Negative Acute Phase Response Research Articles

Low Testosterone on Hospital Admission with COVID-19 Infection Is Associated with Increased Mortality

Objective: Males, despite equal sex-related susceptibility to COVID-19, appear at a greater risk of poor clinical outcomes and death. This suggests that serum testosterone could be a mediator. The aim of this retrospective study was to evaluate the association between serum total testosterone (TT), other prognostic indicators, and mortality in men with COVID-19. Methods: Of the 110 men consecutively admitted to Walsall Manor Hospital (with COVID-19 related symptoms) tested for SARS-CoV-2, 85 were positive and 27 of these men died. Serum TT was compared (rank-sum test) between men negative and positive for SARS-CoV-2, and this was followed by establishing factors associated with mortality in the latter group (rank-sum, logistic, Cox regression analyses). No patient was on testosterone therapy (TTh). Results: No significant difference (p = 0.12, rank-sum test) in serum TT between men positive [median TT (IQR) = 3.9 (1.9–7.22) nmol/L, 0 days (median) postadmission] and negative [median TT (IQR) = 5.9 (2.69–10.1) nmol/L, 2 days (median) postadmission] for SARS-CoV-2 was observed. Serum TT was lower (p = 0.0011, rank-sum test) in men with COVID-19 who died [median TT (IQR) = 2.0 (1.5–3.6) nmol/L] compared with survivors [median TT (IQR) = 5.0 (2.6–9.4) nmol/L]. Comorbidities obtained via medication history were not associated with mortality. Mortality (logistic regression) was associated with only age and serum TT (odds ratio: 0.77, 95% confidence intervals [CI]: 0.64–0.91). Survival (Cox regression) was inversely associated with serum TT (continuous variable, hazard ratio [HR]: 0.85) (95% CI: 0.74–0.98), stratified by median, TT ≥3.9 nmol/L (reference, TT <3.9 nmol/L), HR: 0.24 (95% CI: 0.089–0.63). Conclusions: Serum TT was inversely associated with mortality in men with COVID-19 and requires measurement at admission and while managing long COVID. Future research should establish whether low serum TT, possibly associated with negative acute phase response, contributes to poorer prognosis and a role for TTh.

Serum cystatin C levels are decreased in type 1 diabetes mellitus patients with diabetic ketoacidosis.

Cystatin C is a marker of renal function and risk factor for cardiovascular disease. Patients with acute myocardial infarction showed a significant decrease in cystatin C levels. It is unknown whether reduced serum cystatin C levels are connected to acute events or represent a negative acute phase response. The current study aimed to assess the association between cystatin C and the existence of diabetic ketoacidosis (DKA), an acute event in individuals with type 1 diabetes mellitus (T1DM). Cystatin C was measured in the control group (N.=322) and in T1DM patients with (N.=161) and without DKA (N.=146). Data were compared according to diabetes and ketoacidosis status. Correlation analysis was used to identify factors associated with cystatin C levels. A multiple stepwise regression analysis was used to determine which of the parameters that were significantly correlated with cystatin C in univariate analysis were independently related to cystatin C. Then, we assessed the independent association between cystatin C and the occurrence of DKA in T1DM patients. Serum cystatin C levels were lower in patients with DKA than in patients without DKA. After adjustment for age, sex, fasting plasma glucose and creatinine, cystatin C was positively correlated with the duration of diabetes, systolic blood pressure (SBP), total cholesterol, triglycerides, uric acid and low-density lipoprotein cholesterol (P=0.004, P=0.022, P=0.013, P=0.035, P=0.006, P=0.012, respectively) and negatively correlated with hemoglobin (P<0.001). The duration of diabetes (P<0.001), total cholesterol (P=0.002), hemoglobin (P<0.001), SBP (P=0.011) and serum creatinine (P<0.001) were independently associated with cystatin C. Furthermore, we found that cystatin C was independently associated with the occurrence of DKA in T1DM patients (OR=0.004, 95% CI: 0.000-0.079, P<0.001). Cystatin C was decreased in T1DM patients with DKA and was found to be an independent predictor of the occurrence of DKA in T1DM patients. The reduction in cystatin C levels might be significantly connected with acute events.

MiR-155 and other microRNAs downregulate drug metabolizing cytochromes P450 in inflammation

In conditions of acute and chronic inflammation hepatic detoxification capacity is severely impaired due to coordinated downregulation of drug metabolizing enzymes and transporters. Using global transcriptome analysis of liver tissue from donors with pathologically elevated C-reactive protein (CRP), we observed comparable extent of positive and negative acute phase response, where the top upregulated gene sets included immune response and defense pathways while downregulation occurred mostly in metabolic and catabolic pathways including many important drug metabolizing enzymes and transporters. We hypothesized that microRNAs (miRNA), which usually act as negative regulators of gene expression, contribute to this process. Microarray and quantitative real-time PCR analyses identified differentially expressed miRNAs in liver tissues from donors with elevated CRP, cholestasis, steatosis, or non-alcoholic steatohepatitis. Using luciferase reporter constructs harboring native and mutated 3′-untranslated gene regions, several predicted miRNA binding sites on RXRα (miR-130b-3p), CYP2C8 (miR-452-5p), CYP2C9 (miR-155-5p), CYP2C19 (miR-155-5p, miR-6807-5p), and CYP3A4 (miR-224-5p) were validated. HepaRG cells transfected with miRNA mimics showed coordinate reductions in mRNA levels and several cytochrome P450 enzyme activities particularly for miR-155-5p, miR-452-5p, and miR-6807-5p, the only miRNA that was deregulated in all four pathological conditions. Furthermore we observed strong negative correlations between liver tissue miRNA levels and hepatic CYP phenotypes. Since miR-155 is well known for its multifunctional roles in immunity, inflammation, and cancer, our data suggest that this and other miRNAs contribute to coordinated downregulation of drug metabolizing enzymes and transporters in inflammatory conditions.

Comparison of serum procalcitonin, haptoglobin and C-reactive protein levels in goats with Corynebacterium pseudotuberculosis

This study was conducted to investigate the response of acute phase proteins, mainly Haptoglobin, C-reactive protein, Procalcitonin and the negative acute phase response, especially albumin in goats suffering from C. pseudotuberculosis. A total of 19 Turkish hair goats between the ages of 1.5 and 2 years in a special dairy farm was selected for the study, consisting of 9 healthy animals and 10 with C. pseudotuberculosis. There was a statistically significant difference in serum haptoglobin, C-reactive protein, procalcitonin and albumin levels in goats with C. pseudotuberculosis, compared to the control group (p less than 0.05). The results showed that Haptoglobin, C-reactive protein and Procalcitonin produce a higher, and Alb a lower, response in goats with C. pseudotuberculosis compared to the control. The presented study suggests that C. pseudotuberculosis can influence the level of acute phase proteins in goats. These results indicate that monitoring a number of acute phase proteins can increase the diagnostic information available for this disease.

Alteration of haemostatic parameters in uncomplicated canine babesiosis.

Babesiosis is a tick-borne zoonotic disease caused by haemoprotozoan parasites. The aim of this study were to assess markers of coagulation pathways in 25 dogs with naturally occurring babesiosis caused by B. canis, compared to 10 healthy controls. Protein C (PC) and antithrombin III (AT III) activity were assessed using a chromogenic substrate test, while levels of thrombin-antithrombin (TAT) complexes, activated protein C (APC) and endothelial protein C receptor were assessed using canine-specific ELISA. AT III activity was decreased as a result of a negative acute phase response, degradation by elastase, reduced availability of glycosaminoglycans, and, most importantly, consumption as a consequence of thrombin formation. Procoagulant state and haemostatic shift towards thrombin formation are also demonstrated by elevated TAT levels. Regarding PC pathway only significant difference was found for APC. Taken together, haemostatic alterations in uncomplicated babesiosis represent a procoagulant state that is mostly reversed during treatment.

Association of serum albumin and aspartate transaminase with 5-year all-cause mortality in HIV/hepatitis C virus coinfection and HIV monoinfection

Liver disease markers have been associated with mortality in HIV-infected individuals in the modern era of effective antiretroviral therapy. Our objective was to determine which markers are most predictive of mortality in HIV-monoinfected and HIV/hepatitis C virus (HCV)-coinfected persons. We measured serum albumin, total protein, calculated globulin, aspartate transaminase (AST), and alanine transaminase in 193 HIV/HCV-coinfected and 720 HIV-monoinfected persons in the study of Fat Redistribution and Metabolic Change in HIV Infection. We evaluated associations of each marker with 5-year, all-cause mortality, adjusting for cardiovascular, HIV-related factors, inflammation, renal disease, muscle, and adiposity. After 5 years of follow-up, overall mortality was 21% in HIV/HCV-coinfected and 12% in HIV-monoinfected participants. After multivariable adjustment, lower albumin and higher AST were independently associated with increased mortality. Lower albumin was associated with 49% increased odds of mortality overall [per 0.5 g/dl decrease, 95% confidence interval (CI): 1.2-1.9]; the association was stronger in HIV/HCV-coinfected [odds ratio (OR) = 2.1, 95% CI: 1.4-3.2] vs. HIV-monoinfected (OR = 1.3, 95% CI: 1.0-1.7; HCV-by-albumin interaction: P = 0.038). Higher AST was associated with 41% increased odds of mortality (per AST doubling; 95% CI: 1.1-1.8); associations were much stronger among HIV/HCV-coinfected (OR = 2.5, 95% CI: 1.5-4.1) than HIV-monoinfected (OR = 1.1, 95% CI: 0.8-1.5; HCV-by-AST interaction: P = 0.0042). Lower serum albumin and higher AST appear to be important mortality risk factors in HIV/HCV-coinfection, but much less so in HIV-monoinfected individuals. The association of low albumin with mortality may reflect its role as a negative acute phase response protein. AST levels do not appear to be useful in predicting mortality in HIV-monoinfection and should be considered primarily in the context of HCV-coinfection.

Persistent Unresolved Inflammation in the Mecp2-308 Female Mutated Mouse Model of Rett Syndrome.

Rett syndrome (RTT) is a rare neurodevelopmental disorder usually caused by mutations in the X-linked gene methyl-CpG-binding protein 2 (MECP2). Several Mecp2 mutant mouse lines have been developed recapitulating part of the clinical features. In particular, Mecp2-308 female heterozygous mice, bearing a truncating mutation, are a validated model of the disease. While recent data suggest a role for inflammation in RTT, little information on the inflammatory status in murine models of the disease is available. Here, we investigated the inflammatory status by proteomic 2-DE/MALDI-ToF/ToF analyses in symptomatic Mecp2-308 female mice. Ten differentially expressed proteins were evidenced in the Mecp2-308 mutated plasma proteome. In particular, 5 positive acute-phase response (APR) proteins increased (i.e., kininogen-1, alpha-fetoprotein, mannose-binding protein C, alpha-1-antitrypsin, and alpha-2-macroglobulin), and 3 negative APR reactants were decreased (i.e., serotransferrin, albumin, and apolipoprotein A1). CD5 antigen-like and vitamin D-binding protein, two proteins strictly related to inflammation, were also changed. These results indicate for the first time a persistent unresolved inflammation of unknown origin in the Mecp2-308 mouse model.

Influence of Corynebacterium pseudotuberculosis infection on level of acute phase proteins in goats

BackgroundGoat caseous lymphadenitis (CLA) is a chronic disease caused by Corynebacterium pseudotuberculosis. However, there is paucity of data about goat’s acute phase response during the course of CLA. This study was conducted to investigate the response of acute phase proteins, mainly haptoglobin (Hp), serum amyloid A (SAA) and the negative acute phase response, especially albumin after an experimental challenge of C. pseudotuberculosis and phospholipase D (PLD) in Cross bred Boer goats.ResultsSerum Hp concentration in goats challenged with C. pseudotuberculosis (inoculated with 1x109 cfu subcutaneously) showed a significant increase, 5 fold in males (0.98 ± 0.12 mg/ml) and 3 fold in females (0.66 ± 0.12 mg/ml) compared to the control (0.2 ± 0.02 mg/ml). Challenge with PLD (1 ml/20 kg body weight intravenously) also showed significant increase, 4 fold in males and females (0.89 ± 0.11 mg/ml; 0.82 ± 0.12 mg/ml) respectively compared to the control (0.2 ± 0.02 mg/ml). Albumin concentration showed a significant decrease in both treated groups compared to the control. There were no significant changes in SAA concentration between challenged and control goats.ConclusionsThere was a significant response by Hp to C. pseudotuberculosis infection and PLD challenge. This was supported by the early acute response in which Hp was detected before CLA lesions were developed. Therefore, it concluded that C. pseudotuberculosis and PLD can influence the level of acute phase proteins in goats.

Down-regulation of LXR/RXR activation and negative acute phase response pathways in colon adenocarcinoma revealed by proteomics and bioinformatics analysis.

Deficiency of vitamin D could be a major cause of colon cancer as suggested as early as 1980 by Drs. Cedric and Frank Garland of the University of California and has recently been underscored by a large European case control study. Whether vitamin D deficiency is because of inadequate intake (food and sunshine) or because of vitamin D metabolism disorder in the patient body is unknown. A proteomics approach to identify protein pathways associated with vitamin D transportation and metabolism pathways will help us understand better the pathology of the colon cancer. Lysates of colon adenocarcinoma tissues and their matched healthy tissues, from seven colon cancer patients, have been evaluated by quantitative proteomics and bioinformatics analysis to determine protein expression profiles. Unsupervised hierarchical clustering and principle component analysis (PCA) were utilized for protein expression profiling and biomarker identification, while the reporter ion ratios from tandem-mass-tagging (TMT) labeled peptides were used for quantification. Ingenuity Pathway Analysis (IPA) was used to analyze protein pathways. Proteomics analyses demonstrated that the proteins involved in vitamin D/E binding, heme/iron binding and transportation, and lipid/steroid transportation/metabolic systems were down-regulated in colon cancer and the same set of proteins were down-regulated in the LXR/RXR activation and acute-phase response pathways, revealing a plausible mechanistic connection between vitamin D deficiency, iron homeostasis, and colon cancer.

FRI0407 Relation of serum 25 oh vitamin d levels to disease activity in patients with systemic sclerosis

BackgroundThere is increasing evidence that Vitamin D has role in inflammatory processes in various diseases. Lower levels have been reported in rheumatoid arthritis, systemic lupus erythematosus and various other autoimmune...

Abstract 3788: Alpha-2 Heremans Schmid glycoprotein (AHSG) promotes migration in head and neck squamous cell carcinoma (HNSCC) cell lines.

Abstract Head and neck squamous cell carcinoma (HNSCC) is the eighth most common tumor in the world. Approximately 30,000 new cases of HNSCC are reported each year and 8,000 related deaths, in the United States. HNSCC of the oral cavity is highly metastatic and has a recurrence rate of 20%-50%, with a dismal 5-year survival rate of ∼50%. African-American males have a 5-year survival rate of ∼42% while the survival rate for Caucasian males is 52%. To date, there is no consistent means for early detection or a reliable biomarker for HNSCC, thus perpetuating the lack of improvement in mortality despite advances in delivery of treatment and surgical reconstruction. In a proteomic study seeking possible biomarkers for HNSCC, AHSG was detected at elevated levels in serum. Interestingly, we have found that some HNSCC cell lines synthesize and secrete AHSG. We have also shown in earlier studies, that the lack of AHSG reduces mammary tumor incidence and prolongs tumor latency in a mouse model for breast cancer. Together, this suggests that this hepatocellular glycoprotein that is found in most body fluids including serum could be a potential biomarker for HNSCC. AHSG is a negative acute phase response protein, which makes the findings of elevated levels of AHSG in the proteomic study most intriguing. In order to evaluate the role of AHSG in HNSCC progression (proliferation and metastatic properties) in vitro, we depleted AHSG in the HNSCC cell lineSQ20B. Thus far, we show that depletion of AHSG does not affect the proliferation of SQ20B cells. However, the depletion of AHSG mediates a decrease in migration and invasion of SQ20B cells. We are currently elucidating the molecular mechanisms of AHSG-mediated motility. This work was supported by grants from the NIH-NCI-Score 1 SC1 CA134018-01 (JO); DOD W81XWH-07-1-0254 (J.O); 5 T32 HL007735-15 (SA) and U54 CA091408 (subproject, DM). Citation Format: Pamela D. Thompson, Kurt Watson, Amos Sakwe, Josiah Ochieng, Dana Marshall. Alpha-2 Heremans Schmid glycoprotein (AHSG) promotes migration in head and neck squamous cell carcinoma (HNSCC) cell lines. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3788. doi:10.1158/1538-7445.AM2013-3788

Effects of hemodialysis on serum fetuin-A levels

Fetuin-A is a calcification inhibitor, negative acute phase response marker and cardiovascular mortality predictor in hemodialysis patients. Low levels of fetuin-A are associated with malnutrition, inflammation, decreased bone mass density, low-turnover bone and use of high calcium concentration dialysate. Hemodialysis procedure (HD) has been shown to decrease fetuin-A levels by 20%, probably due to HD-induced inflammation or acute changes in calcium metabolism. The aim of our study was to investigate effects of HD on serum fetuin-A levels. Forty clinically and hemodynamically stable hemodialysis patients (21 females, 68 (38-85) years) underwent routine bicarbonate hemodialysis or hemodiafiltration with polysulfone dialyzer. On consecutive HD dialysis solution with different calcium concentration with/without citric acid was used to assess influence of calcium shifts and parathyroid activity on fetuin-A changes during HD. All other parameters of HD were kept constant. Serum fetuin-A, calcium, phosphorus, iPTH, CRP and other biochemical parameters were measured before and after each HD. Our data show that predialysis serum fetuin-A levels have positive correlation with iPTH levels (p

Acute Phase Response of Selenium Status and Glutathione Peroxidase Activity in Blood Plasma Before and After Total Knee Arthroplasty Surgery

Several studies show the consistent results of the decrease in plasma or serum selenium (Se) after surgery, and the change is suggested to be a negative acute phase response of Se to the surgical inflammation. Plasma glutathione peroxidase (GPx), which is included in the acute phase response proteins, is a selenoenzyme. However, previous studies failed to show any changes in GPx activity before and after surgery. In the present study, we investigated the Se- and selenoenzyme responses that accompany the acute inflammatory reactions during and following major surgery. Patients who underwent elective total knee arthroplasty surgery due to knee osteoarthritis at the Department of Orthopaedic Surgery at Gunma University Hospital in Japan were studied. The plasma Se concentration was determined, and the activity of plasma GPx was measured. C-reactive protein (CRP), albumin, blood urea nitrogen (BUN), and white blood cell (WBC) count were also analysed. Increases in the inflammatory biomarkers of CRP and WBC showed inflammatory reactions with the surgery. A significant increase in plasma GPx activity (p < 0.05) and decreases in the plasma Se concentration (p < 0.05) and in serum albumin (p < 0.05) after surgery were observed. Since albumin is a Se-containing protein and represents a negative acute phase protein that provides amino acids for the production of other series of acute phase proteins, the present results suggest that there is a redistribution of plasma Se to GPx that occurs as an acute phase response, and the source of Se for GPx could be, at least partly, from albumin.

Genomic Profiling of Tumor Necrosis Factor Alpha (TNF-α) Receptor and Interleukin-1 Receptor Knockout Mice Reveals a Link between TNF-α Signaling and Increased Severity of 1918 Pandemic Influenza Virus Infection

The influenza pandemic of 1918 to 1919 was one of the worst global pandemics in recent history. The highly pathogenic nature of the 1918 virus is thought to be mediated in part by a dysregulation of the host response, including an exacerbated proinflammatory cytokine response. In the present study, we compared the host transcriptional response to infection with the reconstructed 1918 virus in wild-type, tumor necrosis factor (TNF) receptor-1 knockout (TNFRKO), and interleukin-1 (IL-1) receptor-1 knockout (IL1RKO) mice as a means of further understanding the role of proinflammatory cytokine signaling during the acute response to infection. Despite reported redundancy in the functions of IL-1β and TNF-α, we observed that reducing the signaling capacity of each of these molecules by genetic disruption of their key receptor genes had very different effects on the host response to infection. In TNFRKO mice, we found delayed or decreased expression of genes associated with antiviral and innate immune signaling, complement, coagulation, and negative acute-phase response. In contrast, in IL1RKO mice numerous genes were differentially expressed at 1 day postinoculation, including an increase in the expression of genes that contribute to dendritic and natural killer cell processes and cellular movement, and gene expression profiles remained relatively constant at later time points. We also observed a compensatory increase in TNF-α expression in virus-infected IL1RKO mice. Our data suggest that signaling through the IL-1 receptor is protective, whereas signaling through the TNF-α receptor increases the severity of 1918 virus infection. These findings suggest that manipulation of these pathways may have therapeutic benefit.

Differential Gene Expression of Cutaneous Cells Upon Exposure to Staphylococcal Enterotoxin B (SEB) Superantigen

Staphylococcus aureus, a gram‐positive bacterium initiates lesions through the production of pyrogenic toxins termed Staphylococcal enterotoxins (SEA‐J), and toxic shock syndrome toxin‐1 (TSST‐1) causing staphylococcal food poisoning and toxic shock syndrome. SEs are prototypical superantigens (sAgs), which trigger massive V‐beta specific T cell proliferation without the need for internalization, processing, or presentation resulting in elevated serum cytokine levels. The presence and the detectability of these sAgs in the sera of burn victims is not clearly understood. We have detected circulating SEA, SEB and TSST‐1 toxins among 20% of the burn victims. In this study, we aim to elucidate the chronology of intoxication along with in vitro studies to better understand the potential effects of this SEB toxin on skin cells. Primary cultures of human keratinocytes, melanocytes, dermal vascular endothelial cells and dermal fibrobalsts were grown and treated with varying doses of SEB for different lengths of time. RNA was extracted by trizol method and oligonucleotide microarray was performed. Feature extraction and statistical analysis show that genes encoding negative acute phase response proteins, oxidative stress response, NFκB signalling, Anti‐apoptosis were highly upregulated and genes responsible for death receptor signalling, endothelin‐1 signalling, growth hormone signalling were significantly downregulated. The objective of this study is to elucidate the pathogenesis of SEB intoxication in skin cells and thereby help with new treatment strategies in wound healing.We extend our heartfelt thanks to Washington Hospital ct Res Fund and Fire Fighters Burn res for their support

Selenium in Intravenous Nutrition

Selenium (Se) is an essential nutrient for human beings, with serious consequences resulting from clinical deficiency. It therefore should be provided intravenously to all patients who require parenteral nutrition (PN). Moreover, because the effects of suboptimal status are variable and unclear, this supplementation should be provided from the beginning of the course of PN. In most patients receiving PN at home or after surgery, 60-100 mcg/day will meet their requirements. Patients who commence PN already depleted in selenium may require more. Critically ill patients or those with severe burns may have higher requirements. There is good evidence that up to 400 mcg/day is beneficial in burn patients, but the evidence is inconclusive regarding the benefit of high-dose selenium in severe sepsis. Where increased Se provision is used, or in long-term PN, selenium status should be monitored by measurement of plasma Se together with a measure of systemic inflammatory response syndrome, such as C-reactive protein. There are many research issues, including which biochemical measurements best reflect tissue function, especially immune function in seriously ill patients, the clinical consequences of suboptimal biochemical Se status, whether high-dose Se improves outcome in critically ill patients, and whether extra Se always should be given with extra intakes of other antioxidants.

Down‐regulation of the hepatic selenoprotein biosynthesis machinery impairs selenium metabolism during the acute phase response in mice

The acute-phase response (APR) is characterized by an impaired metabolism of the essential trace element selenium (Se). Moreover, low-Se concentrations correlate to mortality risk in sepsis. Therefore, we analyzed the expression of the central Se transport and storage protein selenoprotein P (Sepp1) during an APR in mice. Serum Se and Sepp1 concentrations declined in parallel after injection of lipopolysaccharide to 50 and 39% of control-injected littermates, respectively. This negative APR proceeded largely independent from hepatic Sepp1 transcript concentrations. Instead, we identified a set of hepatic transcripts involved in Se metabolism, which declined coordinately during the APR, including the selenocysteine-specific elongation factor (EFsec), selenophosphate-synthetase 2 (Sephs2), selenocysteine-tRNA[Ser]Sec synthase (SecS), and phosphoseryl-tRNA[Ser]Sec kinase (Pstk). Pstk reacted most strongly and qualified as a new limiting factor for Sepp1 biosynthesis in siRNA-mediated knockdown experiments in hepatocytes in culture. Analogous experiments were performed with mice transgenic for hepatocyte-specific human Sepp1 cDNA to verify this hypothesis. Similar kinetics and effect sizes of Sepp1 expression were observed as before in wild-type mice. We conclude that hepatic translation of Sepp1 mRNA is specifically impaired during the APR. This deficit disrupts regular Se metabolism, transport, and supply to peripheral tissues and likely aggravates the pathological status.

Association of prealbumin level with mortality in patients with acute kidney injury

Acute kidney injury (AKI) is common in hospitalized patients, a population with a high prevalence of malnutrition. Pre-existing malnutrition is associated with adverse outcomes in patients with AKI. This Practice Point commentary discusses a study by Perez Valdevieso et al. that examined the association between serum prealbumin level and mortality in patients with AKI. Adjusted multivariate analyses showed that a serum prealbumin level below the group median (11 mg/dl) was independently predictive of in-hospital mortality and that for every 5 mg/dl increase in serum prealbumin level, in-hospital mortality decreased by 29%. A decreased serum prealbumin concentration at the time of renal consultation for AKI independently predicted poor prognosis. It is unknown whether this adverse prognostic association is primarily caused by malnutrition, a negative acute phase response to inflammation, transcapillary leak, or a combination of factors. Serum prealbumin levels may aid prognostic stratification and clinical decision making in AKI and should be included in future studies. There is no evidence that attempting to raise low prealbumin levels through aggressive nutritional support improves outcomes in AKI.

New assay for the measurement of selenoprotein P as a sepsis biomarker from serum

Selenium (Se) is incorporated into selenoproteins as the 21st proteinogenic amino acid selenocysteine. Serum Se concentrations decline during critical illness and are indicative of poor prognosis. Serum Se is mainly contained in the hepatically derived selenoprotein P (SePP) which controls the expression of antioxidative selenoproteins. Here, we describe the development of an immunoluminometric sandwich assay that uses two polyclonal sheep antihuman SePP antibodies. After assessing the stability of the analyte, we determined SePP concentrations in samples from healthy individuals and patients with sepsis. The analytical detection limit was 0.016 mg SePP/L serum. The assay was linear on dilution. SePP was stable in serum at room temperature for at least 24 h and resistant to six freeze-thaw cycles. Median SePP concentration in healthy individuals was 3.04 mg SePP/L serum (25th–75th percentiles, 2.6–3.4 mg/L) which corresponded to 98.4 μg Se/L serum. The interlaboratory CV was <20% for SePP values >0.06 mg/L. There was no association with gender, but concentrations differed between young and older individuals. Median SePP concentrations were significantly ( P<0.0001) decreased in patients with sepsis ( n=60) compared to healthy controls ( n=318). Since SePP contains the major fraction of serum Se, we conclude that downregulation of SePP biosynthesis or removal of circulating SePP from blood underlies the negative acute phase response of serum Se in critical illness.

Changes in serum fetuin-A and inflammatory markers levels in end-stage renal disease (ESRD): effect of a single session haemodialysis

The aim of the present study was to evaluate the effect of a single haemodialysis (HD) session on serum fetuin-A levels, considered a negative acute phase response marker; moreover, we evaluated the behaviour of fibrinogen and high sensitivity C-reactive protein (hsCRP) as acute phase response and chronic/subclinical inflammation markers, respectively, after a single HD session. Serum fetuin-A, albumin, hsCRP and fibrinogen were measured in 72 patients before and after a single HD session. After a single HD session, we observed a significant increase in fibrinogen levels, while fetuin-A levels decreased (p<0.05). Also, hsCRP levels were significantly increased. The significant decrease of fetuin-A levels after a single HD session is consistent with the hypothesis of HD-induced inflammation; activated acute phase response and fetuin-A deficiency might account for increased cardiovascular risk and accelerated atherogenesis in dialysis patients.