Acute phase protein levels in dogs with mast cell tumours and sarcomas

<p><b>Context:</b> The acute phase protein response is part of a non-specific and complex host response to inflammation. It occurs shortly after tissue injury and may be induced by a range of different causes, including infectious, inflammatory, neoplastic, traumatic or immunological disease. Although it was conventionally believed that APPs were exclusively hepatocyte derived, there is increasing evidence to support extra-hepatic generation in neoplastic and other disease states. In people, C-reactive protein (CRP) has been shown to be of value in identifying metastatic disease from primary renal tumours as well as showing promise for monitoring rejection of renal transplants. Serum CRP correlates with survival in colorectal cancer and oesophageal squamous cell carcinoma while serum amyloid A (SAA) concentrations correlate with cancer activity, stage and prognosis in gastric tumours. Recent immunohistochemical studies in people with oesophageal carcinoma suggest that tumour tissue may itself elaborate APP with a poorer survival and outcome associated with tumours elaborating higher levels of CRP. A similar association has been seen between alpha-1 acid glycoprotein (AGP) and colorectal tumours and ovarian carcinoma.</p> <p>As yet, studies regarding APP values in neoplastic conditions in dogs are limited, and many are non-specific. In veterinary patients, elevated levels of AGP have been identified in dogs with a range of tumours with localisation to liver and splenic tissue in one study. Another study found higher levels of AGP in dogs with non-specific tumours of grade III-IV based on the WHO Tumour Node Metastasis (TNM) scale and elevated serum AGP has been documented in non-specific tumour-bearing cats. Elevated CRP levels have been documented in both dogs and cats with lymphoma and serum CRP may be used as an indicator of complete remission status in dogs with multicentric lymphoma. Elevated levels of CRP, Haptoglobin (Hp) and SAA have been identified in dogs with mammary tumours, with significant increases over normal in the presence of metastatic disease, primary tumours greater than 5cm in diameter and those with ulceration.</p> <p>In this study we evaluated an APP profile using four APPs (CRP, Hp, SAA and AGP), in dogs with mast cell tumours (MCTs) and sarcomas to assess whether the APP profile would change in reflection of tumour presence; whether the extent of any change would correlate with tumour grade; and whether the changes would differ with tumour type.</p> <p><b>Approach:</b> Patients with naturally occurring MCTs and sarcomas presenting for staging and treatment were included if they met the study criteria. Criteria for inclusion were that the patient was not currently being treated with steroids, did not have a recent history of infectious or inflammatory disease other than the tumour, a definitive histological diagnosis was available and a full staging procedure was completed prior to surgery using standard oncological protocols to identify metastatic disease where present. Following surgical resection each tumour was submitted for full histological evaluation and grading to include assessment of the margins of excision. Cases were only enrolled in the study if blood sampling formed part of the clinical investigation and/or treatment, and where residual blood was available after diagnostic sampling which would otherwise have been disposed of as clinical waste. In brief, the CRP levels were determined by immunoturbidometric assay and Hp by means of haemoglobin binding capacity assay. SAA was measured with a commercial canine ELISA kit (TriDelta Development, Dublin, Ireland) and AGP was measured with a commercial radial immunodiffusion assay (J-Path Inc, Tokyo, Japan).</p> <p><b>Results:</b> All comparisons using continuous data were checked for normality and equality of variances and appropriate statistical tests were employed (student’s t test operationalised as a two-sample Welch’s test for samples of unequal sizes and variances, Mann-Whitney, Chi-square and Fishers exact tests as appropriate). In MCTs, the CRP and AGP were elevated above reference ranges, Hp showed no significant change and SAA dropped relative to the reference range. In sarcoma patients CRP, Hp and AGP were all elevated above reference ranges. None of the tumour grade differences were significant apart from SAA in sarcoma patients where values in grade 2 sarcoma were significantly higher than those in grade 1.</p> <p><b>Interpretation and notes of caution:</b> The numbers in our groups were small which compromises the validity of statistical evaluation so our results must be interpreted with caution. However some interesting relationships have emerged from the initial evaluation which suggests that APP profiles may have potential for screening in patients with neoplastic disease. For patients with MCTs, CRP and AGP levels would be expected to increase, with a concurrent drop in SAA levels. In sarcoma patients CRP, AGP and Hp can all be expected to increase. These initial results need to be evaluated in larger numbers of cases with naturally occurring disease to validate the findings, to assess whether the presence and extent of metastatic disease has a significant effect, and also to confirm whether the values alter after surgical resection of the primary tumour.</p> <p><b>Significance of findings:</b> If there are consistent and specific changes in APP profiles associated with different tumour types in dogs, as is the case with a wide range of cancers in humans, then there may be potential for APP profiles on routine blood samples to be used as indicators of disease, or where monitoring for recurrence. Whether they could also have potential for assessment of the presence of metastatic disease and prognosis as in people is unknown as yet.</p&gt

The negative acute phase response of serum transthyretin following Streptococcus suis infection in the pig

Peer reviewedPublisher PD

Acute phase protein response in an experimental model of ovine caseous lymphadenitis

<p>Abstract</p> <p>Background</p> <p>Caseous lymphadenitis (CLA) is a disease of small ruminants caused by <it>Corynebacterium pseudotuberculosis</it>. The pathogenesis of CLA is a slow process, and produces a chronic rather than an acute disease state. Acute phase proteins (APP) such as haptoglobin (Hp) serum amyloid A (SAA) and α₁acid glycoprotein (AGP) are produced by the liver and released into the circulation in response to pro-inflammatory cytokines. The concentration of Hp in serum increases in experimental CLA but it is not known if SAA and AGP respond in parallel or have differing response profiles.</p> <p>Results</p> <p>The concentration in serum of Hp, SAA and AGP in 6 sheep challenged with 2 × 10⁵cells of <it>C. pseudotuberculosis </it>showed significant increases (P < 0.05) compared to 3 unchallenged control sheep. By day 7 post infection. (p.i.) the Hp and SAA concentrations reached mean (± SEM) values of 1.65 ± 0.21 g/L and 18.1 ± 5.2 mg/L respectively. Thereafter, their concentrations fell with no significant difference to those of the control sheep by day 18 p.i.. In contrast, the serum AGP concentration in infected sheep continued to rise to a peak of 0.38 ± 0.05 g/L on day 13 p.i., after which a slow decline occurred, although the mean concentration remained significantly higher (P < 0.05) than the control group up to 29 days p.i.. Specific IgG to phospholidase D of <it>C. pseudotuberculosis </it>became detectable at 11 days p.i. and continued to rise throughout the experiment.</p> <p>Conclusion</p> <p>The serum concentrations of Hp, SAA and AGP were raised in sheep in an experimental model of CLA. An extended response was found for AGP which occurred at a point when the infection was likely to have been transforming from an acute to a chronic phase. The results suggest that AGP could have a role as a marker for chronic conditions in sheep.</p

Acute phase proteins, interleukin 6, and heat shock protein 70 in broiler chickens administered with corticosterone

An experiment was conducted to determine the effect of corticosterone (CORT) administration on serum ovotransferrin (OVT), α1-acid glycoprotein (AGP), ceruloplasmin (CPN), and IL-6 concentrations, and brain heat shock protein (HSP) 70 expression in broiler chickens. From 14 to 20 d of age, equal numbers of birds were subjected to either (i) daily intramuscular injection with CORT in ethanol:saline (1:1, vol/vol) at 6 mg/kg of BW, or (ii) daily intramuscular injection with 0.5 mL ethanol:saline (1:1, vol/vol; control). Blood samples were collected before CORT treatment (14 d old), 3 and 7 d after CORT injections, and 4 d after cessation of CORT administration for determination of serum levels of CORT, OVT, AGP, CPN, and IL-6. Brain samples (whole cerebrum) were collected to measure HSP 70 density. Although CORT administration significantly increased feed intake, weight gain was significantly depressed. Administration of CORT also increased CORT, OVT, CPN, AGP, IL-6, and HSP 70 expression. Four days following cessation of CORT administration, OVT declined to the basal level but not CPN and AGP. In conclusion, an elevation in CORT can induce an acute-phase response and HSP 70 expression. Thus, APP and HSP 70 may be of value as indicators of stress in poultry

Maternal undernutrition and the ovine acute phase response to vaccination

Background: The acute phase response is the immediate host response to infection, inflammation and trauma and can be monitored by measuring the acute phase proteins (APP) such as haptoglobin ( Hp) or serum amyloid A (SAA). The plane of nutrition during pregnancy is known to affect many mechanisms including the neuroendocrine and neuroimmune systems in neonatal animals but effects on the APP are unknown. To investigate this phenomenon the serum concentration of Hp and SAA was initially determined in non-stimulated lambs from 3 groups (n = 10/group). The dams of the lambs of the respective groups were fed 100% of requirements throughout gestation (High/High; HH); 100% of requirements for the first 65 d of gestation followed by 70% of requirements until 125 d from when they were fed 100% of requirements (High/Low; HL); 65% of liveweight maintenance requirements for the first 65 d gestation followed by 100% of requirements for the remainder of pregnancy ( Low/High; LH). The dynamic APP response in the lambs was estimated by measuring the concentration of Hp and SAA following routine vaccination with a multivalent clostridial vaccine with a Pasteurella component, Heptavac P (TM) following primary and secondary vaccination. Results: The Hp and SAA concentrations were significantly lower at the time of vaccination ( day 8-14) than on the day of birth. Vaccination stimulated the acute phase response in lambs with increases found in both Hp and SAA. Maternal undernutrition led to the SAA response to vaccination being significantly lower in the HL group than in the HH group. The LH group did not differ significantly from either the HH or HL groups. No significant effects of maternal undernutrition were found on the Hp concentrations. A significant reduction was found in all groups in the response of SAA following the second vaccination compared to the response after the primary vaccination but no change occurred in the Hp response. Conclusion: Decreased SAA concentrations, post-vaccination, in lambs born to ewes on the HL diet shows that maternal undernutrition prior to parturition affects the innate immune system of the offspring. The differences in response of Hp and SAA to primary and secondary vaccinations indicate that the cytokine driven APP response mechanisms vary with individual AP

Influence of dietary Spirulin inclusion and lysozyme supplementation on the longissimus lumborum muscle proteome of newly weaned piglets

Research Areas: Biochemistry & Molecular BiologyArthrospira platensis (Spirulina) is a microalga with a high content of crude protein. It has a recalcitrant cell wall that limits the accessibility of the animal endogenous enzymes to its intracellular nutrients. Enzymatic supplementation aiming to degrade cell walls could benefit microalgae digestibility. The objective of this study was to evaluate the impact of dietary Spirulina and lysozyme supplementation over the muscle proteome of piglets during the post-weaning stage. Thirty piglets were randomly distributed among three diets: control (no microalga), SP (10% Spirulina) and SP + L (10% Spirulina +0.01% lysozyme). After 4 weeks, they were sacrificed and samples of the longissimus lumborum muscle were taken. The muscle proteome was analysed using a Tandem Mass Tag (TMT)-based quantitative approach. A total of 832 proteins were identified. Three comparisons were computed: SP vs Ctrl, SP + L vs Ctrl and SP + L vs SP. They had ten, four and twelve differentially abundant proteins. Glycogen metabolism and nutrient reserves utilization are increased in the SP piglets. Structural muscle protein synthesis increased, causing higher energy requirements in SP + L piglets. Our results demonstrate the usefulness of proteomics to disclose the effect of dietary microalgae, whilst unveiling putative mechanisms derived from lysozyme supplementation. Data available via ProteomeXchange with identifier PXD024083. Significance: Spirulina, a microalga, is an alternative to conventional crops which could enhance the environmental sustainability of animal production. Due to its recalcitrant cell wall, its use requires additional measures to prevent anti-nutritional effects on the feeding of piglets in the post-weaning period, during which they endure post-weaning stress. One of such measures could be CAZyme supplementation to help degrade the cell wall during digestion. Muscle proteomics provides insightful data on the effect of dietary microalgae and enzyme activity on piglet metabolism.info:eu-repo/semantics/publishedVersio

Animal board invited review: advances in proteomics for animal and food sciences

Animal production and health (APH) is an important sector in the world economy, representing a large proportion of the budget of all member states in the European Union and in other continents. APH is a highly competitive sector with a strong emphasis on innovation and, albeit with country to country variations, on scientific research. Proteomics (the study of all proteins present in a given tissue or fluid - i.e. the proteome) has an enormous potential when applied to APH. Nevertheless, for a variety of reasons and in contrast to disciplines such as plant sciences or human biomedicine, such potential is only now being tapped. To counter such limited usage, 6 years ago we created a consortium dedicated to the applications of Proteomics to APH, specifically in the form of a Cooperation in Science and Technology (COST) Action, termed FA1002 - Proteomics in Farm Animals: www.cost-faproteomics.org. In 4 years, the consortium quickly enlarged to a total of 31 countries in Europe, as well as Israel, Argentina, Australia and New Zealand. This article has a triple purpose. First, we aim to provide clear examples on the applications and benefits of the use of proteomics in all aspects related to APH. Second, we provide insights and possibilities on the new trends and objectives for APH proteomics applications and technologies for the years to come. Finally, we provide an overview and balance of the major activities and accomplishments of the COST Action on Farm Animal Proteomics. These include activities such as the organization of seminars, workshops and major scientific conferences, organization of summer schools, financing Short-Term Scientific Missions (STSMs) and the generation of scientific literature. Overall, the Action has attained all of the proposed objectives and has made considerable difference by putting proteomics on the global map for animal and veterinary researchers in general and by contributing significantly to reduce the East-West and North-South gaps existing in the European farm animal research. Future activities of significance in the field of scientific research, involving members of the action, as well as others, will likely be established in the future.European Science Foundation (Brussels, Belgium)info:eu-repo/semantics/publishedVersio

High intake of sugars and starch, low number of meals and low roughage intake are associated with equine gastric ulcer syndrome in a Belgian cohort

Equine gastric ulcer syndrome (EGUS) is a pathological condition affecting the glandular and squamous regions of the stomach. It is characterized by non-specific clinical signs, behavioural changes or can also be found without any overt clinical manifestations. Nutritional factors such as intermittent feeding, high sugars and starch intake, large amounts of straw as forage and prolonged time without access to forage have all been associated with an increased risk of equine squamous gastric disease (ESGD). The aim of this study was to investigate which nutritional practices are commonly seen in clinical ESGD cases in Belgium. Medical records of 27 horses referred to the equine nutritional service at Ghent University (2013-2018) due to equine gastric ulcer lesions were reviewed. Twenty-one healthy horses referred for dietary evaluation during the same period were selected as control cases (CC). Dietary evaluation was performed on an individual basis. Forage/concentrate ratio on dry matter basis, forage content in the diet, total dietary sugars and starch intake per day and per meal were analysed. Retrospective descriptive and statistical analyses were performed. Significantly, higher amounts of forage intake (%DM per BW) in the CC vs. ESGD group were noted (p <= .05) with average values of 1.39 (SD +/- 0.27) and 1.27 (SD +/- 0.70) respectively. There were no significant differences for sugars and starch intake in g/kg BW/day (p = .18). However, the sugars and starch intake per meal (g/kg BW/meal) in the CC group (average value 1.06, SD +/- 0.56) was significantly (p < .001) lower than in the EGUS group (average value 1.85 SD +/- 0.78). Forage intake below the recommended absolute minimum value as well as high sugars and starch intake were most commonly associated with EGUS in the present case series. An adequate diet formulation taking into account these main nutritional factors is therefore essential to avoid gastric problems in horses