Review for 10.1186/1471-230X-8-29 (2008)

Reviewer's report
Title:A Wilson protein expression, copper excretion and sweat production in
sweat glands of Wilson disease patients and controls
Version: 1Date:5 March 2008
Reviewer: Rajendra Prasad
Reviewer's report:
In the manuscript entitled “A Wilson protein expression, copper excretion and
sweat
production in sweat glands of Wilson disease patients and
controls” authors have investigated Wilson protein expression in
sweat glands and analyzed its effects on copper excretion into sweat in controls
and patients with Wilson disease. It is observed that the Wilson protein is
expressed in human and rat sweat gland epithelia. Copper concentration in
sweat is not significantly different between controls and Wilson patients. Wilson
patients produce significantly smaller volumes of sweat compared to controls.
Sweat production is partially reversible in Wilson patients under medical
treatment for Wilson disease.
Though authors have clearly stated the limitation of the work, question of the
study is not well defined and writing is not at all acceptable. Moreover data is not
sound, and discussion is not well balanced and adequately supported by the
data.
Paper stands rejected in the present form. Data only supports the fact that sweat
volume produced in Wilson patients is significantly less compared to controls. It
only adds to the list of factors like hypoproteinemia, malnutrition, age, race, skin
conditions in which patients fail to produce to an adequate sweat volume (LeGrys
etal. 1996, J Pediatrics 129 (6): 892-897. It can however be considered if
following major and minor revisions are answered.
Major Compulsory Revisions:
Include equal number of subjects having liver disease other Wilson.
Sweat testing on individual subject should have been done on two separate
occasions.
Mention how many subjects had hypoproteinemia, commonly observed in Wilson
disease subjects, a detrimental factor in sweat yield.
Results:
Association of low sweat volume with Wilson disease protein is hard to believe if
equal numbers of subjects with liver disease other than WD are not tested.
Immunofluorescence studies have been performed to show CuATPase 7B in
sweat glands of rats and humans. What happens in WD subjects? Show
immunofluorescenc/RT PCR.
In my view authors are still far from the fact that Wilson protein has a role in
sweat gland stimulation. In discussion authors have suggested the critical role of
Wilson protein for copper supply to neurotransmitter processing in sweat gland. It
is overstated unless data is documented in the present study.
In discussion, authors have mentioned that sweat copper concentrations are
unaltered comparing Wilson patients and controls, & Wilson protein has no
essential role in copper excretion into sweat. Why they want to conduct additional
investigations in regard to potential interplay between Wilson protein, Menke
protein and copper metabolism of sweat gland epithelial cells?
At present, authors have failed to convince whether Wilson protein has a role in
sweat production or in copper metabolism in sweat glands.
From clinical point of view, how important it would be to study variation in the
concentration of metal and electrolyte between the primary sweat fluid and the
sweat secreted onto the skin due to reabsorption and the active secretion in the
sweat ducts. In my opinion there is no need. Better omit from the discussion.
If it is to believe that reduced sweat volume is a constant feature of Wilson
disease (and not in other liver disorders), I agree with the authors that it could be
elevated copper that may be toxic to sweat glands as for liver liver and other
organs. As there is no data on cellular copper content, it remains an elusive fact.
It has to be studied rather than focusing on Wilson protein per se.
It is further supported by the observation that sweat volume increased on
treatment irrespective of whether Trentine/D-penicillamine were administered
either alone or in combination. All these chelate out excess copper but do not
correct the defect in Wilson protein. It draws out the fact that reduced sweat
volume is not due to the interplay of Wilson protein with ANS but due to the
degeneration of sweat glands probably because of excess of copper.
What do investigators suggest in other copper metabolic disorders like Indian
childhood cirrhosis/Tyrolian childhood cirrhosis.
It is hard to believe that Wilson protein has physiological function in producing
proteins essential for sweat production. Delete this or cite literature.
Minor Essential Revisions
Introduction is long.
There is no need to give a master chart of sweat volume and copper
concentrations in individual subjects, when box plots have been shown. Instead I
am more interested in biochemical profile more specifically total protein, albumin,
serum ceruloplasmin, serum copper (total & free), urine copper (before & after
treatment), and liver copper.
There are lots of typing & grammatical errors. Few are listed below
Page 1, Line5 copper concentration dependent
Page 1, Line6, an late
Page 1, Line11, develop not develop
Page 1, Line 24, excretions are
Page 1, line 32, compounds
Page 2, line 3, safe not save
Page 2, line 10, too not to
Page 2, line 13, D-penicillamine not D-penicillinamin
Page 2, line 16, patients are not measured, it is sweat copper that is measured.
Page 2, line 13, Pilocarpine not pilocarpin
Page 2, line 15, disinfection, not disinfection
Page 2, line 15, distilled not destilled
Page 2, line 16, 0.5% not 0,5%
Page 2, line 18, fibrosis not fibrose
Page 2, line 15, distilled not destilled
Page 2, line 19, may not my
Page 3, line 8, pilocarpine not pilocarping
Page 3, line 14, immunofluorescent not immunofluroscenct