CA2828595C - Utilisation de tetraamines chelatant le cuivre destines au traitement de maladies cardiovasculaires et d'insuffisance cardiaque - Google Patents
Utilisation de tetraamines chelatant le cuivre destines au traitement de maladies cardiovasculaires et d'insuffisance cardiaque Download PDFInfo
- Publication number
- CA2828595C CA2828595C CA2828595A CA2828595A CA2828595C CA 2828595 C CA2828595 C CA 2828595C CA 2828595 A CA2828595 A CA 2828595A CA 2828595 A CA2828595 A CA 2828595A CA 2828595 C CA2828595 C CA 2828595C
- Authority
- CA
- Canada
- Prior art keywords
- copper
- patient
- diabetic
- diabetes
- trientine
- 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.)
- Expired - Fee Related
Links
- 239000010949 copper Substances 0.000 title claims abstract description 532
- 229910052802 copper Inorganic materials 0.000 title claims abstract description 529
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 title claims abstract description 519
- 206010019280 Heart failures Diseases 0.000 title claims description 36
- 208000024172 Cardiovascular disease Diseases 0.000 title description 7
- 230000002792 vascular Effects 0.000 claims abstract description 69
- 210000000056 organ Anatomy 0.000 claims abstract description 45
- 210000004165 myocardium Anatomy 0.000 claims abstract description 38
- 230000001419 dependent effect Effects 0.000 claims abstract description 33
- 206010012601 diabetes mellitus Diseases 0.000 claims description 247
- 210000001519 tissue Anatomy 0.000 claims description 107
- 241000282414 Homo sapiens Species 0.000 claims description 104
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 101
- VILCJCGEZXAXTO-UHFFFAOYSA-N 2,2,2-tetramine Chemical compound NCCNCCNCCN VILCJCGEZXAXTO-UHFFFAOYSA-N 0.000 claims description 79
- 229960001124 trientine Drugs 0.000 claims description 65
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 59
- 210000004204 blood vessel Anatomy 0.000 claims description 50
- 208000031229 Cardiomyopathies Diseases 0.000 claims description 45
- 230000006378 damage Effects 0.000 claims description 39
- 206010048858 Ischaemic cardiomyopathy Diseases 0.000 claims description 38
- 206010058222 Hypertensive cardiomyopathy Diseases 0.000 claims description 35
- 239000003814 drug Substances 0.000 claims description 34
- 210000002216 heart Anatomy 0.000 claims description 33
- 206010020772 Hypertension Diseases 0.000 claims description 31
- 229910052742 iron Inorganic materials 0.000 claims description 30
- 230000000747 cardiac effect Effects 0.000 claims description 29
- 210000001367 artery Anatomy 0.000 claims description 28
- 229940079593 drug Drugs 0.000 claims description 28
- 230000000451 tissue damage Effects 0.000 claims description 28
- 231100000827 tissue damage Toxicity 0.000 claims description 28
- 210000002565 arteriole Anatomy 0.000 claims description 27
- 208000002972 Hepatolenticular Degeneration Diseases 0.000 claims description 26
- 208000018839 Wilson disease Diseases 0.000 claims description 26
- 210000003734 kidney Anatomy 0.000 claims description 24
- 210000000709 aorta Anatomy 0.000 claims description 23
- 231100000331 toxic Toxicity 0.000 claims description 22
- 230000002588 toxic effect Effects 0.000 claims description 22
- 210000004351 coronary vessel Anatomy 0.000 claims description 21
- 230000003902 lesion Effects 0.000 claims description 21
- 210000001715 carotid artery Anatomy 0.000 claims description 19
- 238000004519 manufacturing process Methods 0.000 claims description 19
- 210000003090 iliac artery Anatomy 0.000 claims description 18
- 210000003137 popliteal artery Anatomy 0.000 claims description 18
- 210000002254 renal artery Anatomy 0.000 claims description 18
- 230000002107 myocardial effect Effects 0.000 claims description 14
- AGGKEGLBGGJEBZ-UHFFFAOYSA-N tetramethylenedisulfotetramine Chemical compound C1N(S2(=O)=O)CN3S(=O)(=O)N1CN2C3 AGGKEGLBGGJEBZ-UHFFFAOYSA-N 0.000 claims description 14
- 230000002207 retinal effect Effects 0.000 claims description 13
- 210000001125 vasa nervorum Anatomy 0.000 claims description 13
- 210000001105 femoral artery Anatomy 0.000 claims description 12
- 201000010053 Alcoholic Cardiomyopathy Diseases 0.000 claims description 9
- 206010007637 Cardiomyopathy alcoholic Diseases 0.000 claims description 9
- 206010070909 Metabolic cardiomyopathy Diseases 0.000 claims description 9
- WYHIICXRPHEJKI-UHFFFAOYSA-N Trientine hydrochloride Chemical compound Cl.Cl.NCCNCCNCCN WYHIICXRPHEJKI-UHFFFAOYSA-N 0.000 claims description 9
- 210000003169 central nervous system Anatomy 0.000 claims description 9
- 208000022368 idiopathic cardiomyopathy Diseases 0.000 claims description 9
- 210000001428 peripheral nervous system Anatomy 0.000 claims description 9
- 150000005671 trienes Chemical class 0.000 claims description 9
- 229960002408 trientine hydrochloride Drugs 0.000 claims description 9
- UWMHHZFHBCYGCV-UHFFFAOYSA-N 2,3,2-tetramine Chemical compound NCCNCCCNCCN UWMHHZFHBCYGCV-UHFFFAOYSA-N 0.000 claims description 8
- JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical compound [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 0.000 claims description 8
- 230000001413 cellular effect Effects 0.000 claims description 8
- 239000003085 diluting agent Substances 0.000 claims description 8
- 230000001434 glomerular Effects 0.000 claims description 8
- 208000030159 metabolic disease Diseases 0.000 claims description 8
- 239000000969 carrier Substances 0.000 claims description 7
- OKHMDSCYUWAQPT-UHFFFAOYSA-N n'-[2-(2-aminoethylamino)ethyl]ethane-1,2-diamine;tetrahydrochloride Chemical compound Cl.Cl.Cl.Cl.NCCNCCNCCN OKHMDSCYUWAQPT-UHFFFAOYSA-N 0.000 claims description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- 208000007848 Alcoholism Diseases 0.000 claims description 3
- 201000007930 alcohol dependence Diseases 0.000 claims description 3
- 238000007911 parenteral administration Methods 0.000 claims description 3
- 239000002552 dosage form Substances 0.000 claims 2
- 208000025494 Aortic disease Diseases 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 214
- 239000003795 chemical substances by application Substances 0.000 abstract description 131
- 230000017423 tissue regeneration Effects 0.000 abstract description 46
- 241000124008 Mammalia Species 0.000 description 114
- 230000003247 decreasing effect Effects 0.000 description 100
- 239000002738 chelating agent Substances 0.000 description 96
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 81
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical group 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 70
- 208000002705 Glucose Intolerance Diseases 0.000 description 62
- 201000010099 disease Diseases 0.000 description 61
- 201000009104 prediabetes syndrome Diseases 0.000 description 59
- 210000000130 stem cell Anatomy 0.000 description 55
- 230000001965 increasing effect Effects 0.000 description 53
- 239000011701 zinc Substances 0.000 description 52
- 229910052725 zinc Inorganic materials 0.000 description 51
- 238000012544 monitoring process Methods 0.000 description 49
- 150000001875 compounds Chemical class 0.000 description 48
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 47
- 230000001771 impaired effect Effects 0.000 description 47
- 150000003839 salts Chemical class 0.000 description 42
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 41
- 239000011780 sodium chloride Substances 0.000 description 41
- 241001465754 Metazoa Species 0.000 description 39
- 208000029078 coronary artery disease Diseases 0.000 description 38
- 206010056997 Impaired fasting glucose Diseases 0.000 description 36
- 102000004877 Insulin Human genes 0.000 description 35
- 108090001061 Insulin Proteins 0.000 description 35
- 229940125396 insulin Drugs 0.000 description 35
- 230000007246 mechanism Effects 0.000 description 34
- VVNCNSJFMMFHPL-VKHMYHEASA-N D-penicillamine Chemical compound CC(C)(S)[C@@H](N)C(O)=O VVNCNSJFMMFHPL-VKHMYHEASA-N 0.000 description 33
- 229960001639 penicillamine Drugs 0.000 description 33
- 108010005094 Advanced Glycation End Products Proteins 0.000 description 32
- 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 32
- 238000003745 diagnosis Methods 0.000 description 32
- 239000008103 glucose Substances 0.000 description 32
- 239000000203 mixture Substances 0.000 description 32
- 238000010521 absorption reaction Methods 0.000 description 30
- 230000009920 chelation Effects 0.000 description 30
- 208000035475 disorder Diseases 0.000 description 30
- 210000002700 urine Anatomy 0.000 description 28
- 230000005856 abnormality Effects 0.000 description 27
- 201000001320 Atherosclerosis Diseases 0.000 description 26
- 210000004027 cell Anatomy 0.000 description 26
- 230000036755 cellular response Effects 0.000 description 26
- 229940050410 gluconate Drugs 0.000 description 26
- 230000004217 heart function Effects 0.000 description 26
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 25
- 229910052723 transition metal Inorganic materials 0.000 description 25
- 150000003624 transition metals Chemical class 0.000 description 25
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 23
- 206010022489 Insulin Resistance Diseases 0.000 description 22
- 230000007423 decrease Effects 0.000 description 22
- 230000006735 deficit Effects 0.000 description 22
- 230000001631 hypertensive effect Effects 0.000 description 22
- 230000015572 biosynthetic process Effects 0.000 description 21
- 230000029142 excretion Effects 0.000 description 21
- 230000036252 glycation Effects 0.000 description 21
- 208000010125 myocardial infarction Diseases 0.000 description 21
- 230000008929 regeneration Effects 0.000 description 21
- 238000011069 regeneration method Methods 0.000 description 21
- 230000000694 effects Effects 0.000 description 20
- 230000009467 reduction Effects 0.000 description 20
- 230000008439 repair process Effects 0.000 description 20
- 108010007622 LDL Lipoproteins Proteins 0.000 description 19
- 102000007330 LDL Lipoproteins Human genes 0.000 description 19
- 102000004895 Lipoproteins Human genes 0.000 description 19
- 108090001030 Lipoproteins Proteins 0.000 description 19
- 201000001421 hyperglycemia Diseases 0.000 description 19
- 230000008569 process Effects 0.000 description 19
- 206010000891 acute myocardial infarction Diseases 0.000 description 18
- 230000004153 glucose metabolism Effects 0.000 description 18
- -1 polyol compounds Chemical class 0.000 description 18
- 210000002966 serum Anatomy 0.000 description 18
- 238000009825 accumulation Methods 0.000 description 17
- CXVCSRUYMINUSF-UHFFFAOYSA-N tetrathiomolybdate(2-) Chemical compound [S-][Mo]([S-])(=S)=S CXVCSRUYMINUSF-UHFFFAOYSA-N 0.000 description 17
- 206010054805 Macroangiopathy Diseases 0.000 description 16
- 230000035508 accumulation Effects 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 16
- 229910052751 metal Inorganic materials 0.000 description 16
- 239000002184 metal Substances 0.000 description 16
- 108010062497 VLDL Lipoproteins Proteins 0.000 description 15
- 230000001404 mediated effect Effects 0.000 description 15
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 15
- 206010010957 Copper deficiency Diseases 0.000 description 14
- 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 14
- 229920001436 collagen Polymers 0.000 description 14
- 238000001727 in vivo Methods 0.000 description 14
- 108090000623 proteins and genes Proteins 0.000 description 14
- 150000003254 radicals Chemical class 0.000 description 14
- 102000008186 Collagen Human genes 0.000 description 13
- 108010035532 Collagen Proteins 0.000 description 13
- 208000032781 Diabetic cardiomyopathy Diseases 0.000 description 13
- 108010010234 HDL Lipoproteins Proteins 0.000 description 13
- 102000015779 HDL Lipoproteins Human genes 0.000 description 13
- 230000002526 effect on cardiovascular system Effects 0.000 description 13
- 150000002739 metals Chemical class 0.000 description 13
- 102000004169 proteins and genes Human genes 0.000 description 13
- 238000001356 surgical procedure Methods 0.000 description 13
- 150000003751 zinc Chemical class 0.000 description 13
- SSRIAMRLMUFTNV-UHFFFAOYSA-N 2,6-pyridinedicarbothioic acid Chemical compound SC(=O)C1=CC=CC(C(S)=O)=N1 SSRIAMRLMUFTNV-UHFFFAOYSA-N 0.000 description 12
- YQUVCSBJEUQKSH-UHFFFAOYSA-N 3,4-dihydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C(O)=C1 YQUVCSBJEUQKSH-UHFFFAOYSA-N 0.000 description 12
- 108010049003 Fibrinogen Proteins 0.000 description 12
- 102000008946 Fibrinogen Human genes 0.000 description 12
- MNNBCKASUFBXCO-YFKPBYRVSA-N N-acetyl-D-penicillamine Chemical compound CC(=O)N[C@@H](C(O)=O)C(C)(C)S MNNBCKASUFBXCO-YFKPBYRVSA-N 0.000 description 12
- 102000012335 Plasminogen Activator Inhibitor 1 Human genes 0.000 description 12
- 108010022233 Plasminogen Activator Inhibitor 1 Proteins 0.000 description 12
- 230000001154 acute effect Effects 0.000 description 12
- 210000001508 eye Anatomy 0.000 description 12
- 229940012952 fibrinogen Drugs 0.000 description 12
- 230000006870 function Effects 0.000 description 12
- DCAYPVUWAIABOU-UHFFFAOYSA-N hexadecane Chemical compound CCCCCCCCCCCCCCCC DCAYPVUWAIABOU-UHFFFAOYSA-N 0.000 description 12
- 230000005012 migration Effects 0.000 description 12
- 238000013508 migration Methods 0.000 description 12
- 235000018102 proteins Nutrition 0.000 description 12
- 230000004044 response Effects 0.000 description 12
- 238000002560 therapeutic procedure Methods 0.000 description 12
- 230000002485 urinary effect Effects 0.000 description 12
- MDAXKAUIABOHTD-UHFFFAOYSA-N 1,4,8,11-tetraazacyclotetradecane Chemical compound C1CNCCNCCCNCCNC1 MDAXKAUIABOHTD-UHFFFAOYSA-N 0.000 description 11
- 241000700159 Rattus Species 0.000 description 11
- 230000037396 body weight Effects 0.000 description 11
- 230000001684 chronic effect Effects 0.000 description 11
- 230000001976 improved effect Effects 0.000 description 11
- 229910052748 manganese Inorganic materials 0.000 description 11
- 239000011572 manganese Substances 0.000 description 11
- 230000002503 metabolic effect Effects 0.000 description 11
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 10
- 238000004458 analytical method Methods 0.000 description 10
- 230000002950 deficient Effects 0.000 description 10
- 238000011161 development Methods 0.000 description 10
- 230000018109 developmental process Effects 0.000 description 10
- 210000005003 heart tissue Anatomy 0.000 description 10
- 239000002245 particle Substances 0.000 description 10
- 208000032928 Dyslipidaemia Diseases 0.000 description 9
- 208000025865 Ulcer Diseases 0.000 description 9
- 238000010586 diagram Methods 0.000 description 9
- 238000011049 filling Methods 0.000 description 9
- 239000000523 sample Substances 0.000 description 9
- 230000001629 suppression Effects 0.000 description 9
- 208000024891 symptom Diseases 0.000 description 9
- 230000002861 ventricular Effects 0.000 description 9
- 108010047303 von Willebrand Factor Proteins 0.000 description 9
- 102100036537 von Willebrand factor Human genes 0.000 description 9
- 229960001134 von willebrand factor Drugs 0.000 description 9
- 208000004476 Acute Coronary Syndrome Diseases 0.000 description 8
- 208000002249 Diabetes Complications Diseases 0.000 description 8
- 208000009525 Myocarditis Diseases 0.000 description 8
- ZOIORXHNWRGPMV-UHFFFAOYSA-N acetic acid;zinc Chemical compound [Zn].CC(O)=O.CC(O)=O ZOIORXHNWRGPMV-UHFFFAOYSA-N 0.000 description 8
- 230000009471 action Effects 0.000 description 8
- 210000004369 blood Anatomy 0.000 description 8
- 239000008280 blood Substances 0.000 description 8
- 230000003511 endothelial effect Effects 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 8
- 230000020764 fibrinolysis Effects 0.000 description 8
- 208000006575 hypertriglyceridemia Diseases 0.000 description 8
- 208000015181 infectious disease Diseases 0.000 description 8
- 208000014674 injury Diseases 0.000 description 8
- 150000002632 lipids Chemical class 0.000 description 8
- 239000002207 metabolite Substances 0.000 description 8
- 239000004246 zinc acetate Substances 0.000 description 8
- 102100023804 Coagulation factor VII Human genes 0.000 description 7
- 108010023321 Factor VII Proteins 0.000 description 7
- 108010073385 Fibrin Proteins 0.000 description 7
- 102000009123 Fibrin Human genes 0.000 description 7
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 7
- 241000282412 Homo Species 0.000 description 7
- 208000017170 Lipid metabolism disease Diseases 0.000 description 7
- 208000007536 Thrombosis Diseases 0.000 description 7
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 7
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 7
- 208000026062 Tissue disease Diseases 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 230000003143 atherosclerotic effect Effects 0.000 description 7
- 230000008901 benefit Effects 0.000 description 7
- 230000004087 circulation Effects 0.000 description 7
- AUZONCFQVSMFAP-UHFFFAOYSA-N disulfiram Chemical compound CCN(CC)C(=S)SSC(=S)N(CC)CC AUZONCFQVSMFAP-UHFFFAOYSA-N 0.000 description 7
- 229940012413 factor vii Drugs 0.000 description 7
- 229950003499 fibrin Drugs 0.000 description 7
- 238000001990 intravenous administration Methods 0.000 description 7
- 230000036470 plasma concentration Effects 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 102000005962 receptors Human genes 0.000 description 7
- 108020003175 receptors Proteins 0.000 description 7
- 229960000187 tissue plasminogen activator Drugs 0.000 description 7
- 230000036269 ulceration Effects 0.000 description 7
- JLVSRWOIZZXQAD-UHFFFAOYSA-N 2,3-disulfanylpropane-1-sulfonic acid Chemical compound OS(=O)(=O)CC(S)CS JLVSRWOIZZXQAD-UHFFFAOYSA-N 0.000 description 6
- AGMNQPKGRCRYQP-UHFFFAOYSA-N 2-[2-[2-[bis(carboxymethyl)amino]ethylamino]ethyl-(carboxymethyl)amino]acetic acid Chemical compound OC(=O)CN(CC(O)=O)CCNCCN(CC(O)=O)CC(O)=O AGMNQPKGRCRYQP-UHFFFAOYSA-N 0.000 description 6
- WYMDDFRYORANCC-UHFFFAOYSA-N 2-[[3-[bis(carboxymethyl)amino]-2-hydroxypropyl]-(carboxymethyl)amino]acetic acid Chemical compound OC(=O)CN(CC(O)=O)CC(O)CN(CC(O)=O)CC(O)=O WYMDDFRYORANCC-UHFFFAOYSA-N 0.000 description 6
- LXOPCHVYWBGPND-VOTSOKGWSA-N 4-[(e)-2-phenylethenyl]benzene-1,2,3-triol Chemical compound OC1=C(O)C(O)=CC=C1\C=C\C1=CC=CC=C1 LXOPCHVYWBGPND-VOTSOKGWSA-N 0.000 description 6
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 6
- 108010075016 Ceruloplasmin Proteins 0.000 description 6
- 102100023321 Ceruloplasmin Human genes 0.000 description 6
- QCDFBFJGMNKBDO-UHFFFAOYSA-N Clioquinol Chemical compound C1=CN=C2C(O)=C(I)C=C(Cl)C2=C1 QCDFBFJGMNKBDO-UHFFFAOYSA-N 0.000 description 6
- DSRJIHMZAQEUJV-UHFFFAOYSA-N Cuprizon Chemical compound C1CCCCC1=NNC(=O)C(=O)NN=C1CCCCC1 DSRJIHMZAQEUJV-UHFFFAOYSA-N 0.000 description 6
- 206010060378 Hyperinsulinaemia Diseases 0.000 description 6
- YJPIGAIKUZMOQA-UHFFFAOYSA-N Melatonin Natural products COC1=CC=C2N(C(C)=O)C=C(CCN)C2=C1 YJPIGAIKUZMOQA-UHFFFAOYSA-N 0.000 description 6
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 6
- 208000008589 Obesity Diseases 0.000 description 6
- 208000027418 Wounds and injury Diseases 0.000 description 6
- 230000004913 activation Effects 0.000 description 6
- 230000002411 adverse Effects 0.000 description 6
- 230000032683 aging Effects 0.000 description 6
- FBKZHCDISZZXDK-UHFFFAOYSA-N bathocuproine disulfonic acid Chemical compound C=12C=CC3=C(C=4C=CC(=CC=4)S(O)(=O)=O)C=C(C)N=C3C2=NC(C)=CC=1C1=CC=C(S(O)(=O)=O)C=C1 FBKZHCDISZZXDK-UHFFFAOYSA-N 0.000 description 6
- 230000008859 change Effects 0.000 description 6
- 229960005228 clioquinol Drugs 0.000 description 6
- 230000007812 deficiency Effects 0.000 description 6
- 230000003205 diastolic effect Effects 0.000 description 6
- 229940116901 diethyldithiocarbamate Drugs 0.000 description 6
- 210000002889 endothelial cell Anatomy 0.000 description 6
- 229940088598 enzyme Drugs 0.000 description 6
- 208000019622 heart disease Diseases 0.000 description 6
- 230000006872 improvement Effects 0.000 description 6
- 230000003914 insulin secretion Effects 0.000 description 6
- 230000003834 intracellular effect Effects 0.000 description 6
- 230000000302 ischemic effect Effects 0.000 description 6
- 210000004185 liver Anatomy 0.000 description 6
- 230000007774 longterm Effects 0.000 description 6
- DRLFMBDRBRZALE-UHFFFAOYSA-N melatonin Chemical compound COC1=CC=C2NC=C(CCNC(C)=O)C2=C1 DRLFMBDRBRZALE-UHFFFAOYSA-N 0.000 description 6
- 229960003987 melatonin Drugs 0.000 description 6
- 210000005036 nerve Anatomy 0.000 description 6
- 235000020824 obesity Nutrition 0.000 description 6
- 239000008194 pharmaceutical composition Substances 0.000 description 6
- LUKBXSAWLPMMSZ-UHFFFAOYSA-N resveratrol Chemical compound C1=CC(O)=CC=C1C=CC1=CC(O)=CC(O)=C1 LUKBXSAWLPMMSZ-UHFFFAOYSA-N 0.000 description 6
- FGGPAWQCCGEWTJ-UHFFFAOYSA-M sodium;2,3-bis(sulfanyl)propane-1-sulfonate Chemical compound [Na+].[O-]S(=O)(=O)CC(S)CS FGGPAWQCCGEWTJ-UHFFFAOYSA-M 0.000 description 6
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 6
- ACTRVOBWPAIOHC-UHFFFAOYSA-N succimer Chemical compound OC(=O)C(S)C(S)C(O)=O ACTRVOBWPAIOHC-UHFFFAOYSA-N 0.000 description 6
- ACTRVOBWPAIOHC-XIXRPRMCSA-N succimer Chemical compound OC(=O)[C@@H](S)[C@@H](S)C(O)=O ACTRVOBWPAIOHC-XIXRPRMCSA-N 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- FAGUFWYHJQFNRV-UHFFFAOYSA-N tetraethylenepentamine Chemical compound NCCNCCNCCNCCN FAGUFWYHJQFNRV-UHFFFAOYSA-N 0.000 description 6
- 201000005665 thrombophilia Diseases 0.000 description 6
- OBBKVQRWBGOVCF-UHFFFAOYSA-N 1,4,8,11-tetrazabicyclo[6.6.2]hexadecane Chemical compound C1CCNCCN2CCCNCCN1CC2 OBBKVQRWBGOVCF-UHFFFAOYSA-N 0.000 description 5
- UQQQAKFVWNQYTP-UHFFFAOYSA-N 3,6,10,13,16,19-hexazabicyclo[6.6.6]icosane-1,8-diamine Chemical compound C1NCCNCC2(N)CNCCNCC1(N)CNCCNC2 UQQQAKFVWNQYTP-UHFFFAOYSA-N 0.000 description 5
- 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 5
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 5
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 5
- VSWDORGPIHIGNW-UHFFFAOYSA-N Pyrrolidine dithiocarbamic acid Chemical compound SC(=S)N1CCCC1 VSWDORGPIHIGNW-UHFFFAOYSA-N 0.000 description 5
- 102000005622 Receptor for Advanced Glycation End Products Human genes 0.000 description 5
- 108010045108 Receptor for Advanced Glycation End Products Proteins 0.000 description 5
- 208000001647 Renal Insufficiency Diseases 0.000 description 5
- JVHROZDXPAUZFK-UHFFFAOYSA-N TETA Chemical compound OC(=O)CN1CCCN(CC(O)=O)CCN(CC(O)=O)CCCN(CC(O)=O)CC1 JVHROZDXPAUZFK-UHFFFAOYSA-N 0.000 description 5
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 5
- HAMNKKUPIHEESI-UHFFFAOYSA-N aminoguanidine Chemical compound NNC(N)=N HAMNKKUPIHEESI-UHFFFAOYSA-N 0.000 description 5
- 230000006399 behavior Effects 0.000 description 5
- AYFCVLSUPGCQKD-UHFFFAOYSA-I calcium;trisodium;2-[bis[2-[bis(carboxylatomethyl)amino]ethyl]amino]acetate Chemical compound [Na+].[Na+].[Na+].[Ca+2].[O-]C(=O)CN(CC([O-])=O)CCN(CC(=O)[O-])CCN(CC([O-])=O)CC([O-])=O AYFCVLSUPGCQKD-UHFFFAOYSA-I 0.000 description 5
- 235000012000 cholesterol Nutrition 0.000 description 5
- 108700013553 diamsar chelate Proteins 0.000 description 5
- 235000005911 diet Nutrition 0.000 description 5
- WQABCVAJNWAXTE-UHFFFAOYSA-N dimercaprol Chemical compound OCC(S)CS WQABCVAJNWAXTE-UHFFFAOYSA-N 0.000 description 5
- 229960001484 edetic acid Drugs 0.000 description 5
- 210000003038 endothelium Anatomy 0.000 description 5
- 230000003480 fibrinolytic effect Effects 0.000 description 5
- 230000002068 genetic effect Effects 0.000 description 5
- 238000000673 graphite furnace atomic absorption spectrometry Methods 0.000 description 5
- 230000036541 health Effects 0.000 description 5
- 201000006370 kidney failure Diseases 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- PMRYVIKBURPHAH-UHFFFAOYSA-N methimazole Chemical compound CN1C=CNC1=S PMRYVIKBURPHAH-UHFFFAOYSA-N 0.000 description 5
- IYRGXJIJGHOCFS-UHFFFAOYSA-N neocuproine Chemical compound C1=C(C)N=C2C3=NC(C)=CC=C3C=CC2=C1 IYRGXJIJGHOCFS-UHFFFAOYSA-N 0.000 description 5
- 230000036542 oxidative stress Effects 0.000 description 5
- 239000002243 precursor Substances 0.000 description 5
- 210000001525 retina Anatomy 0.000 description 5
- 229960002178 thiamazole Drugs 0.000 description 5
- 150000003626 triacylglycerols Chemical class 0.000 description 5
- 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 230000029663 wound healing Effects 0.000 description 5
- 241000283690 Bos taurus Species 0.000 description 4
- 108010013563 Lipoprotein Lipase Proteins 0.000 description 4
- 102000043296 Lipoprotein lipases Human genes 0.000 description 4
- 241000288906 Primates Species 0.000 description 4
- 108090000190 Thrombin Proteins 0.000 description 4
- UHWVSEOVJBQKBE-UHFFFAOYSA-N Trimetazidine Chemical compound COC1=C(OC)C(OC)=CC=C1CN1CCNCC1 UHWVSEOVJBQKBE-UHFFFAOYSA-N 0.000 description 4
- 238000010171 animal model Methods 0.000 description 4
- 230000000923 atherogenic effect Effects 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 230000027455 binding Effects 0.000 description 4
- 230000008602 contraction Effects 0.000 description 4
- 238000004132 cross linking Methods 0.000 description 4
- 230000004069 differentiation Effects 0.000 description 4
- 230000003292 diminished effect Effects 0.000 description 4
- 230000002169 extracardiac Effects 0.000 description 4
- 239000003527 fibrinolytic agent Substances 0.000 description 4
- 235000021588 free fatty acids Nutrition 0.000 description 4
- 208000004104 gestational diabetes Diseases 0.000 description 4
- 230000002641 glycemic effect Effects 0.000 description 4
- 230000013595 glycosylation Effects 0.000 description 4
- 238000006206 glycosylation reaction Methods 0.000 description 4
- 230000035876 healing Effects 0.000 description 4
- 210000002064 heart cell Anatomy 0.000 description 4
- 230000003451 hyperinsulinaemic effect Effects 0.000 description 4
- 201000008980 hyperinsulinism Diseases 0.000 description 4
- 230000006698 induction Effects 0.000 description 4
- 238000001095 inductively coupled plasma mass spectrometry Methods 0.000 description 4
- 230000001483 mobilizing effect Effects 0.000 description 4
- VGICAQBLDJAGSJ-UHFFFAOYSA-N n'-[2-[2-(2-aminoethylamino)ethylamino]ethyl]ethane-1,2-diamine;pentahydrochloride Chemical compound Cl.Cl.Cl.Cl.Cl.NCCNCCNCCNCCN VGICAQBLDJAGSJ-UHFFFAOYSA-N 0.000 description 4
- 238000012261 overproduction Methods 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 230000008506 pathogenesis Effects 0.000 description 4
- 230000035935 pregnancy Effects 0.000 description 4
- 230000028327 secretion Effects 0.000 description 4
- 241000894007 species Species 0.000 description 4
- 238000007619 statistical method Methods 0.000 description 4
- 230000035882 stress Effects 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 229960004072 thrombin Drugs 0.000 description 4
- 229960001177 trimetazidine Drugs 0.000 description 4
- 210000005167 vascular cell Anatomy 0.000 description 4
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 4
- JWICNZAGYSIBAR-LEEGLKINSA-N (4s)-4-[[2-[[(2s)-2-[[(2s)-2-[[(2s)-2-aminopropanoyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]acetyl]amino]-5-[[2-[[(2s)-3-carboxy-1-[[(2s)-1-[[1-[[(2s)-1-[[(2s)-4-carboxy-1-[[2-[[2-[[2-[[(2s)-1-[[(1s)-1-carboxy-4-(diaminomethylideneamino Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)CNC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)C(CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](C)N)CC1=CC=CC=C1 JWICNZAGYSIBAR-LEEGLKINSA-N 0.000 description 3
- 208000004611 Abdominal Obesity Diseases 0.000 description 3
- 102100040214 Apolipoprotein(a) Human genes 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- 206010065941 Central obesity Diseases 0.000 description 3
- DSEPTGVNTPAJOE-UHFFFAOYSA-N Cl.Cl.Cl.Cl.NCCN.NCCCNCCNCCN Chemical compound Cl.Cl.Cl.Cl.NCCN.NCCCNCCNCCN DSEPTGVNTPAJOE-UHFFFAOYSA-N 0.000 description 3
- VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical compound [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 description 3
- 208000007342 Diabetic Nephropathies Diseases 0.000 description 3
- 206010012655 Diabetic complications Diseases 0.000 description 3
- 206010052337 Diastolic dysfunction Diseases 0.000 description 3
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 3
- 101800000974 Fibrinopeptide A Proteins 0.000 description 3
- 102400000525 Fibrinopeptide A Human genes 0.000 description 3
- 206010018429 Glucose tolerance impaired Diseases 0.000 description 3
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 3
- 108090000854 Oxidoreductases Proteins 0.000 description 3
- 102000004316 Oxidoreductases Human genes 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 208000008253 Systolic Heart Failure Diseases 0.000 description 3
- 230000004075 alteration Effects 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 230000001363 autoimmune Effects 0.000 description 3
- 210000003719 b-lymphocyte Anatomy 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 229910002092 carbon dioxide Inorganic materials 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 230000015271 coagulation Effects 0.000 description 3
- 238000005345 coagulation Methods 0.000 description 3
- 230000007547 defect Effects 0.000 description 3
- 230000008021 deposition Effects 0.000 description 3
- 208000033679 diabetic kidney disease Diseases 0.000 description 3
- 230000037213 diet Effects 0.000 description 3
- 230000004064 dysfunction Effects 0.000 description 3
- 230000007613 environmental effect Effects 0.000 description 3
- 229940012017 ethylenediamine Drugs 0.000 description 3
- 210000002744 extracellular matrix Anatomy 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 108091005996 glycated proteins Proteins 0.000 description 3
- 239000010439 graphite Substances 0.000 description 3
- 229910002804 graphite Inorganic materials 0.000 description 3
- 230000023597 hemostasis Effects 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 230000002427 irreversible effect Effects 0.000 description 3
- 238000012423 maintenance Methods 0.000 description 3
- 230000004060 metabolic process Effects 0.000 description 3
- 206010062198 microangiopathy Diseases 0.000 description 3
- 229910017604 nitric acid Inorganic materials 0.000 description 3
- 230000007310 pathophysiology Effects 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 230000002093 peripheral effect Effects 0.000 description 3
- 230000004962 physiological condition Effects 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 230000000391 smoking effect Effects 0.000 description 3
- 210000004872 soft tissue Anatomy 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 238000002054 transplantation Methods 0.000 description 3
- 230000008733 trauma Effects 0.000 description 3
- 229910001868 water Inorganic materials 0.000 description 3
- KPGXRSRHYNQIFN-UHFFFAOYSA-L 2-oxoglutarate(2-) Chemical compound [O-]C(=O)CCC(=O)C([O-])=O KPGXRSRHYNQIFN-UHFFFAOYSA-L 0.000 description 2
- 102000011767 Acute-Phase Proteins Human genes 0.000 description 2
- 108010062271 Acute-Phase Proteins Proteins 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 206010003211 Arteriosclerosis coronary artery Diseases 0.000 description 2
- 208000037260 Atherosclerotic Plaque Diseases 0.000 description 2
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 2
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- 206010007559 Cardiac failure congestive Diseases 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- 206010048554 Endothelial dysfunction Diseases 0.000 description 2
- 241000283086 Equidae Species 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- 102000008214 Glutamate decarboxylase Human genes 0.000 description 2
- 108091022930 Glutamate decarboxylase Proteins 0.000 description 2
- 229920002527 Glycogen Polymers 0.000 description 2
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 2
- 208000013038 Hypocalcemia Diseases 0.000 description 2
- 208000031773 Insulin resistance syndrome Diseases 0.000 description 2
- 108010033266 Lipoprotein(a) Proteins 0.000 description 2
- 102000005741 Metalloproteases Human genes 0.000 description 2
- 108010006035 Metalloproteases Proteins 0.000 description 2
- 208000029578 Muscle disease Diseases 0.000 description 2
- 206010052904 Musculoskeletal stiffness Diseases 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- 239000004698 Polyethylene Substances 0.000 description 2
- 206010063493 Premature ageing Diseases 0.000 description 2
- 102000003923 Protein Kinase C Human genes 0.000 description 2
- 108090000315 Protein Kinase C Proteins 0.000 description 2
- 208000017442 Retinal disease Diseases 0.000 description 2
- 206010038923 Retinopathy Diseases 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 description 2
- 241000282887 Suidae Species 0.000 description 2
- 229940123464 Thiazolidinedione Drugs 0.000 description 2
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 2
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 2
- 108010000134 Vascular Cell Adhesion Molecule-1 Proteins 0.000 description 2
- 102100023543 Vascular cell adhesion protein 1 Human genes 0.000 description 2
- VEUACKUBDLVUAC-UHFFFAOYSA-N [Na].[Ca] Chemical compound [Na].[Ca] VEUACKUBDLVUAC-UHFFFAOYSA-N 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000036586 afterload Effects 0.000 description 2
- 230000001668 ameliorated effect Effects 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 238000000540 analysis of variance Methods 0.000 description 2
- 208000007502 anemia Diseases 0.000 description 2
- 239000004019 antithrombin Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000004219 arterial function Effects 0.000 description 2
- 230000001746 atrial effect Effects 0.000 description 2
- 239000003114 blood coagulation factor Substances 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 230000024245 cell differentiation Effects 0.000 description 2
- 230000012292 cell migration Effects 0.000 description 2
- 239000013522 chelant Substances 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000001447 compensatory effect Effects 0.000 description 2
- 208000026758 coronary atherosclerosis Diseases 0.000 description 2
- 239000008367 deionised water Substances 0.000 description 2
- 229910021641 deionized water Inorganic materials 0.000 description 2
- 230000000378 dietary effect Effects 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 238000002592 echocardiography Methods 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 230000008694 endothelial dysfunction Effects 0.000 description 2
- 239000000066 endothelium dependent relaxing factor Substances 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 230000014509 gene expression Effects 0.000 description 2
- 230000009395 genetic defect Effects 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- 229940096919 glycogen Drugs 0.000 description 2
- LEQAOMBKQFMDFZ-UHFFFAOYSA-N glyoxal Chemical compound O=CC=O LEQAOMBKQFMDFZ-UHFFFAOYSA-N 0.000 description 2
- BCQZXOMGPXTTIC-UHFFFAOYSA-N halothane Chemical compound FC(F)(F)C(Cl)Br BCQZXOMGPXTTIC-UHFFFAOYSA-N 0.000 description 2
- 229960003132 halothane Drugs 0.000 description 2
- 230000035879 hyperinsulinaemia Effects 0.000 description 2
- 230000000705 hypocalcaemia Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 229940124975 inotropic drug Drugs 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000002642 intravenous therapy Methods 0.000 description 2
- 208000028867 ischemia Diseases 0.000 description 2
- 208000023589 ischemic disease Diseases 0.000 description 2
- ODBLHEXUDAPZAU-UHFFFAOYSA-N isocitric acid Chemical compound OC(=O)C(O)C(C(O)=O)CC(O)=O ODBLHEXUDAPZAU-UHFFFAOYSA-N 0.000 description 2
- 208000017169 kidney disease Diseases 0.000 description 2
- 229920002521 macromolecule Polymers 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 229940049920 malate Drugs 0.000 description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 2
- 229960003105 metformin Drugs 0.000 description 2
- 210000000653 nervous system Anatomy 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
- 230000033667 organ regeneration Effects 0.000 description 2
- 230000008520 organization Effects 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- 210000000496 pancreas Anatomy 0.000 description 2
- 208000033808 peripheral neuropathy Diseases 0.000 description 2
- 229940012957 plasmin Drugs 0.000 description 2
- 229920000573 polyethylene Polymers 0.000 description 2
- 230000000291 postprandial effect Effects 0.000 description 2
- 230000036316 preload Effects 0.000 description 2
- 230000002028 premature Effects 0.000 description 2
- 238000002203 pretreatment Methods 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 230000003449 preventive effect Effects 0.000 description 2
- 230000000750 progressive effect Effects 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 230000017854 proteolysis Effects 0.000 description 2
- 230000009719 regenerative response Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000003248 secreting effect Effects 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 230000006641 stabilisation Effects 0.000 description 2
- 238000011105 stabilization Methods 0.000 description 2
- 229960001052 streptozocin Drugs 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 150000001467 thiazolidinediones Chemical class 0.000 description 2
- 229910021654 trace metal Inorganic materials 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- 229910001428 transition metal ion Inorganic materials 0.000 description 2
- 230000000472 traumatic effect Effects 0.000 description 2
- 230000004102 tricarboxylic acid cycle Effects 0.000 description 2
- 231100000397 ulcer Toxicity 0.000 description 2
- 229960005356 urokinase Drugs 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 108010002139 very low density lipoprotein triglyceride Proteins 0.000 description 2
- 230000004580 weight loss Effects 0.000 description 2
- 230000037314 wound repair Effects 0.000 description 2
- 235000005074 zinc chloride Nutrition 0.000 description 2
- 239000011592 zinc chloride Substances 0.000 description 2
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 2
- 235000009529 zinc sulphate Nutrition 0.000 description 2
- 239000011686 zinc sulphate Substances 0.000 description 2
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 1
- MNZPFYUUDBYKMD-UHFFFAOYSA-N 2,3,4,5,6-pentachlorophenol;hydrochloride Chemical compound Cl.OC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl MNZPFYUUDBYKMD-UHFFFAOYSA-N 0.000 description 1
- UBDZFAGVPPMTIT-UHFFFAOYSA-N 2-aminoguanidine;hydron;chloride Chemical compound [Cl-].NC(N)=N[NH3+] UBDZFAGVPPMTIT-UHFFFAOYSA-N 0.000 description 1
- 239000005541 ACE inhibitor Substances 0.000 description 1
- 208000021959 Abnormal metabolism Diseases 0.000 description 1
- 206010000599 Acromegaly Diseases 0.000 description 1
- 206010048998 Acute phase reaction Diseases 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 206010001580 Albuminuria Diseases 0.000 description 1
- 238000003691 Amadori rearrangement reaction Methods 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 101150102415 Apob gene Proteins 0.000 description 1
- 101710115418 Apolipoprotein(a) Proteins 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 206010061666 Autonomic neuropathy Diseases 0.000 description 1
- 201000004569 Blindness Diseases 0.000 description 1
- 108010074051 C-Reactive Protein Proteins 0.000 description 1
- 102100032752 C-reactive protein Human genes 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 102000012336 Cholesterol Ester Transfer Proteins Human genes 0.000 description 1
- 108010061846 Cholesterol Ester Transfer Proteins Proteins 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 102000029816 Collagenase Human genes 0.000 description 1
- 108060005980 Collagenase Proteins 0.000 description 1
- 208000003606 Congenital Rubella Syndrome Diseases 0.000 description 1
- 206010010619 Congenital rubella infection Diseases 0.000 description 1
- 102000014824 Crystallins Human genes 0.000 description 1
- 108010064003 Crystallins Proteins 0.000 description 1
- 208000014311 Cushing syndrome Diseases 0.000 description 1
- 201000003883 Cystic fibrosis Diseases 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- 230000005778 DNA damage Effects 0.000 description 1
- 231100000277 DNA damage Toxicity 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- 206010070901 Diabetic dyslipidaemia Diseases 0.000 description 1
- 208000003037 Diastolic Heart Failure Diseases 0.000 description 1
- 201000010374 Down Syndrome Diseases 0.000 description 1
- 102000015689 E-Selectin Human genes 0.000 description 1
- 108010024212 E-Selectin Proteins 0.000 description 1
- 206010014486 Elevated triglycerides Diseases 0.000 description 1
- 102000018711 Facilitative Glucose Transport Proteins Human genes 0.000 description 1
- 108010027279 Facilitative Glucose Transport Proteins Proteins 0.000 description 1
- 208000003790 Foot Ulcer Diseases 0.000 description 1
- 208000024412 Friedreich ataxia Diseases 0.000 description 1
- 206010018404 Glucagonoma Diseases 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 102000017011 Glycated Hemoglobin A Human genes 0.000 description 1
- 208000018565 Hemochromatosis Diseases 0.000 description 1
- 101000614618 Homo sapiens Junctophilin-3 Proteins 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- 208000029422 Hypernatremia Diseases 0.000 description 1
- 206010020850 Hyperthyroidism Diseases 0.000 description 1
- 206010020994 Hypoglycaemia neonatal Diseases 0.000 description 1
- 208000013016 Hypoglycemia Diseases 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 206010061216 Infarction Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010023126 Jaundice Diseases 0.000 description 1
- 102100040488 Junctophilin-3 Human genes 0.000 description 1
- 208000017924 Klinefelter Syndrome Diseases 0.000 description 1
- FFFHZYDWPBMWHY-VKHMYHEASA-N L-homocysteine Chemical compound OC(=O)[C@@H](N)CCS FFFHZYDWPBMWHY-VKHMYHEASA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 108010028554 LDL Cholesterol Proteins 0.000 description 1
- 238000008214 LDL Cholesterol Methods 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 206010025394 Macrosomia Diseases 0.000 description 1
- 206010027525 Microalbuminuria Diseases 0.000 description 1
- 208000020128 Mitral stenosis Diseases 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 102000006386 Myelin Proteins Human genes 0.000 description 1
- 108010083674 Myelin Proteins Proteins 0.000 description 1
- 206010068871 Myotonic dystrophy Diseases 0.000 description 1
- QPCDCPDFJACHGM-UHFFFAOYSA-N N,N-bis{2-[bis(carboxymethyl)amino]ethyl}glycine Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(=O)O)CCN(CC(O)=O)CC(O)=O QPCDCPDFJACHGM-UHFFFAOYSA-N 0.000 description 1
- 229930182474 N-glycoside Natural products 0.000 description 1
- 108010057466 NF-kappa B Proteins 0.000 description 1
- 102000003945 NF-kappa B Human genes 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000028389 Nerve injury Diseases 0.000 description 1
- 208000005268 Neurogenic Arthropathy Diseases 0.000 description 1
- 206010029326 Neuropathic arthropathy Diseases 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- 208000037273 Pathologic Processes Diseases 0.000 description 1
- 208000005764 Peripheral Arterial Disease Diseases 0.000 description 1
- 208000030831 Peripheral arterial occlusive disease Diseases 0.000 description 1
- 208000018262 Peripheral vascular disease Diseases 0.000 description 1
- CXOFVDLJLONNDW-UHFFFAOYSA-N Phenytoin Chemical compound N1C(=O)NC(=O)C1(C=1C=CC=CC=1)C1=CC=CC=C1 CXOFVDLJLONNDW-UHFFFAOYSA-N 0.000 description 1
- 102000001938 Plasminogen Activators Human genes 0.000 description 1
- 108010001014 Plasminogen Activators Proteins 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 208000004880 Polyuria Diseases 0.000 description 1
- 241000097929 Porphyria Species 0.000 description 1
- 208000010642 Porphyrias Diseases 0.000 description 1
- 201000010769 Prader-Willi syndrome Diseases 0.000 description 1
- 208000032038 Premature aging Diseases 0.000 description 1
- 108010076181 Proinsulin Proteins 0.000 description 1
- 102100027378 Prothrombin Human genes 0.000 description 1
- 108010094028 Prothrombin Proteins 0.000 description 1
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 108091006629 SLC13A2 Proteins 0.000 description 1
- 229940122055 Serine protease inhibitor Drugs 0.000 description 1
- 101710102218 Serine protease inhibitor Proteins 0.000 description 1
- 201000001880 Sexual dysfunction Diseases 0.000 description 1
- 206010041329 Somatostatinoma Diseases 0.000 description 1
- 102000000019 Sterol Esterase Human genes 0.000 description 1
- 108010055297 Sterol Esterase Proteins 0.000 description 1
- 101710172711 Structural protein Proteins 0.000 description 1
- 206010042434 Sudden death Diseases 0.000 description 1
- 229940100389 Sulfonylurea Drugs 0.000 description 1
- 102000019197 Superoxide Dismutase Human genes 0.000 description 1
- 108010012715 Superoxide dismutase Proteins 0.000 description 1
- AUYYCJSJGJYCDS-LBPRGKRZSA-N Thyrolar Chemical class IC1=CC(C[C@H](N)C(O)=O)=CC(I)=C1OC1=CC=C(O)C(I)=C1 AUYYCJSJGJYCDS-LBPRGKRZSA-N 0.000 description 1
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
- 231100000605 Toxicity Class Toxicity 0.000 description 1
- 208000026928 Turner syndrome Diseases 0.000 description 1
- 206010060953 Ventricular failure Diseases 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 108091005605 Vitamin K-dependent proteins Proteins 0.000 description 1
- 238000006993 Weiss annulation reaction Methods 0.000 description 1
- 201000010802 Wolfram syndrome Diseases 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- GIEAQDPIWWODTH-UHFFFAOYSA-N [Na].[Na].[Na].[Ca] Chemical compound [Na].[Na].[Na].[Ca] GIEAQDPIWWODTH-UHFFFAOYSA-N 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 210000001789 adipocyte Anatomy 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 206010001323 adrenal adenoma Diseases 0.000 description 1
- 239000000808 adrenergic beta-agonist Substances 0.000 description 1
- 208000014594 aldosterone-producing adenoma with seizures and neurological abnormalities Diseases 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 238000002266 amputation Methods 0.000 description 1
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
- 229940098194 antabuse Drugs 0.000 description 1
- 230000002221 antabuse Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- 230000004872 arterial blood pressure Effects 0.000 description 1
- 108010083526 asialo-von Willebrand Factor Proteins 0.000 description 1
- 230000036523 atherogenesis Effects 0.000 description 1
- 238000003705 background correction Methods 0.000 description 1
- 230000008721 basement membrane thickening Effects 0.000 description 1
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 1
- 230000004791 biological behavior Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000008512 biological response Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 239000003130 blood coagulation factor inhibitor Substances 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 230000000711 cancerogenic effect Effects 0.000 description 1
- FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 description 1
- 229960000830 captopril Drugs 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 231100000357 carcinogen Toxicity 0.000 description 1
- 238000012754 cardiac puncture Methods 0.000 description 1
- 230000007211 cardiovascular event Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000004637 cellular stress Effects 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- ZCDOYSPFYFSLEW-UHFFFAOYSA-N chromate(2-) Chemical compound [O-][Cr]([O-])(=O)=O ZCDOYSPFYFSLEW-UHFFFAOYSA-N 0.000 description 1
- RKCWRYBOSIJRNH-UHFFFAOYSA-N chromium(5+) Chemical compound [Cr+5] RKCWRYBOSIJRNH-UHFFFAOYSA-N 0.000 description 1
- 230000001010 compromised effect Effects 0.000 description 1
- 230000002153 concerted effect Effects 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 230000036757 core body temperature Effects 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 231100000517 death Toxicity 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 229960004042 diazoxide Drugs 0.000 description 1
- 235000013367 dietary fats Nutrition 0.000 description 1
- 235000018823 dietary intake Nutrition 0.000 description 1
- 235000001434 dietary modification Nutrition 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 229940030606 diuretics Drugs 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000000456 dynamic reaction cell inductively coupled plasma mass spectrometry Methods 0.000 description 1
- 230000001258 dyslipidemic effect Effects 0.000 description 1
- 208000030172 endocrine system disease Diseases 0.000 description 1
- 230000008497 endothelial barrier function Effects 0.000 description 1
- 210000003989 endothelium vascular Anatomy 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 210000003020 exocrine pancreas Anatomy 0.000 description 1
- 210000003191 femoral vein Anatomy 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 102000034356 gene-regulatory proteins Human genes 0.000 description 1
- 108091006104 gene-regulatory proteins Proteins 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 238000007446 glucose tolerance test Methods 0.000 description 1
- 230000006377 glucose transport Effects 0.000 description 1
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 108091005995 glycated hemoglobin Proteins 0.000 description 1
- 230000034659 glycolysis Effects 0.000 description 1
- 229940015043 glyoxal Drugs 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000003284 homeostatic effect Effects 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 238000012151 immunohistochemical method Methods 0.000 description 1
- 239000002933 immunoreactive insulin Substances 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 238000009616 inductively coupled plasma Methods 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 210000004692 intercellular junction Anatomy 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 210000004153 islets of langerhan Anatomy 0.000 description 1
- 150000004715 keto acids Chemical class 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 238000009533 lab test Methods 0.000 description 1
- 210000005240 left ventricle Anatomy 0.000 description 1
- 230000023404 leukocyte cell-cell adhesion Effects 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 235000019626 lipase activity Nutrition 0.000 description 1
- 230000037356 lipid metabolism Effects 0.000 description 1
- 230000008604 lipoprotein metabolism Effects 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 208000018769 loss of vision Diseases 0.000 description 1
- 231100000864 loss of vision Toxicity 0.000 description 1
- 230000008774 maternal effect Effects 0.000 description 1
- 230000006371 metabolic abnormality Effects 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 230000002297 mitogenic effect Effects 0.000 description 1
- 208000006887 mitral valve stenosis Diseases 0.000 description 1
- 230000009149 molecular binding Effects 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 210000002433 mononuclear leukocyte Anatomy 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- UFLJAVBLQHSCDD-UHFFFAOYSA-N n'-[2-(2-aminoethylamino)ethyl]propane-1,3-diamine Chemical compound NCCCNCCNCCN UFLJAVBLQHSCDD-UHFFFAOYSA-N 0.000 description 1
- WDLWFIMADVGTED-UHFFFAOYSA-N n'-[2-(2-aminoethylamino)ethyl]propane-1,3-diamine;tetrahydrochloride Chemical compound Cl.Cl.Cl.Cl.NCCCNCCNCCN WDLWFIMADVGTED-UHFFFAOYSA-N 0.000 description 1
- 230000009826 neoplastic cell growth Effects 0.000 description 1
- 230000008764 nerve damage Effects 0.000 description 1
- 210000000944 nerve tissue Anatomy 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- PXHVJJICTQNCMI-UHFFFAOYSA-N nickel Substances [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 108010071584 oxidized low density lipoprotein Proteins 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 231100000255 pathogenic effect Toxicity 0.000 description 1
- 230000009543 pathological alteration Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000009054 pathological process Effects 0.000 description 1
- 230000001991 pathophysiological effect Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- XDRYMKDFEDOLFX-UHFFFAOYSA-N pentamidine Chemical compound C1=CC(C(=N)N)=CC=C1OCCCCCOC1=CC=C(C(N)=N)C=C1 XDRYMKDFEDOLFX-UHFFFAOYSA-N 0.000 description 1
- 229960004448 pentamidine Drugs 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 208000028169 periodontal disease Diseases 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229960002036 phenytoin Drugs 0.000 description 1
- 208000028591 pheochromocytoma Diseases 0.000 description 1
- 229940127126 plasminogen activator Drugs 0.000 description 1
- 230000010118 platelet activation Effects 0.000 description 1
- 206010036067 polydipsia Diseases 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 201000009395 primary hyperaldosteronism Diseases 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000009145 protein modification Effects 0.000 description 1
- 229940039716 prothrombin Drugs 0.000 description 1
- CLKZWXHKFXZIMA-UHFFFAOYSA-N pyrinuron Chemical compound C1=CC([N+](=O)[O-])=CC=C1NC(=O)NCC1=CC=CN=C1 CLKZWXHKFXZIMA-UHFFFAOYSA-N 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 239000012925 reference material Substances 0.000 description 1
- 210000005084 renal tissue Anatomy 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000036387 respiratory rate Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 239000003128 rodenticide Substances 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 239000003001 serine protease inhibitor Substances 0.000 description 1
- 231100000004 severe toxicity Toxicity 0.000 description 1
- 231100000872 sexual dysfunction Toxicity 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 239000012086 standard solution Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 208000023516 stroke disease Diseases 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000008093 supporting effect Effects 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 229940037128 systemic glucocorticoids Drugs 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 239000003451 thiazide diuretic agent Substances 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 229940036555 thyroid hormone Drugs 0.000 description 1
- 239000005495 thyroid hormone Substances 0.000 description 1
- 210000001578 tight junction Anatomy 0.000 description 1
- 230000003868 tissue accumulation Effects 0.000 description 1
- 230000008467 tissue growth Effects 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 229910021642 ultra pure water Inorganic materials 0.000 description 1
- 239000012498 ultrapure water Substances 0.000 description 1
- 238000011870 unpaired t-test Methods 0.000 description 1
- 210000000626 ureter Anatomy 0.000 description 1
- 210000001604 vasa vasorum Anatomy 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 230000006492 vascular dysfunction Effects 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 230000003639 vasoconstrictive effect Effects 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 230000004393 visual impairment Effects 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 239000013585 weight reducing agent Substances 0.000 description 1
- 239000012224 working solution Substances 0.000 description 1
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Une méthode damélioration de la réparation de tissu endommagé de tissu chez un patient mammalien à partir de celui du myocarde, de larbre vasculaire et des organes qui dépendent de larbre vasculaire, ladite méthode comprenant ou intégrant létape de donner au patient, ou dadministrer au patient, un agent ou des agents efficaces pour réduire les valeurs de cuivre du corps du patient à une teneur suffisante pour améliorer la réparation des tissus.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA2982327A CA2982327A1 (fr) | 2002-03-08 | 2003-03-10 | Utilisation de tetraamines chelatant le cuivre destines au traitement de maladies cardiovasculaires et d'insuffisance cardiaque |
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NZ517721 | 2002-03-08 | ||
| NZ51772102 | 2002-03-08 | ||
| NZ517725 | 2002-03-11 | ||
| NZ51772502 | 2002-03-11 | ||
| US36438202P | 2002-03-12 | 2002-03-12 | |
| US60/364,382 | 2002-03-12 | ||
| CA2478997A CA2478997C (fr) | 2002-03-08 | 2003-03-10 | Utilisation de tetraamines chelatant le cuivre destines au traitement de maladies cardiovasculaires et d'insuffisance cardiaque |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2478997A Division CA2478997C (fr) | 2002-03-08 | 2003-03-10 | Utilisation de tetraamines chelatant le cuivre destines au traitement de maladies cardiovasculaires et d'insuffisance cardiaque |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2982327A Division CA2982327A1 (fr) | 2002-03-08 | 2003-03-10 | Utilisation de tetraamines chelatant le cuivre destines au traitement de maladies cardiovasculaires et d'insuffisance cardiaque |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2828595A1 CA2828595A1 (fr) | 2003-09-25 |
| CA2828595C true CA2828595C (fr) | 2017-11-28 |
Family
ID=46801737
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2828595A Expired - Fee Related CA2828595C (fr) | 2002-03-08 | 2003-03-10 | Utilisation de tetraamines chelatant le cuivre destines au traitement de maladies cardiovasculaires et d'insuffisance cardiaque |
| CA2982327A Abandoned CA2982327A1 (fr) | 2002-03-08 | 2003-03-10 | Utilisation de tetraamines chelatant le cuivre destines au traitement de maladies cardiovasculaires et d'insuffisance cardiaque |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2982327A Abandoned CA2982327A1 (fr) | 2002-03-08 | 2003-03-10 | Utilisation de tetraamines chelatant le cuivre destines au traitement de maladies cardiovasculaires et d'insuffisance cardiaque |
Country Status (3)
| Country | Link |
|---|---|
| CA (2) | CA2828595C (fr) |
| ES (1) | ES2642633T3 (fr) |
| PT (2) | PT1487431E (fr) |
-
2003
- 2003-03-10 CA CA2828595A patent/CA2828595C/fr not_active Expired - Fee Related
- 2003-03-10 ES ES11187394.9T patent/ES2642633T3/es not_active Expired - Lifetime
- 2003-03-10 CA CA2982327A patent/CA2982327A1/fr not_active Abandoned
- 2003-03-10 PT PT03744567T patent/PT1487431E/pt unknown
- 2003-03-10 PT PT111873949T patent/PT2500018T/pt unknown
Also Published As
| Publication number | Publication date |
|---|---|
| PT2500018T (pt) | 2017-10-04 |
| CA2828595A1 (fr) | 2003-09-25 |
| CA2982327A1 (fr) | 2003-09-25 |
| PT1487431E (pt) | 2012-08-02 |
| ES2642633T3 (es) | 2017-11-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2478997C (fr) | Utilisation de tetraamines chelatant le cuivre destines au traitement de maladies cardiovasculaires et d'insuffisance cardiaque | |
| WO2004017957A1 (fr) | Prevention et/ou traitement de maladies cardio-vasculaires et/ou insuffisance cardiaque associee | |
| WO2003075910A1 (fr) | Prevention et/ou traitement d'une maladie vasculaire, d'une cardiomyopathie et/ou d'une defaillance cardiaque associee | |
| Huebschmann et al. | Diabetes and advanced glycoxidation end products | |
| Hoffman et al. | Myocardial reperfusion injury: etiology, mechanisms, and therapies | |
| Folli et al. | The role of oxidative stress in the pathogenesis of type 2 diabetes mellitus micro-and macrovascular complications: avenues for a mechanistic-based therapeutic approach | |
| Tan et al. | AGE, RAGE, and ROS in diabetic nephropathy | |
| Alfadda et al. | Reactive oxygen species in health and disease | |
| Cheng et al. | What is responsible for the initiating chemistry of iron-mediated lipid peroxidation: an update | |
| Bolton et al. | Pimagedine: a novel therapy for diabetic nephropathy | |
| Tsutsui et al. | Oxidative stress in cardiac and skeletal muscle dysfunction associated with diabetes mellitus | |
| US7652037B2 (en) | Methods of lowering lipid levels in a mammal | |
| CA2828595C (fr) | Utilisation de tetraamines chelatant le cuivre destines au traitement de maladies cardiovasculaires et d'insuffisance cardiaque | |
| Nagareddy et al. | N-acetylcysteine prevents nitrosative stress-associated depression of blood pressure and heart rate in streptozotocin diabetic rats | |
| NZ545724A (en) | Use of a copper chelator for preventing and/or treating cardiovascular disease and/or associated heart failure | |
| Antonopoulos et al. | Novel therapeutic strategies targeting vascular redox in human atherosclerosis | |
| Ferreira et al. | Concurrent exercise training potentiates the effects of angiotensin-converting enzyme inhibitor on regulatory systems of blood pressure control in ovariectomized hypertensive rats | |
| Schalkwijk | Therapeutic interventions in the glyc (oxid) ation pathway | |
| US8580854B2 (en) | Methods of suppression of rage gene expression and rage triggered inflammatory genes by selected age-inhibitors | |
| Coughlan et al. | Can you reduce your AGE?: Strategies to prevent AGE accumulation in diabetes | |
| Alvarez et al. | Impact of Advanced Glycation End Products on | |
| HK1071313B (en) | Preventing and/or treating cardiovascular disease and/or associated heart failure | |
| Folli et al. | The Role of Oxidative Stress in the Pathogenesis of Type 2 Diabetes Mellitus Micro-and Macrovascular Complications: Avenues... | |
| Wong | Advanced glycation endproducts and oxidative stress from the neutrophil respiratory burst | |
| Al-Rousan | Efficacy of Deferasirox in Preventing Complications of Iron Overload in the Iron Overloaded Gerbil |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20131001 |
|
| MKLA | Lapsed |
Effective date: 20210310 |