Reviewer's report
Title:Lubiprostone ameliorates the cystic fibrosis mouse intestinal phenotype
Version: 1Date:23 February 2010
Reviewer: Christina Haston
Reviewer's report:
In this manuscript De Lisle et al. evaluate the effect of lubiprostone treatment on
the intestinal phenotype of cystic fibrosis mice. The data are new and largely
clearly presented but two main limitations, the lack of cell physiology data, and
the n=1 sample number for the array data which negates a significance
determination, need to be addressed.
Major compulsory revisions
1. introduction. References are needed to substantiate statements in the first
paragraph, and the assertion that "Various novel approaches that correct mutant
CFTR function, or activate alternate electrolyte secretory mechanisms are under
investigation." The references for the CF phenotype being similar in patients and
mice are all to mice. References to clinical data are needed here.
2. The effect of lubiprostone on CLC2 is hypothesized but not evaluated. The
hypothesis actually tested should be indicated or the effect on CLC2 function in
the intestines of treated mice assessed.
3. Preliminary experiments showed that a dose of 10 µg/kg-day was maximally
effective (data not shown). What effect was maximal at this dose?
4. In figure 1 the comparison tested is not clear. What is the weight of CF mice
on peptamen alone, for comparison? Why is CF mouse weight gain compared to
WT?
5. The effect of the intervention on mucous accumulation is modest, at best,
within the CF mice. What is the p value comparing the distribution of lubiprostone
treated CF mice to that of CF controls in fig 3b? The analysis presented in fig 3C
should be statistically justified or removed.
6. What statistical test was applied to show the effect of lubiprostone treatment
on bacterial counts in CF mice? Is there literature support for this change as
physiologically relevant? Would such a change alter the intestinal distress in the
CF mouse?
7. Gene regulation was not assessed in this study so references to up/down
regulation in the Tables and text should be corrected. How were functions listed
in table determined? The table notes should indicate n=1.
8. A more complete description of the RT experiment is needed. Are the data
technical replicates of the chip result? If yes, the chip result should be removed
as the more valid data are from the RT experiment.
9. That Mcpt2 is increased in CF and decreased by treatment is not enough data
to support an effect on the innate immune response. This conclusion should be
justified with more data or removed.
Minor:
1. Mouse strain…C57BL/6J is stated in abstract, not methods.
2. The effects of lubiprostone on body weight gain was assessed. Grammatical
change needed.
3. page 14, drug name misspelled.
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:Lubiprostone ameliorates the cystic fibrosis mouse intestinal phenotype
Version: 1Date:23 February 2010
Reviewer: Christina Haston
Reviewer's report:
In this manuscript De Lisle et al. evaluate the effect of lubiprostone treatment on
the intestinal phenotype of cystic fibrosis mice. The data are new and largely
clearly presented but two main limitations, the lack of cell physiology data, and
the n=1 sample number for the array data which negates a significance
determination, need to be addressed.
Major compulsory revisions
1. introduction. References are needed to substantiate statements in the first
paragraph, and the assertion that "Various novel approaches that correct mutant
CFTR function, or activate alternate electrolyte secretory mechanisms are under
investigation." The references for the CF phenotype being similar in patients and
mice are all to mice. References to clinical data are needed here.
2. The effect of lubiprostone on CLC2 is hypothesized but not evaluated. The
hypothesis actually tested should be indicated or the effect on CLC2 function in
the intestines of treated mice assessed.
3. Preliminary experiments showed that a dose of 10 µg/kg-day was maximally
effective (data not shown). What effect was maximal at this dose?
4. In figure 1 the comparison tested is not clear. What is the weight of CF mice
on peptamen alone, for comparison? Why is CF mouse weight gain compared to
WT?
5. The effect of the intervention on mucous accumulation is modest, at best,
within the CF mice. What is the p value comparing the distribution of lubiprostone
treated CF mice to that of CF controls in fig 3b? The analysis presented in fig 3C
should be statistically justified or removed.
6. What statistical test was applied to show the effect of lubiprostone treatment
on bacterial counts in CF mice? Is there literature support for this change as
physiologically relevant? Would such a change alter the intestinal distress in the
CF mouse?
7. Gene regulation was not assessed in this study so references to up/down
regulation in the Tables and text should be corrected. How were functions listed
in table determined? The table notes should indicate n=1.
8. A more complete description of the RT experiment is needed. Are the data
technical replicates of the chip result? If yes, the chip result should be removed
as the more valid data are from the RT experiment.
9. That Mcpt2 is increased in CF and decreased by treatment is not enough data
to support an effect on the innate immune response. This conclusion should be
justified with more data or removed.
Minor:
1. Mouse strain…C57BL/6J is stated in abstract, not methods.
2. The effects of lubiprostone on body weight gain was assessed. Grammatical
change needed.
3. page 14, drug name misspelled.
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:Lubiprostone ameliorates the cystic fibrosis mouse intestinal phenotype
Version: 1Date:23 February 2010
Reviewer: Christina Haston
Reviewer's report:
In this manuscript De Lisle et al. evaluate the effect of lubiprostone treatment on
the intestinal phenotype of cystic fibrosis mice. The data are new and largely
clearly presented but two main limitations, the lack of cell physiology data, and
the n=1 sample number for the array data which negates a significance
determination, need to be addressed.
Major compulsory revisions
1. introduction. References are needed to substantiate statements in the first
paragraph, and the assertion that "Various novel approaches that correct mutant
CFTR function, or activate alternate electrolyte secretory mechanisms are under
investigation." The references for the CF phenotype being similar in patients and
mice are all to mice. References to clinical data are needed here.
2. The effect of lubiprostone on CLC2 is hypothesized but not evaluated. The
hypothesis actually tested should be indicated or the effect on CLC2 function in
the intestines of treated mice assessed.
3. Preliminary experiments showed that a dose of 10 µg/kg-day was maximally
effective (data not shown). What effect was maximal at this dose?
4. In figure 1 the comparison tested is not clear. What is the weight of CF mice
on peptamen alone, for comparison? Why is CF mouse weight gain compared to
WT?
5. The effect of the intervention on mucous accumulation is modest, at best,
within the CF mice. What is the p value comparing the distribution of lubiprostone
treated CF mice to that of CF controls in fig 3b? The analysis presented in fig 3C
should be statistically justified or removed.
6. What statistical test was applied to show the effect of lubiprostone treatment
on bacterial counts in CF mice? Is there literature support for this change as
physiologically relevant? Would such a change alter the intestinal distress in the
CF mouse?
7. Gene regulation was not assessed in this study so references to up/down
regulation in the Tables and text should be corrected. How were functions listed
in table determined? The table notes should indicate n=1.
8. A more complete description of the RT experiment is needed. Are the data
technical replicates of the chip result? If yes, the chip result should be removed
as the more valid data are from the RT experiment.
9. That Mcpt2 is increased in CF and decreased by treatment is not enough data
to support an effect on the innate immune response. This conclusion should be
justified with more data or removed.
Minor:
1. Mouse strain…C57BL/6J is stated in abstract, not methods.
2. The effects of lubiprostone on body weight gain was assessed. Grammatical
change needed.
3. page 14, drug name misspelled.
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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