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10.1136/lupus-2015-000121 http://scihub22266oqcxt.onion/10.1136/lupus-2015-000121 C4691954!4691954 !26719810     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=26719810 &cmd=llinks): Failed to open stream: HTTP request failed! 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Pharmacodynamic monitoring of (immuno)proteasome inhibition during bortezomib treatment of a critically ill patient with lupus nephritis and myocarditis |pdf=|usr=}}{{26719810 }} gab.com Text Pharmacodynamic monitoring of (immuno)proteasome inhibition during bortezomib treatment of a critically ill patient with lupus nephritis and myocarditis JO: Lupus Sci Med http://www.kidney.de/pget.php?&tw=1&pmid=26719810 #FOAvip OBJECTIVE: To describe the pharmacodynamic monitoring of (immuno)proteasome inhibition following treatment with bortezomib in a therapy-refractory systemic lupus erythematosus (SLE) patient with life-threatening myocarditis and lupus nephritis. PATIENT AND METHODS: Inhibition of catalytic activities of the proteasome subunits ?5 (constitutive proteasome), ?5i and ?1i (immunoproteasome) were measured in peripheral blood mononuclear cells using subunit-specific fluorogenic peptide substrates in a patient who received three cycles of bortezomib (1.3?mg/m(2) subcutaneously, days 1, 4, 8 and 11; every three?weeks) along with plasma exchange during the first two cycles. RESULTS: Proteasome ?5, ?5i and ?1i subunit activities were readily inhibited 1?h after bortezomib administration. Twenty-four hours post-bortezomib administration, ?5 and ?5i activities were largely restored, whereas inhibition of ?1i activity was sustained. Clinically, after three cycles, cardiac function had improved, with concurrent improvement of haemodynamic stability during haemodialysis. Anti-ds-DNA dropped from >400 to 12?IU/mL along with normalisation of complement C3 and C4. Bortezomib therapy was well tolerated, and patient now has a sustained remission for >16?months. CONCLUSIONS: This case illustrates the potential benefit of pharmacodynamic monitoring of (immune)proteasome subunit-specific activity after bortezomib dosing in patients with therapy refractory SLE. This tool may hold potential to guide personalised/precision dosing aiming to achieve maximal efficacy and minimal toxicity. Twit Text FOAVip Pharmacodynamic monitoring of (immuno)proteasome inhibition during bortezomib treatment of a critically ill patient with lupus nephritis and myocarditis ????Lupus Sci Med http://www.kidney.de/pget.php?&tw=1&pmid=26719810 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=26719810 #FOAvip English Wikipedia <ref>{{Cite pmid|26719810 }}</ref> Pharmacodynamic monitoring of (immuno)proteasome inhibition during bortezomib treatment of a critically ill patient with lupus nephritis and myocarditis #MMPMID26719810 de Groot KA ; Tsang A Sjoe M ; Niewerth D ; Cloos J ; Blank JL ; Niessen HW ; Zweegman S ; Voskuyl AE ; Jansen G ; van der Heijden JW Lupus Sci Med 2015[]; 2 (1 ): e000121 PMID26719810 show ga OBJECTIVE: To describe the pharmacodynamic monitoring of (immuno)proteasome inhibition following treatment with bortezomib in a therapy-refractory systemic lupus erythematosus (SLE) patient with life-threatening myocarditis and lupus nephritis. PATIENT AND METHODS: Inhibition of catalytic activities of the proteasome subunits ?5 (constitutive proteasome), ?5i and ?1i (immunoproteasome) were measured in peripheral blood mononuclear cells using subunit-specific fluorogenic peptide substrates in a patient who received three cycles of bortezomib (1.3?mg/m(2) subcutaneously, days 1, 4, 8 and 11; every three?weeks) along with plasma exchange during the first two cycles. RESULTS: Proteasome ?5, ?5i and ?1i subunit activities were readily inhibited 1?h after bortezomib administration. Twenty-four hours post-bortezomib administration, ?5 and ?5i activities were largely restored, whereas inhibition of ?1i activity was sustained. Clinically, after three cycles, cardiac function had improved, with concurrent improvement of haemodynamic stability during haemodialysis. Anti-ds-DNA dropped from >400 to 12?IU/mL along with normalisation of complement C3 and C4. Bortezomib therapy was well tolerated, and patient now has a sustained remission for >16?months. CONCLUSIONS: This case illustrates the potential benefit of pharmacodynamic monitoring of (immune)proteasome subunit-specific activity after bortezomib dosing in patients with therapy refractory SLE. This tool may hold potential to guide personalised/precision dosing aiming to achieve maximal efficacy and minimal toxicity. äPharmacodynamic monitoring of (immuno)proteasome inhibition during bor(epmc).pdf DeepDyve Pubget Overpricing