SG175133A1

SG175133A1 - Methods of treating edema related to ischemia-reperfusion

Methods of treating edema related to ischemia-reperfusion Download PDF

Info

Publication number: SG175133A1
Authority: SG; Singapore
Prior art keywords: tissue; compound; ischemia; transplant; reperfusion
Prior art date: 2009-04-09

Application number

SG2011073475A

Other languages

English (en)

Inventor

Thomas Michael Egan

Original Assignee

Univ North Carolina

Priority date

2009-04-09

Filing date

2010-04-09

Publication date

2011-12-29

2010-04-09 Application filed by Univ North Carolina filed Critical Univ North Carolina

2011-12-29 Publication of SG175133A1 publication Critical patent/SG175133A1/en

Links

238000000034 method Methods 0.000 title claims abstract description 103
206010030113 Oedema Diseases 0.000 title claims abstract description 87
208000028867 ischemia Diseases 0.000 title claims abstract description 84
210000000056 organ Anatomy 0.000 claims abstract description 77
229910019142 PO4 Inorganic materials 0.000 claims abstract description 7
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims abstract description 7
239000010452 phosphate Substances 0.000 claims abstract description 7
125000004103 aminoalkyl group Chemical group 0.000 claims abstract description 4
150000008271 glucosaminides Chemical class 0.000 claims abstract description 4
210000001519 tissue Anatomy 0.000 claims description 141
150000001875 compounds Chemical class 0.000 claims description 139
210000004072 lung Anatomy 0.000 claims description 138
108010060804 Toll-Like Receptor 4 Proteins 0.000 claims description 91
102100039360 Toll-like receptor 4 Human genes 0.000 claims description 91
230000010410 reperfusion Effects 0.000 claims description 53
150000003839 salts Chemical class 0.000 claims description 53
102000008228 Toll-like receptor 2 Human genes 0.000 claims description 40
108010060888 Toll-like receptor 2 Proteins 0.000 claims description 40
125000000217 alkyl group Chemical group 0.000 claims description 40
125000002252 acyl group Chemical group 0.000 claims description 31
239000005557 antagonist Substances 0.000 claims description 24
210000002027 skeletal muscle Anatomy 0.000 claims description 16
238000001356 surgical procedure Methods 0.000 claims description 16
241000282414 Homo sapiens Species 0.000 claims description 14
239000003761 preservation solution Substances 0.000 claims description 12
210000004872 soft tissue Anatomy 0.000 claims description 12
210000004185 liver Anatomy 0.000 claims description 11
210000002216 heart Anatomy 0.000 claims description 10
229910052739 hydrogen Inorganic materials 0.000 claims description 10
230000002829 reductive effect Effects 0.000 claims description 10
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 9
210000003734 kidney Anatomy 0.000 claims description 9
230000010412 perfusion Effects 0.000 claims description 9
230000010247 heart contraction Effects 0.000 claims description 7
210000004556 brain Anatomy 0.000 claims description 6
238000007675 cardiac surgery Methods 0.000 claims description 6
230000000302 ischemic effect Effects 0.000 claims description 6
230000000399 orthopedic effect Effects 0.000 claims description 6
210000000496 pancreas Anatomy 0.000 claims description 6
210000003491 skin Anatomy 0.000 claims description 6
210000003205 muscle Anatomy 0.000 claims description 5
208000010125 myocardial infarction Diseases 0.000 claims description 5
210000004923 pancreatic tissue Anatomy 0.000 claims description 4
210000001147 pulmonary artery Anatomy 0.000 claims description 4
210000005013 brain tissue Anatomy 0.000 claims description 3
210000003492 pulmonary vein Anatomy 0.000 claims description 3
210000005003 heart tissue Anatomy 0.000 claims description 2
210000005228 liver tissue Anatomy 0.000 claims description 2
210000005084 renal tissue Anatomy 0.000 claims description 2
241000699670 Mus sp. Species 0.000 description 87
239000000203 mixture Substances 0.000 description 31
PRIXXGNJDNLMBH-DPGPRPECSA-N (2s)-2-[[(3r)-3-hexanoyloxytetradecanoyl]amino]-3-[(2r,3r,4r,5s,6r)-3-[[(3r)-3-hexanoyloxytetradecanoyl]amino]-4-[(3r)-3-hexanoyloxytetradecanoyl]oxy-6-(hydroxymethyl)-5-phosphonooxyoxan-2-yl]oxypropanoic acid Chemical compound CCCCCCCCCCC[C@@H](OC(=O)CCCCC)CC(=O)N[C@H](C(O)=O)CO[C@@H]1O[C@H](CO)[C@@H](OP(O)(O)=O)[C@H](OC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCC)[C@H]1NC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCC PRIXXGNJDNLMBH-DPGPRPECSA-N 0.000 description 25
230000000694 effects Effects 0.000 description 25
230000004913 activation Effects 0.000 description 22
210000001132 alveolar macrophage Anatomy 0.000 description 21
108010057466 NF-kappa B Proteins 0.000 description 20
102000003945 NF-kappa B Human genes 0.000 description 20
230000002950 deficient Effects 0.000 description 20
-1 Phospho Chemical class 0.000 description 19
125000003118 aryl group Chemical group 0.000 description 19
206010063837 Reperfusion injury Diseases 0.000 description 18
208000012947 ischemia reperfusion injury Diseases 0.000 description 18
210000004027 cell Anatomy 0.000 description 17
239000002158 endotoxin Substances 0.000 description 15
241001465754 Metazoa Species 0.000 description 14
229920006008 lipopolysaccharide Polymers 0.000 description 14
238000009472 formulation Methods 0.000 description 13
239000000243 solution Substances 0.000 description 13
238000011746 C57BL/6J (JAX™ mouse strain) Methods 0.000 description 12
239000008194 pharmaceutical composition Substances 0.000 description 12
102000005962 receptors Human genes 0.000 description 12
108020003175 receptors Proteins 0.000 description 12
102000002689 Toll-like receptor Human genes 0.000 description 11
108020000411 Toll-like receptor Proteins 0.000 description 11
150000002772 monosaccharides Chemical class 0.000 description 11
241000699666 Mus <mouse, genus> Species 0.000 description 10
206010037423 Pulmonary oedema Diseases 0.000 description 10
210000001185 bone marrow Anatomy 0.000 description 10
125000004432 carbon atom Chemical group C* 0.000 description 10
108090000623 proteins and genes Proteins 0.000 description 10
230000002685 pulmonary effect Effects 0.000 description 10
238000002054 transplantation Methods 0.000 description 10
239000003446 ligand Substances 0.000 description 9
210000004738 parenchymal cell Anatomy 0.000 description 9
239000002245 particle Substances 0.000 description 9
102000004169 proteins and genes Human genes 0.000 description 9
241000282412 Homo Species 0.000 description 8
102000043136 MAP kinase family Human genes 0.000 description 8
108091054455 MAP kinase family Proteins 0.000 description 8
102000010168 Myeloid Differentiation Factor 88 Human genes 0.000 description 8
108010077432 Myeloid Differentiation Factor 88 Proteins 0.000 description 8
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
125000002947 alkylene group Chemical group 0.000 description 8
230000017531 blood circulation Effects 0.000 description 8
230000006378 damage Effects 0.000 description 8
LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 8
125000002887 hydroxy group Chemical group [H]O* 0.000 description 8
208000014674 injury Diseases 0.000 description 8
239000002953 phosphate buffered saline Substances 0.000 description 8
208000005333 pulmonary edema Diseases 0.000 description 8
239000007787 solid Substances 0.000 description 8
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
102100029064 Serine/threonine-protein kinase WNK1 Human genes 0.000 description 7
208000027418 Wounds and injury Diseases 0.000 description 7
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
125000000547 substituted alkyl group Chemical group 0.000 description 7
239000000725 suspension Substances 0.000 description 7
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 6
108091003079 Bovine Serum Albumin Proteins 0.000 description 6
102000003855 L-lactate dehydrogenase Human genes 0.000 description 6
108700023483 L-lactate dehydrogenases Proteins 0.000 description 6
241000124008 Mammalia Species 0.000 description 6
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
206010069351 acute lung injury Diseases 0.000 description 6
201000000028 adult respiratory distress syndrome Diseases 0.000 description 6
239000000556 agonist Substances 0.000 description 6
238000000540 analysis of variance Methods 0.000 description 6
230000015572 biosynthetic process Effects 0.000 description 6
238000011161 development Methods 0.000 description 6
230000018109 developmental process Effects 0.000 description 6
239000012091 fetal bovine serum Substances 0.000 description 6
239000012530 fluid Substances 0.000 description 6
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 6
229910052760 oxygen Inorganic materials 0.000 description 6
238000010186 staining Methods 0.000 description 6
125000003107 substituted aryl group Chemical group 0.000 description 6
206010001052 Acute respiratory distress syndrome Diseases 0.000 description 5
108090000331 Firefly luciferases Proteins 0.000 description 5
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
102000019145 JUN kinase activity proteins Human genes 0.000 description 5
241001529936 Murinae Species 0.000 description 5
208000013616 Respiratory Distress Syndrome Diseases 0.000 description 5
208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 5
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
238000005516 engineering process Methods 0.000 description 5
210000003414 extremity Anatomy 0.000 description 5
239000003112 inhibitor Substances 0.000 description 5
239000002502 liposome Substances 0.000 description 5
239000007788 liquid Substances 0.000 description 5
210000004925 microvascular endothelial cell Anatomy 0.000 description 5
239000001301 oxygen Substances 0.000 description 5
102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 description 5
244000052769 pathogen Species 0.000 description 5
230000035699 permeability Effects 0.000 description 5
YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 5
230000000638 stimulation Effects 0.000 description 5
239000000126 substance Substances 0.000 description 5
125000003396 thiol group Chemical class [H]S* 0.000 description 5
239000003981 vehicle Substances 0.000 description 5
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
101150116940 AGPS gene Proteins 0.000 description 4
108010088751 Albumins Proteins 0.000 description 4
102000009027 Albumins Human genes 0.000 description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
102000004127 Cytokines Human genes 0.000 description 4
108090000695 Cytokines Proteins 0.000 description 4
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
MSFSPUZXLOGKHJ-UHFFFAOYSA-N Muraminsaeure Natural products OC(=O)C(C)OC1C(N)C(O)OC(CO)C1O MSFSPUZXLOGKHJ-UHFFFAOYSA-N 0.000 description 4
108010013639 Peptidoglycan Proteins 0.000 description 4
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
241000282887 Suidae Species 0.000 description 4
206010051379 Systemic Inflammatory Response Syndrome Diseases 0.000 description 4
239000002253 acid Substances 0.000 description 4
239000000443 aerosol Substances 0.000 description 4
125000003545 alkoxy group Chemical group 0.000 description 4
125000004429 atom Chemical group 0.000 description 4
239000002585 base Substances 0.000 description 4
230000008901 benefit Effects 0.000 description 4
230000004071 biological effect Effects 0.000 description 4
210000004369 blood Anatomy 0.000 description 4
239000008280 blood Substances 0.000 description 4
150000007942 carboxylates Chemical class 0.000 description 4
239000003795 chemical substances by application Substances 0.000 description 4
USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 4
DMBHHRLKUKUOEG-UHFFFAOYSA-N diphenylamine Chemical compound C=1C=CC=CC=1NC1=CC=CC=C1 DMBHHRLKUKUOEG-UHFFFAOYSA-N 0.000 description 4
201000010099 disease Diseases 0.000 description 4
238000002474 experimental method Methods 0.000 description 4
125000000524 functional group Chemical group 0.000 description 4
150000002337 glycosamines Chemical class 0.000 description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
208000015181 infectious disease Diseases 0.000 description 4
238000001802 infusion Methods 0.000 description 4
230000002401 inhibitory effect Effects 0.000 description 4
238000001990 intravenous administration Methods 0.000 description 4
239000000463 material Substances 0.000 description 4
230000001404 mediated effect Effects 0.000 description 4
210000000066 myeloid cell Anatomy 0.000 description 4
238000004321 preservation Methods 0.000 description 4
230000019491 signal transduction Effects 0.000 description 4
239000011780 sodium chloride Substances 0.000 description 4
230000035899 viability Effects 0.000 description 4
108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
102000040650 (ribonucleotides)n+m Human genes 0.000 description 3
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
241000271566 Aves Species 0.000 description 3
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
239000005089 Luciferase Substances 0.000 description 3
MQUQNUAYKLCRME-INIZCTEOSA-N N-tosyl-L-phenylalanyl chloromethyl ketone Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N[C@H](C(=O)CCl)CC1=CC=CC=C1 MQUQNUAYKLCRME-INIZCTEOSA-N 0.000 description 3
101150091206 Nfkbia gene Proteins 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
208000006011 Stroke Diseases 0.000 description 3
241000282898 Sus scrofa Species 0.000 description 3
238000009825 accumulation Methods 0.000 description 3
125000003342 alkenyl group Chemical group 0.000 description 3
150000001412 amines Chemical class 0.000 description 3
230000000845 anti-microbial effect Effects 0.000 description 3
JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 3
230000008512 biological response Effects 0.000 description 3
210000004204 blood vessel Anatomy 0.000 description 3
239000000872 buffer Substances 0.000 description 3
125000002091 cationic group Chemical group 0.000 description 3
210000000038 chest Anatomy 0.000 description 3
230000002860 competitive effect Effects 0.000 description 3
208000035475 disorder Diseases 0.000 description 3
239000002552 dosage form Substances 0.000 description 3
239000003937 drug carrier Substances 0.000 description 3
239000003995 emulsifying agent Substances 0.000 description 3
239000006274 endogenous ligand Substances 0.000 description 3
230000003511 endothelial effect Effects 0.000 description 3
230000006870 function Effects 0.000 description 3
230000014509 gene expression Effects 0.000 description 3
239000001257 hydrogen Substances 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
238000012744 immunostaining Methods 0.000 description 3
150000002632 lipids Chemical class 0.000 description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
239000000178 monomer Substances 0.000 description 3
230000001473 noxious effect Effects 0.000 description 3
238000012758 nuclear staining Methods 0.000 description 3
230000003287 optical effect Effects 0.000 description 3
238000007427 paired t-test Methods 0.000 description 3
230000037361 pathway Effects 0.000 description 3
239000003755 preservative agent Substances 0.000 description 3
238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 3
241000894007 species Species 0.000 description 3
229910052717 sulfur Inorganic materials 0.000 description 3
239000003656 tris buffered saline Substances 0.000 description 3
238000011870 unpaired t-test Methods 0.000 description 3
238000001262 western blot Methods 0.000 description 3
YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 description 2
241000272517 Anseriformes Species 0.000 description 2
241000894006 Bacteria Species 0.000 description 2
COXVTLYNGOIATD-HVMBLDELSA-N CC1=C(C=CC(=C1)C1=CC(C)=C(C=C1)\N=N\C1=C(O)C2=C(N)C(=CC(=C2C=C1)S(O)(=O)=O)S(O)(=O)=O)\N=N\C1=CC=C2C(=CC(=C(N)C2=C1O)S(O)(=O)=O)S(O)(=O)=O Chemical compound CC1=C(C=CC(=C1)C1=CC(C)=C(C=C1)\N=N\C1=C(O)C2=C(N)C(=CC(=C2C=C1)S(O)(=O)=O)S(O)(=O)=O)\N=N\C1=CC=C2C(=CC(=C(N)C2=C1O)S(O)(=O)=O)S(O)(=O)=O COXVTLYNGOIATD-HVMBLDELSA-N 0.000 description 2
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 2
241000283086 Equidae Species 0.000 description 2
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical group C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 2
239000005977 Ethylene Chemical group 0.000 description 2
206010015866 Extravasation Diseases 0.000 description 2
108010067306 Fibronectins Proteins 0.000 description 2
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
239000007995 HEPES buffer Substances 0.000 description 2
WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 2
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
206010061218 Inflammation Diseases 0.000 description 2
102000015271 Intercellular Adhesion Molecule-1 Human genes 0.000 description 2
108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 description 2
108060001084 Luciferase Proteins 0.000 description 2
MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 2
MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
REFJWTPEDVJJIY-UHFFFAOYSA-N Quercetin Chemical compound C=1C(O)=CC(O)=C(C(C=2O)=O)C=1OC=2C1=CC=C(O)C(O)=C1 REFJWTPEDVJJIY-UHFFFAOYSA-N 0.000 description 2
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
239000012980 RPMI-1640 medium Substances 0.000 description 2
239000008156 Ringer's lactate solution Substances 0.000 description 2
239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 2
241000282849 Ruminantia Species 0.000 description 2
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
229920002472 Starch Polymers 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 2
102100040247 Tumor necrosis factor Human genes 0.000 description 2
241000251539 Vertebrata <Metazoa> Species 0.000 description 2
230000001154 acute effect Effects 0.000 description 2
239000000654 additive Substances 0.000 description 2
230000001464 adherent effect Effects 0.000 description 2
125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
125000000278 alkyl amino alkyl group Chemical group 0.000 description 2
125000003282 alkyl amino group Chemical group 0.000 description 2
125000004414 alkyl thio group Chemical group 0.000 description 2
230000004075 alteration Effects 0.000 description 2
239000000427 antigen Substances 0.000 description 2
102000036639 antigens Human genes 0.000 description 2
108091007433 antigens Proteins 0.000 description 2
238000013459 approach Methods 0.000 description 2
PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 2
125000006615 aromatic heterocyclic group Chemical group 0.000 description 2
125000003710 aryl alkyl group Chemical group 0.000 description 2
125000002102 aryl alkyloxo group Chemical group 0.000 description 2
125000005110 aryl thio group Chemical group 0.000 description 2
125000004104 aryloxy group Chemical group 0.000 description 2
238000003556 assay Methods 0.000 description 2
UPABQMWFWCMOFV-UHFFFAOYSA-N benethamine Chemical compound C=1C=CC=CC=1CNCCC1=CC=CC=C1 UPABQMWFWCMOFV-UHFFFAOYSA-N 0.000 description 2
RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 2
239000012965 benzophenone Substances 0.000 description 2
SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 2
MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 2
239000001045 blue dye Substances 0.000 description 2
210000000988 bone and bone Anatomy 0.000 description 2
229910052791 calcium Inorganic materials 0.000 description 2
239000011575 calcium Substances 0.000 description 2
ZEWYCNBZMPELPF-UHFFFAOYSA-J calcium;potassium;sodium;2-hydroxypropanoic acid;sodium;tetrachloride Chemical compound [Na].[Na+].[Cl-].[Cl-].[Cl-].[Cl-].[K+].[Ca+2].CC(O)C(O)=O ZEWYCNBZMPELPF-UHFFFAOYSA-J 0.000 description 2
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
229910052799 carbon Inorganic materials 0.000 description 2
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
238000004113 cell culture Methods 0.000 description 2
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 2
229960001231 choline Drugs 0.000 description 2
230000000295 complement effect Effects 0.000 description 2
239000006184 cosolvent Substances 0.000 description 2
125000004122 cyclic group Chemical group 0.000 description 2
238000000326 densiometry Methods 0.000 description 2
238000001514 detection method Methods 0.000 description 2
125000004663 dialkyl amino group Chemical group 0.000 description 2
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 2
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
210000002889 endothelial cell Anatomy 0.000 description 2
230000007613 environmental effect Effects 0.000 description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 2
229960003699 evans blue Drugs 0.000 description 2
230000036251 extravasation Effects 0.000 description 2
239000012634 fragment Substances 0.000 description 2
239000007789 gas Substances 0.000 description 2
239000000499 gel Substances 0.000 description 2
229960002442 glucosamine Drugs 0.000 description 2
MSWZFWKMSRAUBD-IVMDWMLBSA-N glucosamine group Chemical group OC1[C@H](N)[C@@H](O)[C@H](O)[C@H](O1)CO MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 2
235000011187 glycerol Nutrition 0.000 description 2
229910052736 halogen Inorganic materials 0.000 description 2
125000001475 halogen functional group Chemical group 0.000 description 2
150000002367 halogens Chemical class 0.000 description 2
150000002430 hydrocarbons Chemical group 0.000 description 2
230000036039 immunity Effects 0.000 description 2
230000001939 inductive effect Effects 0.000 description 2
230000004054 inflammatory process Effects 0.000 description 2
230000028709 inflammatory response Effects 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
230000015788 innate immune response Effects 0.000 description 2
AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
210000004731 jugular vein Anatomy 0.000 description 2
231100000518 lethal Toxicity 0.000 description 2
230000001665 lethal effect Effects 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
238000004519 manufacturing process Methods 0.000 description 2
238000005259 measurement Methods 0.000 description 2
LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
238000002663 nebulization Methods 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
125000004433 nitrogen atom Chemical group N* 0.000 description 2
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
230000001717 pathogenic effect Effects 0.000 description 2
230000001575 pathological effect Effects 0.000 description 2
244000144985 peep Species 0.000 description 2
235000019371 penicillin G benzathine Nutrition 0.000 description 2
102000013415 peroxidase activity proteins Human genes 0.000 description 2
108040007629 peroxidase activity proteins Proteins 0.000 description 2
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
230000026731 phosphorylation Effects 0.000 description 2
238000006366 phosphorylation reaction Methods 0.000 description 2
229920001223 polyethylene glycol Polymers 0.000 description 2
244000144977 poultry Species 0.000 description 2
235000013594 poultry meat Nutrition 0.000 description 2
239000000843 powder Substances 0.000 description 2
230000002265 prevention Effects 0.000 description 2
239000000047 product Substances 0.000 description 2
230000000770 proinflammatory effect Effects 0.000 description 2
230000000069 prophylactic effect Effects 0.000 description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
210000003456 pulmonary alveoli Anatomy 0.000 description 2
239000007845 reactive nitrogen species Substances 0.000 description 2
239000003642 reactive oxygen metabolite Substances 0.000 description 2
238000011084 recovery Methods 0.000 description 2
230000004044 response Effects 0.000 description 2
230000011664 signaling Effects 0.000 description 2
210000002460 smooth muscle Anatomy 0.000 description 2
239000011734 sodium Substances 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
239000001509 sodium citrate Substances 0.000 description 2
NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 2
239000002904 solvent Substances 0.000 description 2
239000008107 starch Substances 0.000 description 2
235000019698 starch Nutrition 0.000 description 2
UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
239000011593 sulfur Substances 0.000 description 2
239000006228 supernatant Substances 0.000 description 2
208000024891 symptom Diseases 0.000 description 2
208000011580 syndromic disease Diseases 0.000 description 2
230000008718 systemic inflammatory response Effects 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
230000000451 tissue damage Effects 0.000 description 2
231100000827 tissue damage Toxicity 0.000 description 2
208000037816 tissue injury Diseases 0.000 description 2
231100000419 toxicity Toxicity 0.000 description 2
230000001988 toxicity Effects 0.000 description 2
210000003437 trachea Anatomy 0.000 description 2
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
239000013598 vector Substances 0.000 description 2
KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
PYHRZPFZZDCOPH-QXGOIDDHSA-N (S)-amphetamine sulfate Chemical compound [H+].[H+].[O-]S([O-])(=O)=O.C[C@H](N)CC1=CC=CC=C1.C[C@H](N)CC1=CC=CC=C1 PYHRZPFZZDCOPH-QXGOIDDHSA-N 0.000 description 1
JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 1
IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
AEQDJSLRWYMAQI-UHFFFAOYSA-N 2,3,9,10-tetramethoxy-6,8,13,13a-tetrahydro-5H-isoquinolino[2,1-b]isoquinoline Chemical compound C1CN2CC(C(=C(OC)C=C3)OC)=C3CC2C2=C1C=C(OC)C(OC)=C2 AEQDJSLRWYMAQI-UHFFFAOYSA-N 0.000 description 1
HQEBCSOGYOCAEQ-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;2-[bis(2-hydroxyethyl)amino]ethanol Chemical compound OCC(N)(CO)CO.OCCN(CCO)CCO HQEBCSOGYOCAEQ-UHFFFAOYSA-N 0.000 description 1
AXAVXPMQTGXXJZ-UHFFFAOYSA-N 2-aminoacetic acid;2-amino-2-(hydroxymethyl)propane-1,3-diol Chemical compound NCC(O)=O.OCC(N)(CO)CO AXAVXPMQTGXXJZ-UHFFFAOYSA-N 0.000 description 1
MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 description 1
102100038222 60 kDa heat shock protein, mitochondrial Human genes 0.000 description 1
102100032814 ATP-dependent zinc metalloprotease YME1L1 Human genes 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
108090001008 Avidin Proteins 0.000 description 1
108020000946 Bacterial DNA Proteins 0.000 description 1
241000283726 Bison Species 0.000 description 1
241000283725 Bos Species 0.000 description 1
241000283690 Bos taurus Species 0.000 description 1
241000282832 Camelidae Species 0.000 description 1
241000282472 Canis lupus familiaris Species 0.000 description 1
241000283707 Capra Species 0.000 description 1
239000004215 Carbon black (E152) Substances 0.000 description 1
241001466804 Carnivora Species 0.000 description 1
241000282994 Cervidae Species 0.000 description 1
101710163595 Chaperone protein DnaK Proteins 0.000 description 1
108010058432 Chaperonin 60 Proteins 0.000 description 1
102000019034 Chemokines Human genes 0.000 description 1
108010012236 Chemokines Proteins 0.000 description 1
WQZGKKKJIJFFOK-CBPJZXOFSA-N D-Gulose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@H](O)[C@H]1O WQZGKKKJIJFFOK-CBPJZXOFSA-N 0.000 description 1
WQZGKKKJIJFFOK-WHZQZERISA-N D-aldose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-WHZQZERISA-N 0.000 description 1
WQZGKKKJIJFFOK-IVMDWMLBSA-N D-allopyranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@H](O)[C@@H]1O WQZGKKKJIJFFOK-IVMDWMLBSA-N 0.000 description 1
LKDRXBCSQODPBY-JDJSBBGDSA-N D-allulose Chemical compound OCC1(O)OC[C@@H](O)[C@@H](O)[C@H]1O LKDRXBCSQODPBY-JDJSBBGDSA-N 0.000 description 1
WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
ZAQJHHRNXZUBTE-NQXXGFSBSA-N D-ribulose Chemical compound OC[C@@H](O)[C@@H](O)C(=O)CO ZAQJHHRNXZUBTE-NQXXGFSBSA-N 0.000 description 1
ZAQJHHRNXZUBTE-UHFFFAOYSA-N D-threo-2-Pentulose Natural products OCC(O)C(O)C(=O)CO ZAQJHHRNXZUBTE-UHFFFAOYSA-N 0.000 description 1
ZAQJHHRNXZUBTE-WUJLRWPWSA-N D-xylulose Chemical compound OC[C@@H](O)[C@H](O)C(=O)CO ZAQJHHRNXZUBTE-WUJLRWPWSA-N 0.000 description 1
108700020359 Drosophila Tl Proteins 0.000 description 1
231100000491 EC50 Toxicity 0.000 description 1
PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
102000007665 Extracellular Signal-Regulated MAP Kinases Human genes 0.000 description 1
241000282326 Felis catus Species 0.000 description 1
102000009123 Fibrin Human genes 0.000 description 1
108010073385 Fibrin Proteins 0.000 description 1
BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
102000008946 Fibrinogen Human genes 0.000 description 1
108010049003 Fibrinogen Proteins 0.000 description 1
102100037362 Fibronectin Human genes 0.000 description 1
102000016359 Fibronectins Human genes 0.000 description 1
108010040721 Flagellin Proteins 0.000 description 1
229930091371 Fructose Natural products 0.000 description 1
239000005715 Fructose Substances 0.000 description 1
RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
241000233866 Fungi Species 0.000 description 1
102000002464 Galactosidases Human genes 0.000 description 1
108010093031 Galactosidases Proteins 0.000 description 1
241000287828 Gallus gallus Species 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
241000282818 Giraffidae Species 0.000 description 1
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
101710088172 HTH-type transcriptional regulator RipA Proteins 0.000 description 1
101710178376 Heat shock 70 kDa protein Proteins 0.000 description 1
101710152018 Heat shock cognate 70 kDa protein Proteins 0.000 description 1
102000002812 Heat-Shock Proteins Human genes 0.000 description 1
108010004889 Heat-Shock Proteins Proteins 0.000 description 1
229920002971 Heparan sulfate Polymers 0.000 description 1
239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
101001033249 Homo sapiens Interleukin-1 beta Proteins 0.000 description 1
101000852483 Homo sapiens Interleukin-1 receptor-associated kinase 1 Proteins 0.000 description 1
101001057752 Human cytomegalovirus (strain AD169) Uncharacterized protein IRL4 Proteins 0.000 description 1
108010032038 Interferon Regulatory Factor-3 Proteins 0.000 description 1
108090000890 Interferon regulatory factor 1 Proteins 0.000 description 1
102000004289 Interferon regulatory factor 1 Human genes 0.000 description 1
102100029843 Interferon regulatory factor 3 Human genes 0.000 description 1
102100039065 Interleukin-1 beta Human genes 0.000 description 1
102000019223 Interleukin-1 receptor Human genes 0.000 description 1
108050006617 Interleukin-1 receptor Proteins 0.000 description 1
102100036342 Interleukin-1 receptor-associated kinase 1 Human genes 0.000 description 1
YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 1
LKDRXBCSQODPBY-AMVSKUEXSA-N L-(-)-Sorbose Chemical compound OCC1(O)OC[C@H](O)[C@@H](O)[C@@H]1O LKDRXBCSQODPBY-AMVSKUEXSA-N 0.000 description 1
WQZGKKKJIJFFOK-VSOAQEOCSA-N L-altropyranose Chemical compound OC[C@@H]1OC(O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-VSOAQEOCSA-N 0.000 description 1
ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
125000000174 L-prolyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 description 1
240000007472 Leucaena leucocephala Species 0.000 description 1
235000010643 Leucaena leucocephala Nutrition 0.000 description 1
ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
239000004367 Lipase Substances 0.000 description 1
102000004882 Lipase Human genes 0.000 description 1
108090001060 Lipase Proteins 0.000 description 1
239000000232 Lipid Bilayer Substances 0.000 description 1
108010028921 Lipopeptides Proteins 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
240000003183 Manihot esculenta Species 0.000 description 1
235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
206010029538 Non-cardiogenic pulmonary oedema Diseases 0.000 description 1
101710163270 Nuclease Proteins 0.000 description 1
241000272458 Numididae Species 0.000 description 1
241000283973 Oryctolagus cuniculus Species 0.000 description 1
241001278385 Panthera tigris altaica Species 0.000 description 1
229930040373 Paraformaldehyde Natural products 0.000 description 1
241001494479 Pecora Species 0.000 description 1
102000035195 Peptidases Human genes 0.000 description 1
108091005804 Peptidases Proteins 0.000 description 1
241000286209 Phasianidae Species 0.000 description 1
PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
102000045595 Phosphoprotein Phosphatases Human genes 0.000 description 1
108700019535 Phosphoprotein Phosphatases Proteins 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
229920001213 Polysorbate 20 Polymers 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
208000023146 Pre-existing disease Diseases 0.000 description 1
101800000795 Proadrenomedullin N-20 terminal peptide Proteins 0.000 description 1
239000004365 Protease Substances 0.000 description 1
102000001253 Protein Kinase Human genes 0.000 description 1
WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
ZVOLCUVKHLEPEV-UHFFFAOYSA-N Quercetagetin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=C(O)C(O)=C(O)C=C2O1 ZVOLCUVKHLEPEV-UHFFFAOYSA-N 0.000 description 1
HWTZYBCRDDUBJY-UHFFFAOYSA-N Rhynchosin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=CC(O)=C(O)C=C2O1 HWTZYBCRDDUBJY-UHFFFAOYSA-N 0.000 description 1
PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
206010053879 Sepsis syndrome Diseases 0.000 description 1
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
244000061456 Solanum tuberosum Species 0.000 description 1
235000002595 Solanum tuberosum Nutrition 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
102100036073 TIR domain-containing adapter molecule 1 Human genes 0.000 description 1
101710157101 TIR domain-containing adapter molecule 1 Proteins 0.000 description 1
108700012920 TNF Proteins 0.000 description 1
239000007983 Tris buffer Substances 0.000 description 1
GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 1
238000010162 Tukey test Methods 0.000 description 1
241000364021 Tulsa Species 0.000 description 1
108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
241000700605 Viruses Species 0.000 description 1
238000002835 absorbance Methods 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
230000009471 action Effects 0.000 description 1
239000004480 active ingredient Substances 0.000 description 1
125000004442 acylamino group Chemical group 0.000 description 1
125000004423 acyloxy group Chemical group 0.000 description 1
230000033289 adaptive immune response Effects 0.000 description 1
230000004721 adaptive immunity Effects 0.000 description 1
102000035181 adaptor proteins Human genes 0.000 description 1
108091005764 adaptor proteins Proteins 0.000 description 1
150000001312 aldohexoses Chemical class 0.000 description 1
150000001320 aldopentoses Chemical class 0.000 description 1
125000001931 aliphatic group Chemical group 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
229910052784 alkaline earth metal Inorganic materials 0.000 description 1
125000005115 alkyl carbamoyl group Chemical group 0.000 description 1
125000000304 alkynyl group Chemical group 0.000 description 1
125000005282 allenyl group Chemical group 0.000 description 1
208000026935 allergic disease Diseases 0.000 description 1
HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
SRBFZHDQGSBBOR-STGXQOJASA-N alpha-D-lyxopyranose Chemical compound O[C@@H]1CO[C@H](O)[C@@H](O)[C@H]1O SRBFZHDQGSBBOR-STGXQOJASA-N 0.000 description 1
AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
150000003863 ammonium salts Chemical class 0.000 description 1
125000000129 anionic group Chemical group 0.000 description 1
150000001450 anions Chemical class 0.000 description 1
230000003110 anti-inflammatory effect Effects 0.000 description 1
239000003146 anticoagulant agent Substances 0.000 description 1
210000000709 aorta Anatomy 0.000 description 1
239000008365 aqueous carrier Substances 0.000 description 1
239000007900 aqueous suspension Substances 0.000 description 1
PYMYPHUHKUWMLA-WDCZJNDASA-N arabinose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WDCZJNDASA-N 0.000 description 1
125000005239 aroylamino group Chemical group 0.000 description 1
210000001367 artery Anatomy 0.000 description 1
125000004659 aryl alkyl thio group Chemical group 0.000 description 1
125000001769 aryl amino group Chemical group 0.000 description 1
125000005161 aryl oxy carbonyl group Chemical group 0.000 description 1
230000001580 bacterial effect Effects 0.000 description 1
230000004888 barrier function Effects 0.000 description 1
235000019445 benzyl alcohol Nutrition 0.000 description 1
229960004217 benzyl alcohol Drugs 0.000 description 1
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
229960000074 biopharmaceutical Drugs 0.000 description 1
229960002685 biotin Drugs 0.000 description 1
235000020958 biotin Nutrition 0.000 description 1
239000011616 biotin Substances 0.000 description 1
239000004305 biphenyl Substances 0.000 description 1
235000010290 biphenyl Nutrition 0.000 description 1
OWMVSZAMULFTJU-UHFFFAOYSA-N bis-tris Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 description 1
230000037396 body weight Effects 0.000 description 1
229910021538 borax Inorganic materials 0.000 description 1
210000000481 breast Anatomy 0.000 description 1
125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
229910000019 calcium carbonate Inorganic materials 0.000 description 1
AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
239000000920 calcium hydroxide Substances 0.000 description 1
229910001861 calcium hydroxide Inorganic materials 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
229910000389 calcium phosphate Inorganic materials 0.000 description 1
235000011010 calcium phosphates Nutrition 0.000 description 1
239000002775 capsule Substances 0.000 description 1
150000001720 carbohydrates Chemical class 0.000 description 1
235000014633 carbohydrates Nutrition 0.000 description 1
239000001569 carbon dioxide Substances 0.000 description 1
229910002092 carbon dioxide Inorganic materials 0.000 description 1
239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
125000002843 carboxylic acid group Chemical group 0.000 description 1
230000000747 cardiac effect Effects 0.000 description 1
229940100084 cardioplegia solution Drugs 0.000 description 1
230000002612 cardiopulmonary effect Effects 0.000 description 1
210000000845 cartilage Anatomy 0.000 description 1
230000015556 catabolic process Effects 0.000 description 1
150000001768 cations Chemical class 0.000 description 1
239000006143 cell culture medium Substances 0.000 description 1
230000003915 cell function Effects 0.000 description 1
230000003833 cell viability Effects 0.000 description 1
210000002421 cell wall Anatomy 0.000 description 1
230000005754 cellular signaling Effects 0.000 description 1
210000003169 central nervous system Anatomy 0.000 description 1
230000002490 cerebral effect Effects 0.000 description 1
125000003636 chemical group Chemical group 0.000 description 1
238000006243 chemical reaction Methods 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
235000013330 chicken meat Nutrition 0.000 description 1
235000012000 cholesterol Nutrition 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
230000001684 chronic effect Effects 0.000 description 1
230000015271 coagulation Effects 0.000 description 1
238000005345 coagulation Methods 0.000 description 1
239000003086 colorant Substances 0.000 description 1
238000007906 compression Methods 0.000 description 1
230000006835 compression Effects 0.000 description 1
239000013068 control sample Substances 0.000 description 1
210000004087 cornea Anatomy 0.000 description 1
238000007887 coronary angioplasty Methods 0.000 description 1
210000004351 coronary vessel Anatomy 0.000 description 1
238000002316 cosmetic surgery Methods 0.000 description 1
125000000753 cycloalkyl group Chemical group 0.000 description 1
125000004956 cyclohexylene group Chemical group 0.000 description 1
125000000058 cyclopentadienyl group Chemical group C1(=CC=CC1)* 0.000 description 1
210000005220 cytoplasmic tail Anatomy 0.000 description 1
231100000135 cytotoxicity Toxicity 0.000 description 1
230000003013 cytotoxicity Effects 0.000 description 1
238000002784 cytotoxicity assay Methods 0.000 description 1
231100000263 cytotoxicity test Toxicity 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
230000007812 deficiency Effects 0.000 description 1
238000006731 degradation reaction Methods 0.000 description 1
230000003111 delayed effect Effects 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
125000005117 dialkylcarbamoyl group Chemical group 0.000 description 1
229960004132 diethyl ether Drugs 0.000 description 1
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
239000007884 disintegrant Substances 0.000 description 1
230000029036 donor selection Effects 0.000 description 1
230000007783 downstream signaling Effects 0.000 description 1
239000000975 dye Substances 0.000 description 1
239000012636 effector Substances 0.000 description 1
238000013156 embolectomy Methods 0.000 description 1
230000013020 embryo development Effects 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
ZSWFCLXCOIISFI-UHFFFAOYSA-N endo-cyclopentadiene Natural products C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 description 1
YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
210000002919 epithelial cell Anatomy 0.000 description 1
SLFUXNFVAANERW-UHFFFAOYSA-N ethyl hexanoate;potassium Chemical compound [K].CCCCCC(=O)OCC SLFUXNFVAANERW-UHFFFAOYSA-N 0.000 description 1
230000007717 exclusion Effects 0.000 description 1
210000003722 extracellular fluid Anatomy 0.000 description 1
210000003195 fascia Anatomy 0.000 description 1
235000013861 fat-free Nutrition 0.000 description 1
229950003499 fibrin Drugs 0.000 description 1
229940012952 fibrinogen Drugs 0.000 description 1
239000000945 filler Substances 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
238000011010 flushing procedure Methods 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
238000001640 fractional crystallisation Methods 0.000 description 1
229930182830 galactose Natural products 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
238000007429 general method Methods 0.000 description 1
239000011521 glass Substances 0.000 description 1
239000008103 glucose Substances 0.000 description 1
239000001963 growth medium Substances 0.000 description 1
238000003306 harvesting Methods 0.000 description 1
210000003709 heart valve Anatomy 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
150000002373 hemiacetals Chemical class 0.000 description 1
229920000669 heparin Polymers 0.000 description 1
229960002897 heparin Drugs 0.000 description 1
230000002440 hepatic effect Effects 0.000 description 1
150000002386 heptoses Chemical class 0.000 description 1
125000006038 hexenyl group Chemical group 0.000 description 1
150000002402 hexoses Chemical class 0.000 description 1
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000005980 hexynyl group Chemical group 0.000 description 1
230000002962 histologic effect Effects 0.000 description 1
238000000265 homogenisation Methods 0.000 description 1
229920002674 hyaluronan Polymers 0.000 description 1
KIUKXJAPPMFGSW-MNSSHETKSA-N hyaluronan Chemical group CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)C1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H](C(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-MNSSHETKSA-N 0.000 description 1
229960003160 hyaluronic acid Drugs 0.000 description 1
230000036571 hydration Effects 0.000 description 1
238000006703 hydration reaction Methods 0.000 description 1
229930195733 hydrocarbon Natural products 0.000 description 1
230000003301 hydrolyzing effect Effects 0.000 description 1
230000002209 hydrophobic effect Effects 0.000 description 1
150000002454 idoses Chemical class 0.000 description 1
238000003119 immunoblot Methods 0.000 description 1
238000011532 immunohistochemical staining Methods 0.000 description 1
230000001771 impaired effect Effects 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
238000000099 in vitro assay Methods 0.000 description 1
238000005462 in vivo assay Methods 0.000 description 1
238000011534 incubation Methods 0.000 description 1
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
230000002757 inflammatory effect Effects 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
210000005007 innate immune system Anatomy 0.000 description 1
239000002198 insoluble material Substances 0.000 description 1
230000010468 interferon response Effects 0.000 description 1
230000000968 intestinal effect Effects 0.000 description 1
210000000936 intestine Anatomy 0.000 description 1
230000003834 intracellular effect Effects 0.000 description 1
238000010255 intramuscular injection Methods 0.000 description 1
239000007927 intramuscular injection Substances 0.000 description 1
230000001678 irradiating effect Effects 0.000 description 1
230000002427 irreversible effect Effects 0.000 description 1
230000007794 irritation Effects 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
MWDZOUNAPSSOEL-UHFFFAOYSA-N kaempferol Natural products OC1=C(C(=O)c2cc(O)cc(O)c2O1)c3ccc(O)cc3 MWDZOUNAPSSOEL-UHFFFAOYSA-N 0.000 description 1
229960003299 ketamine Drugs 0.000 description 1
BJHIKXHVCXFQLS-PQLUHFTBSA-N keto-D-tagatose Chemical compound OC[C@@H](O)[C@H](O)[C@H](O)C(=O)CO BJHIKXHVCXFQLS-PQLUHFTBSA-N 0.000 description 1
150000002574 ketohexoses Chemical class 0.000 description 1
150000002581 ketopentoses Chemical class 0.000 description 1
239000008101 lactose Substances 0.000 description 1
239000000787 lecithin Substances 0.000 description 1
235000010445 lecithin Nutrition 0.000 description 1
229940067606 lecithin Drugs 0.000 description 1
210000005248 left atrial appendage Anatomy 0.000 description 1
GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
108010052968 leupeptin Proteins 0.000 description 1
210000003041 ligament Anatomy 0.000 description 1
125000005647 linker group Chemical group 0.000 description 1
235000019421 lipase Nutrition 0.000 description 1
GZQKNULLWNGMCW-PWQABINMSA-N lipid A (E. coli) Chemical compound O1[C@H](CO)[C@@H](OP(O)(O)=O)[C@H](OC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCCCC)[C@@H](NC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCC)[C@@H]1OC[C@@H]1[C@@H](O)[C@H](OC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](NC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](OP(O)(O)=O)O1 GZQKNULLWNGMCW-PWQABINMSA-N 0.000 description 1
239000012669 liquid formulation Substances 0.000 description 1
244000144972 livestock Species 0.000 description 1
238000011068 loading method Methods 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
239000012139 lysis buffer Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
239000000347 magnesium hydroxide Substances 0.000 description 1
229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
238000005399 mechanical ventilation Methods 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
239000002609 medium Substances 0.000 description 1
229960003194 meglumine Drugs 0.000 description 1
239000012528 membrane Substances 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
AXLHVTKGDPVANO-UHFFFAOYSA-N methyl 2-amino-3-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound COC(=O)C(N)CNC(=O)OC(C)(C)C AXLHVTKGDPVANO-UHFFFAOYSA-N 0.000 description 1
239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
229960002216 methylparaben Drugs 0.000 description 1
244000000010 microbial pathogen Species 0.000 description 1
244000005700 microbiome Species 0.000 description 1
235000013336 milk Nutrition 0.000 description 1
239000008267 milk Substances 0.000 description 1
210000004080 milk Anatomy 0.000 description 1
230000006705 mitochondrial oxidative phosphorylation Effects 0.000 description 1
238000002156 mixing Methods 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
230000002107 myocardial effect Effects 0.000 description 1
210000004165 myocardium Anatomy 0.000 description 1
239000002105 nanoparticle Substances 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
210000005036 nerve Anatomy 0.000 description 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
230000030648 nucleus localization Effects 0.000 description 1
125000004365 octenyl group Chemical group C(=CCCCCCC)* 0.000 description 1
125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
229920001542 oligosaccharide Polymers 0.000 description 1
150000002482 oligosaccharides Chemical class 0.000 description 1
230000036542 oxidative stress Effects 0.000 description 1
125000004043 oxo group Chemical group O=* 0.000 description 1
239000003002 pH adjusting agent Substances 0.000 description 1
PIRWNASAJNPKHT-SHZATDIYSA-N pamp Chemical compound C([C@@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](C)N)C(C)C)C1=CC=CC=C1 PIRWNASAJNPKHT-SHZATDIYSA-N 0.000 description 1
239000012188 paraffin wax Substances 0.000 description 1
229920002866 paraformaldehyde Polymers 0.000 description 1
230000003071 parasitic effect Effects 0.000 description 1
239000004031 partial agonist Substances 0.000 description 1
230000036961 partial effect Effects 0.000 description 1
239000008188 pellet Substances 0.000 description 1
229940056360 penicillin g Drugs 0.000 description 1
125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
150000002972 pentoses Chemical class 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
125000005981 pentynyl group Chemical group 0.000 description 1
108010091212 pepstatin Proteins 0.000 description 1
FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
150000008105 phosphatidylcholines Chemical class 0.000 description 1
239000006187 pill Substances 0.000 description 1
239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
230000002335 preservative effect Effects 0.000 description 1
238000002203 pretreatment Methods 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
229960004919 procaine Drugs 0.000 description 1
238000012545 processing Methods 0.000 description 1
125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
229960003415 propylparaben Drugs 0.000 description 1
125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
108060006633 protein kinase Proteins 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
229960001285 quercetin Drugs 0.000 description 1
235000005875 quercetin Nutrition 0.000 description 1
150000003254 radicals Chemical class 0.000 description 1
238000010814 radioimmunoprecipitation assay Methods 0.000 description 1
230000007115 recruitment Effects 0.000 description 1
230000009467 reduction Effects 0.000 description 1
230000036387 respiratory rate Effects 0.000 description 1
230000000452 restraining effect Effects 0.000 description 1
210000001525 retina Anatomy 0.000 description 1
230000002207 retinal effect Effects 0.000 description 1
230000002441 reversible effect Effects 0.000 description 1
239000000523 sample Substances 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
230000028327 secretion Effects 0.000 description 1
230000035939 shock Effects 0.000 description 1
150000004760 silicates Chemical class 0.000 description 1
230000000391 smoking effect Effects 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
235000011083 sodium citrates Nutrition 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
239000000176 sodium gluconate Substances 0.000 description 1
235000012207 sodium gluconate Nutrition 0.000 description 1
229940005574 sodium gluconate Drugs 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
239000001540 sodium lactate Substances 0.000 description 1
229940005581 sodium lactate Drugs 0.000 description 1
235000011088 sodium lactate Nutrition 0.000 description 1
235000019333 sodium laurylsulphate Nutrition 0.000 description 1
239000001488 sodium phosphate Substances 0.000 description 1
229910000162 sodium phosphate Inorganic materials 0.000 description 1
235000011008 sodium phosphates Nutrition 0.000 description 1
235000010339 sodium tetraborate Nutrition 0.000 description 1
RWVGQQGBQSJDQV-UHFFFAOYSA-M sodium;3-[[4-[(e)-[4-(4-ethoxyanilino)phenyl]-[4-[ethyl-[(3-sulfonatophenyl)methyl]azaniumylidene]-2-methylcyclohexa-2,5-dien-1-ylidene]methyl]-n-ethyl-3-methylanilino]methyl]benzenesulfonate Chemical compound [Na+].C1=CC(OCC)=CC=C1NC1=CC=C(C(=C2C(=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C)C=2C(=CC(=CC=2)N(CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C)C=C1 RWVGQQGBQSJDQV-UHFFFAOYSA-M 0.000 description 1
239000008247 solid mixture Substances 0.000 description 1
238000000527 sonication Methods 0.000 description 1
210000000278 spinal cord Anatomy 0.000 description 1
238000007619 statistical method Methods 0.000 description 1
230000001954 sterilising effect Effects 0.000 description 1
238000004659 sterilization and disinfection Methods 0.000 description 1
229960005322 streptomycin Drugs 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
230000001502 supplementing effect Effects 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
210000001258 synovial membrane Anatomy 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
230000001839 systemic circulation Effects 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
239000003826 tablet Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
210000002435 tendon Anatomy 0.000 description 1
150000003538 tetroses Chemical class 0.000 description 1
230000008719 thickening Effects 0.000 description 1
229930192474 thiophene Natural products 0.000 description 1
230000002537 thrombolytic effect Effects 0.000 description 1
210000002303 tibia Anatomy 0.000 description 1
239000003053 toxin Substances 0.000 description 1
231100000765 toxin Toxicity 0.000 description 1
230000002103 transcriptional effect Effects 0.000 description 1
238000001890 transfection Methods 0.000 description 1
230000005945 translocation Effects 0.000 description 1
102000035160 transmembrane proteins Human genes 0.000 description 1
108091005703 transmembrane proteins Proteins 0.000 description 1
230000032258 transport Effects 0.000 description 1
230000008733 trauma Effects 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
150000003641 trioses Chemical class 0.000 description 1
BSVBQGMMJUBVOD-UHFFFAOYSA-N trisodium borate Chemical compound [Na+].[Na+].[Na+].[O-]B([O-])[O-] BSVBQGMMJUBVOD-UHFFFAOYSA-N 0.000 description 1
RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
102000003390 tumor necrosis factor Human genes 0.000 description 1
241000701161 unidentified adenovirus Species 0.000 description 1
210000000689 upper leg Anatomy 0.000 description 1
210000005166 vasculature Anatomy 0.000 description 1
210000003462 vein Anatomy 0.000 description 1
238000009423 ventilation Methods 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
230000003612 virological effect Effects 0.000 description 1
238000012800 visualization Methods 0.000 description 1
238000002689 xenotransplantation Methods 0.000 description 1
BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
229960001600 xylazine Drugs 0.000 description 1
DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1