Browsing by Subject "Acute phase response"

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  • Danielsen, Pernille Høgh; Knudsen, Kristina Bram; Štrancar, Janez; Umek, Polona; Koklič, Tilen; Garvas, Maja; Vanhala, Esa; Savukoski, Sauli; Ding, Yaobo; Madsen, Anne Mette; Jacobsen, Nicklas Raun; Weydahl, Ingrid Konow; Berthing, Trine; Poulsen, Sarah Søs; Schmid, Otmar; Wolff, Henrik; Vogel, Ulla (2020)
    Nanomaterial (NM) characteristics may affect the pulmonary toxicity and inflammatory response, including specific surface area, size, shape, crystal phase or other surface characteristics. Grouping of TiO2 in hazard assessment might be challenging because of variation in physicochemical properties. We exposed C57BL/6 J mice to a single dose of four anatase TiO2 NMs with various sizes and shapes by intratracheal instillation and assessed the pulmonary toxicity 1, 3, 28, 90 or 180 days post-exposure. The quartz DQ12 was included as benchmark particle. Pulmonary responses were evaluated by histopathology, electron microscopy, bronchoalveolar lavage (BAL) fluid cell composition and acute phase response. Genotoxicity was evaluated by DNA strand break levels in BAL cells, lung and liver in the comet assay. Multiple regression analyses were applied to identify specific TiO2 NMs properties important for the pulmonary inflammation and acute phase response. The TiO2 NMs induced similar inflammatory responses when surface area was used as dose metrics, although inflammatory and acute phase response was greatest and more persistent for the TiO2 tube. Similar histopathological changes were observed for the TiO2 tube and DQ12 including pulmonary alveolar proteinosis indicating profound effects related to the tube shape. Comparison with previously published data on rutile TiO2 NMs indicated that rutile TiO2 NMs were more inflammogenic in terms of neutrophil influx than anatase TiO2 NMs when normalized to total deposited surface area. Overall, the results suggest that specific surface area, crystal phase and shape of TiO2 NMs are important predictors for the observed pulmonary effects of TiO2 NMs.
  • Niine, Tarmo; Peetsalu, Kristel; Nieminen, Mauri; Oksanen, Antti; Soveri, Timo; Orro, Toomas (2017)
    This longitudinal observational study was conducted to investigate the spontaneous effect of Giardia and Cryptosporidium infections on acute phase response (APR) in reindeer calves (Rangifer tarandus tarandus) in Finnish Lapland. Serum (n = 609) and faecal samples (n = 366) were collected from 54 reindeer calves aged zero to 33 days. The samples were analysed for Giardia, Cryptosporidium, acute phase proteins (APP) and gamma-globulins. Linear regression models were used to investigate associations of early Giardia infection (before 12 days of life) with the response of APPs and acquiring of passive immunity. Giardia was detected in 100% and Cryptosporidium in 23% of calves. There was a negative association between early Giardia infection and gamma-globulin concentrations (p = 0.032) and a positive association with serum amyloid A (SAA) concentrations (p = 0.042). The results suggest a protective effect of colostrum against Giardia infection and that early infection may induce activation of APR.
  • Seppä-Lassila, Leena; Eerola, Ulla; Orro, Toomas; Härtel, Heidi; Simojoki, Heli; Autio, Tiina; Pelkonen, Sinikka; Soveri, Timo (2017)
    Healthy, thriving calves are essential for beef calf production. We studied the health status and factors associated with the growth of beef calves in six cow-calf herds during the first month of the calves’ lives and at weaning age (200 days). The six herds were visited three times, when calves were approximately 3 days, 16 days and 30 days of age. On each visit calves (n=37) were clinically examined, weighed or measured, blood samples were collected, faecal samples obtained and deep nasopharyngeal swabs were taken. Each blood sample was analysed for acute phase proteins (haptoglobin, serum amyloid-A, fibrinogen), total proteins and albumin, the faecal sample for intestinal tract pathogens (rotavirus, bovine coronavirus, enterotoxigenic Escherichia coli and Salmonella, oocysts of Eimeria coccidia and Cryptosporidium, and nematode eggs), and the nasopharyngeal swab for respiratory tract pathogens (bovine coronavirus (BCV), respiratory syncytial virus (RSV), bacteria and mycoplasma). Clinical diagnosis of respiratory tract disease, diarrhoea or umbilical disease was set at 15.0% for all the three consecutive examinations combined (n=107), but only few pathogens were detected from the samples. The increased levels of acute phase proteins were neither associated with any of the diseases nor with the pathogens. Random intercept linear models were used to explore factors affecting early (3–30 days) and long-term (3–200 days) growth, showing that calves with elevated serum amyloid-A concentrations at the age of 16 days had lower long-term growth. Increased albumin concentration at 30 days of age and higher parity of the dam increased early-term growth. The lack of association between a disease and the acute phase protein may stem from the low disease prevalence in the beef calves examined. The measurement of acute phase proteins of a young calf can help identify animals with possible future growth deficiencies, although the mechanisms through which the association between acute phase proteins and growth has yet to be explained. © 2016 Elsevier B.V.
  • Seppä-Lassila, Leena; Orro, Toomas; Lassen, Brian; Lasonen, Riikka; Autio, Tiina; Pelkonen, Sinikka; Soveri, Timo (2015)
    In this study, the association between Eimeria spp. related signs and innate immune response in dairy calves was examined. Calves (n= 100) aged 15-60 days were clinically examined and faecal samples, blood samples and deep nasopharyngeal swabs obtained. The samples were analysed for intestinal pathogens, acute phase proteins and WBC count, and respiratory tract pathogens, respectively. Diarrhoea was diagnosed in 32.6% (23.3-43.0%, 95% CI) of calves. An association between the pathogenic Eimeria spp. and diarrhoea was detected by multiple correspondence analysis. Eimeria related signs (diarrhoea, presence of pathogenic species and total oocyst count) were combined resulting a four level variable. Calves with weak signs of eimeriosis had decreased haptoglobin concentrations (p = 0.02) and increased fibrinogen concentrations (p = 0.048) compared to no signs. Increased haptoglobin and fibrinogen concentrations were associated with respiratory tract infection and umbilical infection. Serum amyloid A and WBC counts showed no association with signs of eimeriosis or clinical diagnoses. (C) 2015 Elsevier Ltd. All rights reserved.
  • Nissinen, Tuuli A.; Hentilä, Jaakko; Penna, Fabio; Lampinen, Anita; Lautaoja, Juulia H.; Fachada, Vasco; Holopainen, Tanja; Ritvos, Olli; Kivelä, Riikka; Hulmi, Juha J. (2018)
    Background Cancer cachexia increases morbidity and mortality, and blocking of activin receptor ligands has improved survival in experimental cancer. However, the underlying mechanisms have not yet been fully uncovered. Methods The effects of blocking activin receptor type 2 (ACVR2) ligands on both muscle and non-muscle tissues were investigated in a preclinical model of cancer cachexia using a recombinant soluble ACVR2B (sACVR2B-Fc). Treatment with sACVR2B-Fc was applied either only before the tumour formation or with continued treatment both before and after tumour formation. The potential roles of muscle and non-muscle tissues in cancer cachexia were investigated in order to understand the possible mechanisms of improved survival mediated by ACVR2 ligand blocking. Results Blocking of ACVR2 ligands improved survival in tumour-bearing mice only when the mice were treated both before and after the tumour formation. This occurred without effects on tumour growth, production of pro-inflammatory cytokines or the level of physical activity. ACVR2 ligand blocking was associated with increased muscle (limb and diaphragm) mass and attenuation of both hepatic protein synthesis and splenomegaly. Especially, the effects on the liver and the spleen were observed independent of the treatment protocol. The prevention of splenomegaly by sACVR2B-Fc was not explained by decreased markers of myeloid-derived suppressor cells. Decreased tibialis anterior, diaphragm, and heart protein synthesis were observed in cachectic mice. This was associated with decreased mechanistic target of rapamycin (mTOR) colocalization with late-endosomes/lysosomes, which correlated with cachexia and reduced muscle protein synthesis. Conclusions The prolonged survival with continued ACVR2 ligand blocking could potentially be attributed in part to the maintenance of limb and respiratory muscle mass, but many observed non-muscle effects suggest that the effect may be more complex than previously thought. Our novel finding showing decreased mTOR localization in skeletal muscle with lysosomes/late-endosomes in cancer opens up new research questions and possible treatment options for cachexia.