INT7126

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Context Info
Confidence 0.58
First Reported 1983
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 26
Total Number 26
Disease Relevance 12.97
Pain Relevance 5.64

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

extracellular space (PLA2G2A) extracellular region (PLA2G2A) endoplasmic reticulum (PLA2G2A)
Anatomy Link Frequency
chondrocytes 1
synovial fluid 1
plaque 1
respiratory 1
PMNs 1
PLA2G2A (Homo sapiens)
Pain Link Frequency Relevance Heat
dexamethasone 1 99.56 Very High Very High Very High
Osteoarthritis 14 99.32 Very High Very High Very High
antagonist 6 99.28 Very High Very High Very High
Inflammation 325 99.20 Very High Very High Very High
addiction 1 99.02 Very High Very High Very High
cINOD 81 97.80 Very High Very High Very High
vincristine 5 95.84 Very High Very High Very High
Arthritis 13 93.76 High High
Potency 31 93.56 High High
COX-2 inhibitor 21 92.48 High High
Disease Link Frequency Relevance Heat
Cancer 107 99.98 Very High Very High Very High
Osteoarthritis 14 99.32 Very High Very High Very High
INFLAMMATION 403 99.20 Very High Very High Very High
Atherosclerosis 85 99.20 Very High Very High Very High
Targeted Disruption 4 99.18 Very High Very High Very High
Disease 138 98.68 Very High Very High Very High
Disorder Of Lipid Metabolism 27 98.36 Very High Very High Very High
Diabetes Mellitus 6 98.00 Very High Very High Very High
Neurodegenerative Disease 4 96.68 Very High Very High Very High
Shock 5 95.52 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Many potent, bioavailable and selective inhibitors of human sPLA2 group IIA have been available for more than a decade and have provided compelling support for a causative role of sPLA2 group IIA in numerous studies involving animal models of inflammatory diseases.
Negative_regulation (inhibitors) of sPLA2 associated with inflammation and disease
1) Confidence 0.58 Published 2005 Journal Curr. Med. Chem. Section Abstract Doc Link 16378502 Disease Relevance 0.60 Pain Relevance 0.26
Intravenous or oral administration of LY315920 to transgenic mice expressing the human sPLA2 protein inhibited serum sPLA2 activity in a dose-related manner over a 4-h time course.
Negative_regulation (inhibited) of sPLA2 associated with targeted disruption
2) Confidence 0.56 Published 1999 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 10027849 Disease Relevance 0.17 Pain Relevance 0.19
In a chromogenic isolated enzyme assay, LY315920 inhibited sPLA2 activity with an IC50 of 9 +/- 1 nM or 7.3 x 10(-6) mole fraction, which approached the stiochiometric limit of this assay.
Negative_regulation (inhibited) of sPLA2
3) Confidence 0.56 Published 1999 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 10027849 Disease Relevance 0.07 Pain Relevance 0.12
In contrast, the non-steroidal anti-inflammatory drugs (indomethacin, meclofenamic acid and aspirin), which only block the cyclo-oxygenase pathway of AA metabolism, had little effect on enzyme release from PMNs induced by the same stimuli. 5,8,11-Eicosatriynoic acid (ETI), a selective inhibitor of the lipoxygenase pathway of AA metabolism, caused a dose-dependent inhibition of lysosomal enzyme release elicited by Zx, f-met peptide, and A23187. p-Bromophenacyl bromide (BPB), which inhibits the phospholipase A2 (PLA2) activity in several tissues, was found to cause a dose-dependent inhibition of lysosomal enzyme release induced by the same immunological and non-immunological stimuli.
Negative_regulation (inhibits) of PLA2 in PMNs associated with aspirin, inflammation and cinod
4) Confidence 0.51 Published 1983 Journal J Clin Lab Immunol Section Abstract Doc Link 6644791 Disease Relevance 0.09 Pain Relevance 0.14
Functional inhibitors of phospholipase A2 (PLA2), such as dexamethasone and quinacrine, do not mimick the effects of NSAID.
Negative_regulation (inhibitors) of PLA2 associated with cinod and dexamethasone
5) Confidence 0.47 Published 1999 Journal Biochem. Biophys. Res. Commun. Section Abstract Doc Link 10364464 Disease Relevance 0.33 Pain Relevance 1.06
This model, joined to the previous one developed for the indole inhibitors of human non-pancreatic secretory phospholipase A2 (hnps-PLA2), an enzyme involved in inflammation processes, will allow for the selection of new strong anti-inflammatory drugs with negligible side effects, at least at the level of hp-PLA2.
Negative_regulation (inhibitors) of non-pancreatic secretory phospholipase A2 associated with inflammation and cinod
6) Confidence 0.45 Published 2001 Journal Eur J Med Chem Section Abstract Doc Link 11231046 Disease Relevance 0.19 Pain Relevance 0.15
CHEC-9, a peptide inhibitor of sPLA2-IIA, was shown to ameliorate PLA2-directed inflammation in both acute and chronic neurodegenerative disease models [36].
Negative_regulation (inhibitor) of sPLA2 associated with inflammation and neurodegenerative disease
7) Confidence 0.43 Published 2006 Journal J Neuroinflammation Section Body Doc Link PMC1613236 Disease Relevance 1.12 Pain Relevance 0.36
Inhibitors of PLA2 therefore offer the potential to block production of a more complete set of inflammatory substances through blockade at the onset of the cascade of reactions that follow arachidonic acid release.
Negative_regulation (Inhibitors) of PLA2 associated with inflammation
8) Confidence 0.43 Published 2005 Journal Curr. Med. Chem. Section Abstract Doc Link 16378502 Disease Relevance 0.55 Pain Relevance 0.27
A direct comparison between the purified recombinant human PLA2 and PLA2 purified from human synovial fluid, including molecular weight, antigenicity, ionic dependence, substrate specificity and sensitivity to known PLA2 inhibitors, indicated that the two enzymes exhibit identical biochemical properties.
Negative_regulation (inhibitors) of PLA2 in synovial fluid associated with addiction
9) Confidence 0.43 Published 1992 Journal J. Mol. Recognit. Section Abstract Doc Link 1339483 Disease Relevance 0.13 Pain Relevance 0.19
However, sPLA2 activity was reduced only in patients treated with the adjunction of pravastatin and irbesartan.
Negative_regulation (reduced) of sPLA2
10) Confidence 0.42 Published 2008 Journal Vascular Health and Risk Management Section Body Doc Link PMC2515419 Disease Relevance 0.57 Pain Relevance 0.08
Therefore, direct inhibition of sPLA2-IIA through specific antagonists, or indirectly through AT1-receptor blockade, might be a new therapeutic option used to intervene in this detrimental process of plaque development.
Negative_regulation (inhibition) of sPLA2-IIA in plaque associated with antagonist
11) Confidence 0.42 Published 2008 Journal Vascular Health and Risk Management Section Body Doc Link PMC2515419 Disease Relevance 0.77 Pain Relevance 0.10
LY315920 is a potent and selective sPLA2 inhibitor and represents a new class of anti-inflammatory agent designated SPI.
Negative_regulation (inhibitor) of sPLA2 associated with inflammation
12) Confidence 0.41 Published 1999 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 10027849 Disease Relevance 0.27 Pain Relevance 0.19
These data suggest that the anti-inflammatory property of C8 in chondrocytes mainly depends on its capacity to inhibit PLA2 activity.
Negative_regulation (inhibit) of PLA2 in chondrocytes associated with inflammation
13) Confidence 0.41 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2879362 Disease Relevance 0.51 Pain Relevance 0.50
Among petrosaspongiolide derivatives, 46 and 48a inhibited mainly human synovial PLA2 with IC50 values of 1.6 and 5.8 ?
Negative_regulation (inhibited) of PLA2
14) Confidence 0.33 Published 2010 Journal Marine Drugs Section Body Doc Link PMC2852841 Disease Relevance 0.53 Pain Relevance 0.12
Overall, 84 PLA2 inhibitors were docked to the 12 proteins in order to produce a robust affinity matrix.
Negative_regulation (inhibitors) of PLA2
15) Confidence 0.31 Published 2010 Journal BMC Struct Biol Section Body Doc Link PMC2972294 Disease Relevance 0 Pain Relevance 0
Varespladib, a sPLA2 inhibitor, was recently found to reduce atherosclerosis in apolipoprotein-E-null mice [16].
Negative_regulation (inhibitor) of sPLA2 associated with atherosclerosis and disorder of lipid metabolism
16) Confidence 0.30 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2879362 Disease Relevance 1.68 Pain Relevance 0.43
PLA2 activity was evaluated as previously described [34] with ?
Negative_regulation (evaluated) of PLA2
17) Confidence 0.30 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2879362 Disease Relevance 0.19 Pain Relevance 0.09
Since manoalide revealed an irreversible inhibition of phospholipase A2 (PLA2) [33], the structure-activity relationships (SAR) of this compound attracted scientific interests to study and to understand both PLA2 function and mechanism of action in the whole cell.
Negative_regulation (inhibition) of PLA2
18) Confidence 0.28 Published 2010 Journal Marine Drugs Section Body Doc Link PMC2852841 Disease Relevance 0.24 Pain Relevance 0
Manoalide was further investigated and found to be a potent inhibitor of phospholipase A2 (PLA2) [31–38].
Negative_regulation (inhibitor) of PLA2
19) Confidence 0.28 Published 2010 Journal Marine Drugs Section Body Doc Link PMC2852841 Disease Relevance 0.32 Pain Relevance 0
Inhibition of specific PLA2 constitutes a potentially useful approach for treating a wide variety of inflammatory disorders such as spetic shock, adult respiratory distress syndrome, arthritis, and acute pancreatitis [61].
Negative_regulation (Inhibition) of PLA2 in respiratory associated with inflammation, pancreatitis, shock, adult respiratory distress syndrome and arthritis
20) Confidence 0.27 Published 2010 Journal Marine Drugs Section Body Doc Link PMC2852841 Disease Relevance 0.81 Pain Relevance 0.13

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