INT49983

Context Info Confidence 0.58 First Reported 1995 Last Reported 2010 Negated 0 Speculated 0 Reported most in Abstract Documents 12 Total Number 12 Disease Relevance 3.16 Pain Relevance 7.92

Anatomy Link Frequency neuronal 1 plasma 1 liver 1 Aap (Mus musculus)

Pain Link Frequency Relevance Heat Paracetamol 263 100.00 Bioavailability 3 99.92 antagonist 3 96.88 Chronic pancreatitis 1 74.08 fibrosis 1 45.36 Analgesic 2 38.88 COX2 6 25.00 cOX1 3 25.00 cINOD 3 5.00 Inflammation 3 5.00

Disease Link Frequency Relevance Heat Pancreatitis 6 100.00 Death 46 99.28 Leukemia 2 98.82 Injury 7 97.40 Apoptosis 22 93.60 Cognitive Disorder 3 91.76 Toxicity 21 90.84 Hepatotoxicity 9 89.60 Stress 4 87.96 Diabetes Mellitus 1 78.80

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

It was considered that this controlled release pattern was caused by a reduced AAP particle surface area due to compression.

Negative_regulation (reduced) of AAP associated with paracetamol

1) Confidence 0.58 Published 2003 Journal Int J Pharm Section Abstract Doc Link 14602385 Disease Relevance 0 Pain Relevance 0.35

Although the mechanism of action of acetaminophen (AAP) is not fully understood, some studies suggest that AAP and phenacetin (PHE) are selective cyclooxygenase (COX)-3 inhibitors.

Negative_regulation (inhibitors) of AAP associated with paracetamol

2) Confidence 0.50 Published 2007 Journal J. Psychopharmacol. (Oxford) Section Abstract Doc Link 17606472 Disease Relevance 0 Pain Relevance 0.60

In addition, electrophilic metabolites of AAP may inactivate caspases or their activation pathway.

Negative_regulation (metabolites) of AAP associated with paracetamol

3) Confidence 0.38 Published 1999 Journal Toxicol. Appl. Pharmacol. Section Abstract Doc Link 10222310 Disease Relevance 0.50 Pain Relevance 0.72

The middle-dose [69.5 mg/kg (IC50 for COX-3)] of AAP, the PHE [17.9 mg/kg (IC50 for COX-3)] and a specific COX-1 inhibitor (piroxicam: 10-20 mg/kg) did not influence performance in either task.

Negative_regulation (inhibitor) of AAP associated with paracetamol

4) Confidence 0.37 Published 2007 Journal J. Psychopharmacol. (Oxford) Section Abstract Doc Link 17606472 Disease Relevance 0.09 Pain Relevance 0.93

These results will suggest that with repeated dosing of AAP special care must be taken in schistosomal patients since the elimination of AAP from plasma is remarkably reduced.

Negative_regulation (reduced) of AAP in plasma associated with paracetamol

5) Confidence 0.37 Published 1996 Journal Int J Clin Pharmacol Ther Section Abstract Doc Link 8832306 Disease Relevance 0.40 Pain Relevance 0.66

At a dose of AAP 20 mg/kg, the systemic bioavailability of AAP was 100% in the case of dosing at phase III, but was reduced by half when dosing at phase I.

Negative_regulation (reduced) of AAP associated with paracetamol and bioavailability

6) Confidence 0.37 Published 1995 Journal Pharm. Res. Section Abstract Doc Link 7596997 Disease Relevance 0.07 Pain Relevance 0.79

GSH treatment at 3 h after AAP was ineffective.

Negative_regulation (ineffective) of AAP associated with paracetamol

7) Confidence 0.37 Published 2002 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 12388625 Disease Relevance 0.52 Pain Relevance 0.59

Of the 59 children with acute lymphoblastic leukemia (ALL) receiving E. coli L-asparaginase, 5 patients (8.5%) developed AAP.

Negative_regulation (developed) of AAP associated with leukemia and pancreatitis

8) Confidence 0.19 Published 2008 Journal Pediatr Blood Cancer Section Abstract Doc Link 18726919 Disease Relevance 0.69 Pain Relevance 0.07

To examine the participation of COX-3 in memory formation, water maze performance was studied in mice treated with AAP, PHE or other COX inhibitors.

Negative_regulation (inhibitors) of AAP associated with paracetamol

9) Confidence 0.16 Published 2007 Journal J. Psychopharmacol. (Oxford) Section Abstract Doc Link 17606472 Disease Relevance 0 Pain Relevance 0.70

In addition, TTD, an inhibitor of the 2E1isoform of cytochrome P-450, significantly reduced AAP-induced neuronal death, suggesting a role for this enzymatic activity in the mechanism involved in AAP-mediated neuronal death.

Negative_regulation (reduced) of AAP in neuronal associated with paracetamol and death

10) Confidence 0.12 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3000821 Disease Relevance 0.64 Pain Relevance 0.96

WST 1 test showed decrease of dehydrogenase activity in 5, 10 and 20 mM AAP to 75 % of control values after 1 hour of incubation.

Negative_regulation (decrease) of AAP associated with paracetamol

11) Confidence 0.09 Published 2009 Journal Physiol Res Section Abstract Doc Link 18380536 Disease Relevance 0.09 Pain Relevance 0.85

The decrease in liver cytosolic GST activity by AAP, reflecting the release of the enzyme into serum, was also blocked by the mold.

Negative_regulation (decrease) of AAP in liver associated with paracetamol

12) Confidence 0.05 Published 1998 Journal Jpn. J. Pharmacol. Section Abstract Doc Link 9804066 Disease Relevance 0.16 Pain Relevance 0.71

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