INT35668

Context Info Confidence 0.10 First Reported 1983 Last Reported 2007 Negated 0 Speculated 0 Reported most in Abstract Documents 21 Total Number 21 Disease Relevance 3.10 Pain Relevance 3.95

cytoplasm (PLEKHM1)

Anatomy Link Frequency platelet 10 blood 2 plasma 1 polymorphonuclear leukocytes 1 PLEKHM1 (Homo sapiens)

Pain Link Frequency Relevance Heat cINOD 30 99.20 aspirin 22 97.18 diclofenac 10 96.24 Inflammation 12 93.84 local anesthetic 5 92.20 Analgesic 2 81.52 palliative 1 80.64 Inflammatory response 1 69.08 headache 2 25.00 chemokine 6 5.00

Disease Link Frequency Relevance Heat Coagulation Disorder 9 99.44 Hemorrhage 3 99.42 INFLAMMATION 27 97.54 Leukemia 1 95.08 Pressure Volume 2 Under Development 1 92.28 Injury 2 75.00 Chlamydia Infection 1 57.84 Bacterial Respiratory Disease 1 56.88 Coronavirus Infection 1 53.56 Parainfluenza Virus Infection 1 51.28

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Anatomy

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Pain term

Disease term

The basal production of TxB2 by fetal platelets (181.5 +/- 22.5 ng/ml, mean +/- SEM) was comparable with that of adults (216.1 +/- 11.5 ng/ml).

Gene_expression (production) of TxB2 in platelets

1) Confidence 0.10 Published 1983 Journal Prostaglandins Section Abstract Doc Link 6405453 Disease Relevance 0.24 Pain Relevance 0.25

Addition of acetylsalicylic acid (IC50 = 2.8 microM) or other nonsteroidal antiinflammatory drugs (NSAIDs) 15 min or 4.5h prior to 30 min stimulation with ionophore results in concentration dependent inhibition of TxB2 production.

Gene_expression (production) of TxB2 associated with aspirin, inflammation and cinod

2) Confidence 0.10 Published 1996 Journal Inflamm. Res. Section Abstract Doc Link 8737748 Disease Relevance 0.10 Pain Relevance 0.25

In a 5h assay, NSAIDs added at 0 h were compared for inhibition of TxB2 production stimulated by addition of ionophore A23187 at 4.5h (PGHS-1), or by addition of LPS at 0 h (PGHS-2).

Gene_expression (production) of TxB2 associated with cinod

3) Confidence 0.10 Published 1996 Journal Inflamm. Res. Section Abstract Doc Link 8737748 Disease Relevance 0.07 Pain Relevance 0.39

On the other hand, flunixin was clearly a more potent inhibitor of TxB2 production and adrenaline-induced platelet aggregation than tolfenamic acid, the IC50 values in TxB2 production being 0.28 +/- 0.02 microM and 2.6 +/- 0.3 microM for flunixin and tolfenamic acid, respectively.

Gene_expression (production) of TxB2 in platelet

4) Confidence 0.09 Published 1993 Journal Inflammation Section Abstract Doc Link 8406686 Disease Relevance 0.24 Pain Relevance 0.08

Serum levels of TxB2 and Pgl2 and platelet aggregation to arachidonic acid (AA) (1.75 mM) and collagen (1 microg/ml) were assessed.

Gene_expression (levels) of TxB2 in platelet

5) Confidence 0.07 Published 2004 Journal Int J Clin Pharmacol Res Section Abstract Doc Link 15689052 Disease Relevance 0 Pain Relevance 0

This double-blinded, randomized, placebo-controlled study was undertaken to investigate whether D-003 (20 mg/day) modifies serum levels of TxB2 and Pgl2 and inhibits platelet aggregation in human healthy volunteers.

Gene_expression (levels) of TxB2 in platelet

6) Confidence 0.07 Published 2004 Journal Int J Clin Pharmacol Res Section Abstract Doc Link 15689052 Disease Relevance 0 Pain Relevance 0

The concentrations of the drugs needed for 50% inhibition of TxB2 generation were 19.0 mumol/l for acetyl-salicylic acid, 0.09 mumol/l for indomethacin, 0.06 mumol/l for diclofenac sodium and 4.2 mumol/l for naproxen sodium.

Gene_expression (generation) of TxB2 associated with diclofenac

7) Confidence 0.07 Published 1983 Journal Prostaglandins Section Abstract Doc Link 6405453 Disease Relevance 0.23 Pain Relevance 0.27

When freshly drawn, heparinized human whole blood is incubated with 50 microM calcium ionophore A23187, platelets are stimulated to produce thromboxane B2 (TxB2) by activation of prostaglandin G/H synthase-l (PGHS-1).

Gene_expression (produce) of TxB2 in platelets

8) Confidence 0.06 Published 1996 Journal Inflamm. Res. Section Abstract Doc Link 8737748 Disease Relevance 0.08 Pain Relevance 0.15

Using a 5h incubation with 10 micrograms/ml LPS, aspirin (10 microM added at 0 h), which is rapidly metabolized to salicylic acid, had no effect on 10 micrograms/ml LPS-induced TxB2, but inhibited TxB2 production by ionophore A23187 added at 4.5h through acetylation of pre-existing PGHS-1.

Gene_expression (production) of TxB2 associated with aspirin

9) Confidence 0.06 Published 1996 Journal Inflamm. Res. Section Abstract Doc Link 8737748 Disease Relevance 0.08 Pain Relevance 0.38

PACBA in the same doses did not affect the production of TxB2.

Gene_expression (production) of TxB2

10) Confidence 0.06 Published 1997 Journal Thromb. Res. Section Abstract Doc Link 9175234 Disease Relevance 0.08 Pain Relevance 0.20

In conclusion, our results demonstrate for the first time that PABA, a substance occurring in nature, inhibits endogenous TxB2 synthesis in human platelets and might thus exert profound effects on platelet AA metabolism.

Gene_expression (synthesis) of TxB2 in platelet

11) Confidence 0.06 Published 1997 Journal Thromb. Res. Section Abstract Doc Link 9175234 Disease Relevance 0.06 Pain Relevance 0.16

On the other hand, flunixin was clearly a more potent inhibitor of TxB2 production and adrenaline-induced platelet aggregation than tolfenamic acid, the IC50 values in TxB2 production being 0.28 +/- 0.02 microM and 2.6 +/- 0.3 microM for flunixin and tolfenamic acid, respectively.

Gene_expression (production) of TxB2 in platelet

12) Confidence 0.06 Published 1993 Journal Inflammation Section Abstract Doc Link 8406686 Disease Relevance 0.24 Pain Relevance 0.07

A study was made to compare the effects of two nonsteroidal antiinflammatory drugs (NSAIDs), flunixin and tolfenamic acid, on the leukotriene B4 (LTB4) production and migration of human polymorphonuclear leukocytes (PMNs) as well as on platelet aggregation and thromboxane B2 (TxB2) production during blood clotting.

Gene_expression (production) of TxB2 in polymorphonuclear leukocytes associated with coagulation disorder, inflammation and cinod

13) Confidence 0.06 Published 1993 Journal Inflammation Section Abstract Doc Link 8406686 Disease Relevance 0.20 Pain Relevance 0.10

At 328 microM PABA the production of TxB2 diminished by 87% (p = 0.013).

Gene_expression (production) of TxB2

14) Confidence 0.05 Published 1997 Journal Thromb. Res. Section Abstract Doc Link 9175234 Disease Relevance 0.09 Pain Relevance 0.20

Early postoperative TFPI levels were significantly lower (p < 0.01) and TxB2 levels were significantly higher (p < 0.05) in patients with TCPC in comparison with those undergoing BV.

Gene_expression (levels) of TxB2

15) Confidence 0.05 Published 2007 Journal Crit Care Section Body Doc Link PMC2206501 Disease Relevance 0.34 Pain Relevance 0.12

When platelets were incubated with [1-14C]AA, in the presence of PABA, the production of [1-14C]TxB2 was only slightly inhibited, according to analysis by high pressure liquid chromatography.

Gene_expression (production) of TxB2 in platelets

16) Confidence 0.04 Published 1997 Journal Thromb. Res. Section Abstract Doc Link 9175234 Disease Relevance 0.08 Pain Relevance 0.19

When human platelets were stimulated with thrombin to liberate AA, we found that PABA inhibited the production of thromboxane (TxB2) as measured with enzyme-linked immunosorbent assay.

Gene_expression (production) of TxB2 in platelets

17) Confidence 0.04 Published 1997 Journal Thromb. Res. Section Abstract Doc Link 9175234 Disease Relevance 0.09 Pain Relevance 0.21

The relationship between endoscopically observed gastric mucosal damage, elicited following repeated oral intake for 7 d of four NSAIDs, to their effects on antral and fundic production of PGE2, 6-keto-PGF1 alpha and TxB2 (assayed by GC-MS), mucosal histology and plasma concentration profiles was studied in 40 normal males.

Gene_expression (production) of TxB2 in plasma associated with cinod

18) Confidence 0.03 Published 1993 Journal Agents Actions Section Abstract Doc Link 8273571 Disease Relevance 0.07 Pain Relevance 0.25

To investigate the role of the acetyl moiety in the inhibition of platelet thromboxane biosynthesis, we studied the effect of CMT and ASA on bleeding time, serum thromboxane B2 (TxB2) and thromboxane (Tx) generation in healthy volunteers.

Gene_expression (generation) of TxB2 in platelet associated with hemorrhage

19) Confidence 0.02 Published 1988 Journal Scott Med J Section Abstract Doc Link 3187504 Disease Relevance 0.56 Pain Relevance 0.31

In vitro enzyme results were supported by a human whole blood assay where etodolac also demonstrated a 10-fold selectivity for inhibition of PGHS-2 mediated TxB2 production.

Gene_expression (production) of TxB2 in blood

20) Confidence 0.02 Published 1995 Journal Eur. J. Pharmacol. Section Abstract Doc Link 8566109 Disease Relevance 0.08 Pain Relevance 0.34

General Comments

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