9.5 52.9 44.1 51.4 29.3 106.5 98.3 72 38.2 90.6 53.3 69.3 52.0 89.0 52.9 The protein sequences have no homolog sequence in UniProtKB database. doi:10.1371/journal.pone.0031031.t003 increased risk of HIV has been substantiated by multiple studies. Despite treatment, HIV infection is associated with a significant degree of neurocognitive impairment in one out of every seven subjects. In SIV infected rhesus monkeys, METH treatment led to immune changes as well as increased virus in the brain. Therefore, it can be 
expected that the ” combined effects of HIV infection and METH use will have not only additive or 393514-24-4 perhaps synergistic adverse effects on the brain, but also will have a detrimental impact on many physiological functions including the immune system. We postulated that such effects would be reflected by changes in plasma proteome. Alterations in the plasma can affect the brain via communications between the periphery and the CNS, as well as through breach of blood-brain barrier that can occur in HIV infection as well as drug abuse. Interestingly the majority of significant changes were observed between visits in Group 1, those who did not discontinue using METH. Two major pathways were affected. First, was the complement cascade. This system is usually activated by HIV-1 infection alone; here continued METH use leads to further increase of C4A and C5 components. Such an increase likely represents non-specific response to an insult. The second activated system was blood coagulation and up-regulation of plasminogen, fibrinogen and kininogen. It has been shown that one toxic effect of METH use is disseminated intravascular coagulation, which is a pathological activation of coagulation mechanisms. As the small clots consume coagulation proteins and platelets, normal coagulation is disrupted; normal blood flow to organs is disrupted and this can lead to abnormal bleeding. None of the subjects in this analysis had DIC but reported use of METH, at least in the setting of concurrent HIV infection, appears to result in less severe activation of coagulation pathways. Increased expression of ceruloplasmin and hemopexin can represent a response to modulate increases in oxidative stress resulting from HIV infection and METH use. We expected that in response to METH exposure oxidative stress should be significantly enhanced and be correlated to increased expression of antioxidant enzymes, similar to our findings in SIV infected monkeys administered a chronic METH regimen. Ceruloplasmin is a copper-binding glycoprotein oxidizing Fe2+ to Fe3+ ferroxidase without releasing radical oxygen species. Its main reported function is transport of iron across the cell membrane; however, several recent reports link this protein to an overall February 2012 | Volume 7 | Issue 2 | e31031 HIV and Drug Abuse Names Alpha 2 macroglobulin variant Alpha-1-antichymotrypsin Alpha-2-glycoprotein 1, zinc-binding Alpha-2-HS-glycoprotein Alpha2-HS glycoprotein Antithrombin III Apolipoprotein B-100 ” precursor C4A variant protein cDNA FLJ55673, highly similar to Complement factor B cDNA FLJ56652, highly similar to Hemopexin Ceruloplasmin precursor Coagulation factor XI precursor Complement C5 preproprotein Fibrinogen gamma chain Group-specific component Guanine nucleotide regulatory protein Hemopexin precursor Immunoglobulin kappa light chain V Inter-alpha globulin inhibitor H2 Inter-alpha-trypsin inhibitor family heavy chain-related protein Kininogen-1 isoform 2 Leucine-rich al