INT60500

Context Info Confidence 0.41 First Reported 1993 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 21 Total Number 23 Disease Relevance 13.30 Pain Relevance 11.10

unfolded protein binding (Tbce) protein folding (Tbce) cytoskeleton (Tbce) cytoplasm (Tbce)

Anatomy Link Frequency macrophage 4 lung 2 PMN 2 hip 1 leaf 1 Tbce (Mus musculus)

Pain Link Frequency Relevance Heat lidocaine 1229 99.98 isoflurane 421 99.98 Inflammation 1383 99.66 adenocard 222 98.96 agonist 111 96.68 cytokine 358 95.20 chemokine 188 94.64 local anesthetic 72 93.44 cINOD 2 90.08 ischemia 29 88.72

Disease Link Frequency Relevance Heat Apoptosis 255 100.00 Adhesions 22 99.96 Peritonitis 72 99.88 Injury 220 99.68 INFLAMMATION 1447 99.66 Cramps 132 99.20 Thrombosis 2 98.62 Thrombosis Related Under Development 3 98.52 Adult Respiratory Distress Syndrome 183 98.40 Sepsis 18 97.12

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1-PI inhibiting both PMN serine proteinase-mediated ECM destruction and thrombin- or plasmin-induced increases in macrophage MMP-12 production (Churg et al 2003b, 2007b).

Negative_regulation (inhibiting) of PMN in macrophage

1) Confidence 0.41 Published 2008 Journal International Journal of Chronic Obstructive Pulmonary Disease Section Body Doc Link PMC2629972 Disease Relevance 0.35 Pain Relevance 0.11

When compared to mice that received zymosan alone, at the peak of inflammation, Tmax, isoflurane decreased maximal PMN numbers (?

Negative_regulation (decreased) of PMN associated with inflammation and isoflurane

2) Confidence 0.05 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2268966 Disease Relevance 0.19 Pain Relevance 0.98

The impact of lidocaine is documented herein at multi-levels in resolution and reflects (i) increased exudate PMNs, (ii) impaired PMN apoptosis as well as their uptake by macrophages, (iii) modulating both pro- and anti-inflammatory proteins, including cytokines and chemokines.

Negative_regulation (impaired) of PMN in macrophages associated with chemokine, inflammation, apoptosis, lidocaine and cytokine

3) Confidence 0.04 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2268966 Disease Relevance 0.71 Pain Relevance 1.03

Lidocaine inhibited both PMN apoptosis and macrophage uptake of apoptotic PMN, events that contributed to impaired PMN removal from exudates and thereby delayed the onset of resolution of acute inflammation and return to homeostasis.

Negative_regulation (removal) of PMN in macrophage associated with inflammation, apoptosis and lidocaine

4) Confidence 0.04 Published 2008 Journal PLoS ONE Section Abstract Doc Link PMC2268966 Disease Relevance 0.96 Pain Relevance 1.02

Peritoneal cells collected from mice receiving lidocaine (at both 0.08% and 0.008%) together with zymosan showed significantly decreased annexin-V+Gr-1+ cells by 50% and 64%, respectively, indicating reduced PMN apoptosis (Fig. 3A).

Negative_regulation (reduced) of PMN associated with apoptosis and lidocaine

5) Confidence 0.04 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2268966 Disease Relevance 0.49 Pain Relevance 0.76

As shown in Figures 1A and S1C, in the zymosan-initiated peritonitis, the number of PMN reached a maximum at 12 h.

Negative_regulation (number) of PMN associated with peritonitis

6) Confidence 0.04 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2268966 Disease Relevance 0.20 Pain Relevance 0.69

Thus, exudate CRAMP/LL-37 may also contribute to increased PMN numbers obtained at 4 h in lidocaine-treated mice (Fig. 1A).

Negative_regulation (numbers) of PMN associated with cramps and lidocaine

7) Confidence 0.04 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2268966 Disease Relevance 0.28 Pain Relevance 0.57

Lidocaine inhibited both PMN apoptosis and macrophage uptake of apoptotic PMN, events that contributed to impaired PMN removal from exudates and thereby delayed the onset of resolution of acute inflammation and return to homeostasis.

Negative_regulation (inhibited) of PMN in macrophage associated with inflammation, apoptosis and lidocaine

8) Confidence 0.04 Published 2008 Journal PLoS ONE Section Abstract Doc Link PMC2268966 Disease Relevance 0.95 Pain Relevance 0.95

The time intervals between 12 h (Tmax) and 35 h (T50), exudate PMN decreased in number from 17.5×106 PMN (?

Negative_regulation (decreased) of PMN

9) Confidence 0.04 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2268966 Disease Relevance 0.19 Pain Relevance 0.68

At 48 h after zymosan challenge, lidocaine at 0.08% also reduced PMN apoptosis ?

Negative_regulation (reduced) of PMN associated with apoptosis and lidocaine

10) Confidence 0.04 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2268966 Disease Relevance 0.48 Pain Relevance 0.77

Hence resolution agonists have two main mechanisms of actions at the tissue level; they lower the numbers of infiltrating PMN to the inflamed sites and tissues; and they stimulate the active removal of debris and apoptotic PMN from the inflamed sites by non-phlogistic activation of macrophages [5].

Negative_regulation (removal) of PMN in PMN associated with agonist and apoptosis

11) Confidence 0.04 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2268966 Disease Relevance 0.95 Pain Relevance 0.51

In the mice treated with both lidocaine and zymosan, the numbers of PMN continued to increase after 12 h and reached a maximum at 24 h.

Negative_regulation (numbers) of PMN associated with lidocaine

12) Confidence 0.04 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2268966 Disease Relevance 0.32 Pain Relevance 0.72

max; maximal PMN number) to 8.8×106 PMN (R50; essentially 50% reduction of PMN).

Negative_regulation (reduction) of PMN

13) Confidence 0.04 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2268966 Disease Relevance 0.23 Pain Relevance 0.76

Lidocaine and one of its derivatives inhibited leukocyte adhesion to veins in dogs and lidocaine reduced the incidence of deep venous thrombosis (DVT) in patients after hip replacement, suggesting but not proving that inhibition of PMN adhesion might have contributed.

Negative_regulation (inhibition) of PMN in hip associated with thrombosis related under development, lidocaine, thrombosis and adhesions

14) Confidence 0.03 Published 1993 Journal Haemostasis Section Abstract Doc Link 8495864 Disease Relevance 1.18 Pain Relevance 0.26

In that study A3-/- mice exhibited reduced pulmonary damage, and PMN migration into the lung was decreased.

Negative_regulation (decreased) of PMN in lung

15) Confidence 0.02 Published 2008 Journal Crit Care Section Body Doc Link PMC2592730 Disease Relevance 0.67 Pain Relevance 0.23

For instance, PMN depletion attenuates experimental lung damage, pulmonary function in neutropenic patients with lung injury can deteriorate as neutropenia resolves [5], and persistent pulmonary neutrophilia in ARDS is associated with poor outcomes [6].

Negative_regulation (depletion) of PMN in lung associated with neutropenia, lung injury and adult respiratory distress syndrome

16) Confidence 0.02 Published 2008 Journal Crit Care Section Body Doc Link PMC2592730 Disease Relevance 1.21 Pain Relevance 0.18

Pharmacological blockade of PMN infiltration into reperfused tissues mitigates the extent of I/R injury [19].

Negative_regulation (blockade) of PMN associated with injury

17) Confidence 0.02 Published 2008 Journal Crit Care Section Body Doc Link PMC2592730 Disease Relevance 1.01 Pain Relevance 0.51

Bronchoalveolar lavage fluid PMN count in group I was reduced (0.36 x 10(6)PMN/mL versus 6.2 x 10(6) PML/mL; p < 0.03).

Negative_regulation (reduced) of PMN

18) Confidence 0.02 Published 1996 Journal Ann. Thorac. Surg. Section Body Doc Link 8619724 Disease Relevance 0 Pain Relevance 0

Adenosine is an endogenous anti-inflammatory metabolite that decreases PMN activation.

Negative_regulation (decreases) of PMN in PMN associated with adenocard and inflammation

19) Confidence 0.02 Published 2001 Journal Shock Section Abstract Doc Link 11386622 Disease Relevance 0.89 Pain Relevance 0.23

Our findings on neutrophils impairment are significant in view of early landmark studies by Murphy and colleagues [67], who reported an important distinction between C. gattii and C. neoformans; the former, but not the latter, could inhibit PMN chemotaxis and chemokinesis.

Negative_regulation (inhibit) of PMN in Murphy

20) Confidence 0.01 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2881863 Disease Relevance 0.57 Pain Relevance 0

General Comments

This test has worked.