INT22967

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Context Info
Confidence 0.56
First Reported 1983
Last Reported 2010
Negated 2
Speculated 4
Reported most in Abstract
Documents 94
Total Number 100
Disease Relevance 37.04
Pain Relevance 85.92

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

nucleoplasm (RYBP) nucleus (RYBP) intracellular (RYBP)
DNA binding (RYBP) cytoplasm (RYBP)
Anatomy Link Frequency
liver 15
plasma 10
kidney 9
hepatocytes 4
body 2
RYBP (Homo sapiens)
Pain Link Frequency Relevance Heat
Paracetamol 1259 100.00 Very High Very High Very High
Endocannabinoid 1 99.40 Very High Very High Very High
dexamethasone 15 99.16 Very High Very High Very High
Leflunomide 8 97.56 Very High Very High Very High
anesthesia 2 97.12 Very High Very High Very High
Bile 14 97.00 Very High Very High Very High
Analgesic 27 96.92 Very High Very High Very High
aspirin 2 95.20 Very High Very High Very High
alcohol 11 94.00 High High
addiction 4 92.80 High High
Disease Link Frequency Relevance Heat
Hepatotoxicity 161 99.96 Very High Very High Very High
Toxicity 131 99.96 Very High Very High Very High
Nephrotoxicity 72 99.96 Very High Very High Very High
Injury 34 99.88 Very High Very High Very High
Death 26 99.76 Very High Very High Very High
Cholangiocarcinoma 7 99.76 Very High Very High Very High
Diabetes Mellitus 12 99.38 Very High Very High Very High
Overdose 13 99.36 Very High Very High Very High
Cancer 281 99.32 Very High Very High Very High
Body Weight 4 99.32 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
However, as the concentration of APAP-GSH was increased so did the excretion of APAP-CYS.
Positive_regulation (increased) of APAP-GSH
1) Confidence 0.56 Published 1986 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 2871175 Disease Relevance 0 Pain Relevance 0.19
In vivo studies suggest that in situ activation of APAP contributes to the development of nephrotoxicity.
Positive_regulation (activation) of APAP associated with nephrotoxicity and paracetamol
2) Confidence 0.48 Published 1996 Journal Fundam Appl Toxicol Section Abstract Doc Link 8937897 Disease Relevance 0.63 Pain Relevance 0.73
The mechanism underlying APAP-induced liver injury remains unclear, but experimental evidence strongly suggests that activation of APAP and subsequent formation of protein adducts are involved in hepatotoxicity.
Positive_regulation (activation) of APAP in liver associated with paracetamol, injury and hepatotoxicity
3) Confidence 0.46 Published 2000 Journal Electrophoresis Section Abstract Doc Link 10892726 Disease Relevance 0.53 Pain Relevance 0.61
To selectively inhibit APAP activation in the kidney but not in the liver, 10-week-old male CD-1 mice were castrated under ether anesthesia and allowed to recover for a minimum of 2 weeks before use.
Positive_regulation (activation) of APAP in liver associated with anesthesia and paracetamol
4) Confidence 0.45 Published 1994 Journal Toxicol. Appl. Pharmacol. Section Abstract Doc Link 8209379 Disease Relevance 0.30 Pain Relevance 0.86
Microsomal activation of APAP in vitro was monitored by trapping the APAP-derived electrophile as an N-acetylcysteine conjugate.
Positive_regulation (activation) of APAP associated with paracetamol
5) Confidence 0.45 Published 1994 Journal Toxicol. Appl. Pharmacol. Section Abstract Doc Link 8209379 Disease Relevance 0.31 Pain Relevance 0.99
Furthermore, endocannabinoid signaling may play a role in APAP's activation of the serotonergic descending inhibitory pathways.
Positive_regulation (activation) of APAP associated with endocannabinoid and paracetamol
6) Confidence 0.42 Published 2009 Journal Pain Physician Section Abstract Doc Link 19165309 Disease Relevance 0.23 Pain Relevance 1.52
APAP alone caused a significant increase in liver weight/body weight ratio and hepatic glutathione (GSH) depletion.
Positive_regulation (increase) of APAP in body associated with paracetamol and body weight
7) Confidence 0.39 Published 1988 Journal Toxicol. Lett. Section Abstract Doc Link 3263718 Disease Relevance 0.26 Pain Relevance 1.05
We therefore examined the role of P450IIE1 in human liver microsomal APAP activation.
Spec (examined) Positive_regulation (activation) of APAP in liver associated with paracetamol
8) Confidence 0.39 Published 1989 Journal Arch. Biochem. Biophys. Section Abstract Doc Link 2729995 Disease Relevance 0.32 Pain Relevance 1.07
At the dosage levels used, oral NAC, IV NAC, and IV sodium sulfate were equally effective antidotes, as measured by decreased methemoglobinemia, increased whole blood reduced glutathione, decreased APAP half-lives, and increased urinary excretion of the APAP-sulfate conjugate.
Positive_regulation (increased) of APAP-sulfate conjugate in blood associated with paracetamol and methemoglobinemia
9) Confidence 0.39 Published 1985 Journal Am. J. Vet. Res. Section Abstract Doc Link 4026031 Disease Relevance 0.17 Pain Relevance 0.89
These results suggest that protection afforded by probenecid in vivo could be a consequence of the inhibition of APAP S-conjugate renal uptake and/or an increase in APAP renal clearance.
Positive_regulation (increase) of APAP associated with paracetamol
10) Confidence 0.38 Published 1998 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 9454804 Disease Relevance 0.14 Pain Relevance 1.44
When APAP and LEF were incubated with human recombinant P450 enzymes, CYP1A2 was found to be the isozyme responsible for the inhibition of APAP bioactivation.
Positive_regulation (bioactivation) of APAP associated with paracetamol and leflunomide
11) Confidence 0.36 Published 2008 Journal Toxicol. Lett. Section Abstract Doc Link 18588957 Disease Relevance 0.40 Pain Relevance 1.26
These results demonstrate the ability of human CYP2E1 to activate APAP to reactive metabolites which form covalent protein adducts and cause toxicity to a hepatoma cell line.
Positive_regulation (activate) of APAP associated with toxicity, paracetamol and hepatocellular cancer
12) Confidence 0.35 Published 1995 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 7791125 Disease Relevance 0.24 Pain Relevance 0.95
Generation of APAP-GSH in microsomes from control mice was inhibited by DMSO in a dose-dependent manner.
Positive_regulation (Generation) of APAP associated with paracetamol
13) Confidence 0.33 Published 2006 Journal Biol. Pharm. Bull. Section Abstract Doc Link 16880615 Disease Relevance 0.23 Pain Relevance 0.96
The association of 58-ABP arylation with APAP toxicity in this mouse kidney slice model is consistent with earlier, in vivo results and demonstrates the importance of in situ activation of APAP for the development of nephrotoxicity.
Positive_regulation (activation) of APAP in kidney associated with nephrotoxicity, toxicity and paracetamol
14) Confidence 0.32 Published 1996 Journal Fundam Appl Toxicol Section Abstract Doc Link 8937897 Disease Relevance 0.74 Pain Relevance 0.90
In this study a mouse kidney slice model was developed to further evaluate the contribution of in situ activation of APAP to the development of nephrotoxicity and to determine the selectivity of protein arylation.
Positive_regulation (activation) of APAP in kidney associated with nephrotoxicity and paracetamol
15) Confidence 0.32 Published 1996 Journal Fundam Appl Toxicol Section Abstract Doc Link 8937897 Disease Relevance 0.74 Pain Relevance 0.87
Therefore, enhanced susceptibility to APAP-nephrotoxicity in fructose-pretreated rats may be due, at least in part, to increased renal APAP concentration and increased intrinsic susceptibility to the metabolic nephrotoxicant.
Positive_regulation (increased) of APAP associated with nephrotoxicity and paracetamol
16) Confidence 0.32 Published 1997 Journal Exp. Toxicol. Pathol. Section Abstract Doc Link 9314055 Disease Relevance 0.37 Pain Relevance 1.07
A dose of DMSO (1 ml/kg, i.p.) inhibited the induction of APAP hepatotoxicity almost completely as indicated by changes in serum hepatotoxic parameters.
Positive_regulation (induction) of APAP associated with paracetamol and hepatotoxicity
17) Confidence 0.31 Published 2006 Journal Biol. Pharm. Bull. Section Abstract Doc Link 16880615 Disease Relevance 0.27 Pain Relevance 0.84
Quantification of major APAP metabolites in plasma showed that APAP-glutathione (GSH), a conjugate generated via metabolic activation of APAP, was reduced significantly while APAP-sulfate and APAP-glucuronide, detoxified metabolites both produced directly from the parent drug, were increased in mice pretreated with DMSO.
Positive_regulation (activation) of APAP in plasma associated with paracetamol
18) Confidence 0.31 Published 2006 Journal Biol. Pharm. Bull. Section Abstract Doc Link 16880615 Disease Relevance 0.25 Pain Relevance 0.91
Quantification of major APAP metabolites in plasma showed that APAP-glutathione (GSH), a conjugate generated via metabolic activation of APAP, was reduced significantly while APAP-sulfate and APAP-glucuronide, detoxified metabolites both produced directly from the parent drug, were increased in mice pretreated with DMSO.
Positive_regulation (increased) of APAP in plasma associated with paracetamol
19) Confidence 0.31 Published 2006 Journal Biol. Pharm. Bull. Section Abstract Doc Link 16880615 Disease Relevance 0.25 Pain Relevance 0.98
Quantification of major APAP metabolites in plasma showed that APAP-glutathione (GSH), a conjugate generated via metabolic activation of APAP, was reduced significantly while APAP-sulfate and APAP-glucuronide, detoxified metabolites both produced directly from the parent drug, were increased in mice pretreated with DMSO.
Positive_regulation (increased) of APAP-glucuronide in plasma associated with paracetamol
20) Confidence 0.31 Published 2006 Journal Biol. Pharm. Bull. Section Abstract Doc Link 16880615 Disease Relevance 0.25 Pain Relevance 0.97

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