INT127459

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Context Info
Confidence 0.56
First Reported 2005
Last Reported 2010
Negated 0
Speculated 1
Reported most in Body
Documents 18
Total Number 19
Disease Relevance 15.15
Pain Relevance 1.05

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

cytosol (PAH) small molecule metabolic process (PAH) cellular nitrogen compound metabolic process (PAH)
Anatomy Link Frequency
lung 1
heart 1
PAH (Homo sapiens)
Pain Link Frequency Relevance Heat
Inflammation 63 100.00 Very High Very High Very High
fluoxetine 3 99.40 Very High Very High Very High
imagery 2 98.48 Very High Very High Very High
antagonist 77 93.28 High High
fibrosis 59 90.48 High High
potassium channel 4 90.08 High High
Serotonin 9 88.56 High High
tolerance 7 79.32 Quite High
cytokine 9 62.20 Quite High
Central nervous system 1 55.76 Quite High
Disease Link Frequency Relevance Heat
Pulmonary Hypertension 465 100.00 Very High Very High Very High
Hypoxia 327 100.00 Very High Very High Very High
INFLAMMATION 63 100.00 Very High Very High Very High
Hypertension 42 100.00 Very High Very High Very High
Metabolic Disorder 5 99.78 Very High Very High Very High
Disease Progression 5 99.52 Very High Very High Very High
Pneumonia 5 99.00 Very High Very High Very High
Phenylketonuria 30 98.86 Very High Very High Very High
Death 134 98.60 Very High Very High Very High
Dementia 2 95.28 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Phenylketonuria (PKU) is an autosomal recessive metabolic disorder caused by phenylalanine hydroxylase (PAH) deficiency.
Negative_regulation (deficiency) of phenylalanine hydroxylase associated with metabolic disorder and phenylketonuria
1) Confidence 0.56 Published 2005 Journal Mol. Genet. Metab. Section Abstract Doc Link 16150627 Disease Relevance 0.85 Pain Relevance 0
Phenylketonuria (PKU) is an autosomal recessive metabolic disorder caused by phenylalanine hydroxylase (PAH) deficiency.
Negative_regulation (deficiency) of PAH associated with metabolic disorder and phenylketonuria
2) Confidence 0.56 Published 2005 Journal Mol. Genet. Metab. Section Abstract Doc Link 16150627 Disease Relevance 0.85 Pain Relevance 0
Phenylketonuria (PKU) (OMIM 221600) is inborn error of the metabolism resulting from a deficiency of phenylalanine hydroxylase (PAH).
Negative_regulation (deficiency) of PAH associated with phenylketonuria
3) Confidence 0.42 Published 2010 Journal BMC Pediatr Section Body Doc Link PMC2885380 Disease Relevance 0.76 Pain Relevance 0.03
DHEA prevents hypoxic PH in old mice
Negative_regulation (prevents) of PH associated with pulmonary hypertension and hypoxia
4) Confidence 0.42 Published 2006 Journal Respir Res Section Body Doc Link PMC1764736 Disease Relevance 1.63 Pain Relevance 0.04
Bosentan improved 6WMD in idiopathic PAH, whereas it prevented deterioration in CTD-PAH: a 3 m improvement was seen compared to a 40 m decline in placebo-treated CTD-PAH patients.29 Combined analysis of the CTD-PAH patients in study 351 and BREATHE-1 suggests a trend favoring bosentan with a 22 m improvement in 6MWD.39 This was despite less favorable baseline 6MWD and PVR.
Negative_regulation (prevented) of CTD-PAH associated with pulmonary hypertension
5) Confidence 0.37 Published 2009 Journal Vascular Health and Risk Management Section Body Doc Link PMC2725793 Disease Relevance 0.98 Pain Relevance 0
We considered dehydroepiandrosterone (DHEA), that has recently been shown to prevent and treat chronic hypoxic PH in rats when administered orally in its free (30 mg/kg every other day, 0.5 atm, [23]) or sulfate form (DHEAS; 9 mg/kg/day in drinking water, 11% FIO2, [24]; after oral ingestion most if not all the sulfate is converted into the free form).
Negative_regulation (prevent) of PH associated with pulmonary hypertension and hypoxia
6) Confidence 0.31 Published 2006 Journal Respir Res Section Body Doc Link PMC1764736 Disease Relevance 1.60 Pain Relevance 0
DHEA has already been shown to prevent and reverse PH in rats [23,24].
Negative_regulation (reverse) of PH associated with pulmonary hypertension
7) Confidence 0.31 Published 2006 Journal Respir Res Section Body Doc Link PMC1764736 Disease Relevance 1.67 Pain Relevance 0.05
DHEA prevented hypoxic PH in mice
Negative_regulation (prevented) of PH associated with pulmonary hypertension and hypoxia
8) Confidence 0.31 Published 2006 Journal Respir Res Section Body Doc Link PMC1764736 Disease Relevance 1.68 Pain Relevance 0.04
However, none of these drugs has been able to consistently reverse PAH or prevent disease progression and most are too recently developed to determine their long-term effect on survival.
Negative_regulation (reverse) of PAH associated with pulmonary hypertension and disease progression
9) Confidence 0.15 Published 2008 Journal Drug design, development and therapy Section Body Doc Link PMC2761178 Disease Relevance 0.35 Pain Relevance 0.04
Fluoxetine (10 mg . kg(-1) . d(-1) PO) started 3 weeks after MCT injection completely reversed established PH, normalizing PA pressure and structure.
Negative_regulation (reversed) of PH
10) Confidence 0.12 Published 2005 Journal Circulation Section Body Doc Link 15927991 Disease Relevance 0 Pain Relevance 0
Given the postulated causal relation between 5-HTT overexpression and PH, we herein investigated whether the highly selective 5-HTT inhibitor fluoxetine prevented and/or reversed PH induced by monocrotaline (MCT) in rats.
Spec (whether) Negative_regulation (reversed) of PH associated with hypertension and fluoxetine
11) Confidence 0.11 Published 2005 Journal Circulation Section Abstract Doc Link 15927991 Disease Relevance 0.54 Pain Relevance 0.23
In addition, clinical chemistry revealed a significant increase in serum aspartate aminotransferases (AST) and alanine aminotransferases (ALT) following PH and PH/TIPS.
Negative_regulation (following) of PH
12) Confidence 0.03 Published 2007 Journal Comp Hepatol Section Body Doc Link PMC1920532 Disease Relevance 0.32 Pain Relevance 0.03
In addition, clinical chemistry revealed a significant increase in serum aspartate aminotransferases (AST) and alanine aminotransferases (ALT) following PH and PH/TIPS.
Negative_regulation (following) of PH
13) Confidence 0.03 Published 2007 Journal Comp Hepatol Section Body Doc Link PMC1920532 Disease Relevance 0.32 Pain Relevance 0.03
Furthermore, a steady and significant increase in serum bilirubin was detected in PH and PH/TIPS animals.
Negative_regulation (detected) of PH
14) Confidence 0.03 Published 2007 Journal Comp Hepatol Section Body Doc Link PMC1920532 Disease Relevance 0.31 Pain Relevance 0.03
Furthermore, a steady and significant increase in serum bilirubin was detected in PH and PH/TIPS animals.
Negative_regulation (detected) of PH
15) Confidence 0.03 Published 2007 Journal Comp Hepatol Section Body Doc Link PMC1920532 Disease Relevance 0.31 Pain Relevance 0.03
Note the paradox: S-nitrosothiols delivered acutely to the pulmonary vascular bed are vasodilators and will reverse PH; whereas, chronic exposure of the pulmonary vascular bed to S-nitrosothiols gradually causes pulmonary vascular remodeling and chronic pulmonary hypertension.
Negative_regulation (reverse) of PH associated with hypertension
16) Confidence 0.01 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2982841 Disease Relevance 1.38 Pain Relevance 0.13
Current UK guidelines state that right heart catheterization is essential in the investigation of new patients with suspected PH, and should be undertaken to assess specific and accurate measurements of PA pressure and PVR.15 Vasodilator testing with inhaled nitric oxide16 or prostacyclin17 can also be carried out at the time of catheterization to assess the degree of reversibility of PH.
Negative_regulation (reversibility) of PH in heart associated with pulmonary hypertension
17) Confidence 0.01 Published 2009 Journal Vascular Health and Risk Management Section Body Doc Link PMC2697585 Disease Relevance 0.72 Pain Relevance 0.09
In addition, there are decreases in lung lipid peroxidation (a marker of inflammation index), prolyl hydroxylase (PH) activity (an enzyme responsible for post-translational modification of collagen), hydroxyproline content, and pro-collagen I and III mRNA accumulation.
Negative_regulation (decreases) of PH in lung associated with inflammation
18) Confidence 0.01 Published 2010 Journal Fibrogenesis Tissue Repair Section Body Doc Link PMC2944211 Disease Relevance 0.81 Pain Relevance 0.29
In addition to the lack of PX and PH domains, TM-PLDs likely possess altered amino-acid sequences in the critical domains that correspond to the PXPH-PLD phosphate-binding structure.


Negative_regulation (lack) of PH
19) Confidence 0.01 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2978679 Disease Relevance 0.09 Pain Relevance 0

General Comments

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