Reviewer's report
Title:Afferent signalling from the acid-challenged rat stomach is inhibited and
gastric acid elimination is enhanced by lafutidine
Version: 1Date:17 March 2009
Reviewer: Benedicte De Winter
Reviewer's report:
The manuscript describes the effects of lafutidine on acid-induced afferent
signalling to the brainstem, mucosal injury, intragastric acidity and gastric
emptying concluding that lafutidine has protective effects apart from its ability to
suppress gastric acid secretion. The authors describe an increase in intragastric
pH that might be related to either dilution and/or to acceleration of gastric
emptying. However, the mechanism of action and the distinct role of these two
potential mechanisms is not unravelled.
major remarks
1. The results and conclusion are largely based on the c-Fos experiments and
the estimate of gastric emptying. However, I do have some methodological
concerns. The decrease in c-FOS immunoreactivity is small and reaches only
statistical significance if the authors assume that a p-value of 0.1 is significantly
different. As this forms the basis of the hypothesis concerning the effects of
lafutidine on vagal afferent activity, we suggest to increase the number of rats
(despite the exploratory nature of the study) to be able to draw firm conclusions.
It would also be interesting to show a picture of the c-Fos immunoreactivity in
control rats to be able to compare the results.
2. I also wonder why the authors used the weight of the gastric content as an
indirect technique to measure gastric emptying. It would be interesting to
measure gastric emptying as a direct parameter to support the hypothesis on the
accelerating effect of lafutidine on gastric emptying firmly. In my view, the use of
this technique makes it hard to distinguish between an effect on dilution and on
gastric emptying per se. The technique with the solid beads could help to
distinguish between both parameters.
3. In the methodology on the determination of the gastric volume a second
analysis is used expressing the gastric volumes at time 60 and 120 min relatively
to time 0. As there is a difference in the values of the gastric volume in the
lafutidine- and cimetidine-treated rats at time 0, we wonder whether this
methodology can be used.
4. Does lafutidine has an effect per se on any of the parameters measured?
Does lafutidine for instance has an effect on gastric emptying in control rats?
These control experiments are lacking.
5. The authors compare the potency of lafutidine to cimetidine in the second
set-up of experiments. The effects of cimetidine are less pronounced. We wonder
whether this could be related to the different dose that was used for cimetidine
(10 mg/kg) whereas in these experiments lafutidine was used in the higher dose
of 30 mg/kg.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
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:Afferent signalling from the acid-challenged rat stomach is inhibited and
gastric acid elimination is enhanced by lafutidine
Version: 1Date:17 March 2009
Reviewer: Benedicte De Winter
Reviewer's report:
The manuscript describes the effects of lafutidine on acid-induced afferent
signalling to the brainstem, mucosal injury, intragastric acidity and gastric
emptying concluding that lafutidine has protective effects apart from its ability to
suppress gastric acid secretion. The authors describe an increase in intragastric
pH that might be related to either dilution and/or to acceleration of gastric
emptying. However, the mechanism of action and the distinct role of these two
potential mechanisms is not unravelled.
major remarks
1. The results and conclusion are largely based on the c-Fos experiments and
the estimate of gastric emptying. However, I do have some methodological
concerns. The decrease in c-FOS immunoreactivity is small and reaches only
statistical significance if the authors assume that a p-value of 0.1 is significantly
different. As this forms the basis of the hypothesis concerning the effects of
lafutidine on vagal afferent activity, we suggest to increase the number of rats
(despite the exploratory nature of the study) to be able to draw firm conclusions.
It would also be interesting to show a picture of the c-Fos immunoreactivity in
control rats to be able to compare the results.
2. I also wonder why the authors used the weight of the gastric content as an
indirect technique to measure gastric emptying. It would be interesting to
measure gastric emptying as a direct parameter to support the hypothesis on the
accelerating effect of lafutidine on gastric emptying firmly. In my view, the use of
this technique makes it hard to distinguish between an effect on dilution and on
gastric emptying per se. The technique with the solid beads could help to
distinguish between both parameters.
3. In the methodology on the determination of the gastric volume a second
analysis is used expressing the gastric volumes at time 60 and 120 min relatively
to time 0. As there is a difference in the values of the gastric volume in the
lafutidine- and cimetidine-treated rats at time 0, we wonder whether this
methodology can be used.
4. Does lafutidine has an effect per se on any of the parameters measured?
Does lafutidine for instance has an effect on gastric emptying in control rats?
These control experiments are lacking.
5. The authors compare the potency of lafutidine to cimetidine in the second
set-up of experiments. The effects of cimetidine are less pronounced. We wonder
whether this could be related to the different dose that was used for cimetidine
(10 mg/kg) whereas in these experiments lafutidine was used in the higher dose
of 30 mg/kg.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
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:Afferent signalling from the acid-challenged rat stomach is inhibited and
gastric acid elimination is enhanced by lafutidine
Version: 1Date:17 March 2009
Reviewer: Benedicte De Winter
Reviewer's report:
The manuscript describes the effects of lafutidine on acid-induced afferent
signalling to the brainstem, mucosal injury, intragastric acidity and gastric
emptying concluding that lafutidine has protective effects apart from its ability to
suppress gastric acid secretion. The authors describe an increase in intragastric
pH that might be related to either dilution and/or to acceleration of gastric
emptying. However, the mechanism of action and the distinct role of these two
potential mechanisms is not unravelled.
major remarks
1. The results and conclusion are largely based on the c-Fos experiments and
the estimate of gastric emptying. However, I do have some methodological
concerns. The decrease in c-FOS immunoreactivity is small and reaches only
statistical significance if the authors assume that a p-value of 0.1 is significantly
different. As this forms the basis of the hypothesis concerning the effects of
lafutidine on vagal afferent activity, we suggest to increase the number of rats
(despite the exploratory nature of the study) to be able to draw firm conclusions.
It would also be interesting to show a picture of the c-Fos immunoreactivity in
control rats to be able to compare the results.
2. I also wonder why the authors used the weight of the gastric content as an
indirect technique to measure gastric emptying. It would be interesting to
measure gastric emptying as a direct parameter to support the hypothesis on the
accelerating effect of lafutidine on gastric emptying firmly. In my view, the use of
this technique makes it hard to distinguish between an effect on dilution and on
gastric emptying per se. The technique with the solid beads could help to
distinguish between both parameters.
3. In the methodology on the determination of the gastric volume a second
analysis is used expressing the gastric volumes at time 60 and 120 min relatively
to time 0. As there is a difference in the values of the gastric volume in the
lafutidine- and cimetidine-treated rats at time 0, we wonder whether this
methodology can be used.
4. Does lafutidine has an effect per se on any of the parameters measured?
Does lafutidine for instance has an effect on gastric emptying in control rats?
These control experiments are lacking.
5. The authors compare the potency of lafutidine to cimetidine in the second
set-up of experiments. The effects of cimetidine are less pronounced. We wonder
whether this could be related to the different dose that was used for cimetidine
(10 mg/kg) whereas in these experiments lafutidine was used in the higher dose
of 30 mg/kg.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
'I declare that I have no competing interests'
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