MESH] |Complement C3-C5 Convertases/*antagonists & inhibitors [MESH] |Cytokines/blood/metabolism [MESH] |Humans [MESH] |Interleukin Receptor Common gamma Subunit/genetics [MESH] |Islets of Langerhans/*drug effects/metabolism [MESH] |Mice, Inbred NOD [MESH] |Mice, Knockout [MESH] |Mice, SCID [MESH]APT070 (mirococept), a membrane-localizing C3 convertase inhibitor, at(epmc).pdf DeepDyve Pubget Overpricing