Comparison between procalcitonin and C-reactive protein for early diagnosis of children with sepsis or septic shock

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Sensitive Affimer and Antibody Based Impedimetric Label-Free Assays for C-Reactive Protein

C-reactive protein (CRP) is an acute phase protein whose levels are increased in many disorders. Levels greater than 3 mu g/mL serum have hitherto been considered to indicate pathology, but there is increasing interest in assessments between 0.1 and 10 mu g/mL, which have been found to correlate with severity of risk for cardiovascular disease. We report herein the generation of both antibody and Affimer based impedance immunoassays for CRP that are substantially more sensitive than clinically utilized immunonephelometry and immunoturbidity assessments. Significant in this study is not only the use of a constrained peptide to detect a clinically important target but also that derived electrochemical impedance assays can be highly sensitive even with probes whose relatively weak (mu M) affinities are not amenable to target detection by surface plasmon resonance (SPR). Key to this finding is acknowledging that receptive surfaces of comparatively low initial steric bulk and charge transfer resistance are especially primed to be highly responsive to target binding in electroanalytical assays of this type.

An optimised electrochemical biosensor for the label-free detection of C-reactive protein in blood

C-reactive protein (CRP) is an acute phase protein whose levels are increased in many disorders. There exists, in particular, a great deal of interest in the correlation between blood serum levels and the severity of risk for cardiovascular disease. A sensitive, label-free, non-amplified and reusable electrochemical impedimetric biosensor for the detection of CRP in blood serum was developed herein based on controlled and coverage optimised antibody immobilization on standard polycrystalline gold electrodes. Charge transfer resistance changes were highly target specific, linear with log. CRP. concentration across a 0.5-50. nM range and associated with a limit of detection of 176. pM. Significantly, the detection limits are better than those of current CRP clinical methods and the assays are potentially cheap, relatively automated, reusable, multiplexed and highly portable. The generated interfaces were capable not only of comfortably quantifying CRP across a clinically relevant range of concentrations but also of doing this in whole blood serum with interfaces that were, subsequently, reusable. The importance of optimising receptor layer resistance in maximising assay sensitivity is also detailed. © 2012.

Pathological and behavioral risk factors for higher serum c-reactive protein concentrations in free-living adults - A Brazilian community-based study

Low-grade chronic systemic inflammation is often associated with chronic non-communicable diseases, and its most frequently used marker, the C-reactive protein (CRP), has become an identifier of such diseases as well as an independent predictor for cardiovascular disorders and mortality. CRP is produced in response to pro-inflammatory signaling and to individual and behavioral factors, leading to pathological states. The aim of this study was to rank the predicting factors of high CRP concentrations in free-living adults from a community-based sample. We evaluated 522 adults (40-84 years old; 381 women) for anthropometric characteristics, dietary intake, clinical and physical tests, and blood analysis. Subjects were assigned to groups, according to CRP concentrations, as normal CRP (G1;<3.0 mg/L; n = 269), high CRP (G2; 3.0-6.0 mg/L; n = 139), and very high CRP (G3; >6.0 mg/dL; n = 116). Statistical comparison between groups used one-way ANOVA or Kruskal-Wallis tests, and prediction of altered values in increasing CRP was evaluated by proportional hazard models (odds ratio). CRP distribution was influenced by gender, body mass index, body and abdominal fatness, blood leukocytes, and neutrophil counts. The higher CRP group was discriminated by the above variables in addition to lower VO2max, serum metabolic syndrome components (triglycerides, glucose, and HDL cholesterol), higher insulin, homeostasis assessment of insulin resistance, uric acid, gamma-GT, and homocysteine. After adjustments, only fatness, blood leukocytes, and hyperglycemia remained as independent predictors for increased serum CRP concentrations. Intervention procedures to treat low-grade chronic inflammation in overweight women would mainly focus on restoring muscle mass and functions in addition to an antioxidant-rich diet. © 2012 Springer Science+Business Media, LLC.

Three-year follow-up of Interleukin 6 and C-reactive protein in chronic obstructive pulmonary disease

Background: Past studies have shown that mean values of Interleukin-6 (IL-6) and C-reactive protein (CRP) do not change significantly in COPD patients over a one-year period. However, longer period follow-up studies are still lacking. Thus, the aim of this study is to evaluate plasma CRP and IL-6 concentration over three years in COPD patients and to test the association between these inflammatory mediators and disease outcome markers. Methods: A cohort of 77 outpatients with stable COPD was evaluated at baseline, and 53 (mean FEV1, 56% predicted) were included in the prospective study. We evaluated Interleukin-6 (IL-6), C-reactive protein (CRP), six-minute walking distance (6MWD), and body mass index (BMI) at baseline and after three years. Plasma concentration of IL-6 was measured by high sensitivity ELISA, and CRP was obtained by high sensitivity particle-enhanced immunonephelometry. Results: IL-6 increased significantly after 3 years compared to baseline measurements [0.8 (0.5-1.3) vs 2.4 (1.3-4.4) pg/ml; p < 0.001] and was associated with worse 6MWD performance. In the Cox regression, increased IL-6 at baseline was associated with mortality [Hazard Ratio (95% CI) = 2.68 (0.13, 1.84); p = 0.02]. CRP mean values did not change [5 (1.6-7.9) vs 4.7 (1.7-10) pg/L; p = 0.84], although eleven patients (21%) presented with changes >3 mg/L in CRP after 3 years. Conclusions: The systemic inflammatory process, evaluated by IL-6, seems to be persistent, progressive and associated with mortality and worse physical performance in COPD patients. Trial registration: No.:NCT00605540. © 2013 Ferrari et al; licensee BioMed Central Ltd.

Cardiorespiratory fitness, but not central obesity or C-reactive protein, is related to liver function in obese children

Nonalcoholic fatty liver disease (NAFLD) is one of the most frequent complications associated with excess adiposity. Its pathogenesis is complex and there are multiple factors that may contribute to it. AIM: To analyze whether cardiorespiratory ftness (CRF), waist circumference (WC), and C-reactive protein (CRP) are associated with alanine aminotransferase (ALT) in children with obesity. METHODS: 79 overweight/obese children of both genders, 11-13 year-olds, with abnormal serum ALT from Porto public schools comprised the sample. Measurements included CRF (20-m Shuttle Run Test), WC (NHANES protocol), CRP and ALT (Cholestech LDX analyzer). Logistic regression adjusted for gender, maturation, and weight with ALT levels as dependent variable (risk vs. non risk), and WC (risk vs. non risk), CRP (risk vs. non risk), and CRF (fit vs. unfit) as independent variables. Level of significance was set at 95%. RESULTS: Logistic regression showed that obese fit children were less likely to have abnormal ALT values (OR=.031) CONCLUSION: In obese children, higher cardiovascular fitness appears to reduce the chance of decreased liver function. © 2013 Human Kinetics, Inc.

C-reactive protein and vasospasm after aneurysmal subarachnoid hemorrhage1

PURPOSE:To evaluate the relationship between C reactive protein levels and clinical and radiological parameters with delayed ischemic neurological deficits and outcome after aneurysmal subarachnoid hemorrhage.METHODS:One hundred adult patients with aneurismal SAH were prospectively evaluated. Besides the baseline characteristics, daily C-reactive protein levels were prospectively measured until day 10 after subarachnoid hemorrhage. The primary end point was outcome assessed by Glasgow Outcome Scale, the secondary was the occurrence of delayed ischemic neurological deficits (DINDs).RESULTS:A progressive increase in the CRP levels from the admission to 3rd postictal day was observed, followed by a slow decrease until the 9th day. Hemodynamic changes in TCD were associated with higher serum CRP levels. Patients with lower GCS scores presented with increased CRP levels. Patients with higher Hunt and Hess grades on admission developed significantly higher CRP serum levels. Patients with higher admission Fisher grades showed increased levels of CRP. A statistically significant inverse correlation was established in our series between CRP serum levels and GOS on discharge and CRP levels.CONCLUSIONS:Higher C-reactive protein serum levels are associated with worse clinical outcome and the occurrence of delayed ischemic neurological deficits. Because C-reactive protein levels were significantly elevated in the early phase, they might be a useful parameter to monitor.

Changes in malondialdehyde and C-reactive protein concentrations after lifestyle modification are related to different metabolic syndrome-associated pathophysiological processes

Metabolic syndrome (MetS) is often accompanied by pro-oxidative and pro-inflammatory processes. Lifestyle modification (LiSM) may act as primary treatment for these processes. This study aimed to elucidate influencing factors on changes of malondialdehyde (MDA) and C-reactive protein (CRP) concentrations after a LiSM intervention. Sixty subjects (53 yrs, 84% women) clinically approved to attend a 20 weeks LiSM-program were submitted to weekly nutritional counseling and physical activities combining aerobic (3 times/week) and resistance (2 times/week) exercises. Before and after intervention they were assessed for anthropometric, clinical, cardiorespiratory fitness test (CRF) and laboratory markers. Statistical analyses performed were multiple regression analysis and backward stepwise with p<0.05 and R(2) as influence index. LiSM was responsible for elevations in CRF, healthy eating index (HEI), total plasma antioxidant capacity (TAP) and HDL-C along with reductions in waist circumference measures and MetS (47-40%) prevalence. MDA and CRP did not change after LiSM, however, we observed that MDA concentrations were positively influenced (R(2)=0.35) by fasting blood glucose (β=0.64) and HOMA-IR (β=0.58) whereas CRP concentrations were by plasma gamma-glutamyltransferase activity (β=0.54; R(2)=0.29). Pro-oxidant and pro-inflammatory states of MetS can be attenuated after lifestyle modification if glucose metabolism homeostasis were recovered and if liver inflammation were reduced, respectively.

Predicting vasospasm after aneurismal subarachnoid hemorrhage with C reactive protein levels

Aim: The interest of inflammatory marker increased in the last years, even in preventing clinical outcome after subarachnoid hemorrhage (SAH). Our objective was to study the relationships between C-reactive protein levels and clinical outcome and the development of cerebral vasospasm after aneurismal SAH. Methods: One hundred adult patients with aneurismal SAH were prospectively evaluated. Glasgow Coma Scale (GCS) score, Hunt and Hess grade, Fisher grade, CT scans, digital subtraction angiography studies, transcranial doppler (TCD) and daily neurological examinations were recorded. Serial serum CRP measurements were obtained on daily between admission and 10th days. Glasgow Outcome Scale (GOS) and the modified Rankin Scale (mRS) were used to predict outcome. Results: A progressive increase in the CRP levels from the admission to the 3rd postictal day was observed, followed by a slow decrease until the 9th day. Hemodynamic changes in TCD were associated with higher serum CRP levels. Patients with lower GCS scores presented with increased CRP levels. Patients with higher Hunt and Hess grades on admission developed significantly higher CRP serum levels. Patients with higher admission Fisher grades showed increased levels of CRP. A statistically significant inverse correlation was established in our series between CRP serum levels and GOS and mRS scores on discharge and CRP levels. Conclusion: Increased CRP levels were strongly associated with poor clinical outcome. CRP levels can predict cerebral vasospasm and delayed ischemic deficits with higher statistic significance. There are relationships between hemodynamic chances in TCD and higher CRP levels.

Changes in plasma protein concentrations in ponies with experimentally induced alimentary laminitis

Objective-To determine whether plasma protein concentrations were altered in ponies with alimentary laminitis.Animals-12 adult ponies.Procedure-Acute laminitis was induced in 6 ponies by oral administration of carbohydrate (85% corn starch, 15% wood flour); the other 6 ponies were used as controls. A physical examination was performed and blood samples were collected immediately before and 4, 8, 12, 24, and 28 hours after administration of carbohydrate. Plasma protein concentrations were determined by means of sodium dodecyl sulphate-polyacrylamide gel electrophoresis.Results-19 plasma proteins ranging from a molecular weight of 24,000 to a molecular weight of 350,000 were identified in all 12 ponies. Plasma concentrations of proteins with molecular weights of 350,000 (fibrinogen), 130,000 (ceruloplasmin), 118,000 (c-reactive protein), 67,000 (alpha(1)-antitrypsin I), 65,000 (alpha(1)-antitrypsin II), 50,000 (haptoglobulin), and 45,000 (acid glycoprotein) were significantly increased in ponies with laminitis, compared with concentrations in control ponies.Conclusion-Changes in plasma protein concentrations are detectable within 4 hours after the onset of alimentary laminitis in ponies.Clinical Relevance-Measurement of plasma protein concentrations may be useful in monitoring the progression of laminitis in ponies.

Razão triglicérides/HDL-C e proteína C reativa de alta sensibilidade na avaliação do risco cardiovascular

Introduction: Calculated indexes from laboratory measurements and the determination of plasma markers are commonly used in cardiovascular risk assessment. Objective: To use triglycerides/high-density lipoprotein cholesterol (HDL-C) ratio, estimate of low-density lipoprotein (LDL) particle size and high sensitive C-reactive protein (hs-CRP) levels to the clinical and laboratorial assessment of coronary risk among patients with coronary disease. Material and methods: Sixty patients were chosen accordingly, 36 female (F) (65 ± 9 years of age) and 24 male (M) (55 ± 10 years of age) diagnosed with stable ischemic cardiopathy at Ana Neri Hospital, Salvador, Bahia, Brazil. The investigation was carried out at the Clinical Biochemistry Laboratory of the College of Pharmacy at Federal University of Bahia (UFBA). Blood samples were collected after a 12-hour fast to determine hs-CRP, lipid profile and risk indicators. All data were assessed through Syncron LX®20 Beckman Coulter. The inferential analysis results were considered significant when p ≤ 5%. Data analysis was carried out with GraphPad Prism® (4.03 version) software. Results: Data analysis showed a positive correlation between hs-CRP and triglycerides/HDL-C ratio only among women (r = 0.4; p = 0.0442), n = 36. The analysis of other parameters did not show any significance. Conclusion: The triglycerides/HDL-C ratio and hs-CRP may be used as indicators of increase in cardiovascular risk among women with coronary artery disease (CAD).

Estudo tranversal e longitudinal da associação entre asma e proteína C reativa: interferência da obesidade nos valores da proteína C reativa em asmáticos

Pós-graduação em Fisiopatologia em Clínica Médica - FMB

Associação das concentrações plasmáticas de proteína C-reativa com fatores de risco e componentes da síndrome metabólica e comorbidades

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Diagnóstico da trombose venosa profunda dos membros inferiores, utilizando o modelo clínico de Wells et al. (2003), Dímero-D, Mapeamento Dúplex e avaliação da Proteina C Reativa

Pós-graduação em Bases Gerais da Cirurgia - FMB