Review for 10.1186/1471-230X-12-115 (2012)

Reviewer's report
Title:The effect of sulindac, a non-steroidal anti-inflammatory drug, attenuates
inflammation and fibrosis in a mouse model of chronic pancreatitis
Version: 4Date:28 April 2012
Reviewer: Jan D'Haese
Reviewer's report:
In this manuscript, Han Bai et al. investigated the effect of sulindac, an NSAID, in
a mouse model of chronic pancreatitis.
The authors present interesting data; however, there are some major critics on
their submitted manuscript which need major compulsory revisions:
1. In the introduction of the manuscript, paragraph 2, the authors “justify” working
on chronic pancreatitis since attenuation of chronic pancreatitis “would be
significant for the prevention of pancreatic carcinogenesis”. CP is of course
known as a risk factor for pancreatic cancer, however the overall risk for CP
patients remains low (except for those with hereditary CP). This connection to
pancreatic cancer seems a little too farfetched and should be revised (see also
Nr. 5).
2. On page 4 the passage “The primary physiological effect of CCK and its
analogs on the pancreas is to stimulate protein-rich secretion”; “supramaximal
stimulation generates a distinct pancreatic response that includes diminished
secretion, accumulation of secretory proteins within the pancreas and pancreatic
injury.” is copied one to one from the cited publication (Aghdassi et al.). Even
though it is cited correctly, it is unacceptable to copy/past whole passages like
the authors have done here.
3. Reference Nr.10 is a paper on the role pancreatic stellate cells (PSC) in
pancreatic fibrosis and does not fit to the text on page 5 where the authors write
about the method of cerulein pancreatitis.
4. Unfortunately the authors miss to mention the crucial role of pancreatic stellate
cells for fibrosis in CP. Especially since activated PSCs express COX-2 and
since activation of COX-2 was reported to be required for the initiation of PSC
activation by inflammatory cytokines. Landmark papers like (Aoki H et al
“Cyclooxygenase-2 is required for activated pancreatic stellate cells to respond to
proinfl ammatory cytokines.” Am J Physiol Cell Physiol 2007;292:C259–68. )
should be included and discussed.
5. Page 5, paragraph 2: authors again discuss role of NSAID and COX in cancer.
This manuscript however presents data on chronic pancreatitis. On the other
hand, the authors miss to mention the role of COX and NSAID in chronic
pancreatitis, which should be discussed instead and landmark papers should be
cited (e.g. Silva A et al. Am J Physiol Gastrointest Liver Physiol. 2011
Jun;300(6):G968-75. And Polito F et al Br J Pharmacol. 2010
Nov;161(5):1002-11. And Seo SW et al World J Gastroenterol. 2007 Apr
28;13(16) and Reding T, et al Gut. 2006 Aug;55(8):1165-73)
6. Spelling error on page 9: cearulein instead of caerulein
7. How did the authors make sure that dosing of sulindac diet was sufficient?
Either food intake or even better plasma exposure should be measured. The
authors state that “food and water consumption were monitored every day”.
Please specify.
8. In our experience IHC of p-ERK can be quite difficult to establish. Please
specify how you validated your results.
9. Please specify which hypothesis guided the authors to look for p-ERK in IHC
and WB. Did the authors check other key pathways?
10. The authors should aim for confirmation of QRT PCR Results on Protein
level.
11. Figure 5: Image 5B look like a lot less magnified than 5A+C to me. If that is
the case, the image should be replaced by an image with the same magnification
as images 5A+C.
In general, the authors present interesting data but show weaknesses in their
interpretation and discussion.
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