Reviewer's report 
 Jejunal microvilli atrophy and reduced nutrient transport in rats with abvanced liver cirrhosis: Title: 
improvement by Insulin-like Growth Factor I (IGF-I) 
 3  28 February 2004 Version: Date: 
 Jordi J MuntanÃ© Reviewer: 
Reviewer's report: 
General 
The manuscript entitled "Jejunal microvilli atrophy and reduced nutrient transport in rats with 
advanced liver cirrhosis: improvement by insulin-like growth factor I (IGF-I)" by Castilla-Cortazar et 
al shows that the experimental induction of cirrhosis is accompained with an atrophy of intestinal 
microvilli and altered absorption of sugar and aminoacids. All these changes are improved by IGF-I treatment. ------------------------------------------------------------------------------- 
Major Compulsory Revisions (that the author must respond to before a decision on publication can 
be reached) 1) The present study is similar to other previously publish by the same group (Pascual et al. Am J Physiol Gastrointest Liver Physiol 2000;279:G319-G324). In this previous study, cirrhosis was 
induced by CCl4 and phenobarbital during 11 weeks. In the present study if the disturbances of aa 
(aminoacid) uptake was related to the atrophy of microvilli we could expect a lower values of aa uptake (figure 2) in comparison with those obtained in the previous study. In other words, there are no difference between aa uptake from BBMVs obtained from rats with cirrhosis or advanced 
cirrhosis. The beneficial effect of IGF in both groups are similar. Could the authors explain this lack 
of differences on aa uptake between those both groups? This is important because the authors claim that a relationship exist between an atrophy of microvilli and the decreased aa uptake. An atrophy of microvilli has not been observed by the same group (Castilla et al. Am J Physiol 
1999:276;G37-G42)in compensated cirrhotic rats. 
2) The authors should include in the manuscript some data about the effect of IGF on ascites and 
liver markers in advanced cirrhotic rats. 
3) Authors indicate that sodium-potasium-ATPase activity was twenty fold smaller after BBMV 
isolation compared to that observed in homogenate (lines 1-4 from bottom, preparation of BBMV). 
As sodium gradient generation has been neccessary to detect differences between untreated 
cirrhotic animals and control (first paragraph in results section) I would appreciate if authors could 
indicate if the lost of sodium-potasium ATPase during the isolation of BBMV could affect the results obtained. 
4) Authors should explain the reason by which a pool of BBMV from 10 animals has been used to 
carry out the kinetic studies of D-galactose and aa uptake. In this study is not possible to evaluate the differential animals response to cirrhosis in presence or not of IGF. 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the 
author can be trusted to correct) 
1) Authors should clearly identify the symbol used in figure 1 and 2. In the legend of figure 2, authors 
indicate statistical significances between groups. Nevertheless, the corresponding symbols are not 
presented in the figure. 
------------------------------------------------------------------------------- 
Discretionary Revisions (which the author can choose to ignore) 
1) It could be useful for the study the measurement of TNF-alfa in serum from rats with advanced 
cirrhosis treated or not with IGF. It could be possible that the recovery of malnutrition induced by cirrhosis during IGF treatment might be also related to a regulation of TNF-alfa by IGF-I. TNF-alfa is a cytokine involved in malnutrition during liver diseases. 
 Unable to decide on acceptance or rejection until the authors have responded to the What next?: 
major compulsory revisions 
 An article of importance in its field Level of interest: 
 Acceptable Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
None 
Reviewer's report 
 Jejunal microvilli atrophy and reduced nutrient transport in rats with abvanced liver cirrhosis: Title: 
improvement by Insulin-like Growth Factor I (IGF-I) 
 3  28 February 2004 Version: Date: 
 Jordi J MuntanÃ© Reviewer: 
Reviewer's report: 
General 
The manuscript entitled "Jejunal microvilli atrophy and reduced nutrient transport in rats with 
advanced liver cirrhosis: improvement by insulin-like growth factor I (IGF-I)" by Castilla-Cortazar et 
al shows that the experimental induction of cirrhosis is accompained with an atrophy of intestinal 
microvilli and altered absorption of sugar and aminoacids. All these changes are improved by IGF-I treatment. ------------------------------------------------------------------------------- 
Major Compulsory Revisions (that the author must respond to before a decision on publication can 
be reached) 1) The present study is similar to other previously publish by the same group (Pascual et al. Am J Physiol Gastrointest Liver Physiol 2000;279:G319-G324). In this previous study, cirrhosis was 
induced by CCl4 and phenobarbital during 11 weeks. In the present study if the disturbances of aa 
(aminoacid) uptake was related to the atrophy of microvilli we could expect a lower values of aa uptake (figure 2) in comparison with those obtained in the previous study. In other words, there are no difference between aa uptake from BBMVs obtained from rats with cirrhosis or advanced 
cirrhosis. The beneficial effect of IGF in both groups are similar. Could the authors explain this lack 
of differences on aa uptake between those both groups? This is important because the authors claim that a relationship exist between an atrophy of microvilli and the decreased aa uptake. An atrophy of microvilli has not been observed by the same group (Castilla et al. Am J Physiol 
1999:276;G37-G42)in compensated cirrhotic rats. 
2) The authors should include in the manuscript some data about the effect of IGF on ascites and 
liver markers in advanced cirrhotic rats. 
3) Authors indicate that sodium-potasium-ATPase activity was twenty fold smaller after BBMV 
isolation compared to that observed in homogenate (lines 1-4 from bottom, preparation of BBMV). 
As sodium gradient generation has been neccessary to detect differences between untreated 
cirrhotic animals and control (first paragraph in results section) I would appreciate if authors could 
indicate if the lost of sodium-potasium ATPase during the isolation of BBMV could affect the results obtained. 
4) Authors should explain the reason by which a pool of BBMV from 10 animals has been used to 
carry out the kinetic studies of D-galactose and aa uptake. In this study is not possible to evaluate the differential animals response to cirrhosis in presence or not of IGF. 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the 
author can be trusted to correct) 
1) Authors should clearly identify the symbol used in figure 1 and 2. In the legend of figure 2, authors 
indicate statistical significances between groups. Nevertheless, the corresponding symbols are not 
presented in the figure. 
------------------------------------------------------------------------------- 
Discretionary Revisions (which the author can choose to ignore) 
1) It could be useful for the study the measurement of TNF-alfa in serum from rats with advanced 
cirrhosis treated or not with IGF. It could be possible that the recovery of malnutrition induced by cirrhosis during IGF treatment might be also related to a regulation of TNF-alfa by IGF-I. TNF-alfa is a cytokine involved in malnutrition during liver diseases. 
 Unable to decide on acceptance or rejection until the authors have responded to the What next?: 
major compulsory revisions 
 An article of importance in its field Level of interest: 
 Acceptable Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
None 
Please review this paper.
user
Reviewer's report 
 Jejunal microvilli atrophy and reduced nutrient transport in rats with abvanced liver cirrhosis: Title: 
improvement by Insulin-like Growth Factor I (IGF-I) 
 3  28 February 2004 Version: Date: 
 Jordi J MuntanÃ© Reviewer: 
Reviewer's report: 
General 
The manuscript entitled "Jejunal microvilli atrophy and reduced nutrient transport in rats with 
advanced liver cirrhosis: improvement by insulin-like growth factor I (IGF-I)" by Castilla-Cortazar et 
al shows that the experimental induction of cirrhosis is accompained with an atrophy of intestinal 
microvilli and altered absorption of sugar and aminoacids. All these changes are improved by IGF-I treatment. ------------------------------------------------------------------------------- 
Major Compulsory Revisions (that the author must respond to before a decision on publication can 
be reached) 1) The present study is similar to other previously publish by the same group (Pascual et al. Am J Physiol Gastrointest Liver Physiol 2000;279:G319-G324). In this previous study, cirrhosis was 
induced by CCl4 and phenobarbital during 11 weeks. In the present study if the disturbances of aa 
(aminoacid) uptake was related to the atrophy of microvilli we could expect a lower values of aa uptake (figure 2) in comparison with those obtained in the previous study. In other words, there are no difference between aa uptake from BBMVs obtained from rats with cirrhosis or advanced 
cirrhosis. The beneficial effect of IGF in both groups are similar. Could the authors explain this lack 
of differences on aa uptake between those both groups? This is important because the authors claim that a relationship exist between an atrophy of microvilli and the decreased aa uptake. An atrophy of microvilli has not been observed by the same group (Castilla et al. Am J Physiol 
1999:276;G37-G42)in compensated cirrhotic rats. 
2) The authors should include in the manuscript some data about the effect of IGF on ascites and 
liver markers in advanced cirrhotic rats. 
3) Authors indicate that sodium-potasium-ATPase activity was twenty fold smaller after BBMV 
isolation compared to that observed in homogenate (lines 1-4 from bottom, preparation of BBMV). 
As sodium gradient generation has been neccessary to detect differences between untreated 
cirrhotic animals and control (first paragraph in results section) I would appreciate if authors could 
indicate if the lost of sodium-potasium ATPase during the isolation of BBMV could affect the results obtained. 
4) Authors should explain the reason by which a pool of BBMV from 10 animals has been used to 
carry out the kinetic studies of D-galactose and aa uptake. In this study is not possible to evaluate the differential animals response to cirrhosis in presence or not of IGF. 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the 
author can be trusted to correct) 
1) Authors should clearly identify the symbol used in figure 1 and 2. In the legend of figure 2, authors 
indicate statistical significances between groups. Nevertheless, the corresponding symbols are not 
presented in the figure. 
------------------------------------------------------------------------------- 
Discretionary Revisions (which the author can choose to ignore) 
1) It could be useful for the study the measurement of TNF-alfa in serum from rats with advanced 
cirrhosis treated or not with IGF. It could be possible that the recovery of malnutrition induced by cirrhosis during IGF treatment might be also related to a regulation of TNF-alfa by IGF-I. TNF-alfa is a cytokine involved in malnutrition during liver diseases. 
 Unable to decide on acceptance or rejection until the authors have responded to the What next?: 
major compulsory revisions 
 An article of importance in its field Level of interest: 
 Acceptable Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
None 
assistant