Reviewer's report
Title:Effect of 5-HT7 receptor blockade on liver regeneration after 60-70% partial
hepatectomy
Version:4Date:27 March 2014
Reviewer: Bruno Christ
Reviewer's report:
Major Compulsory Revisions
The authors investigated the impact of the inhibition of 5-HT7-receptor signaling
on liver regeneration after 2/3 hepatectomy. They used 3 different methods to
evaluate regeneration and came to the result that receptor inhibition attenuated
and inhibited maximal regeneration rates. The study is straightforward and
presents clear results. Yet, a few issues need to be addressed before
publication.
1. What is the rational for using two different inhibitors of the 5-HT7-receptor?
Some comment on the specificity of the inhibitors´ action would be helpful. What
about the systemic pharmacological effects of the inhibitors? Is transient
inhibition of liver regeneration due to a short half-life of the drugs?
2. In that context it should be discussed how far side actions of the inhibitors can
be excluded. It has been shown that SB269970 inhibits also the
alpha2-adrenergic receptor. This is of relevance since data of beta-adrenergic
inhibition of liver regeneration are available. How specific is the action esp. of
SB269970 on the 5-HT7-receptor? Is there a dose-response relationship?
3. The mechanism, which is operative in inhibition of regeneration by
5-HT7-receptor blockade, is only speculated upon. It has been shown that
beta-receptor inhibition might have an indirect effect on regeneration inhibition by
attenuation of fatty acid supply from adipose tissue, thus limiting energy supply
for regeneration. Are there any experimental data available showing the direct
involvement of 5-HT7-receptor blockade in the liver? Or vice versa, can the
authors exclude systemic effects of receptor inhibition such as inhibition of
lipolysis in the adipose tissue?
4. The authors show both attenuation and inhibition of liver regeneration by
receptor inhibition. It would be expected that the liver mass is only partially
restored in comparison with controls. Did the authors determine the
liver-to-body-weight ratio, which would important to estimate liver function after
resection under 5-HT7-receptor blockade?
Minor Essential Revisions
Please indicate positive nuclei to be counted by arrows in Figs 4 and 5
Level of interest: An article of importance in its field
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:Effect of 5-HT7 receptor blockade on liver regeneration after 60-70% partial
hepatectomy
Version:4Date:27 March 2014
Reviewer: Bruno Christ
Reviewer's report:
Major Compulsory Revisions
The authors investigated the impact of the inhibition of 5-HT7-receptor signaling
on liver regeneration after 2/3 hepatectomy. They used 3 different methods to
evaluate regeneration and came to the result that receptor inhibition attenuated
and inhibited maximal regeneration rates. The study is straightforward and
presents clear results. Yet, a few issues need to be addressed before
publication.
1. What is the rational for using two different inhibitors of the 5-HT7-receptor?
Some comment on the specificity of the inhibitors´ action would be helpful. What
about the systemic pharmacological effects of the inhibitors? Is transient
inhibition of liver regeneration due to a short half-life of the drugs?
2. In that context it should be discussed how far side actions of the inhibitors can
be excluded. It has been shown that SB269970 inhibits also the
alpha2-adrenergic receptor. This is of relevance since data of beta-adrenergic
inhibition of liver regeneration are available. How specific is the action esp. of
SB269970 on the 5-HT7-receptor? Is there a dose-response relationship?
3. The mechanism, which is operative in inhibition of regeneration by
5-HT7-receptor blockade, is only speculated upon. It has been shown that
beta-receptor inhibition might have an indirect effect on regeneration inhibition by
attenuation of fatty acid supply from adipose tissue, thus limiting energy supply
for regeneration. Are there any experimental data available showing the direct
involvement of 5-HT7-receptor blockade in the liver? Or vice versa, can the
authors exclude systemic effects of receptor inhibition such as inhibition of
lipolysis in the adipose tissue?
4. The authors show both attenuation and inhibition of liver regeneration by
receptor inhibition. It would be expected that the liver mass is only partially
restored in comparison with controls. Did the authors determine the
liver-to-body-weight ratio, which would important to estimate liver function after
resection under 5-HT7-receptor blockade?
Minor Essential Revisions
Please indicate positive nuclei to be counted by arrows in Figs 4 and 5
Level of interest: An article of importance in its field
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:Effect of 5-HT7 receptor blockade on liver regeneration after 60-70% partial
hepatectomy
Version:4Date:27 March 2014
Reviewer: Bruno Christ
Reviewer's report:
Major Compulsory Revisions
The authors investigated the impact of the inhibition of 5-HT7-receptor signaling
on liver regeneration after 2/3 hepatectomy. They used 3 different methods to
evaluate regeneration and came to the result that receptor inhibition attenuated
and inhibited maximal regeneration rates. The study is straightforward and
presents clear results. Yet, a few issues need to be addressed before
publication.
1. What is the rational for using two different inhibitors of the 5-HT7-receptor?
Some comment on the specificity of the inhibitors´ action would be helpful. What
about the systemic pharmacological effects of the inhibitors? Is transient
inhibition of liver regeneration due to a short half-life of the drugs?
2. In that context it should be discussed how far side actions of the inhibitors can
be excluded. It has been shown that SB269970 inhibits also the
alpha2-adrenergic receptor. This is of relevance since data of beta-adrenergic
inhibition of liver regeneration are available. How specific is the action esp. of
SB269970 on the 5-HT7-receptor? Is there a dose-response relationship?
3. The mechanism, which is operative in inhibition of regeneration by
5-HT7-receptor blockade, is only speculated upon. It has been shown that
beta-receptor inhibition might have an indirect effect on regeneration inhibition by
attenuation of fatty acid supply from adipose tissue, thus limiting energy supply
for regeneration. Are there any experimental data available showing the direct
involvement of 5-HT7-receptor blockade in the liver? Or vice versa, can the
authors exclude systemic effects of receptor inhibition such as inhibition of
lipolysis in the adipose tissue?
4. The authors show both attenuation and inhibition of liver regeneration by
receptor inhibition. It would be expected that the liver mass is only partially
restored in comparison with controls. Did the authors determine the
liver-to-body-weight ratio, which would important to estimate liver function after
resection under 5-HT7-receptor blockade?
Minor Essential Revisions
Please indicate positive nuclei to be counted by arrows in Figs 4 and 5
Level of interest: An article of importance in its field
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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