Acute Phase Reactant Protein Research Articles

Peculiarities of acute phase reaction and its correction in surgical pathology in pigs

Surgical pathology in animals is quite broad and has various forms of manifestation. It covers various anatomic-topographic areas and organs, in particular in pigs quite often presented with abdominal pathology. There have been published reports of an incidence of hernias in 0.8-3.5% of the pig population, which is 50% of all surgical pathology of the whole animal species. In the group of clinically healthy pigs (n = 10), a significant level of anti-inflammatory IL-10 is noticeable. At the same time, rather high cytokine indices of the ratio of anti-inflammatory to proinflammatory cytokines in healthy animals – 13.9: 1 – 19.4: 1, with the index between the latter – 0.7: 1. That is, in general, IL-10, under physiological norms, exercises a powerful control over the phylogenic cytokine systems of the pig body. At the same time, animals with surgical pathology show a sharp increase in the levels of proinflammatory cytokines. For hernias accompanied by an adhesive-inflammatory aseptic process, serum TNF-α content is increased 4.9-fold and IL-1β is slightly less – only 2.1-fold, with a moderate increase in the concentration of 1.3-fold anti-inflammatory IL- 10. In this case, cytokine indices are significantly reduced, which indicates a decrease in the activity of antiflogogenic mechanisms. The dynamics of the development of purulent arthritis is characterized by a remarkable increase in blood levels of TNF-α – 18.3 times, and a moderate increase in the concentrations of IL-1 and IL-10. In this case, the cytokine index of IL-10: TNF-α acquired a critical value of 1.5: 1, and the number of the latter exceeded the level of IL-1β by more than 5 times. At the same time, elevation of IL-1β and IL-10 levels did not lead to a significant difference with the indigenous animals. Most likely, the powerful synthesis of TNF-α is associated with the appearance of a large number of cells of its producers in the area of ​​destruction of the joints. In this case, insufficient increase in the level of IL-10 triggers the process of cascading production of inflammatory mediators and the development of systemic inflammatory syndrome. Fibrinogen, as one of the acute phase reaction proteins, fluctuates within 2–4 g / L by physiological norms. In the early postoperative period, its level increases significantly, however, the peaks of increasing plasma fibrinogen concentration in control animals are recorded on day 1 and day 7. By using the immune depot, on the contrary, it is dynamically normalized to the 7th day after the hernia. The dynamics of fibrinogen concentration with the use of thiotriazoline were somewhat different. It peaked after the first day and was 2.3 times higher than immuno depot injections. In the following, only after the 3rd day the level of fibrinogenemia began to normalize dynamically, which can be explained by the pronounced hepatoprotective effect of thiotriazoline with increased synthesis of fibrinogen by the liver. The level of haptoglobin, like fibrinogen, remained virtually unchanged in the first hours after herniotomy. However, its concentration increased substantially 24 hours after surgery in the first and second study groups, compared to the preoperative period. Moreover, the level of haptoglobin in the 1st group was 2 times higher than in the 2nd (p <0.01), which indicates a more pronounced anti-inflammatory effect of thiotriazoline. On the 3rd day of the postoperative period there was a peak increase of this indicator, but again in the 2nd experimental group it was twice lower. A further dynamic decrease in serum haptoglobin concentration was more pronounced with the use of thiotriazoline. With regard to ceruloplasmin, it reached its highest level by the 6th hour after surgical intervention in pigs of group 1 and amounted to 421.9 ± 39.69 mg / l. The rather rapid increase in serum ceruloplasmin is due, most likely, to the inhibition of prooxidant enzymes by the components of the immune depot, in particular selenium and copper. However, given the established dynamics of the concentration of ceruloplasmin in groups, it is not possible to attest to its specificity for aseptic inflammation in pigs. The cytokine profile in pigs with surgical pathology depends on its complexity. Moderate cytokinemia of phlogenic character develops over hernia, which becomes extremely pronounced with purulent arthritis. However, the production of anti-inflammatory cytokines is not adequate enough to require pharmacological correction of the inflammatory response in surgical pathology in pigs. The acute-phase reaction after herniotomy in pigs is mainly manifested by an increase in the concentration of fibrinogen and haptoglobin in the blood, but not ceruloplasmin. The mechanisms of its correction with thiotriazoline and immune depot differ, which needs further research. Key words: pigs, cytokines, acute phase proteins, herniotomy, immune depot, thioriazoline.

Dose-dependent immunomodulatory effect of intravenous allogeneic umbilical cord-derived mesenchymal stromal cells (Cytopeutics CLV-100) infusion in healthy volunteers

Background & Aim Background Mesenchymal stromal cells (MSCs) express growth factors and other cytokines that stimulate repair and control the immune response. MSCs are also immunoprivileged with low risk of rejection. Umbilical cord derived MSC (UCMSCs) are particularly attractive as off-the-shelf allogeneic treatment in emergency medical conditions. Objective We aim to determine the safety and feasibility of intravenous allogeneic infusion of UCMSCs (CLV-100) by Cytopeutics® (Selangor, Malaysia) in healthy volunteers, and to determine the effective dose at which an immunomodulatory effect is observed. Methods, Results & Conclusion Methodology Umbilical cord samples were collected after delivery of full-term, healthy babies with written consent from both parents. All 3 generations (newborn, parents and grandparents) were screened for genetic mutations, infections, cancers and other inherited diseases. Samples were transferred to a certified Good Manufacturing Practice laboratory for processing. Subjects were infused with either low dose (LD, 65 million cells) or high dose (HD, 130 million cells) of CLV-100 followed up for 6 months. We measured cytokines level using ELISA including the acute phase reactant high-sensitivity C-reactive protein (hs-CRP), anti-inflammatory cytokines interleukin 1 receptor antigen (IL-1RA) and interleukin 10 (IL-10), and the pro-inflammatory cytokine Tumor Necrosis Factor-Alpha (TNF-α). The study was approved by the National Medical Research and Ethics Committee (MREC). Results 11 healthy subjects (LD, n=5; HD, n=6; mean age of 55±13 years) were recruited. All subjects tolerated the CLV-100 infusion well with no adverse reaction throughout the study. While there was no change in vital parameters and routine blood tests, there was a transient rise in hs-CRP at Day 3 post infusion (1.2±1.5 vs. 4.5±3.9 mg/L; p=0.03) which resolved at Day 7. The anti-inflammatory IL-1RA was significantly elevated in HD patients at 1 month post infusion (436±128 vs. 615±148 pg/mL; p=0.028). At 6 months, HD group had significantly higher levels of anti-inflammatory markers IL1-RA (705±160 vs. 306±36 pg/mL; p=0.02) and IL-10 (321±27 vs. 251±28 pg/mL; p=0.02); and lower levels of pro-inflammatory marker TNF-α (74±23 vs. 115±15 pg/mL; p=0.038) compared to LD group. Conclusion Allogeneic UCMSCs CLV-100 infusion is safe and well-tolerated in low and high doses. Anti-inflammatory effect is observed with high dose infusion.

Abstract P029: Inflammation Measured by Glyc-A as a Mediating Factor Between Subclinical Thyroid and Cardiovascular Diseases. The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

Introduction: An auto-immune process strongly determines subclinical thyroid disorders generating a high grade of inflammation. However, the evidence from epidemiologic studies of the association between subclinical thyroid disorders with coronary heart disease has not been reported as mediated or moderated by a traditional inflammatory marker such as the high-sensitivity C-Reactive Protein. Recently, another inflammatory marker that reflects protein glycosylation in acute-phase reactant proteins - GlycA was associated with coronary heart disease events. Hypothesis: The association of GlycA, a more comprehensive biomarker of inflammation, with subclinical hypothyroidism, and subclinical hyperthyroidism, should explain some mechanisms of the association subclinical thyroid disorders and coronary heart disease. Methods: We tested this hypothesis among 5060 men and women aged 35 to 74 years-old enrolled in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) at baseline. Subclinical thyroid disorders were defined as thyroid-stimulating hormone (TSH) >4 IU/ml (subclinical hypothyroidism) and TSH <0.4 IU/ml (subclinical hyperthyroidism) with normal free-thyroxine levels. The variable of exposure was GlycA measured in serum by proton nuclear magnetic resonance (1H NMR) spectroscopy at (LabCorp, Raleigh, NC). We excluded participants who reported previous cardiovascular disease, use of lipid-lowering agents or drugs that interfere with thyroid function. The cross-sectional relationship between GlycA and subclinical hyperthyroidism and subclinical thyroid was evaluated separately by linear regression models using the category of the subjects with euthyroidism as the reference. Both crude unadjusted and adjusted (age, sex, race, education, smoking, alcohol use, physical activity body-mass index, hypertension, diabetes, smoking, alcohol use, and physical activity data are presented Results: After exclusions, we analyzed 47 individuals with subclinical hyperthyroidism (mean age 53.1 (±9.4) years; 61.7% women), 258 with subclinical hypothyroidism (mean age 52.3 (±8.9); 58.1% of women) and 3,642 participants with normal thyroid function (mean age: 50.1 (±8.6); 52% of women). Crude linear regression models showed no significant association between GlycA and subclinical hyperthyroidism (Beta-coefficient [B], 15.77; P = 0.10) or subclinical hypothyroidism (B, 3.60; P=0.39). Results remained nonsignificant after multivariate adjustment for subclinical hyperthyroidism (B, 12.96; P=0.15) and subclinical hypothyroidism (B, 0.44; (P=0.91). Conclusions: There is no association between subclinical thyroid disorders and GlycA. Other presumptive inflammatory pathways should be contemplated in further studies addressing the link between subclinical thyroid disorders and coronary heart disease.

Atherosclerosis as an Inflammatory Disease - Pathophysiology, Clinical Relevance and Therapeutic Implications

Since the early 1990 s, both experimental and clinical data have clearly demonstrated that inflammatory processes accompany atherosclerotic disease from its initiation to the development of clinical complications. Numerous biomarkers involved at various levels of the inflammation cascade have been shown to be associated with adverse cardiovascular outcomes. Among them, the classical acute phase reactant C-reactive protein (CRP) has been most intensively investigated. Recent research in this field has been driven by the observation that despite low LDL-cholesterol levels, a remarkably high number of patients are still at increased risk for recurrent cardiovascular events. This is argued to be attributable to the presence of a prolonged inflammatory response (reflected by a persistently elevated hsCRP), a concept, which is currently known as "residual inflammatory risk". The unequivocal proof that the inflammatory process is not only a simple bystander but is also causally involved in atherogenesis, came from the recent CANTOS trial, showing a 15 % reduction of primary MACE outcomes despite aggressive statin therapy and lower LDL-cholesterol levels. Thus, an anti-inflammatory treatment strategy might represent a promising tool to improve the outcome of this still deadly disease.

Abstract # 3091 Inflammation is Associated with Decreased Amygdala to Ventromedial Prefrontal Functional Connectivity in Association with Symptoms of Anxiety in Patients with Depression

Inflammation, as evidenced by inflammatory cytokines and the acute-phase reactant C-reactive protein (CRP), is reliably elevated in patients with depression and fear and anxiety-related disorders and is thought to contribute to symptom severity. Previous work shows that administration of inflammatory stimuli affects brain regions such as amygdala that are involved in fear, anxiety, and emotional processing. However, whether increased inflammation affects the amygdala or its functional connectivity in patients with depression and/or fear and anxiety-related disorders is only beginning to be explored. We conducted resting-state functional MRI in medically-stable, unmedicated outpatients with depression (n = 48) to investigate whether increased inflammation was associated with altered functional connectivity of the amygdala to whole brain in relation to symptoms of anxiety. Results indicated that increased inflammation (plasma CRP and cytokines) was associated with decreased functional connectivity between the right amygdala and ventromedial prefrontal cortex (vmPFC; corrected p

Pilot study on serum C-reactive protein in pet rabbits: clinical usefulness

ObjectivesThe present study was performed to evaluate the usefulness of serum C-reactive protein (CRP) as an acute phase reactive protein in pet rabbits in clinical practice.MethodsThe CRP level using a...

Acute phase reactant proteins, anthropometric and dyslipidaemic changes associated with type 2 diabetic mellitus among Nigerian population

Diabetes mellitus is a serious metabolic disorder of multiple aetiology. This disorder is on the increase in some developing countries such as Nigeria. It is characterized by chronic hyperglycaemia with disturbances in carbohydrate, fat and protein metabolism resulting from either defects in insulin secretion, insulin action or both.In some cases, the disease may be insidious until the patients develop complications. A total number of three hundred and seventy five individuals participated in this study out of which two hundred and twenty five were type 2 diabetic mellitus volunteers while one hundred and fifty served as control. Anthropometric measurements were taken using weighing balance, tape rule, and meter rule. C-reactive protein, fasting blood glucose, total protein, albumin and lipid profile were determined using enzyme-linked immunosorbent assay (ELISA) and Cobas chemistry auto analyzer respectively. There were a significant increase (p<0.05) in weight, body mass index (BMI) waist hip ratio, fasting blood sugar, C-reactive protein, total cholesterol, triglyceride, triglyceride/high density lipoprotein (TG/HDLC), low density lipoprotein/ high density lipoprotein (LDLC/HDLC) and TC/HDLC in type 2 diabetic mellitus patients when compared with the controls. On the other hand, albumin, albumin globulin ratio and HDLC were observed to be significantly (p<0.05) low in diabetic volunteers when compared with controls. There was a positive association (r = 0.66, p<0.05) between Creactive protein (CRP) and glucose whereas a negative association (r = -0.31, p<0.05) was observed between CRP and albumin among diabetic mellitus group. This study suggests that diabetes mellitus is associated with increased risk of inflammation and lipid dysfunction.Keywords: Diabetes mellitus, Acute phase reactants, Lipid profile, Blood sugar

Inflammation negatively correlates with amygdala-ventromedial prefrontal functional connectivity in association with anxiety in patients with depression: Preliminary results

Biomarkers of inflammation, including inflammatory cytokines and the acute-phase reactant C-reactive protein (CRP), are reliably increased in a subset of patients with depression, anxiety disorders and post-traumatic stress disorder (PTSD). Administration of innate immune stimuli to laboratory subjects and the associated release of inflammatory cytokines has been shown to affect brain regions involved in fear, anxiety and emotional processing such as the amygdala. However, the role of inflammation in altered circuitry involving amygdala and other brain regions and its subsequent contribution to symptom severity in depression, anxiety disorders and PTSD is only beginning to be explored. Herein, medically-stable, currently unmedicated outpatients with a primary diagnosis of major depressive disorder (MDD; n = 48) underwent resting-state functional MRI (rfMRI) to determine whether altered connectivity between the amygdala and whole brain was observed in a subset of patients with high inflammation and symptoms of anxiety. Whole-brain, voxel-wise functional connectivity analysis of the right and left amygdala as a function of inflammation (plasma CRP concentrations) revealed that increased CRP predicted decreased functional connectivity between right amygdala and left ventromedial prefrontal cortex (vmPFC) (corrected p < 0.05). Amygdala-vmPFC connectivity was, in turn, negatively correlated with symptoms of anxiety (r = −0.33, df = 46, p = 0.022). In exploratory analyses, relationships between low amygdala-vmPFC connectivity and high anxiety were only observed in patients with a secondary diagnosis of an anxiety disorder or PTSD (r = −0.54 to −0.87, p < 0.05). More work is needed to understand the role of inflammation and its effects on amygdala-vmPFC circuitry and symptoms of anxiety in MDD patients with comorbid anxiety disorders or PTSD.

C-Reactive Protein Stimulates Nicotinic Acetylcholine Receptors to Control ATP-Mediated Monocytic Inflammasome Activation.

Blood levels of the acute phase reactant C-reactive protein (CRP) are frequently measured as a clinical marker for inflammation, but the biological functions of CRP are still controversial. CRP is a phosphocholine (PC)-binding pentraxin, mainly produced in the liver in response to elevated levels of interleukin-1β (IL-1β) and of the IL-1β-dependent cytokine IL-6. While both cytokines play important roles in host defense, excessive systemic IL-1β levels can cause life-threatening diseases such as trauma-associated systemic inflammation. We hypothesized that CRP acts as a negative feedback regulator of monocytic IL-1β maturation and secretion. Here, we demonstrate that CRP, in association with PC, efficiently reduces ATP-induced inflammasome activation and IL-1β release from human peripheral blood mononuclear leukocytes and monocytic U937 cells. Effective concentrations are in the range of marginally pathologic CRP levels (IC50 = 4.9 µg/ml). CRP elicits metabotropic functions at nicotinic acetylcholine (ACh) receptors (nAChRs) containing subunits α7, α9, and α10 and suppresses the function of ATP-sensitive P2X7 receptors in monocytic cells. Of note, CRP does not induce ion currents at conventional nAChRs, suggesting that CRP is a potent nicotinic agonist controlling innate immunity without entailing the risk of adverse effects in the nervous system. In a prospective study on multiple trauma patients, IL-1β plasma concentrations negatively correlated with preceding CRP levels, whereas inflammasome-independent cytokines IL-6, IL-18, and TNF-α positively correlated. In conclusion, PC-laden CRP is an unconventional nicotinic agonist that potently inhibits ATP-induced inflammasome activation and might protect against trauma-associated sterile inflammation.

Matrix sieving-enforced retrograde transcytosis regulates tissue accumulation of C-reactive protein.

Circulating proteins larger than 3 nm can be transported across continuous endothelial barrier of blood vessels via transcytosis. However, excessive accumulation of serum proteins within the vessel walls is uncommon even for those abundant in the circulation. The aim of this study was to investigate how transcytosis regulates tissue accumulation of the prototypical acute-phase reactant C-reactive protein (CRP) and other serum proteins. Transcytosis of CRP as well as of transferrin and low-density lipoprotein across aortic endothelial cells is bidirectional with directional preference from the apical (blood) to basolateral (tissue) direction both in vitro and in vivo. This directional preference is, however, reversed by the basement membrane (BM) matrix underlying the basolateral surface of endothelial cells. This is due to the sieving effect of the BM that physically hinders the diffusion of transcytosed proteins from the apical compartment towards underlying tissues, resulting in immediate retrograde transcytosis that limits basolateral protein accumulation. Conversely, CRP produced within vessel wall lesions can also be transported into the circulation. Our findings identify matrix sieving-enforced retrograde transcytosis as a general mechanism that prevents excessive tissue accumulation of blood-borne proteins and suggest that lesion-derived CRP might also contribute to elevated serum CRP levels associated with increased risk for cardiovascular diseases.

Financial strain modifies the association between inflammation and cardiovascular disease risk: The English longitudinal study of ageing

Introduction Atherosclerosis and cardiovascular disease (CVD) have an inflammatory origin. Moreover, chronic psychosocial stress is associated both with inflammation and CVD. Fibrinogen, a coagulation factor and CVD risk factor, is also a positive acute-phase reactant protein, its concentration increasing with presence of inflammation. Elevated inflammation measured on a single occasion can reflect either systemic inflammation and be the consequence of chronic psychosocial stress or the acute response to a recent stressful event or infection in an otherwise healthy, non-psychosocially stressed individual. Therefore, the prognostic value for future CVD risk of a single inflammation test may depend on the presence of chronic psychosocial stress. We tested this hypothesis in middle-aged to older adults aged 52 and above participating in a nationally representative cohort study. Methods A total of 4541 men and women, free of CVD and aged 52 to 92 at baseline (2004–2005), participants in the English Longitudinal Study of Ageing, provided serum levels of fibrinogen during the nurse visit at baseline, alongside with clinical measurements and other blood biomarkers. Psychosocial factors were collected during the computer assisted personal interview and included financial strain, depression, social isolation, loneliness and social support. The outcome of interest was CVD mortality as ascertained up to February 2013. Cox proportional hazards regression models using age as the underlying time variable were fitted to estimate the relationship (hazard ratios [HR] and 95% confidence intervals) between fibrinogen and CVD death. Interactions terms between fibrinogen and each psychosocial factor were tested. Models were stratified by sex and adjusted for age, smoking, body mass index, physical activity, cholesterol, triglycerides and diabetes. Restricted cubic splines were used to assess the shape of the associations and test nonlinearity by using the likelihood ratio test, comparing nested models with a linear or linear and cubic spline terms. Results In this sample with a baseline median age of 63 years (interquartile range 57–71), there were 130 CVD deaths after a median follow-up of 8.1 y. The association between fibrinogen and hazard of CVD mortality was linear and positive: HR for the increase in 1 g/L of fibrinogen = 1.56; 95% CI: 1.26, 1.94, P Conclusions The positive association between fibrinogen and CVD death was much stronger in the presence of financial strain. An implication of our findings is that, when assessing the presence of inflammation with a single test for estimation of CVD risk, it may be necessary to take into account the presence of chronic psychosocial stress.

Decrease in Serum Amyloid a Protein Levels Following Three-month Stays in Negatively Charged Particle-dominant Indoor Air Conditions

ObjectiveThe changes in serum adipokines and cytokines related to oxidative stress were examined during 3 months ‘Off to On' and ‘On to Off' periods using negatively charged particle-dominant indoor air conditions (NCPDIAC). MethodsSeven volunteers participated in the study, which included ‘OFF to 3 months ON' periods (ON trials) for a total of 16 times, and ‘ON to 3 months OFF' (OFF trials) periods for a total of 13 times. ResultsWith the exception of one case, serum amyloid A (SAA) levels decreased significantly during the ON trials. ConclusionConsidering that SAA is an acute phase reactive protein such as C reactive protein (CRP), this observed decrease might indicate the prevention of cardiovascular and atherosclerotic changes, since an increase in high-sensitive CRP is associated with the subsequent detection of these events.

Neuropsychiatric lupus is lipocalin-2 dependent

Abstract Neuropsychiatric manifestations of systemic lupus erythematosus (NPSLE) affect approximately 40% of patients. Lipocalin-2 (LCN2), an acute-phase reactant protein, is an established urinary biomarker in lupus patients. Previous studies using LCN2-deficient mice have demonstrated its role in glial migration and chemokine regulation in the brain. We therefore hypothesized that LCN2 is involved in NPSLE pathogenesis. We investigated the lupus prone B6.Sle1.Sle3 (Sle1,3) mouse and the effects of LCN2 deficiency on the development of the neuropsychiatric phenotype exhibited by this strain. Sle1,3, B6.LCN2KO, B6, and Sle1,3-LCN2KO mice (6–10 month old; n=5–10/group) underwent comprehensive neurobehavioral assessment, and brains were evaluated by flow cytometry and RNA sequencing. Sle1,3 mice exhibited significant impairment in spatial (p&amp;lt;0.04) and recognition (p&amp;lt;0.02) memory when compared with B6 mice, and these deficits were attenuated in Sle1,3-LCN2KO mice (p&amp;lt;0.001, p&amp;lt;0.02). Furthermore, Sle1,3 mice demonstrated anhedonia, and this depression-like behavior was significantly reduced with LCN2 deficiency (p=0.01). Flow cytometry showed a significant increase in brain infiltrating CD8+ T cells in Sle1,3 mice, with a reduction in infiltration in the Sle1,3-LCN2KO strain (p=0.06). Preliminary analysis of RNA sequencing from sorted microglia revealed genes involved in cognition and memory that were differentially expressed in Sle1,3 mice were restored to background B6 expression levels in Sle1,3-LCN2KO mice. Our findings establish the Sle1,3 mouse as an NPSLE model and demonstrate that LCN2 deficiency attenuates neurobehavioral deficits and regulates microglial expression of genes essential to NPSLE development.

To Compare the Competency of Prognostic Markers- ESR, CRP against ZN Staining in Determining Pulmonary Tuberculosis Cases

Background: Tuberculosis (TB) is a highly prevalent chronic infectious disease caused by Mycobacterium tuberculosis an aerobic intracellular binding bacterium (bacillus). Active TB disease can be fatal if left untreated. The disease today is considered curable and preventable. This retrospective study was undertaken to compare and analyzed the relationship between acute phase reactant proteins CRP (quantitative) and ESR in sputum smear positive for AFB patients and to evaluate their diagnostic and prognostic significance. Methods: The present prospective study was carried on a randomly selected study group comprising of 180 cases of pulmonary TB patients who were sputum smear positive for AFB and 25 normal healthy (sputum smear negative for AFB) individual were taken as control. The cases of PTB group was further categorized on the basis of recommendation of RNTCP grading system of AFB in Sputum ZN staining into four subgroups AFB – 3+, AFB – 2+, AFB –1+ and scanty. The control groups were negative for the Acid Fast bacilli in sputum. Results: In our study showed that the maximum patients seen in grade III (36.11%) followed by grade II (31.66%), grade I (19.44%) and 12.77% scanty according to RNTCP grading system of ZN staining of sputum for acid fast bacilli. The distribution of mean values of CRP, ESR in different grades of ZN staining of sputum in AFB positive patients as well as controls. CRP mean value was 55.4, 40.8 & 22.9 in grade III, grade II & grade I respectively and ESR was 48.1, 38.8 & 23 respectively in different grading significantly higher (p vol < 0.0001) in group II there were no serious adverse reactions in either group. Conclusions: Our study concluded that during the compression of values of CRP and ESR along with the grading of sputum AFB positive patients, the CRP raised more significantly as compare to ESR; with markedly raised values in all the grades of sputum AFB positive patients.

Can the acute-phase reactant proteins be used as cancer biomarkers?

The association between the acute-phase reactant proteins (APRPs) and cancer has long been established. There have been numerous reports correlating altered levels of various APRPs with different types of cancers. However, researchers are often quick to dismiss the use of these APRPs as potential biomarkers for the diagnosis and monitoring of cancer because alterations in APRP concentrations are observed in a wide range of diseases. Recent progress in proteomics studies which profiled the serum proteins of cancer patients and those of normal individuals indicated that the altered APRP expressions were different for distinct types, subtypes, and even stages of cancer. Interestingly, these data are in agreement with those observed earlier using immunochemical and biochemical assays. In view of this compelling association of different patterns of APRPs with various types of cancers and in an apparent shift of paradigm, we present in this review some indications that APRP fingerprinting may be used as complementary cancer biomarkers.

Acute phase reactant, Pentraxin 3, as a novel marker for the diagnosis of rheumatoid arthritis

IntroductionPentraxins are a group of highly conserved acute-phase reactant proteins and play crucial role as modulators of inflammatory processes. Pentraxin 3 (PTX3) is primarily produced and released by vascular cell wall, hence, we attempt to establish the role of PTX3 as a biomarker for Rheumatoid Arthritis (RA) compared to CRP. MethodsThirty patients having active RA as cases and 30 osteoarthritis (OA) patients as controls were recruited. Paired serum and synovial fluid samples were analysed for concentrations of both PTX3 and CRP by using high sensitivity ELISA kit and ROC curve was plotted. ResultsConcentrations of PTX3 and CRP were significantly higher in RA patient serum (p < 0.0001) as well as in synovial fluid (p < 0.0001) and correlated with disease severity. Upon correlation analysis, positive correlation was found between serum and synovial fluid concentrations of PTX3 and CRP. The diagnostic potential of PTX3 was observed in synovial fluid while combination of PTX3 and CRP showed better sensitivity in serum. ConclusionPTX3 found to be sensitive non-invasive indicator of clinical arthritic activity in RA patients when compared to traditional markers like CRP. Combination of PTX3 and CRP could serve as better differential diagnostic markers for RA after validation in larger patient cohort.

C-Reactive Protein Correlates with Negative Symptoms in Patients with Schizophrenia.

Peripheral and CNS-localized inflammatory processes are hypothesized to contribute to the complex pathophysiology of schizophrenia. Elevated levels of the acute phase reactant C-reactive protein (CRP) have been observed in schizophrenia, yet relatively few studies have investigated the association between this inflammatory biomarker and psychotic symptoms in schizophrenia. This study is a pilot cross-sectional analysis investigating the relation of plasma CRP levels and the positive and negative symptoms of schizophrenia (the primary aim), assessed by the Positive and Negative Syndrome Scale (PANSS). A secondary analysis was also performed evaluating the potential association of CRP with cognitive function using the NIH Toolbox Cognitive Test Battery. After adjusting for age, sex, race, and body mass index, a positive correlation was observed between CRP and PANSS negative symptoms (rho = 0.37, p = 0.05). There was no correlation between plasma CRP and any of the NIH Toolbox measures of cognitive function in the unadjusted or adjusted analyses. Though limited by a relatively small sample size and the unavailability of longitudinal data, the correlation between CRP and psychopathology in this sample of patients supports a role for inflammation in the pathophysiology of schizophrenia.

18F-FDG-PET/CT: an accurate method to assess the activity of Takayasu's arteritis.

The objective of the study is to investigate the value of 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT) for assessment of the activity of Takayasu's arteritis (TA) and the correlation between acute-phase reactive proteins (ARPs) and standard uptake value (SUV). Analyses of the clinical characteristics and 42 18F-FDG-PET/CT scans in 39 TA patients were undertaken. The degree of FDG uptake in the blood vessel walls was assessed quantitatively by SUV. TA activity was analyzed by physician global assessment (PGA). Clinical and 18F-FDG-PET/CT characteristics were compared between patients with clinically active and clinically inactive TA. Maximum SUV (SUVmax), mean SUV (SUVmean), and SUV ratio (SUVratio) were significantly higher in the clinically active group than in the clinically inactive group (3.63 ± 1.96 vs. 1.82 ± 0.43, p = 0.007; 2.07 ± 0.71 vs. 1.43 ± 0.32, p = 0.009; 2.08 ± 1.17 vs. 0.95 ± 0.19, p = 0.000). Analyses of receiver operating characteristic (ROC) curves revealed a cutoff value of SUVmax of 2.21, with sensitivity and specificity of 86.2 and 90.0%, respectively, for clinically active TA. The SUVratio cutoff was 1.27 with a sensitivity and specificity of 79.3 and 100.0%, respectively. SUVratio was slightly superior to SUVmax and ARPs in the area under the curve (AUC) comparison. SUVmax and SUVratio showed a significant increasing trend with increasing US National Institutes of Health (NIH) score and levels of ARPs, interleukin-6, and serum amyloid-A protein. 18F-FDG-PET/CT is a promising non-invasive, quantitative measurement with high sensitivity and specificity for determining TA activity.

Phase angle is related with inflammatory and oxidative stress biomarkers in older women

BackgroundThe aim of this study was to examine the relation between phase angle (PhA) and inflammatory and oxidative stress biomarkers in older women. MethodsOne hundred and fifty-five physically independent older women participated in this study (67.7±5.7years, 27.0±4.4kg/m2). Inflammatory markers included interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), and acute phase reactive protein (CRP). Oxidative stress biomarkers comprised superoxide dismutase (SOD), catalase (CAT), advanced oxidation protein products (AOPP), and total radical-trapping antioxidant potential (TRAP). A spectral bioelectrical impedance device was used to estimate resistance (R) and reactance (Xc) at frequency 50kHz, and subsequently PhA was calculated as arc-tangent (Xc/R)×180°/π. The covariates appendicular lean soft-tissue (ALST), trunk fat mass, and total body fat were determined by whole-body dual-energy X-ray absorptiometry. Linear regression analysis was conducted to further test if PhA is related with the dependent variables, after adjusting for potential covariates. ResultsAfter controlling for the potential covariates (age, trunk fat mass, ALST, and number of diseases) PhA exhibited a significant inverse relation with IL-6 (β=−0.97; P<0.01), TNF-α (β=−0.84; P<0.01), and CRP (β=−0.58; P<0.01). Conversely, PhA was significantly related to CAT (β=7.27; P<0.01), SOD (β=10.55; P<0.01) and TRAP (β=73.08; P<0.01). The AOPP did not demonstrate a significant correlation with PhA (P>0.05). ConclusionOur findings show that PhA is a simple and relevant explanatory variable which is related inflammatory and stress oxidative markers in physically independent older women, regardless of age, number of diseases, and body composition.

Effect of processing banked suspended red blood cells with cell saver before priming on perioperative systemic inflammatory responses of infants undergoing cardiac surgery under cardiopulmonary bypass

Objective To evaluate the effects of processing banked suspended red blood cells (RBCs) with cell saver before priming on perioperative systemic inflammatory responses of infants undergoing cardiac surgery under cardiopulmonary bypass (CPB). Methods Forty pediatric patients of both sexes, aged 3 months-2 yr, weighing 5-13 kg, of American Society of Anesthesiologists physical status Ⅱ-Ⅳ, undergoing repair of atrial or ventricular septal defect under CPB, were divided into control group (group C, n=20) and processing group (group P, n=20) using a random number table.Banked suspended RBCs were primed directly after being added to CPB circuit in group C. Banked suspended RBCs were washed with cell saver and then primed after being added to CPB circuit in group P. At 5 min before skin incision, at 30 min after the start of CPB, at 10 min after aortic unclamping, immediately after the end of CPB and at 6, 12 and 24 h after the end of CPB (T1-7), blood samples were collected from the radial artery for determination of the concentrations of tumor necrosis factor, interleukin-1β (IL-1β), IL-6, IL-8, IL-10 and neutrophil elastase in plasma by enzyme-linked immunosorbent assay.Blood samples were taken from the radial artery at T1 and T4-7 for measurement of blood routine and plasma acute phase reactive protein concentrations. Results Compared with group C, the concentrations of tumor necrosis factor, IL-1β, IL-6, IL-8 and neutrophil elastase in plasma were significantly decreased at T6, 7, the total number of white blood cells, neutrophil count and concentration of plasma acute phase reactive protein were decreased at T7, and duration of stay in intensive care unit was shortened in group P (P<0.05). Conclusion Processing banked suspended RBCs with cell saver before priming can reduce perioperative systemic inflammatory responses of infants undergoing cardiac surgery under CPB. Key words: Erythrocytes; Cardiopulmonary bypass; Inflammation; Infant