Levels Of Acute Phase Proteins Research Articles

FengLiao affects gut microbiota and the expression levels of Na+/H+ exchangers, aquaporins and acute phase proteinsin mice with castor oil-induced diarrhea.

The severe side effects of chemosynthetic anti-diarrhea drugs have created an interest in low-toxic alternative plant-derived compounds. FengLiao consists of Polygonum hydropiper Linn. and Daphniphyllum calycinum Bench., and is widely used in China to treat diarrhea due to low levels of toxicity. In this study, the effects of FengLiao were analyzed in a castor oil-induced diarrhea model, using the anti-diarrhea drug, loperamide, as the positive control. The effects were evaluated using stool characteristics and the expression levels of various diarrhea-related factors in the jejunum and liver, as well as changes in the microbiota of the jejunum. The symptoms of diarrhea and stool consistency were improved through FengLiao and loperamide treatment. Furthermore, FengLiao down-regulated alpha 1-acid glycoprotein (AGP) and C-reactive protein (CRP) levels, and up-regulated transferrin (TRF) mRNA levels in the liver, and down-regulated Aquaporin 3 (AQP3) and Na+/H+ exchanger isoform 8 (NHE8) expression in the epithelial cells of the jejunum. It also increased the relative abundance of Bifidobacterium, Aerococcus, Corynebacterium_1 and Pseudomonas, and lowered the Firmicutes/Bacteroidetes (F/B) ratio, which maintained the balance between immunity and intestinal health. Taken together, FengLiao alleviated castor oil-induced diarrhea by altering gut microbiota, and levels of jejunum epithelial transport proteins and acute phase proteins.

Normal ve Güç Doğum Yapan İneklerde Bazı Akut Faz Proteinlerinin ve Oksidatif Stres Düzeyinin Belirlenmesi*

Pregnancy, which includes many different mechanisms and is a physiological process, may cause an increase or decrease in the levels of acute phase proteins (APP) due to the acute phase response occurring in the organism, since it affects many mechanisms in animals. Acute phase proteins can be used not only to determine the diagnosis and prognosis of the inflammatory process, but also to identify non-inflammatory conditions such as pregnancy, childbirth, metabolic diseases, and stress. The aim of this study was to determine some APP and oxidative stress levels in normal parturition and in cows with dystocia. For this purpose, 15 normal parturition and 15 cows with dystocia (Simental breed) were used in the study. Some of the blood collected from animals' Vena jugularis after birth (between 3-48 hours) was placed in tubes with anticoagulant, and the remainder in tubes without anticoagulation. As a result of the analysis, it was determined that haptoglobin, ceruloplasmine and malondialdehyde increased in cows with dystocia while albumin and reduced glutathione concentrations decreased. In conclusion, it was observed that the acute phase response and oxidative stress were increased in cows that were under intensive stress and obstetric intervention during dystocia. It was concluded that antioxidant applications against oxidative stress may be beneficial in addition to the applications to prevent infection in cows, especially in dystocia.

P1190OXIDATIVE STRESS AND INFLAMMATION IN PERITONEAL DIALYSIS: DANGEROUS AND TO BE SOLVED

Abstract Background and Aims Cardiovascular disease is the leading cause of excess mortality in chronic kidney disease (CKD) and dialysis patients with oxidative stress (OxSt) and inflammation playing a pivotal role, as non-traditional risk factors and OxSt and inflammation have been shown to increase in peritoneal dialysis. Rho kinase (ROCK) activation is deeply involved in the induction of OxSt and inflammation and is closely linked to cardiovascular-renal remodeling. We aimed to evaluate in peritoneal dialysis patients with a molecular biology approach OxSt, in terms of phosphorylation state of MYPT-1 (marker of ROCK activity), the protein expression of p22phox (subunit of NADPH oxidase, essential for the generation of ROS), and inflammation state, in terms of acute-phase proteins level (Interleukin 6 (IL-6), ultra-sensitive C-reactive protein (US-CRP), Ferritin, Albumin and Transferrin). Method 9 male ESRD patients (39-81 years old) were enrolled and analyzed before (baseline) and after three and six months of peritoneal dialysis treatment (CAPD 7 patients, APD 2 patients). Mononuclear cells (PBMCs) MYPT-1 phosphorylation state and p22phox protein expression were determined by Western Blot. Specific acute-phase proteins as IL-6, US-CRP, Ferritin, Albumin and Transferrin were assessed through blood chemistry tests. Results MYPT-1 phosphorylation was increased after six months of treatment with peritoneal dialysis compared with three months and predialysis (1.03±0.07 vs 1.02±0.04 vs 1.57±0.16 d.u., p<0.0001). p22phox protein expression (0.72±0.05 vs 0.73±0.10 vs 1.28±0.12 d.u., p<0.0001) and ferritin level (101.4±15.3 vs 173.6±11.5 vs 189.0±20.3 µg/l, p=0.002) increased as well. Albumin was decreased after six months of peritoneal dialysis treatment compared with three months and predialysis (43.38±0.10 vs 40.00±1.59 vs 36.46±1.43 g/l, p=0.007). IL-6 and US-CRP remained unchanged at a high level. Conclusion The increase of OxSt and inflammation during peritoneal dialysis is confirmed also at molecular biology level and may lead in the medium-long term to dangerous consequences. The necessary improvement of OxSt status in peritoneal dialysis needs a multitarget approach. It might include the use of neutral pH, low glucose degradation products, low lactate and iso-osmolar peritoneal dialysis solutions, strict glycemic control, optimal volume management and, likely, a supplementation with antioxidants as N-acetylcysteine.

Altered systemic levels of acute phase proteins in tuberculous lymphadenitis and modulation after treatment.

BackgroundPulmonary tuberculosis (PTB) is characterized by elevated levels of acute phase proteins (APPs), but their association with tuberculous lymphadenitis (TBL) is poorly studied.MethodsWe examined the systemic levels of APPs (alpha-2-macroglobulin [⍺-2MG], serum amyloid A [SAA], C-reactive protein [CRP] and haptoglobin [Hp]) in TBL, PTB, latent tuberculosis (LTB) and healthy controls (HC) at baseline and in TBL after the completion of anti-tuberculosis treatment (ATT). We have also examined the association of these proteins with lymph node (LN) size, culture grade and multiple versus single LN involvement.ResultsTBL individuals exhibited increased systemic levels of ⍺-2MG, SAA, CRP and Hp in comparison to HCs and increased CRP levels in comparison to LTB individuals. TBL individuals also exhibited decreased systemic levels of Hp compared to PTB individuals. APPs were not significantly associated with LN size, LN involvement and culture grade, indicating a lack of association with disease severity. Following ATT, post-treatment levels of ⍺-2MG, CRP and Hp were significantly diminished compared to pre-treatment levels.ConclusionTBL disease is characterized by altered levels of APPs at baseline and modulated following treatment, indicating the presence of systemic inflammation.

Evaluation of blood-based proteomic biomarkers associated with response to anti-PD-1 treatment in NSCLC.

e21531 Background: Immune checkpoint inhibitors have remarkably improved the natural history of patients with non-small cell lung cancer (NSCLC), with improved clinical responses and overall survival compared to standard therapy. However, most unselected NSCLC patients do not respond, highlighting the need of theranostic biomarker discovery. In a cohort of NCSLC patients treated with anti-PD-1-blockade, we investigate baseline blood-based parameters with a high-throughput quantitative proteomics workflow, based on data independent acquisition mass spectrometry (DIA-MS). Quantified proteins are evaluated as potential circulating biomarkers for predicting the response to therapy. Methods: Plasma samples from 49 NSCLC subjects treated with anti-PD-1-blockade were prepared for mass spectrometry. All samples were analyzed on a Thermo Scientific Q Exactive HF-X operated in a DIA mode using capillary flow liquid chromatography with separation over a 40 min gradient. DIA data was extracted with Spectronaut to quantify expressed proteins. Results: Across all samples, 605 proteins were quantified and 17 were significantly associated (log2 fold change > 0.58 and q-value < 0.05) with Responders (SD + PR) vs Non-Responder (PD) groups. Functional mapping and unsupervised clustering of regulated proteins identifies three major subject groups based on protein expression profiles: Group A is characterized by high expression of acute phase proteins (e.g. SAA1/2, CRP), Group B has low overall protein expression, and Group C has high expression glycolysis related enzymes (ALDOA, GAPDH) and focal adhesion proteins (VCL). Consistent with previous studies the Group A, with high levels of acute phase proteins, had poor overall survival relative to the other two families (HR = 2.2 [1.2-4.2], p = 0.003). Notably, Group C is comprised largely of Non-Responders (8/12) yet had improved overall survival relative to Group A (HR = 2.5 [1.2-5.0], p = 0.004). Conclusions: Plasma proteomic profiling with capillary flow DIA-MS enables quantification protein profiles in a hypothesis free manner. Poor outcomes on anti-PD-1 therapy was confirmed for subjects with elevated acute phase proteins. However, a subgroup with high focal adhesion and glycolysis proteins had improved survival despite containing non-responder subjects, requiring further investigation.

The effect of feed supplementation with Transcarpathian zeolite (clinoptilolite) on the concentrations of acute phase proteins and cytokines in the serum and hepatic tissue of chickens

The aim of the this study was to determine the effect of different levels of Transcarpathian zeolite (clinoptilolite) on selected indicators of the immune response in chickens by assessing the concentrations of the acute phase proteins haptoglobin, C-reactive protein (CRP), serum amyloid A, transferrin, and alpha-1-acid glycoprotein and the cytokines tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), IL-2, and IL-10 in the serum and hepatic tissues of chickens. The study was conducted on 450 one-day-old male Ross 308 chickens. The total rearing period was 42 D. The samples of blood and liver were collected before the start of the study (day 0) and on day 42, after rearing was completed. ELISA kits specific for chicken CRP, haptoglobin, alpha-1-acid glycoprotein, serum amyloid A, transferrin, TNF-α, IFN-γ, IL-2, and IL-10 were used to determine the levels of acute phase proteins and cytokines in the serum and liver homogenates. The results of immunological tests suggest that for long-term maintenance of homeostasis in chickens, the addition of 2% zeolite as a feed additive is most beneficial. The results indicate that 3% clinoptilolite induce production of Th1 pro-inflammatory cytokines, increasing the synthesis of IL-2, IFN-γ, and TNF-α. The high concentration of IL-10 after the use of zeolite in conjunction with the high concentration of IL-2, TNF-α, and IFN-γ indicates a reduction in the intensity of inflammatory processes, the enhancement of the humoral immune response, and the simultaneous inhibition of the production of Th1-type cytokines. The increase of CRP concentration in conjunction with high concentrations of pro- and anti-inflammatory cytokines in the birds from the group receiving 3% clinoptilolite demonstrates indicates that it can influence the development of local inflammatory processes and enhance immune regulation in birds. Our research has shown that clinoptilolite influences on an increase in birds' resistance to infection, as confirmed by clinical observations and anatomopathological examination and by the increase in the synthesis of acute phase proteins with immunoregulatory properties.

Training Program Intensity Induces an Acute Phase Response in Clinically Healthy Horses

Physiological and hematochemical changes associated with exercise have been extensively investigated in equine species. It is known that stress elevates circulating levels of acute phase proteins (APPs). This survey evaluated whether horses trained with different training programs exhibit changes in APP levels after exercise event. Twenty Saddle Italian horses (11 geldings and 9 females, 9 ± 1 years old, body weight of 425 ± 35 kg) were divided into two equal groups according to the intensity of training programs they were subjected: group A was subjected to an intense training program, group B was subjected to a moderate training program. At the end of the training period, horses were subjected to a simulated exercise event (show jumping course of 400 m length with 12 obstacles). From horses, blood samples were collected at rest conditions (TREST) and after 12 and 24 hour from the end of exercise (T12 h and T24 h); the concentration of serum amyloid A (SAA), haptoglobin, albumin, total proteins, iron, and fibrinogen was assessed. The circulating levels of SAA, fibrinogen, and iron were influenced by simulated exercise event (P < .01), starting from 12 hour after the end of exercise, suggesting the onset of an acute phase–like response, and it would seem that training program intensity the horses underwent also affected the degree of response, although only SAA values were significantly different between groups (P < .001). The findings obtained suggest that jumping exercise induces an acute phase response; however, further studies are advocated to better evaluate mechanisms by which exercise activates this response in the athletic horse.

Determination of serum amyloid A, haptoglobin and hepcidin levels in calves with endemic viral pneumonia

The aim of this study was to investigate serum amyloid A, haptoglobin and hepcidin levels in respiratory infections caused by various viral agents in calves. Pneumonia is an infectious or non-infectious disease affecting the lungs of all animals, and during the inflammation, blood levels of acute phase proteins increase rapidly. Hepcidin is a hormone that has many functions and is known as type II acute phase reactant. The blood samples were collected from a total of 20 calves to form the study group. The control group consisted of 10 healthy animals. Sera were analyzed with ELISA for antigen detection. According to the results, Bovine herpesvirus type-1 (BHV-1) was positive in 3 calves, Bovine viral diarrhea virus (BVDV) was positive in 3 calves, Bovine respiratory syncytial virus (BRSV) was positive in 1 calf, and Bovine parainfluenza virus type 3 (BPI3) was positive in 1 calf. Adenovirus infection was detected in 5 animals together with other viruses. Mixed infections were observed in 12 calves. Haptoglobin, serum amyloid A and hepcidin values were measured in sera. According to the results, statistically significant differences were observed between the two groups for the haptoglobin (P&amp;lt;0.01), serum amyloid A (P&amp;lt;0.05) and hepcidin (P&amp;lt;0.05). It was concluded that these parameters can be used to support the diagnosis of respiratory infections of the calves.

Survey on Serum Amyloid A and Haptoglobin Concentrations in Normal or Sensitive to Rumen Acidosis Holstein Dairy Cows

BACKGROUND: Diagnosis and prognosis of inflammatory conditions based on acute phase proteins (APPs) level in blood has been exploited for a long time in human medicine and their changes in SARA condition is considered in veterinary medicine. OBJECTIVES: To evaluate the variations of serum amyloid A (SAA) and haptoglobin (Hp) as main acute phase proteins in cow with normal pH or cows that experienced rumen pH ≤5.8 during first days after parturition. METHODS: A total of 106 multiparous Holstein dairy cows were randomly selected after parturition in two different seasons of winter and summer 2017. Cows were divided into 2 groups as normal cows with pH >5.8 or rumen pH ≤5.8. Ruminal fluid samples were collected through stomach tube for rumen pH and blood samples were taken from the coccygeal vein of cows concurrently once per day at days 4, 11 and 18 post-partum. SAA and Hp were determined in blood samples. The PROC MIXED of SAS (2003) was used for all determined variables with repeated measures. BCS, parity and milk yield were included as fixed and cows as random effect. The significant level was declared at P≤0.05, and tendency toward significance was considered at 0.05 5.8. For all examined cows, SAA concentration was greater in winter than summer (P 5.8. CONCLUSIONS: Results showed that rumen pH ≤5.8 seems not to stimulate the APPs production

Effects of vaccination on acute-phase protein response in broiler chicken.

Broiler chickens experience an acute-phase response (APR) through vaccination, which reflects the innate immunity and stress related to immunization. It is also considered that APR can modulate adaptive immunity and response to infection. As biomarkers for APR, assessing the acute-phase proteins (APPs) function and their levels in response to immunization is of great value for vaccine design, development and administration. In this study, the heterophils/lymphocyte (H/L) ratio and the level of APPs was evaluated in broilers with three different Newcastle disease (ND) vaccination regimens. Inactivated ND vaccine (IND) was administered by the intramuscular route. Live attenuated strains, Lasota and Vitapest, was administered by ocular routes. H/L ratio, serum amyloid A (SAA) and alpha-1 acid glycoprotein (AGP) were measured before and after two rounds of vaccination on days 10 and 21. In a comparison between the three vaccines, H/L ratio in IND group significantly increased to 3 fold (1.48 ± 0.41) after the first vaccination while the Lasota and Vitapest showed a milder response. The concentration of SAA increased after 24h by 1.8-fold in IND group (0.116 ± 0.015 mg/L) and 2-fold in Lasota group (0.14 ± 0.002 mg/L). Significant changes were found in Vitapest group after 48h post vaccination (0.113 ± 0.016 mg/L). Elevation pattern of AGP, 24 hours after first vaccination in IND (3.5-fold) and Vitapest (2.5-fold) was different from Lasota in which the peak was reached after 48 hours (2.9-fold). Except for IND group, no significant changes in SAA and AGP concentrations were detected after the second vaccination. A significant positive correlation between SAA values at day 22 and HI titers at day 28 (r = 0.998, P≤0. 0.005) was found. According to these results, different types of ND vaccines can cause different patterns of acute phase responses. Assessment of stress and level of acute-phase proteins can be used for prediction of immune response outcomes in vaccine design and development.

Analytical characterization of trace elements (zinc, copper, cadmium, lead and selenium) in saliva of pigs under common pathological conditions in the field: a pilot study

BackgroundThis study is focused on the measurement of trace elements (zinc, copper, cadmium, lead and selenium) in the saliva of pigs in order to study their levels on different porcine pathological conditions in the field. The experiment involved 15 pigs without clinical signs of disease and 42 diseased pigs (suffering from lameness, rectal prolapse, fatigue or growth rate retardation). Individual saliva samples were collected, allowing the pigs to chew a sponge each for trace element quantifications through atomic absorption spectrometry (AAS). Since this is the first report on the measurements of trace elements in porcine saliva, a routine analytical validation study was performed for the quantification of all the studied elements. Moreover, the acute phase proteins C-reactive protein (CRP) and haptoblobin (Hp), the total antioxidant capacity (TAC) and adenosine deaminase (ADA) were quantified in the saliva samples for the animal’s health status assessment.ResultsModifications in the levels of acute phase proteins or ADA were only recorded in animals with lameness and rectal prolapse and those with fatigue respectively. Moreover, TAC level changes were observed in pigs with growth-rate retardation. However, alterations in the levels of two or more trace elements were reported for all the different groups of diseased pigs with evident variations within pathologies.ConclusionsThe salivary quantification of trace elements could be considered as a complementary tool to acute phase proteins, TAC and ADA determinations for disease detection and differentiation in the pig and should be explored in greater depth.

Transcriptional regulation of retinol binding protein 4 by Interleukin-6 via peroxisome proliferator-activated receptor α and CCAAT/Enhancer binding proteins

Interleukin-6 (IL-6) is a major mediator of the acute phase response (APR) that regulates the transcription of acute phase proteins (APPs) in the liver. During APR, the plasma levels of negative APPs including retinol binding protein 4 (RBP4) are reduced. Activation of the IL-6 receptor and subsequent signaling pathways leads to the activation of transcription factors, including peroxisome proliferator-activated receptor alpha (PPARα) and CCAAT/enhancer binding protein (C/EBP), which then modulate APP gene expression. The transcriptional regulation of RBP4 by IL-6 is not fully understood. Therefore, this study aimed to elucidate the molecular mechanisms of PPARα and C/EBP isoforms in mediating IL-6 regulation of RBP4 gene expression. IL-6 was shown to reduce the transcriptional activity of RBP4, and functional dissection of the RBP4 promoter further identified the cis-acting regulatory elements that are responsible in mediating the inhibitory effect of IL-6. The binding sites for PPARα and C/EBP present in the RBP4 promoter were predicted at −1079 bp to −1057 bp and −1460 bp to −1439 bp, respectively. The binding of PPARα and C/EBPs to their respective cis-acting elements may lead to antagonistic interactions that modulate the IL-6 regulation of RBP4 promoter activity. Therefore, this study proposed a new mechanism of interaction involving PPARα and different C/EBP isoforms. This interaction is necessary for the regulation of RBP4 gene expression in response to external stimuli, particularly IL-6, during physiological changes.

Dynamics of serum levels of acute phase proteins as a factor in the prenatal prognosis of intrauterine infection of newborns during prolongation of pregnancy in the period of 24—33 weeks with premature rupture of the fetal membranes

Dynamics of serum levels of acute phase proteins as a factor in the prenatal prognosis of intrauterine infection of newborns during prolongation of pregnancy in the period of 24—33 weeks with premature rupture of the fetal membranes

Пролиферативные заболевания матки: клинико-анамнестические, иммунологические и молекулярно-генетические аспекты

Objective. To perform comparative analysis of clinical data, serum levels of acute-phase proteins, cytokines, steroid hormones, and expression of genes encoding sex hormone receptors in tissues of patients with proliferative diseases of the uterus. Patients and methods. We analyzed clinical data of 349 patients with various proliferative diseases of the uterus. We also evaluated their serum levels of α2-macroglobulin, pregnancy-associated α2-glycoprotein, their immunocomplexes with IgG, lactoferrin, VEGF, IL-6, TNFa, IL-8, and sex hormones. Uterine tissue samples were tested for the expression of genes encoding estrogen receptors α and β (ЕRα, ЕRβ) and progesterone receptors (PGR). Data analysis was performed using the statistical packages of SAS 9.4, STATISTICA12, and IBM-SPSS Statistics 22. Results. The changes in the level of acute-phase proteins indicated inflammation. In isolated uterine fibroids, expression of genes encoding progesterone receptors prevailed, whereas in isolated adenomyosis, expression of genes encoding estrogen receptors prevailed. Patients with both uterine fibroids and adenomyosis demonstrated similar levels of expression of genes encoding sex steroid hormone receptors. Tissues of uterine leiomyosarcoma were characterized by downregulated expression of genes encoding sex steroid hormone receptors. Conclusion. Upregulation of genes encoding progesterone receptors in isolated uterine fibroids confirms that therapy with progesterone receptor blockers is appropriate in this case. The predominance of expression of genes encoding estrogen receptors in isolated adenomyosis indicates local hyperestrogenism, justifying the use of progestogens and antiestrogens. Equal expression of genes encoding estrogen and progesterone receptors in patients with combined disease, as wells as high frequency of inflammatory changes in tissues and increased serum levels of inflammatory markers, proves the need for antiinflammatory therapy. Key words: adenomyosis, inflammation, steroid receptor genes, leiomyosarcoma, uterine fibroids, gene expression

Contribution of acute-phase reaction proteins to the diagnosis and treatment of 2019 novel coronavirus disease (COVID-19)

The emergence of 2019 novel coronavirus disease (COVID-19) is currently a global concern. In this study, our goal was to explore the changing expression levels of acute-phase reaction proteins (APRPs) in the serum of COVID-19 patients and to elucidate the immunological characteristics of COVID-19. In the study design, we recruited 72 COVID-19 patients, including 22 cases of mild degree, 38 cases of moderate degree and 12 cases of severe degree. We also recruited 20 patients with community-acquired pneumonia (CAP) and 20 normal control subjects as a comparison. Fasting venous blood was taken to detect the content of complement 3 (C3), complement 4 (C4), C-reactive protein (CRP), serum amyloid A (SAA) and prealbumin (PA). When compared the COVID-19 group with the CAP and normal control groups, respectively, the mean value of CRP and SAA in the COVID-19 group (including mild, moderate and severe patients) had increased significantly (P < 0.01), whereas the mean values of C3, C4 and PA decreased (P < 0.01). For the asymptomatic or mild symptomatic patients with COVID-19, the actual aggravation of disease may be more advanced than the clinical appearances. Meanwhile, the statistical analyses indicated that the development of COVID-19 brought about a significant increase in the content of CRP and SAA (P < 0.01), and a decline in the content of C3, C4 and PA (P < 0.01). These findings suggested that the changes in the level of APRPs could be used as indicators to identify the degree and progression of COVID-19, and the significant changes might demonstrate the aggravation of disease. This study provided a new approach to improve the clinical management plan and prognosis of COVID-19.

Evaluation of Plasmatic Levels of Negative and Positive Acute Hepatic Phase Proteins in Patients who Underwent Major Surgery

The acute hepatic phase response is defined as a reaction that includes hepatic synthesis of proteins, consisting in the increase of some proteins called positive acute phase proteins and the simultaneous decrease of others called negative acute phase proteins. This study describes this hepatic reaction, based on a series of consecutive determinations, at three different time intervals (right before a major surgery event, 24 and 48 hours after the intervention), of the plasmatic levels of transferrin, albumin, fibrinogen and C reactive protein (CRP). Subsequently, the data was analyzed using Jamovi 2019, version 0.9. The inferential statistics consisted in calculating an ANOVA test that compared the values at 24 hours and 48 hours versus the values right before the major surgery. The results were validated by calculating the p value (p[0.05) as well as conducting correlation tests by determining the Pearson coefficient which shows the values of CRP, fibrinogen, transferrin and albumin are independent of each other and do not interact. The multiple ANOVA comparative test reveals the lack of interaction between the values of determined proteins, regardless of the moment of determination.

Evaluation of Plasmatic Levels of Negative and Positive Acute Hepatic Phase Proteins in Patients who Underwent Major Surgery

The acute hepatic phase response is defined as a reaction that includes hepatic synthesis of proteins, consisting in the increase of some proteins called positive acute phase proteins and the simultaneous decrease of others called negative acute phase proteins. This study describes this hepatic reaction, based on a series of consecutive determinations, at three different time intervals (right before a major surgery event, 24 and 48 hours after the intervention), of the plasmatic levels of transferrin, albumin, fibrinogen and C reactive protein (CRP). Subsequently, the data was analyzed using Jamovi 2019, version 0.9. The inferential statistics consisted in calculating an ANOVA test that compared the values at 24 hours and 48 hours versus the values right before the major surgery. The results were validated by calculating the p value (p[0.05) as well as conducting correlation tests by determining the Pearson coefficient which shows the values of CRP, fibrinogen, transferrin and albumin are independent of each other and do not interact. The multiple ANOVA comparative test reveals the lack of interaction between the values of determined proteins, regardless of the moment of determination.

A reporter mouse for non-invasive detection of toll-like receptor ligands induced acute phase responses

The acute phase response (APR) is a systemic first-line defense against challenges including infection, trauma, stress, and neoplasia. Alteration of acute phase protein (APP) levels in plasma is the most important change during acute phase response. C-reactive protein (CRP), which increases dramatically during inflammation onset, is an indicator of inflammation. To monitor the process of APR, we generated human CRP promoter-driven luciferase transgenic (hCRP-Luc) mice to quantify the hCRP promoter activation in vivo. The naïve female hCRP-Luc mice express low basal levels of liver bioluminescence, but the naïve male hCRP-Luc mice do not. Thus, female hCRP-Luc mice are suitable for monitoring the process of APR. The liver bioluminescence of female hCRP-Luc mice can be induced by several toll-like receptor (TLR) ligands. The expression of liver bioluminescence was highly sensitive to endotoxin stimulation in a dose-dependent manner. On-off-on bioluminescence response was noted in female hCRP-Luc mice upon two endotoxin stimulations one month apart. The LPS-induced bioluminescence of the female hCRP-Luc mice was IL-6-mediated and associated with APP alpha-1-acid glycoprotein expression. In conclusion, the female hCRP-Luc mouse is a non-invasive, sensitive and reusable reporter tool for APR.

Serum Alpha-1 Antitrypsin Levels and the Clinical Course of Chronic Obstructive Pulmonary Disease.

PurposeAlpha-1 antitrypsin deficiency is associated with the development of chronic obstructive pulmonary disease (COPD), whereas increased levels of serum alpha-1antitrypsin occur in response to inflammation. The effects of alpha-1 antitrypsin levels on the clinical course of COPD had been unclear. We investigated the association of serum alpha-1 antitrypsin levels with the clinical course of COPD patients based on data from a 10-year prospective cohort study.Patients and methodsWe analyzed 278 COPD patients who participated in the Hokkaido COPD cohort study and who did not meet the criteria for alpha-1 antitrypsin deficiency. We divided the subjects into 3 groups according to quartiles of serum alpha-1 antitrypsin levels at baseline: lower group (<116 mg/dL, n = 66); middle group (116 to ≤141 mg/dL, n = 145); and higher group (>141 mg/dL, n = 67). The annual change in forced expiratory volume in 1 s (FEV1) and events of COPD exacerbation were monitored during the first 5 years, and mortality was followed-up during the entire 10 years.ResultsAt baseline, the higher group showed lower body mass index; higher computed tomography emphysema score; lower diffusing capacity; higher levels of acute-phase proteins; and higher blood neutrophil counts. Longitudinal analyses revealed that in the higher group, the annual decline in FEV1 was rapid and the 10-year mortality was higher, but there was no association between serum alpha-1 antitrypsin levels and time to first exacerbation.ConclusionCOPD subjects with higher serum alpha-1 antitrypsin levels were associated with a worse systemic inflammation status and higher 10-year mortality.

Measurement of Organ-Specific and Acute-Phase Blood Protein Levels in Early Lyme Disease.

Lyme disease results from infection of humans with the spirochete Borrelia burgdorferi. The first and most common clinical manifestation is the circular, inflamed skin lesion referred to as erythema migrans; later manifestations result from infections of other body sites. Laboratory diagnosis of Lyme disease can be challenging in patients with erythema migrans because of the time delay in the development of specific diagnostic antibodies against Borrelia. Reliable blood biomarkers for the early diagnosis of Lyme disease in patients with erythema migrans are needed. Here, we performed selected reaction monitoring, a targeted mass spectrometry-based approach, to measure selected proteins that (1) are known to be predominantly expressed in one organ (i.e., organ-specific blood proteins) and whose blood concentrations may change as a result of Lyme disease, or (2) are involved in acute immune responses. In a longitudinal cohort of 40 Lyme disease patients and 20 healthy controls, we identified 10 proteins with significantly altered serum levels in patients at the time of diagnosis, and we also developed a 10-protein panel identified through multivariate analysis. In an independent cohort of patients with erythema migrans, six of these proteins, APOA4, C9, CRP, CST6, PGLYRP2, and S100A9, were confirmed to show significantly altered serum levels in patients at time of presentation. Nine of the 10 proteins from the multivariate panel were also verified in the second cohort. These proteins, primarily innate immune response proteins or proteins specific to liver, skin, or white blood cells, may serve as candidate blood biomarkers requiring further validation to aid in the laboratory diagnosis of early Lyme disease.