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Open AccessArticlePost Publication Peer ReviewVersion 2, Revised

Copper-to-Zinc Ratio Correlates with an Inflammatory Marker in Patients with Sickle Cell Disease (Version 2, Revised)

Department of Medical Laboratory Science, School of Basic Medical Sciences, College of Medical Sciences, University of Benin, Benin City, Nigeria
Author to whom correspondence should be addressed.
Received: 13 June 2019 / Accepted: 20 June 2019 / Published: 18 September 2019
Peer review status: 2nd round review Read review reports

Reviewer 1 Jungshan Chang Taipei Medical University Reviewer 2 Muhammad Jawad Nasim Saarland University, Saarbruecken, Germany
Version 1
Not approved
Authors' response
Approved with revisions
Authors' response
Version 2
Approved with revisions
Version 2, Revised
Published: 18 September 2019
DOI: 10.3390/sci1020055
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Version 1, Original
Published: 4 July 2019
DOI: 10.3390/sci1020034
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Sickle cell disease (SCD) is an inherited disorder of major health challenge in Nigeria. Micronutrients deficiencies often associated with the disorder may cause inflammation and abnormal metabolisms in the body. The copper-to-zinc ratio is a more important assessment than the concentrations of either of the metals in clinical practice. This study seeks to evaluate serum levels of c-reactive protein (CRP), copper, zinc and copper-to-zinc ratio and to correlate copper-to-zinc ratio with CRP in adult subjects with SCD. Serum copper, zinc, CRP and plasma fibrinogen were assayed in 100 confirmed SCD patients in steady clinical state and 100 age and sex matched subjects with normal haemoglobin. Serum copper and zinc were assayed by colorimetric method using reagents supplied by Centronic, Germany while CRP and fibrinogen were assayed using reagents supplied by Sigma (St. Louis, MO, USA) and Anogen (Ontario, Canada), respectively. The copper to zinc ratio was calculated from serum levels of copper and zinc. The measured parameters were compared between the groups using Students t-test and Pearson correlation coefficient was used to relate CRP with the other parameters. Serum copper, CRP, fibrinogen and copper-to-zinc ratio were significantly higher (p < 0.001) while zinc level was lower in SCD patients than controls. Serum CRP concentration correlated with copper (r = 0.10; p < 0.02), zinc (r = −0.199; p < 0.05) and Copper-to-zinc ratio (r = 0.312; p < 0.002) but the correlation between CRP and fibrinogen was not significant. Inflammatory condition may modulate copper and zinc homeostasis and copper-to-zinc ratio may be used as marker of nutritional deficiency and inflammation in SCD patients. View Full-Text
Keywords: copper; c-reactive protein; inflammation; sickle cell disease; zinc copper; c-reactive protein; inflammation; sickle cell disease; zinc
MDPI and ACS Style

Emokpae, M.A.; Fatimehin, E.B. Copper-to-Zinc Ratio Correlates with an Inflammatory Marker in Patients with Sickle Cell Disease. Sci 2019, 1, 55.

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Reviewer 1

Sent on 25 Jul 2019 by Jungshan Chang | Not approved
Taipei Medical University

This finding was really correlated or similar to the discovery by the Antwi-Boasiako research group published in the Medicina 2019, 55(5), 180 with the title of Serum Iron Levels and Copper-to-Zinc Ratio in Sickle Cell Disease. This study came with better research designed and more insightful results and conclusion. It also demonstrated that the copper-to-zinc ratio was significantly higher in the SCD patients, suggesting elevated copper-to-zinc ratio may be a biomarker of sickle cell oxidative stress and associated complications. The ratio may also be informative for the management of sickle cell oxidative burden. The authors suggested increased correlates with an Inflammatory Marker in Patients with Sickle Cell. This published article does impair the value of your studies and manuscript.

Response to Reviewer 1

Sent on 15 Jul 2020 by Mathias, Abiodun Emokpae, Emmanuel, Babatunde Fatimehin

We quite appreciate the comment of this reviewer and it is an opinion. This study evaluated serum levels of c-reactive proteins, copper, zinc and calculated the cu/zn ratio in SCD subjects on clinical steady state and did not include those with vaso-occlusive crisis. The study referred to evaluated serum iron, copper, zinc and calculated cu/zn ratio in SCD patients on steady clinical state and vaso-occlusive crisis. The findings from both studies are similar except for iron and CRP which were not similar to the studies. Whereas we correlated cu/zn ratio with CRP the other correlated cu/zn ratio with iron. Please we would like to know the fundamental flaws detected by the reviewer please. Thank you for the good job.

Reviewer 2

Sent on 09 Sep 2019 by Muhammad Jawad Nasim | Approved with revisions
Saarland University, Saarbruecken, Germany

Authors report correlation of serum levels of copper, zinc, copper-to-zinc ratio with  an inflammatory marker (c-reactive protein) in the patients with sickle cell anemia in the population of Nigeria. It is a very interesting study which confirms the correlation of abovementioned parameters towards the inflammation in the patients of sickle cell disease. A similar study has been reported by the Antwi-Boasiako research group published in the Medicina 2019, 55(5), 180 which also includes the serum levels of iron as an additional contributing factor. Moreover, the study reported by the Antwi-Boasiako et al was carried out in Ghana so it will be interesting to correlate both studies to provide a broader overview of the scope of the study. Over all it a very nice manuscript but can be improved.

Response to Reviewer 2

Sent on 15 Jul 2020 by Mathias, Abiodun Emokpae, Emmanuel, Babatunde Fatimehin

We thank this reviewer for job done, but has not suggested specific change(s) to the article. In this study the subjects were all on steady clinical state and none with vaso-occlusive crisis. In addition serum iron was not evaluated in present study. Regards, Emokpae

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