Reviewer's report
Title:Prostaglandin E2-induced colonic secretion in patients with colorectal
neoplasia
Version: 1Date:7 October 2009
Reviewer: Markus Bleich
Reviewer's report:
The present manuscript describes the results from a creditable study on human
colon sigmoideum biopsy samples. The biopsies have been obtained from
healthy areas of control patients and patients with the diagnosis of colorectal
neoplasia. Ussing chamber measurements of short circuit current (SCC) show a
small but significant difference between tissues with respect to the effect of
indomethacin. In addition the data support the view that there is no difference in
SCC after maximal stimulation of adenylate cyclase by forskolin, receptor
mediated activation of cAMP pathway via PGE2 or after inhibiton of
phosphodiesterases by theophylline. Altogether, suggesting that the observed
difference is based on the local synthesis of prostaglandins rather than on the
endogenous generation or degradation of cAMP. Identification of the receptors
involved and quantification of their contribution to SCC stimulation is prevented
by a large scatter of the effects.
A major concern is that the authors measure baseline SCC and all effects on a
non standardized background of electrogenic absorptive and secretory currents.
This is indirectly shown in figure 4 where ouabain unmasks a current which
amounts to approximately 50% of the signal but which is not secretory
(bumetanide sensitive). Hence, all interpretations have to done with the limitation
that also this current might have been affected or in the worst case that affection
of this current even would have veiled the real observations.
Technically the tissue conductance is very high and suggests a significant edge
damage of the mounted epithelium. This might explain the low numbers in SCC
after stimulation e.g. by forskolin. On the other hand the observed absolute
currents are at the detection limit of the technology since already a zero shift of
0.5mV at the voltage electrodes would influence the signal by 100%.
Nevertheless this does not change the observations qualitatively.
Taken together the present data should be taken as valuable qualitative dataset
from human tissue but conclusions have to be taken with care.
On this background the discussion should be revised accordingly (abstract
conclusions are clear).
Language and abstract are clear.
• Discretionary Revisions (which are recommendations for improvement but
which the author can choose to ignore)
Histology figure 5 could be omitted. Add scale bar.
• Minor Essential Revisions (such as missing labels on figures, or the wrong use
of a term, which the author can be trusted to correct)
Figure 1 is much too complex. Please modify to be as simple as the hypothesis
and data are.
Abstract line 10: miniaturized
Methods, last sentence: please clarify the sequence of substance addition in the
case of ouabain and bumentanide
Please correct for SI units (sec = s)
• Major Compulsory Revisions (which the author must respond to before a
decision on publication can be reached)
Please add a serious discussion on the technical limitations caused by leakiness
of the preparation and the absence of luminal amiloride.
Please discuss your data in comparison to other published data from human
colon biopsy samples e.g. from cystic fibrosis patients.
Please reduce the title, the aims of the study and the discussion to the items
which can be seriously concluded on the basis of the data available.
After careful consideration of these points the manuscript can be considered for
publication.
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:Prostaglandin E2-induced colonic secretion in patients with colorectal
neoplasia
Version: 1Date:7 October 2009
Reviewer: Markus Bleich
Reviewer's report:
The present manuscript describes the results from a creditable study on human
colon sigmoideum biopsy samples. The biopsies have been obtained from
healthy areas of control patients and patients with the diagnosis of colorectal
neoplasia. Ussing chamber measurements of short circuit current (SCC) show a
small but significant difference between tissues with respect to the effect of
indomethacin. In addition the data support the view that there is no difference in
SCC after maximal stimulation of adenylate cyclase by forskolin, receptor
mediated activation of cAMP pathway via PGE2 or after inhibiton of
phosphodiesterases by theophylline. Altogether, suggesting that the observed
difference is based on the local synthesis of prostaglandins rather than on the
endogenous generation or degradation of cAMP. Identification of the receptors
involved and quantification of their contribution to SCC stimulation is prevented
by a large scatter of the effects.
A major concern is that the authors measure baseline SCC and all effects on a
non standardized background of electrogenic absorptive and secretory currents.
This is indirectly shown in figure 4 where ouabain unmasks a current which
amounts to approximately 50% of the signal but which is not secretory
(bumetanide sensitive). Hence, all interpretations have to done with the limitation
that also this current might have been affected or in the worst case that affection
of this current even would have veiled the real observations.
Technically the tissue conductance is very high and suggests a significant edge
damage of the mounted epithelium. This might explain the low numbers in SCC
after stimulation e.g. by forskolin. On the other hand the observed absolute
currents are at the detection limit of the technology since already a zero shift of
0.5mV at the voltage electrodes would influence the signal by 100%.
Nevertheless this does not change the observations qualitatively.
Taken together the present data should be taken as valuable qualitative dataset
from human tissue but conclusions have to be taken with care.
On this background the discussion should be revised accordingly (abstract
conclusions are clear).
Language and abstract are clear.
• Discretionary Revisions (which are recommendations for improvement but
which the author can choose to ignore)
Histology figure 5 could be omitted. Add scale bar.
• Minor Essential Revisions (such as missing labels on figures, or the wrong use
of a term, which the author can be trusted to correct)
Figure 1 is much too complex. Please modify to be as simple as the hypothesis
and data are.
Abstract line 10: miniaturized
Methods, last sentence: please clarify the sequence of substance addition in the
case of ouabain and bumentanide
Please correct for SI units (sec = s)
• Major Compulsory Revisions (which the author must respond to before a
decision on publication can be reached)
Please add a serious discussion on the technical limitations caused by leakiness
of the preparation and the absence of luminal amiloride.
Please discuss your data in comparison to other published data from human
colon biopsy samples e.g. from cystic fibrosis patients.
Please reduce the title, the aims of the study and the discussion to the items
which can be seriously concluded on the basis of the data available.
After careful consideration of these points the manuscript can be considered for
publication.
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:Prostaglandin E2-induced colonic secretion in patients with colorectal
neoplasia
Version: 1Date:7 October 2009
Reviewer: Markus Bleich
Reviewer's report:
The present manuscript describes the results from a creditable study on human
colon sigmoideum biopsy samples. The biopsies have been obtained from
healthy areas of control patients and patients with the diagnosis of colorectal
neoplasia. Ussing chamber measurements of short circuit current (SCC) show a
small but significant difference between tissues with respect to the effect of
indomethacin. In addition the data support the view that there is no difference in
SCC after maximal stimulation of adenylate cyclase by forskolin, receptor
mediated activation of cAMP pathway via PGE2 or after inhibiton of
phosphodiesterases by theophylline. Altogether, suggesting that the observed
difference is based on the local synthesis of prostaglandins rather than on the
endogenous generation or degradation of cAMP. Identification of the receptors
involved and quantification of their contribution to SCC stimulation is prevented
by a large scatter of the effects.
A major concern is that the authors measure baseline SCC and all effects on a
non standardized background of electrogenic absorptive and secretory currents.
This is indirectly shown in figure 4 where ouabain unmasks a current which
amounts to approximately 50% of the signal but which is not secretory
(bumetanide sensitive). Hence, all interpretations have to done with the limitation
that also this current might have been affected or in the worst case that affection
of this current even would have veiled the real observations.
Technically the tissue conductance is very high and suggests a significant edge
damage of the mounted epithelium. This might explain the low numbers in SCC
after stimulation e.g. by forskolin. On the other hand the observed absolute
currents are at the detection limit of the technology since already a zero shift of
0.5mV at the voltage electrodes would influence the signal by 100%.
Nevertheless this does not change the observations qualitatively.
Taken together the present data should be taken as valuable qualitative dataset
from human tissue but conclusions have to be taken with care.
On this background the discussion should be revised accordingly (abstract
conclusions are clear).
Language and abstract are clear.
• Discretionary Revisions (which are recommendations for improvement but
which the author can choose to ignore)
Histology figure 5 could be omitted. Add scale bar.
• Minor Essential Revisions (such as missing labels on figures, or the wrong use
of a term, which the author can be trusted to correct)
Figure 1 is much too complex. Please modify to be as simple as the hypothesis
and data are.
Abstract line 10: miniaturized
Methods, last sentence: please clarify the sequence of substance addition in the
case of ouabain and bumentanide
Please correct for SI units (sec = s)
• Major Compulsory Revisions (which the author must respond to before a
decision on publication can be reached)
Please add a serious discussion on the technical limitations caused by leakiness
of the preparation and the absence of luminal amiloride.
Please discuss your data in comparison to other published data from human
colon biopsy samples e.g. from cystic fibrosis patients.
Please reduce the title, the aims of the study and the discussion to the items
which can be seriously concluded on the basis of the data available.
After careful consideration of these points the manuscript can be considered for
publication.
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
assistant