Reviewer's report
 Electron Paramagnetic Resonance Spectroscopic Studies Of Intestinal Homogenates From Title:
NSAIDs Treated Rats.
Authors:
Sivagurunathan Somasundaram (sivasoma@med.unc.edu )
Jasvinder Shergill (j_shergill@kcl.ac.uk )
John Wrigglesworth (john-wrigglesworth@kcl.ac.uk )
Sue Rafi (s_rafi@kcl.ac.uk )
Ingvar Bjarnason (ingvar_bjarnason@kcl.ac.uk )
 2  14 Mar 2002 Version: Date:
 Prof H Sakurai Reviewer:
 not specified Level of interest:
 Accept after discretionary revisions Advice on publication:
The submitted manuscript by Somasundaram et al reports the mechanistic study of NSAIDs in terms of 
inhibition of electron transport on the basis of the experiments on EPR, permeability and morphology. 
The obtained results are interesting to understand the pharmacological activity and toxicity of 
indomethacin in relation to the mitochondrial respiratory chain, suggesting that NO plays an important 
role. However, in the sections of Materials and Methods, Results, and Discussion, many questions 
arose as follows. 
1) The title of the manuscript does not appear to reflect the results of the investigation. 
2) When the authors isolated the submitochondrial fraction, did they check the purity of the fraction by 
some enzyme activities such as succinate dehydrogenase and glucose-6-phosphatase? 3) Did the authors test the other types of inhibitors of iNOS in the experimental stages. 
4) The expression of, for example, 90 uL of submitochondrial particles is not suitable, instead, the 
authors should use the expression such as protein amounts or contents in an EPR tube. 
5) The measurement conditions for EPR should be described in detail in the Materials and Methods section. 
6) In Results, more detail explanations are needed, especially in the figures 3, 4, and 5. 
7) It might be natural to consider that the center S3 reacts with NO generated in the system. Why the intensities of EPR signal due to g=2.02 are almost the same between the systems for indomethacin, indomethacin plus DAHP, and control? 
8) Many spell errors are found in the manuscript. 
Then the manuscript is recommended to accept in the journal, however, the authors should extensively 
improve and revise the manuscript before the publication. 
Competing interests:
None declared.
Reviewer's report
 Electron Paramagnetic Resonance Spectroscopic Studies Of Intestinal Homogenates From Title:
NSAIDs Treated Rats.
Authors:
Sivagurunathan Somasundaram (sivasoma@med.unc.edu )
Jasvinder Shergill (j_shergill@kcl.ac.uk )
John Wrigglesworth (john-wrigglesworth@kcl.ac.uk )
Sue Rafi (s_rafi@kcl.ac.uk )
Ingvar Bjarnason (ingvar_bjarnason@kcl.ac.uk )
 2  14 Mar 2002 Version: Date:
 Prof H Sakurai Reviewer:
 not specified Level of interest:
 Accept after discretionary revisions Advice on publication:
The submitted manuscript by Somasundaram et al reports the mechanistic study of NSAIDs in terms of 
inhibition of electron transport on the basis of the experiments on EPR, permeability and morphology. 
The obtained results are interesting to understand the pharmacological activity and toxicity of 
indomethacin in relation to the mitochondrial respiratory chain, suggesting that NO plays an important 
role. However, in the sections of Materials and Methods, Results, and Discussion, many questions 
arose as follows. 
1) The title of the manuscript does not appear to reflect the results of the investigation. 
2) When the authors isolated the submitochondrial fraction, did they check the purity of the fraction by 
some enzyme activities such as succinate dehydrogenase and glucose-6-phosphatase? 3) Did the authors test the other types of inhibitors of iNOS in the experimental stages. 
4) The expression of, for example, 90 uL of submitochondrial particles is not suitable, instead, the 
authors should use the expression such as protein amounts or contents in an EPR tube. 
5) The measurement conditions for EPR should be described in detail in the Materials and Methods section. 
6) In Results, more detail explanations are needed, especially in the figures 3, 4, and 5. 
7) It might be natural to consider that the center S3 reacts with NO generated in the system. Why the intensities of EPR signal due to g=2.02 are almost the same between the systems for indomethacin, indomethacin plus DAHP, and control? 
8) Many spell errors are found in the manuscript. 
Then the manuscript is recommended to accept in the journal, however, the authors should extensively 
improve and revise the manuscript before the publication. 
Competing interests:
None declared.
Please review this paper.
user
Reviewer's report
 Electron Paramagnetic Resonance Spectroscopic Studies Of Intestinal Homogenates From Title:
NSAIDs Treated Rats.
Authors:
Sivagurunathan Somasundaram (sivasoma@med.unc.edu )
Jasvinder Shergill (j_shergill@kcl.ac.uk )
John Wrigglesworth (john-wrigglesworth@kcl.ac.uk )
Sue Rafi (s_rafi@kcl.ac.uk )
Ingvar Bjarnason (ingvar_bjarnason@kcl.ac.uk )
 2  14 Mar 2002 Version: Date:
 Prof H Sakurai Reviewer:
 not specified Level of interest:
 Accept after discretionary revisions Advice on publication:
The submitted manuscript by Somasundaram et al reports the mechanistic study of NSAIDs in terms of 
inhibition of electron transport on the basis of the experiments on EPR, permeability and morphology. 
The obtained results are interesting to understand the pharmacological activity and toxicity of 
indomethacin in relation to the mitochondrial respiratory chain, suggesting that NO plays an important 
role. However, in the sections of Materials and Methods, Results, and Discussion, many questions 
arose as follows. 
1) The title of the manuscript does not appear to reflect the results of the investigation. 
2) When the authors isolated the submitochondrial fraction, did they check the purity of the fraction by 
some enzyme activities such as succinate dehydrogenase and glucose-6-phosphatase? 3) Did the authors test the other types of inhibitors of iNOS in the experimental stages. 
4) The expression of, for example, 90 uL of submitochondrial particles is not suitable, instead, the 
authors should use the expression such as protein amounts or contents in an EPR tube. 
5) The measurement conditions for EPR should be described in detail in the Materials and Methods section. 
6) In Results, more detail explanations are needed, especially in the figures 3, 4, and 5. 
7) It might be natural to consider that the center S3 reacts with NO generated in the system. Why the intensities of EPR signal due to g=2.02 are almost the same between the systems for indomethacin, indomethacin plus DAHP, and control? 
8) Many spell errors are found in the manuscript. 
Then the manuscript is recommended to accept in the journal, however, the authors should extensively 
improve and revise the manuscript before the publication. 
Competing interests:
None declared.
assistant