INT57560

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Context Info
Confidence 0.54
First Reported 1994
Last Reported 2010
Negated 0
Speculated 3
Reported most in Body
Documents 14
Total Number 20
Disease Relevance 5.01
Pain Relevance 0.83

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

small molecule metabolic process (GLA) extracellular region (GLA) Golgi apparatus (GLA)
lysosome (GLA) cytoplasm (GLA)
Anatomy Link Frequency
plasma 1
cleavage 1
GLA (Homo sapiens)
Pain Link Frequency Relevance Heat
Duloxetine 1 99.52 Very High Very High Very High
dexamethasone 1 98.20 Very High Very High Very High
antagonist 15 93.84 High High
Pain 68 91.24 High High
Adalimumab 1 90.42 High High
Gabapentin 7 87.40 High High
Nicotine 64 79.08 Quite High
Morphine 1 68.00 Quite High
Glutamate 112 62.56 Quite High
pregabalin 1 59.16 Quite High
Disease Link Frequency Relevance Heat
Hepatocellular Cancer 1 99.88 Very High Very High Very High
Fabry Disease 370 99.14 Very High Very High Very High
Disease 187 99.04 Very High Very High Very High
Lysosome Storage Disease 48 97.28 Very High Very High Very High
Deafness 6 96.28 Very High Very High Very High
Liver Disease 1 94.88 High High
Targeted Disruption 68 93.76 High High
Pain 87 91.24 High High
Proteinuria 358 90.28 High High
Papillomavirus Infection 1 86.12 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Compounds capable of enhancing GLA activity in patient cells would be considered potential chemical chaperones.


Positive_regulation (enhancing) of GLA
1) Confidence 0.54 Published 2010 Journal Current Chemical Genomics Section Body Doc Link PMC2995157 Disease Relevance 0 Pain Relevance 0
This usually can be done either by determining if the lead compounds are able to increase enzyme activity in whole cells or by visualizing decreased substrate storage or increased GLA protein in lysosomes.


Positive_regulation (increased) of GLA
2) Confidence 0.54 Published 2010 Journal Current Chemical Genomics Section Body Doc Link PMC2995157 Disease Relevance 0 Pain Relevance 0
Chaperone compounds would increase the amount of GLA in lysosomes, thereby increasing cleavage of the substrate.
Positive_regulation (increase) of GLA in cleavage
3) Confidence 0.54 Published 2010 Journal Current Chemical Genomics Section Body Doc Link PMC2995157 Disease Relevance 0 Pain Relevance 0
Specific small molecule promoter activators may increase the amount of GLA in lysosomes by stimulating expression of the target protein.
Spec (may) Positive_regulation (increase) of GLA
4) Confidence 0.54 Published 2010 Journal Current Chemical Genomics Section Body Doc Link PMC2995157 Disease Relevance 0.33 Pain Relevance 0
One of our most important observations is that the efficacy of ERT, whether using agalsidase alfa or beta, in general is disappointing.
Spec (whether) Positive_regulation (using) of agalsidase alfa
5) Confidence 0.41 Published 2007 Journal PLoS ONE Section Body Doc Link PMC1913555 Disease Relevance 0.07 Pain Relevance 0
0.51) following agalsidase alfa treatment and ?
Positive_regulation (following) of agalsidase alfa
6) Confidence 0.41 Published 2007 Journal PLoS ONE Section Body Doc Link PMC1913555 Disease Relevance 0.19 Pain Relevance 0
CONCLUSION: If early intervention with ERT in females is to be advocated, it is necessary to demonstrate not only that females with Anderson-Fabry disease have clinical and biochemical features of alpha-galactosidase A deficiency and respond to ERT, but also that early intervention prevents the onset of the later manifestations of the disorder.
Positive_regulation (respond) of alpha-galactosidase associated with fabry disease
7) Confidence 0.35 Published 2008 Journal Acta Paediatr Suppl Section Abstract Doc Link 18339187 Disease Relevance 0.39 Pain Relevance 0.09
Briefly, the cells are cultured with or without the compounds in standard cell culture conditions for 2-5 days, and then GLA activity is measured in whole cells using a fluorogenic substrate, either 4MU-?
Positive_regulation (measured) of GLA
8) Confidence 0.34 Published 2010 Journal Current Chemical Genomics Section Body Doc Link PMC2995157 Disease Relevance 0 Pain Relevance 0
Enzyme activators may increase the residual activity of mutant GLA in the lysosomes of patients with Fabry disease, thereby lessening lysosomal storage of the substrate and alleviating symptoms.
Spec (may) Positive_regulation (increase) of GLA associated with fabry disease and lysosome storage disease
9) Confidence 0.31 Published 2010 Journal Current Chemical Genomics Section Body Doc Link PMC2995157 Disease Relevance 0.49 Pain Relevance 0
Modifying genes may include those involved in glycolipid metabolism, which may increase the availability of substrates for alpha-galactosidase A, thus increasing the disease severity.
Positive_regulation (increase) of alpha-galactosidase associated with disease
10) Confidence 0.29 Published 2008 Journal Biologics : Targets & Therapy Section Body Doc Link PMC2727881 Disease Relevance 0.81 Pain Relevance 0
This defect results in alpha-galactosidase A deficiency, with progressive accumulation of neutral glycosphingolipids, (predominately globotriaosylceramide; GL-3) in lysosomes, as well as other cellular compartments and the extracellular space (Askari et al 2007).
Positive_regulation (results) of alpha-galactosidase
11) Confidence 0.29 Published 2008 Journal Biologics : Targets & Therapy Section Body Doc Link PMC2727881 Disease Relevance 0.49 Pain Relevance 0
More complete clearance of plasma and urinary GL-3 in male patients treated with the 1.0 mg/kg agalsidase-beta was observed than in those treated with either preparation at 0.2 mg/kg every 2 weeks.
Positive_regulation (/) of agalsidase in plasma
12) Confidence 0.25 Published 2008 Journal Biologics : Targets & Therapy Section Body Doc Link PMC2727881 Disease Relevance 0.07 Pain Relevance 0
A similar experience with increasing the dose of agalsidase-alfa from 0.2 mg/kg every other week to 0.4 mg/kg every other week in an off-label, compassionate-use basis has been described (Torra et al 2008).
Positive_regulation (increasing) of agalsidase
13) Confidence 0.23 Published 2008 Journal Biologics : Targets & Therapy Section Body Doc Link PMC2727881 Disease Relevance 0.33 Pain Relevance 0
During hepatocellular carcinoma with elevated desgamma carboxyprothrombin, gla was found normal, denying an global impairement of the vitamin K metabolism.
Positive_regulation (elevated) of gla associated with hepatocellular cancer
14) Confidence 0.21 Published 1994 Journal Thromb. Res. Section Abstract Doc Link 8191412 Disease Relevance 0.57 Pain Relevance 0.13
Similarly, the phasic CT response was not affected with increasing GalA-MRP concentrations relative to N + Bz.
Positive_regulation (increasing) of GalA
15) Confidence 0.12 Published 2008 Journal Chemical Senses Section Body Doc Link PMC2533421 Disease Relevance 0.40 Pain Relevance 0.03
Similar to the case in rats (Figure 1), in wild-type mice, the phasic and tonic Bz-insensitive NaCl CT responses demonstrated a biphasic response to increasing GalA-MRP concentrations (Figure 5A).
Positive_regulation (increasing) of GalA
16) Confidence 0.12 Published 2008 Journal Chemical Senses Section Body Doc Link PMC2533421 Disease Relevance 0.32 Pain Relevance 0
Thus, at 45 °C both the GalA-MRP–induced increase in the Bz-insensitive NaCl CT response and the GalA-MRP–induced increase in the salt taste perception in humans are most likely due to the amiloride- and Bz-insensitive salt taste receptor and not due to the amiloride-sensitive epithelial Na+ channels.
Positive_regulation (increase) of GalA
17) Confidence 0.11 Published 2008 Journal Chemical Senses Section Body Doc Link PMC2533421 Disease Relevance 0 Pain Relevance 0.10
At all temperatures studied, GalA-MRP produced a significantly greater increase (P < 0.0001) in the tonic CT response (N + Bz + GalA-MRP) relative to (N + Bz) (Figure 3B).
Positive_regulation (increase) of GalA
18) Confidence 0.11 Published 2008 Journal Chemical Senses Section Body Doc Link PMC2533421 Disease Relevance 0 Pain Relevance 0.06
Agalsidase alpha stabilizes, and possibly improves, hearing in Fabry patients who have not already progressed to severe hearing loss.
Positive_regulation (stabilizes) of Agalsidase alpha associated with deafness
19) Confidence 0.06 Published 2006 Journal Eur. J. Clin. Invest. Section Abstract Doc Link 16919050 Disease Relevance 0.46 Pain Relevance 0.06
This issue focuses on the following selection of drugs: AAV1/SERCA2a, Abacavir sulfate/lamivudine, Adalimumab, Aliskiren fumarate, Ambrisentan, Aripiprazole, AT-7519, Atazanavir sulfate, Atomoxetine hydrochloride, Azacitidine, Azelnidipine; Besifloxacin hydrochloride, Bevacizumab, Bioabsorbable everolimus-eluting coronary stent, Bortezomib, Bosentan, Budesonide/formoterol fumarate; CAIV-T, Carisbamate, Casopitant mesylate, Certolizumab pegol, Cetuximab, Ciclesonide, Ciprofloxacin/dexamethasone, CTCE-9908; Dalcetrapib, Darunavir, Deferasirox, Desloratadine, Disitertide, Drotrecogin alfa (activated), DTA-H19, Duloxetine hydrochloride, Dutasteride; Ecogramostim, Efalizumab, Emtricitabine, Eribulin mesilate, Escitalopram oxalate, Eszopiclone, EUR-1008, Everolimus-eluting coronary stent, Exenatide; Fampridine, Fluticasone furoate, Formoterol fumarate/fluticasone propionate, Fosamprenavir calcium, Fulvestrant; Gabapentin enacarbil, GS-7904L; HPV-6/11/16/18, Human Secretin, Hydralazine hydrochloride/isosorbide dinitrate; Imatinib mesylate, Imexon, Inalimarev/Falimarev, Indacaterol, Indacaterol maleate, Inhalable human insulin, Insulin detemir, Insulin glargine, Ixabepilone; L-Alanosine, Lapatinib ditosylate, Lenalidomide, Levocetirizine dihydrochloride, Liraglutide, Lisdexamfetamine mesilate, Lopinavir, Loratadine/montelukast sodium, Lutropin alfa; MeNZB, Mepolizumab, Micafungin sodium, Morphine hydrochloride; Nabiximols, Nikkomycin Z; Olmesartan medoxomil, Omalizumab; Paclitaxel-eluting stent, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Perifosine, PF-489791, Plitidepsin, Posaconazole, Pregabalin; QAX-576; Raltegravir potassium, Ramelteon, Rasagiline mesilate, Recombinant human relaxin H2, rhGAD65, Rivaroxaban, Rosuvastatin calcium, Rotigotine; Saxagliptin, SCH-530348, Sirolimus-eluting stent, SLIT-amikacin, Sorafenib, Sotrastaurin, SR-16234, Sulforaphane; Tadalafil, Tanespimycin, Tapentadol hydrochloride, Teriparatide, Tesofensine, Tiotropium bromide, Tipifarnib, Tirapazamine, TMC-207, Tocilizumab, Tolvaptan, Tosedostat, Treprostinil sodium; Ustekinumab; Varespladib methyl, Vicriviroc, Vildagliptin, Vildagliptin/metformin hydrochloride, Volociximab, Voriconazole; Ziconotide, Ziprasidone hydrochloride.
Positive_regulation (activated) of alfa associated with pregabalin, papillomavirus infection, ziconotide, adalimumab, gabapentin, duloxetine, dexamethasone and morphine
20) Confidence 0.05 Published 2009 Journal Methods Find Exp Clin Pharmacol Section Abstract Doc Link 19907722 Disease Relevance 0.09 Pain Relevance 0.36

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