Reviewer's report
Title:HMGB1 neutralization is associated with bacterial translocation during
APAP hepatotoxicity
Version:2Date:24 November 2013
Reviewer: Carol R Gardner
Reviewer's report:
Major Compulsory Revisions:
Results:
Liver Injury:
This section is a discussion of previously reported data and some of the data that
has also been reported on page 13 of the manuscript. Either combine this section
with the BrdU staining section or include the ALT/AST data with the prior section
on bioactivation and call it "liver injury". There is also no mention in the materials
and methods on how the authors determined the percentage of the necrotic
areas within the liver sections.
Bacterial translocations to MLN and the liver:
The first sentence makes no sense: it reads: "Bacterial translocation was
measured in our published APAP toxicity studies (data not published) and the
results showed that: when i.p. injected into mice....." Please correct.
Discussion:
In general, the discussion is difficult to read and the sentence structure is poor.
The authors were asked to address the possibility that the proliferating
macrophages within the livers at 48 h could be either pro- or anti-inflammatory.
Their response to the reviewer was that they were confused and simply put the
statement in the discussion without a reference or context. Current literature
recognizes the existence of multiple populations of macrophages (classically
activated-M1 and alternatively activated-M2) which can be present at different
stages during the course of toxic events. This is what needs to be addressed in
view of the fact that macrophages are proliferating and/or migrating into the liver.
The 2nd sentence in the paragraph on gut permeability does not make sense.
Figure 4: The backgrounds don't match and the background on 4E is so bright it
obscures the area of interest.
Minor Essential Revisions:
Figure 3: The X-axis labels are spaced to closely and difficult to read.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Not suitable for publication unless extensively edited
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests
Reviewer's report
Title:HMGB1 neutralization is associated with bacterial translocation during
APAP hepatotoxicity
Version:2Date:24 November 2013
Reviewer: Carol R Gardner
Reviewer's report:
Major Compulsory Revisions:
Results:
Liver Injury:
This section is a discussion of previously reported data and some of the data that
has also been reported on page 13 of the manuscript. Either combine this section
with the BrdU staining section or include the ALT/AST data with the prior section
on bioactivation and call it "liver injury". There is also no mention in the materials
and methods on how the authors determined the percentage of the necrotic
areas within the liver sections.
Bacterial translocations to MLN and the liver:
The first sentence makes no sense: it reads: "Bacterial translocation was
measured in our published APAP toxicity studies (data not published) and the
results showed that: when i.p. injected into mice....." Please correct.
Discussion:
In general, the discussion is difficult to read and the sentence structure is poor.
The authors were asked to address the possibility that the proliferating
macrophages within the livers at 48 h could be either pro- or anti-inflammatory.
Their response to the reviewer was that they were confused and simply put the
statement in the discussion without a reference or context. Current literature
recognizes the existence of multiple populations of macrophages (classically
activated-M1 and alternatively activated-M2) which can be present at different
stages during the course of toxic events. This is what needs to be addressed in
view of the fact that macrophages are proliferating and/or migrating into the liver.
The 2nd sentence in the paragraph on gut permeability does not make sense.
Figure 4: The backgrounds don't match and the background on 4E is so bright it
obscures the area of interest.
Minor Essential Revisions:
Figure 3: The X-axis labels are spaced to closely and difficult to read.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Not suitable for publication unless extensively edited
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests
Please review this paper.
user
Reviewer's report
Title:HMGB1 neutralization is associated with bacterial translocation during
APAP hepatotoxicity
Version:2Date:24 November 2013
Reviewer: Carol R Gardner
Reviewer's report:
Major Compulsory Revisions:
Results:
Liver Injury:
This section is a discussion of previously reported data and some of the data that
has also been reported on page 13 of the manuscript. Either combine this section
with the BrdU staining section or include the ALT/AST data with the prior section
on bioactivation and call it "liver injury". There is also no mention in the materials
and methods on how the authors determined the percentage of the necrotic
areas within the liver sections.
Bacterial translocations to MLN and the liver:
The first sentence makes no sense: it reads: "Bacterial translocation was
measured in our published APAP toxicity studies (data not published) and the
results showed that: when i.p. injected into mice....." Please correct.
Discussion:
In general, the discussion is difficult to read and the sentence structure is poor.
The authors were asked to address the possibility that the proliferating
macrophages within the livers at 48 h could be either pro- or anti-inflammatory.
Their response to the reviewer was that they were confused and simply put the
statement in the discussion without a reference or context. Current literature
recognizes the existence of multiple populations of macrophages (classically
activated-M1 and alternatively activated-M2) which can be present at different
stages during the course of toxic events. This is what needs to be addressed in
view of the fact that macrophages are proliferating and/or migrating into the liver.
The 2nd sentence in the paragraph on gut permeability does not make sense.
Figure 4: The backgrounds don't match and the background on 4E is so bright it
obscures the area of interest.
Minor Essential Revisions:
Figure 3: The X-axis labels are spaced to closely and difficult to read.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Not suitable for publication unless extensively edited
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests
assistant