Reviewer's report
Title:Zinc treatment ameliorated diarrhea and intestinal inflammation in
undernourished rats
Version:2Date:15 April 2014
Reviewer: Hemant Kulkarni
Reviewer's report:
The authors have conducted elegant experiments to understand the potential
mechanisms of zinc action as a supplementary therapy of acute diarrhea. In spite
of the generally accepted principle that zinc supplementation may be beneficial in
the treatment of acute diarrhea; the mechanisms of zinc action are currently
poorly understood. The authors have demonstrated that zinc supplementation, in
the context of a rat model of osmotic diarrhea, reduces the severity (as measured
by diarrheal scores), improves jejunal histology, diminishes bacterial
translocation and intestinal pro-inflammatory cytokines like IL-1beta and
TNF-alpha. While this is an important and interesting knowledge, I have some
concerns that need to be addressed by the authors.
Major Compulsory Revisions
1. As written, this manuscript seems to report what the authors found rather than
testing what the authors had thought. In other words, the manuscript is not based
on a clear testable set of hypotheses but it appears that the authors conducted
conceptually connected experiments and then wrote a manuscript. The authors
need to rewrite the latter part of Introduction in such a way as to clearly state the
hypothesis (or hypotheses) and then address each hypothesis in the Results
section.
2. The Abstract and the Discussion sections seem to imply a generalizability of
these results. In that regard, there are some limitations of the study that the
authors need to clearly mention. These limitations are:
a. This is an animal study and the temptation to draw parallels with humans
(unless explicitly studied) should be avoided.
b. The experimental model is for osmotic diarrhea. Whether these findings hold in
the context of infective diarrhea is unknown. In the scenario of infections, the
mechanisms involved could be very different than just osmotic diarrhea.
c. It has been shown in humans that zinc supplementation is not equally
beneficial across a spectrum of diarrhea-causing organisms. This study cannot
explain the mechanisms of zinc action in the context of differing causes of
diarrhea.
d. Garenne et al have shown that zinc supplementation could be differentially
beneficial in boys and girls. This study was conducted in male rats only and
therefore accont address potential sex-based differences in the benefits of zinc
supplementation.
Minor Essential Revisions
1. The authors need to check the manuscript for grammatical errors. For
example, the Background section in the Abstract is actually two sentences but,
as written, it appears to be one long sentence that is grammatically incorrect.
There are several instances throughout the manuscript that need a careful
revision from the viewpoint of grammar.
2. Table 1: Needs Ns.
3. Table 2: Footnotes are unclear. What are the values: median (range) or
median (quartile range)?
4. In the manuscript, I did not get to see Figure Legends. The authors need to
provide those.
5. In the Figures, authors have used the abbreviation “MN” that might pertain to
“malnourished”. However, in text the authors have used the term
“undernourished”. The authors need to be consistent with the use of terminology
throughout the manuscript.
Discretionary Revisions
1. Do the authors have access to any genetic data from these rats? For example,
gene expression in PBMCs, relevant DNA sequence variants or DNA methylation
profiles? Those data can definitely take the study to a higher level but are not
necessary to test the (unwritten) hypothesis that the authors are testing.
Level of interest: An article of importance in its field
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests.
Reviewer's report
Title:Zinc treatment ameliorated diarrhea and intestinal inflammation in
undernourished rats
Version:2Date:15 April 2014
Reviewer: Hemant Kulkarni
Reviewer's report:
The authors have conducted elegant experiments to understand the potential
mechanisms of zinc action as a supplementary therapy of acute diarrhea. In spite
of the generally accepted principle that zinc supplementation may be beneficial in
the treatment of acute diarrhea; the mechanisms of zinc action are currently
poorly understood. The authors have demonstrated that zinc supplementation, in
the context of a rat model of osmotic diarrhea, reduces the severity (as measured
by diarrheal scores), improves jejunal histology, diminishes bacterial
translocation and intestinal pro-inflammatory cytokines like IL-1beta and
TNF-alpha. While this is an important and interesting knowledge, I have some
concerns that need to be addressed by the authors.
Major Compulsory Revisions
1. As written, this manuscript seems to report what the authors found rather than
testing what the authors had thought. In other words, the manuscript is not based
on a clear testable set of hypotheses but it appears that the authors conducted
conceptually connected experiments and then wrote a manuscript. The authors
need to rewrite the latter part of Introduction in such a way as to clearly state the
hypothesis (or hypotheses) and then address each hypothesis in the Results
section.
2. The Abstract and the Discussion sections seem to imply a generalizability of
these results. In that regard, there are some limitations of the study that the
authors need to clearly mention. These limitations are:
a. This is an animal study and the temptation to draw parallels with humans
(unless explicitly studied) should be avoided.
b. The experimental model is for osmotic diarrhea. Whether these findings hold in
the context of infective diarrhea is unknown. In the scenario of infections, the
mechanisms involved could be very different than just osmotic diarrhea.
c. It has been shown in humans that zinc supplementation is not equally
beneficial across a spectrum of diarrhea-causing organisms. This study cannot
explain the mechanisms of zinc action in the context of differing causes of
diarrhea.
d. Garenne et al have shown that zinc supplementation could be differentially
beneficial in boys and girls. This study was conducted in male rats only and
therefore accont address potential sex-based differences in the benefits of zinc
supplementation.
Minor Essential Revisions
1. The authors need to check the manuscript for grammatical errors. For
example, the Background section in the Abstract is actually two sentences but,
as written, it appears to be one long sentence that is grammatically incorrect.
There are several instances throughout the manuscript that need a careful
revision from the viewpoint of grammar.
2. Table 1: Needs Ns.
3. Table 2: Footnotes are unclear. What are the values: median (range) or
median (quartile range)?
4. In the manuscript, I did not get to see Figure Legends. The authors need to
provide those.
5. In the Figures, authors have used the abbreviation “MN” that might pertain to
“malnourished”. However, in text the authors have used the term
“undernourished”. The authors need to be consistent with the use of terminology
throughout the manuscript.
Discretionary Revisions
1. Do the authors have access to any genetic data from these rats? For example,
gene expression in PBMCs, relevant DNA sequence variants or DNA methylation
profiles? Those data can definitely take the study to a higher level but are not
necessary to test the (unwritten) hypothesis that the authors are testing.
Level of interest: An article of importance in its field
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests.
Please review this paper.
user
Reviewer's report
Title:Zinc treatment ameliorated diarrhea and intestinal inflammation in
undernourished rats
Version:2Date:15 April 2014
Reviewer: Hemant Kulkarni
Reviewer's report:
The authors have conducted elegant experiments to understand the potential
mechanisms of zinc action as a supplementary therapy of acute diarrhea. In spite
of the generally accepted principle that zinc supplementation may be beneficial in
the treatment of acute diarrhea; the mechanisms of zinc action are currently
poorly understood. The authors have demonstrated that zinc supplementation, in
the context of a rat model of osmotic diarrhea, reduces the severity (as measured
by diarrheal scores), improves jejunal histology, diminishes bacterial
translocation and intestinal pro-inflammatory cytokines like IL-1beta and
TNF-alpha. While this is an important and interesting knowledge, I have some
concerns that need to be addressed by the authors.
Major Compulsory Revisions
1. As written, this manuscript seems to report what the authors found rather than
testing what the authors had thought. In other words, the manuscript is not based
on a clear testable set of hypotheses but it appears that the authors conducted
conceptually connected experiments and then wrote a manuscript. The authors
need to rewrite the latter part of Introduction in such a way as to clearly state the
hypothesis (or hypotheses) and then address each hypothesis in the Results
section.
2. The Abstract and the Discussion sections seem to imply a generalizability of
these results. In that regard, there are some limitations of the study that the
authors need to clearly mention. These limitations are:
a. This is an animal study and the temptation to draw parallels with humans
(unless explicitly studied) should be avoided.
b. The experimental model is for osmotic diarrhea. Whether these findings hold in
the context of infective diarrhea is unknown. In the scenario of infections, the
mechanisms involved could be very different than just osmotic diarrhea.
c. It has been shown in humans that zinc supplementation is not equally
beneficial across a spectrum of diarrhea-causing organisms. This study cannot
explain the mechanisms of zinc action in the context of differing causes of
diarrhea.
d. Garenne et al have shown that zinc supplementation could be differentially
beneficial in boys and girls. This study was conducted in male rats only and
therefore accont address potential sex-based differences in the benefits of zinc
supplementation.
Minor Essential Revisions
1. The authors need to check the manuscript for grammatical errors. For
example, the Background section in the Abstract is actually two sentences but,
as written, it appears to be one long sentence that is grammatically incorrect.
There are several instances throughout the manuscript that need a careful
revision from the viewpoint of grammar.
2. Table 1: Needs Ns.
3. Table 2: Footnotes are unclear. What are the values: median (range) or
median (quartile range)?
4. In the manuscript, I did not get to see Figure Legends. The authors need to
provide those.
5. In the Figures, authors have used the abbreviation “MN” that might pertain to
“malnourished”. However, in text the authors have used the term
“undernourished”. The authors need to be consistent with the use of terminology
throughout the manuscript.
Discretionary Revisions
1. Do the authors have access to any genetic data from these rats? For example,
gene expression in PBMCs, relevant DNA sequence variants or DNA methylation
profiles? Those data can definitely take the study to a higher level but are not
necessary to test the (unwritten) hypothesis that the authors are testing.
Level of interest: An article of importance in its field
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests.
assistant