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Sola City Hall
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(Material-mediated Pyrogens)
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1. Kikuchi, Y. et al., Collaborative Study on the Bacterial Endotoxins Test Using Recombinant Factor C-based Procedure for Detection of Lipopoly-saccharides. Pharmaceutical and Medical Device Regulatory Science 48 (4), 252-260 (2017) .
2. Kikuchi, Y. et al., Collaborative Study on the Bacterial Endotoxins Test Using Recombinant Factor C-based Procedure for Detection of Lipopoly-saccharides, Part 2. Pharmaceutical and Medical Device Regulatory Science 49 (10), 706-718 (2018) .
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Chen, J., Low Endotoxin Recovery in Common Biologics Products. Presented at PDA 8th Annual Global Conference on Pharmaceutical Microbiology,
Bethesda, MD, (2013).
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RSE: Reference Standard Endotoxin, CSE: Control Standard Endotoxin, NOE: Naturally Occurring Endotoxin
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LPS LPS
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Work described in Case Study #3, “Use of Purified and Non-purified Endotoxins in Hold-time Studies”, has shown that masking susceptibility depends on the bacterial species and that culture conditions do affect the masking susceptibility of endotoxins. Additionally, this work demonstrated that isolation methods do not alter the primary structure of the lipid A profiles (i.e., lipid A profiles from NOEs are similar to their highly purified counterparts); however, the supramolecular structures of endotoxin may be influenced by the preparation method.
NOE
RSE, CSE
TLR 1/2, 2/6 LTA, LP, etc. TLR 3 Viral double-stranded RNA TLR 4 LPS TLR 5 Bacterial flagellin TLR 7,8 Small synthetic antiviral molecule, RNA TLR 9 CpG DNA
Toll-Like Receptor (TLR) family
LBP LPS
sCD14
TLR4
MD2
TLR4
MD2
TLR2
mCD14 mCD14
PGN
MyD88IRAKTRAF6IKK
NF-κΒ activation
TIR TIRTIR
Induction of inflammatory cytokines such as IL-1, IL-6, TNFα
LTA
Schwarz H, et al. Scientific Report, 7:44750 (2017)
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Endotoxin
β(1,3)-D-glucanFactor C Activated Factor C
Activated Factor G Factor GFactor B
Activated Factor B
Proclotting Enzyme Clotting Enzyme Gelation ����� ���
Boc-Leu-Gly-Arg-pNA � ����
Boc-Leu-Gly-Arg + pNA (OD 405 nm) � ��� � ���
Diazo-coupling (OD 545 nm) � ��� ���� ��
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Endotoxin
β(1,3)-D-glucanFactor C Activated Factor C
Activated Factor G Factor GFactor B
Activated Factor B
Proclotting Enzyme Clotting Enzyme Gelation ����� ���
Boc-Leu-Gly-Arg-pNA � ����
Boc-Leu-Gly-Arg + pNA (OD 405 nm) � ��� � ���
Diazo-coupling (OD 545 nm) � ��� ���� ��
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HCPT
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