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10.1016/j.smim.2016.05.007 http://scihub22266oqcxt.onion/10.1016/j.smim.2016.05.007 C4987277!4987277 !27282113     free     free     free Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 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\27282113 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Semin+Immunol 2016 ; 28 (3 ): 260-7 Nephropedia Template TP {{tp|p=27282113 |t=2016. New therapeutic and diagnostic opportunities for injured tissue-specific targeting of complement inhibitors and imaging modalities |pdf=|usr=}}{{27282113 }} gab.com Text New therapeutic and diagnostic opportunities for injured tissue-specific targeting of complement inhibitors and imaging modalities JO: Semin Immunol http://www.kidney.de/pget.php?&tw=1&pmid=27282113 #FOAvip Despite substantial opportunity and commercial interest in developing drugs that modulate the complement system in a broad range of non-orphan indications, several obstacles remain to be overcome. Among these issues is the biophysical nature of complement proteins, whose circulating levels are typically very high and whose turnover rates are relatively rapid, especially in the setting of chronic inflammatory conditions. This situation necessitates the use of very high levels of therapeutic compounds in order to achieve both multi-pathway and multiple effector mechanism inhibition. In addition, one must avoid infectious complications or the systemic impairment of the other important physiological functions of complement. Herein we focus on the development of a novel therapeutic strategy based on injured tissue-specific targeting of complement inhibitors using the antigen-combining domains of a small subset of natural IgM antibodies, which as endogenous antibodies specifically recognize sites of local damage across a broad range of tissues and locally activate complement C3, resulting in C3 fragment covalent fixation. Because the use of such recombinant tissue-targeting inhibitors precludes the utility of measuring systemic levels of complement biomarkers or function, since a goal of this targeting strategy is to leave those processes intact and unimpeded, we also briefly describe a new method designed to quantitatively measure using imaging modalities the inhibition of generation of fixed C3 fragments at sites of inflammation/injury. In addition to the ability to determine whether complement activation is locally constrained with the use of inhibitors, there is also a broader application of this imaging approach to inflammatory and autoimmune diseases characterized by local complement activation. Twit Text FOAVip New therapeutic and diagnostic opportunities for injured tissue-specific targeting of complement inhibitors and imaging modalities ????Semin Immunol http://www.kidney.de/pget.php?&tw=1&pmid=27282113 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=27282113 #FOAvip English Wikipedia <ref>{{Cite pmid|27282113 }}</ref> New therapeutic and diagnostic opportunities for injured tissue-specific targeting of complement inhibitors and imaging modalities #MMPMID27282113 Holers VM ; Tomlinson S ; Kulik L ; Atkinson C ; Rohrer B ; Banda N ; Thurman JM Semin Immunol 2016[Jun]; 28 (3 ): 260-7 PMID27282113 show ga Despite substantial opportunity and commercial interest in developing drugs that modulate the complement system in a broad range of non-orphan indications, several obstacles remain to be overcome. Among these issues is the biophysical nature of complement proteins, whose circulating levels are typically very high and whose turnover rates are relatively rapid, especially in the setting of chronic inflammatory conditions. This situation necessitates the use of very high levels of therapeutic compounds in order to achieve both multi-pathway and multiple effector mechanism inhibition. In addition, one must avoid infectious complications or the systemic impairment of the other important physiological functions of complement. Herein we focus on the development of a novel therapeutic strategy based on injured tissue-specific targeting of complement inhibitors using the antigen-combining domains of a small subset of natural IgM antibodies, which as endogenous antibodies specifically recognize sites of local damage across a broad range of tissues and locally activate complement C3, resulting in C3 fragment covalent fixation. Because the use of such recombinant tissue-targeting inhibitors precludes the utility of measuring systemic levels of complement biomarkers or function, since a goal of this targeting strategy is to leave those processes intact and unimpeded, we also briefly describe a new method designed to quantitatively measure using imaging modalities the inhibition of generation of fixed C3 fragments at sites of inflammation/injury. In addition to the ability to determine whether complement activation is locally constrained with the use of inhibitors, there is also a broader application of this imaging approach to inflammatory and autoimmune diseases characterized by local complement activation. |Animals [MESH] |Autoimmunity [MESH] |Complement Activation [MESH] |Complement Inactivating Agents/*therapeutic use [MESH] |Complement System Proteins/*metabolism [MESH] |Diagnostic Imaging [MESH] |Humans [MESH] |Inflammation/*diagnosis/*therapy [MESH] |Molecular Targeted Therapy [MESH]New therapeutic and diagnostic opportunities for injured tissue-specif(epmc).pdf DeepDyve Pubget Overpricing