GB2470803A - Diagnosis and treatment of arthritis - Google Patents
Diagnosis and treatment of arthritis Download PDFInfo
- Publication number
- GB2470803A GB2470803A GB1004994A GB201004994A GB2470803A GB 2470803 A GB2470803 A GB 2470803A GB 1004994 A GB1004994 A GB 1004994A GB 201004994 A GB201004994 A GB 201004994A GB 2470803 A GB2470803 A GB 2470803A
- Authority
- GB
- United Kingdom
- Prior art keywords
- subject
- endogenous metabolites
- metabolic profile
- biological sample
- levels
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 238000003745 diagnosis Methods 0.000 title claims abstract description 70
- 238000011282 treatment Methods 0.000 title claims abstract description 46
- 206010003246 arthritis Diseases 0.000 title claims abstract description 17
- 238000000034 method Methods 0.000 claims abstract description 168
- 206010039073 rheumatoid arthritis Diseases 0.000 claims abstract description 119
- 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 109
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims abstract description 93
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims abstract description 55
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims abstract description 54
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 claims abstract description 44
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims abstract description 40
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims abstract description 40
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims abstract description 38
- 239000004471 Glycine Substances 0.000 claims abstract description 37
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims abstract description 37
- 229960000310 isoleucine Drugs 0.000 claims abstract description 37
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 claims abstract description 37
- 229930182817 methionine Natural products 0.000 claims abstract description 37
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims abstract description 36
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims abstract description 36
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims abstract description 35
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 claims abstract description 35
- FGEWTNKUNGVHKT-UHFFFAOYSA-N 2-[(2-chloro-3,4-dimethoxyphenyl)methylideneamino]guanidine Chemical compound COC1=CC=C(C=NNC(N)=N)C(Cl)=C1OC FGEWTNKUNGVHKT-UHFFFAOYSA-N 0.000 claims abstract description 33
- 238000012544 monitoring process Methods 0.000 claims abstract description 29
- 238000001514 detection method Methods 0.000 claims abstract description 27
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims abstract description 24
- 239000004475 Arginine Substances 0.000 claims abstract description 22
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 claims abstract description 22
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims abstract description 22
- 229930195712 glutamate Natural products 0.000 claims abstract description 22
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims abstract description 21
- 229940009098 aspartate Drugs 0.000 claims abstract description 21
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims abstract description 20
- 239000004474 valine Substances 0.000 claims abstract description 19
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 claims abstract description 17
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims abstract description 17
- 239000004472 Lysine Substances 0.000 claims abstract description 17
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 claims abstract description 17
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 claims abstract description 17
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims abstract description 17
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 claims abstract description 17
- 239000004473 Threonine Substances 0.000 claims abstract description 17
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 claims abstract description 17
- 229960003104 ornithine Drugs 0.000 claims abstract description 17
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 claims abstract description 16
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 claims abstract description 15
- 229960001230 asparagine Drugs 0.000 claims abstract description 15
- 235000009582 asparagine Nutrition 0.000 claims abstract description 15
- 239000002207 metabolite Substances 0.000 claims description 308
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 196
- 239000012472 biological sample Substances 0.000 claims description 130
- 239000000090 biomarker Substances 0.000 claims description 110
- 201000010099 disease Diseases 0.000 claims description 107
- 230000002503 metabolic effect Effects 0.000 claims description 100
- 208000035475 disorder Diseases 0.000 claims description 89
- 230000007423 decrease Effects 0.000 claims description 55
- 239000003814 drug Substances 0.000 claims description 49
- 150000003839 salts Chemical group 0.000 claims description 36
- 239000012458 free base Substances 0.000 claims description 35
- HAMNKKUPIHEESI-UHFFFAOYSA-N aminoguanidine Chemical compound NNC(N)=N HAMNKKUPIHEESI-UHFFFAOYSA-N 0.000 claims description 32
- 238000004458 analytical method Methods 0.000 claims description 22
- 230000015556 catabolic process Effects 0.000 claims description 22
- 238000006731 degradation reaction Methods 0.000 claims description 22
- 210000004369 blood Anatomy 0.000 claims description 19
- 239000008280 blood Substances 0.000 claims description 19
- 206010012601 diabetes mellitus Diseases 0.000 claims description 19
- 238000000605 extraction Methods 0.000 claims description 14
- 230000002917 arthritic effect Effects 0.000 claims description 11
- 239000003153 chemical reaction reagent Substances 0.000 claims description 11
- 210000002808 connective tissue Anatomy 0.000 claims description 11
- 230000006872 improvement Effects 0.000 claims description 11
- 102100028284 Collagen alpha-1(XXVI) chain Human genes 0.000 claims description 9
- 101000860862 Homo sapiens Collagen alpha-1(XXVI) chain Proteins 0.000 claims description 9
- 230000036961 partial effect Effects 0.000 claims description 9
- 102000004190 Enzymes Human genes 0.000 claims description 8
- 108090000790 Enzymes Proteins 0.000 claims description 8
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 8
- 102000006386 Myelin Proteins Human genes 0.000 claims description 8
- 108010083674 Myelin Proteins Proteins 0.000 claims description 8
- 210000005012 myelin Anatomy 0.000 claims description 8
- 241001465754 Metazoa Species 0.000 claims description 7
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 claims description 7
- 101100389259 Echinococcus multilocularis EM13 gene Proteins 0.000 claims description 5
- 210000000748 cardiovascular system Anatomy 0.000 claims description 5
- 210000003169 central nervous system Anatomy 0.000 claims description 5
- 210000002249 digestive system Anatomy 0.000 claims description 5
- 210000003734 kidney Anatomy 0.000 claims description 5
- 210000004072 lung Anatomy 0.000 claims description 5
- 230000000926 neurological effect Effects 0.000 claims description 5
- 238000004611 spectroscopical analysis Methods 0.000 claims description 5
- 239000000758 substrate Substances 0.000 claims description 5
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 4
- 238000004587 chromatography analysis Methods 0.000 claims description 4
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 4
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 claims description 4
- 238000000513 principal component analysis Methods 0.000 claims description 4
- 230000008354 tissue degradation Effects 0.000 claims description 4
- 102100026109 F-box only protein 43 Human genes 0.000 claims description 3
- 241000124008 Mammalia Species 0.000 claims description 3
- 101100333307 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) EMI2 gene Proteins 0.000 claims description 3
- 101150037264 fbxo43 gene Proteins 0.000 claims description 3
- 238000005259 measurement Methods 0.000 claims description 3
- 210000001179 synovial fluid Anatomy 0.000 claims description 3
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 claims description 2
- 238000005481 NMR spectroscopy Methods 0.000 claims description 2
- 239000013060 biological fluid Substances 0.000 claims description 2
- 238000012569 chemometric method Methods 0.000 claims description 2
- 239000003480 eluent Substances 0.000 claims description 2
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 2
- 238000000338 in vitro Methods 0.000 claims description 2
- 238000012306 spectroscopic technique Methods 0.000 claims description 2
- 201000008482 osteoarthritis Diseases 0.000 abstract description 38
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 abstract description 32
- 229960005190 phenylalanine Drugs 0.000 abstract description 26
- 229960004441 tyrosine Drugs 0.000 abstract description 26
- 210000002966 serum Anatomy 0.000 abstract description 23
- 229960002429 proline Drugs 0.000 abstract description 19
- 229960003121 arginine Drugs 0.000 abstract description 17
- 229940049906 glutamate Drugs 0.000 abstract description 17
- 229960003136 leucine Drugs 0.000 abstract description 15
- 229960004295 valine Drugs 0.000 abstract description 15
- 229940024606 amino acid Drugs 0.000 abstract description 12
- 235000001014 amino acid Nutrition 0.000 abstract description 12
- 229960001153 serine Drugs 0.000 abstract description 12
- 229960002898 threonine Drugs 0.000 abstract description 12
- 150000001413 amino acids Chemical class 0.000 abstract description 11
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 abstract description 3
- 229960002743 glutamine Drugs 0.000 abstract 2
- 229960002449 glycine Drugs 0.000 abstract 2
- 229960004452 methionine Drugs 0.000 abstract 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 abstract 1
- WNPXUCYRKHVMAD-UHFFFAOYSA-N 2-(benzylideneamino)guanidine Chemical compound NC(N)=NN=CC1=CC=CC=C1 WNPXUCYRKHVMAD-UHFFFAOYSA-N 0.000 abstract 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 abstract 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 abstract 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 abstract 1
- 230000003292 diminished effect Effects 0.000 abstract 1
- 229960003646 lysine Drugs 0.000 abstract 1
- 229960004799 tryptophan Drugs 0.000 abstract 1
- 230000000875 corresponding effect Effects 0.000 description 45
- 238000000926 separation method Methods 0.000 description 32
- 239000000523 sample Substances 0.000 description 29
- 238000011068 loading method Methods 0.000 description 22
- 238000004393 prognosis Methods 0.000 description 22
- 241000700159 Rattus Species 0.000 description 18
- 238000010171 animal model Methods 0.000 description 16
- 210000000056 organ Anatomy 0.000 description 15
- 150000001875 compounds Chemical class 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 230000003389 potentiating effect Effects 0.000 description 12
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 11
- 241000282412 Homo Species 0.000 description 10
- 230000002757 inflammatory effect Effects 0.000 description 10
- 208000024891 symptom Diseases 0.000 description 10
- 238000001269 time-of-flight mass spectrometry Methods 0.000 description 10
- 150000002500 ions Chemical class 0.000 description 9
- 210000001503 joint Anatomy 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 238000011161 development Methods 0.000 description 7
- 230000018109 developmental process Effects 0.000 description 7
- 238000003018 immunoassay Methods 0.000 description 7
- 230000008506 pathogenesis Effects 0.000 description 7
- 238000011321 prophylaxis Methods 0.000 description 7
- 210000001519 tissue Anatomy 0.000 description 7
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 6
- HPEUJPJOZXNMSJ-UHFFFAOYSA-N Methyl stearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC HPEUJPJOZXNMSJ-UHFFFAOYSA-N 0.000 description 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 210000004204 blood vessel Anatomy 0.000 description 6
- 230000006378 damage Effects 0.000 description 6
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 6
- 229960002591 hydroxyproline Drugs 0.000 description 6
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 6
- 238000010926 purge Methods 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 230000001363 autoimmune Effects 0.000 description 5
- 239000000470 constituent Substances 0.000 description 5
- 230000003247 decreasing effect Effects 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 201000006417 multiple sclerosis Diseases 0.000 description 5
- 230000001105 regulatory effect Effects 0.000 description 5
- 238000010200 validation analysis Methods 0.000 description 5
- 241001596784 Pegasus Species 0.000 description 4
- 241000219061 Rheum Species 0.000 description 4
- 230000006472 autoimmune response Effects 0.000 description 4
- 230000005784 autoimmunity Effects 0.000 description 4
- 210000004556 brain Anatomy 0.000 description 4
- 238000013461 design Methods 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 239000012530 fluid Substances 0.000 description 4
- 230000002068 genetic effect Effects 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 238000012545 processing Methods 0.000 description 4
- 238000011552 rat model Methods 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 238000001228 spectrum Methods 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 4
- 241000024188 Andala Species 0.000 description 3
- 230000005526 G1 to G0 transition Effects 0.000 description 3
- 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 3
- 206010061218 Inflammation Diseases 0.000 description 3
- 102000004877 Insulin Human genes 0.000 description 3
- 108090001061 Insulin Proteins 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- MSPCIZMDDUQPGJ-UHFFFAOYSA-N N-methyl-N-(trimethylsilyl)trifluoroacetamide Chemical compound C[Si](C)(C)N(C)C(=O)C(F)(F)F MSPCIZMDDUQPGJ-UHFFFAOYSA-N 0.000 description 3
- 206010036030 Polyarthritis Diseases 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 3
- 230000001133 acceleration Effects 0.000 description 3
- 208000002552 acute disseminated encephalomyelitis Diseases 0.000 description 3
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 239000012159 carrier gas Substances 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 150000005829 chemical entities Chemical class 0.000 description 3
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 3
- 229920001577 copolymer Polymers 0.000 description 3
- 238000012937 correction Methods 0.000 description 3
- 238000007405 data analysis Methods 0.000 description 3
- 238000013399 early diagnosis Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000010894 electron beam technology Methods 0.000 description 3
- CAMHHLOGFDZBBG-UHFFFAOYSA-N epoxidized methyl oleate Natural products CCCCCCCCC1OC1CCCCCCCC(=O)OC CAMHHLOGFDZBBG-UHFFFAOYSA-N 0.000 description 3
- 238000011067 equilibration Methods 0.000 description 3
- 239000003797 essential amino acid Substances 0.000 description 3
- 235000020776 essential amino acid Nutrition 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 239000005350 fused silica glass Substances 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 239000001307 helium Substances 0.000 description 3
- 229910052734 helium Inorganic materials 0.000 description 3
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 3
- XNXVOSBNFZWHBV-UHFFFAOYSA-N hydron;o-methylhydroxylamine;chloride Chemical compound Cl.CON XNXVOSBNFZWHBV-UHFFFAOYSA-N 0.000 description 3
- 210000000987 immune system Anatomy 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 229940125396 insulin Drugs 0.000 description 3
- 230000003902 lesion Effects 0.000 description 3
- 238000011694 lewis rat Methods 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 210000002381 plasma Anatomy 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 238000013515 script Methods 0.000 description 3
- 238000006884 silylation reaction Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- PHIQHXFUZVPYII-ZCFIWIBFSA-N (R)-carnitine Chemical compound C[N+](C)(C)C[C@H](O)CC([O-])=O PHIQHXFUZVPYII-ZCFIWIBFSA-N 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 2
- ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 206010061818 Disease progression Diseases 0.000 description 2
- 208000007465 Giant cell arteritis Diseases 0.000 description 2
- 208000003807 Graves Disease Diseases 0.000 description 2
- 208000015023 Graves' disease Diseases 0.000 description 2
- 208000030836 Hashimoto thyroiditis Diseases 0.000 description 2
- RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical compound NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-N 0.000 description 2
- 206010049567 Miller Fisher syndrome Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 2
- 239000003435 antirheumatic agent Substances 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000006470 autoimmune attack Effects 0.000 description 2
- 208000010928 autoimmune thyroid disease Diseases 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 229960004203 carnitine Drugs 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 230000002860 competitive effect Effects 0.000 description 2
- 229940125898 compound 5 Drugs 0.000 description 2
- 230000002596 correlated effect Effects 0.000 description 2
- 239000002988 disease modifying antirheumatic drug Substances 0.000 description 2
- 230000005750 disease progression Effects 0.000 description 2
- 230000003828 downregulation Effects 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 201000001421 hyperglycemia Diseases 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 230000002427 irreversible effect Effects 0.000 description 2
- 208000018937 joint inflammation Diseases 0.000 description 2
- 239000001630 malic acid Substances 0.000 description 2
- 235000011090 malic acid Nutrition 0.000 description 2
- 201000000083 maturity-onset diabetes of the young type 1 Diseases 0.000 description 2
- 230000004066 metabolic change Effects 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 210000000496 pancreas Anatomy 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 229940002612 prodrug Drugs 0.000 description 2
- 239000000651 prodrug Substances 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 229940043131 pyroglutamate Drugs 0.000 description 2
- 201000000980 schizophrenia Diseases 0.000 description 2
- 230000003595 spectral effect Effects 0.000 description 2
- 210000000130 stem cell Anatomy 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 2
- 206010043207 temporal arteritis Diseases 0.000 description 2
- 229960001295 tocopherol Drugs 0.000 description 2
- 239000011732 tocopherol Substances 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 2
- 238000001946 ultra-performance liquid chromatography-mass spectrometry Methods 0.000 description 2
- 230000003827 upregulation Effects 0.000 description 2
- 239000003643 water by type Substances 0.000 description 2
- RBNPOMFGQQGHHO-UHFFFAOYSA-N -2,3-Dihydroxypropanoic acid Natural products OCC(O)C(O)=O RBNPOMFGQQGHHO-UHFFFAOYSA-N 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- INAPMGSXUVUWAF-UOTPTPDRSA-N 1D-myo-inositol 1-phosphate Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](OP(O)(O)=O)[C@H](O)[C@@H]1O INAPMGSXUVUWAF-UOTPTPDRSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000026872 Addison Disease Diseases 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 206010001935 American trypanosomiasis Diseases 0.000 description 1
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
- 208000003343 Antiphospholipid Syndrome Diseases 0.000 description 1
- 206010003445 Ascites Diseases 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 206010003805 Autism Diseases 0.000 description 1
- 208000020706 Autistic disease Diseases 0.000 description 1
- 206010003827 Autoimmune hepatitis Diseases 0.000 description 1
- 208000000659 Autoimmune lymphoproliferative syndrome Diseases 0.000 description 1
- 208000031212 Autoimmune polyendocrinopathy Diseases 0.000 description 1
- 208000009137 Behcet syndrome Diseases 0.000 description 1
- 208000006373 Bell palsy Diseases 0.000 description 1
- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 description 1
- 208000033222 Biliary cirrhosis primary Diseases 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 208000024699 Chagas disease Diseases 0.000 description 1
- 206010008609 Cholangitis sclerosing Diseases 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 206010008874 Chronic Fatigue Syndrome Diseases 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- 208000015943 Coeliac disease Diseases 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- ZAKOWWREFLAJOT-CEFNRUSXSA-N D-alpha-tocopherylacetate Chemical compound CC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-CEFNRUSXSA-N 0.000 description 1
- RBNPOMFGQQGHHO-UWTATZPHSA-N D-glyceric acid Chemical compound OC[C@@H](O)C(O)=O RBNPOMFGQQGHHO-UWTATZPHSA-N 0.000 description 1
- JPIJQSOTBSSVTP-GBXIJSLDSA-N D-threonic acid Chemical compound OC[C@@H](O)[C@H](O)C(O)=O JPIJQSOTBSSVTP-GBXIJSLDSA-N 0.000 description 1
- 206010012468 Dermatitis herpetiformis Diseases 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 238000009007 Diagnostic Kit Methods 0.000 description 1
- 208000006926 Discoid Lupus Erythematosus Diseases 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 206010018364 Glomerulonephritis Diseases 0.000 description 1
- 208000024869 Goodpasture syndrome Diseases 0.000 description 1
- 206010072579 Granulomatosis with polyangiitis Diseases 0.000 description 1
- 208000035895 Guillain-Barré syndrome Diseases 0.000 description 1
- 208000031220 Hemophilia Diseases 0.000 description 1
- 208000009292 Hemophilia A Diseases 0.000 description 1
- 206010021245 Idiopathic thrombocytopenic purpura Diseases 0.000 description 1
- 208000010159 IgA glomerulonephritis Diseases 0.000 description 1
- 206010021263 IgA nephropathy Diseases 0.000 description 1
- 206010022489 Insulin Resistance Diseases 0.000 description 1
- 206010023203 Joint destruction Diseases 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- 125000000899 L-alpha-glutamyl group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C([H])([H])C([H])([H])C(O[H])=O 0.000 description 1
- 125000003440 L-leucyl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])C(C([H])([H])[H])([H])C([H])([H])[H] 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- 208000000185 Localized scleroderma Diseases 0.000 description 1
- 208000003250 Mixed connective tissue disease Diseases 0.000 description 1
- 206010027982 Morphoea Diseases 0.000 description 1
- 208000023178 Musculoskeletal disease Diseases 0.000 description 1
- 206010028570 Myelopathy Diseases 0.000 description 1
- RHGKLRLOHDJJDR-UHFFFAOYSA-N Ndelta-carbamoyl-DL-ornithine Natural products OC(=O)C(N)CCCNC(N)=O RHGKLRLOHDJJDR-UHFFFAOYSA-N 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 206010034277 Pemphigoid Diseases 0.000 description 1
- 241000721454 Pemphigus Species 0.000 description 1
- 208000031845 Pernicious anaemia Diseases 0.000 description 1
- 206010065159 Polychondritis Diseases 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 208000012654 Primary biliary cholangitis Diseases 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 201000001263 Psoriatic Arthritis Diseases 0.000 description 1
- 208000036824 Psoriatic arthropathy Diseases 0.000 description 1
- 206010065874 Psoriatic conditions Diseases 0.000 description 1
- 206010071141 Rasmussen encephalitis Diseases 0.000 description 1
- 208000004160 Rasmussen subacute encephalitis Diseases 0.000 description 1
- MEFKEPWMEQBLKI-AIRLBKTGSA-O S-adenosyl-L-methionine Chemical compound O[C@@H]1[C@H](O)[C@@H](C[S+](CC[C@H]([NH3+])C([O-])=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 MEFKEPWMEQBLKI-AIRLBKTGSA-O 0.000 description 1
- 206010039710 Scleroderma Diseases 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- 229930182558 Sterol Natural products 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 208000024780 Urticaria Diseases 0.000 description 1
- 206010046851 Uveitis Diseases 0.000 description 1
- 208000036826 VIIth nerve paralysis Diseases 0.000 description 1
- 206010047115 Vasculitis Diseases 0.000 description 1
- 102100026383 Vasopressin-neurophysin 2-copeptin Human genes 0.000 description 1
- 206010047642 Vitiligo Diseases 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 230000004520 agglutination Effects 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 208000004631 alopecia areata Diseases 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 210000001188 articular cartilage Anatomy 0.000 description 1
- 210000003567 ascitic fluid Anatomy 0.000 description 1
- 201000011385 autoimmune polyendocrine syndrome Diseases 0.000 description 1
- 201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 208000000594 bullous pemphigoid Diseases 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 208000025302 chronic primary adrenal insufficiency Diseases 0.000 description 1
- 229960002173 citrulline Drugs 0.000 description 1
- 235000013477 citrulline Nutrition 0.000 description 1
- 238000003759 clinical diagnosis Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 208000004921 cutaneous lupus erythematosus Diseases 0.000 description 1
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 201000001981 dermatomyositis Diseases 0.000 description 1
- 230000001066 destructive effect Effects 0.000 description 1
- 201000010064 diabetes insipidus Diseases 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 230000009266 disease activity Effects 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 206010014599 encephalitis Diseases 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000003205 genotyping method Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 230000035931 haemagglutination Effects 0.000 description 1
- 208000007475 hemolytic anemia Diseases 0.000 description 1
- 208000002557 hidradenitis Diseases 0.000 description 1
- 201000007162 hidradenitis suppurativa Diseases 0.000 description 1
- 230000001744 histochemical effect Effects 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 210000004153 islets of langerhan Anatomy 0.000 description 1
- 239000004816 latex Substances 0.000 description 1
- 229920000126 latex Polymers 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 238000002705 metabolomic analysis Methods 0.000 description 1
- 230000001431 metabolomic effect Effects 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000000491 multivariate analysis Methods 0.000 description 1
- 208000029766 myalgic encephalomeyelitis/chronic fatigue syndrome Diseases 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 230000036963 noncompetitive effect Effects 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 230000008816 organ damage Effects 0.000 description 1
- 210000004789 organ system Anatomy 0.000 description 1
- 239000000123 paper Substances 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 238000000053 physical method Methods 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000002985 plastic film Substances 0.000 description 1
- 229920006255 plastic film Polymers 0.000 description 1
- 208000005987 polymyositis Diseases 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 238000002203 pretreatment Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 201000000742 primary sclerosing cholangitis Diseases 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 238000007409 radiographic assessment Methods 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 208000009169 relapsing polychondritis Diseases 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000011808 rodent model Methods 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 208000010157 sclerosing cholangitis Diseases 0.000 description 1
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 210000005065 subchondral bone plate Anatomy 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 210000004243 sweat Anatomy 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 206010043778 thyroiditis Diseases 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 238000000411 transmission spectrum Methods 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6803—General methods of protein analysis not limited to specific proteins or families of proteins
- G01N33/6806—Determination of free amino acids
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6803—General methods of protein analysis not limited to specific proteins or families of proteins
- G01N33/6806—Determination of free amino acids
- G01N33/6812—Assays for specific amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/564—Immunoassay; Biospecific binding assay; Materials therefor for pre-existing immune complex or autoimmune disease, i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/10—Musculoskeletal or connective tissue disorders
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/10—Musculoskeletal or connective tissue disorders
- G01N2800/101—Diffuse connective tissue disease, e.g. Sjögren, Wegener's granulomatosis
- G01N2800/102—Arthritis; Rheumatoid arthritis, i.e. inflammation of peripheral joints
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/10—Musculoskeletal or connective tissue disorders
- G01N2800/105—Osteoarthritis, e.g. cartilage alteration, hypertrophy of bone
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/24—Immunology or allergic disorders
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/52—Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/56—Staging of a disease; Further complications associated with the disease
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/60—Complex ways of combining multiple protein biomarkers for diagnosis
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Hematology (AREA)
- Chemical & Material Sciences (AREA)
- Urology & Nephrology (AREA)
- Biomedical Technology (AREA)
- Physics & Mathematics (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Food Science & Technology (AREA)
- Microbiology (AREA)
- Cell Biology (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Bioinformatics & Computational Biology (AREA)
- Rheumatology (AREA)
- Rehabilitation Therapy (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Physical Education & Sports Medicine (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0905098A GB0905098D0 (en) | 2009-03-24 | 2009-03-24 | Use of biomarkers |
| GB0905096A GB0905096D0 (en) | 2009-03-24 | 2009-03-24 | Biomarkers |
| GB0905090A GB0905090D0 (en) | 2009-03-24 | 2009-03-24 | Biomarkers |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| GB201004994D0 GB201004994D0 (en) | 2010-05-12 |
| GB2470803A true GB2470803A (en) | 2010-12-08 |
Family
ID=42228305
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB1004994A Withdrawn GB2470803A (en) | 2009-03-24 | 2010-03-24 | Diagnosis and treatment of arthritis |
Country Status (6)
| Country | Link |
|---|---|
| US (2) | US20120108668A1 (https=) |
| EP (1) | EP2411812B1 (https=) |
| JP (1) | JP5607719B2 (https=) |
| ES (1) | ES2432534T3 (https=) |
| GB (1) | GB2470803A (https=) |
| WO (1) | WO2010109192A1 (https=) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2470270A1 (en) * | 2009-07-31 | 2012-07-04 | AnaMar AB | Compounds for treatment of inflammation |
| JP6198377B2 (ja) * | 2012-09-14 | 2017-09-20 | キヤノン株式会社 | 表示制御装置、表示制御方法、及びプログラム |
| US20160061812A1 (en) * | 2013-03-15 | 2016-03-03 | The University Of Birmingham | Diagnosis and Treatment of Arthritic Conditions |
| CN103675181A (zh) * | 2013-12-05 | 2014-03-26 | 陈东 | 气相色谱-质谱检测细胞内外液中有机酸、氨基酸、糖的方法 |
| CN106175684B (zh) * | 2016-07-13 | 2018-12-21 | 华南师范大学 | 基于激光光谱技术的人体股骨头病变早期诊断设备及其操作方法 |
| CN109115905A (zh) * | 2018-07-31 | 2019-01-01 | 苏州旭辉检测有限公司 | 一种血液样本中鸟氨酸的检测方法 |
| CN111307792A (zh) * | 2020-02-20 | 2020-06-19 | 江苏大学 | 一种猪肉食源性致病菌挥发性代谢物的色敏仿生传感检测方法 |
| GB202102105D0 (en) * | 2021-02-15 | 2021-03-31 | Novabiotics Ltd | Prognostic method |
| CN115290797A (zh) * | 2022-09-13 | 2022-11-04 | 贵州医科大学 | 基于气质联用技术的黑骨藤抗类风湿性关节炎代谢组学研究方法 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070088085A1 (en) * | 2000-08-07 | 2007-04-19 | Melacure Therapeutics Ab | Use of benzylideneaminoguanidines and hydroxyguanidines as melanocortin receptor ligands |
| US20070218561A1 (en) * | 2004-10-12 | 2007-09-20 | Quest Diagnostics Investments Incorporated | Analysis of amino acids in body fluid by liquid chromatography-mass spectrometry |
| WO2009006338A1 (en) * | 2007-06-29 | 2009-01-08 | Quest Diagnostics Investments Incorporated | Analysis of amino acids in body fluid by liquid chromatography-mass spectrometry |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4946778A (en) | 1987-09-21 | 1990-08-07 | Genex Corporation | Single polypeptide chain binding molecules |
| WO2005094200A2 (en) | 2003-06-20 | 2005-10-13 | University Of Florida | Biomarkers for differentiating between type 2 and type 2 diabetes |
| WO2006066263A1 (en) | 2004-12-17 | 2006-06-22 | Entelos, Inc. | Assessing insulin resistance using biomarkers |
| EP2339346B1 (en) | 2006-03-24 | 2014-09-03 | Metanomics GmbH | Methods for predicting diabetes type II |
| DE102006026173A1 (de) | 2006-06-06 | 2007-12-20 | Fachhochschule Südwestfalen | Verfahren zur nichtinvasiven Diagnose von Diabetes |
| EP2047278B1 (en) | 2006-07-28 | 2013-01-02 | Gian Franco Bottazzo | Prediction of type 1 diabetes |
| US20090318392A1 (en) | 2006-09-14 | 2009-12-24 | Zora Biosciences Oy | Biofluid metabolite profiling as a tool for early prediction of autoimmunity and type 1 diabetes risk |
-
2010
- 2010-03-24 GB GB1004994A patent/GB2470803A/en not_active Withdrawn
- 2010-03-24 WO PCT/GB2010/000557 patent/WO2010109192A1/en not_active Ceased
- 2010-03-24 JP JP2012501376A patent/JP5607719B2/ja not_active Expired - Fee Related
- 2010-03-24 US US13/259,733 patent/US20120108668A1/en not_active Abandoned
- 2010-03-24 ES ES10710609T patent/ES2432534T3/es active Active
- 2010-03-24 EP EP10710609.8A patent/EP2411812B1/en not_active Not-in-force
-
2015
- 2015-07-24 US US14/807,920 patent/US20160018407A1/en not_active Abandoned
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070088085A1 (en) * | 2000-08-07 | 2007-04-19 | Melacure Therapeutics Ab | Use of benzylideneaminoguanidines and hydroxyguanidines as melanocortin receptor ligands |
| US20070218561A1 (en) * | 2004-10-12 | 2007-09-20 | Quest Diagnostics Investments Incorporated | Analysis of amino acids in body fluid by liquid chromatography-mass spectrometry |
| WO2009006338A1 (en) * | 2007-06-29 | 2009-01-08 | Quest Diagnostics Investments Incorporated | Analysis of amino acids in body fluid by liquid chromatography-mass spectrometry |
Non-Patent Citations (3)
| Title |
|---|
| Annals of Rheumatic Diseases 22 (1963) Nettelbladt and Sandell 'Amino-acid content of serum in Rheumatoid Arthritis' 269-272 * |
| Clinical Rheumatology 25 (2006) Schroecksnadel et al 'Tryptophan degradation increases with stage in patients with rheumatoid arthritis' 334-337 * |
| Zeitschrift fur Rheumatologie 37 (1978) Partsch et al 'Plasma amino-acid level in Rheumatoid Arthritis and Ankylosing Spondylitis and its variation during age' 105-111 * |
Also Published As
| Publication number | Publication date |
|---|---|
| GB201004994D0 (en) | 2010-05-12 |
| JP2012521551A (ja) | 2012-09-13 |
| ES2432534T3 (es) | 2013-12-04 |
| US20160018407A1 (en) | 2016-01-21 |
| EP2411812A1 (en) | 2012-02-01 |
| US20120108668A1 (en) | 2012-05-03 |
| WO2010109192A1 (en) | 2010-09-30 |
| EP2411812B1 (en) | 2013-10-02 |
| JP5607719B2 (ja) | 2014-10-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20160018407A1 (en) | Metabolic profiles | |
| Popoviciu et al. | Type 1 diabetes mellitus and autoimmune diseases: a critical review of the association and the application of personalized medicine | |
| Wandinger et al. | Anti-NMDA-receptor encephalitis: a severe, multistage, treatable disorder presenting with psychosis | |
| Jorissen et al. | Relapsing-remitting multiple sclerosis patients display an altered lipoprotein profile with dysfunctional HDL | |
| De Jong et al. | Automated mass spectrometric analysis of urinary and plasma serotonin | |
| EP3028049B1 (en) | Diagnostic tools for alzheimer's disease | |
| JP6333731B2 (ja) | 低伝導率条件下の高感度を有する自己抗体測定法 | |
| Zhou et al. | Decreased levels of serum retinoic acid in chinese children with autism spectrum disorder | |
| Yang et al. | H4K12 lactylation potentiates mitochondrial oxidative stress via the Foxo1 pathway in diabetes-induced cognitive impairment | |
| RU2524641C2 (ru) | Способ детекции дегенеративных мышечных заболеваний и способ определения терапевтической эффективности при заболеваниях | |
| WO2021157634A1 (ja) | タウオパチーおよび認知症関連疾患の判定薬および判定方法 | |
| CN112639476B (zh) | 肾病变蛋白生物标记及其应用 | |
| Krieg et al. | An MRM-based multiplexed quantification assay for human adipokines and apolipoproteins | |
| Al-Dajani et al. | Liquid chromatography-mass spectrometry analytical methods for the quantitation of p-cresol sulfate and indoxyl sulfate in human matrices: biological applications and diagnostic potentials | |
| JP6663000B2 (ja) | 関節リウマチの診断のための自己抗原 | |
| Park et al. | Evaluation of a specific diagnostic marker for rheumatoid arthritis based on cyclic citrullinated peptide | |
| Peng et al. | Metabolomic profiling of bronchoalveolar lavage fluids by isotope labeling liquid chromatography mass spectrometry: a promising approach to studying experimental asthma | |
| Zhu et al. | GC-MS based comparative metabolomic analysis of human cancellous bone reveals the critical role of linoleic acid metabolism in femur head necrosis | |
| Ogrin et al. | Positive test for antithyroglobulin antibodies due to administration of immunoglobulin replacement therapy in a patient with thyroid cancer | |
| WO2001025787A1 (en) | p-CRESOL SULFATE, A COMPONENT OF URINARY MYELIN BASIC PROTEIN-LIKE MATERIAL, AS A CORRELATE OF MULTIPLE SCLEROSIS STATUS | |
| JP6830899B2 (ja) | 冠動脈疾患の診断マーカー | |
| Tang et al. | Increased plasma acylation-stimulating protein in pediatric proteinuric renal disease | |
| WO2019111797A1 (ja) | 筋疾患の診断のためのバイオマーカー | |
| Pranzatelli et al. | Neurometabolic effects of ACTH on free amino compounds in opsoclonus-myoclonus syndrome | |
| Fernández-Puente et al. | Proteomic Profiling of Human Synovial Fluid Reveals AKR1C1 as a Biomarker of Osteoarthritis Severity |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| WAP | Application withdrawn, taken to be withdrawn or refused ** after publication under section 16(1) |