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1. Serine Endopeptidases; Data from MetroHealth Medical Center provide new insights into serine
endopeptidases............................................................................................................................................... 1

11 October 2015 ii ProQuest

Document 1 of 1

Serine Endopeptidases; Data from MetroHealth Medical Center provide new insights into serine
endopeptidases
Author: Anonymous

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Abstract (Abstract): We have reproduced these biochemical changes as well as FM weakening in vitro using
tumor necrosis factor-alpha (TNF) and interleukin (IL)-1(SZ ligature), inflammatory cytokines implicated in
PPROM. Additionally, we have reported that the antioxidant and NF?B inhibitor alpha-lipoic Acid (LA) blocks
these TNF-induced effects. We now present the first direct evidence that thrombin also can induce FM
weakening in vitro, and LA treatment inhibits this thrombin-induced-weakening. Full thickness FM fragments
from unlabored Cesarean deliveries were incubated with increasing doses of thrombin (0-100 u/ml) for 48 h.
Fragments were then strength tested (breaking force and work to rupture) using our published methodology.
MMP3 and 9 levels in tissue extracts were determined by Western blot and densitometry. To determine the
effect of LA, FM fragments were incubated with control medium or 10 u/ml thrombin, with or without 0.25 mM
LA. Strength testing and MMP induction were determined.

Full text: 2010 OCT 23 - (<http://www.newsrx.com> NewsRx.com) -- Investigators publish new data in the report
'Alpha-lipoic acid inhibits thrombin-induced fetal membrane weakening in vitro.' "Cytokine-mediated
inflammation and abruption-induced thrombin generation are separately implicated in matrix metalloproteinase
(MMP)-mediated weakening of fetal membranes (FM) leading to preterm premature rupture of the fetal
membranes (PPROM) (see also <http://www.newsrx.com/library/topics/Serine-Endopeptidases.html> Serine
Endopeptidases). At term, FM of both labored vaginal and unlabored Cesarean deliveries exhibit a weak zone
overlying the cervix exhibiting ECM remodeling characterized by increased MMP9 protein and activity,"
investigators in the United States report.
"We have reproduced these biochemical changes as well as FM weakening in vitro using tumor necrosis factor-
alpha (TNF) and interleukin (IL)-1(SZ ligature), inflammatory cytokines implicated in PPROM. Additionally, we
have reported that the antioxidant and NF?B inhibitor alpha-lipoic Acid (LA) blocks these TNF-induced effects.
We now present the first direct evidence that thrombin also can induce FM weakening in vitro, and LA treatment
inhibits this thrombin-induced-weakening. Full thickness FM fragments from unlabored Cesarean deliveries
were incubated with increasing doses of thrombin (0-100 u/ml) for 48 h. Fragments were then strength tested
(breaking force and work to rupture) using our published methodology. MMP3 and 9 levels in tissue extracts
were determined by Western blot and densitometry. To determine the effect of LA, FM fragments were
incubated with control medium or 10 u/ml thrombin, with or without 0.25 mM LA. Strength testing and MMP
induction were determined. Thrombin induced a dose-dependent decrease in FM strength (42% baseline
rupture force and 45% work to rupture) coupled with a dose-dependent increase in MMP3 and 9 expression (all
p<0.001). Treatment of FM with 0.25 mM LA completely inhibited thrombin-induced FM weakening and MMP
expression (all p<0.001). Thrombin treatment of cultured FM induces mechanical weakening and increased
MMP3 and 9. Treatment of FM with LA inhibits these thrombin-induced effects," wrote R.M. Moore and
colleagues, MetroHealth Medical Center.
The researchers concluded: "We speculate LA may prove clinically useful in prevention of PPROM associated
with abruption."
Moore and colleagues published their study in Placenta (Alpha-lipoic acid inhibits thrombin-induced fetal
membrane weakening in vitro. Placenta, 2010;31(10):886-92).
For additional information, contact R.M. Moore, Case Western Reserve University, Departments of Pediatrics,
MetroHealth Medical Center, 2500 MetroHealth Drive, Cleveland OH USA.

11 October 2015 Page 1 of 2 ProQuest

Keywords: State:Cleveland, Country:United States, Blood Coagulation Factors, Enzymes, Peptide Hydrolases,
Serine Endopeptidases, Thrombin.
This article was prepared by Obesity, Fitness &Wellness Week editors from staff and other reports. Copyright
2010, Obesity, Fitness &Wellness Week via <http://www.newsrx.com> NewsRx.com.

Publication title: Obesity, Fitness & Wellness Week

First page: 405

Publication year: 2010

Publication date: Oct 23, 2010

Year: 2010

Publisher: NewsRx

Place of publication: Atlanta

Country of publication: United States

Publication subject: Medical Sciences

ISSN: 15316386

Source type: Trade Journals

Language of publication: English

Document type: Expanded Reporting

ProQuest document ID: 757585233

Document URL: http://search.proquest.com/docview/757585233?accountid=25704

Copyright: (c)Copyright 2010, Obesity, Fitness & Wellness Week via NewsRx.com

Last updated: 2010-10-13

Database: ProQuest Public Health,ProQuest Family Health

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