INT134743

Context Info Confidence 0.36 First Reported 2006 Last Reported 2010 Negated 0 Speculated 2 Reported most in Body Documents 6 Total Number 8 Disease Relevance 5.33 Pain Relevance 1.14

nucleus (TEAD1) DNA binding (TEAD1)

Anatomy Link Frequency nucleus 1 TEAD1 (Homo sapiens)

Pain Link Frequency Relevance Heat Inflammation 31 100.00 Electroencephalography 6 98.72 opioid receptor 16 98.68 cva 43 86.36 Opioid 1 75.00 headache 5 66.08 Pain 4 62.72 Morphine 2 43.84 Catecholamine 1 39.88 Central nervous system 54 34.64

Disease Link Frequency Relevance Heat INFLAMMATION 36 100.00 Hemorrhage 229 99.20 Sepsis 130 97.20 Coma 5 97.04 Death 43 95.88 Encephalopathy 36 95.68 Edema 10 90.56 Syndrome 6 90.40 Multiple Organ Failure 4 86.64 Cv General 3 Under Development 31 86.36

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

It has been postulated that the anticoagulant effect of DrotAA may play a less important role in increasing survival rate in severe sepsis patients at high risk for death.

Positive_regulation (effect) of DrotAA associated with death and sepsis

1) Confidence 0.36 Published 2007 Journal Crit Care Section Body Doc Link PMC2230610 Disease Relevance 1.31 Pain Relevance 0.16

Administration of DrotAA was associated with an increased risk for serious bleeding during the infusion period in both the overall PROWESS patients (P = 0.024) and the surgical cohort (P = 0.006); however, the surgical patients did not demonstrate excessive risk of bleeding compared with nonsurgical patients who received DrotAA.

Positive_regulation (received) of DrotAA associated with hemorrhage

2) Confidence 0.36 Published 2007 Journal Crit Care Section Body Doc Link PMC2230610 Disease Relevance 0.62 Pain Relevance 0

From the very first clinical study, safety analyses have been included in each controlled trial conducted in DrotAA, and continuous safety surveillance has formed part of all studies undertaken for the purposes of registering the drug for commercial use.

Positive_regulation (conducted) of DrotAA

3) Confidence 0.36 Published 2007 Journal Crit Care Section Body Doc Link PMC2230610 Disease Relevance 0.65 Pain Relevance 0.16

Administration of DrotAA was associated with an increased risk for serious bleeding during the infusion period in both the overall PROWESS patients (P = 0.024) and the surgical cohort (P = 0.006); however, the surgical patients did not demonstrate excessive risk of bleeding compared with nonsurgical patients who received DrotAA.

Positive_regulation (Administration) of DrotAA associated with hemorrhage

4) Confidence 0.36 Published 2007 Journal Crit Care Section Body Doc Link PMC2230610 Disease Relevance 0.60 Pain Relevance 0

Although AP-1 proteins become constitutively expressed, the level of Ref-1, which is required for the DNA binding activity of AP-1, is significantly reduced in the nucleus of MDMs [201,202].

Positive_regulation (required) of Ref-1 in nucleus

5) Confidence 0.07 Published 2009 Journal Retrovirology Section Body Doc Link PMC2805609 Disease Relevance 0.22 Pain Relevance 0

These data support a potential role of SV1 and SV2 proteins as possible biological modulator of human mu-opioid receptor.

Spec (possible) Positive_regulation (role) of SV1 associated with opioid receptor

6) Confidence 0.04 Published 2006 Journal Biochem. Biophys. Res. Commun. Section Abstract Doc Link 16580639 Disease Relevance 0.08 Pain Relevance 0.59

Immunohistochemistry analysis was performed in order to assess whether the activation of the inflammatory transcriptional factor, NF-?

Spec (whether) Positive_regulation (activation) of inflammatory transcriptional factor associated with inflammation

7) Confidence 0.01 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2745573 Disease Relevance 0.55 Pain Relevance 0.13

APACHE: Acute Physiology and Chronic Health Evaluation; APC: activated protein C; DrotAA: Drotrecogin alfa (activated); EEG: electroencephalography; GCS: Glasgow Coma Scale; ICU: intensive care unit; SAE: sepsis-associated encephalopathy; SEP: somatosensory evoked potentials; SOFA: Sequential Organ Failure Assessment.

Positive_regulation (activated) of DrotAA associated with encephalopathy, electroencephalography, sepsis and coma

8) Confidence 0.01 Published 2010 Journal Crit Care Section Body Doc Link PMC2887172 Disease Relevance 1.30 Pain Relevance 0.10

General Comments

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