Reviewer's report
Title:1HNMR-based Metabonomic profile of Rats with Experimental Acute
Pancreatitis: a controlled experiment
Version:1Date:18 March 2014
Reviewer: Nigel Turner
Reviewer's report:
In this manuscript Li et al have examined the metabolite profile of plasma, 12 hrs
after the induction of experimental induction of acute pancreatitis in rats. They
observed changes in a number of key metabolites and propose that these
metabolites may serve as biomarkers for acute pancreatitis. Some issues require
attention.
Major Compulsory Revisions
1) The authors do not provide any evidence for the effectiveness of the sodium
taurochlorate treatment in inducing pancreatitis in their model (e.g. histological or
biochemical evidence of pancreatic inflammation). This is a limitation of the study
and at the very least they should provide a reference to previous literature that
has successfully used this experimental approach (i.e. dose and timing) to induce
pancreatitis.
2) Several of the changes seen in metabolites are not consistent with what has
been observed in serum or urine samples from patients with pancreatitis (Ref 22
and 24). For example, although TMAO changes in a similar direction to that in ref
24, 3-hydroxybutyrate is reduced in humans with pancreatitis (ref 24), but
increased in the current rodent model. Similarly, lactate levels are increased in
this rodent model, but are not substantially altered in urine of humans with acute
or chronic pancreatitis (Ref 22). These inconsistencies are concerning, given the
authors’ proposal to use the metabolites in the current study as biomarkers for
pancreatitis. Some additional discussion of this point is needed, including
experimental differences that may explain these discrepancies, as well as
reference to other available metabolite data in this area from animal models and
humans.
3) In the discussion, the authors have made very definitive conclusions about the
observed metabolite changes and how these relate to changes in biological
parameters/pathways. However, they do not provide any references to back up
their assumptions/conclusions on what their data means. For example, an
increase in unsaturated fatty acids in the circulation could occur for multiple
reasons (e.g. altered uptake or utilisation of lipids), but the authors have
concluded that this must reflect a release of fatty acids from from membrane
lipids and a subsequent change in cell membrane stability. There is no reference
for this or discussion of what else a change in circulating unsaturated fatty acids
could signify. This is similar for most of the metabolites and this section needs to
be improved dramatically.
Level of interest: An article of limited interest
Quality of written English: Acceptable
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:1HNMR-based Metabonomic profile of Rats with Experimental Acute
Pancreatitis: a controlled experiment
Version:1Date:18 March 2014
Reviewer: Nigel Turner
Reviewer's report:
In this manuscript Li et al have examined the metabolite profile of plasma, 12 hrs
after the induction of experimental induction of acute pancreatitis in rats. They
observed changes in a number of key metabolites and propose that these
metabolites may serve as biomarkers for acute pancreatitis. Some issues require
attention.
Major Compulsory Revisions
1) The authors do not provide any evidence for the effectiveness of the sodium
taurochlorate treatment in inducing pancreatitis in their model (e.g. histological or
biochemical evidence of pancreatic inflammation). This is a limitation of the study
and at the very least they should provide a reference to previous literature that
has successfully used this experimental approach (i.e. dose and timing) to induce
pancreatitis.
2) Several of the changes seen in metabolites are not consistent with what has
been observed in serum or urine samples from patients with pancreatitis (Ref 22
and 24). For example, although TMAO changes in a similar direction to that in ref
24, 3-hydroxybutyrate is reduced in humans with pancreatitis (ref 24), but
increased in the current rodent model. Similarly, lactate levels are increased in
this rodent model, but are not substantially altered in urine of humans with acute
or chronic pancreatitis (Ref 22). These inconsistencies are concerning, given the
authors’ proposal to use the metabolites in the current study as biomarkers for
pancreatitis. Some additional discussion of this point is needed, including
experimental differences that may explain these discrepancies, as well as
reference to other available metabolite data in this area from animal models and
humans.
3) In the discussion, the authors have made very definitive conclusions about the
observed metabolite changes and how these relate to changes in biological
parameters/pathways. However, they do not provide any references to back up
their assumptions/conclusions on what their data means. For example, an
increase in unsaturated fatty acids in the circulation could occur for multiple
reasons (e.g. altered uptake or utilisation of lipids), but the authors have
concluded that this must reflect a release of fatty acids from from membrane
lipids and a subsequent change in cell membrane stability. There is no reference
for this or discussion of what else a change in circulating unsaturated fatty acids
could signify. This is similar for most of the metabolites and this section needs to
be improved dramatically.
Level of interest: An article of limited interest
Quality of written English: Acceptable
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:1HNMR-based Metabonomic profile of Rats with Experimental Acute
Pancreatitis: a controlled experiment
Version:1Date:18 March 2014
Reviewer: Nigel Turner
Reviewer's report:
In this manuscript Li et al have examined the metabolite profile of plasma, 12 hrs
after the induction of experimental induction of acute pancreatitis in rats. They
observed changes in a number of key metabolites and propose that these
metabolites may serve as biomarkers for acute pancreatitis. Some issues require
attention.
Major Compulsory Revisions
1) The authors do not provide any evidence for the effectiveness of the sodium
taurochlorate treatment in inducing pancreatitis in their model (e.g. histological or
biochemical evidence of pancreatic inflammation). This is a limitation of the study
and at the very least they should provide a reference to previous literature that
has successfully used this experimental approach (i.e. dose and timing) to induce
pancreatitis.
2) Several of the changes seen in metabolites are not consistent with what has
been observed in serum or urine samples from patients with pancreatitis (Ref 22
and 24). For example, although TMAO changes in a similar direction to that in ref
24, 3-hydroxybutyrate is reduced in humans with pancreatitis (ref 24), but
increased in the current rodent model. Similarly, lactate levels are increased in
this rodent model, but are not substantially altered in urine of humans with acute
or chronic pancreatitis (Ref 22). These inconsistencies are concerning, given the
authors’ proposal to use the metabolites in the current study as biomarkers for
pancreatitis. Some additional discussion of this point is needed, including
experimental differences that may explain these discrepancies, as well as
reference to other available metabolite data in this area from animal models and
humans.
3) In the discussion, the authors have made very definitive conclusions about the
observed metabolite changes and how these relate to changes in biological
parameters/pathways. However, they do not provide any references to back up
their assumptions/conclusions on what their data means. For example, an
increase in unsaturated fatty acids in the circulation could occur for multiple
reasons (e.g. altered uptake or utilisation of lipids), but the authors have
concluded that this must reflect a release of fatty acids from from membrane
lipids and a subsequent change in cell membrane stability. There is no reference
for this or discussion of what else a change in circulating unsaturated fatty acids
could signify. This is similar for most of the metabolites and this section needs to
be improved dramatically.
Level of interest: An article of limited interest
Quality of written English: Acceptable
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
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