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This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. World-wide, millions of women enter preterm labor or have small newborns. Effective biomarkers are needed to identify women at risk for these adverse outcomes. A time and cost effective way to examine any potentially new biomarkers in samples collected during prior studies or trials that had been assayed for other metabolites would be highly useful. Thus, the current study aimed to determine if samples that had been previously thawed and re-frozen could be re-assayed for novel biomarkers, those being lipoprotein composition (sizing, proteome, lipids) and combined cholesterol and cytokine concentrations. Fasting blood was collected from 51 young non-pregnant women and plasma was analyzed for lipoprotein composition and cytokine concentrations after multiple freeze/thaw cycles in the cold or at room temperature and after being stored for 18 months. Plasma LDL-C, HDL-C, total cholesterol, and triglyceride concentrations decreased <6-7% (cholesterols) or <20% (triglyceride) after 7 thaws in the cold, 3 thaws at room temperature, and after 18 months of storage. As these decreases were less than day-to-day reported variation of lipids, they do not appear to be physiologically significant. Cytokine (IL-6, TNF α, IL-8, IL-1β) and hsCRP concentrations decreased by 22%, 8%, 8%, 22%, and 35%, respectively; only IL-6, IL-1β and hsCRP concentrations showed significant decreases greater than day-to-day variations of 20%. For measured triglyceride and cytokine, but not cholesterol concentrations, decreases with freeze/thaw cycles were greater when concentrations were elevated. Multiple thaws also led to changes in lipoprotein sizing, specifically to a shift from medium- and large-sized HDL particles to small-sized HDL particles and from large LDL to IDL. No changes occurred for VLDL particle numbers. Though particle sizes changed, the HDL proteome did not change with multiple thaw cycles or after long term storage. Overall, the results demonstrate that it is possible to use previously obtained frozen samples for plasma cholesterol and triglyceride levels and the lipoprotein proteome, and lipoprotein sizing and cytokine concentrations if one knows the history of the sample as changes should be relative to one another. Sandra L Rebholz1 John T Melchior1 Jeffrey A Welge2 Alan T Remaley3 W SeanDavidson1 and Laura A Woollett1* Cholesterol Cytokines Lipoprotein sizing HDL proteome Apolipoprotein A-I preterm low birthweight 2017-06-15T14:51:15+05:30 2017-06-15T14:51:17+05:30 2017-06-15T14:51:17+05:30 5 Adobe InDesign CS6 (Windows) uuid:2cc07d71-5d43-405b-875e-e580c1c9b845 xmp.did:FE00469DB0C7E411AEB789ACBE3823B3 xmp.id:307F92FBAB51E711A74BFCCB8DEDAD05 proof:pdf converted from application/x-indesign to application/pdf Adobe InDesign CS6 (Windows) / 2017-06-15T14:51:16+05:30 xmp.iid:F383C0EBAB51E711A74BFCCB8DEDAD05 xmp.did:FE00469DB0C7E411AEB789ACBE3823B3 xmp.did:FE00469DB0C7E411AEB789ACBE3823B3 default Laura A Woollett, Departments of Pathology and Laboratory Medicine,Ohio, USA, E-mail: laura.woollett@uc.edu Citation: Rebholz SL, Melchior JT, Welge JA,Remaley AT, Davidson WS, et al. (2017) Effects ofMultiple Freeze/Thaw Cycles on Measurements ofPotential Novel Biomarkers Associated With AdversePregnancy Outcomes. 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Adverse Pregnancy Outcomes © 2017 Rebholz SL, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. World-wide, millions of women enter preterm labor or have small newborns. Effective biomarkers are needed to identify women at risk for these adverse outcomes. A time and cost effective way to examine any potentially new biomarkers in samples collected during prior studies or trials that had been assayed for other metabolites would be highly useful. Thus, the current study aimed to determine if samples that had been previously thawed and re-frozen could be re-assayed for novel biomarkers, those being lipoprotein composition (sizing, proteome, lipids) and combined cholesterol and cytokine concentrations. Fasting blood was collected from 51 young non-pregnant women and plasma was analyzed for lipoprotein composition and cytokine concentrations after multiple freeze/thaw cycles in the cold or at room temperature and after being stored for 18 months. Plasma LDL-C, HDL-C, total cholesterol, and triglyceride concentrations decreased <6-7% (cholesterols) or <20% (triglyceride) after 7 thaws in the cold, 3 thaws at room temperature, and after 18 months of storage. As these decreases were less than day-to-day reported variation of lipids, they do not appear to be physiologically significant. Cytokine (IL-6, TNF α, IL-8, IL-1β) and hsCRP concentrations decreased by 22%, 8%, 8%, 22%, and 35%, respectively; only IL-6, IL-1β and hsCRP concentrations showed significant decreases greater than day-to-day variations of 20%. For measured triglyceride and cytokine, but not cholesterol concentrations, decreases with freeze/thaw cycles were greater when concentrations were elevated. Multiple thaws also led to changes in lipoprotein sizing, specifically to a shift from medium- and large-sized HDL particles to small-sized HDL particles and from large LDL to IDL. No changes occurred for VLDL particle numbers. Though particle sizes changed, the HDL proteome did not change with multiple thaw cycles or after long term storage. Overall, the results demonstrate that it is possible to use previously obtained frozen samples for plasma cholesterol and triglyceride levels and the lipoprotein proteome, and lipoprotein sizing and cytokine concentrations if one knows the history of the sample as changes should be relative to one another. Sandra L Rebholz1 John T Melchior1 Jeffrey A Welge2 Alan T Remaley3 W SeanDavidson1 and Laura A Woollett1* Cholesterol Cytokines Lipoprotein sizing HDL proteome Apolipoprotein A-I preterm low birthweight 2017-06-15T14:51:15+05:30 2017-06-15T14:51:24+05:30 2017-06-15T14:51:24+05:30 5 Adobe InDesign CS6 (Windows) uuid:3e58a650-89aa-4735-9fae-ff18e1a82d3b xmp.did:FE00469DB0C7E411AEB789ACBE3823B3 xmp.id:307F92FBAB51E711A74BFCCB8DEDAD05 proof:pdf converted from application/x-indesign to application/pdf Adobe InDesign CS6 (Windows) / 2017-06-15T14:51:16+05:30 xmp.iid:F383C0EBAB51E711A74BFCCB8DEDAD05 xmp.did:FE00469DB0C7E411AEB789ACBE3823B3 xmp.did:FE00469DB0C7E411AEB789ACBE3823B3 default Laura A Woollett, Departments of Pathology and Laboratory Medicine,Ohio, USA, E-mail: laura.woollett@uc.edu Citation: Rebholz SL, Melchior JT, Welge JA,Remaley AT, Davidson WS, et al. (2017) Effects ofMultiple Freeze/Thaw Cycles on Measurements ofPotential Novel Biomarkers Associated With AdversePregnancy Outcomes. J Clin Lab Med 2(1): doi http://dx.doi.org/10.16966/jclm.107 Adobe PDF Library 10.0.1 False endstream endobj 408 0 obj <> endobj 2503 0 obj <>/Metadata 407 0 R/Names 2504 0 R/Outlines 327 0 R/PageMode/UseOutlines/Pages 406 0 R/StructTreeRoot 409 0 R/Type/Catalog/ViewerPreferences<>>> endobj xref 0 1 0000000000 65535 f 407 2 0000896940 00000 n 0000906047 00000 n 2503 1 0000910939 00000 n trailer <<4321E17DD60F8049BD49F1F78AE93072>]/Prev 116>> startxref 911143 %%EOF