INT59464

Context Info Confidence 0.43 First Reported 1993 Last Reported 2010 Negated 5 Speculated 7 Reported most in Abstract Documents 21 Total Number 28 Disease Relevance 12.15 Pain Relevance 4.63

isomerase activity (ISYNA1) cytoplasm (ISYNA1)

Anatomy Link Frequency ECs 2 plasma 1 macrophages 1 hepatocytes 1 bladder 1 ISYNA1 (Homo sapiens)

Pain Link Frequency Relevance Heat opioid receptor 2 100.00 Bioavailability 1 99.16 agonist 16 99.14 Morphine 7 99.12 chemokine 19 98.58 Inflammation 258 98.54 cytokine 89 98.34 interstitial cystitis 5 97.96 Inflammatory mediators 9 97.92 Enkephalin 6 97.74

Disease Link Frequency Relevance Heat Bordatella Infection 2 99.84 Liver Disease 130 99.52 Injury 206 99.48 Infection 116 99.04 Chronic Fatigue Syndrome 11 98.88 Adhesions 8 98.78 INFLAMMATION 324 98.54 Interstitial Cystitis 5 97.96 Stress 332 97.32 Cystitis 1 96.60

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Because inflammation and iNOS are potential therapeutic targets, we examined transcriptional regulation of iNOS following GTN infusion and the consequences of its inhibition within dura mater.

Spec (examined) Regulation (regulation) of iNOS in dura mater associated with inflammation

1) Confidence 0.43 Published 2002 Journal Ann. Neurol. Section Abstract Doc Link 11921057 Disease Relevance 0.44 Pain Relevance 0.30

Exposure of ECs to the NO donor, SNAP, before the addition of LPS + IFN, blocked iNOS induction, whereas preincubation of ECs with inhibitors of NOS, before morphine or anandamide exposure, restored LPS + IFN induction of iNOS, suggesting a direct impact of NO on the regulation of iNOS activity.

Regulation (regulation) of iNOS in ECs associated with morphine

2) Confidence 0.42 Published 1998 Journal J. Cardiovasc. Pharmacol. Section Abstract Doc Link 9641464 Disease Relevance 0 Pain Relevance 0.63

The bioavailability of NO and the activity and expression of iNOS are regulated by anesthetic agents.

Regulation (regulated) of iNOS associated with bioavailability

3) Confidence 0.37 Published 2008 Journal J Anesth Section Abstract Doc Link 18500613 Disease Relevance 0.44 Pain Relevance 0.25

No iNOS labelling was detected on these first days of infection.

Regulation (detected) of iNOS associated with infection

4) Confidence 0.33 Published 2005 Journal BMC Infect Dis Section Body Doc Link PMC1208887 Disease Relevance 0.91 Pain Relevance 0

Thus, in the current study we investigated whether inducible NO synthase (iNOS) mediated NO production is altered in the bladder of cats with a naturally occurring model of IC termed feline IC (FIC).

Spec (whether) Regulation (altered) of iNOS in bladder associated with interstitial cystitis

5) Confidence 0.23 Published 2005 Journal J. Urol. Section Abstract Doc Link 15643277 Disease Relevance 0.56 Pain Relevance 0.46

We also observed that various pro-inflammatory mediators, including cytokines, chemokines, adhesion molecules, prostaglandin E(2) and its key enzyme COX-2, not iNOS or caspase-1, were markedly up-regulated by stimulation with these TLR and NOD agonists.

Regulation (regulated) of iNOS associated with chemokine, inflammatory mediators, agonist, adhesions and cytokine

6) Confidence 0.22 Published 2009 Journal J. Dent. Res. Section Abstract Doc Link 19734466 Disease Relevance 0.52 Pain Relevance 0.56

Spermine did not affect the up-regulation of iNOS mRNA levels but in a concentration-dependent manner significantly attenuated iNOS protein levels and NO production.

Neg (not) Regulation (affect) of iNOS

7) Confidence 0.19 Published 2005 Journal J. Biol. Chem. Section Abstract Doc Link 15548540 Disease Relevance 0.29 Pain Relevance 0.04

ODC knockdown with small interfering (si) RNA resulted in increased H. pylori-stimulated iNOS protein expression and NO production without altering iNOS mRNA levels.

Neg (without) Regulation (altering) of iNOS

8) Confidence 0.19 Published 2005 Journal J. Biol. Chem. Section Abstract Doc Link 15548540 Disease Relevance 0.25 Pain Relevance 0.10

Characterization of target cells for DENV and iNOS expression in peripheral blood mononuclear leukocytes (PBMLs) originating from patients with Dengue Fever

Regulation (target) of iNOS in blood associated with dengue

9) Confidence 0.17 Published 2005 Journal BMC Infect Dis Section Body Doc Link PMC1208887 Disease Relevance 0.24 Pain Relevance 0

This paper examines the role of the inducible enzymes cyclo-oxygenase (COX-2) and inducible NO synthase (iNOS) in the pathophysiology of CFS.

Spec (examines) Regulation (role) of iNOS associated with chronic fatigue syndrome

10) Confidence 0.11 Published 2007 Journal Neuro Endocrinol. Lett. Section Abstract Doc Link 17693978 Disease Relevance 0.96 Pain Relevance 0.09

Cyclic AMP formation, induced by forskolin or PGE2, had no effect on the stimulated levels of [3H]IPs.

Neg (no) Regulation (effect) of IPs

11) Confidence 0.11 Published 1993 Journal J. Endocrinol. Section Abstract Doc Link 8386215 Disease Relevance 0.24 Pain Relevance 0.10

We have reported that in macrophages, H. pylori up-regulates inducible NO synthase (iNOS) and antimicrobial NO production, but in parallel there is induction of arginase II, generating ornithine, and of ornithine decarboxylase (ODC), generating polyamines.

Regulation (regulates) of iNOS in macrophages

12) Confidence 0.08 Published 2005 Journal J. Biol. Chem. Section Abstract Doc Link 15548540 Disease Relevance 0.35 Pain Relevance 0.05

Spermine did not affect the up-regulation of iNOS mRNA levels but in a concentration-dependent manner significantly attenuated iNOS protein levels and NO production.

Regulation (regulation) of iNOS

13) Confidence 0.08 Published 2005 Journal J. Biol. Chem. Section Abstract Doc Link 15548540 Disease Relevance 0.29 Pain Relevance 0.04

Here one should just recall that if liver injury is concerned, NO levels (and then those of RNS) are usually increased in CLDs as a consequence of up-regulation of iNOS in hepatocytes, endothelial cells, Kupffer cells and, possibly, HSC/MFs [235-238,241,242].

Spec (possibly) Regulation (regulation) of iNOS in endothelial cells associated with liver disease and injury

14) Confidence 0.07 Published 2008 Journal Fibrogenesis Tissue Repair Section Body Doc Link PMC2584013 Disease Relevance 0.69 Pain Relevance 0.07

In addition the activity of iNOS, the inducible enzyme responsible for the synthesis of NO, is temperature-dependent [29], therefore elevated airway temperatures in patients with asthma [5] may induce further synthesis of NO.

Regulation (responsible) of iNOS associated with asthma

15) Confidence 0.07 Published 2005 Journal Respir Res Section Body Doc Link PMC553993 Disease Relevance 0.86 Pain Relevance 0.15

iNOS can be modulated by COX-2.

Regulation (modulated) of iNOS

16) Confidence 0.06 Published 2007 Journal Mediators of Inflammation Section Body Doc Link PMC1874678 Disease Relevance 0 Pain Relevance 0

C-1 decreased NO production in LPS/IFN-gamma-stimulated RAW 264.7 cells in a concentration-dependent manner, with an IC50 of approximately 2.16 microM; however, it had no direct effect on the iNOS activity of fully LPS/IFN-gamma-stimulated RAW 264.7 cells.

Neg (no) Regulation (effect) of iNOS in RAW 264

17) Confidence 0.06 Published 2001 Journal Biochem. Pharmacol. Section Abstract Doc Link 11274976 Disease Relevance 0.22 Pain Relevance 0.15

Albeit the changes in mRNA of eNOS and iNOS were not statistically significant, they tended to be elevated prior to the increase in protein expression of the respective isoenzyme.

Regulation (changes) of iNOS

18) Confidence 0.05 Published 2010 Journal Crit Care Section Body Doc Link PMC2945093 Disease Relevance 0.58 Pain Relevance 0

Since LPS-induced iNOS and COX-2 expression is primarily regulated by NF-?

Regulation (regulated) of iNOS

19) Confidence 0.04 Published 2007 Journal Mediators of Inflammation Section Body Doc Link PMC1874678 Disease Relevance 0.06 Pain Relevance 0

This effect of kinetin has also been previously observed in control iPS cells [22].

Regulation (control) of iPS

20) Confidence 0.03 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3004942 Disease Relevance 0.35 Pain Relevance 0

General Comments

This test has worked.