Reviewer's report
Title:Afferent signalling from the acid-challenged rat stomach is inhibited and
gastric acid elimination is enhanced by lafutidine
Version: 2Date:20 May 2009
Reviewer: Benedicte De Winter
Reviewer's report:
The authors addressed the topics raised by the three reviewers sufficiently in the
manuscript: they clarified some aspects and put other aspects into a broader
perspective, discussing the advantages and disadvantages of the model used
into more detail (for instance the indirect method used to give an appraisal on
gastric emptying).
However, they did not perform the additional experiments asked by the referees
due to several reasons such as the leaving of the PhD student and concerns of
the Ethical committee. I do have a remark concerning the ethical considerations:
I do agree that the amount of animals used should be as low as possible
certainly in experiments involving a pain stimulus. On the other hand it seems
very unethical to me to perform these experiments in a number of animals that is
too small to allow the study design to represent enough power to detect
differences. An underpowered study will not allow any conclusions at all and
therefore I feel that the rats used in such a protocol are wasted anyway.
Therefore a statement as “maximal 6 rats in a group” seems not scientifically
valid to me.
The control experiments we indicated refer to experiments in animals treated with
vehicle or lafutidine without the acid challenge in order to investigate the effects
of the drugs in basal conditions for instance on c-FOS expression and gastric
emptying or secretion. For the c-FOS experiments this would allow the readers to
confirm themselves the absence of c-FOS staining in non-challenged rats and
the increase obtained by acid challenge, for the gastric emptying studies it would
allow to investigate the presence/absence of an effect of lafutidine per se on
gastric emptying (without the acid challenge). These controls seem valuable to
us since they offer the possibility to further investigate the pathogenetic
mechanisms involved in control conditions versus a condition of gastric acid
challenge.
Concerning the lower dose of cimetidine compared to lafutidine I suggest to
include this dose difference also in the discussion on page 16, it might represent
another explanation for the less pronounced effect of cimetidine.
Benedicte De Winter
Level of interest: An article whose findings are important to those with closely
related research interests
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:Afferent signalling from the acid-challenged rat stomach is inhibited and
gastric acid elimination is enhanced by lafutidine
Version: 2Date:20 May 2009
Reviewer: Benedicte De Winter
Reviewer's report:
The authors addressed the topics raised by the three reviewers sufficiently in the
manuscript: they clarified some aspects and put other aspects into a broader
perspective, discussing the advantages and disadvantages of the model used
into more detail (for instance the indirect method used to give an appraisal on
gastric emptying).
However, they did not perform the additional experiments asked by the referees
due to several reasons such as the leaving of the PhD student and concerns of
the Ethical committee. I do have a remark concerning the ethical considerations:
I do agree that the amount of animals used should be as low as possible
certainly in experiments involving a pain stimulus. On the other hand it seems
very unethical to me to perform these experiments in a number of animals that is
too small to allow the study design to represent enough power to detect
differences. An underpowered study will not allow any conclusions at all and
therefore I feel that the rats used in such a protocol are wasted anyway.
Therefore a statement as “maximal 6 rats in a group” seems not scientifically
valid to me.
The control experiments we indicated refer to experiments in animals treated with
vehicle or lafutidine without the acid challenge in order to investigate the effects
of the drugs in basal conditions for instance on c-FOS expression and gastric
emptying or secretion. For the c-FOS experiments this would allow the readers to
confirm themselves the absence of c-FOS staining in non-challenged rats and
the increase obtained by acid challenge, for the gastric emptying studies it would
allow to investigate the presence/absence of an effect of lafutidine per se on
gastric emptying (without the acid challenge). These controls seem valuable to
us since they offer the possibility to further investigate the pathogenetic
mechanisms involved in control conditions versus a condition of gastric acid
challenge.
Concerning the lower dose of cimetidine compared to lafutidine I suggest to
include this dose difference also in the discussion on page 16, it might represent
another explanation for the less pronounced effect of cimetidine.
Benedicte De Winter
Level of interest: An article whose findings are important to those with closely
related research interests
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:Afferent signalling from the acid-challenged rat stomach is inhibited and
gastric acid elimination is enhanced by lafutidine
Version: 2Date:20 May 2009
Reviewer: Benedicte De Winter
Reviewer's report:
The authors addressed the topics raised by the three reviewers sufficiently in the
manuscript: they clarified some aspects and put other aspects into a broader
perspective, discussing the advantages and disadvantages of the model used
into more detail (for instance the indirect method used to give an appraisal on
gastric emptying).
However, they did not perform the additional experiments asked by the referees
due to several reasons such as the leaving of the PhD student and concerns of
the Ethical committee. I do have a remark concerning the ethical considerations:
I do agree that the amount of animals used should be as low as possible
certainly in experiments involving a pain stimulus. On the other hand it seems
very unethical to me to perform these experiments in a number of animals that is
too small to allow the study design to represent enough power to detect
differences. An underpowered study will not allow any conclusions at all and
therefore I feel that the rats used in such a protocol are wasted anyway.
Therefore a statement as “maximal 6 rats in a group” seems not scientifically
valid to me.
The control experiments we indicated refer to experiments in animals treated with
vehicle or lafutidine without the acid challenge in order to investigate the effects
of the drugs in basal conditions for instance on c-FOS expression and gastric
emptying or secretion. For the c-FOS experiments this would allow the readers to
confirm themselves the absence of c-FOS staining in non-challenged rats and
the increase obtained by acid challenge, for the gastric emptying studies it would
allow to investigate the presence/absence of an effect of lafutidine per se on
gastric emptying (without the acid challenge). These controls seem valuable to
us since they offer the possibility to further investigate the pathogenetic
mechanisms involved in control conditions versus a condition of gastric acid
challenge.
Concerning the lower dose of cimetidine compared to lafutidine I suggest to
include this dose difference also in the discussion on page 16, it might represent
another explanation for the less pronounced effect of cimetidine.
Benedicte De Winter
Level of interest: An article whose findings are important to those with closely
related research interests
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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