JP5106738B2 - 心不整脈治療法 - Google Patents
心不整脈治療法 Download PDFInfo
- Publication number
- JP5106738B2 JP5106738B2 JP2002524451A JP2002524451A JP5106738B2 JP 5106738 B2 JP5106738 B2 JP 5106738B2 JP 2002524451 A JP2002524451 A JP 2002524451A JP 2002524451 A JP2002524451 A JP 2002524451A JP 5106738 B2 JP5106738 B2 JP 5106738B2
- Authority
- JP
- Japan
- Prior art keywords
- pharmaceutical composition
- polynucleotide
- composition according
- measured
- heart
- 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
- 206010003119 arrhythmia Diseases 0.000 title claims description 49
- 238000002560 therapeutic procedure Methods 0.000 title description 10
- 108090000623 proteins and genes Proteins 0.000 claims description 131
- 108091033319 polynucleotide Proteins 0.000 claims description 96
- 102000040430 polynucleotide Human genes 0.000 claims description 96
- 239000002157 polynucleotide Substances 0.000 claims description 96
- 210000002216 heart Anatomy 0.000 claims description 89
- 206010003658 Atrial Fibrillation Diseases 0.000 claims description 67
- 102000004169 proteins and genes Human genes 0.000 claims description 61
- 230000014509 gene expression Effects 0.000 claims description 43
- 238000003556 assay Methods 0.000 claims description 42
- 230000002861 ventricular Effects 0.000 claims description 27
- 241000701161 unidentified adenovirus Species 0.000 claims description 26
- 230000010412 perfusion Effects 0.000 claims description 24
- 150000007523 nucleic acids Chemical class 0.000 claims description 23
- 238000011282 treatment Methods 0.000 claims description 22
- 230000002401 inhibitory effect Effects 0.000 claims description 21
- 210000001992 atrioventricular node Anatomy 0.000 claims description 20
- 102000039446 nucleic acids Human genes 0.000 claims description 20
- 108020004707 nucleic acids Proteins 0.000 claims description 20
- 239000013603 viral vector Substances 0.000 claims description 20
- 108091006027 G proteins Proteins 0.000 claims description 19
- 102000030782 GTP binding Human genes 0.000 claims description 19
- 108091000058 GTP-Binding Proteins 0.000 claims description 19
- 241000124008 Mammalia Species 0.000 claims description 18
- 230000007423 decrease Effects 0.000 claims description 17
- 239000003814 drug Substances 0.000 claims description 17
- 230000001965 increasing effect Effects 0.000 claims description 17
- 230000002107 myocardial effect Effects 0.000 claims description 16
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 claims description 14
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims description 14
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims description 14
- 239000012634 fragment Substances 0.000 claims description 14
- 230000036279 refractory period Effects 0.000 claims description 13
- 229920001184 polypeptide Polymers 0.000 claims description 12
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 12
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 12
- 210000004165 myocardium Anatomy 0.000 claims description 11
- 208000001871 Tachycardia Diseases 0.000 claims description 10
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 10
- 238000001262 western blot Methods 0.000 claims description 10
- 241000701022 Cytomegalovirus Species 0.000 claims description 9
- 210000001367 artery Anatomy 0.000 claims description 9
- 210000004413 cardiac myocyte Anatomy 0.000 claims description 9
- 238000001514 detection method Methods 0.000 claims description 9
- 206010047302 ventricular tachycardia Diseases 0.000 claims description 9
- 229940079593 drug Drugs 0.000 claims description 8
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 claims description 8
- 208000003663 ventricular fibrillation Diseases 0.000 claims description 8
- 230000035699 permeability Effects 0.000 claims description 7
- 230000004044 response Effects 0.000 claims description 7
- 230000006794 tachycardia Effects 0.000 claims description 7
- 206010003668 atrial tachycardia Diseases 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 230000001419 dependent effect Effects 0.000 claims description 5
- 239000002502 liposome Substances 0.000 claims description 5
- 230000009467 reduction Effects 0.000 claims description 5
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 4
- 206010003662 Atrial flutter Diseases 0.000 claims description 4
- 241000702421 Dependoparvovirus Species 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- 229940076279 serotonin Drugs 0.000 claims description 4
- 230000008728 vascular permeability Effects 0.000 claims description 4
- 206010003671 Atrioventricular Block Diseases 0.000 claims description 3
- 208000007888 Sinus Tachycardia Diseases 0.000 claims description 3
- 206010040741 Sinus bradycardia Diseases 0.000 claims description 3
- 241001430294 unidentified retrovirus Species 0.000 claims description 3
- 208000006808 Atrioventricular Nodal Reentry Tachycardia Diseases 0.000 claims description 2
- 238000009472 formulation Methods 0.000 claims description 2
- 150000004676 glycans Chemical class 0.000 claims description 2
- 150000002632 lipids Chemical class 0.000 claims description 2
- 239000002773 nucleotide Substances 0.000 claims description 2
- 125000003729 nucleotide group Chemical group 0.000 claims description 2
- 229920001282 polysaccharide Polymers 0.000 claims description 2
- 239000005017 polysaccharide Substances 0.000 claims description 2
- 230000000306 recurrent effect Effects 0.000 claims description 2
- 230000002792 vascular Effects 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 41
- 238000012377 drug delivery Methods 0.000 claims 1
- 238000001839 endoscopy Methods 0.000 claims 1
- 238000000034 method Methods 0.000 description 63
- 235000018102 proteins Nutrition 0.000 description 56
- 238000012546 transfer Methods 0.000 description 53
- 230000000694 effects Effects 0.000 description 39
- 241001465754 Metazoa Species 0.000 description 37
- 239000013598 vector Substances 0.000 description 35
- 230000036982 action potential Effects 0.000 description 31
- 210000004027 cell Anatomy 0.000 description 26
- 230000002018 overexpression Effects 0.000 description 23
- 210000001519 tissue Anatomy 0.000 description 23
- 108091006146 Channels Proteins 0.000 description 22
- 108010005774 beta-Galactosidase Proteins 0.000 description 19
- 230000006793 arrhythmia Effects 0.000 description 18
- 241000700605 Viruses Species 0.000 description 16
- 230000006870 function Effects 0.000 description 16
- 108090000862 Ion Channels Proteins 0.000 description 15
- 102000004310 Ion Channels Human genes 0.000 description 14
- 238000002347 injection Methods 0.000 description 14
- 239000007924 injection Substances 0.000 description 14
- 235000001014 amino acid Nutrition 0.000 description 13
- 239000011575 calcium Substances 0.000 description 13
- 230000000747 cardiac effect Effects 0.000 description 12
- 101001047090 Homo sapiens Potassium voltage-gated channel subfamily H member 2 Proteins 0.000 description 11
- 102100022807 Potassium voltage-gated channel subfamily H member 2 Human genes 0.000 description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
- 238000001415 gene therapy Methods 0.000 description 11
- 210000005003 heart tissue Anatomy 0.000 description 11
- 238000005259 measurement Methods 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- 230000001225 therapeutic effect Effects 0.000 description 11
- 150000001413 amino acids Chemical class 0.000 description 10
- WQZGKKKJIJFFOK-FPRJBGLDSA-N beta-D-galactose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-FPRJBGLDSA-N 0.000 description 10
- 210000000056 organ Anatomy 0.000 description 10
- BNRNXUUZRGQAQC-UHFFFAOYSA-N sildenafil Chemical compound CCCC1=NN(C)C(C(N2)=O)=C1N=C2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(C)CC1 BNRNXUUZRGQAQC-UHFFFAOYSA-N 0.000 description 10
- OPIFSICVWOWJMJ-AEOCFKNESA-N 5-bromo-4-chloro-3-indolyl beta-D-galactoside Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1OC1=CNC2=CC=C(Br)C(Cl)=C12 OPIFSICVWOWJMJ-AEOCFKNESA-N 0.000 description 9
- 230000001746 atrial effect Effects 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- 229940124597 therapeutic agent Drugs 0.000 description 9
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 8
- 206010019280 Heart failures Diseases 0.000 description 8
- 239000003416 antiarrhythmic agent Substances 0.000 description 8
- 102000005936 beta-Galactosidase Human genes 0.000 description 8
- 229910052791 calcium Inorganic materials 0.000 description 8
- 239000002299 complementary DNA Substances 0.000 description 8
- 238000001727 in vivo Methods 0.000 description 8
- 230000001404 mediated effect Effects 0.000 description 8
- 108020001213 potassium channel Proteins 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- 239000011734 sodium Substances 0.000 description 8
- 238000010186 staining Methods 0.000 description 8
- 229930182837 (R)-adrenaline Natural products 0.000 description 7
- SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 description 7
- 239000000006 Nitroglycerin Substances 0.000 description 7
- 102000004257 Potassium Channel Human genes 0.000 description 7
- 230000003288 anthiarrhythmic effect Effects 0.000 description 7
- 230000004087 circulation Effects 0.000 description 7
- 229960005139 epinephrine Drugs 0.000 description 7
- 229960003711 glyceryl trinitrate Drugs 0.000 description 7
- 210000002837 heart atrium Anatomy 0.000 description 7
- 208000015181 infectious disease Diseases 0.000 description 7
- 230000004048 modification Effects 0.000 description 7
- 238000012986 modification Methods 0.000 description 7
- 206010002091 Anaesthesia Diseases 0.000 description 6
- 102000034573 Channels Human genes 0.000 description 6
- 108020004414 DNA Proteins 0.000 description 6
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 6
- 102000030621 adenylate cyclase Human genes 0.000 description 6
- 108060000200 adenylate cyclase Proteins 0.000 description 6
- 230000037005 anaesthesia Effects 0.000 description 6
- 210000004351 coronary vessel Anatomy 0.000 description 6
- 230000034994 death Effects 0.000 description 6
- 231100000517 death Toxicity 0.000 description 6
- 230000003247 decreasing effect Effects 0.000 description 6
- 230000003902 lesion Effects 0.000 description 6
- 239000011591 potassium Substances 0.000 description 6
- 229910052700 potassium Inorganic materials 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- 230000033764 rhythmic process Effects 0.000 description 6
- 229910052708 sodium Inorganic materials 0.000 description 6
- 230000000638 stimulation Effects 0.000 description 6
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 5
- 102000010970 Connexin Human genes 0.000 description 5
- 108050001175 Connexin Proteins 0.000 description 5
- 108010052164 Sodium Channels Proteins 0.000 description 5
- 230000001154 acute effect Effects 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- 238000001476 gene delivery Methods 0.000 description 5
- 230000010076 replication Effects 0.000 description 5
- 229960003310 sildenafil Drugs 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 206010007559 Cardiac failure congestive Diseases 0.000 description 4
- 241000700198 Cavia Species 0.000 description 4
- 241000283973 Oryctolagus cuniculus Species 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 102000018674 Sodium Channels Human genes 0.000 description 4
- 108700019146 Transgenes Proteins 0.000 description 4
- 206010047281 Ventricular arrhythmia Diseases 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 238000013459 approach Methods 0.000 description 4
- 210000001715 carotid artery Anatomy 0.000 description 4
- 230000001413 cellular effect Effects 0.000 description 4
- 230000001684 chronic effect Effects 0.000 description 4
- 210000003191 femoral vein Anatomy 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 210000004731 jugular vein Anatomy 0.000 description 4
- 210000003734 kidney Anatomy 0.000 description 4
- 210000004185 liver Anatomy 0.000 description 4
- 210000004072 lung Anatomy 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 108091005573 modified proteins Proteins 0.000 description 4
- 102000035118 modified proteins Human genes 0.000 description 4
- 210000001672 ovary Anatomy 0.000 description 4
- -1 oxygen radical Chemical class 0.000 description 4
- 238000007674 radiofrequency ablation Methods 0.000 description 4
- 210000001567 regular cardiac muscle cell of ventricle Anatomy 0.000 description 4
- 238000012552 review Methods 0.000 description 4
- 210000002027 skeletal muscle Anatomy 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 206010003130 Arrhythmia supraventricular Diseases 0.000 description 3
- 108090000312 Calcium Channels Proteins 0.000 description 3
- 102000003922 Calcium Channels Human genes 0.000 description 3
- 241000588724 Escherichia coli Species 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- 108091028043 Nucleic acid sequence Proteins 0.000 description 3
- 108700008625 Reporter Genes Proteins 0.000 description 3
- 241000282887 Suidae Species 0.000 description 3
- 206010049447 Tachyarrhythmia Diseases 0.000 description 3
- 230000002159 abnormal effect Effects 0.000 description 3
- 229960004373 acetylcholine Drugs 0.000 description 3
- 210000000709 aorta Anatomy 0.000 description 3
- 102000012740 beta Adrenergic Receptors Human genes 0.000 description 3
- 108010079452 beta Adrenergic Receptors Proteins 0.000 description 3
- 208000006218 bradycardia Diseases 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 230000002950 deficient Effects 0.000 description 3
- 238000012217 deletion Methods 0.000 description 3
- 230000037430 deletion Effects 0.000 description 3
- 238000001647 drug administration Methods 0.000 description 3
- 238000002651 drug therapy Methods 0.000 description 3
- 208000015700 familial long QT syndrome Diseases 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 238000010369 molecular cloning Methods 0.000 description 3
- 210000000107 myocyte Anatomy 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 230000002035 prolonged effect Effects 0.000 description 3
- 230000019491 signal transduction Effects 0.000 description 3
- 210000001013 sinoatrial node Anatomy 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- 208000011580 syndromic disease Diseases 0.000 description 3
- 230000009885 systemic effect Effects 0.000 description 3
- 230000001052 transient effect Effects 0.000 description 3
- 241000283707 Capra Species 0.000 description 2
- 208000031229 Cardiomyopathies Diseases 0.000 description 2
- 108010062745 Chloride Channels Proteins 0.000 description 2
- 102000011045 Chloride Channels Human genes 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- UPEZCKBFRMILAV-JNEQICEOSA-N Ecdysone Natural products O=C1[C@H]2[C@@](C)([C@@H]3C([C@@]4(O)[C@@](C)([C@H]([C@H]([C@@H](O)CCC(O)(C)C)C)CC4)CC3)=C1)C[C@H](O)[C@H](O)C2 UPEZCKBFRMILAV-JNEQICEOSA-N 0.000 description 2
- 108700024394 Exon Proteins 0.000 description 2
- 108091006099 G alpha subunit Proteins 0.000 description 2
- 102000034353 G alpha subunit Human genes 0.000 description 2
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 2
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 2
- 206010049694 Left Ventricular Dysfunction Diseases 0.000 description 2
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
- 241000714474 Rous sarcoma virus Species 0.000 description 2
- 206010039897 Sedation Diseases 0.000 description 2
- 108700005077 Viral Genes Proteins 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- NOSIYYJFMPDDSA-UHFFFAOYSA-N acepromazine Chemical compound C1=C(C(C)=O)C=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 NOSIYYJFMPDDSA-UHFFFAOYSA-N 0.000 description 2
- 229960005054 acepromazine Drugs 0.000 description 2
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 2
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
- UCTWMZQNUQWSLP-UHFFFAOYSA-N adrenaline Chemical compound CNCC(O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-UHFFFAOYSA-N 0.000 description 2
- UPEZCKBFRMILAV-UHFFFAOYSA-N alpha-Ecdysone Natural products C1C(O)C(O)CC2(C)C(CCC3(C(C(C(O)CCC(C)(C)O)C)CCC33O)C)C3=CC(=O)C21 UPEZCKBFRMILAV-UHFFFAOYSA-N 0.000 description 2
- 208000007502 anemia Diseases 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000010100 anticoagulation Effects 0.000 description 2
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 2
- 230000002763 arrhythmic effect Effects 0.000 description 2
- 229940098003 aspirin 325 mg Drugs 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 239000002876 beta blocker Substances 0.000 description 2
- 229940097320 beta blocking agent Drugs 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 210000004375 bundle of his Anatomy 0.000 description 2
- 230000011128 cardiac conduction Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000008602 contraction Effects 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000002716 delivery method Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 230000003828 downregulation Effects 0.000 description 2
- UPEZCKBFRMILAV-JMZLNJERSA-N ecdysone Chemical compound C1[C@@H](O)[C@@H](O)C[C@]2(C)[C@@H](CC[C@@]3([C@@H]([C@@H]([C@H](O)CCC(C)(C)O)C)CC[C@]33O)C)C3=CC(=O)[C@@H]21 UPEZCKBFRMILAV-JMZLNJERSA-N 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 230000007831 electrophysiology Effects 0.000 description 2
- 238000002001 electrophysiology Methods 0.000 description 2
- 230000003511 endothelial effect Effects 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000002825 functional assay Methods 0.000 description 2
- 238000011554 guinea pig model Methods 0.000 description 2
- 208000019622 heart disease Diseases 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 238000009396 hybridization Methods 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 229960002725 isoflurane Drugs 0.000 description 2
- 229960003299 ketamine Drugs 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 238000007726 management method Methods 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 210000005036 nerve Anatomy 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 239000013600 plasmid vector Substances 0.000 description 2
- 208000014321 polymorphic ventricular tachycardia Diseases 0.000 description 2
- 238000002203 pretreatment Methods 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 238000003908 quality control method Methods 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000002336 repolarization Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 210000005245 right atrium Anatomy 0.000 description 2
- 230000036280 sedation Effects 0.000 description 2
- 229940099366 sildenafil 25 mg Drugs 0.000 description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
- 230000002269 spontaneous effect Effects 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 206010043554 thrombocytopenia Diseases 0.000 description 2
- 210000005166 vasculature Anatomy 0.000 description 2
- 210000000596 ventricular septum Anatomy 0.000 description 2
- XVARCVCWNFACQC-MBJXGIAVSA-N (2r,3r,4s,5r,6s)-2-(hydroxymethyl)-6-(1h-indol-3-yloxy)oxane-3,4,5-triol Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1OC1=CNC2=CC=CC=C12 XVARCVCWNFACQC-MBJXGIAVSA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- ZIIUUSVHCHPIQD-UHFFFAOYSA-N 2,4,6-trimethyl-N-[3-(trifluoromethyl)phenyl]benzenesulfonamide Chemical compound CC1=CC(C)=CC(C)=C1S(=O)(=O)NC1=CC=CC(C(F)(F)F)=C1 ZIIUUSVHCHPIQD-UHFFFAOYSA-N 0.000 description 1
- HVAUUPRFYPCOCA-AREMUKBSSA-N 2-O-acetyl-1-O-hexadecyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCOC[C@@H](OC(C)=O)COP([O-])(=O)OCC[N+](C)(C)C HVAUUPRFYPCOCA-AREMUKBSSA-N 0.000 description 1
- 101150007969 ADORA1 gene Proteins 0.000 description 1
- 108091006112 ATPases Proteins 0.000 description 1
- 108010060263 Adenosine A1 Receptor Proteins 0.000 description 1
- 102000030814 Adenosine A1 receptor Human genes 0.000 description 1
- 102000057290 Adenosine Triphosphatases Human genes 0.000 description 1
- 108050000203 Adenosine receptors Proteins 0.000 description 1
- 102000009346 Adenosine receptors Human genes 0.000 description 1
- 208000010370 Adenoviridae Infections Diseases 0.000 description 1
- 206010060931 Adenovirus infection Diseases 0.000 description 1
- 206010001497 Agitation Diseases 0.000 description 1
- 108020005544 Antisense RNA Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 206010003178 Arterial thrombosis Diseases 0.000 description 1
- 206010003673 Atrioventricular block complete Diseases 0.000 description 1
- 241000700663 Avipoxvirus Species 0.000 description 1
- 206010049765 Bradyarrhythmia Diseases 0.000 description 1
- 102400000967 Bradykinin Human genes 0.000 description 1
- 101800004538 Bradykinin Proteins 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 108091005462 Cation channels Proteins 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 108010009685 Cholinergic Receptors Proteins 0.000 description 1
- 101150012960 Chrm2 gene Proteins 0.000 description 1
- 206010008874 Chronic Fatigue Syndrome Diseases 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- 108010069241 Connexin 43 Proteins 0.000 description 1
- 241000557626 Corvus corax Species 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 108010076804 DNA Restriction Enzymes Proteins 0.000 description 1
- 230000007018 DNA scission Effects 0.000 description 1
- 108090000204 Dipeptidase 1 Proteins 0.000 description 1
- 108050009340 Endothelin Proteins 0.000 description 1
- 102000002045 Endothelin Human genes 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 206010049466 Erythroblastosis Diseases 0.000 description 1
- 206010015548 Euthanasia Diseases 0.000 description 1
- 206010015856 Extrasystoles Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- DJBNUMBKLMJRSA-UHFFFAOYSA-N Flecainide Chemical compound FC(F)(F)COC1=CC=C(OCC(F)(F)F)C(C(=O)NCC2NCCCC2)=C1 DJBNUMBKLMJRSA-UHFFFAOYSA-N 0.000 description 1
- 102100021337 Gap junction alpha-1 protein Human genes 0.000 description 1
- 102100030540 Gap junction alpha-5 protein Human genes 0.000 description 1
- 102100039290 Gap junction gamma-1 protein Human genes 0.000 description 1
- 108091006063 Gi2α Proteins 0.000 description 1
- QXZGBUJJYSLZLT-UHFFFAOYSA-N H-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-OH Natural products NC(N)=NCCCC(N)C(=O)N1CCCC1C(=O)N1C(C(=O)NCC(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CO)C(=O)N2C(CCC2)C(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CCCN=C(N)N)C(O)=O)CCC1 QXZGBUJJYSLZLT-UHFFFAOYSA-N 0.000 description 1
- 208000010496 Heart Arrest Diseases 0.000 description 1
- 208000009889 Herpes Simplex Diseases 0.000 description 1
- 101000944277 Homo sapiens Inward rectifier potassium channel 2 Proteins 0.000 description 1
- 101000974726 Homo sapiens Potassium voltage-gated channel subfamily E member 1 Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 241000701024 Human betaherpesvirus 5 Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 235000003332 Ilex aquifolium Nutrition 0.000 description 1
- 241000209027 Ilex aquifolium Species 0.000 description 1
- 102000000588 Interleukin-2 Human genes 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 108010068964 Intracellular Signaling Peptides and Proteins Proteins 0.000 description 1
- 102100033114 Inward rectifier potassium channel 2 Human genes 0.000 description 1
- 101150008942 J gene Proteins 0.000 description 1
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
- 108090000543 Ligand-Gated Ion Channels Proteins 0.000 description 1
- 102000004086 Ligand-Gated Ion Channels Human genes 0.000 description 1
- 108010085220 Multiprotein Complexes Proteins 0.000 description 1
- 102000007474 Multiprotein Complexes Human genes 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 102000007205 Muscarinic M2 Receptor Human genes 0.000 description 1
- 108010008407 Muscarinic M2 Receptor Proteins 0.000 description 1
- 229940123921 Nitric oxide synthase inhibitor Drugs 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 238000000636 Northern blotting Methods 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 206010033557 Palpitations Diseases 0.000 description 1
- 241000282579 Pan Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 102000015439 Phospholipases Human genes 0.000 description 1
- 108010064785 Phospholipases Proteins 0.000 description 1
- 108010003541 Platelet Activating Factor Proteins 0.000 description 1
- 102100022755 Potassium voltage-gated channel subfamily E member 1 Human genes 0.000 description 1
- 208000000418 Premature Cardiac Complexes Diseases 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 102000007327 Protamines Human genes 0.000 description 1
- 108010007568 Protamines Proteins 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 102000007355 Sarcoplasmic Reticulum Calcium-Transporting ATPases Human genes 0.000 description 1
- 108010032750 Sarcoplasmic Reticulum Calcium-Transporting ATPases Proteins 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- 108010040240 Sodium-Calcium Exchanger Proteins 0.000 description 1
- 102000001794 Sodium-Calcium Exchanger Human genes 0.000 description 1
- 102000052126 Sodium-Hydrogen Exchangers Human genes 0.000 description 1
- 108091006672 Sodium–hydrogen antiporter Proteins 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 206010042434 Sudden death Diseases 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 208000003443 Unconsciousness Diseases 0.000 description 1
- 210000003815 abdominal wall Anatomy 0.000 description 1
- 102000034337 acetylcholine receptors Human genes 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000017488 activation-induced cell death of T cell Effects 0.000 description 1
- 206010000891 acute myocardial infarction Diseases 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- 150000003838 adenosines Chemical class 0.000 description 1
- 208000011589 adenoviridae infectious disease Diseases 0.000 description 1
- 230000001800 adrenalinergic effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000006229 amino acid addition Effects 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 229940114079 arachidonic acid Drugs 0.000 description 1
- 235000021342 arachidonic acid Nutrition 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 150000001483 arginine derivatives Chemical group 0.000 description 1
- 230000003143 atherosclerotic effect Effects 0.000 description 1
- 210000002072 atrial myocyte Anatomy 0.000 description 1
- 210000003157 atrial septum Anatomy 0.000 description 1
- YEESUBCSWGVPCE-UHFFFAOYSA-N azanylidyneoxidanium iron(2+) pentacyanide Chemical compound [Fe++].[C-]#N.[C-]#N.[C-]#N.[C-]#N.[C-]#N.N#[O+] YEESUBCSWGVPCE-UHFFFAOYSA-N 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 230000036471 bradycardia Effects 0.000 description 1
- QXZGBUJJYSLZLT-FDISYFBBSA-N bradykinin Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)CCC1 QXZGBUJJYSLZLT-FDISYFBBSA-N 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 238000013194 cardioversion Methods 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000007248 cellular mechanism Effects 0.000 description 1
- 230000000739 chaotic effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000012411 cloning technique Methods 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 239000003184 complementary RNA Substances 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 230000001143 conditioned effect Effects 0.000 description 1
- 208000028925 conduction system disease Diseases 0.000 description 1
- 108010014510 connexin 40 Proteins 0.000 description 1
- 108010015426 connexin 45 Proteins 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 239000002872 contrast media Substances 0.000 description 1
- 229940039231 contrast media Drugs 0.000 description 1
- 238000002586 coronary angiography Methods 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000010217 densitometric analysis Methods 0.000 description 1
- 230000002999 depolarising effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- HSUGRBWQSSZJOP-RTWAWAEBSA-N diltiazem Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-RTWAWAEBSA-N 0.000 description 1
- 229960004166 diltiazem Drugs 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 230000037024 effective refractory period Effects 0.000 description 1
- 230000005611 electricity Effects 0.000 description 1
- 238000001378 electrochemiluminescence detection Methods 0.000 description 1
- 238000003372 electrophysiological method Methods 0.000 description 1
- PJWPNDMDCLXCOM-UHFFFAOYSA-N encainide Chemical compound C1=CC(OC)=CC=C1C(=O)NC1=CC=CC=C1CCC1N(C)CCCC1 PJWPNDMDCLXCOM-UHFFFAOYSA-N 0.000 description 1
- 229960001142 encainide Drugs 0.000 description 1
- 210000001174 endocardium Anatomy 0.000 description 1
- 230000008519 endogenous mechanism Effects 0.000 description 1
- 230000008753 endothelial function Effects 0.000 description 1
- ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 108010048367 enhanced green fluorescent protein Proteins 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 108700004025 env Genes Proteins 0.000 description 1
- 101150030339 env gene Proteins 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 230000002964 excitative effect Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 229960000449 flecainide Drugs 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 108700004026 gag Genes Proteins 0.000 description 1
- 210000003976 gap junction Anatomy 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 238000012224 gene deletion Methods 0.000 description 1
- 238000012239 gene modification Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 230000005017 genetic modification Effects 0.000 description 1
- 235000013617 genetically modified food Nutrition 0.000 description 1
- 239000011544 gradient gel Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000002064 heart cell Anatomy 0.000 description 1
- 230000004217 heart function Effects 0.000 description 1
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 230000001969 hypertrophic effect Effects 0.000 description 1
- 208000022368 idiopathic cardiomyopathy Diseases 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 238000007373 indentation Methods 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 230000006525 intracellular process Effects 0.000 description 1
- 230000031146 intracellular signal transduction Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 150000002617 leukotrienes Chemical class 0.000 description 1
- 229960004194 lidocaine Drugs 0.000 description 1
- 238000000670 ligand binding assay Methods 0.000 description 1
- 208000004731 long QT syndrome Diseases 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- CWWARWOPSKGELM-SARDKLJWSA-N methyl (2s)-2-[[(2s)-2-[[2-[[(2s)-2-[[(2s)-2-[[(2s)-5-amino-2-[[(2s)-5-amino-2-[[(2s)-1-[(2s)-6-amino-2-[[(2s)-1-[(2s)-2-amino-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-5 Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)OC)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CCCN=C(N)N)C1=CC=CC=C1 CWWARWOPSKGELM-SARDKLJWSA-N 0.000 description 1
- 238000007431 microscopic evaluation Methods 0.000 description 1
- 210000005087 mononuclear cell Anatomy 0.000 description 1
- 229940126619 mouse monoclonal antibody Drugs 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 208000029766 myalgic encephalomeyelitis/chronic fatigue syndrome Diseases 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 230000010807 negative regulation of binding Effects 0.000 description 1
- 229960003753 nitric oxide Drugs 0.000 description 1
- 239000000236 nitric oxide synthase inhibitor Substances 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 229960002460 nitroprusside Drugs 0.000 description 1
- 230000001293 nucleolytic effect Effects 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000001314 paroxysmal effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000008447 perception Effects 0.000 description 1
- 210000003516 pericardium Anatomy 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N phenylalanine group Chemical group N[C@@H](CC1=CC=CC=C1)C(=O)O COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- 230000008288 physiological mechanism Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 201000003144 pneumothorax Diseases 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 108700004029 pol Genes Proteins 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- BITYAPCSNKJESK-UHFFFAOYSA-N potassiosodium Chemical compound [Na].[K] BITYAPCSNKJESK-UHFFFAOYSA-N 0.000 description 1
- 239000003450 potassium channel blocker Substances 0.000 description 1
- 239000000276 potassium ferrocyanide Substances 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 230000001536 pro-arrhythmogenic effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 229940048914 protamine Drugs 0.000 description 1
- 238000002331 protein detection Methods 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 230000010349 pulsation Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 230000001177 retroviral effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 210000005241 right ventricle Anatomy 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000000392 somatic effect Effects 0.000 description 1
- 229960002370 sotalol Drugs 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 206010042772 syncope Diseases 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- XOGGUFAVLNCTRS-UHFFFAOYSA-N tetrapotassium;iron(2+);hexacyanide Chemical compound [K+].[K+].[K+].[K+].[Fe+2].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-] XOGGUFAVLNCTRS-UHFFFAOYSA-N 0.000 description 1
- 201000002931 third-degree atrioventricular block Diseases 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 210000000591 tricuspid valve Anatomy 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 102000003390 tumor necrosis factor Human genes 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
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 230000002227 vasoactive effect Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 210000000264 venule Anatomy 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/177—Receptors; Cell surface antigens; Cell surface determinants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/18—Growth factors; Growth regulators
- A61K38/1858—Platelet-derived growth factor [PDGF]
- A61K38/1866—Vascular endothelial growth factor [VEGF]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K48/005—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M25/00—Catheters; Hollow probes
- A61M25/0067—Catheters; Hollow probes characterised by the distal end, e.g. tips
- A61M25/0082—Catheter tip comprising a tool
- A61M25/0084—Catheter tip comprising a tool being one or more injection needles
- A61M2025/0089—Single injection needle protruding axially, i.e. along the longitudinal axis of the catheter, from the distal tip
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2210/00—Anatomical parts of the body
- A61M2210/12—Blood circulatory system
- A61M2210/125—Heart
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Cell Biology (AREA)
- Vascular Medicine (AREA)
- Biophysics (AREA)
- Toxicology (AREA)
- Biochemistry (AREA)
- Cardiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Heart & Thoracic Surgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US23031100P | 2000-09-06 | 2000-09-06 | |
| US60/230,311 | 2000-09-06 | ||
| US29588901P | 2001-06-05 | 2001-06-05 | |
| US60/295,889 | 2001-06-05 | ||
| PCT/US2001/027623 WO2002019966A2 (en) | 2000-09-06 | 2001-09-06 | Cardiac arrhythmia treatment methods |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2004533405A JP2004533405A (ja) | 2004-11-04 |
| JP2004533405A5 JP2004533405A5 (enExample) | 2008-11-13 |
| JP5106738B2 true JP5106738B2 (ja) | 2012-12-26 |
Family
ID=26924110
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2002524451A Expired - Fee Related JP5106738B2 (ja) | 2000-09-06 | 2001-09-06 | 心不整脈治療法 |
Country Status (7)
| Country | Link |
|---|---|
| US (6) | US7034008B2 (enExample) |
| EP (2) | EP1324780A4 (enExample) |
| JP (1) | JP5106738B2 (enExample) |
| AU (2) | AU8880701A (enExample) |
| CA (1) | CA2421584C (enExample) |
| IL (1) | IL154769A0 (enExample) |
| WO (1) | WO2002019966A2 (enExample) |
Families Citing this family (105)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2437397A (en) * | 1996-07-17 | 1998-02-09 | Medtronic, Inc. | System for enhancing cardiac signal sensing by cardiac pacemakers through genetic treatment |
| EP1324780A4 (en) * | 2000-09-06 | 2005-06-22 | Univ Johns Hopkins | METHODS OF TREATING CARDIAC ARRHYTHMIA |
| US20090175790A1 (en) * | 2000-09-06 | 2009-07-09 | The Johns Hopkins University | Cardiac arrhythmia treatment methods and biological pacemaker |
| US7294333B1 (en) * | 2000-10-20 | 2007-11-13 | Genegrafts Ltd. | Nucleic acid constructs and cells, and methods utilizing same for modifying the electrophysiological function of excitable tissues |
| US7699790B2 (en) | 2000-12-20 | 2010-04-20 | Ev3, Inc. | Debulking catheters and methods |
| US7927784B2 (en) | 2000-12-20 | 2011-04-19 | Ev3 | Vascular lumen debulking catheters and methods |
| AU2002338529A1 (en) * | 2001-04-27 | 2002-11-11 | Johns Hopkins University | Biological pacemaker |
| WO2002098287A2 (en) * | 2001-06-06 | 2002-12-12 | The Trustees Of Columbia University In The City Of New York | A high throughput biological heart rate monitor that is molecularly determined |
| US6849611B2 (en) * | 2001-06-06 | 2005-02-01 | The Trustees Of Columbia University In The City Of New York | Implantation of biological pacemaker that is molecularly determined |
| US6783979B2 (en) | 2001-06-06 | 2004-08-31 | The Trustees Of Columbia University In The City Of New York Research Foundation Of State University Of New York | Vectors encoding HCN channels and MiRP1 |
| US7252819B2 (en) | 2001-11-08 | 2007-08-07 | The Regents Of The University Of California | Methods and compositions for correction of cardiac conduction disturbances |
| US6743797B2 (en) * | 2002-02-22 | 2004-06-01 | Chantest, Inc. | Methods for treating cardiac arrhythmia |
| US6811777B2 (en) | 2002-04-13 | 2004-11-02 | Allan Mishra | Compositions and minimally invasive methods for treating incomplete connective tissue repair |
| WO2003095016A1 (en) * | 2002-05-08 | 2003-11-20 | The Regents Of The University Of California | System and method for forming a non-ablative cardiac conduction block |
| AU2003299204A1 (en) * | 2002-10-02 | 2004-04-23 | The Johns Hopkins University | Focal calcium channel modulation |
| US7627373B2 (en) | 2002-11-30 | 2009-12-01 | Cardiac Pacemakers, Inc. | Method and apparatus for cell and electrical therapy of living tissue |
| US20040220655A1 (en) | 2003-03-03 | 2004-11-04 | Sinus Rhythm Technologies, Inc. | Electrical conduction block implant device |
| US20070021375A1 (en) * | 2003-04-25 | 2007-01-25 | Vinod Sharma | Genetic modification of targeted regions of the cardiac conduction system |
| US8013133B2 (en) | 2003-04-25 | 2011-09-06 | Medtronic, Inc. | Genetic modification of targeted regions of the cardiac conduction system |
| US20050021089A1 (en) * | 2003-07-24 | 2005-01-27 | Medtronic, Inc. | Compositions and methods for treating cardiac dysfunction |
| ITRM20030376A1 (it) | 2003-07-31 | 2005-02-01 | Univ Roma | Procedimento per l'isolamento e l'espansione di cellule staminali cardiache da biopsia. |
| CN101415458A (zh) * | 2003-11-10 | 2009-04-22 | 辛弗尼医药有限公司 | 控制心房纤维性颤动患者心室律的方法 |
| EP1690933B1 (en) | 2003-11-17 | 2013-04-24 | Eisai R&D Management Co., Ltd. | hERG CHANNEL-EXPRESSING CELL |
| SE526861C2 (sv) | 2003-11-17 | 2005-11-15 | Syntach Ag | Vävnadslesionsskapande anordning samt en uppsättning av anordningar för behandling av störningar i hjärtrytmregleringssystemet |
| WO2005062857A2 (en) * | 2003-12-24 | 2005-07-14 | The Trustees Of Columbia University In The City Of New York | Creation of a biological atrioventricular bypass to compensate for atrioventricular block |
| US8859273B2 (en) * | 2003-12-24 | 2014-10-14 | Medtronic, Inc. | Methods of using HCN genes to treat cardiac arrhythmias |
| US20060128647A1 (en) * | 2003-12-24 | 2006-06-15 | Daniel Sigg | Novel oligonucleotides and treating cardiac disorders by using the same |
| US20070134157A1 (en) * | 2004-02-26 | 2007-06-14 | Regan Christopher P | Biological assay |
| US7840263B2 (en) * | 2004-02-27 | 2010-11-23 | Cardiac Pacemakers, Inc. | Method and apparatus for device controlled gene expression |
| US9398967B2 (en) | 2004-03-02 | 2016-07-26 | Syntach Ag | Electrical conduction block implant device |
| US7764995B2 (en) | 2004-06-07 | 2010-07-27 | Cardiac Pacemakers, Inc. | Method and apparatus to modulate cellular regeneration post myocardial infarct |
| US7729761B2 (en) | 2004-07-14 | 2010-06-01 | Cardiac Pacemakers, Inc. | Method and apparatus for controlled gene or protein delivery |
| EP1781371A4 (en) * | 2004-07-19 | 2007-12-19 | Univ Columbia | ASSAY SYSTEM FOR MONITORING THE EFFECTS OF GENETICALLY MANUFACTURED CELLS TO CHANGE THE FUNCTION OF A SYNCYTIUM |
| JP5057362B2 (ja) * | 2004-11-02 | 2012-10-24 | 国立大学法人 東京医科歯科大学 | リポソーム及びこれを用いた細胞に対する物質注入方法 |
| US11660317B2 (en) | 2004-11-08 | 2023-05-30 | The Johns Hopkins University | Compositions comprising cardiosphere-derived cells for use in cell therapy |
| US7981065B2 (en) | 2004-12-20 | 2011-07-19 | Cardiac Pacemakers, Inc. | Lead electrode incorporating extracellular matrix |
| US8060219B2 (en) | 2004-12-20 | 2011-11-15 | Cardiac Pacemakers, Inc. | Epicardial patch including isolated extracellular matrix with pacing electrodes |
| WO2006084322A1 (en) * | 2005-02-09 | 2006-08-17 | Craig Steven Mclachlan | Treatment method for modifying tissue passive electrical conductance |
| US8565898B2 (en) * | 2005-04-28 | 2013-10-22 | Medtronic, Inc. | Rate control during AF using cellular intervention to modulate AV node |
| EP1917350A4 (en) * | 2005-07-29 | 2009-04-22 | Univ Columbia | BIOLOGICAL BYPASS BRIDGE WITH SODIUM CHANNELS, CALCIUM CHANNELS AND / OR KALIUM CHANNELS FOR COMPENSATING A LEAD BLOCK IN THE HEART |
| US7774057B2 (en) | 2005-09-06 | 2010-08-10 | Cardiac Pacemakers, Inc. | Method and apparatus for device controlled gene expression for cardiac protection |
| CA2626067A1 (en) * | 2005-10-14 | 2007-04-26 | The Johns Hopkins University | Biologically excitable cells |
| US20070190028A1 (en) * | 2006-02-13 | 2007-08-16 | Jihong Qu | Method and apparatus for heat or electromagnetic control of gene expression |
| US7989207B2 (en) | 2006-02-17 | 2011-08-02 | Tyco Healthcare Group Lp | Testing lumenectomy samples for markers of non-vascular diseases |
| PL2044199T3 (pl) * | 2006-07-25 | 2013-04-30 | Celladon Corp | Przedłużony, podawany z prądem krwi, nasierdziowy, wieńcowy wlew wektorów wirusowych na bazie wirusów towarzyszących adenowirusom, zawierający SERCA2a do terapii genowej |
| US8825677B2 (en) | 2006-09-20 | 2014-09-02 | Ebay Inc. | Listing generation utilizing catalog information |
| US20080082415A1 (en) * | 2006-09-20 | 2008-04-03 | Vishwanath Shastry | Listing generation and advertising management utilizing catalog information |
| WO2008079412A2 (en) * | 2006-12-22 | 2008-07-03 | The Trustees Of Columbia University In The City Of New York | Methods and compositions to treat arrhythmias |
| WO2008090472A2 (en) * | 2007-01-25 | 2008-07-31 | Uti Limited Partnership | Tissue progenitor cells that overexpress erg |
| US20090047703A1 (en) * | 2007-08-17 | 2009-02-19 | University Of Maryland, Baltimore | ERG-1 Peptides and Polynucleotides and Their Use in the Treatment and Diagnosis of Disease |
| US20090054828A1 (en) * | 2007-08-22 | 2009-02-26 | Cardiac Pacemakers, Inc. | Systems for transient conduction control |
| US8311620B2 (en) * | 2007-08-22 | 2012-11-13 | Cardiac Pacemakers, Inc. | Methods and apparatus to treat and prevent atrial tachyarrhythmias |
| EP2198010A4 (en) | 2007-09-12 | 2010-10-06 | Univ California | COMPOSITIONS AND METHODS FOR IMPROVING THE FUNCTIONAL EFFECTIVENESS OF STEM CELLS OF DERIVED HEART MUSCLES |
| US20090233990A1 (en) * | 2007-11-01 | 2009-09-17 | Hee Cheol Cho | Generation of biological pacemaker activity |
| EP2244740A1 (en) | 2008-02-19 | 2010-11-03 | Celladon Corporation | Compositions for enhanced uptake of viral vectors in the myocardium |
| WO2009111755A2 (en) * | 2008-03-07 | 2009-09-11 | The Trustees Of Columbia University In The City Of New York | Compensating for atrioventricular block using a nucleic acid encoding a sodium channel or gap junction protein |
| WO2009120082A2 (en) * | 2008-03-27 | 2009-10-01 | Academisch Medisch Centrum Bij De Universiteit Van Amsterdam | Means and methods for influencing electrical activity of cells |
| US20100112081A1 (en) | 2008-10-07 | 2010-05-06 | Bioparadox, Llc | Use of platelet rich plasma composition in the treatment of cardiac conduction abnormalities |
| WO2011056685A1 (en) * | 2009-10-27 | 2011-05-12 | Cedars-Sinai Medical Center | External magnetic force for targeted cell delivery with enhanced cell retention |
| US9393198B2 (en) * | 2010-03-22 | 2016-07-19 | Signpath Pharma Inc. | Intravenous curcumin and derivatives for treatment of neurodegenerative and stress disorders |
| US9249392B2 (en) | 2010-04-30 | 2016-02-02 | Cedars-Sinai Medical Center | Methods and compositions for maintaining genomic stability in cultured stem cells |
| US9845457B2 (en) | 2010-04-30 | 2017-12-19 | Cedars-Sinai Medical Center | Maintenance of genomic stability in cultured stem cells |
| US10695432B2 (en) * | 2010-10-29 | 2020-06-30 | Infirst Healthcare Limited | Solid solution compositions and use in severe pain |
| US10695431B2 (en) | 2010-10-29 | 2020-06-30 | Infirst Healthcare Limited | Solid solution compositions and use in cardiovascular disease |
| US9504664B2 (en) | 2010-10-29 | 2016-11-29 | Infirst Healthcare Limited | Compositions and methods for treating severe pain |
| US9271950B2 (en) | 2010-10-29 | 2016-03-01 | Infirst Healthcare Limited | Compositions for treating chronic inflammation and inflammatory diseases |
| US11730709B2 (en) | 2010-10-29 | 2023-08-22 | Infirst Healthcare Limited | Compositions and methods for treating severe pain |
| US9308213B2 (en) | 2010-10-29 | 2016-04-12 | Infirst Healthcare Limited | Solid solution compositions and use in chronic inflammation |
| US11202831B2 (en) | 2010-10-29 | 2021-12-21 | Infirst Healthcare Limited | Solid solution compositions and use in cardiovascular disease |
| US11224659B2 (en) | 2010-10-29 | 2022-01-18 | Infirst Healthcare Limited | Solid solution compositions and use in severe pain |
| US8895537B2 (en) | 2010-10-29 | 2014-11-25 | Infirst Healthcare Ltd. | Compositions and methods for treating cardiovascular diseases |
| US9744132B2 (en) | 2010-10-29 | 2017-08-29 | Infirst Healthcare Limited | Solid solution compositions and use in chronic inflammation |
| US8639323B2 (en) | 2010-11-01 | 2014-01-28 | Medtronic, Inc. | System and apparatus to monitor biopacemaker maturation |
| US9962552B2 (en) | 2010-11-18 | 2018-05-08 | Medtronic, Inc. | Implantable medical device with swappable headers |
| US9592398B2 (en) | 2011-05-12 | 2017-03-14 | Medtronic, Inc. | Leadless implantable medical device with osmotic pump |
| ES2896105T3 (es) | 2011-06-03 | 2022-02-23 | Signpath Pharma Inc | Mitigación liposomal del síndrome de QT largo inducido por un fármaco y corriente rectificadora retardada de potasio |
| US10449193B2 (en) | 2011-06-03 | 2019-10-22 | Signpath Pharma Inc. | Protective effect of DMPC, DMPG, DMPC/DMPG, lysoPG and lysoPC against drugs that cause channelopathies |
| US10238602B2 (en) | 2011-06-03 | 2019-03-26 | Signpath Pharma, Inc. | Protective effect of DMPC, DMPG, DMPC/DMPG, LysoPG and LysoPC against drugs that cause channelopathies |
| US10117881B2 (en) | 2011-06-03 | 2018-11-06 | Signpath Pharma, Inc. | Protective effect of DMPC, DMPG, DMPC/DMPG, LYSOPG and LYSOPC against drugs that cause channelopathies |
| US8753674B2 (en) | 2011-06-03 | 2014-06-17 | Signpath Pharma Inc. | Liposomal mitigation of drug-induced long QT syndrome and potassium delayed-rectifier current |
| US12004868B2 (en) | 2011-06-03 | 2024-06-11 | Signpath Pharma Inc. | Liposomal mitigation of drug-induced inhibition of the cardiac IKr channel |
| US10349884B2 (en) | 2011-06-03 | 2019-07-16 | Sighpath Pharma Inc. | Liposomal mitigation of drug-induced inhibition of the cardiac ikr channel |
| US9681836B2 (en) | 2012-04-23 | 2017-06-20 | Cyberonics, Inc. | Methods, systems and apparatuses for detecting seizure and non-seizure states |
| WO2013184527A1 (en) | 2012-06-05 | 2013-12-12 | Capricor, Inc. | Optimized methods for generation of cardiac stem cells from cardiac tissue and their use in cardiac therapy |
| EP3563859B1 (en) | 2012-08-13 | 2021-10-13 | Cedars-Sinai Medical Center | Cardiosphere-derived exosomes for tissue regeneration |
| WO2014036534A1 (en) | 2012-08-31 | 2014-03-06 | University Of North Texas Health Science Center | Curcumin-er, a liposomal-plga sustained release nanocurcumin for minimizing qt prolongation for cancer therapy |
| GB201309882D0 (en) * | 2013-06-03 | 2013-07-17 | Isis Innovation | Prevention and treatment of atrial fibrillation |
| US20140356893A1 (en) | 2013-06-04 | 2014-12-04 | Allan Mishra | Compositions and methods for using platelet-rich plasma for drug discovery, cell nuclear reprogramming, proliferation or differentiation |
| JP6895252B2 (ja) | 2013-12-18 | 2021-06-30 | サインパス ファルマ, インク.Signpath Pharma, Inc. | 心筋ｉｋｒチャネルの薬剤誘発性阻害のリポソームによる軽減 |
| US10087436B2 (en) | 2014-02-06 | 2018-10-02 | The Regents Of The University Of California | Electrophysiologically mature cardiomyocytes and methods for making same |
| EP3151837B1 (en) | 2014-06-03 | 2023-03-15 | Signpath Pharma, Inc. | Protective effect of dmpc, dmpg, dmpc/dmpg, egpg, lysopg and lysopc against drugs that cause channelopathies |
| CA2962444C (en) | 2014-10-03 | 2023-09-05 | Cedars-Sinai Medical Center | Cardiosphere-derived cells and exosomes secreted by such cells in the treatment of muscular dystrophy |
| WO2016059191A1 (en) * | 2014-10-16 | 2016-04-21 | Academisch Medisch Centrum | Nk3 agonist for use in the treatment of a patient suffering from atrial arrhythmia or fibrillation |
| EP3402543B1 (en) | 2016-01-11 | 2021-09-08 | Cedars-Sinai Medical Center | Cardiosphere-derived cells and exosomes secreted by such cells in the treatment of heart failure with preserved ejection fraction |
| EP3448374B1 (en) | 2016-04-27 | 2025-02-12 | Signpath Pharma Inc. | Prevention of drug-induced atrio-ventricular block |
| US11351200B2 (en) | 2016-06-03 | 2022-06-07 | Cedars-Sinai Medical Center | CDC-derived exosomes for treatment of ventricular tachyarrythmias |
| WO2018057542A1 (en) | 2016-09-20 | 2018-03-29 | Cedars-Sinai Medical Center | Cardiosphere-derived cells and their extracellular vesicles to retard or reverse aging and age-related disorders |
| EP3612191B1 (en) | 2017-04-19 | 2026-03-11 | Cedars-Sinai Medical Center | Methods and compositions for treating skeletal muscular dystrophy |
| US12098385B2 (en) | 2017-09-20 | 2024-09-24 | The Regents Of The University Of California | Gene therapy strategy to restore cardiac electrical and structural function in arrhythmogenic right ventricular cardiomyopathy |
| WO2019060619A1 (en) | 2017-09-20 | 2019-03-28 | The Regents Of The University Of California | STRATEGY OF GENE THERAPY FOR RESTORING ELECTRICAL AND CARDIAC FUNCTION AND CARDIAC STRUCTURE IN ARYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY |
| ES2960541T3 (es) | 2017-10-19 | 2024-03-05 | Signpath Pharma Inc | Composiciones líquidas para una utilización peroral que comprenden derivados de fosfatidilglicerol y excipientes tixotrópicos para tratar canalopatías cardíacas causadas por agentes farmacológicos |
| US11660355B2 (en) | 2017-12-20 | 2023-05-30 | Cedars-Sinai Medical Center | Engineered extracellular vesicles for enhanced tissue delivery |
| EP3749344A4 (en) | 2018-02-05 | 2022-01-26 | Cedars-Sinai Medical Center | METHODS OF THERAPEUTIC USE OF EXOSOMES AND Y-RNAS |
| WO2020206103A1 (en) * | 2019-04-04 | 2020-10-08 | University Of Massachusetts | Ventricular arrhythmias and related methods |
| CN117024557B (zh) * | 2023-10-10 | 2024-01-30 | 天津外泌体科技有限公司 | 14-3-3蛋白theta异构体作为细胞外囊泡支架蛋白的应用和细胞外囊泡 |
Family Cites Families (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5401629A (en) | 1990-08-07 | 1995-03-28 | The Salk Institute Biotechnology/Industrial Associates, Inc. | Assay methods and compositions useful for measuring the transduction of an intracellular signal |
| US5163950A (en) * | 1990-08-24 | 1992-11-17 | Medical Engineering Corporation | Balloon catheter and endoscope kit |
| JPH10501681A (ja) | 1994-02-22 | 1998-02-17 | ダナ−ファーバー キャンサー インスティチュート | 核酸送達システムならびにその合成および使用方法 |
| US5662585A (en) * | 1994-05-05 | 1997-09-02 | Imagyn Medical, Inc. | Endoscope with protruding member and method of utilizing the same |
| US5836905A (en) * | 1994-06-20 | 1998-11-17 | Lemelson; Jerome H. | Apparatus and methods for gene therapy |
| US5824550A (en) * | 1994-10-28 | 1998-10-20 | Barnes-Jewish Hopital | Voltage-gated calcium channel and antisense oligonucleotides thereto |
| WO1996028537A1 (en) * | 1995-03-09 | 1996-09-19 | University Of Utah Research Foundation | Long qt genes and method for diagnosing or preventing the occurrence of long qt syndrome |
| US6605274B1 (en) * | 1995-04-11 | 2003-08-12 | The Regents Of The University Of California | Method for in vivo regulation of cardiac muscle contractility |
| ES2325820T3 (es) * | 1995-12-22 | 2009-09-18 | University Of Utah Research Foundation | Gen del sindrome qt largo que codifica kvlqt1 y su asociacion con mink. |
| US5944710A (en) * | 1996-06-24 | 1999-08-31 | Genetronics, Inc. | Electroporation-mediated intravascular delivery |
| AU734576B2 (en) * | 1996-08-02 | 2001-06-14 | Elan Pharmaceuticals, Inc. | Voltage-gated calcium channel antagonist and methods |
| US20020009772A1 (en) * | 1997-02-28 | 2002-01-24 | Terry P. Snutch | Novel human calcium channels and related probes, cell lines and mehtods |
| US6086582A (en) * | 1997-03-13 | 2000-07-11 | Altman; Peter A. | Cardiac drug delivery system |
| US6123699A (en) * | 1997-09-05 | 2000-09-26 | Cordis Webster, Inc. | Omni-directional steerable catheter |
| US6183444B1 (en) * | 1998-05-16 | 2001-02-06 | Microheart, Inc. | Drug delivery module |
| WO1999023880A1 (en) | 1997-11-07 | 1999-05-20 | Johns Hopkins University | Somatic transfer of modified genes to predict drug effects |
| US6703485B2 (en) * | 1997-12-23 | 2004-03-09 | The Trustees Of Columbia University In The City Of New York | Brain and heart cyclic nucleotide gated ion channel compounds and uses thereof |
| US5965396A (en) * | 1998-01-13 | 1999-10-12 | Zeneca Limited | Human lymph node derived GTPase |
| US6776987B1 (en) * | 1998-01-13 | 2004-08-17 | Massachusetts Institute Of Technology | Enhancement of cardiac chronotropy |
| US6207422B1 (en) * | 1998-04-17 | 2001-03-27 | The Metrohealth System | Protein that enhances expression of potassium channels on cell surfaces and nucleic acids that encode the same |
| US6623474B1 (en) * | 1998-06-04 | 2003-09-23 | Biosense Webster, Inc. | Injection catheter with needle stop |
| US6365337B1 (en) * | 1998-07-27 | 2002-04-02 | University Of Iowa Research Foundation | Genes encoding neuronal voltage-gated calcium channel gamma subunits |
| WO2000018903A2 (en) * | 1998-09-29 | 2000-04-06 | The Johns Hopkins University | Inducible genetic suppression of cellular excitability |
| EP1139751A4 (en) * | 1998-12-28 | 2003-03-19 | Arch Dev Corp | EFFICIENT AND STABLE -I (IN VIVO) GENE TRANSFER TO CARDIOMYCETS USING RECOMBINANT ADENO-ASSOCIATED VIRUS VECTORS |
| AU2732000A (en) | 1999-01-19 | 2000-08-01 | Children's Hospital Of Philadelphia, The | Reverse gene therapy |
| EP1324780A4 (en) * | 2000-09-06 | 2005-06-22 | Univ Johns Hopkins | METHODS OF TREATING CARDIAC ARRHYTHMIA |
| ATE445417T1 (de) * | 2000-10-13 | 2009-10-15 | Univ Johns Hopkins | Ex vivo verfahren und zusammensetzungen zur nukleinsäureverabreichung |
| US7294333B1 (en) * | 2000-10-20 | 2007-11-13 | Genegrafts Ltd. | Nucleic acid constructs and cells, and methods utilizing same for modifying the electrophysiological function of excitable tissues |
| AU2002338529A1 (en) * | 2001-04-27 | 2002-11-11 | Johns Hopkins University | Biological pacemaker |
| WO2002098287A2 (en) * | 2001-06-06 | 2002-12-12 | The Trustees Of Columbia University In The City Of New York | A high throughput biological heart rate monitor that is molecularly determined |
| US6783979B2 (en) * | 2001-06-06 | 2004-08-31 | The Trustees Of Columbia University In The City Of New York Research Foundation Of State University Of New York | Vectors encoding HCN channels and MiRP1 |
| AU2003299204A1 (en) * | 2002-10-02 | 2004-04-23 | The Johns Hopkins University | Focal calcium channel modulation |
| WO2005033139A2 (en) * | 2003-05-28 | 2005-04-14 | Synta Pharmaceuticals Corp. | Novel calcium channels and uses thereof |
| WO2006017566A2 (en) * | 2004-08-02 | 2006-02-16 | The Johns Hopkins University | Modulation of bio-electrical rhythms via a novel engineering approach |
| US9116846B2 (en) | 2013-06-10 | 2015-08-25 | Veeam Software Ag | Virtual machine backup from storage snapshot |
-
2001
- 2001-09-06 EP EP20010968567 patent/EP1324780A4/en not_active Withdrawn
- 2001-09-06 WO PCT/US2001/027623 patent/WO2002019966A2/en not_active Ceased
- 2001-09-06 CA CA2421584A patent/CA2421584C/en not_active Expired - Fee Related
- 2001-09-06 JP JP2002524451A patent/JP5106738B2/ja not_active Expired - Fee Related
- 2001-09-06 EP EP10185602A patent/EP2363152A1/en not_active Withdrawn
- 2001-09-06 AU AU8880701A patent/AU8880701A/xx active Pending
- 2001-09-06 US US09/947,953 patent/US7034008B2/en not_active Expired - Fee Related
- 2001-09-06 AU AU2001288807A patent/AU2001288807B2/en not_active Ceased
- 2001-09-06 IL IL15476901A patent/IL154769A0/xx unknown
-
2004
- 2004-05-28 US US10/855,892 patent/US20040266716A1/en not_active Abandoned
- 2004-05-28 US US10/855,805 patent/US20050107323A1/en not_active Abandoned
- 2004-05-28 US US10/855,989 patent/US20040266717A1/en not_active Abandoned
-
2006
- 2006-08-24 US US11/508,957 patent/US20070048284A1/en not_active Abandoned
-
2014
- 2014-09-15 US US14/486,020 patent/US20150183842A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| EP1324780A2 (en) | 2003-07-09 |
| EP2363152A1 (en) | 2011-09-07 |
| JP2004533405A (ja) | 2004-11-04 |
| AU8880701A (en) | 2002-03-22 |
| US20070048284A1 (en) | 2007-03-01 |
| US20050107323A1 (en) | 2005-05-19 |
| AU2001288807B2 (en) | 2007-07-19 |
| IL154769A0 (en) | 2003-10-31 |
| US7034008B2 (en) | 2006-04-25 |
| US20040266716A1 (en) | 2004-12-30 |
| WO2002019966A2 (en) | 2002-03-14 |
| CA2421584A1 (en) | 2002-03-14 |
| US20040266717A1 (en) | 2004-12-30 |
| US20020155101A1 (en) | 2002-10-24 |
| US20150183842A1 (en) | 2015-07-02 |
| EP1324780A4 (en) | 2005-06-22 |
| WO2002019966A3 (en) | 2002-08-15 |
| CA2421584C (en) | 2013-12-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2421584C (en) | Gene therapy for cardiac arrythmias | |
| AU2001288807A1 (en) | Cardiac arrhythmia treatment methods | |
| JP4279558B2 (ja) | 生物学的ペースメーカー | |
| JPH10501423A (ja) | 遺伝子転移媒介の血管形成療法 | |
| EP1648521B1 (en) | Compositions and methods for treating cardiac dysfunction | |
| US20110245772A1 (en) | Focal calcium channel modulation | |
| JP2003513942A (ja) | インビボ遺伝子送達による心血管疾患を処理するための技術および組成物 | |
| JP2002515065A (ja) | 脈管形成トランスジーンのインビボ送達により心不全および心室再構成を処置するための技術および組成物 | |
| Hou et al. | Widespread regional myocardial transfection by plasmid encoding Del‐1 following retrograde coronary venous delivery | |
| US7247618B2 (en) | Methods for inhibiting macrophage colony stimulating factor and c-FMS-dependent cell signaling | |
| US20110286931A1 (en) | Cardiac arrhythmia treatment methods and biological pacemaker | |
| US20250143624A1 (en) | Ventricular Arrhythmias and Related Methods | |
| EP2044199B1 (en) | Extended antegrade epicardial coronary infusion of adeno-associated viral vectors comprising serca2a for gene therapy | |
| CN120939230A (zh) | Tdp2作为靶点在预防和治疗心肌缺血再灌注损伤中的应用 | |
| Bae et al. | Gene therapy for heart failure |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20080904 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20080904 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20080904 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20110531 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20110819 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20110826 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20111121 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20120424 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20120724 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20120904 |
|
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20121003 |
|
| R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20151012 Year of fee payment: 3 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |