INT66460

From wiki-pain
Jump to: navigation, search
Context Info
Confidence 0.43
First Reported 1996
Last Reported 2009
Negated 0
Speculated 0
Reported most in Body
Documents 15
Total Number 26
Disease Relevance 8.98
Pain Relevance 8.03

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

nucleolus (Cabin1) nucleus (Cabin1) cytoplasm (Cabin1)
Anatomy Link Frequency
plasma 1
muscle 1
plaque 1
fibroblast 1
dorsal root ganglion 1
Cabin1 (Rattus norvegicus)
Pain Link Frequency Relevance Heat
qutenza 29 100.00 Very High Very High Very High
b2 receptor 4 100.00 Very High Very High Very High
cytokine 12 99.92 Very High Very High Very High
antagonist 9 99.88 Very High Very High Very High
anesthesia 2 99.74 Very High Very High Very High
Abeta 2 99.52 Very High Very High Very High
Thermal hyperalgesia 5 99.36 Very High Very High Very High
Glutamate 3 99.32 Very High Very High Very High
dopamine receptor 1 99.28 Very High Very High Very High
psoriasis 84 98.98 Very High Very High Very High
Disease Link Frequency Relevance Heat
Hyperalgesia 5 99.36 Very High Very High Very High
Stress 6 99.32 Very High Very High Very High
Psoriasis 84 98.98 Very High Very High Very High
Ganglion Cysts 12 96.68 Very High Very High Very High
Uveitis 288 96.44 Very High Very High Very High
INFLAMMATION 99 94.96 High High
Disease 48 94.80 High High
Schizophrenia 3 94.16 High High
Shock 1 93.48 High High
Disorders Of Creatine Metabolism 36 92.64 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Effects of a calcineurin inhibitor, tacrolimus, on glutamate-dependent potentiation in pelvic-urethral reflex in anesthetized rats.
Negative_regulation (inhibitor) of calcineurin associated with anesthesia and glutamate
1) Confidence 0.43 Published 2006 Journal Neuroscience Section Title Doc Link 16359812 Disease Relevance 0.09 Pain Relevance 0.37
Drug concentration was highly correlated with calcineurin inhibition (r = 0.79), and percent calcineurin inhibition was highly correlated with mean percent reduction in the efficacy endpoint (PASI; r = 0.86), illustrating the strong PK/PD correlation of voclosporin (Figure 3) (Gupta et al 2006).


Negative_regulation (inhibition) of calcineurin
2) Confidence 0.39 Published 2008 Journal Clinical Ophthalmology (Auckland, N.Z.) Section Body Doc Link PMC2699819 Disease Relevance 0.23 Pain Relevance 0.12
Administration of CsA, a specific inhibitor for calcineurin, depressed heat-stress-associated increase of muscle weight and calcineurin expression, especially in soleus.
Negative_regulation (inhibitor) of calcineurin in muscle associated with stress
3) Confidence 0.35 Published 2005 Journal Biochem. Biophys. Res. Commun. Section Abstract Doc Link 15883017 Disease Relevance 0.82 Pain Relevance 0.08
Voclosporin, a rationally designed novel calcineurin inhibitor, exhibits a favorable safety profile, a strong correlation between pharmacokinetic and pharmacodynamic response, and a wide therapeutic window.
Negative_regulation (inhibitor) of calcineurin
4) Confidence 0.33 Published 2008 Journal Clinical Ophthalmology (Auckland, N.Z.) Section Abstract Doc Link PMC2699819 Disease Relevance 0.51 Pain Relevance 0.04
Calcineurin inhibitors also block lymphokine production and release, fibroblast proliferation, and vascular endothelial growth factor expression (Dumont 1996; Ho et al 1996; Cho et al 2002).
Negative_regulation (inhibitors) of Calcineurin in fibroblast
5) Confidence 0.33 Published 2008 Journal Clinical Ophthalmology (Auckland, N.Z.) Section Body Doc Link PMC2699819 Disease Relevance 0.28 Pain Relevance 0.09
Jersey City, NJ) is a rationally designed novel calcineurin inhibitor (Isotechnika, Inc., 2008) currently in phase 2/3 clinical development for noninfectious uveitis.
Negative_regulation (inhibitor) of calcineurin associated with uveitis
6) Confidence 0.33 Published 2008 Journal Clinical Ophthalmology (Auckland, N.Z.) Section Body Doc Link PMC2699819 Disease Relevance 0.69 Pain Relevance 0.16
Voclosporin achieved a clinically relevant range of calcineurin inhibition (40% to 70%) in phase 1 and 2a trials.
Negative_regulation (inhibition) of calcineurin
7) Confidence 0.29 Published 2008 Journal Clinical Ophthalmology (Auckland, N.Z.) Section Body Doc Link PMC2699819 Disease Relevance 0.17 Pain Relevance 0
Preclinical and clinical data suggest that approximately 50% calcineurin inhibition (achieved with voclosporin at a dosage of 0.4 mg/kg bid) leads to a meaningful clinical effect (Aspeslet et al 2004; Gupta et al 2006).
Negative_regulation (inhibition) of calcineurin
8) Confidence 0.29 Published 2008 Journal Clinical Ophthalmology (Auckland, N.Z.) Section Body Doc Link PMC2699819 Disease Relevance 0.35 Pain Relevance 0.13
More recent data indicate that 40% calcineurin inhibition is achieved with voclosporin at an AUC of 226 ng*h/mL, but a 15% rise in serum creatinine (the lower threshold of clinical significance) occurs only at an voclosporin AUC of 3448 ng*h/mL (Figure 4) (Yatscoff et al 2002; Isotechnika, Inc., 2008).


Negative_regulation (inhibition) of calcineurin
9) Confidence 0.29 Published 2008 Journal Clinical Ophthalmology (Auckland, N.Z.) Section Body Doc Link PMC2699819 Disease Relevance 0.25 Pain Relevance 0.04
This was demonstrated in a recently conducted randomized double-blind placebo-controlled study of patients with plaque psoriasis in which voclosporin (0.4 mg/kg bid) produced 50% calcineurin inhibition and proved to be both effective and well tolerated.
Negative_regulation (inhibition) of calcineurin in plaque associated with psoriasis
10) Confidence 0.29 Published 2008 Journal Clinical Ophthalmology (Auckland, N.Z.) Section Body Doc Link PMC2699819 Disease Relevance 0.33 Pain Relevance 0.12
Voclosporin is a next-generation calcineurin inhibitor.
Negative_regulation (inhibitor) of calcineurin
11) Confidence 0.29 Published 2008 Journal Clinical Ophthalmology (Auckland, N.Z.) Section Body Doc Link PMC2699819 Disease Relevance 0.56 Pain Relevance 0.09
A dosage of 0.2 mg/kg in that study was associated with 30% calcineurin inhibition and found to be subtherapeutic (Gupta et al 2006; Langley et al 2006).
Negative_regulation (inhibition) of calcineurin
12) Confidence 0.29 Published 2008 Journal Clinical Ophthalmology (Auckland, N.Z.) Section Body Doc Link PMC2699819 Disease Relevance 0.43 Pain Relevance 0.14
Calcineurin inhibitors are potent immunosuppressants that reversibly inhibit T-cell proliferation and prevent release of proinflammatory cytokines by blocking the activity of the calcium-regulated serine-threonine phosphatase calcineurin, an enzyme found in cell cytoplasm (Schreiber and Crabtree 1992; Dumont 1996).
Negative_regulation (blocking) of calcineurin in T-cell associated with cytokine
13) Confidence 0.29 Published 2008 Journal Clinical Ophthalmology (Auckland, N.Z.) Section Body Doc Link PMC2699819 Disease Relevance 0.36 Pain Relevance 0.09
Strong correlations were seen between C0 (concentration of drug in plasma at the time of an instantaneous intravenous injection of a drug that is instantaneously distributed to its volume of distribution) and both AUC and calcineurin inhibition for voclosporin, but not for CsA (Figure 2).
Negative_regulation (inhibition) of calcineurin in plasma
14) Confidence 0.29 Published 2008 Journal Clinical Ophthalmology (Auckland, N.Z.) Section Body Doc Link PMC2699819 Disease Relevance 0.46 Pain Relevance 0.03
Desensitization is greatly reduced by cyclosporin A complexed to cyclophilin, which is a specific inhibitor of protein phoshatase 2B (calcineurin).
Negative_regulation (inhibitor) of calcineurin
15) Confidence 0.27 Published 1996 Journal Pflugers Arch. Section Abstract Doc Link 8927498 Disease Relevance 0.14 Pain Relevance 0.60
Inhibition of calcineurin inhibits the desensitization of capsaicin-evoked currents in cultured dorsal root ganglion neurones from adult rats.
Negative_regulation (Inhibition) of calcineurin in dorsal root ganglion associated with ganglion cysts, dorsal root ganglion and qutenza
16) Confidence 0.27 Published 1996 Journal Pflugers Arch. Section Title Doc Link 8927498 Disease Relevance 0.18 Pain Relevance 0.62
Activation of ERK and suppression of calcineurin are interacting mechanisms of cardioprotection afforded by delta-opioid receptor activation.
Negative_regulation (suppression) of calcineurin associated with opioid receptor
17) Confidence 0.23 Published 2006 Journal Basic Res. Cardiol. Section Title Doc Link 16619106 Disease Relevance 0.33 Pain Relevance 0.40
Notably, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, calmodulin antagonists, and calcineurin inhibitors each alone significantly increased the amplitude of voltage-activated Ca(2+) channel current.
Negative_regulation (inhibitors) of calcineurin associated with antagonist
18) Confidence 0.23 Published 2006 Journal Neuroscience Section Abstract Doc Link 16678970 Disease Relevance 0.20 Pain Relevance 0.32
Suppression of calcineurin activity by FK506 was associated with modest activation of ERK1/2.
Negative_regulation (Suppression) of calcineurin
19) Confidence 0.20 Published 2006 Journal Basic Res. Cardiol. Section Abstract Doc Link 16619106 Disease Relevance 0.25 Pain Relevance 0.39
These results suggest that suppression of calcineurin and activation of ERK1/2 are interacting mechanisms involved in cardioprotection by delta-opioid receptor activation.
Negative_regulation (suppression) of calcineurin associated with opioid receptor
20) Confidence 0.20 Published 2006 Journal Basic Res. Cardiol. Section Abstract Doc Link 16619106 Disease Relevance 0.23 Pain Relevance 0.37

General Comments

This test has worked.

Personal tools
Namespaces

Variants
Actions
Navigation
Toolbox