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Srithunyarat, T., Hagman, R., Hoglund, O. V., Stridsberg, M., Hanson, J., Lagerstedt, A. S. & Pettersson, A. (2018). Catestatin, vasostatin, cortisol, and visual analog scale scoring for stress assessment in healthy dogs. Research in Veterinary Science, 117, 74-80
Open this publication in new window or tab >>Catestatin, vasostatin, cortisol, and visual analog scale scoring for stress assessment in healthy dogs
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2018 (English)In: Research in Veterinary Science, ISSN 0034-5288, E-ISSN 1532-2661, Vol. 117, p. 74-80Article in journal (Refereed) Published
Abstract [en]

The neuroendocrine glycoprotein chromogranin A is a useful biomarker for stress in humans. Chromogranin A epitopes catestatin and vasostatin can be measured in dogs using radioimmunoassays. The objective of this study was to evaluate catestatin and vasostatin as canine stress biomarkers in a clinical setting. Blood and saliva were collected from 33 healthy dogs that were familiar with sampling procedures and the animal hospital environment (control group) and 30 healthy dogs that were unacquainted (stress group). During sampling, stress behavior was scored by the same observer using visual analog scale (VAS). Plasma was analyzed for catestatin and vasostatin, serum for cortisol, and saliva for catestatin. Differences between groups were analyzed using two sample t-tests and P < 0.05 was considered significant. Stress behavior VAS score in the control group was significantly lower than in the stress group during blood (P = 0.002) and saliva (P = 0.0009) sampling. Serum cortisol and saliva catestatin concentrations in the stress group were higher than the control group (P = 0.003 and P < 0.0001, respectively). Serum cortisol concentrations were correlated with those of saliva (r = 0.34, P = 0.04) and plasma catestatin (r = 0.29, P = 0.03). Plasma catestatin and vasostatin did not differ significantly between groups. In conclusion, concentrations of saliva catestatin, and serum cortisol, and stress behavior VAS scores were significantly higher in the stress group. The results indicate that saliva catestatin may be useful as a biomarker for acute psychological stress in dogs.

Keywords
Biomarker, Canine, Chromogranin A, Psychological stress, Saliva
National Category
Veterinary Science
Identifiers
urn:nbn:se:uu:diva-354254 (URN)10.1016/j.rvsc.2017.11.015 (DOI)000430646300011 ()29195227 (PubMedID)
Available from: 2018-06-29 Created: 2018-06-29 Last updated: 2018-06-29Bibliographically approved
Srithunyarat, T., Hagman, R., Höglund, O. V., Olsson, U., Stridsberg, M., Jitpean, S., . . . Pettersson, A. (2017). Catestatin and vasostatin concentrations in healthy dogs. ACTA VETERINARIA SCANDINAVICA, 59, Article ID 1.
Open this publication in new window or tab >>Catestatin and vasostatin concentrations in healthy dogs
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2017 (English)In: ACTA VETERINARIA SCANDINAVICA, ISSN 0044-605X, Vol. 59, article id 1Article in journal (Refereed) Published
Abstract [en]

Background: The neuroendocrine glycoprotein chromogranin A is a useful biomarker in humans for neuroendocrine tumors and stress. Chromogranin A can be measured in both blood and saliva. The objective of this study was to investigate concentrations of and correlation between the chromogranin A epitopes catestatin and vasostatin in healthy dogs accustomed to the sample collection procedures. Blood and saliva samples were collected from 10 research Beagle dogs twice daily for 5 consecutive days, and from 33 privately-owned blood donor dogs in association with 50 different blood donation occasions. All dogs were familiar with sample collection procedures. During each sampling, stress behavior was scored by the same observer using a visual analog scale (VAS) and serum cortisol concentrations. Catestatin and vasostatin were analyzed using radioimmunoassays for dogs. Results: The dogs showed minimal stress behavior during both saliva sampling and blood sampling as monitored by VAS scores and serum cortisol concentrations. Few and insufficient saliva volumes were obtained and therefore only catestatin could be analyzed. Catestatin concentrations differed significantly and did not correlate significantly with vasostatin concentrations (P < 0.0001). Age, gender, breed, and time of sample collection did not significantly affect concentrations of plasma catestatin, vasostatin, and saliva catestatin. Conclusions: The normal ranges of plasma catestatin (0.53-0.98 nmol/l), vasostatin (0.11-1.30 nmol/l), and saliva catestatin (0.31-1.03 nmol/l) concentrations in healthy dogs accustomed to the sampling procedures were determined. Separate interpretation of the different chromogranin A epitopes from either saliva or plasma is recommended.

Keywords
Catestatin, Chromogranin A, Healthy dogs, Stress behavior visual analog scale, Vasostatin
National Category
Veterinary Science
Identifiers
urn:nbn:se:uu:diva-315824 (URN)10.1186/s13028-016-0274-8 (DOI)000391892700001 ()28049540 (PubMedID)
Available from: 2017-02-21 Created: 2017-02-21 Last updated: 2017-02-21Bibliographically approved
Myhre, P. L., Stridsberg, M., Linko, R., Okkonen, M., Nygård, S., Christensen, G., . . . Røsjø, H. (2017). Circulating chromogranin B levels in patients with acute respiratory failure: data from the FINNALI Study. Biomarkers, 22(8), 775-781
Open this publication in new window or tab >>Circulating chromogranin B levels in patients with acute respiratory failure: data from the FINNALI Study
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2017 (English)In: Biomarkers, ISSN 1354-750X, E-ISSN 1366-5804, Vol. 22, no 8, p. 775-781Article in journal (Refereed) Published
Abstract [en]

PURPOSE: Circulating chromogranin B (CgB) levels are increased in situations characterized by systemic and myocardial stress, but whether CgB provides prognostic information in patients with acute respiratory failure (ARF) is unknown.

METHODS: We included 584 patients with ARF, defined as ventilatory support >6 h, and with blood samples available on Intensive Care Unit (ICU) admission and day 3 (n = 479). CgB levels were measured by radioimmunoassay and follow-up was 90 days.

RESULTS: One-hundred-sixty-nine patients (29%) died during follow-up. Admission CgB levels separated non-survivors from survivors: median 1234 (Q1-3 989-1742) vs. 917 (753-1224) pmol/L, respectively, p < 0.001. CgB levels on ICU admission (logarithmically transformed) were associated with time to death after adjustment for established risk indices available on ICU admission, including N-terminal pro-B-type natriuretic levels: HR 2.62 (95%C.I. 1.82-3.77), p < 0.001. Admission CgB levels also improved prognostication on top of SOFA and SAPS II scores as assessed by Cox regression analyses and the category-free net reclassification index. The area under the curve (AUC) for admission CgB levels to separate survivors and non-survivors was 0.72 (95%CI 0.67-0.76), while the AUC on day 3 was 0.60 (0.54-0.66).

CONCLUSIONS: CgB levels measured on ICU admission provided additional prognostic information to established risk indices in ARF patients.

Keywords
Chromogranin B, acute respiratory failure, biomarker, prognosis
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-318356 (URN)10.1080/1354750X.2016.1269200 (DOI)000416064700010 ()28049363 (PubMedID)
Available from: 2017-03-24 Created: 2017-03-24 Last updated: 2018-02-26Bibliographically approved
Amcoff, K., Stridsberg, M., Lampinen, M., Magnuson, A., Carlson, M. & Halfvarson, J. (2017). Clinical implications of assay specific differences in f-calprotectin when monitoring inflammatory bowel disease activity over time. Scandinavian Journal of Gastroenterology, 52(3), 344-350
Open this publication in new window or tab >>Clinical implications of assay specific differences in f-calprotectin when monitoring inflammatory bowel disease activity over time
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2017 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, no 3, p. 344-350Article in journal (Refereed) Published
Abstract [en]

Objective: With several faecal calprotectin (FC) assays on the market, it has been difficult to define a uniform threshold for discriminating between remission and active disease in patients with inflammatory bowel disease (IBD). We aimed to compare the results of different FC-assays in IBD patients, followed over time.Material and methods: IBD patients provided faecal samples and reported clinical activity every third month prospectively over a two year period. FC was measured with two ELISA - (Buhlmann and Immunodiagnostik) and one automated fluoroimmunoassay (Phadia).Results: In total, 13 patients provided 91 faecal samples. The median (IQR) concentration of FC was higher at active disease than at remission for all assays: Buhlmann 845 (1061-226) g/g versus 62 (224-39) g/g, Phadia 369 (975-122) g/g versus 11 (52-11) g/g, and Immundiagnostik 135 (302-69) g/g versus 8 (56-4) g/g. The Buhlmann assay produced the largest absolute difference but the corresponding relative difference seemed to be more pronounced when analysed by the Phadia - (ratio of means 8.5; 95% CI 3.3-21.9) or the Immundiagnostik assay (ratio of means 7.4; 95% CI 3.1-17.6) than by the Buhlmann assay (ratio of means 5.3; 95% CI 2.7-10.6). Consequently, the specificity for discriminating active disease from remission varied between assays (34-75%) when the cut-off 50g/g was used, whereas the differences in sensitivity were less pronounced.Conclusions: Cross-comparisons revealed overall poor agreement between the assays as well as differences in the dynamics of FC. These findings suggest that standardisation of the method is needed to implement FC as a disease monitoring tool at large-scale.

Keywords
Biomarker, Crohn's disease, faecal calprotectin, inflammatory bowel disease, ulcerative colitis
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:uu:diva-316426 (URN)10.1080/00365521.2016.1256424 (DOI)000392488800015 ()27881032 (PubMedID)
Funder
Swedish Research Council, 521-2011-2764
Available from: 2017-03-01 Created: 2017-03-01 Last updated: 2017-11-29Bibliographically approved
Ottesen, A. H., Carlson, C. R., Louch, W. E., Dahl, M. B., Sandbu, R. A., Johansen, R. F., . . . Røsjø, H. (2017). Glycosylated Chromogranin A in Heart Failure: Implications for Processing and Cardiomyocyte Calcium Homeostasis. Circulation Heart Failure, 10(2), Article ID e003675.
Open this publication in new window or tab >>Glycosylated Chromogranin A in Heart Failure: Implications for Processing and Cardiomyocyte Calcium Homeostasis
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2017 (English)In: Circulation Heart Failure, ISSN 1941-3289, E-ISSN 1941-3297, Vol. 10, no 2, article id e003675Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Chromogranin A (CgA) levels have previously been found to predict mortality in heart failure (HF), but currently no information is available regarding CgA processing in HF and whether the CgA fragment catestatin (CST) may directly influence cardiomyocyte function.

METHODS AND RESULTS: CgA processing was characterized in postinfarction HF mice and in patients with acute HF, and the functional role of CST was explored in experimental models. Myocardial biopsies from HF, but not sham-operated mice, demonstrated high molecular weight CgA bands. Deglycosylation treatment attenuated high molecular weight bands, induced a mobility shift, and increased shorter CgA fragments. Adjusting for established risk indices and biomarkers, circulating CgA levels were found to be associated with mortality in patients with acute HF, but not in patients with acute exacerbation of chronic obstructive pulmonary disease. Low CgA-to-CST conversion was also associated with increased mortality in acute HF, thus, supporting functional relevance of impaired CgA processing in cardiovascular disease. CST was identified as a direct inhibitor of CaMKIIδ (Ca(2+)/calmodulin-dependent protein kinase IIδ) activity, and CST reduced CaMKIIδ-dependent phosphorylation of phospholamban and the ryanodine receptor 2. In line with CaMKIIδ inhibition, CST reduced Ca(2+) spark and wave frequency, reduced Ca(2+) spark dimensions, increased sarcoplasmic reticulum Ca(2+) content, and augmented the magnitude and kinetics of cardiomyocyte Ca(2+) transients and contractions.

CONCLUSIONS: CgA-to-CST conversion in HF is impaired because of hyperglycosylation, which is associated with clinical outcomes in acute HF. The mechanism for increased mortality may be dysregulated cardiomyocyte Ca(2+) handling because of reduced CaMKIIδ inhibition.

Keywords
Ca2+/calmodulin–dependent protein kinase II, biomarker, catestatin, chromogranin A
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-318352 (URN)10.1161/CIRCHEARTFAILURE.116.003675 (DOI)000394521300009 ()28209766 (PubMedID)
Funder
AstraZeneca
Available from: 2017-03-24 Created: 2017-03-24 Last updated: 2017-04-25Bibliographically approved
Benyamin, B., Maihofer, A. X., Schork, A. J., Hamilton, B. A., Rao, F., Schmid-Schönbein, G. W., . . . O'Connor, D. T. (2017). Identification of novel loci affecting circulating chromogranins and related peptides. Human Molecular Genetics, 26(1), 233-242
Open this publication in new window or tab >>Identification of novel loci affecting circulating chromogranins and related peptides
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2017 (English)In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 26, no 1, p. 233-242Article in journal (Refereed) Published
Abstract [en]

Chromogranins are pro-hormone secretory proteins released from neuroendocrine cells, with effects on control of blood pressure. We conducted a genome-wide association study for plasma catestatin, the catecholamine release inhibitory peptide derived from chromogranin A (CHGA), and other CHGA- or chromogranin B (CHGB)-related peptides, in 545 US and 1252 Australian subjects. This identified loci on chromosomes 4q35 and 5q34 affecting catestatin concentration (P = 3.40 × 10(-30) for rs4253311 and 1.85 × 10(-19) for rs2731672, respectively). Genes in these regions include the proteolytic enzymes kallikrein (KLKB1) and Factor XII (F12). In chromaffin cells, CHGA and KLKB1 proteins co-localized in catecholamine storage granules. In vitro, kallikrein cleaved recombinant human CHGA to catestatin, verified by mass spectrometry. The peptide identified from this digestion (CHGA360-373) selectively inhibited nicotinic cholinergic stimulated catecholamine release from chromaffin cells. A proteolytic cascade involving kallikrein and Factor XII cleaves chromogranins to active compounds both in vivo and in vitro.

National Category
Clinical Laboratory Medicine
Identifiers
urn:nbn:se:uu:diva-318357 (URN)10.1093/hmg/ddw380 (DOI)000397064600019 ()28011710 (PubMedID)
Funder
NIH (National Institute of Health), P01HL058120-10 R01MH093500
Available from: 2017-03-24 Created: 2017-03-24 Last updated: 2017-11-29Bibliographically approved
Ottesen, A. H., Carlson, C. R., Laver, D. R., Myhre, P. L., Dalhus, B., Lunde, P. K., . . . Louch, W. E. (2017). Secretoneurin attenuates Ca2+-dependent arrhythmogenesis. Paper presented at 42nd Congress of the Federation-of-European-Biochemical-Societies (FEBS) on From Molecules to Cells and Back, SEP 10-14, 2017, Jerusalem, ISRAEL. The FEBS Journal, 284(SI), 146-147, Article ID P.1.5-081.
Open this publication in new window or tab >>Secretoneurin attenuates Ca2+-dependent arrhythmogenesis
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2017 (English)In: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 284, no SI, p. 146-147, article id P.1.5-081Article in journal, Meeting abstract (Other academic) Published
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-347295 (URN)000409918902136 ()
Conference
42nd Congress of the Federation-of-European-Biochemical-Societies (FEBS) on From Molecules to Cells and Back, SEP 10-14, 2017, Jerusalem, ISRAEL
Available from: 2018-04-03 Created: 2018-04-03 Last updated: 2018-04-03Bibliographically approved
Brännström, A., Yu, J.-G., Jonsson, P., Åkerfeldt, T., Stridsberg, M. & Svensson, M. (2017). Vitamin D in relation to bone health and muscle function in young female soccer players. European Journal of Sport Science, 17(2), 249-256
Open this publication in new window or tab >>Vitamin D in relation to bone health and muscle function in young female soccer players
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2017 (English)In: European Journal of Sport Science, ISSN 1746-1391, E-ISSN 1536-7290, Vol. 17, no 2, p. 249-256Article in journal (Refereed) Published
Abstract [en]

The present work investigated serum vitamin D (25(OH)D) status in relation to bone and muscle qualities and functions in 19 female soccer players (13-16 years) resident at northern latitude with very low sun exposure (∼32-36 h/month) during winter season (late January to early March). Serum 25(OH)D, parathyroid hormone and bone turnover markers osteocalcin (OC) and beta carboxy-terminal collagen cross-links (β-Ctx), as well as body composition and muscle performance were examined. Hormones were tested using routine laboratory methods. Fat mass, lean mass, and bone mineral density in whole body, as well as femur and lumbar spine were evaluated with dual-energy X-ray absorptiometry. Muscle performance was assessed through isokinetic knee extension and flexion, countermovement jump, and sprint running. 25(OH)D was low (50.5 ±   12.8 nmol l(-1)), whereas the values of bone turnover markers were markedly high (OC: 59.4 ±   18.6 µg l(-1); β-Ctx: 1075 ±   408 ng l(-1)). All bone and muscle measurements were normal or above normal. 25(OH)D was not significantly correlated with most of the parameters of bone and muscle quality or function, except the knee extension time to peak torque (r   =   -0.50, p =   .03). In conclusion, the level of vitamin D is markedly low in adolescent female soccer players during the winter in Sweden. However, vitamin D levels did not significantly correlate with measures of bone and muscle except a moderate correlation in time to peak torque in the knee extensors. The practical implication of low vitamin D levels in young growing female athletes remains unclear.

Keywords
Exercise, education, fitness, health, kinesiology
National Category
Clinical Laboratory Medicine
Identifiers
urn:nbn:se:uu:diva-318361 (URN)10.1080/17461391.2016.1225823 (DOI)000394035100017 ()27633075 (PubMedID)
Available from: 2017-03-24 Created: 2017-03-24 Last updated: 2017-11-29Bibliographically approved
Myhre, P., Ottesen, A. H., Linko, R., Okkonen, M., Stridsberg, M., Nygaard, S., . . . Rosjö, H. (2016). Circulating chromogranin B levels and outcome in patients with cardiovascular related-acute respiratory failure. In: : . Paper presented at Congress of the European-Society-of-Cardiology (ESC), AUG 27-31, 2016, Rome, ITALY (pp. 115-115). , 37
Open this publication in new window or tab >>Circulating chromogranin B levels and outcome in patients with cardiovascular related-acute respiratory failure
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2016 (English)Conference paper, Oral presentation with published abstract (Refereed)
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-313865 (URN)000383869500372 ()
Conference
Congress of the European-Society-of-Cardiology (ESC), AUG 27-31, 2016, Rome, ITALY
Available from: 2017-01-26 Created: 2017-01-25 Last updated: 2017-01-26Bibliographically approved
Lignell, S., Aune, M., Darnerud, P. O., Stridsberg, M., Hanberg, A., Larsson, S. C. & Glynn, A. (2016). Maternal body burdens of PCDD/Fs and PBDEs are associated with maternal serum levels of thyroid hormones in early pregnancy: a cross-sectional study. Environmental health, 15, Article ID 55.
Open this publication in new window or tab >>Maternal body burdens of PCDD/Fs and PBDEs are associated with maternal serum levels of thyroid hormones in early pregnancy: a cross-sectional study
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2016 (English)In: Environmental health, ISSN 1476-069X, E-ISSN 1476-069X, Vol. 15, article id 55Article in journal (Refereed) Published
Abstract [en]

Background: Thyroid hormones (THs) regulate many biological functions in the human body and are essential for normal brain development. Epidemiological studies have observed diverging associations between halogenated persistent organic pollutant (POP) exposure and concentrations of THs in pregnant women and their infants. We investigated whether background exposure to polybrominated diphenyl ethers (PBDEs) is related to TH status in a Swedish population of pregnant women and their infants. Furthermore, we examined associations between polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs) and polychlorinated biphenyls (PCBs) and TH status in early pregnancy as an extension of an earlier study focusing on late pregnancy TH status. Methods: Free thyroxine (T4), total triiodo-thyronine (T3) and thyroid stimulating hormone (TSH) were analysed in serum from first-time mothers (N = 220-281) in the first and third trimester, and in infants (N = 115-150) 3 weeks and 3 months after delivery. Antibodies to thyroid peroxidase (anti-TPO) (N = 260) were measured in maternal third trimester serum. Maternal body burdens of PCBs (N = 281) were estimated from serum lipid PCB concentrations in late pregnancy, and PCDD/F (N = 97) and PBDE (N = 186) body burdens were estimated from concentrations in mother's milk lipids 3 weeks after delivery. Linear regression models allowed for covariate adjustment of the associations between ln-transformed POP body burdens and concentrations of TH and anti-TPO. Results: Maternal body burden of BDE-153 was inversely associated with first trimester total T3, otherwise no associations between PBDEs and first and second trimester THs were observed. No associations were found between maternal PBDE body burdens and infant THs. Maternal body burden of PCDD/Fs were inversely associated with first trimester total T3. No associations were observed between PCBs and first trimester THs. Third trimester anti-TPO was not associated with maternal PCBs, PCDD/Fs and PBDEs. Conclusions: Our results suggest that maternal PCDD/F and BDE-153 body burdens influence maternal TH status in early pregnancy, which is a critical period when maternal TH status influences fetal development.

Keywords
Thyroid hormone, T4, T3, TSH, Dioxins, PCBs, PBDEs
National Category
Occupational Health and Environmental Health
Identifiers
urn:nbn:se:uu:diva-297354 (URN)10.1186/s12940-016-0139-7 (DOI)000374930100002 ()
Funder
Swedish Environmental Protection Agency
Available from: 2016-06-23 Created: 2016-06-22 Last updated: 2018-01-10Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-9198-4193

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