The role of the immune system in depersonalisation disorder.

OBJECTIVES: Depersonalisation-derealization disorder (DPD) is a dissociative disorder that impairs cognitive function and occupational performance. Emerging evidence indicate the levels of tumour necrosis factor-α and interleukin associated with the dissociative symptoms. In this study, we aimed to explore the role of the immune system in the pathology of DPD. METHODS: We screened the protein expression in serum samples of 30 DPD patients and 32 healthy controls. Using a mass spectrometry-based proteomic approach, we identified differential proteins that were verified in another group of 25 DPD patients and 30 healthy controls using immune assays. Finally, we performed a correlation analysis between the expression of differential proteins and clinical symptoms of patients with DPD. RESULTS: We identified several dysregulated proteins in patients with DPD compared to HCs, including decreased levels of C-reactive protein (CRP), complement C1q subcomponent subunit B, apolipoprotein A-IV, and increased levels of alpha-1-antichymotrypsin (SERPINA3). Moreover, the expression of CRP was positively correlated with visuospatial memory and the ability to inhibit cognitive interference of DPD. The expression of SERPINA3 was positively correlated with the ability to inhibit cognitive interference and negatively correlated with the perceptual alterations of DPD. CONCLUSIONS: The dysregulation of the immune system may be the underlying biological mechanism in DPD. And the expressions of CRP and SERPINA3 can be the potential predictors for the cognitive performance of DPD.

Parallel reaction monitoring with multiplex immunoprecipitation of N-glycoproteins in human serum for detection of hepatocellular carcinoma.

The N-glycosylation of proteins is one of the most important post-translational modifications relevant to various biological functions. The identification and quantification of N-glycoproteins in liquid chromatography-mass spectrometry (LC-MS) is challenging because of their low analytical sensitivity and selectivity. This is due to their microheterogeneity and the difficulty of synthesizing N-glycopeptides as an internal standard. Parallel reaction monitoring (PRM) is widely used in targeted LC-MS. The key advantage of LC-PRM is that it can identify N-glycopeptides using tandem mass spectrometry (MS/MS) fragmentation, even without an internal standard. We investigated the feasibility of analyzing N-glycoproteins using multiplex immunoprecipitation to improve sensitivity and selectivity. We targeted N-glycoproteins [α-fetoprotein (AFP), vitronectin (VTN), and α-1-antichymotrypsin (AACT)] that are abnormally glycosylated in hepatocellular carcinoma (HCC). Their tryptic N-glycopeptides were selected to determine the percentages of fucosylated N-glycopeptides using Y ions, which include glycopeptide fragments with amino acid sequences. Finally, we confirmed that the area under the receiver operating characteristic curve (AUC = 0.944) for the combination of AFP and VTN increased more so than for a single glycopeptide (AUC = 0.889 for AFP and 0.792 for VTN) with respect to discriminating between HCC and cirrhosis serum. This study shows that an LC-PRM method using multiplex N-glycoproteins immunoprecipitated from serum could be applied to develop and verify cancer biomarkers. Graphical abstract.

Circulating inflammatory biomarkers are related to cerebrovascular disease in older adults.

Objective: This investigation aimed at examining whether circulating inflammatory biomarkers C-reactive protein (CRP), interleukin-6 (IL6), and alpha 1-antichymotrypsin (ACT) were related to cerebrovascular disease (CVD) assessed by MRI. Methods: The study included nondemented elderly participants of a community-based, multiethnic cohort, who received baseline MRI scans and had CRP (n = 508), ACT (435), and IL6 (N = 357) measured by ELISA. Silent brain infarcts and white matter hyperintensities (WMH) were derived from all available MRI scans at baseline, approximately 4.4 years after blood sample collection for inflammatory biomarkers. Repeated assessments of infarcts and WMH, as well as microbleeds assessment, were performed at follow-up MRI visits around 4.5 years later. Cross-sectional and longitudinal relationship between inflammatory biomarkers and CVD were analyzed using appropriate logistic regression models, generalized linear models, or COX models. Results: After adjusting for age, sex, ethnicity, education, APOE genotype, and intracranial volume, 1 SD increase in log10IL6 was associated with infarcts on MRI {odds ratio [OR] (95% confidence interval [CI]) = 1.28 [1.02-1.60], p = 0.033}, and 1 SD increase in log10CRP and log10ACT was associated with microbleeds (OR [95% CI] = 1.46 [1.02-2.09], p = 0.041; and 1.65 [1.11-2.46], p = 0.013; respectively). One SD increase in log10ACT was also associated with larger WMH at the follow-up MRI (b = 0.103, p = 0.012) and increased accumulation of WMH volume (b = 0.062, p = 0.041) during follow-up. The associations remained significant after additional adjustment of vascular risk factors and excluding participants with clinical stroke. Conclusions: Among older adults, increased circulating inflammatory biomarkers were associated with the presence of infarcts and microbleeds, WMH burden, and progression of WMH.

Determining the Ratio of Two Types of Prostate Specific Antigens with Biochips and Gold Nanoparticles for Accurate Prostate Cancer Diagnosis.

Prostate-specific antigen (PSA) is a well-known biomarker for prostate-cancer diagnosis. However, the serum PSA measurement alone is insufficient for accurate diagnoses because the correlation with cancer is weak within the gray zone-the biomarker level range wherein a clear-cut diagnosis is impossible. As such, accurate prostate cancer diagnosis has been supplemented by measurements of the ratio of two types of PSA: free PSA (fPSA) and complexed PSA (cPSA; α-1-antichymotrypsin-bound PSA). Herein, we describe a new method for measuring the ratio of these two types of PSA by using gold nanoparticles (AuNPs) and biochips. Both types of PSA in a sample are captured by the antibody immobilized on a biochip based on self-assembled monolayers on gold. fPSA and cPSA on the biochip are then distinguished by AuNPs that present antibodies against fPSA and cPSA, respectively. The presence of PSAs in a sample is detected with laser desorption/ionization time-of-flight mass spectrometry by observing reporter molecules, called amplification tags (Am-tags), on the AuNPs. One of the reporter molecules is an Am-tag without isotope labeling, and the other is a deuterium-labeled Am-tag (dAm-tag). These tags amplify mass signals so as to enhance the sensitivity of the method. A comparison of the mass intensities between the Am-tag and dAm-tag signals allows the determination of the ratio between fPSA and cPSA. We validated the selective measurement of fPSA and cPSA at different ratios in 50, 75, and 100 pM of total PSA (fPSA + cPSA) solutions corresponding to the gray zone in prostate-cancer diagnosis (4 - 10 ng/mL). Finally, the two types of PSA were spiked in fetal bovine serum at various ratios, and our strategy greatly afforded their accurate ratios as spiked based on a constructed calibration curve. These results clearly indicate that the strategy is applicable to human serum as a diagnostic and prognostic assay for prostate cancer.

Identification of haptoglobin peptide as a novel serum biomarker for lung squamous cell carcinoma by serum proteome and peptidome profiling.

To date, a number of potential biomarkers for lung squamous cell cancer (SCC) have been identified; however, sensitive biomarkers are currently lacking to detect early stage SCC due to low sensitivity and specificity. In the present study, we compared the 7 serum proteomic profiles of 11 SCC patients, 7 chronic obstructive pulmonary disease (COPD) patients and 7 healthy smokers as controls to identify potential serum biomarkers associated with SCC and COPD. Two-dimensional difference gel electrophoresis (2D-DIGE) and mass-spectrometric analysis (MS) using an affinity column revealed two candidate proteins, haptoglobin (HP) and apolipoprotein 4, as biomarkers of SCC, and α-1-antichymotrypsin as a marker of COPD. The iTRAQ technique was also used to identify SCC-specific peptides. HP protein expression was significantly higher in SCC patients than in COPD patients. Furthermore, two HP protein peptides showed significantly higher serum levels in SCC patients than in COPD patients. We established novel polyclonal antibodies for the two HP peptides and subsequently a sandwich enzyme-linked immunosorbent assay (ELISA) for the quantification of these specific peptides in patient and control sera. The sensitivity of detection by ELISA of one HP peptide (HP216) was 70% of SCC patients, 40% of COPDs patients and 13% of healthy controls. We also measured CYFRA, a cytokeratin fragment clinically used as an SCC tumor marker, in all the 28 cases and found CYFRA was detected in only seven SCC cases. However, when the measurement of HP216 was combined with that of CYFRA, 100% (10 of 10 patients) of SCC cases were detected. Our proteomic profiling demonstrates that the SCC-specific HP peptide HP216 may potentially be used as a diagnostic biomarker for SCC.

Markers of iron status are associated with stage of pregnancy and acute-phase response, but not with parity among pregnant women in Guinea-Bissau.

While prenatal Fe supplementation prevents maternal Fe deficiency and anaemia, it is uncertain whether it improves infant health outcomes, at least when taken by Fe-replete women. Inflammation as well as physiological changes complicates the assessment of Fe status during pregnancy. In the present study, we measured the concentrations of serum ferritin and soluble transferrin receptors (sTfR), Hb and the acute-phase proteins C-reactive protein (CRP) and α1-antichymotrypsin (ACT) in a cross-sectional study among 738 pregnant women attending antenatal care in Guinea-Bissau, West Africa. Multiple linear regression analysis was used to identify the predictors of Fe status markers. The mean gestational age was 23 (sd 7) weeks. Serum ferritin values were lower with progressing gestation, from 27% lower during weeks 16-20 of gestation up to 59% lower after 29 weeks of gestation compared with early pregnancy. Using cut-off values for Fe deficiency as established in non-pregnant individuals, 52% of the women had sTfR levels >2·3 mg/l, while only 25% had serum ferritin levels 2·3 mg/l decreased to 47% after adjustment for elevated serum CRP and ACT levels. On the contrary, the proportion of serum ferritin < 12 µg/l increased to 33% after adjustment for ACT and CRP. The high proportion of elevated serum sTfR calls for pregnancy-specific cut-offs since increased erythropoiesis is expected in response to increased plasma volume of pregnancy. The present study further underlines the need to adjust for inflammation when serum sTfR and serum ferritin are used to assess Fe status in pregnancy.

Biopsy Quantitative Patohistology and Seral Values of Prostate Specific Antigen-Alpha (1) Antichymotrypsine Complex in Prediction of Adverse Pathology Findings after Radical Prostatectomy.

In this prospective study we examined the utility of parameters obtained on prostate needle biopsy and prostate specific antigen-alpha(1)-antichymotripsine complex (PSA-ACT) to predict adverse pathologic findings after radical prostatectomy. 45 consecutive patients assigned for radical prostatectomy due to clinically localized prostate cancer were included in the study. Prostate biopsy parameters such as number of positive cores, the greatest percentage of tumor in the positive cores, Gleason score, perineural invasion, unilaterality or bilaterality of the tumor were recorded. PSA-ACT was determined using sandwich immunoassay chemiluminiscent method (Bayer, Tarrytown, New York). We analyzed relationship of preoperative PSA, PSA-ACTand quantitative biopsy parameters with final pathology after prostatectomy. Adverse findings were considered when extracapsular extension of cancer (pT3) was noted. Postoperatively, 29 (64.4%) patients were diagnosed with pT2 disease and 16 (35.6%) with pT3 disease. There was a significant difference in localized vs. locally advanced disease in number of positive biopsy cores (p<0.001), greatest percentage of tumor in the core (p=0.008), localization of the tumor (p=0.003) and perineural invasion (p=0.004). Logistic regression was used to develop a model on the multivariate level. It included number of positive cores and PSA-ACT and was significant on our cohort with the reliability of 82.22%. The combination of PSA-ACT and a large scale of biopsy parameters could be used in prediction of adverse pathologic findings after radical prostatectomy. Clinical decisions and patients counselling could be influenced by these predictors but further confirmation on a larger population is necessary.

Alpha-1 protease inhibitor and antichymotrypsin levels in acute pancreatitis.

BACKGROUND: Acute pancreatitis with high mortality of severe onset is still a major problem in medicine. Early identification of the severity of the disease is critical for effective treatment. Many markers have been tried and are still being tested. The ideal marker should be able to identify the cases and distinguish between mild and severe. METHODS: This prospective study included 34 cases (14 males, 20 females, mean age: 58 years) of acute pancreatitis and 33 cases (17 males, 16 females, mean age: 53 years) as a control group. Mild (n=29) and severe (n=5) cases were compared with respect to serum levels of amylase, C-reactive protein (CRP), alpha-1-protease inhibitor, and antichymotrypsin on admission and 24 and 48 hours (h) after admission. RESULTS: Alpha-1 protease inhibitor and antichymotrypsin levels were significantly elevated in the first 24 h; however, CRP peaked after 48 h in the acute pancreatitis group. While CRP showed significantly higher concentrations in patients with severe pancreatitis, alpha-1-protease inhibitor and antichymotrypsin levels changed slightly, but without significance, in severe cases. CONCLUSION: Alpha-1 protease inhibitor and antichymotrypsin are early events in acute pancreatitis, with high levels on admission. Activation of these variables declines after 24 h. These markers may have early diagnostic value in patients with acute pancreatitis. Because neither of them is good at discrimination of mild and severe cases in the disease, they should not be incorporated into routine clinical investigations.

S-glutathionylated serine proteinase inhibitors as plasma biomarkers in assessing response to redox-modulating drugs.

Many cancer drugs impact cancer cell redox regulatory mechanisms and disrupt redox homeostasis. Pharmacodynamic biomarkers that measure therapeutic efficacy or toxicity could improve patient management. Using immunoblot analyses and mass spectrometry, we identified that serpins A1 and A3 were S-glutathionylated in a dose- and time-dependent manner following treatment of mice with drugs that alter reactive oxygen or nitrogen species. Tandem mass spectrometry analyses identified Cys(256) of serpin A1 and Cys(263) of serpin A3 as the S-glutathionylated residues. In human plasma from cancer patients, there were higher levels of unmodified serpin A1 and A3, but following treatments with redox active drugs, relative S-glutathionylation of these serpins was higher in plasma from normal individuals. There is potential for S-glutathionylated serpins A1 and A3 to act as pharmacodynamic biomarkers for evaluation of patient response to drugs that target redox pathways.

Identification of potential prognostic biomarkers in patients with untreated, advanced pancreatic cancer from a phase 3 trial (Cancer and Leukemia Group B 80303).

BACKGROUND: Patients with advanced stage adenocarcinoma of the pancreas have a poor prognosis. The identification of prognostic and/or predictive biomarkers may help stratify patients so that therapy can be individualized. METHODS: Serum samples from patients enrolled in the Cancer and Leukemia Group B 80303 phase 3 trial, "Randomized Study of Gemcitabine With Versus Without Bevacizumab in Patients With Locally Advanced or Metastatic Adenocarcinoma of the Pancreas" were used to discover novel biomarkers. For the discovery phase, 40 sera were selected based on length of survival and type of therapy, and subjected to liquid chromatography coupled to tandem mass spectrometry analysis (LC-MS-MS). The top features (proteins) were then further selected for validation by enzyme-linked immunosorbent assay (ELISA). RESULTS: Quantification by nano-LC-MS-MS resulted in 1452 peptides mapping to 156 proteins across all 40 samples, 92 of which had 2 or more peptides. After curation of the data, the authors selected 1 putative prognostic protein, alpha 1-antichymotrypsin (AACT), and 2 putative predictive proteins, histidine-rich glycoprotein (HRG) and complement factor H (CFH), for validation by ELISA. AACT was found to be negatively correlated with overall survival (τ = -0.30 [-0.38, -0.22]; P < .00001). There was no evidence for interaction with bevacizumab and HRG, but there was some evidence for a weak positive correlation of HRG with overall survival (τ = 0.11 [0.03, 0.19]; P < .01). CFH was found to be neither a predictive nor a prognostic factor for overall survival. CONCLUSIONS: AACT may be a useful prognostic marker in patients with advanced stage pancreatic carcinoma, although additional validation studies are needed.

Signal amplification by magnetic force on polydiacetylene supramolecules for detection of prostate cancer.

A method in which a permanent magnet is introduced onto polydiacetylene (PDA) vesicle chips is introduced for enhancement of the fluorescence of PDA vesicles. This strategy can be applied to general antibody-based PDA vesicle chips to detect clinically important biomarkers for disease diagnosis.

Levels of acute inflammatory biomarkers in advanced prostate cancer patients with α2-macroglobulin deficiency.

C-reactive protein (CRP), serum amyloid A (SAA), interleukin-6 (IL-6), α1-antitrypsin (α1AT), α1-acid glycoprotein (α1AG) and ceruloplasmin (CP) are acute inflammatory biomarkers that increase in various conditions including infection, inflammation, malignancy and tissue disturbance. In contrast, α2-macroglobulin (α2M) is involved in inflammation through its function as a carrier protein of IL-6. We had previously reported on advanced prostate cancer (PCa) patients with multiple distant bone metastases in whom serum α2M levels were markedly decreased (α2M deficiency). However, the relationship between serum levels of α2M and acute inflammatory biomarkers in PCa patients with or without α2M deficiency has not been demonstrated. In the present study, we examined serum levels of CRP, SAA, IL-6, α1AT, α1AG and CP in PCa patients with or without α2M deficiency to establish clinical significance and changes in these biomarkers during PCa disease progression. We found that upon addition of recombinant IL-6 (rIL-6) to serum from PCa patients with α2M deficiency, since a function of α2M is to bind and stabilize IL-6, the α2M-IL-6 complex and free endogenous IL-6 were not detectable. Serum levels of the α2M-independent markers, α1AT, α1AG and CP, in all PCa patients regardless of α2M deficiency were significantly higher than in healthy controls, but those of the α2M-dependent molecules, CRP, SAA and IL-6, were not increased in PCa patients with α2M deficiency. Therefore, quantitation of both α2M-dependent (CRP, SAA and IL-6) and α2M-independent (α1AT, α1AG and CP) acute inflammatory biomarkers in advanced PCa patients may be an auxiliary indicator, together with prostate-specific antigen (PSA), to monitor PCa disease progression.

Discovery of lung cancer biomarkers by profiling the plasma proteome with monoclonal antibody libraries.

A challenge in the treatment of lung cancer is the lack of early diagnostics. Here, we describe the application of monoclonal antibody proteomics for discovery of a panel of biomarkers for early detection (stage I) of non-small cell lung cancer (NSCLC). We produced large monoclonal antibody libraries directed against the natural form of protein antigens present in the plasma of NSCLC patients. Plasma biomarkers associated with the presence of lung cancer were detected via high throughput ELISA. Differential profiling of plasma proteomes of four clinical cohorts, totaling 301 patients with lung cancer and 235 healthy controls, identified 13 lung cancer-associated (p < 0.05) monoclonal antibodies. The monoclonal antibodies recognize five different cognate proteins identified using immunoprecipitation followed by mass spectrometry. Four of the five antigens were present in non-small cell lung cancer cells in situ. The approach is capable of generating independent antibodies against different epitopes of the same proteins, allowing fast translation to multiplexed sandwich assays. Based on these results, we have verified in two independent clinical collections a panel of five biomarkers for classifying patient disease status with a diagnostics performance of 77% sensitivity and 87% specificity. Combining CYFRA, an established cancer marker, with the panel resulted in a performance of 83% sensitivity at 95% specificity for stage I NSCLC.

Apolipoprotein A1 and C-terminal fragment of α-1 antichymotrypsin are candidate plasma biomarkers associated with acute renal allograft rejection.

BACKGROUND: Current diagnostic methods of renal allograft rejection are neither sensitive nor specific. Needle biopsies are invasive and associated with patient morbidity. Thus, it is desirable to develop noninvasive tests to predict and diagnose rejection. METHODS: Using a case-control approach, surface-enhanced laser desorption/ionization time-of-flight mass spectrometry was used to identify plasma proteins associated with renal allograft rejection. From each rejection patient (n=16), two plasma samples (one near the biopsy date and the other at a time postbiopsy) were compared. Biopsy-confirmed nonrejection patients (n=48) were further analyzed as controls. Antibody-based quantitative enzyme-linked immunosorbent assay was performed to validate candidate biomarker apolipoprotein A1 (Apo A1) in a subset of the original and a second cohort of biopsy-confirmed rejection (n=40) and nonrejection (n=70) patients. RESULTS: Twenty-two proteins/peptides showed significant differences between rejection and postrejection samples. Peptides 5191 Da and 4467 Da detected rejection with 100% sensitivity and 94% specificity. The 4467 Da peptide was identified as the C-terminal fragment of α-1 antichymotrypsin and a 28 kDa protein was determined as Apo A1. Both protein levels were significantly lower at rejection compared with postrejection. Protein levels of nonrejection patients were similar to the postrejection samples. Apo A1 enzyme-linked immunosorbent assay results showed significantly lower Apo A1 levels (P=0.001 for the original and P=4.14E-11 for the second cohort) at the time of rejection compared with nonrejection which coincides with the SELDI findings. CONCLUSIONS: Together α-1 antichymotrypsin, Apo A1, and the unidentified 5191 Da peptide provide a plasma molecular profile, and this is associated with acute cellular renal allograft rejection.

Development of quantitative plasma N-glycoproteomics using label-free 2-D LC-MALDI MS and its applicability for biomarker discovery in hepatocellular carcinoma.

There has been rapid progress in the development of clinical proteomic methodologies with improvements in mass spectrometric technologies and bioinformatics, leading to many new methodologies for biomarker discovery from human plasma. However, it is not easy to find new biomarkers because of the wide dynamic range of plasma proteins and the need for their quantification. Here, we report a new methodology for relative quantitative proteomic analysis combining large-scale glycoproteomics with label-free 2-D LC-MALDI MS. In this method, enrichment of glycopeptides using hydrazide resin enables focusing on plasma proteins with lower abundance corresponding to the tissue leakage region. On quantitative analysis, signal intensities by 2-D LC-MALDI MS were normalized using a peptide internal control, and the values linked to LC data were treated with DeView™ software. Our proteomic method revealed that the quantitative dynamic ranged from 10² to 106 pg/mL of plasma proteins with good reproducibility, and the limit of detection was of the order of a few ng/mL of proteins in biological samples. To evaluate the applicability of our method for biomarker discovery, we performed a feasibility study using plasma samples from patients with hepatocellular carcinoma, and identified biomarker candidates, including ceruloplasmin, alpha-1 antichymotrypsin, and multimerin-1.

Development of a sensitive detection method of cancer biomarkers in human serum (75%) using a quartz crystal microbalance sensor and nanoparticles amplification system.

A simple and sensitive sensor method for cancer biomarkers [prostate specific antigen (PSA) and PSA-alpha 1-antichymotrypsin (ACT) complex] analysis was developed, to be applied directly with human serum (75%) by using antibody modified quartz crystal microbalance sensor and nanoparticles amplification system. A QCM sensor chip consisting of two sensing array enabling the measurement of an active and control binding events simultaneously on the sensor surface was used in this work. The performance of the assay and the sensor was first optimised and characterised in pure buffer conditions before applying to serum samples. Extensive interference to the QCM signal was observed upon the analysis of serum. Different buffer systems were then formulated and tested for the reduction of the non-specific binding of sera proteins on the sensor surface. A PBS buffer containing 200 microg mL(-1) BSA, 0.5 M NaCl, 500 microg mL(-1) dextran and 0.5% Tween 20, was then selected which eliminated the interfering signal by 98% and enabled the biomarker detection assay to be performed in 75% human serum. By using Au nanoparticles to enhance the QCM sensor signal, a limit of detection of 0.29 ng mL(-1) PSA and PSA-ACT complex (in 75% serum) with a linear dynamic detection range up to 150 ng mL(-1) was obtained. With the achieved detection limit in serum samples, the developed QCM assay shows a promising technology for cancer biomarker analysis in patient samples.

Proteomic analysis of plasma from patients undergoing coronary artery bypass grafting reveals a protease/antiprotease imbalance in favor of the serpin alpha1-antichymotrypsin.

We used proteomics to identify systematic changes in the plasma proteins of patients undergoing coronary artery bypass grafting (CABG) by means of cardiopulmonary bypass surgery. It is known that, after CABG, a complex systemic inflammatory responses ensues that favors the occurrence of adverse postoperative complications frequently recognizing inflammation itself and/or thrombosis as the underlying mechanism. We found a marked and persistent postoperative increase in the levels of the serpin-protease inhibitor alpha(1)-antichymotrypsin (alpha(1)-ACT) that fully maintains the inhibitory activity blunting its protease substrate cathepsin G. An intraoperative increase followed by a rapid decline in proteases activation was documented, accompanied by a substantial induction of leucine-rich-alpha-2-glycoprotein, a protein involved in neutrophilic granulocyte differentiation. Finally, a time-dependent alteration in the expression of haptoglobin, transthyretin, clusterin, and apoE was observed. In conclusion, we showed that after CABG, a protease/antiprotease imbalance occurs with early cathepsin G activation and a more delayed increase in alpha(1)-ACT. As cathepsin G is a serpin involved both in inflammation and coagulation activation, this confirms and expands the concept of a marked dysregulation of both inflammatory and hemostatic balances occurring after CABG. The pharmacologic modulation of this imbalance may be a new therapeutic target to reduce postoperative complications.

Body composition of HIV-positive patients with pulmonary tuberculosis: a cross-sectional study in Mwanza, Tanzania.

To estimate the weight deficit and body composition of cases of pulmonary TB (PTB), and assess the roles of HIV and the acute-phase response, a cross-sectional study was carried out in Tanzania. Weight, body mass index (BMI), arm muscle area (AMA), arm fat area (AFA) and the serum concentration of the acute-phase protein alpha(1)-antichymotrypsin (serum ACT) were evaluated for each of 532 cases of PTB and 150 'non-TB' controls. On average, the female cases of PTB not only weighed 7.8 kg less but also had BMI that were 3.1-kg/m(2) lower, AMA that were 14.8-cm(2) lower, and AFA that were 7.6-cm(2) lower than those seen in the female subjects without TB. Similarly, on average, the male cases of PTB weighed 7.1 kg less and had BMI that were 2.5-kg/m(2) lower, AMA that were 18.8-cm(2) lower and AFA that were 1.6-cm(2) lower than those seen in the male subjects without TB. Although HIV infection was associated with a 1.7-kg lower weight and a 0.6-kg/m(2) lower BMI (with deficits in both AMA and AFA) among males, it was not associated with any such deficits among the female subjects. Elevated serum ACT was found to be a negative predictor of BMI, AMA and AFA, partially explaining the effects of the PTB but not those of the HIV. There is need for a better understanding of the determinants and effects of loss of fat and lean body mass in HIV-positive tuberculosis.

Potential biomarkers of muscle injury after eccentric exercise.

Proteomics was utilized to identify novel potential plasma biomarkers of exercise-induced muscle injury. Muscle injury was induced in nine human volunteers by eccentric upper extremity exercise. Liquid chromatography-mass spectrometry identified 30 peptides derived from nine proteins which showed significant change in abundance post-exercise. Four of these proteins, haemoglobin alpha chain, haemoglobin beta chain, alpha1-antichymotrypsin (ACT) and plasma C-1 protease inhibitor (C1 Inh), met the criterion for inclusion based on changes in at least two distinct peptides. ACT and C1 Inh peptides peaked earlier post-exercise than creatine kinase, and thus appear to provide new information on muscle response to injury.