pha-2-glycoprotein 1 Plasminogenisoform 1 precursor PREDICTED: similar to immunoglobulin lambda-like polypeptide 1 Prothrombin; coagulation factor II Putative uncharacterized protein DKFZp686G11190 Recombinant IgG3 heavy chain Vitamin D-binding protein/group specific component Group 1 1.44 2.09 21.12 3.86 2.94 2.25 1.20 1.44 1.33 2.21 1.65 1.89 2.01 21.43 3.05 22.63 1.85 1.82 1.55 1.99 1.58 1.58 1.74 2.57 1.96 2.65 2.59 2.37 p-value,0.05,0.001 NS,0.001,0.001,0.001 NS,0.005,0.05,0.001,0.001,0.05,0.05 NS,0.001 NS,0.001,0.05,0.05,0.01,0.001,0.05,0.005,0.01,0.001,0.005,0.05,0.001 Group 2 21.10 21.01 21.94 21.48 21.52 1.02 1.41 1.06 1.15 21.13 21.19 21.31 1.30 21.31 21.13 1.27 21.13 21.12 1.11 21.03 1.02 21.11 1.00 21.39 1.08 21.33 21.28 21.09 p-value NS NS,0.05 NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS Group 3 1.35 1.84 1.02 1.09 1.14 1.43 1.60 21.04 1.44 1.24 1.29 1.42 1.28 1.57 1.53 21.50 1.30 1.06 1.70 1.52 1.07 1.82 1.12 1.21 1.20 1.32 1.36 1.37 p-value NS,0.01 NS NS NS,0.05,0.05 NS,0.005 NS NS NS NS NS NS NS NS NS,0.05 NS NS,0.05 NS NS NS NS NS NS Group 4 1.17 2.01 21.82 21.01 1.12 1.08 1.36 21.27 21.32 21.15 21.29 1.01 1.83 21.61 21.03 p-value NS,0.01,0.05 NS NS NS NS NS NS NS NS NS NS NS NS NS 21.06 1.38 1.14 21.16 1.17 21.03 21.19 1.18 1.06 1.26 1.21 21.07 NS NS NS NS NS NS NS NS NS NS NS NS NS: p-value is not significant. – Changes are relative increases or decreases from the second visit compared to the first expressed as averaged for each group. doi:10.1371/journal.pone.0031031.t004 1 protective response of the host during increase of an oxidative stress. Ceruloplasmin is produced in the liver and our findings suggest that its expression increases during periods of METH use. These changes may remit following cessation of METH use, explaining why we did not observe changes in ceruloplasmin expression in patients after short or long term METH abstinence. In our previous plasma and cerebrospinal fluid profiling experiments of HIV-infected individuals “1635054 we also found ceruloplasmin to be differentially expressed. Interestingly, this protein was down regulated in CSF of subjects with HIV dementia whereas it was up-regulated in plasma, suggesting that the CSF-toplasma ratio of ceruloplasmin may be an important correlate of HIV-associated neurocognitive impairment. The observation that changes in the plasma proteome were largely limited to subjects who continued to use METH was also unexpected. Because of this, we could not confidently identify a signature of METH use versus METH abstinence. Continued use of METH is by its nature an unstable condition, and users “crash”after METH binges. Similarly the plasma proteome 9353416 changes we found in Group 1 were not consistent with purchase PF-562271 adaptive long-term changes, suggesting that METH use continues to lead to instability in normal physiology such as the complement and coagulation systems even during chronic use. It has to be noted that some of the subjects in Groups 2 and 3 were on treatment for HIV infection whereas none of those in Group 1 were treated for HIV. Our previous studies revealed that the proteome changes rapidly within the first two weeks of infection and comes back to background, especially if cART is implemented. HIVinduced changes in proteome become obvious when viral infection is not well controlled and inflammation is on the rise. Therefore the relationship between METH use and HIV infection and the changes found in Group 1 is likely complex. During the la

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