SK284334B6 - Farmaceutická kompozícia na liečenie neurodegeneratívnej choroby - Google Patents

Farmaceutická kompozícia na liečenie neurodegeneratívnej choroby Download PDF

Info

Publication number: SK284334B6
Authority: SK; Slovakia
Prior art keywords: cox; nimesulide; pharmaceutical composition; treatment; mrna
Prior art date: 1996-11-21

Application number

SK671-99A

Other languages

English (en)

Slovak (sk)

Other versions

SK67199A3 (en

Inventor

Giulio Maria Pasinetti

Paul S. Aisen

Original Assignee

The Mount Sinai School Of Medicine Of The City University Of

Priority date (The priority date 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 date listed.)

1996-11-21

Filing date

1997-11-19

Publication date

2005-02-04

1997-11-19 Application filed by The Mount Sinai School Of Medicine Of The City University Of filed Critical The Mount Sinai School Of Medicine Of The City University Of

2001-01-18 Publication of SK67199A3 publication Critical patent/SK67199A3/sk

2005-02-04 Publication of SK284334B6 publication Critical patent/SK284334B6/sk

Links

239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 25
230000000626 neurodegenerative effect Effects 0.000 title abstract description 8
HYWYRSMBCFDLJT-UHFFFAOYSA-N nimesulide Chemical compound CS(=O)(=O)NC1=CC=C([N+]([O-])=O)C=C1OC1=CC=CC=C1 HYWYRSMBCFDLJT-UHFFFAOYSA-N 0.000 claims abstract description 58
229960000965 nimesulide Drugs 0.000 claims abstract description 57
208000024827 Alzheimer disease Diseases 0.000 claims abstract description 19
206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims abstract description 8
206010015037 epilepsy Diseases 0.000 claims abstract description 7
210000002569 neuron Anatomy 0.000 claims description 36
238000004519 manufacturing process Methods 0.000 claims description 15
230000016273 neuron death Effects 0.000 claims description 14
230000004770 neurodegeneration Effects 0.000 claims description 12
208000015122 neurodegenerative disease Diseases 0.000 claims description 6
238000002360 preparation method Methods 0.000 abstract description 11
108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 148
102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 148
108020004999 messenger RNA Proteins 0.000 description 60
230000014509 gene expression Effects 0.000 description 50
210000004556 brain Anatomy 0.000 description 46
241000700159 Rattus Species 0.000 description 39
210000004027 cell Anatomy 0.000 description 36
230000001537 neural effect Effects 0.000 description 23
230000000694 effects Effects 0.000 description 22
230000006698 induction Effects 0.000 description 20
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 19
229930195712 glutamate Natural products 0.000 description 19
102100038277 Prostaglandin G/H synthase 1 Human genes 0.000 description 15
108050003243 Prostaglandin G/H synthase 1 Proteins 0.000 description 15
230000004044 response Effects 0.000 description 15
210000001519 tissue Anatomy 0.000 description 14
241000282414 Homo sapiens Species 0.000 description 13
108091032973 (ribonucleotides)n+m Proteins 0.000 description 12
238000007901 in situ hybridization Methods 0.000 description 12
239000000126 substance Substances 0.000 description 12
230000006907 apoptotic process Effects 0.000 description 11
210000001320 hippocampus Anatomy 0.000 description 11
230000033228 biological regulation Effects 0.000 description 10
230000001404 mediated effect Effects 0.000 description 10
108090000765 processed proteins & peptides Proteins 0.000 description 10
206010010904 Convulsion Diseases 0.000 description 9
239000010410 layer Substances 0.000 description 9
150000003180 prostaglandins Chemical class 0.000 description 9
108090000623 proteins and genes Proteins 0.000 description 9
230000001640 apoptogenic effect Effects 0.000 description 8
238000009396 hybridization Methods 0.000 description 8
108020004414 DNA Proteins 0.000 description 7
230000002018 overexpression Effects 0.000 description 7
210000002966 serum Anatomy 0.000 description 7
239000011734 sodium Substances 0.000 description 7
208000037259 Amyloid Plaque Diseases 0.000 description 6
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
239000003795 chemical substances by application Substances 0.000 description 6
230000000971 hippocampal effect Effects 0.000 description 6
238000012744 immunostaining Methods 0.000 description 6
CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 6
231100000419 toxicity Toxicity 0.000 description 6
230000001988 toxicity Effects 0.000 description 6
238000004458 analytical method Methods 0.000 description 5
210000001947 dentate gyrus Anatomy 0.000 description 5
238000009826 distribution Methods 0.000 description 5
239000002158 endotoxin Substances 0.000 description 5
230000037456 inflammatory mechanism Effects 0.000 description 5
230000000926 neurological effect Effects 0.000 description 5
230000003287 optical effect Effects 0.000 description 5
229940094443 oxytocics prostaglandins Drugs 0.000 description 5
102000004196 processed proteins & peptides Human genes 0.000 description 5
239000011780 sodium chloride Substances 0.000 description 5
102000007469 Actins Human genes 0.000 description 4
108010085238 Actins Proteins 0.000 description 4
102000013455 Amyloid beta-Peptides Human genes 0.000 description 4
108010090849 Amyloid beta-Peptides Proteins 0.000 description 4
108010035563 Chloramphenicol O-acetyltransferase Proteins 0.000 description 4
206010061218 Inflammation Diseases 0.000 description 4
241000699666 Mus <mouse, genus> Species 0.000 description 4
206010029350 Neurotoxicity Diseases 0.000 description 4
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 4
206010044221 Toxic encephalopathy Diseases 0.000 description 4
GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 4
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 4
238000000376 autoradiography Methods 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
210000003710 cerebral cortex Anatomy 0.000 description 4
239000002299 complementary DNA Substances 0.000 description 4
230000006378 damage Effects 0.000 description 4
239000000839 emulsion Substances 0.000 description 4
230000001037 epileptic effect Effects 0.000 description 4
238000010191 image analysis Methods 0.000 description 4
238000000338 in vitro Methods 0.000 description 4
230000004054 inflammatory process Effects 0.000 description 4
230000003902 lesion Effects 0.000 description 4
230000035800 maturation Effects 0.000 description 4
230000007246 mechanism Effects 0.000 description 4
239000002609 medium Substances 0.000 description 4
210000004498 neuroglial cell Anatomy 0.000 description 4
230000007135 neurotoxicity Effects 0.000 description 4
231100000228 neurotoxicity Toxicity 0.000 description 4
102000013415 peroxidase activity proteins Human genes 0.000 description 4
108040007629 peroxidase activity proteins Proteins 0.000 description 4
230000001105 regulatory effect Effects 0.000 description 4
238000011830 transgenic mouse model Methods 0.000 description 4
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
102000004190 Enzymes Human genes 0.000 description 3
108090000790 Enzymes Proteins 0.000 description 3
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
102000003855 L-lactate dehydrogenase Human genes 0.000 description 3
108700023483 L-lactate dehydrogenases Proteins 0.000 description 3
241000699660 Mus musculus Species 0.000 description 3
241000699670 Mus sp. Species 0.000 description 3
238000000692 Student's t-test Methods 0.000 description 3
108060008682 Tumor Necrosis Factor Proteins 0.000 description 3
230000032683 aging Effects 0.000 description 3
VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 3
238000004113 cell culture Methods 0.000 description 3
238000001514 detection method Methods 0.000 description 3
238000003119 immunoblot Methods 0.000 description 3
238000003365 immunocytochemistry Methods 0.000 description 3
238000011065 in-situ storage Methods 0.000 description 3
229960000905 indomethacin Drugs 0.000 description 3
230000002757 inflammatory effect Effects 0.000 description 3
201000010901 lateral sclerosis Diseases 0.000 description 3
229920006008 lipopolysaccharide Polymers 0.000 description 3
239000012528 membrane Substances 0.000 description 3
210000000274 microglia Anatomy 0.000 description 3
238000001000 micrograph Methods 0.000 description 3
208000005264 motor neuron disease Diseases 0.000 description 3
239000013612 plasmid Substances 0.000 description 3
KAQKFAOMNZTLHT-OZUDYXHBSA-N prostaglandin I2 Chemical compound O1\C(=C/CCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-OZUDYXHBSA-N 0.000 description 3
230000001681 protective effect Effects 0.000 description 3
102000004169 proteins and genes Human genes 0.000 description 3
230000028327 secretion Effects 0.000 description 3
238000012353 t test Methods 0.000 description 3
102000003390 tumor necrosis factor Human genes 0.000 description 3
239000013598 vector Substances 0.000 description 3
102000014303 Amyloid beta-Protein Precursor Human genes 0.000 description 2
108010079054 Amyloid beta-Protein Precursor Proteins 0.000 description 2
101150071146 COX2 gene Proteins 0.000 description 2
101100114534 Caenorhabditis elegans ctc-2 gene Proteins 0.000 description 2
108091026890 Coding region Proteins 0.000 description 2
108010037462 Cyclooxygenase 2 Proteins 0.000 description 2
102000004127 Cytokines Human genes 0.000 description 2
108090000695 Cytokines Proteins 0.000 description 2
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
238000006595 Griess deamination reaction Methods 0.000 description 2
101000605127 Homo sapiens Prostaglandin G/H synthase 2 Proteins 0.000 description 2
231100000002 MTT assay Toxicity 0.000 description 2
238000000134 MTT assay Methods 0.000 description 2
241001465754 Metazoa Species 0.000 description 2
101000605126 Mus musculus Prostaglandin G/H synthase 2 Proteins 0.000 description 2
KTDZCOWXCWUPEO-UHFFFAOYSA-N NS-398 Chemical compound CS(=O)(=O)NC1=CC=C([N+]([O-])=O)C=C1OC1CCCCC1 KTDZCOWXCWUPEO-UHFFFAOYSA-N 0.000 description 2
IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 2
GQPLMRYTRLFLPF-UHFFFAOYSA-N Nitrous Oxide Chemical compound [O-][N+]#N GQPLMRYTRLFLPF-UHFFFAOYSA-N 0.000 description 2
101710195703 Oxygen-dependent coproporphyrinogen-III oxidase Proteins 0.000 description 2
102100036201 Oxygen-dependent coproporphyrinogen-III oxidase, mitochondrial Human genes 0.000 description 2
101710200437 Oxygen-dependent coproporphyrinogen-III oxidase, mitochondrial Proteins 0.000 description 2
101150000187 PTGS2 gene Proteins 0.000 description 2
229930040373 Paraformaldehyde Natural products 0.000 description 2
102000012288 Phosphopyruvate Hydratase Human genes 0.000 description 2
108010022181 Phosphopyruvate Hydratase Proteins 0.000 description 2
102100022033 Presenilin-1 Human genes 0.000 description 2
108010036933 Presenilin-1 Proteins 0.000 description 2
102100022036 Presenilin-2 Human genes 0.000 description 2
108010036908 Presenilin-2 Proteins 0.000 description 2
102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 2
108010029485 Protein Isoforms Proteins 0.000 description 2
102000001708 Protein Isoforms Human genes 0.000 description 2
101000605131 Rattus norvegicus Prostaglandin G/H synthase 2 Proteins 0.000 description 2
208000027418 Wounds and injury Diseases 0.000 description 2
VLSMHEGGTFMBBZ-UHFFFAOYSA-N alpha-Kainic acid Natural products CC(=C)C1CNC(C(O)=O)C1CC(O)=O VLSMHEGGTFMBBZ-UHFFFAOYSA-N 0.000 description 2
125000003277 amino group Chemical group 0.000 description 2
238000000540 analysis of variance Methods 0.000 description 2
230000000692 anti-sense effect Effects 0.000 description 2
230000009925 apoptotic mechanism Effects 0.000 description 2
229940114079 arachidonic acid Drugs 0.000 description 2
235000021342 arachidonic acid Nutrition 0.000 description 2
238000003556 assay Methods 0.000 description 2
238000001574 biopsy Methods 0.000 description 2
238000002038 chemiluminescence detection Methods 0.000 description 2
230000001054 cortical effect Effects 0.000 description 2
238000007405 data analysis Methods 0.000 description 2
230000007547 defect Effects 0.000 description 2
230000029087 digestion Effects 0.000 description 2
201000010099 disease Diseases 0.000 description 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
238000001962 electrophoresis Methods 0.000 description 2
230000003492 excitotoxic effect Effects 0.000 description 2
238000005755 formation reaction Methods 0.000 description 2
239000000499 gel Substances 0.000 description 2
239000008187 granular material Substances 0.000 description 2
210000004884 grey matter Anatomy 0.000 description 2
150000003278 haem Chemical class 0.000 description 2
208000014674 injury Diseases 0.000 description 2
VLSMHEGGTFMBBZ-OOZYFLPDSA-N kainic acid Chemical compound CC(=C)[C@H]1CN[C@H](C(O)=O)[C@H]1CC(O)=O VLSMHEGGTFMBBZ-OOZYFLPDSA-N 0.000 description 2
229950006874 kainic acid Drugs 0.000 description 2
238000002372 labelling Methods 0.000 description 2
238000005259 measurement Methods 0.000 description 2
238000000034 method Methods 0.000 description 2
230000002025 microglial effect Effects 0.000 description 2
230000006576 neuronal survival Effects 0.000 description 2
230000000324 neuroprotective effect Effects 0.000 description 2
230000004792 oxidative damage Effects 0.000 description 2
230000036542 oxidative stress Effects 0.000 description 2
229920002866 paraformaldehyde Polymers 0.000 description 2
230000002093 peripheral effect Effects 0.000 description 2
230000003389 potentiating effect Effects 0.000 description 2
230000002265 prevention Effects 0.000 description 2
230000002829 reductive effect Effects 0.000 description 2
239000000523 sample Substances 0.000 description 2
241000894007 species Species 0.000 description 2
210000000278 spinal cord Anatomy 0.000 description 2
210000000498 stratum granulosum Anatomy 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
230000002123 temporal effect Effects 0.000 description 2
231100000331 toxic Toxicity 0.000 description 2
230000002588 toxic effect Effects 0.000 description 2
238000012546 transfer Methods 0.000 description 2
230000010474 transient expression Effects 0.000 description 2
239000003981 vehicle Substances 0.000 description 2
238000001262 western blot Methods 0.000 description 2
210000004885 white matter Anatomy 0.000 description 2
QRXMUCSWCMTJGU-UHFFFAOYSA-L (5-bromo-4-chloro-1h-indol-3-yl) phosphate Chemical compound C1=C(Br)C(Cl)=C2C(OP([O-])(=O)[O-])=CNC2=C1 QRXMUCSWCMTJGU-UHFFFAOYSA-L 0.000 description 1
102000040650 (ribonucleotides)n+m Human genes 0.000 description 1
GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 description 1
108020004463 18S ribosomal RNA Proteins 0.000 description 1
QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
125000000972 4,5-dimethylthiazol-2-yl group Chemical group [H]C([H])([H])C1=C(N=C(*)S1)C([H])([H])[H] 0.000 description 1
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
102000011767 Acute-Phase Proteins Human genes 0.000 description 1
108010062271 Acute-Phase Proteins Proteins 0.000 description 1
229920000936 Agarose Polymers 0.000 description 1
102000002260 Alkaline Phosphatase Human genes 0.000 description 1
108020004774 Alkaline Phosphatase Proteins 0.000 description 1
108700028369 Alleles Proteins 0.000 description 1
102000007592 Apolipoproteins Human genes 0.000 description 1
108010071619 Apolipoproteins Proteins 0.000 description 1
YKZJPIPFKGYHKY-DCAQKATOSA-N Arg-Leu-Asp Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O YKZJPIPFKGYHKY-DCAQKATOSA-N 0.000 description 1
HOQGTAIGQSDCHR-SRVKXCTJSA-N Asp-Asn-Phe Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O HOQGTAIGQSDCHR-SRVKXCTJSA-N 0.000 description 1
241000972773 Aulopiformes Species 0.000 description 1
208000023275 Autoimmune disease Diseases 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
229940124638 COX inhibitor Drugs 0.000 description 1
BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
108020004635 Complementary DNA Proteins 0.000 description 1
HRJLVSQKBLZHSR-ZLUOBGJFSA-N Cys-Asn-Ala Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(O)=O HRJLVSQKBLZHSR-ZLUOBGJFSA-N 0.000 description 1
102000004594 DNA Polymerase I Human genes 0.000 description 1
108010017826 DNA Polymerase I Proteins 0.000 description 1
206010012289 Dementia Diseases 0.000 description 1
201000010374 Down Syndrome Diseases 0.000 description 1
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 1
206010062767 Hypophysitis Diseases 0.000 description 1
108700002232 Immediate-Early Genes Proteins 0.000 description 1
238000012404 In vitro experiment Methods 0.000 description 1
231100000416 LDH assay Toxicity 0.000 description 1
JLVVSXFLKOJNIY-UHFFFAOYSA-N Magnesium ion Chemical compound [Mg+2] JLVVSXFLKOJNIY-UHFFFAOYSA-N 0.000 description 1
206010028980 Neoplasm Diseases 0.000 description 1
102000008299 Nitric Oxide Synthase Human genes 0.000 description 1
108010021487 Nitric Oxide Synthase Proteins 0.000 description 1
239000004677 Nylon Substances 0.000 description 1
229920002302 Nylon 6,6 Polymers 0.000 description 1
241000283973 Oryctolagus cuniculus Species 0.000 description 1
-1 PG-D2 Chemical class 0.000 description 1
208000018737 Parkinson disease Diseases 0.000 description 1
241001494479 Pecora Species 0.000 description 1
108010039918 Polylysine Proteins 0.000 description 1
102000015433 Prostaglandin Receptors Human genes 0.000 description 1
108010050183 Prostaglandin Receptors Proteins 0.000 description 1
102000013535 Proto-Oncogene Proteins c-bcl-2 Human genes 0.000 description 1
108010090931 Proto-Oncogene Proteins c-bcl-2 Proteins 0.000 description 1
238000002123 RNA extraction Methods 0.000 description 1
101001058233 Rattus norvegicus Gamma-enolase Proteins 0.000 description 1
240000004808 Saccharomyces cerevisiae Species 0.000 description 1
229940124639 Selective inhibitor Drugs 0.000 description 1
108091081021 Sense strand Proteins 0.000 description 1
CAOYHZOWXFFAIR-CIUDSAMLSA-N Ser-His-Ser Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CO)C(O)=O CAOYHZOWXFFAIR-CIUDSAMLSA-N 0.000 description 1
208000037065 Subacute sclerosing leukoencephalitis Diseases 0.000 description 1
206010042297 Subacute sclerosing panencephalitis Diseases 0.000 description 1
102100023132 Transcription factor Jun Human genes 0.000 description 1
102000011117 Transforming Growth Factor beta2 Human genes 0.000 description 1
101800000304 Transforming growth factor beta-2 Proteins 0.000 description 1
206010044688 Trisomy 21 Diseases 0.000 description 1
ZHAFUINZIZIXFC-UHFFFAOYSA-N [9-(dimethylamino)-10-methylbenzo[a]phenoxazin-5-ylidene]azanium;chloride Chemical compound [Cl-].O1C2=CC(=[NH2+])C3=CC=CC=C3C2=NC2=C1C=C(N(C)C)C(C)=C2 ZHAFUINZIZIXFC-UHFFFAOYSA-N 0.000 description 1
238000009825 accumulation Methods 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
230000002411 adverse Effects 0.000 description 1
239000011543 agarose gel Substances 0.000 description 1
150000001413 amino acids Chemical group 0.000 description 1
230000003941 amyloidogenesis Effects 0.000 description 1
229940121363 anti-inflammatory agent Drugs 0.000 description 1
239000002260 anti-inflammatory agent Substances 0.000 description 1
108010040443 aspartyl-aspartic acid Proteins 0.000 description 1
210000001130 astrocyte Anatomy 0.000 description 1
238000000211 autoradiogram Methods 0.000 description 1
230000001580 bacterial effect Effects 0.000 description 1
125000002619 bicyclic group Chemical group 0.000 description 1
230000000903 blocking effect Effects 0.000 description 1
230000037185 brain physiology Effects 0.000 description 1
210000005013 brain tissue Anatomy 0.000 description 1
210000004899 c-terminal region Anatomy 0.000 description 1
229910001424 calcium ion Inorganic materials 0.000 description 1
201000011510 cancer Diseases 0.000 description 1
230000015556 catabolic process Effects 0.000 description 1
230000021164 cell adhesion Effects 0.000 description 1
230000030833 cell death Effects 0.000 description 1
230000008809 cell oxidative stress Effects 0.000 description 1
230000001413 cellular effect Effects 0.000 description 1
230000007541 cellular toxicity Effects 0.000 description 1
230000008859 change Effects 0.000 description 1
238000006243 chemical reaction Methods 0.000 description 1
230000000295 complement effect Effects 0.000 description 1
239000003184 complementary RNA Substances 0.000 description 1
230000008094 contradictory effect Effects 0.000 description 1
229940111134 coxibs Drugs 0.000 description 1
239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 1
SUYVUBYJARFZHO-RRKCRQDMSA-N dATP Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@H]1C[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 SUYVUBYJARFZHO-RRKCRQDMSA-N 0.000 description 1
SUYVUBYJARFZHO-UHFFFAOYSA-N dATP Natural products C1=NC=2C(N)=NC=NC=2N1C1CC(O)C(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 SUYVUBYJARFZHO-UHFFFAOYSA-N 0.000 description 1
RGWHQCVHVJXOKC-SHYZEUOFSA-J dCTP(4-) Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)C1 RGWHQCVHVJXOKC-SHYZEUOFSA-J 0.000 description 1
HAAZLUGHYHWQIW-KVQBGUIXSA-N dGTP Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 HAAZLUGHYHWQIW-KVQBGUIXSA-N 0.000 description 1
NHVNXKFIZYSCEB-XLPZGREQSA-N dTTP Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)C1 NHVNXKFIZYSCEB-XLPZGREQSA-N 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
230000007812 deficiency Effects 0.000 description 1
238000006731 degradation reaction Methods 0.000 description 1
230000028315 developmental maturation Effects 0.000 description 1
238000002050 diffraction method Methods 0.000 description 1
XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 1
229960002986 dinoprostone Drugs 0.000 description 1
229940079593 drug Drugs 0.000 description 1
239000003814 drug Substances 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
238000001035 drying Methods 0.000 description 1
210000002257 embryonic structure Anatomy 0.000 description 1
230000009088 enzymatic function Effects 0.000 description 1
210000002919 epithelial cell Anatomy 0.000 description 1
229960001123 epoprostenol Drugs 0.000 description 1
238000012869 ethanol precipitation Methods 0.000 description 1
231100000318 excitotoxic Toxicity 0.000 description 1
231100000063 excitotoxicity Toxicity 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
239000013604 expression vector Substances 0.000 description 1
239000000284 extract Substances 0.000 description 1
235000013305 food Nutrition 0.000 description 1
239000012634 fragment Substances 0.000 description 1
238000013467 fragmentation Methods 0.000 description 1
238000006062 fragmentation reaction Methods 0.000 description 1
239000012737 fresh medium Substances 0.000 description 1
230000006870 function Effects 0.000 description 1
230000002068 genetic effect Effects 0.000 description 1
230000002518 glial effect Effects 0.000 description 1
239000003862 glucocorticoid Substances 0.000 description 1
210000004565 granule cell Anatomy 0.000 description 1
ZJYYHGLJYGJLLN-UHFFFAOYSA-N guanidinium thiocyanate Chemical compound SC#N.NC(N)=N ZJYYHGLJYGJLLN-UHFFFAOYSA-N 0.000 description 1
210000004295 hippocampal neuron Anatomy 0.000 description 1
229940088597 hormone Drugs 0.000 description 1
239000005556 hormone Substances 0.000 description 1
125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
210000003016 hypothalamus Anatomy 0.000 description 1
238000005286 illumination Methods 0.000 description 1
230000000984 immunochemical effect Effects 0.000 description 1
230000036046 immunoreaction Effects 0.000 description 1
230000001771 impaired effect Effects 0.000 description 1
238000010874 in vitro model Methods 0.000 description 1
238000010249 in-situ analysis Methods 0.000 description 1
238000011534 incubation Methods 0.000 description 1
230000001939 inductive effect Effects 0.000 description 1
230000028709 inflammatory response Effects 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
239000000543 intermediate Substances 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000007913 intrathecal administration Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
QWTDNUCVQCZILF-UHFFFAOYSA-N isopentane Chemical compound CCC(C)C QWTDNUCVQCZILF-UHFFFAOYSA-N 0.000 description 1
238000002843 lactate dehydrogenase assay Methods 0.000 description 1
231100000636 lethal dose Toxicity 0.000 description 1
230000002197 limbic effect Effects 0.000 description 1
210000003715 limbic system Anatomy 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
230000004904 long-term response Effects 0.000 description 1
229910001425 magnesium ion Inorganic materials 0.000 description 1
239000003550 marker Substances 0.000 description 1
239000000463 material Substances 0.000 description 1
238000007431 microscopic evaluation Methods 0.000 description 1
235000013336 milk Nutrition 0.000 description 1
239000008267 milk Substances 0.000 description 1
210000004080 milk Anatomy 0.000 description 1
239000003226 mitogen Substances 0.000 description 1
239000000203 mixture Substances 0.000 description 1
238000012544 monitoring process Methods 0.000 description 1
230000000877 morphologic effect Effects 0.000 description 1
230000035772 mutation Effects 0.000 description 1
210000000478 neocortex Anatomy 0.000 description 1
210000000653 nervous system Anatomy 0.000 description 1
210000002241 neurite Anatomy 0.000 description 1
210000002682 neurofibrillary tangle Anatomy 0.000 description 1
230000019581 neuron apoptotic process Effects 0.000 description 1
230000009223 neuronal apoptosis Effects 0.000 description 1
230000005015 neuronal process Effects 0.000 description 1
150000002826 nitrites Chemical class 0.000 description 1
JPXMTWWFLBLUCD-UHFFFAOYSA-N nitro blue tetrazolium(2+) Chemical compound COC1=CC(C=2C=C(OC)C(=CC=2)[N+]=2N(N=C(N=2)C=2C=CC=CC=2)C=2C=CC(=CC=2)[N+]([O-])=O)=CC=C1[N+]1=NC(C=2C=CC=CC=2)=NN1C1=CC=C([N+]([O-])=O)C=C1 JPXMTWWFLBLUCD-UHFFFAOYSA-N 0.000 description 1
239000001272 nitrous oxide Substances 0.000 description 1
239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
231100000956 nontoxicity Toxicity 0.000 description 1
238000010606 normalization Methods 0.000 description 1
229920001778 nylon Polymers 0.000 description 1
230000001936 parietal effect Effects 0.000 description 1
230000008506 pathogenesis Effects 0.000 description 1
231100000915 pathological change Toxicity 0.000 description 1
230000036285 pathological change Effects 0.000 description 1
239000008188 pellet Substances 0.000 description 1
238000002205 phenol-chloroform extraction Methods 0.000 description 1
239000008363 phosphate buffer Substances 0.000 description 1
229920000656 polylysine Polymers 0.000 description 1
238000013105 post hoc analysis Methods 0.000 description 1
229940124606 potential therapeutic agent Drugs 0.000 description 1
239000000843 powder Substances 0.000 description 1
230000008569 process Effects 0.000 description 1
238000012545 processing Methods 0.000 description 1
210000001176 projection neuron Anatomy 0.000 description 1
XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 description 1
210000002763 pyramidal cell Anatomy 0.000 description 1
238000011002 quantification Methods 0.000 description 1
238000004445 quantitative analysis Methods 0.000 description 1
238000011158 quantitative evaluation Methods 0.000 description 1
108020003175 receptors Proteins 0.000 description 1
102000005962 receptors Human genes 0.000 description 1
230000009467 reduction Effects 0.000 description 1
235000019515 salmon Nutrition 0.000 description 1
230000011664 signaling Effects 0.000 description 1
239000001509 sodium citrate Substances 0.000 description 1
NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
238000001179 sorption measurement Methods 0.000 description 1
208000020431 spinal cord injury Diseases 0.000 description 1
238000013222 sprague-dawley male rat Methods 0.000 description 1
238000010186 staining Methods 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
238000010254 subcutaneous injection Methods 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
239000002344 surface layer Substances 0.000 description 1
230000004083 survival effect Effects 0.000 description 1
238000013268 sustained release Methods 0.000 description 1
239000012730 sustained-release form Substances 0.000 description 1
230000000946 synaptic effect Effects 0.000 description 1
229940037128 systemic glucocorticoids Drugs 0.000 description 1
230000000542 thalamic effect Effects 0.000 description 1
210000001103 thalamus Anatomy 0.000 description 1
150000003595 thromboxanes Chemical class 0.000 description 1
238000013518 transcription Methods 0.000 description 1
230000035897 transcription Effects 0.000 description 1
229940072041 transforming growth factor beta 2 Drugs 0.000 description 1
230000009261 transgenic effect Effects 0.000 description 1
238000012250 transgenic expression Methods 0.000 description 1
238000012301 transgenic model Methods 0.000 description 1
230000001052 transient effect Effects 0.000 description 1
230000003363 transsynaptic effect Effects 0.000 description 1
239000005526 vasoconstrictor agent Substances 0.000 description 1
229940124549 vasodilator Drugs 0.000 description 1
239000003071 vasodilator agent Substances 0.000 description 1
238000012800 visualization Methods 0.000 description 1
238000005406 washing Methods 0.000 description 1
DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/8509—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
- A01K67/027—New or modified breeds of vertebrates
- A01K67/0275—Genetically modified vertebrates, e.g. transgenic
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
- A01K67/027—New or modified breeds of vertebrates
- A01K67/0275—Genetically modified vertebrates, e.g. transgenic
- A01K67/0278—Knock-in vertebrates, e.g. humanised vertebrates
- 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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/18—Sulfonamides
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/0004—Oxidoreductases (1.)
- C12N9/0071—Oxidoreductases (1.) acting on paired donors with incorporation of molecular oxygen (1.14)
- C12N9/0083—Miscellaneous (1.14.99)
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2207/00—Modified animals
- A01K2207/15—Humanized animals
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/05—Animals comprising random inserted nucleic acids (transgenic)
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2227/00—Animals characterised by species
- A01K2227/10—Mammal
- A01K2227/105—Murine
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2267/00—Animals characterised by purpose
- A01K2267/03—Animal model, e.g. for test or diseases
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2267/00—Animals characterised by purpose
- A01K2267/03—Animal model, e.g. for test or diseases
- A01K2267/0306—Animal model for genetic diseases
- A01K2267/0312—Animal model for Alzheimer's disease
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2267/00—Animals characterised by purpose
- A01K2267/03—Animal model, e.g. for test or diseases
- A01K2267/0306—Animal model for genetic diseases
- A01K2267/0318—Animal model for neurodegenerative disease, e.g. non- Alzheimer's
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2517/00—Cells related to new breeds of animals
- C12N2517/02—Cells from transgenic animals
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2830/00—Vector systems having a special element relevant for transcription
- C12N2830/008—Vector systems having a special element relevant for transcription cell type or tissue specific enhancer/promoter combination

Landscapes

Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Engineering & Computer Science (AREA)
Chemical & Material Sciences (AREA)
General Health & Medical Sciences (AREA)
Genetics & Genomics (AREA)
Zoology (AREA)
Bioinformatics & Cheminformatics (AREA)
Biotechnology (AREA)
Veterinary Medicine (AREA)
Organic Chemistry (AREA)
Environmental Sciences (AREA)
Biomedical Technology (AREA)
Wood Science & Technology (AREA)
Animal Behavior & Ethology (AREA)
General Engineering & Computer Science (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Biodiversity & Conservation Biology (AREA)
Animal Husbandry (AREA)
Public Health (AREA)
Molecular Biology (AREA)
Microbiology (AREA)
Biochemistry (AREA)
Epidemiology (AREA)
Physics & Mathematics (AREA)
Biophysics (AREA)
Neurosurgery (AREA)
Neurology (AREA)
Plant Pathology (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Psychiatry (AREA)
Hospice & Palliative Care (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Saccharide Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Steroid Compounds (AREA)

SK671-99A 1996-11-21 1997-11-19 Farmaceutická kompozícia na liečenie neurodegeneratívnej choroby SK284334B6 (sk)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US3333296P	1996-11-21	1996-11-21
US08/831,402 US5985930A (en)	1996-11-21	1997-04-01	Treatment of neurodegenerative conditions with nimesulide
PCT/US1997/021484 WO1998022104A2 (en)	1996-11-21	1997-11-19	Treatment of neurodegenerative conditions with nimesulide

Publications (2)

Publication Number	Publication Date
SK67199A3 SK67199A3 (en)	2001-01-18
SK284334B6 true SK284334B6 (sk)	2005-02-04

Family

ID=26709565

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK671-99A SK284334B6 (sk)	1996-11-21	1997-11-19	Farmaceutická kompozícia na liečenie neurodegeneratívnej choroby

Country Status (18)

Country	Link
US (3)	US5985930A (da)
EP (1)	EP0956009B9 (da)
JP (1)	JP2001505206A (da)
KR (1)	KR20000069061A (da)
AT (1)	ATE212546T1 (da)
AU (1)	AU725141B2 (da)
BR (1)	BR9714303A (da)
CA (1)	CA2272249A1 (da)
DE (1)	DE69710224T2 (da)
DK (1)	DK0956009T3 (da)
ES (1)	ES2172822T3 (da)
IL (1)	IL129949A (da)
NO (1)	NO992374L (da)
NZ (1)	NZ335726A (da)
PT (1)	PT956009E (da)
SK (1)	SK284334B6 (da)
TR (1)	TR199901120T2 (da)
WO (1)	WO1998022104A2 (da)

Families Citing this family (38)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5985930A (en) *	1996-11-21	1999-11-16	Pasinetti; Giulio M.	Treatment of neurodegenerative conditions with nimesulide
US7291626B1 (en)	1998-04-09	2007-11-06	John Hopkins University School Of Medicine	Inhibitors of hedgehog signaling pathways, compositions and uses related thereto
US6441152B1 (en) *	1998-12-08	2002-08-27	Boston Probes, Inc.	Methods, kits and compositions for the identification of nucleic acids electrostatically bound to matrices
MXPA01008606A (es) *	1999-02-26	2003-05-05	Merck & Co Inc	Compuestos de sulfonamida novedosos y uso de los mismos.
CA2386190C (en)	1999-10-13	2009-04-14	Johns Hopkins University School Of Medicine	Regulators of the hedgehog pathway, compositions and uses related thereto
US6657070B2 (en)	2000-12-13	2003-12-02	Wyeth	Production of chirally pure α-amino acids and N-sulfonyl α-amino acids
ES2267853T3 (es)	2000-12-13	2007-03-16	Wyeth	Inhibidroes de sulfonamida heteriociclicos de la produccion de beta amiloides.
US20040063752A1 (en) *	2002-05-31	2004-04-01	Pharmacia Corporation	Monotherapy for the treatment of amyotrophic lateral sclerosis with cyclooxygenase-2 (COX-2) inhibitor(s)
EP1549303A4 (en) *	2002-06-13	2007-08-08	Sinai School Medicine	INHIBITION OF PROGRESSIVE COGNITIVE IMPAIRMENT
US20060041022A1 (en) *	2002-11-06	2006-02-23	Pasinetti Giulio M	Treatment of amyotrophic lateral sclerosis with nimesulide
AU2003218345A1 (en) *	2002-11-06	2004-06-03	Mount Sinai School Of Medicine	Treatment of amyotrophic lateral sclerosis with nimesulide
UA82093C2 (uk)	2003-03-31	2008-03-11	Уайт	Фтор- та трифторалкіловмісні гетероциклічні сульфонамідні інгібітори утворення бета-амілоїду та їх похідні
US20090155903A1 (en) *	2004-03-19	2009-06-18	Myriad Genetics, Incorporated	Pharmaceutical composition and method
EP2046119A2 (en) *	2006-07-07	2009-04-15	Myriad Genetics, Inc.	Treatment of psychiatric disorders
US20110016543A1 (en) *	2008-12-04	2011-01-20	Sigma-Aldrich Co.	Genomic editing of genes involved in inflammation
JP2012520883A (ja) *	2009-03-16	2012-09-10	アイピントゥル，エルエルシー	アルツハイマー病及び骨粗鬆症の治療並びに老化の軽減
US8324450B2 (en)	2009-06-02	2012-12-04	Academia Sinica	Non-human animal model for frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U)
PT2717893T (pt)	2011-06-08	2019-08-20	Translate Bio Inc	Composições de nanopartículas lipídicas e métodos para transferência de arnm
EP3524676A1 (en)	2011-12-16	2019-08-14	The Board of Trustees of The Leland Stanford Junior University	Opsin polypeptides and methods of use thereof
WO2013185067A1 (en)	2012-06-08	2013-12-12	Shire Human Genetic Therapies, Inc.	Nuclease resistant polynucleotides and uses thereof
ES2981185T3 (es)	2013-03-14	2024-10-07	Translate Bio Inc	Métodos para la purificación de ARN mensajero
EP2968586B1 (en)	2013-03-14	2018-07-25	Translate Bio, Inc.	Cftr mrna compositions and related methods and uses
CN105829538A (zh)	2013-08-14	2016-08-03	小利兰·斯坦福大学托管委员会	用于控制疼痛的组合物和方法
US11224642B2 (en)	2013-10-22	2022-01-18	Translate Bio, Inc.	MRNA therapy for argininosuccinate synthetase deficiency
EP3122761B1 (en)	2014-03-28	2019-03-06	The Board of Trustees of The Leland Stanford Junior University	Engineered light-activated anion channel proteins and methods of use thereof
JP6571679B2 (ja)	2014-04-25	2019-09-04	トランスレイトバイオ，インコーポレイテッド	メッセンジャーｒｎａの精製方法
US11168369B2 (en)	2014-11-25	2021-11-09	The Brigham And Women's Hospital, Inc.	Method of identifying and treating a person having a predisposition to or afflicted with a cardiometabolic disease
US10683552B2 (en)	2014-11-25	2020-06-16	Presidents And Fellows Of Harvard College	Clonal haematopoiesis
WO2017040538A1 (en)	2015-08-31	2017-03-09	The Board Of Trustees Of The Leland Stanford Junior University	Compressed sensing high resolution functional magnetic resonance imaging
WO2017100058A1 (en)	2015-12-09	2017-06-15	The Board Of Trustees Of The Leland Stanford Junior University	Methods for functional brain circuit analysis
KR102855002B1 (ko)	2016-02-01	2025-09-04	더 보드 오브 트러스티스 오브 더 리랜드 스탠포드 쥬니어 유니버시티	기능성 영상 데이터 분석 방법 및 시스템
AU2018224326B2 (en)	2017-02-27	2024-01-04	Translate Bio, Inc.	Novel codon-optimized CFTR mRNA
MX2019013752A (es)	2017-05-16	2020-07-20	Translate Bio Inc	Tratamiento de la fibrosis quística mediante el suministro de arnm que codifica cftr optimizado en codones.
CN118421617A (zh)	2018-08-24	2024-08-02	川斯勒佰尔公司	用于纯化信使rna的方法
EP3883592A1 (en)	2018-11-21	2021-09-29	Translate Bio, Inc.	Treatment of cystic fibrosis by delivery of nebulized mrna encoding cftr
IL265486A (en)	2019-03-19	2020-09-30	Yeda Res & Dev	Type II stable opsins and methods of using them
WO2021055609A1 (en)	2019-09-20	2021-03-25	Translate Bio, Inc.	Mrna encoding engineered cftr
WO2025189030A1 (en)	2024-03-07	2025-09-12	Stellaromics, Inc.	Methods and systems for volumetric imaging

Family Cites Families (22)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3403096A (en) *	1963-10-02	1968-09-24	Ceskoslovenska Akademie Ved	Method and device for separation of a suspension
US4966692A (en) *	1989-05-05	1990-10-30	Flint & Walling, Inc.	Filtration system having flow control means and tank adapter with selective venting
US5604260A (en) *	1992-12-11	1997-02-18	Merck Frosst Canada Inc.	5-methanesulfonamido-1-indanones as an inhibitor of cyclooxygenase-2
US5543297A (en) *	1992-12-22	1996-08-06	Merck Frosst Canada, Inc.	Human cyclooxygenase-2 cDNA and assays for evaluating cyclooxygenase-2 activity
GB9420616D0 (en) *	1994-10-12	1994-11-30	Merck Sharp & Dohme	Method, compositions and use
US5474995A (en) *	1993-06-24	1995-12-12	Merck Frosst Canada, Inc.	Phenyl heterocycles as cox-2 inhibitors
US5486534A (en) *	1994-07-21	1996-01-23	G. D. Searle & Co.	3,4-substituted pyrazoles for the treatment of inflammation
ES2301161T3 (es) *	1994-07-27	2008-06-16	Vanderbilt University	Compuestos de dihidrobenzofurano y compuestos relacionados utiles como agentes anti-inflamatorios.
US5684002A (en) *	1994-09-07	1997-11-04	The Procter & Gamble Company	Dihydorbenzofuran and related compounds useful as anti-inflammatory agents
US5585504A (en) *	1994-09-16	1996-12-17	Merck & Co., Inc.	Process of making cox-2 inhibitors having a lactone bridge
US5547975A (en) *	1994-09-20	1996-08-20	Talley; John J.	Benzopyranopyrazolyl derivatives for the treatment of inflammation
US5510361A (en) *	1994-10-20	1996-04-23	The Procter & Gamble Company	Di-tert-butylphenol compounds with heterocyclic moiety, useful as anti-inflammatory agents
US5739166A (en) *	1994-11-29	1998-04-14	G.D. Searle & Co.	Substituted terphenyl compounds for the treatment of inflammation
CA2164559A1 (en) *	1994-12-09	1996-06-10	Chun-Sing Li	5-methanesulfonamido-6-(2-pyridylthio)-1-indanones as inhibitors of cyclooxygenase-2
EP0799218B1 (en) *	1994-12-21	2003-02-19	Merck Frosst Canada & Co.	Diaryl-2-(5h)-furanones as cox-2 inhibitors
CA2211320C (en) *	1995-01-31	2007-03-20	Merck Frosst Canada Inc.	5-methanesulfonamido-3h-isobenzofuran-1-ones as inhibitors of cyclooxygenase-2
ATE223390T1 (de) *	1995-02-13	2002-09-15	Searle & Co	Substituierte isoxazole zur behandlung von entzündung
US5545656A (en) *	1995-04-05	1996-08-13	Pfizer Inc.	2-Oxidole-1-carboxamide pharmaceutical agents for the treatment of alzheimer's disease
US5510368A (en) *	1995-05-22	1996-04-23	Merck Frosst Canada, Inc.	N-benzyl-3-indoleacetic acids as antiinflammatory drugs
US5753694A (en) *	1996-06-28	1998-05-19	Ortho Pharmaceutical Corporation	Anticonvulsant derivatives useful in treating amyotrophic lateral sclerosis (ALS)
ITMI962356A1 (it) *	1996-11-13	1998-05-13	Uni Degli Studi Di Brescia D I	Uso di composti derivati da molecole ad attivita' antinfiammatoria di tipo non steroideo per la prevenzione e il trattamento di
US5985930A (en) *	1996-11-21	1999-11-16	Pasinetti; Giulio M.	Treatment of neurodegenerative conditions with nimesulide

1997
- 1997-04-01 US US08/831,402 patent/US5985930A/en not_active Expired - Lifetime
- 1997-11-19 TR TR1999/01120T patent/TR199901120T2/xx unknown
- 1997-11-19 BR BR9714303-0A patent/BR9714303A/pt not_active Application Discontinuation
- 1997-11-19 NZ NZ335726A patent/NZ335726A/xx unknown
- 1997-11-19 EP EP97950672A patent/EP0956009B9/en not_active Expired - Lifetime
- 1997-11-19 DE DE69710224T patent/DE69710224T2/de not_active Expired - Fee Related
- 1997-11-19 CA CA002272249A patent/CA2272249A1/en not_active Abandoned
- 1997-11-19 ES ES97950672T patent/ES2172822T3/es not_active Expired - Lifetime
- 1997-11-19 IL IL12994997A patent/IL129949A/xx not_active IP Right Cessation
- 1997-11-19 AT AT97950672T patent/ATE212546T1/de not_active IP Right Cessation
- 1997-11-19 WO PCT/US1997/021484 patent/WO1998022104A2/en not_active Ceased
- 1997-11-19 DK DK97950672T patent/DK0956009T3/da active
- 1997-11-19 US US09/308,424 patent/US6649811B2/en not_active Expired - Fee Related
- 1997-11-19 JP JP52395698A patent/JP2001505206A/ja not_active Ceased
- 1997-11-19 SK SK671-99A patent/SK284334B6/sk unknown
- 1997-11-19 KR KR1019997004481A patent/KR20000069061A/ko not_active Ceased
- 1997-11-19 PT PT97950672T patent/PT956009E/pt unknown
- 1997-11-19 AU AU53612/98A patent/AU725141B2/en not_active Ceased
1999
- 1999-05-18 NO NO992374A patent/NO992374L/no unknown
2002
- 2002-05-17 US US10/150,461 patent/US7226948B2/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
CA2272249A1 (en)	1998-05-28
AU5361298A (en)	1998-06-10
US20060059576A1 (en)	2006-03-16
KR20000069061A (ko)	2000-11-25
IL129949A (en)	2003-05-29
WO1998022104A3 (en)	1998-10-08
AU725141B2 (en)	2000-10-05
BR9714303A (pt)	2000-04-25
TR199901120T2 (xx)	1999-07-21
JP2001505206A (ja)	2001-04-17
PT956009E (pt)	2002-07-31
EP0956009B9 (en)	2002-12-11
SK67199A3 (en)	2001-01-18
US5985930A (en)	1999-11-16
WO1998022104A2 (en)	1998-05-28
US20020162130A1 (en)	2002-10-31
DK0956009T3 (da)	2002-05-21
US7226948B2 (en)	2007-06-05
ATE212546T1 (de)	2002-02-15
DE69710224T2 (de)	2002-10-02
DE69710224D1 (de)	2002-03-14
ES2172822T3 (es)	2002-10-01
EP0956009B1 (en)	2002-01-30
US6649811B2 (en)	2003-11-18
EP0956009A1 (en)	1999-11-17
NO992374D0 (no)	1999-05-18
IL129949A0 (en)	2000-02-29
NZ335726A (en)	2000-10-27
NO992374L (no)	1999-07-21

Publication	Publication Date	Title
SK67199A3 (en)	2001-01-18	Treatment of neurodegenerative conditions with nimesulide
WO1998022104A9 (en)	1998-11-26	Treatment of neurodegenerative conditions with nimesulide
Tocco et al.	1997	Maturational regulation and regional induction of cyclooxygenase-2 in rat brain: implications for Alzheimer's disease
Bales et al.	1998	The NF-κB/Rel family of proteins mediates Aβ-induced neurotoxicity and glial activation
Corona et al.	2015	PPARγ and PGC-1α as therapeutic targets in Parkinson’s
Sousa et al.	2002	Evidence for early cytotoxic aggregates in transgenic mice for human transthyretin Leu55Pro
Wallis et al.	2010	The thyroid hormone receptor α1 protein is expressed in embryonic postmitotic neurons and persists in most adult neurons
Klarsfeld et al.	1989	Regulation of muscle AChR α subunit gene expression by electrical activity: Involvement of protein kinase C and Ca 2+
Kelley et al.	1999	Potentiation of excitotoxicity in transgenic mice overexpressing neuronal cyclooxygenase-2
Nakamura et al.	2008	Transcription factor epiprofin is essential for tooth morphogenesis by regulating epithelial cell fate and tooth number
Nilsson et al.	2004	Cognitive impairment in PDAPP mice depends on ApoE and ACT-catalyzed amyloid formation
Daschil et al.	2013	CaV1. 2 calcium channel expression in reactive astrocytes is associated with the formation of amyloid-β plaques in an Alzheimer's disease mouse model
Vanden Heuvel et al.	1996	Expression of a cut-related homeobox gene in developing and polycystic mouse kidney
JP2002507898A (ja)	2002-03-12	アポリポ蛋白質ｅトランスジェニック動物および解析方法
de la Monte et al.	1997	Aberrant expression of the constitutive endothelial nitric oxide synthase gene in Alzheimer disease
Sugaya et al.	1998	Indicators of glial activation and brain oxidative stress after intraventricular infusion of endotoxin
Sommer et al.	2000	Mouse models of α-synucleinopathy and Lewy pathology
Kim et al.	2000	Changes of hippocampal Cu/Zn-superoxide dismutase after kainate treatment in the rat
Calza et al.	2000	Expression of peptides and other neurochemical markers in hypothalamus and olfactory bulb of mice devoid of all known thyroid hormone receptors
Hoozemans et al.	2001	Immunological aspects of alzheimer’s disease: therapeutic implications
Van Uden et al.	1999	A novel role for receptor-associated protein in somatostatin modulation: implications for Alzheimer's disease
Kusakari et al.	2025	Excessive expression of progranulin leads to neurotoxicity rather than neuroprotection
Anglada-Huguet et al.	2016	Loss of striatal 90-kDa ribosomal S6 kinase (Rsk) is a key factor for motor, synaptic and transcription dysfunction in Huntington's disease
Lakshmana et al.	1998	Chronic (−) deprenyl administration increases dendritic arborization in CA3 neurons of hippocampus and AChE activity in specific regions of the primate brain
EP1138324A9 (en)	2002-04-24	Treatment of neurodegenerative conditions with nimesulide