Positive Acute Phase Proteins Research Articles

C-reactief proteïneconcentraties in het serum van honden met idiopathische epilepsie

Inflammatoire reacties bij honden zijn geassocieerd met systemische veranderingen in het serum, de acute fase respons genaamd. Deze gaat gepaard met veranderde concentraties acutefase-eiwitten in het serum. Het C-reactief proteïne (CRP) is een positief acutefase-eiwit en stijgt bijgevolg bij een ontsteking. Er bestaat veel onduidelijkheid over de relatie tussen epilepsie en ontsteking. Daarom werd in deze studie de rol van ontsteking onderzocht bij honden met idiopathische epilepsie (IE). Drie doelstellingen werden vooropgesteld: 1. het meten van serum-CRP-concentraties bij honden met IE en bij gezonde honden, 2. het meten van serum-CRP-concentraties bij honden met acute clusteraanvallen en bij honden met geïsoleerde aanvallen en 3. het opvolgen van de evolutie in serum-CRP-concentraties in de tijd na de laatste epilepsieaanval. In deze studie kon geen significant verschil in serum-CRPconcentratie tussen honden met IE en de honden van de controlegroep worden aangetoond. Verder waren de gemiddelde serum-CRP-concentraties hoger bij honden met clusteraanvallen (8,3 mg/l) dan bij honden met geïsoleerde aanvallen (7,8 mg/l). Deze resultaten waren echter statistisch niet significant (P = 0,077). Ten slotte werd een statistisch niet-significante daling in serum-CRP-concentraties gezien na de laatste epileptische aanval bij de honden met IE (P = 0,077).

The Role of Chloroquine Phosphate on Acute Phase Reactant Proteins in Patients with Knee Osteoarthritis

The acute phase response is a major pathophysiologic phenomenon that accompanies inflammation whether acute or chronic. Complement (C3 and C4) and C - reactive protein (CRP) are positive acute phase proteins (+ ve APPs ). Their production takes place in hepatocyte and the blood concentration of these parameters are increased in osteoarthritis (OA). Chloroquine (CQ) is a diprotic weak base traditionally used to treat malaria. Recently the phosphate salt of CQ is used to decrease this type of (+ve APPs) . In this study, patients who suffered from knee osteoarthritis (KOA) are treated with oral dosage form of chloroquine phosphate (CQP) for one month, twice daily. Our results demonstrate that CQP improves the patient status by decreasing complement and C-reactive protein in blood.
 Key words: Chloroquine , knee osteoarthritis , acute phase proteins , complement , C-reactive protein.

Plasma fetuin-A/α2-HS-glycoprotein correlates negatively with inflammatory cytokines, chemokines and activation biomarkers in individuals with type-2 diabetes.

BackgroundFetuin-A/AHSH is a novel hepatokine that acts as a vascular calcification inhibitor and as an endogenous TLR-4 ligand. Fetuin-A may act as a positive or negative acute phase protein (APP) in disease conditions. The relationship between circulatory fetuin-A and inflammatory biomarkers in type-2 diabetes (T2D) remains controversial. Therefore, the purpose of this study was to determine the plasma fetuin-A levels in 53 T2D (BMI = 29.7 ± 4.5 kg/m2) and 72 non-diabetic individuals (BMI = 28.2 ± 5.8 kg/m2) using premixed 38-plex MAP human cytokine/chemokine magnetic bead immunoassays and the data (mean ± SEM) were statistically analyzed to determine Pearson’s correlation (r) between fetuin-A and detected analytes; P-values ≤0.05 were considered significant.ResultsThe data show that plasma fetuin-A levels were comparable in both groups (P = 0.27) and in T2D individuals, fetuin-A associated negatively (P ≤ 0.05) with a large number of proinflammatory cytokines/chemokines and activation biomarkers including TNF-α, IFN-α2, IFN-γ, IL-1α, IL-1β, IL-1RA, IL-3, IL-4, IL-7, IL-9, IL-12p40/p70, IL-15, CCL-2, CCL-4, CCL-11, CCL-22, CXCL-8, CX3CL-1, EFF-2, EGF, G-CSF, GM-CSF, GRO, sCD40L, and VEGF. In non-diabetics, fetuin-A also correlated positively with certain TH2 cytokines (IL-5, IL-13) and chemokines (CCL-3, CCL-5, CCL-7). Notably, in vitro fetuin-A production was significantly suppressed in HepG2 cells treated with TNF-α, IL-1β, and IFN-γ which supported the clinical findings of a negative association between fetuin A and inflammatory mediators.ConclusionsThe negative association between circulatory fetuin-A and systemic inflammatory mediators in T2D patients suggests that plasma fetuin-A may have predictive significance as a negative APP in metabolic disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s12865-016-0171-y) contains supplementary material, which is available to authorized users.

Elevated Values of C-Reactive Protein Induced by Imported Infectious Diseases: A Controlled Cross-Sectional Study of 11,079 Diseased German Travelers Returning from the Tropics and Subtropics.

The present controlled cross-sectional study aimed to assess elevated values of C-reactive protein (CRP), a positive acute-phase protein, induced by imported infectious diseases (IDs) seen in patients consulting the University of Munich (1999-2015) after being in the tropics/subtropics. The analysis investigated data sets from 11,079 diseased German travelers (cases) returning from Latin America (1,986), Africa (3,387), and Asia (5,706), and from 714 healthy Germans who had not recently traveled (controls). The proportions of elevated values of CRP (> 0.5 mg/dL) were significantly larger among cases (44.3%) than among controls (20.7%). Among cases, this proportion was largest among males (49.2%) in comparison to females (39.9%), among travelers with short travel duration of 1-14 days (49.6%) in comparison to travelers with a travel duration of > 180 days (30.8%), and with travel destination in Africa (47.0%) in comparison to Asia (44.2%) and Latin America (39.9%), among all-inclusive travelers (47.4%) in comparison to business travelers (46.7%) and backpackers (44.1%), and among patients presenting with fever (70.9%) and arthralgia (54.3%). The study identified various imported IDs with significantly larger proportions of elevated values of CRP including viral (cytomegalovirus infection [94.7%], influenza [88.9%], infectious mononucleosis [71.8%]), bacterial (typhoid fever [100%], paratyphoid fever [92.9%], shigellosis [76.8%], rickettsiosis [74.2%], Salmonella enteritis [71.3%], Campylobacter infection [68.7%]), and protozoan (vivax malaria [100%], ovale malaria [100%], falciparum malaria [95.4%], noninvasive Entamoeba infection [65.9%]) IDs. This study demonstrates that elevated values of CRP can be a useful laboratory finding for travelers returning from the tropics/subtropics, as these findings are typically caused mainly by certain imported bacterial IDs, but also by viral and protozoan IDs.

Purification and determination of C-reactive protein and inter-α-trypsin inhibitor heavy chain 4 in dogs after major surgery through generation of specific antibodies

Inter-α-trypsin inhibitor heavy chain 4 (ITIH4) and C-reactive protein (CRP) have been isolated from acute phase dog sera by affinity chromatography with insolubilized polyclonal antibodies anti pig Major Acute phase Protein (Pig-MAP) and with p-Aminophenyl Phosphoryl Choline, respectively. Isolated proteins were used to prepare specific polyclonal rabbit antisera that have allowed quantifying their concentration in serum samples by single radial immunodifussion. Both proteins were quantified in sera from female dogs that had undergone ovariohysterectomy (OVH, n=9) or mastectomy (n=10). The observed increases in CRP concentrations showed that surgical traumas induced an acute phase response of a great magnitude in the dogs. In both surgeries a four-fold increase of ITIH4 concentrations was detected. It can be concluded that ITIH4 is a new positive acute phase protein in dogs, as reported in other species.

Study of acute phase proteins in liver disease

Acute-phase proteins are a class of proteins whose plasma concentrations increase (positive acute-phase proteins) or decrease (negative acute-phase proteins) in response to inflammation. Hence the present study was conducted to evaluate the levels of the acute phase proteins in the normal healthy group & the liver diseases patient. The 40 liver diseases patients were enrolled in to the study. All the patients are informed consents. The liver diseases include the liver cirrohosis, jaundice, infective hepatitis. The age group of the patients are from 20-50 years. 20 normal healthy groups were also selected as control to study the levels of acute phase proteins in them. Ceruloplasmin and Serum transferrin is estimated from the pathological findings. From the above study it can be concluded that the acute phase proteins in liver disorders plays important role. The increases level of the ceruloplasmin and transferrin shows the liver disorders.

Acute phase response in lactating dairy cows during hyperinsulinemic hypoglycaemic and hyperinsulinemic euglycaemic clamps and after intramammary LPS challenge

The link between energy availability, turnover of energy substrates and the onset of inflammation in dairy cows is complex and poorly investigated. To clarify this, plasma inflammatory variables were measured in mid-lactating dairy cows allocated to three groups: hyperinsulinemic hypoglycaemic clamp, induced by insulin infusion (HypoG, n=5); hyperinsulinemic euglycaemic clamp, induced by insulin and glucose infusion (EuG; n=6); control, receiving a saline solution infusion (NaCl; n=6). At 48h after the start of i.v. infusions, two udder quarters per cow were challenged with 200μg of E.coli lipopolysaccharide (LPS). Individual blood samples were taken before clamps, before LPS challenge (i.e. 48h after clamps) and 6.5h after. At 48h, positive acute phase proteins (posAPP) did not differ among groups, whereas albumin and cholesterol (index of lipoproteins), negative APP (negAPP), were lower (p<0.05) in EuG compared to NaCl and HypoG. The concentration of IL-6 was greater in EuG (p<0.05) but only vs. HypoG. At 6.5h following LPS challenge, IL-6 increased in the NaCl and EuG clamps (p<0.05), while TNF-α increased (p<0.05) in the EuG only. Among the posAPP, haptoglobin markedly increased in EuG (p<0.05), but not in NaCl (p=0.76) and in HypoG; ceruloplasmin tended to decline during LPS challenge, the reduction was significant when all animals were considered (p<0.05). Conversely, all the negAPP showed a marked reduction 6.5h after LPS challenge in the three groups. In conclusion, EuG caused an inflammatory status after 48-h infusion (i.e. decrease of negAPP) and induced a quicker acute phase response (e.g. marked rise of TNF-α, IL-6) after the intramammary LPS challenge. These data suggest that the simultaneous high availability of glucose and insulin at the tissue-level makes dairy cows more susceptible to inflammatory events. In contrast, HypoG seems to attenuate the inflammatory response.

Validation of an enzyme-linked immunosorbent assay for measurement of feline haptoglobin.

Haptoglobin is a positive moderate acute phase protein (APP) in cats. Measurement of haptoglobin can be used in the diagnosis, prognosis, and monitoring of systemic inflammatory disease, especially by creating profiles with major APPs. The aim of our study was to validate a sandwich enzyme-linked immunosorbent assay (ELISA) for measurement of feline haptoglobin. The validation included an assessment of precision, accuracy, detection limit, method comparison with a spectrophotometric assay, and evaluation of the overlap performance. The concentration of haptoglobin was measured in serum from 27 healthy and 23 sick cats. The coefficients of variation were 2.5-4.7% for intra-assay variability and 7.1-11.6% for interassay variability. The ratio of observed to expected dilutional parallelism of 4 serum samples was 108.1-118.4%. The ratio of observed to expected spike recovery of 4 serum samples was 90.8-94.0%. The lower detection limit was 0.19 g/L. Method comparison revealed a positive correlation (rs = 0.949, P < 0.0001) and a proportional bias between the methods of -38.9%. Agreement between the methods was not clinically acceptable. Overlap performance of the ELISA was deemed satisfactory. The sandwich ELISA measures feline haptoglobin with an analytical and overlap performance acceptable for clinical purposes. Given the observed bias, the ELISA cannot be used interchangeably with the spectrophotometric assay.

Haematological and acute-phase response of dogs with experimental skin Pseudomonas aeruginosa infection to treatment with antibiotic and parthenolide

Changes in white blood cells, leukogram patterns, the positive acute-phase protein (APP) fibrinogen and negative APPs (albumin and arylesterase) were monitored to evaluate their potential as sensitive indicators throughout the course of therapy in canine skin Pseudomonas aeruginosa infection. The study was performed on 15 male mixed-breed dogs, divided in three groups of 5 dogs each. Dogs from group A were injected subcutaneously with P. aeruginosa bacterial culture (1 × 108 CFU/mL) at a dose of 0.3 mL/kg and treated with enrofloxacin (5 mg/kg, s.c.) on post infection hour 48 for 10 consecutive days. Dogs from group B were infected and treated with a combination of enrofloxacin (at above-mentioned dose and intervals) and parthenolide (feverfew extract 90 mg, 0.7 % parthenolide). The schedule consisted of daily oral intake of two capsules of feverfew beginning on post infection hour 4 and continued for 6 days. The control group C included healthy dogs, injected s.c. with 0.3 mL/kg physiological saline. The haematological indices and APPs were assayed before infection and on 4th, 24th, 48th and 72nd hours and on 7th, 10th and 14th days after infection. Infected and antibiotic-treated dogs responded with significant leukocytosis, left shift, eosinopaenia and lymphopaenia between hours 24 and 72. In this group, fibrinogen increased substantially by post infection hours 24 (p < 0.01 vs 0 h; p < 0.05 vs group C), 48 (p < 0.001 vs 0 h; p < 0.05 vs group C) and 72 (p < 0.001 vs 0 h; p < 0.01 vs group C) while albumin reduction was marked by hours 48 (p < 0.05 vs 0 h) and 72 (p < 0.05 vs 0 h; p < 0.001 vs group C) and day 7 (p < 0.01 vs 0 h; p < 0.001 vs group C). The combination of enrofloxacin and parthenolide modified, at a significant extent, the deviations in studied parameters except for eosinophil percentage, which persisted low.

Acute-phase glycoprotein N-glycome of ovarian cancer patients analyzed by CE-LIF.

Epithelial ovarian cancer (EOC) is the most frequent cause of death from all gynecological malignancies because of its late diagnosis. As N-glycosylation is modified in the course of ovarian cancer, it is a promising source of tumor biomarkers. In this work, serum glycoproteins, depleted from albumin and IgG, were separated by 2DE. Protein spots of acute-phase proteins were identified by peptide mapping and their corresponding glycan moieties were released enzymatically, fluorescently labeled and analyzed by CE-LIF. In the positive acute-phase proteins, haptoglobin, α1-antitrypsin, and α1-antichymotrypsin, an increase of antennarity and Lewis(X) motif could be measured in EOC patients on tri- and/or tetraantennary N-glycans. Tetraantennary N-glycans containing three Lewis(X) epitopes and triantennary N-glycans containing a β(1-6) branch and a Lewis(X) epitope were only present in EOC patients. We also showed for the first time that the core-fucosylated biantennary digalactosylated N-glycan of α1-acid glycoprotein is a potential biomarker for EOC. To conclude, core-fucosylated biantennary N-glycans on α1-acid glycoprotein as well as higher antennarity and increased amounts of Lewis(X) motif on haptoglobin, α1-antitrypsin, and α1-antichymotrypsin are promising biomarkers for EOC. Nevertheless, their specificity and selectivity for the early detection of EOC should be evaluated in a larger study.

Amyloid fibril formation by bovine α1-acid glycoprotein in a reducing environment: The role of disulfide bridges on the observed aggregation kinetics.

Bovine α1-acid glycoprotein (bAGP), a thermostable counterpart of its human homologue, is a positive acute phase protein involved in binding and transportation of a large number of bio-active molecules and drugs across the body. We have investigated the effect of low pH and reducing conditions on the structure of the protein and found that it aggregates at high temperatures. The aggregates show a fibrillar structure when observed with electron microscopy. Aggregation assays using the amyloid-specific dye Thioflavin T show the presence of a lag phase which was neither abolished nor shortened when seeds were added. A priori reduction of the two disulfide bridges of bAGP, on the other hand, abolished the lag phase and reveals a connection between the kinetics of reduction and aggregation. We provide a kinetic interpretation and the corresponding rate laws allowing to model the process of fibril formation by bAGP under reducing conditions. Our interpretation allows to assess the role of disulfide bridges on the fibrillation kinetics of bAGP and can provide a more accurate interpretation of the fibrillation kinetics of other amyloidogenic proteins containing disulfide bridges.

PL108. Inflammatory mechanisms in preeclampsia

Introduction Preeclampsia is a severe complication of pregnancy characterized by an excessive maternal systemic inflammatory response. Objectives Our aim was to determine cellular and humoral components of the innate and adaptive immune system in normal pregnancy and preeclampsia. Methods In our case-control studies, we used flow cytometry, multiplex suspension array, ELISA, immunoturbidimetry and radial immunodiffusion for our measurements. Results High-throughput multiplex cytokine measurements demonstrate an overall pro-inflammatory systemic environment in preeclampsia with elevated amounts of pro-inflammatory cytokines, chemokines and adhesion molecules in the maternal circulation. In addition, circulating levels of positive acute phase proteins increase, whereas those of negative acute phase proteins decrease in preeclampsia, indicating an acute phase response. The complement system is activated systematically with increased terminal complex formation, as shown by the elevated amounts of activation markers in the systemic circulation. All three complement pathways (the classical, lectin and alternative) are involved in the excessive complement activation in preeclampsia. Regulatory T cells (Tregs) play an important role in the development of pregnancy-specific immune tolerance. The frequency of conventional CD4+ CD25high FoxP3+ and non-conventional CD4+ CD25− FoxP3+ Tregs is lower in preeclampsia, suggesting inadequate induction of tolerance to paternal antigens. The prevalence of the functionally most active effector Tregs is decreased, while that of exhausted Tregs is increased in preeclampsia. The combination of lower effector Treg and higher exhausted Treg prevalence may account for the decrease in the functionality of Tregs in preeclampsia. There is a shift not only in the Th1/Th2, but also in the Th17/Treg balance favouring skewness towards a pro-inflammatory status in preeclampsia. The prevalence of IL-17-producing CD8 (Tc17) and NK cells is also elevated in this pregnancy-specific disorder. Conclusion Our results indicate that both the innate and adaptive arms of the immune system are involved in the development of the exaggerated maternal systemic inflammation observed in preeclampsia.

A Plasma Proteome Associated with Inflammation in Nepalese School‐aged Children

Micronutrient status may be influenced by inflammation, however, it is typically characterized by only C‐reactive protein (CRP) or alpha‐1‐acid glycoprotein (AGP) in nutrition studies. We applied quantitative proteomics to explore plasma proteins that co‐vary with inflammation, reflected by AGP in 500 children 6‐8 yr of age in rural Nepal where elevated AGP was common. Among 982 proteins, 41 and 58 proteins were positively and negatively associated with AGP, respectively, passing a false discovery rate threshold of 0.001%. Positively associated proteins included major positive acute phase proteins including CRP, complement components, protease inhibitors, transport proteins with anti‐oxidative activity, and intracellular signaling molecules. Negatively associated proteins showed a distinct pattern in the abundance profile, characterized by tissue origin: proteins of hepatic origin included plasma transporters for lipids, micronutrients (vitamin A and calcium), growth factors and sex hormones, while extra‐hepatic proteins included structural components of extracellular matrix (ECM) or regulators of ECM metabolism. Our findings reveal a vast number of plasma proteins associated with AGP that reflect active homeostasis of the host defense systems, metabolism of nutrients and other biomolecules, and tissue repair processes. Using population data, we provide evidence of a “plasma inflammasome”, reflecting proteomic dynamics of inflammation, as an extended list of potential candidates for inflammation biomarkers.This study was funded by Bill and Melinda Gates Foundation (OPP5241 and GH614).

Regulation of alpha-1 acid glycoprotein synthesis by porcine hepatocytes in monolayer culture

Alpha-1 acid glycoprotein (AGP, orosomucoid, ORM-1) is a highly glycosylated mammalian acute-phase protein, which is synthesized primarily in the liver and represents the major serum protein in newborn pigs. Recent data have suggested that the pig is unique in that AGP is a negative acute-phase protein in this species, and its circulating concentration appears to be associated with growth rate. The purpose of the present study was to investigate the regulation of AGP synthesis in hepatocytes prepared from suckling piglets and to provide a framework to compare its regulation with that of haptoglobin (HP), a positive acute-phase protein. Hepatocytes were isolated from preweaned piglets and maintained in serum-free monolayer culture for up to 72 h. The influences of hormones, cytokines, and redox modifiers on the expression and secretion of AGP and HP were determined by relative polymerase chain reaction and by measuring the concentration of each protein secreted into culture medium. The messenger RNA abundance and/or secretion of AGP protein was enhanced by interleukin (IL)-17a, IL-1, and resveratrol and inhibited by tumor necrosis factor-α (TNF), oncostatin M, and thyroid hormone (P < 0.05). HP expression and synthesis were upregulated by oncostatin M, IL-6, and dexamethasone and downregulated by TNF (P < 0.01). The overall messenger RNA expression at 24 h was in agreement with the secreted protein patterns confirming that control of these proteins in hepatocytes is largely transcriptional. Moreover, these data support the consideration that AGP is a negative acute-phase reactant and appears to be regulated by cytokines (with the exception of TNF) and hormones primarily in a manner opposite to that of the positive acute-phase protein, HP.

Acute Phase Proteins and Their Role in Periodontitis: A Review.

Acute phase proteins are a class of proteins whose plasma concentration increase (positive acute phase proteins) or decrease (negative acute phase proteins) in response to inflammation. This response is called as the acute phase reaction, also called as acute phase response, which occurs approximately 90 minutes after the onset of a systemic inflammatory reaction. In Periodontitis endotoxins released from gram negative organisms present in the sub gingival plaque samples interact with Toll- like receptors (TLR) that are expressed on the surface of Polymorphonuclear leucocytes (PMNs) and monocytes which are in abundance in periodontal inflammation. The complex formed due to interaction of Endotoxins and TLR activates the Signal transduction pathway in both innate and adaptive immunity resulting in production of Cytokines that co- ordinate the local and systemic inflammatory response. The pro inflammatory cytokines originating at the diseased site activates the liver cells to produce acute phase proteins as a part of non specific response. The production of Acute phase proteins is regulated to a great extent by Cytokines such as IL-1, IL-6, IL-8, TNF-α and to a lesser extent by Glucocorticoid hormones. These proteins bind to bacteria leading to activation of complement proteins that destroys pathogenic organisms. Studies have shown that levels of acute phase proteins are increased in otherwise healthy adults with poor periodontal status. This article highlights about the synthesis, structure, types and function of acute phase proteins and the associated relation of acute phase proteins in Periodontitis.

Relationship between serum amyloid A3 in serum and milk of Mastitic Cows

Bovine mastitis, an important disease of dairy cattle, causes a significant change in normal milk composition as well as changes the overall blood biochemistry. We grouped the animals of Jersey and Holstein Frisian (HF) crossbred into normal, subclinical and clinical mastitis groups (n = 10 each) based on clinical history and diagnostic tests. The serum albumin showed a non-significant variation between the groups of both breeds following mastitis at subclinical and clinical stages. Mammary assosiated serum amyloid A3 (M-SAA3) protein in serum of Jersey crossbred cows showed non-significant difference between the groups, while in milk significant rise in M-SAA3 levels between mastitic groups was observed. In HF crossbred, there was significant increase in M-SAA3 levels in both milk and serum. The study revealed that M-SAA3 is a positive acute phase protein (APP) in both milk and serum and could be used as an adjunct biomarker to diagnose subclinical mastitis.

Monitoring of Serial Presurgical and Postsurgical Changes in the Serum Proteome in a Series of Patients with Calcific Aortic Stenosis.

Background. Comprehensive analysis of proteome differentially expressed in response to surgery or drug treatment is useful to understand biological responses to dispensed interventions. Here we investigated expression changes in sera of patients who suffered from calcific aortic stenosis (CAS), before and after surgery for aortic valve replacement. Materials and Methods. Sera obtained before and after surgery with depletion of highly abundant proteins were analyzed with iTRAQ labeling followed by nanoLC-MALDI-TOF/TOF-MS/MS. Results. Fifty-one proteins shared in five patients were identified with differential levels in postsurgical and presurgical sera. Finally, 16 proteins that show statistically significant levels in patients' sera compared with those in control sera (P < 0.05) were identified. Most of the identified proteins were positive acute-phase proteins. Among three proteins other than acute-phase proteins, we confirmed increased levels of antithrombin-III and zinc-α-2-glycoprotein in postsurgical sera by Western blot analysis using other CAS patients' sera. Furthermore, antithrombin-III and zinc-α-2-glycoprotein were not found among proteins with differential levels in postsurgical and presurgical sera of patients with aortic aneurysms that we identified in a previous study. Conclusions. The results indicated that antithrombin-III and zinc-α-2-glycoprotein would become unique monitoring proteins for evaluating pathophysiological and biochemical processes occurring before and after surgery for CAS.

Serum concentration of haptoglobin in European mouflon (Ovis musimon L.) from a game reserve

Acute phase proteins are used as markers of inflammation and sub-clinical disease, and are considered potential biomarkers for animal health and welfare. The objective of this study was to analyse haptoglobin as the main positive acute phase protein in the mouflon. A total of 30 clinically healthy mouflon of different age and sex, reared in a game reserve, were used for this study. Haptoglobin was determined in blood serum by colorimetric assay with a commercially accessible kit. The mean value of haptoglobin in the herd was 0.215 ± 0.068 mg/ml. There was no significant difference between animals divided by sex: male 0.228 ± 0.073 mg/ml, female 0.202 ± 0.062 mg/ml. The mean value in young animals was higher than the mean value in the adults 0.260 ± 0.081 mg/ml and 0.201 ± 0.059 mg/ml, respectively (P &lt; 0.05). This work was designed to identify the baseline concentration of haptoglobin in a clinically healthy population, thus allowing the comparison of welfare and general health status of the herds or different structured groups within the game reserve. This is the first similar study of haptoglobin as a biomarker in the mouflon.

Acute-phase responses in healthy and diseased rhesus macaques (Macaca mulatta).

Five acute-phase reactants-serum amyloid A (SAA), C-reactive protein (CRP), haptoglobin, albumin, and iron-were measured using commercially available assays in 110 healthy rhesus macaques (Macaca mulatta), and reference intervals were established for future use in health monitoring of this species. Reference intervals established were as follows: SAA, 29.5-87.7 mg/L; CRP, 0-17.5 mg/L; haptoglobin, 354.3-2,414.7 mg/ L; albumin, 36.1-53.0 g/L; and iron, 13.3-40.2 micromol/L. Furthermore, changes in the acute-phase reactants were studied in two additional groups of animals: eight rhesus macaques suffering from acute traumatic injuries and nine rhesus macaques experimentally infected with Mycobacterium tuberculosis reflecting a chronic active inflammation. In animals with inflammation, SAA and haptoglobin concentrations were moderately increased, while CRP increased more than 200-fold. In addition, marked decreases in albumin and iron concentrations were observed. These results show that SAA, CRP, and haptoglobin are positive acute-phase proteins, whereas albumin and iron are negative acute-phase reactants in rhesus macaques.

Acute-phase proteins in relation to neuropsychiatric symptoms and use of psychotropic medication in Huntington׳s disease

Activation of the innate immune system has been postulated in the pathogenesis of Huntington׳s disease (HD). We studied serum concentrations of C-reactive protein (CRP) and low albumin as positive and negative acute-phase proteins in HD. Multivariate linear and logistic regression was used to study the association between acute-phase protein levels in relation to clinical, neuropsychiatric, cognitive, and psychotropic use characteristics in a cohort consisting of 122 HD mutation carriers and 42 controls at first biomarker measurement, and 85 HD mutation carriers and 32 controls at second biomarker measurement. Significant associations were found between acute-phase protein levels and Total Functioning Capacity (TFC) score, severity of apathy, cognitive impairment, and the use of antipsychotics. Interestingly, all significant results with neuropsychiatric symptoms disappeared after additional adjusting for antipsychotic use. High sensitivity CRP levels were highest and albumin levels were lowest in mutation carriers who continuously used antipsychotics during follow-up versus those that had never used antipsychotics (mean difference for CRP 1.4SEmg/L; P=0.04; mean difference for albumin 3SEg/L; P<0.001). The associations found between acute-phase proteins and TFC score, apathy, and cognitive impairment could mainly be attributed to the use of antipsychotics. This study provides evidence that HD mutation carriers who use antipsychotics are prone to develop an acute-phase response.