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  • 1.
    Ahlsson, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Diderholm, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Ewald, Uwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Jonsson, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Forslund, Anders H
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Adipokines and their relation to maternal energy substrate production, insulin resistance and fetal size2013In: European Journal of Obstetrics, Gynecology, and Reproductive Biology, ISSN 0301-2115, E-ISSN 1872-7654, Vol. 168, no 1, p. 26-29Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    The role of adipokines in the regulation of energy substrate production in non-diabetic pregnant women has not been elucidated. We hypothesize that serum concentrations of adiponectin are related to fetal growth via maternal fat mass, insulin resistance and glucose production, and further, that serum levels of leptin are associated with lipolysis and that this also influences fetal growth. Hence, we investigated the relationship between adipokines, energy substrate production, insulin resistance, body composition and fetal weight in non-diabetic pregnant women in late gestation.

    STUDY DESIGN:

    Twenty pregnant women with normal glucose tolerance were investigated at 36 weeks of gestation at Uppsala University Hospital. Levels of adipokines were related to rates of glucose production and lipolysis, maternal body composition, insulin resistance, resting energy expenditure and estimated fetal weights. Rates of glucose production and lipolysis were estimated by stable isotope dilution technique.

    RESULTS:

    Median (range) rate of glucose production was 805 (653-1337)μmol/min and that of glycerol production, reflecting lipolysis, was 214 (110-576)μmol/min. HOMA insulin resistance averaged 1.5±0.75 and estimated fetal weights ranged between 2670 and 4175g (-0.2 to 2.7 SDS). Mean concentration of adiponectin was 7.2±2.5mg/L and median level of leptin was 47.1 (9.9-58.0)μg/L. Adiponectin concentrations (7.2±2.5mg/L) correlated inversely with maternal fat mass, insulin resistance, glucose production and fetal weight, r=-0.50, p<0.035, r=-0.77, p<0.001, r=-0.67, p<0.002, and r=-0.51, p<0.032, respectively. Leptin concentrations correlated with maternal fat mass and insulin resistance, r=0.76, p<0.001 and r=0.73, p<0.001, respectively. There was no correlation between maternal levels of leptin and rate of glucose production or fetal weight. Neither were any correlations found between levels of leptin or adiponectin and maternal lipolysis or resting energy expenditure.

    CONCLUSION:

    The inverse correlations between levels of maternal adiponectin and insulin resistance as well as endogenous glucose production rates indicate that low levels of adiponectin in obese pregnant women may represent one mechanism behind increased fetal size. Maternal levels of leptin are linked to maternal fat mass and its metabolic consequences, but the data indicate that leptin lacks a regulatory role with regard to maternal lipolysis in late pregnancy.

  • 2.
    Ahlsson, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Diderholm, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Jonsson, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Nordén Lindeberg, Solveig
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Olsson, Roger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Ewald, Uwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Forslund, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Insulin Resistance, a Link between Maternal Overweight and Fetal Macrosomia in Nondiabetic Pregnancies2010In: Hormone research in paediatrics, ISSN 1663-2818, Vol. 74, no 4, p. 267-274Article in journal (Refereed)
    Abstract [en]

    Background/Aims: During the last decades the number of large for gestational age infants delivered by nondiabetic mothers has increased. Our aim was to investigate to what extent fetal growth in nondiabetic pregnant women can be explained by rates of maternal energy substrate production and resting energy expenditure. Methods: Twenty nonsmoking pregnant women without impaired glucose tolerance and with a wide range of fetal weights (0.2-2.7 SDS) were investigated at 36 weeks of gestation. Maternal lipolysis, glucose production, resting energy expenditure, body composition and insulin resistance were assessed.Results: Median (range) glucose production rate was 805 (653-1,337) mumol/min and that of glycerol, reflecting lipolysis, was 214 (110-576) mumol/min. Multiple linear regression analysis showed that maternal fat mass explained 36% of the variation in insulin resistance, accounting for 62% of the variation in glucose production. Further, glucose production explained 31% of the variation in fetal weight. Resting energy expenditure explained 51% of the variation in estimated fetal weight. Conclusion: Fetal weight is dependent on maternal glucose production, which is in turn determined by the degree of insulin resistance, induced in part by the maternal fat mass. The variation in maternal resting energy expenditure is closely related to fetal weight.

  • 3. Alderman, J. McKee
    et al.
    Flurkey, Kevin
    Brooks, Natasha L.
    Naik, Sneha B.
    Gutierrez, Jonathan M.
    Srinivas, Urmila
    Ziara, Kristen B.
    Jing, Linhong
    Boysen, Gunnar
    Bronson, Rod
    Klebanov, Simon
    Chen, Xian
    Swenberg, James A.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Parker, Carol E.
    Harrison, David E.
    Combs, Terry P.
    Neuroendocrine inhibition of glucose production and resistance to cancer in dwarf mice2009In: Experimental Gerontology, ISSN 0531-5565, E-ISSN 1873-6815, Vol. 44, no 1-2, p. 26-33Article in journal (Refereed)
    Abstract [en]

    Pit1 null (Snell dwarf) and Proph1 null (Ames dwarf) mutant mice lack GH, PRL and TSH. Snell and Ames dwarf mice also exhibit reduced IGF-I, resistance to cancer and a longer lifespan than control mice. Endogenous glucose production during fasting is reduced in Snell dwarf mice compared to fasting control mice. In view of cancer cell dependence on glucose for energy, low endogenous glucose production may provide Snell dwarf mice with resistance to cancer. We investigated whether endogenous glucose production is lower in Snell dwarf mice during feeding. Inhibition of endogenous glucose production by glucose injection was enhanced in 12 to 14 month-old female Snell dwarf mice. Thus, we hypothesize that lower endogenous glucose production during feeding and fasting reduces cancer cell glucose utilization providing Snell dwarf mice with resistance to cancer. The elevation of circulating adiponectin, a hormone produced by adipose tissue, may contribute to the suppression of endogenous glucose production in 12 to 14 month-old Snell dwarf mice. We compared the incidence of cancer at time of death between old Snell dwarf and control mice. Only 18% of old Snell dwarf mice had malignant lesions at the time of death compared to 82% of control mice. The median ages at death for old Snell dwarf and control mice were 33 and 26 months, respectively. By contrast, previous studies showed a high incidence of cancer in old Ames dwarf mice at the time of death. Hence, resistance to cancer in old Snell dwarf mice may be mediated by neuroendocrine factors that reduce glucose utilization besides elevated adiponectin, reduced IGF-I and a lack of GH, PRL and TSH, seen in both Snell and Ames dwarf mice. Proteomics analysis of pituitary secretions from Snell dwarf mice confirmed the absence of GH and PRL, the secretion of ACTH and elevated secretion of Chromogranin B and Secretogranin II. Radioimmune assays confirmed that circulating Chromogranin B and Secretogranin II were elevated in 12 to 14 month-old Snell dwarf mice. In summary, our results in Snell dwarf mice suggest that the pituitary gland and adipose tissue are part of a neuroendocrine loop that lowers the risk of cancer during aging by reducing the availability of glucose.

  • 4.
    Amcoff, Karin
    et al.
    Univ Orebro, Fac Med & Hlth, Dept Gastroenterol, SE-70182 Orebro, Sweden..
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Lampinen, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Magnuson, Anders
    Univ Orebro, Sch Med Sci, Clin Epidemiol & Biostat, Orebro, Sweden..
    Carlson, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Halfvarson, Jonas
    Univ Orebro, Fac Med & Hlth, Dept Gastroenterol, SE-70182 Orebro, Sweden..
    Clinical implications of assay specific differences in f-calprotectin when monitoring inflammatory bowel disease activity over time2017In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, no 3, p. 344-350Article in journal (Refereed)
    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.

  • 5. Benyamin, Beben
    et al.
    Maihofer, Adam X
    Schork, Andrew J
    Hamilton, Bruce A
    Rao, Fangwen
    Schmid-Schönbein, Geert W
    Zhang, Kuixing
    Mahata, Manjula
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology. Univ Calif San Diego, La Jolla, CA 92093 USA..
    Schork, Nicholas J
    Biswas, Nilima
    Hook, Vivian Y
    Wei, Zhiyun
    Montgomery, Grant W
    Martin, Nicholas G
    Nievergelt, Caroline M
    Whitfield, John B
    O'Connor, Daniel T
    Identification of novel loci affecting circulating chromogranins and related peptides2017In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 26, no 1, p. 233-242Article in journal (Refereed)
    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.

  • 6. Brattsand, G.
    et al.
    Nordin, G.
    Isaksson, A.
    Bjellerup, P.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Hård, L.
    Ankarberg-Lindgren, C.
    Becker, C.
    Gustafsson, S.
    Larsson, K.
    Equalis/SFKK rekommenderar harmonisering av enheter vid hormonbestämningar för säkrare vård2012In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 109, no 39, p. 1773-1773Article in journal (Refereed)
  • 7.
    Brynildsen, J.
    et al.
    Univ Oslo, Akershus Univ Hosp, Dept Med, Lorenskog, Norway..
    Petaja, L.
    Univ Helsinki, Helsinki Univ Hosp, Intens Care Med, Dept Perioperat Intens & Pain Med, Helsinki, Finland..
    Lyngbakken, M. N.
    Univ Oslo, Akershus Univ Hosp, Dept Med, Lorenskog, Norway..
    Ottesen, A. H.
    Univ Oslo, Ulleval Univ Hosp, Expt Med Res Inst, Oslo, Norway..
    Stridsberg, Mats N.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Pettila, V.
    Univ Helsinki, Helsinki Univ Hosp, Intens Care Med, Dept Perioperat Intens & Pain Med, Helsinki, Finland..
    Christensen, G.
    Univ Oslo, Ulleval Univ Hosp, Expt Med Res Inst, Oslo, Norway..
    Omland, T.
    Univ Oslo, Akershus Univ Hosp, Dept Med, Lorenskog, Norway..
    Rosjö, H.
    Univ Oslo, Akershus Univ Hosp, Dept Med, Lorenskog, Norway..
    Secretoneurin levels provide prognostic information after cardiac surgery2016Conference paper (Refereed)
  • 8.
    Brännström, André
    et al.
    Umea Univ, Sports Med Unit, Dept Community Med & Rehabil, SE-90187 Umea, Sweden..
    Yu, Ji-Guo
    Umea Univ, Sports Med Unit, Dept Community Med & Rehabil, SE-90187 Umea, Sweden..
    Jonsson, Per
    Umea Univ, Div Orthopaed, Dept Surg & Perioperat Sci, Umea, Sweden..
    Åkerfeldt, Torbjörn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Svensson, Michael
    Umea Univ, Sports Med Unit, Dept Community Med & Rehabil, SE-90187 Umea, Sweden..
    Vitamin D in relation to bone health and muscle function in young female soccer players2017In: European Journal of Sport Science, ISSN 1746-1391, E-ISSN 1536-7290, Vol. 17, no 2, p. 249-256Article in journal (Refereed)
    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.

  • 9.
    Cunningham, Janet L.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Janson, Eva Tiensuu
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Agarwal, Smriti
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Grimelius, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Tachykinins in endocrine tumors and the carcinoid syndrome2008In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 159, no 3, p. 275-282Article in journal (Refereed)
    Abstract [en]

    Objective

    A new antibody, active against the common tachykinin (TK) C-terminal. was used to study TK expression in patients with endocrine tumors and a possible association between plasma-TK levels and symptoms of diarrhea and flush in patients with metastasizing ileocecal serotonin-producing carcinoid tumors (MSPCs).

    Method

    TK, serotonin and chromogranin A (CgA) immunoreactivity (IR) was studied by immunohistochemistry in tissue samples from 33 midgut carcinoids and 72 other endocrine tumors. Circulating TK (P-TK) and urinary-5 hydroxyindoleacetic acid (U-5HIAA) concentrations were measured in 42 patients with MSPCs before treatment and related to symptoms in patients with the carcinoid syndrome. Circulating CgA concentrations were also measured in 39 out of the 42 patients.

    Results

    All MSPCs displayed serotonin and strong TK expression. TK-IR was also seen in all serotonin-producing lung and appendix carcinoids. None of the other tumors examined contained TK-IR cells. Concentrations of P-TK, P-CgA, and U-5HIAA were elevated in patients experiencing daily episodes of either flush or diarrhea, when compared with patients experiencing occasional or none of these symptoms. In a Spearman partial rank test, the correlation of P-TK with daily diarrhea was independent of both U-5HIAA and CgA levels.

    Conclusion

    We found that TK synthesis occurs in serotonin-IR tumors and that P-TK levels are significantly correlated with symptoms of flush and diarrhea in patients with MSPCs. This is. to our knowledge, the first report demonstrating an independent correlation of P-TKs with carcinoid diarrhea, a symptom that is customarily regarded as serotonin mediated. Further investigations may present opportunities for new therapeutic possibilities.

  • 10.
    Danielsson, Katarina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Markström, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Broman, Jan-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Dim light melatonin onset in normal adults and its relationship with sleep timing and diurnal preference2012In: Biological rhythm research, ISSN 0929-1016, E-ISSN 1744-4179, Vol. 43, no 5, p. 497-503Article in journal (Refereed)
    Abstract [en]

    Dim light melatonin onset (DLMO) is defined as the start of the melatonin production in the evening during dim light conditions and has become a reliable phase marker of the circadian clock. The aim of the study was to investigate DLMO and its association with sleep timing and diurnal preferences in healthy working adults during real-life conditions. Fourteen adults were investigated. A sleep diary was kept during the preceding week, but no fixed sleep–wake schedule was implemented. Diurnal preferences were measured with the Horne–O¨ stberg Morningness–Eveningness Questionnaire. DLMO was defined as the time point when melatonin in saliva exceeded a threshold of 3 ng/L. Results showed that DLMO appeared in the expected time interval but was not significantly associated with sleep timing or diurnal preference. The results illustrate the complexity of monitoring sleep patterns in real-life settings.

  • 11.
    Dubois, Louise
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Kharaziha, Pedram
    Chioureas, Dimitris
    Meersman, Niels
    Panaretakis, Theocharis
    Ronquist, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Malignant Cell-Derived Extracellular Vesicles Express Different Chromogranin Epitopes Compared to Prostasomes2015In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 75, no 10, p. 1063-1073Article in journal (Refereed)
    Abstract [en]

    BACKGROUND. Prostasomes are nanosized extracellular vesicles exocytosed by prostate epithelial cells. They have been assigned many roles propitious to sperm in favor of fertilization. Prostatic cancer cells can also produce and secrete extracellular vesicles. METHODS. We assessed using ELISA, the surface expression of chromogranin proproteins on prostasomes and malignant extracellular vesicles of four different prostate cancer cell-lines, two hormone sensitive and two hormone refractory. We used a panel of chromogranin A and chromogranin B antibodies against peptides in-between hypothetical cleavage sites along the proproteins. RESULTS. A diverging pattern of chromogranin peptides was apparent when comparing prostasomes and malignant extracellular vesicles indicating a phenotypical change. We also compared western blot patterns (prostasomes and malignant extracellular vesicles) for selected antibodies that displayed high absorbances in the ELISA. Western blot analyses revealed various cleavage patterns of those proproteins that were analyzed in prostasomes and extracellular vesicles. CONCLUSION. Chromogranins are constituents of not only prostasomes but also of malignant prostate cell-derived extracellular vesicles with different amino acid sequences exposed at the membrane surface giving rise to a mosaic pattern. These findings may be of relevance for designing new assays for detection or even possible treatment of prostate cancers.

  • 12.
    Ekeblad, Sara
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Lejonklou, Margareta Halin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Grimfjärd, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Johansson, Térèse
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Grimelius, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Co-expression of ghrelin and its receptor in pancreatic endocrine tumours2007In: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 66, no 1, p. 115-122Article in journal (Refereed)
    Abstract [en]

    Objective 

    Expression of ghrelin has been reported in pancreatic endocrine tumours, but data on ghrelin receptor protein expression are lacking. The aim of this study was to examine the ghrelin receptor, as well as ghrelin, in a selected series of these tumours, including multiple endocrine neoplasia 1 (MEN1) associated tumours, and to correlate data with clinical features including body mass index.

    Design 

    Immunohistochemical detection of ghrelin and its receptor was performed on frozen tissue from 31 tumours: 9 MEN1 and 22 sporadic. Twenty tumours were analysed by quantitative PCR. Plasma ghrelin was assessed in 26 patients.

    Results 

    Twenty-one (68%) of 31 tumours showed immunoreactivity for ghrelin (8/9 MEN1) and 19/20 expressed ghrelin mRNA. Ghrelin receptor protein was detected in 21/30 (70%) tumours (4/8 MEN1), and mRNA was detected in all analysed tumours. Insulinomas had significantly higher levels of receptor mRNA than other tumours. Five patients had elevated plasma ghrelin (> 2 SD above the control group mean). No significant difference in mean plasma ghrelin levels was found between patients (908 ± 569 ng/l) and controls (952 ± 164 ng/l). Mean BMI was 24·3 kg/m2. There was no association between ghrelin or receptor expression and survival.

    Conclusions 

    We report the first immunohistochemical data on expression of the ghrelin receptor in pancreatic endocrine tumours: 70% of tumours in our material. Concomitant ghrelin and receptor expression was seen in 50% of tumours, indicating an autocrine loop. Ghrelin was expressed in 68% of tumours (8/9 MEN1). Despite frequent ghrelin expression, elevated circulating ghrelin is rare in these patients.

  • 13.
    Fjällskog, Marie-Louise
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Ludvigsen, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Janson, Eva T
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Expression of somatostatin receptor subtypes 1 to 5 in tumor tissue and intratumoral vessels in malignant endocrine pancreatic tumors2003In: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 20, no 1, p. 59-67Article in journal (Refereed)
    Abstract [en]

    Somatostatin analogs are well established in the treatment of malignant endocrine pancreatic tumors (EPTs). Our goal is to individualize their treatment using receptor-subtype-specific analogs and, therefore, exploring the receptor expression is highly important. We have examined the expression of somatostatin receptor (sst) subtypes 1–5 on tumor cells and in intratumoral vessels in 28 tumor tissues from malignant EPTs with immunohistochemistry using sst-subtype-specific polyclonal antibodies. We found that sst2 and sst4 stained positive in 90% and sst1 in 70% of the tumor tissues, whereas sst3 and sst5 stained positive in only 50% of the tumor tissues. Sst expression in intratumoral vessels was high for sst2 and sst4 (80%), moderate for sst1 (40%), and low for sst3 and sst5 (10%). The ssts were evenly distributed among the different tumor subtypes. However, tumors belonging to the same subgroup of EPTs showed a variable expression of receptor subtypes. No differences in receptor-subtype expression could be seen between poorly and well-differentiated tumors, nor between primary tumors and metastases. Prior medical treatment did not influence sst expression pattern. In conclusion, sst2 and sst4 were expressed in most tumor tissues and intratumoral vessels from EPTs. However, sst3 and sst5 were lacking in half of the tumor tissues and in most of the intratumoral vessels. These differences indicate the importance of determining each tumor’s subset of receptors before treatment with receptor-subtype-specific analogs is initiated. The importance of sst expression in intratumoral vessels is not yet known.

  • 14. Fung, Maple M.
    et al.
    Salem, Rany M.
    Mehtani, Parag
    Thomas, Brenda
    Lu, Christine F.
    Perez, Brandon
    Rao, Fangwen
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Ziegler, Michael G.
    Mahata, Sushil K.
    O'Connor, Daniel T.
    Direct Vasoactive Effects of the Chromogranin A (CHGA) Peptide Catestatin in Humans In Vivo2010In: Clinical and experimental hypertension (1993, Print), ISSN 1064-1963, E-ISSN 1525-6006, Vol. 32, no 5, p. 278-287Article in journal (Refereed)
    Abstract [en]

    Catestatin is a bioactive peptide of chromogranin A (CHGA) that is co-released with catecholamines from secretory vesicles. Catestatin may function as a vasodilator and is diminished in hypertension. To evaluate this potential vasodilator in vivo without systemic counterregulation, we infused catestatin to target concentrations of similar to 50, similar to 500, similar to 5000 nM into dorsal hand veins of 18 normotensive men and women, after pharmacologic venoconstriction with phenylephrine. Pancreastatin, another CHGA peptide, was infused as a negative control. After preconstriction to similar to 69%, increasing concentrations of catestatin resulted in dose-dependent vasodilation (P = 0.019), in female subjects (to similar to 44%) predominantly. The EC50 (similar to 30 nM) for vasodilation induced by catestatin was the same order of magnitude to circulating endogenous catestatin (4.4 nM). No vasodilation occurred during the control infusion with pancreastatin. Plasma CHGA, catestatin, and CHGA-to-catestatin processing were then determined in 622 healthy subjects without hypertension. Female subjects had higher plasma catestatin levels than males (P = 0.001), yet lower CHGA precursor concentrations (P = 0.006), reflecting increased processing of CHGA-to-catestatin (P < 0.001). Our results demonstrate that catestatin dilates human blood vessels in vivo, especially in females. Catestatin may contribute to sex differences in endogenous vascular tone, thereby influencing the complex predisposition to hypertension.

  • 15.
    Georgantzi, Clary
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Sköldenberg, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Jakobson, A.
    Christofferson, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Chromogranin A In Neuroblastoma: Correlation To Stage And Prognostic Factors2013In: Pediatric Blood & Cancer, ISSN 1545-5009, E-ISSN 1545-5017, Vol. 60, no S3, p. 228-228Article in journal (Refereed)
  • 16.
    Georgantzi, Kleopatra
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Tsolakis, Apostolos V
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Jakobson, Åke
    Department of Womeńs and Childreńs Health, Astrid Lindgren Childreńs Hospital, Karolinska Institute, Stockholm, Sweden.
    Christofferson, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Janson, Eva Tiensuu
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Differentiated expression of somatostatin receptor subtypes in experimental models and clinical neuroblastoma2011In: Pediatric Blood & Cancer, ISSN 1545-5009, E-ISSN 1545-5017, Vol. 56, no 4, p. 584-589Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Neuroblastoma (NB) is a solid tumor of childhood originating from the adrenal medulla or sympathetic nervous system. Somatostatin (SS) is an important regulator of neural and neuroendocrine function, its actions being mediated through five specific membrane receptors. The aim of this study was to investigate the expression of the different somatostatin receptors (SSTRs) in NB tumor cells that may form targets for future therapeutic development.

    PROCEDURE:

    Tumor specimens from 11 children with stage II-IV disease were collected before and/or after chemotherapy. Experimental tumors derived from five human NB cell lines were grown subcutaneously in nude mice. Expression of SSRTs, the neuroendocrine marker chromogranin A (CgA) and SS was detected by immunohistochemistry using specific antibodies.

    RESULTS:

    SSTR2 was detected in 90%, SSTR5 in 79%, SSTR1 in 74%, SSTR3 in 68% whereas SSTR4 was expressed in 21% of the clinical tumors. The experimental tumors expressed SSTRs in a high but variable frequency. All clinical tumors showed immunoreactivity for CgA but not for SS.

    CONCLUSION:

    The frequent expression of SSTRs indicates that treatment with unlabeled or radiolabeled SS analogs should be further explored in NB.

  • 17.
    Granfors, Michaela
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Skogö, Johan
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Targeted Thyroid Testing During Pregnancy in Clinical Practice2014In: Obstetrics and Gynecology, ISSN 0029-7844, E-ISSN 1873-233X, Vol. 124, no 1, p. 10-15Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:To evaluate the efficacy of a targeted thyroid testing approach during pregnancy in clinical practice.

    METHODS:This is a retrospective cohort study performed within Uppsala County, Sweden. Data were derived from the population-based Uppsala Biobank of Pregnant Women, in which blood samples are collected in conjunction with the routine ultrasound screening in gestational week 17-19. For this study, 5,254 pregnant women with an estimated date of delivery between January 1, 2009, and December 31, 2011, were included. On review of their medical records, women who were tested for thyroid dysfunction during pregnancy in clinical practice were identified (n=891). From the remaining untested women, 1,006 women were randomly selected for analyses of thyrotropin (TSH), free thyroxine levels, and thyroid peroxidase antibodies. Thyroid-stimulating hormone levels in both groups were analyzed with regard to trimester-specific upper reference levels as recommended by the International Endocrine Society Guidelines.

    RESULTS:The proportion of trimester-specific TSH elevation was 12.6% in the targeted thyroid testing group and 12.1% in the untested group (P=.8; odds ratio [OR] 1.04, 95% confidence interval [CI] 0.79-1.37). The proportion of overt hypothyroidism was 1.1% and 0.7% in the groups, respectively (P=.4; OR 1.57, 95% CI 0.55-4.45).

    CONCLUSIONS:The prevalence of trimester-specific elevated TSH and overt hypothyroidism was equal in targeted thyroid tested and untested women. When implemented in clinical practice, targeted thyroid testing is unsatisfactory. If ongoing studies provide support for treatment of pregnant women with elevated TSH, universal thyroid testing appears the most reasonable approach.

  • 18.
    Grönberg, Malin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Amini, Rose-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Janson, Eva Tiensuu
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Saras, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Neuroendocrine markers are expressed in human mammary glands2010In: Regulatory Peptides, ISSN 0167-0115, E-ISSN 1873-1686, Vol. 160, no 1-3, p. 68-74Article in journal (Refereed)
    Abstract [en]

    Background

    Regulatory peptides have previously been detected in epithelial cells of human mammary glands. As these peptides are produced by scattered neuroendocrine cells in the epithelium of other tissues the aim of this study was to investigate whether the mammary glands express molecular markers for neuroendocrine cells.

    Material and methods

    Specimens from 28 human mammary glands were retrieved. The distribution of immunoreactive cells was determined using immunohistochemistry with antibodies versus a set of endocrine markers including peptide hormones, chromogranins/secretogranins, vesicular monoamine transporters, synaptophysin, serotonin and synaptic vesicle protein 2.

    Results

    Cells of the luminal epithelium of ducts and lobules of human mammary glands expressed vesicular monoamine transporter 2 and chromogranin B, as well as the previously reported regulatory peptides obestatin, ghrelin, adrenomedullin and apelin. Using consecutive sections, it was revealed that the immunoreactivity patterns of the regulatory peptides and vesicular monoamine transporter 2 were similar. Interestingly, immunoreactivity for secretogranin II, secretogranin III and chromogranin B was identified in myoepithelial cells. No immunoreactivity was detected for chromogranin A or synaptophysin.

    Conclusion

    Specific cells in the epithelium and myoepithelium of mammary glands express neuroendocrine markers suggesting that mammary glands may have neuroendocrine functions.

  • 19.
    Grönberg, Malin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Tsolakis, Apostolos V
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Holmbäck, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Grimelius, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Janson, Eva T
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Ghrelin and Obestatin in Human Neuroendocrine Tumors: Expression and Effect on Obestatin Levels after Food Intake2013In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 97, no 4, p. 291-299Article in journal (Refereed)
    Abstract [en]

    Background:

    Ghrelin and obestatin are derived from the same peptide hormone precursor and are mainly produced by the gastric mucosa. Ghrelin is involved in many biological processes, whereas the physiological function of obestatin needs further investigation. The aims of the present study were to establish the incidence of ghrelin- and obestatin-immunoreactive cells in a comprehensive panel of human neuroendocrine tumors (NETs) and to investigate if blood obestatin concentrations are influenced during a standardized meal stimulation test in healthy individuals and patients with NETs.

    Materials and Methods:

    The expression of ghrelin and obestatin was investigated in NETs (n = 149) and other endocrine-related disorders (n = 3) using immunohistochemistry with specific polyclonal antibodies. Coexpression of the peptides was evaluated by double immunofluorescence. Concentrations of obestatin in blood were measured during a meal test in 6 healthy individuals and 5 patients with pancreatic NETs.

    Results:

    Ghrelin and obestatin were expressed in 14/152 and 19/152 tumor tissues, respectively, mainly representing NETs of foregut origin and in pancreatic tissue from a nesidioblastosis patient. Double immunofluorescence staining showed colocalization of the peptides. During the meal test, obestatin levels in blood were unchanged in all patients but decreased significantly in the healthy individuals.

    Conclusion:

    Only a minority of NETs express ghrelin and obestatin. However, analysis of patients with tumors originating from tissues that express the peptides in normal conditions could be of importance. The results from the meal test indicate that the hormone levels are affected by food intake in healthy individuals, whereas obestatin levels remained unchanged in pancreatic NET patients.

  • 20.
    Gunnarsson, Anna-Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Education in Nursing.
    Åkerfeldt, Torbjörn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Gunningberg, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Increased energy intake in hip fracture patients affects nutritional biochemical markers2012In: Scandinavian Journal of Surgery, ISSN 1457-4969, E-ISSN 1799-7267, Vol. 101, no 3, p. 204-210Article in journal (Refereed)
    Abstract [en]

    Background and Aims: We have previously shown that nutritional guidelines decreased the incidence of pressure ulcers in hip fracture patients. In the present study, we evaluate whether the nutritional biochemical markers S-IGF-1 (Insulin-like Growth Factor 1), S-Transthyretin and S-Albumin are affected by patients' energy intake, and whether the markers are useful as predictors of postoperative complications. Material and Methods: Quasi-experimental design, with one intervention and one control group, as well as pre- and post-study measurements. Eighty-eight hip fracture patients were included: 42 in the control group and 46 in the intervention group. The control group received regular nutritional support pre- and postoperatively, while the intervention group received nutritional support that followed new, improved clinical guidelines from admission to five days postoperatively. S-Albumin, S-Transthyretin, C-Reactive Protein (S-CRP) and S-IGF-1 were analysed at admission and five days postoperatively as well as complications like pressure ulcer and infection. Results: The intervention group had a significantly higher energy intake; for example, 1636 kcal versus 852 kcal postoperative day 1. S-IGF-1 levels decreased significantly in the control group, while no decrease in the intervention group. S-Albumin and S-Transthyretin decreased and S-CRP increased significantly in both groups, indicating that those markers were not affected short-term by a high-energy intake. There was no correlation between short-term postoperative complications and S-IGF-1, S-Transthyretin or S-Albumin at admission. Conclusion: The results of our study showed that S-IGF-1 can be used as a short-term nutritional biochemical marker, as it was affected by a five-day high-energy regimen. However, neither S-IGF-1, S-Transthyretin or S-Albumin were useful in predicting postoperative complications within five days postoperatively.

  • 21.
    Gunningberg, Lena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Persson, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition Research.
    Åkerfeldt, Torbjörn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Swenne, Christine Leo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Pre- andpostoperative nutritional status and predictors for surgical-wound infections in elective orthopaedic and thoracic patients2008In: e-SPEN, The European E-Journal of Clinical Nutrition and Metabolism, Vol. 3, no 3, p. e93-e101Article in journal (Refereed)
    Abstract [en]

    Aim

    To describe pre- and postoperative nutritional status for patients undergoing elective orthopaedic or thoracic surgery, compare different methods for screening and assessment of nutritional status and identify predictors for surgical-wound infection.

    Method

    Ninety-four patients were consecutively included and assessed preoperatively using the Patient-Generated Subjective Global Assessment (PG-SGA), nutritional screening indicators (NSI), nutrition risk index (NRI), and the biochemical indicators serum albumin (S-Albumin) and serum insulin-like growth factor 1 (S-IGF-1). Thirty days postoperatively, a structured infection surveillance questionnaire, weight and blood sampling were conducted.

    Results

    The prevalence of malnutrition preoperatively ranged from 3.2% (PG-SGA) to 17.0–17.1% (S-IGF-1 and NSI). Thirty days postoperatively, the body weight, the body mass index and S-Albumin had decreased, while the S-IGF-1 had increased significantly. The only significant correlation between different methods preoperatively was found between S-Albumin and S-IGF-1. The agreement between NRI and S-Albumin was fair. Six patients (6.4%) developed surgical-wound infections. Preoperative S-Albumin was significantly lower for patients who developed surgical-wound infection compared to those who did not.

    Conclusion

    The prevalence of malnutrition and risk for malnutrition in patients undergoing elective surgery varied depending on which evaluation method was used. Low preoperative S-Albumin was identified as the only significant predictor for surgical-wound infection.

  • 22.
    Hagforsen, Eva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Michaëlsson, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Normal and PPP-affected palmoplantar sweat gland express neuroendocrine markers chromogranins and synaptophysin differently2010In: Archives of Dermatological Research, ISSN 0340-3696, E-ISSN 1432-069X, Vol. 302, no 9, p. 685-693Article in journal (Refereed)
    Abstract [en]

    Earlier findings indicate the acrosyringium as the target for the inflammation in the chronic and intensely inflammatory skin disease palmoplantar pustulosis (PPP). The sweat gland apparatus seems to be an immune-competent structure that probably contributes to the defence of the skin. Furthermore, the sweat gland and duct may be a hitherto unrecognized neuroendocrine organ because it expresses cholineacetyl-transferase and acetylcholinesterase, nicotinic receptors, beta-adrenergic and angiotensin receptors.

    The aim of this study was to obtain further information about neuroendocrine properties of the sweat gland apparatus by examining the expression of common neuroendocrine markers synaptophysin and chromogranins A and B in healthy palmar skin and in PPP skin.

    Synaptophysin and chromogranins were expressed in the sweat glands and ducts with some variation in the pattern and intensity of the expression. In PPP skin the expression differed, being higher and lower, depending on the part of the sweat duct. Chromogranins were further expressed in the epidermis, endothelium and inflammatory cells, but its intensity was weaker in epidermis than in the sweat gland apparatus. In most cases, chromogranins in epidermis in involved PPP were weakly expressed compared to healthy controls. The presence of synaptophysin and chromogranins in palmoplantar skin may have marked neuroendocrine effects, and the palmoplantar skin is likely to have important neuroimmuno-endocrine properties. Moreover, the altered chromogranin expression in PPP skin might influence both the neuroendocrine and neuroimmunologic properties of palmoplantar skin in these patients. These results indicate important neuroendocrine properties of the palmoplantar skin.

  • 23.
    Hagforsen, Eva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Michaëlsson, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Somatostatin receptors are strongly expresssed in palmoplantar sweat glands and ducts: studies of normal and palmoplantar pustulosis skin2011In: Clincal and Experimental Dermatology, ISSN 0307-6938, E-ISSN 1365-2230, Vol. 36, no 5, p. 521-527Article in journal (Refereed)
    Abstract [en]

    Background

    The acrosyringium is the target for inflammation in the chronic and intensely inflammatory skin disease palmoplantar pustulosis (PPP). The sweat-gland apparatus seems to be an immunocompetent structure that probably contributes to skin defence. Furthermore, the sweat gland and duct may be a hitherto unrecognized neuroendocrine organ.

    Aim

    To obtain further information about the neuroendocrine properties of the sweat-gland apparatus by examining expression of the somatostatin receptors (SSTRs) 1-5 in healthy palmar skin and in PPP skin.

    Methods

    Biopsy specimens were taken from 25 patients with PPP and 25 healthy controls. Immunohistochemical analysis was used to investigate expression of SSTRs 1-5.

    Results

    SSTRs 1-5 were expressed in both epidermal and endothelial structures. The staining intensity of the sweat-gland apparatus was more pronounced than that of the epidermis. Expression differed significantly between lesional PPP and normal plantar skin, with increased expression of SSTRs 3 and 4 in ducts in epidermis, and decreased expression of SSTR 1 in ducts in both papillary and reticular dermis. In specimens with pronounced inflammation, numerous dendritic cells with strong expression of SSTRs 1.. 2 and 4 were seen, especially in the papillary dermis.

    Conclusions

    The presence of SSTRs in palmoplantar skin, and specifically at high density in the sweat glands and ducts, might be of particular importance in skin neuroimmunoendocrinology. Although the relevance of the changes in SSTR expression in PPP skin compared with normal skin is unclear, our hypothesis is that these differences might influence the function of both the neuroendocrine and neuroimmunological properties of palmoplantar skin, especially in the sweat-gland apparatus.

  • 24. Hagströmer, Lena
    et al.
    Emtestam, Lennart
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Talme, Toomas
    Expression pattern of somatostatin receptor subtypes 1-5 in human skin: an immunohistochemical study of healthy subjects and patients with psoriasis or atopic dermatitis2006In: Experimental dermatology, ISSN 0906-6705, E-ISSN 1600-0625, Vol. 15, no 12, p. 950-957Article in journal (Refereed)
    Abstract [en]

    In psoriasis and atopic dermatitis, the inflammatory events have neurogenic components and the neuropeptides modify the functions of immuno-active cells in the skin. Somatostatin is a neuropeptide with several neuroendocrine and immunomodulating properties and mediates its actions by five distinct subtypes of G-protein-coupled receptors (SSTR1-5). This study describes the distribution of SSTR1-5, analysed with immunohistochemistry, in psoriasis, atopic dermatitis and controls. Normal human skin and lesional skin from patients with psoriasis or atopic dermatitis showed many similarities, but also some differences, as regards SSTR expression. SSTR1-3 were strongly expressed in the epidermis of healthy skin, and in the skin of patients with psoriasis or atopic dermatitis. It is noteworthy that SSTR4 and 5 were strongly expressed in the epidermis of psoriasis patients, but weakly expressed in the epidermis of those with atopic dermatitis and normal skin. The intensity of the staining also varied considerably between the different layers of the epidermis, especially in psoriasis patients. In all cases, the dendritic cells, found mostly in the papillary and upper reticular dermis, showed a strong expression of SSTR1-4, but a weak expression of SSTR5. SSTR1-5 were strongly expressed in the sweat glands in all skin biopsies. Hair follicles and sebaceous glands expressed all five subtypes. Striated muscle fibres showed an intense positive expression of SSTR1-4, but a weak or negative expression of SSTR5. The wide distribution and expression pattern of all five SSTRs in human skin suggest that somatostatin is involved in the interactions between the nervous system and the skin.

  • 25.
    Hallin, Runa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Arnardottir, Harpa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Olsson, Roger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Emtner, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Branth, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Boman, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Slinde, Frode
    Relation between physical capacity, nutritional status and systemic inflammation in COPD2011In: Clinical Respiratory Journal, ISSN 1752-6981, E-ISSN 1752-699X, Vol. 5, no 3, p. 136-142Article in journal (Refereed)
    Abstract [en]

    Background: Decreased physical capacity, weight loss, fat-free mass depletion and systemic inflammation are frequently observed in patients with chronic obstructive pulmonary disease (COPD).

    Objective: Our aim was to examine relations between physical capacity, nutritional status, systemic inflammation and disease severity in COPD.

    Method: Forty nine patients with moderate to severe COPD were included in the study. Spirometry was preformed. Physical capacity was determined by a progressive symptom limited cycle ergo meter test, incremental shuttle walking test, 12-minute walk distance and hand grip strength test. Nutritional status was investigated by anthropometric measurements, (weight, height, arm and leg circumferences and skinfold thickness) and bioelectrical impedance assessment was performed. Blood samples were analyzed for C-reactive protein (CRP) and fibrinogen.

    Result: Working capacity was positively related to forced expiratory volume in 1 s (FEV(1)) (p < 0.001), body mass index and fat free mass index (p = 0.01) and negatively related to CRP (p = 0.02) and fibrinogen (p = 0.03). Incremental shuttle walk test was positively related to FEV(1) (p < 0.001) and negatively to CRP (p = 0.048). Hand grip strength was positively related to fat free mass index, and arm and leg circumferences. Fifty to 76% of the variation in physical capacity was accounted for when age, gender, FEV(1), fat free mass index and CRP were combined in a multiple regression model.

    Conclusion: Physical capacity in chronic obstructive pulmonary disease is related to lung function, body composition and systemic inflammation. A depiction of all three aspects of the disease might be important when targeting interventions in chronic obstructive pulmonary disease.

  • 26. Hightower, C. Makena
    et al.
    Zhang, Kuixing
    Miramontes-Gonzalez, Jose P.
    Rao, Fangwen
    Wei, Zhiyun
    Schork, Andrew J.
    Nievergelt, Caroline M.
    Biswas, Nilima
    Mahata, Manjula
    Elkelis, Nina
    Taupenot, Laurent
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Ziegler, Michael G.
    O'Connor, Daniel T.
    Genetic variation at the delta-sarcoglycan (SGCD) locus elevates heritable sympathetic nerve activity in human twin pairs2013In: Journal of Neurochemistry, ISSN 0022-3042, E-ISSN 1471-4159, Vol. 127, no 6, p. 750-761Article in journal (Refereed)
    Abstract [en]

    The Syrian Cardiomyopathic Hamster (BIO-14.6/53.58 strains) model of cardiac failure, resulting from naturally occurring deletion at the SGCD (delta-sarcoglycan) locus, displays widespread disturbances in catecholamine metabolism. Rare Mendelian myopathy disorders of human SGCD occur, although common naturally occurring SGCD genetic variation has not been evaluated for effects on human norepinephrine (NE) secretion. This study investigated the effect of SGCD genetic variation on control of NE secretion in healthy twin pairs. Genetic associations profiled SNPs across the SGCD locus. Trait heritability (h(2)) and genetic covariance (pleiotropy; shared h(2)) were evaluated. Sympathochromaffin exocytosis in vivo was probed in plasma by both catecholamines and Chromogranin B (CHGB). Plasma NE is substantially heritable (p=3.19E-16, at 65.2 +/- 5.0% of trait variance), sharing significant (p<0.05) genetic determination with circulating and urinary catecholamines, CHGB, eGFR, and several cardio-metabolic traits. Participants with higher pNE showed significant (p<0.05) differences in several traits, including increased BP and hypertension risk factors. Peak SGCD variant rs1835919 predicted elevated systemic vascular compliance, without changes in specifically myocardial traits. We used a chimeric-regulated secretory pathway photoprotein (CHGA-EAP) to evaluate the effect of SGCD on the exocytotic pathway in transfected PC12 cells; in transfected cells, expression of SGCD augmented CHGA trafficking into the exocytotic regulated secretory pathway. Thus, our investigation determined human NE secretion to be a highly heritable trait, influenced by common genetic variation within the SGCD locus. Circulating NE aggregates with BP and hypertension risk factors. In addition, coordinate NE and CHGB elevation by rs1835919 implicates exocytosis as the mechanism of release.

  • 27.
    Hudecova, Miriam
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Holte, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Moby, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Olovsson, Matts
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology, Diabetes and Metabolism.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Androgen levels, insulin sensitivity, and early insulin response in women with polycystic ovary syndrome: a long-term follow-up study2011In: Fertility and Sterility, ISSN 0015-0282, E-ISSN 1556-5653, Vol. 95, no 3, p. 1146-1148Article in journal (Refereed)
    Abstract [en]

    Thirty-four women with polycystic ovary syndrome who previously had participated in studies with intravenous glucose tolerance test and hyperinsulinemic, euglycemic clamp between 1987 and 1995 underwent anthropometric, endocrine (T and sex-hormone binding globulin serum concentration), and metabolic (intravenous glucose tolerance test, hyperinsulinemic, euglycemic clamp, and androgens) measurements. Free androgen levels and β-cell function decreased over time in women with polycystic ovary syndrome, but insulin sensitivity remained unaltered.

  • 28. Höglund, Odd Viking
    et al.
    Hagman, Ragnvi
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Chromogranin A and cortisol at intraoperative repeated noxious stimuli: Surgical stress in a dog model2015In: SAGE Open Medicine, E-ISSN 2050-3121, Vol. 3, article id 2050312115576432Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES

    Biomarkers representing sympathetic tone and the surgical stress response are measured to objectively evaluate surgical techniques and anaesthetic protocols. If a part of the intraoperative procedure is repeated on the contralateral organ, one animal may potentially serve as its own control and, if so, may minimize the problem of individual differences of the stress response to anaesthesia and surgery. This study aimed to investigate the use of chromogranin A for measurement of the intraoperative sympathetic tone. Additional aims were to investigate chromogranin A and cortisol as indicators of the intraoperative surgical stress response caused by repeated noxious stimuli in dogs subjected to ovariohysterectomy and thereby to investigate the possibility of one dog serving as its own control.

    METHODS

    Experiments were carried out on 10 dogs subjected to ovariohysterectomy. Perioperative blood samples (0-6) were collected after premedication, immediately before induction of anaesthesia (0), after induction of anaesthesia and before incision (1), before (2) and after (3) removal of the first ovary, after a 15-min pause before removal of the second ovary (4), after removal of the second ovary (5) and after closing the abdomen (6). Plasma chromogranin A and cortisol were analysed.

    RESULTS

    Plasma chromogranin A did not change. Plasma cortisol concentration did not change between before anaesthesia and opening of the abdomen. Plasma cortisol increased at removal of the first ovary. Cortisol did not change at removal of the second ovary but remained increased compared to initial sample.

    CONCLUSION

    The results suggest chromogranin A is a poor indicator of intraoperative sympathetic tone during elective surgery in dogs. Cortisol measurement was useful for assessment of intraoperative noxious stimuli. However, at these test conditions, neither plasma chromogranin A nor plasma cortisol was useful for assessment of repeated intraoperative noxious stimuli where one dog served as its own control.

  • 29. Jakobsson, Joel
    et al.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Zetterberg, Henrik
    Blennow, Kaj
    Ekman, Carl-Johan
    Johansson, Anette G M
    Sellgren, Carl
    Landén, Mikael
    Decreased cerebrospinal fluid secretogranin II concentrations in severe forms of bipolar disorder2013In: Journal of Psychiatry & Neuroscience, ISSN 1180-4882, E-ISSN 1488-2434, Vol. 38, no 4, p. E21-E26Article in journal (Refereed)
    Abstract [en]

    Background:

    Bipolar disorder is a common psychiatric mood disorder that is defined by recurrent episodes of abnormally elevated mood and depression. Progressive structural brain changes in individuals with bipolar disorder have been suggested to be associated with defects in the secretion of neurotrophic factors. We sought to assess how the regulated secretory pathway in the brain is affected in patients with bipolar disorder by measuring chromogranin B and secretogranin II, which are 2 cerebrospinal fluid (CSF) biological markers for this process.

    Methods:

    We measured the concentrations of chromogranin B (peptide 439-451) and secretogranin II (peptide 154-165) in the CSF of patients with well-defined bipolar disorder and healthy controls. The lifetime severity of bipolar disorder was rated using the Clinical Global Impression (CGI) scale.

    Results:

    We included 126 patients with bipolar disorder and 71 healthy controls in our analysis. Concentrations of secretogranin II were significantly lower in patients with bipolar disorder type I than in healthy controls. The reduction was most pronounced in patients with high CGI scores (i.e., severe disease).

    Limitations:

    The cross-sectional design of the current study limits the ability to pinpoint the causalities behind the observed associations.

    Conclusion:

    This study shows that the CSF marker secretogranin II has the potential to act as a biological marker for severe forms of bipolar disorder. Our findings indicate that patients with bipolar disorder possess defects in the regulatory secretory pathway, which may be of relevance to the progressive structural brain changes seen in those with severe forms of the disease.

  • 30.
    James, Stefan K.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Timmer, Jorik R.
    Ottervanger, Jan Paul
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Armstrong, Paul
    Califf, Robert
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Simoons, Maarten L.
    Usefulness of biomarkers for predicting long-term mortality in patients with diabetes mellitus and non-ST-elevation acute coronary syndromes (A GUSTO IV substudy)2006In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 97, no 2, p. 167-172Article in journal (Refereed)
    Abstract [en]

    The present study evaluated whether biomarkers of ischemia, inflammation, myocardial damage, and dysfunction are equally useful in patients who have diabetes mellitus (DM) for prediction of cardiac events in non-ST-elevation acute coronary syndrome (ACS). DM was present in 1,677 of 7,800 patients (21.5%) who had non-ST-elevation ACS and were included in the Fourth Global Utilization of Strategies To Open Occluded Arteries (GUSTO IV) trial. Creatinine, N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), troponin T, C-reactive protein, and interleukin-6 were analyzed in serum samples that were obtained at a median of 9.5 hours from symptom onset. One-year mortality rates were 13.5% among patients who had DM (n = 227) and 6.9% among those who did not (n = 418, p < 0.001). The median level of NT-pro-BNP was 2 times as high in patients who had DM, whereas troponin T levels did not differ by DM status. Mortality increased with ascending quartiles of NT-pro-BNP, with 1-year mortality rates of 3.9% (n = 11) in the bottom quartile and 29% (n = 103) in the top quartile. In multivariable analyses, factors that were predictive of 1-year mortality in patients who did not have DM were also significant for those who did. Presence of ST depression > 0.5 mm had the highest odds ratio of 2.3 (95% confidence interval 1.2 to 4.6). NT-pro-BNP levels > 669 ng/L (odds ratio 2.0, 95% confidence interval 1.1 to 3.6) and interleukin-6 levels > 10 ng/L (odds ratio 1.9, 95% confidence interval 1.2 to 3.0) were significant biomarker predictors. In conclusion, DM confers a high long-term mortality in non-ST-elevation ACS. Despite a larger proportion of ST depression and increased levels of NT-pro-BNP and interleukin-6 at admission, these factors provide independent prognostic information that may improve risk stratification and guidance of treatment.

  • 31.
    Jernberg, Tomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Johnston, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Natriuretic peptides in unstable coronary artery disease2004In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 25, no 17, p. 1486-1493Article in journal (Other academic)
    Abstract [en]

    Patients with unstable coronary artery disease (CAD), i.e., unstable angina or non-ST-elevation myocardial infarction, vary widely in clinical presentation, prognosis and response to treatment. To select appropriate therapy, early risk stratification has become increasingly important. This review focuses on the emerging role of natriuretic peptides in the early assessment of patients with unstable CAD. We conclude that levels of brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are strongly associated to mortality and the risk of future congestive heart failure, and carry important prognostic information independent from previously known risk factors in unstable CAD. There are some data indicating that these markers can also be helpful in the selection of appropriate therapy in these patients but further studies are needed. Before a routine use of BNP or NT-proBNP in unstable CAD can be recommended, the cost-effectiveness of adding these new markers to the currently routine markers and their impact on selection of treatment needs further evaluation.

  • 32. Jitpean, Supranee
    et al.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Pettersson, Ann
    Höglund, Odd V
    Ström, Bodil Holst
    Hagman, Ragnvi
    Decreased plasma Chromogranin A361-372 (Catestatin) but not Chromogranin A17-38 (Vasostatin) in female dogs with bacterial uterine infection (pyometra).2015In: BMC veterinary research, ISSN 1746-6148, Vol. 11, no 1, p. 14-Article in journal (Refereed)
    Abstract [en]

    BackgroundPyometra often induces systemic inflammatory response syndrome (SIRS) and early diagnosis is crucial for survival. Chromogranin A (CgA) is a neuroendocrine secretory protein that is co-released with catecholamines from the adrenal medulla and sympathetic nerve endings. A prognostic value of CgA has been found in humans that are critically ill or that have SIRS associated with infection. CgA has not yet been studied in dogs with bacterial infection. The aim of the study was to investigate CgA, measured by Chromogranin A361-372 (Catestatin; Cst) and Chromogranin A17-38 (Vasostatin; VS) in healthy dogs and in dogs with pyometra.ResultsFifty dogs with pyometra, sampled prior to surgery and 64 healthy female dogs were included. In 19 pyometra cases, blood samples were also collected postoperatively. Concentrations of Cst and VS were measured in heparinised plasma and Cst also measured in EDTA plasma, by in-house radioimmunoassays. Student¿s t-test and Wilcoxon two-sample test was used to test for differences between dog groups. Pre- and postoperative samples in dogs with pyometra were analysed by paired t-test. Pearson correlation was used to investigate associations of laboratory variables and hospitalization. P < 0.05 was considered significant.Concentrations of Cst were decreased in pyometra dogs (mean ± SE, 1.01 ± 0.05 nmol/L) compared to healthy dogs (mean ± SE, 1.70 ± 0.03 nmol/L) (p ¿ 0.0001). VS concentrations did not differ significantly between dogs with pyometra (0.40 ± 0.04 nmol/L) and healthy dogs (0.42 ± 0.03 nmol/L). Mean ± SE pre- and postoperative concentration of Cst (1.0 ± 0.04 nmol/L and 0.9 ± 0.2 nmol/L) and VS (0.36 ± 0.04 nmol/L and 0.36 ± 0.04 nmol/L) in dogs with pyometra did not differ significantly. Neither Cst nor VS concentrations were associated with duration of hospitalization and were not significantly different in the four dogs with pyometra that had prolonged (¿3 d) postoperative hospitalization.ConclusionConcentrations of Cst, but not VS, were decreased in pyometra. Cst and VS concentrations before and after ovariohysterectomy did not differ significantly and were not associated with duration of hospitalization. Further studies are warranted to evaluate a possible diagnostic or prognostic value for Cst and VS.

  • 33.
    Johansson, Ann-Christin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Gunnarsson, Lars-Gunnar
    Linton, Steven J.
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Nilsson, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Cornefjord, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Pain, disability and coping reflected in the diurnal cortisol variability in patients scheduled for lumbar disc surgery2008In: European Journal of Pain, ISSN 1090-3801, E-ISSN 1532-2149, Vol. 12, no 5, p. 633-640Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Symptoms of lumbar disc herniation can be induced by both mechanical compression of the nerve roots and by biochemical irritants from the disc tissues. Proinflammatory cytokines, as well as stress are potent stimulators of the hypothalamic-pituitary-adrenal axis, reflected in enhanced release of cortisol from the adrenal cortex. Altered cortisol production is also associated to behaviour and coping patterns. The aim of the present study was to explore the relation between pain, physical function, psychosocial factors and quality of life to the diurnal cortisol variability, in patients with lumbar disc herniation.

    METHOD:

    This study had a cross-sectional design. Forty-two patients with lumbar disc herniation, verified by magnetic resonance imaging and a clinical examination by an orthopaedic surgeon, were included in the study. All patients were scheduled for disc surgery. The diurnal cortisol variability was examined before surgery. The patients were dichotomised into two groups based on low or high diurnal cortisol variability. Pain, disability, work related stress, quality of life, coping and fear avoidance beliefs, were estimated by standardised questionnaires.

    RESULTS:

    The low diurnal cortisol variability group was distinguished by a higher median score regarding leg pain at activity and significantly more disability (p<0.05). The patients with a low diurnal cortisol variability had significantly lower coping self-statement scores, but higher pain coping catastrophising scores (p<0.05).

    CONCLUSION:

    Patients with lumbar disc herniation and a low diurnal cortisol variability had lower physical function, perceived lower possibilities of influencing their pain, and were more prone to catastrophise than patients with lumbar disc herniation and a high diurnal cortisol variability.

  • 34.
    Johnston, Nina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Jernberg, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Biochemical indicators of cardiac and renal function in a healthy elderly population2004In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 37, no 3, p. 210-216Article in journal (Refereed)
    Abstract [en]

    Objectives:

    To examine the distributions of NT-proBNP and cystatin C and their relation to age, gender, and other physiological factors in an apparently healthy elderly population.

    Method:

    NT-proBNP and cystatin C were analyzed in 407 and 408 healthy individuals, median age: 65 (range 40–76).

    Results:

    Increasing age, female gender and CRP were independently associated to higher NT-proBNP levels. Age, body mass index, and CRP level were independently associated to the cystatin C level. In women and men, ≤65 years, the 97.5th percentile value for NT-proBNP was 268 ng/l and 184 ng/l, in those older, 391 ng/l and 269 ng/l. For those ≤65 years the 97.5th percentile value for cystatin C was 1.12 mg/l, and for those older 1.21 mg/l.

    Conclusion:

    In a healthy elderly population, NT-proBNP is influenced by age and gender, whereas cystatin C is influenced by age but not by gender. Both markers seem to be associated to the CRP level.

  • 35.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Hansson, Lars-Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Åkerfeldt, Torbjörn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Weight reduction is associated with decreased CRP levels2013In: Clinical Laboratory, ISSN 1433-6510, Vol. 59, no 9-10, p. 1135-1138Article in journal (Refereed)
    Abstract [en]

    Background:

    Obesity is very costly for society and weight reduction is important to reduce obesity related dis-eases. We have evaluated the effect of weight reduction on CRP values to see if high sensitivity CRP could be used to provide persons on life style intervention programs with positive feedback.

    Methods:

    Study subjects (n = 26) were recruited to a life style intervention program aiming for weight loss among the laboratory staff at Uppsala University Hospital, Sweden. Blood samples for high sensitivity CRP were collect-ed at inclusion and after 4 weeks. Body composition was estimated by measurements performed on an inexpensive bioimpedance analyzer.

    Results:

    CRP reduction was significantly associated with weight reduction after four weeks (p = 0.00005) and eight weeks (p = 0.0002). Data from the bioimpedance analyzer were not useful on an individual level.

    Conclusions:

    High sensitivity CRP could be used to provide positive feedback in workplace weight reduction pro-grams.

  • 36.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Ronquist, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Åkerfeldt, Torbjörn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Lifestyle intervention is associated with decreased concentrations of circulating pentraxin 3 independent of CRP decrease2013In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 118, no 3, p. 165-168Article in journal (Refereed)
    Abstract [en]

    Objectives. Pentraxin 3 (PTX3) is an acute phase marker, which is produced at the site of infection or inflammation in contrast to CRP that is mainly synthesized by the liver. The aim of the present study was to see if lifestyle interventions/weight loss would lead to decreased blood plasma concentrations of PTX3. Methods. Study subjects (n = 31) were recruited to a lifestyle intervention program aiming at increased physical activity, improved eating habits, and weight loss. High-sensitivity C-reactive protein (CRP) and PTX3 methods were used for analysis of CRP and PTX3 in plasma samples collected at inclusion and after 4 and 8 weeks of treatment. Results. Wilcoxon paired samples test showed a significant decrease in PTX3 concentrations from 2068 pg/mL at start to 2007 pg/mL at 4 weeks (P = 0.002) and 1748 pg/mL at 8 weeks (P = 0.003). The PTX3 decrease was not significantly correlated with a corresponding decrease in CRP or weight reduction. Conclusions. The lifestyle intervention program resulted in a significant reduction of circulating concentrations of pentraxin 3 already after 4 and 8 weeks of treatment.

  • 37.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Reference values for fasting insulin in 75 year old females and males2013In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 46, no 12, p. 1125-1127Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES:

    Reference intervals for insulin are often based on fairly small study groups with unknown body mass index (BMI). They are also much younger than most patients seeking care. These values are not optimal for elderly patients, as many biological markers change over time and adequate reference intervals are important for correct clinical decisions.

    DESIGN AND METHODS:

    We studied fasting insulin (f-insulin) values in a cohort of 698 75-year old non-diabetic males and females. The 2.5th and 97.5th percentiles for all individuals, males and females were calculated according to the recommendations of the International Federation of Clinical Chemistry on the statistical treatment of reference intervals.

    RESULTS:

    There was a strong positive correlation between BMI and f-insulin, which led to the calculation of separate reference intervals for individuals with BMI ≤30.

    CONCLUSIONS:

    The reference interval for f-insulin for all study subjects was 1.74-18.27mIU/L and for individuals with BMI ≤30 (n=574) the reference interval was 1.66-15.05mIU/L.

  • 38.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Svensson, Michael B
    Ronquist, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Åkerfeldt, Torbjörn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Life style intervention in moderately overweight individuals is associated with decreased levels of cathepsins L and S in plasma2014In: Annals of Clinical and Laboratory Science, ISSN 0091-7370, E-ISSN 1550-8080, Vol. 44, no 3, p. 283-285Article in journal (Refereed)
    Abstract [en]

    Background Adipose tissue cells produce cathepsins L and S, which have proatherogenic effects. Obesity is strongly linked to atherogenesis, cardiovascular morbidity, and mortality.

    Objective The aim of the present study was to see if life style interventions/weight reduction could decrease cathepsin L and S levels in blood plasma.

    Method Study subjects (n=31) were recruited to a life style intervention program aiming at increased physical activity, more healthy eating habits, and weight reduction for most of the participants. Blood samples were collected at inclusion and after 4 and 8 weeks.

    Results Cathepsin L was significantly reduced at 4 weeks (p<0.0001) and 8 weeks (p=0.0004). A similar reduction was also seen for cathepsin S at 4 weeks (p=0.03) and 8 weeks (p=0.008). No significant change in fractalkine values was observed at 4 weeks (p=0.58), but a significant increase was apparent at 8 weeks (p=0.0002).

    Conclusion The intervention program resulted in significant reductions of cathepsin L and S levels in plasma after 4 and 8 weeks of intervention.

  • 39.
    Lignell, Sanna
    et al.
    Natl Food Agcy, Risk Benefit Assessment Dept, Box 622, SE-75126 Uppsala, Sweden..
    Aune, Marie
    Natl Food Agcy, Dept Chem, Box 622, SE-75126 Uppsala, Sweden..
    Darnerud, Per Ola
    Natl Food Agcy, Risk Benefit Assessment Dept, Box 622, SE-75126 Uppsala, Sweden..
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Hanberg, Annika
    Karolinska Inst, Inst Environm Med, Box 210, SE-17177 Stockholm, Sweden..
    Larsson, Susanna C.
    Karolinska Inst, Inst Environm Med, Box 210, SE-17177 Stockholm, Sweden..
    Glynn, Anders
    Natl Food Agcy, Risk Benefit Assessment Dept, Box 622, SE-75126 Uppsala, Sweden..
    Maternal body burdens of PCDD/Fs and PBDEs are associated with maternal serum levels of thyroid hormones in early pregnancy: a cross-sectional study2016In: Environmental health, ISSN 1476-069X, E-ISSN 1476-069X, Vol. 15, article id 55Article in journal (Refereed)
    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.

  • 40.
    Lindahl, Andreas E
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Sjöberg, Folke
    Ekselius, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Gerdin, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Natriuretic peptide type B in burn intensive care2013In: Journal of Trauma and Acute Care Surgery, ISSN 2163-0755, E-ISSN 2163-0763, Vol. 74, no 3, p. 855-861Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    The plasma concentration of natriuretic peptide type B (BNP) or NT-proBNP (P-BNP or P-NT-proBNP) reflects cardiac load. In intensive care unit settings and in chronic inflammation, it is also affected by non-heart-related mechanisms. It has been suggested to be a marker of hydration after severe burns and to predict outcome in critically ill patients, but results are contradictory. We therefore measured P-NT-proBNP after severe burns and related it to injury related variables and to organ dysfunction.

    METHODS:

    Fifty consecutive patients with a burn size greater than 10% were studied for the first 2 weeks. P-NT-proBNP changes were analyzed in relation to burn size, age, changes in body weight, C-reactive protein in plasma, and organ function assessed as Sequential Organ Failure Assessment (SOFA) scores

    RESULTS:

    P-NT-proBNP showed large day-to-day and between patient variations. Daily change in body weight correlated with P-NT-proBNP only on Day 2, when maximum mobilization of edema occurred. Thereafter, P-NT-proBNP correlated with C-reactive protein in plasma as well as with SOFA scores. Burn size correlated with maximal weight change, which in turn correlated with both time for and value of maximum P-NT-proBNP. Maximal P-NT-proBNP was related to mortality and correlated better with SOFA score on Day 14 compared with age and burn size. In linear regressions, together with age at injury and total body surface area, P-NT-proBNP assessed on Days 3 to 8 was an independent predictor for every subsequent SOFA score measured one or more days later up to Day 14.

    CONCLUSION:

    P-NT-proBNP exhibited considerable interindividual and day-to-day variations. Values were related to mortality, burn size, water accumulation, posttraumatic response, and organ function. Maximum P-NT-proBNP correlated stronger with length of stay and with organ function on Day 14, compared with age and burn size. High values in Days 3 through 8 were also independent predictors of subsequent organ function up to 2 weeks after injury.

    LEVEL OF EVIDENCE:

    Epidemiologic/prognostic study, level III.

  • 41.
    Lindahl, Andreas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Sjöberg, Folke
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Ekselius, Lisa
    Gerdin, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Circadian Cortisol Rhythm after Burn InjuryManuscript (preprint) (Other academic)
    Abstract [en]

    Introduction: The stress response to critical illness includes activation of the hypothalamic-pituitary-adrenal (HPA) axis, and increased release of cortisol and diminished or lost physiological diurnal variation. Details of this response were analyzed in consecutive burn patients.

    Methods: Forty-nine patients, 15 women and 34 men, median age 41(range 19-60), median burn size 31 % (range 10-96)n and treated at Uppsala Burn Center were investigated during their first week after injury. Clinical parameters were registered daily, serum cortisol concentrations were analyzed four times daily for seven days, and the daily diurnal slope starting from the daily maximum was calculated. Relevant confounding variables were identified by means of a directed acyclic graph (DAG).

    Results: The circadian zenith for free cortisol frequently occurred at noon rather that in early morning, it was not related to burn size, ventilator care, or surgery, but was weakly related to the SOFA score. Multilevel modeling revealed that burn size explained cortisol slope. After adjustments for covariates, including the SOFA score, the only significant covariate was the SOFA score itself. Ventilator care explained cortisol slope, but surgery the preceding day did not. Differences between large and small burns were only noticed for the free cortisol concentration at 6pm, suggesting that the flattening of the slope was primarily due to a slower decline in free cortisol from morning to evening.  When adjusting for all covariates, slope at 6pm was explained by burn size and P-CgA as well as SOFA score. Both burn size and SOFA score explained the daily coefficient of variability (CV) in free cortisol concentration. Similarly, burn size, P-CgA and SOFA explained AUC.

    Conclusions: Free cortisol concentration was related to the size of burns, as was the circadian cortisol rhythm. This effect of burn size was related at least in part to its effect on organ function.

  • 42.
    Lindahl, Bertil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Jernberg, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Johnston, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Serial analyses of N-terminal pro-B-type natriuretic peptide in patients with non-ST-segment elevation acute coronary syndromes: a Fragmin and fast Revascularisation during In Stability in Coronary artery disease (FRISC)-II substudy2005In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 45, no 4, p. 533-541Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES:

    The aim of this research was to describe N-terminal part of the pro-B-type natriuretic peptide (NT-proBNP) levels over time in non-ST-segment elevation acute coronary syndromes (NSTEACS), to elucidate factors associated with changes of NT-proBNP levels, and to examine association with long-term mortality.

    BACKGROUND:

    The NT-proBNP levels are associated with mortality. Long-term temporal changes of NT-proBNP levels and their relation to other factors have not been examined.

    METHODS:

    The NT-proBNP was analyzed at randomization and at 48 h, after 6 weeks, 3 and 6 months in NSTEACS patients enrolled in the Fragmin and fast Revascularisation during InStability in Coronary artery disease (FRISC)-II trial. The NT-proB-type natriuretic peptide was analyzed at least three time points in 1,216 patients.

    RESULTS:

    The median NT-proBNP level, which at randomization was 529 ng/l, decreased throughout the whole sampling period to 238 ng/l at six months. Elevated troponin T, C-reactive protein, and female gender were associated with higher reduction rates, and high age, diabetes, previous myocardial infarction, treatment with diuretics, and nitrates on admission with lower reduction rates. At each time point, the NT-proBNP level was predictive of the two-year mortality. However, the adjusted odds ratio increased for each time point.

    CONCLUSIONS:

    The initial rise of NT-proBNP in NSTEACS is mainly reversible. Factors associated with less reversibility are related to chronically impaired left ventricular function, and factors associated with greater reversibility are related to the acute myocardial damage. The NT-proBNP level measured during a chronic, relatively stable phase is a better predictor of mortality than during an acute unstable phase. The clinical setting and timing of measurement will be important to consider when using NT-proBNP for risk assessment.

  • 43. Lindh, Emma
    et al.
    Brännström, Johan
    Jones, Petra
    Wermeling, Fredrik
    Hässler, Signe
    Betterle, Corrado
    Garty, Ben Zion
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Herrmann, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Bacteriology.
    Karlsson, Mikael C I
    Winqvist, Ola
    Autoimmunity and cystatin SA1 deficiency behind chronic mucocutaneous candidiasis in autoimmune polyendocrine syndrome type 12013In: Journal of Autoimmunity, ISSN 0896-8411, E-ISSN 1095-9157, Vol. 42, p. 1-6Article in journal (Refereed)
    Abstract [en]

    Patients with the monogenic disease autoimmune polyendocrine syndrome type I (APSI) develop autoimmunity against multiple endocrine organs and suffer from chronic mucocutaneous candidiasis (CMC), a paradoxical complication with an unknown mechanism. We report here that saliva from APSI patients with CMC is defective in inhibiting growth of Candida albicans in vitro and show reduced levels of a salivary protein identified as cystatin SA1. In contrast, APSI patients without CMC express salivary cystatin SA1 and can inhibit C. albicans to the same extent as healthy controls. We evaluated the anti-fungal activity of cystatin SA1 and found that synthesized full length cystatin SA1 efficiently inhibits growth of C. albicans in vitro. Moreover, APSI patients exhibit salivary IgA autoantibodies recognizing myosin-9, a protein expressed in the salivary glands, thus linking autoimmunity to cystatin SA1 deficiency and CMC. This data suggests an autoimmune mechanism behind CMC in APSI and provides rationale for evaluating cystatin SA1 in antifungal therapy.

  • 44.
    Ludvigsen, Eva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Carlsson, Carina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Janson, Eva Tiensuu
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sandler, Stellan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Somatostatin receptor 1-5; expression profiles during rat development2015In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 120, no 3, p. 157-168Article in journal (Refereed)
    Abstract [en]

    Background. Somatostatin acts through five receptor subtypes (SSTRs 1-5). We aimed to investigate SSTRs mRNA expression and protein distribution in whole rat embryos, with special emphasis on the pancreas. Material and methods. Rat embryos were collected on embryonal days 10, 11, 12, 14, 15, 17, 19, 21, and at birth. Presence of SSTRs was investigated with RT-PCR techniques and immunohistochemistry. Results. There was no SSTR5 mRNA expression in the whole rat embryos. All SSTR1-5 proteins were observed at embryonal day 10, but the localization varied between the different subtypes. From day 11 to birth SSTRs protein presence increased with time in major structures such as skin and cartilage. It remained similar over time in the heart and liver. In the fetal pancreas mRNA expression of SSTR2 and 4 was detected at day 14, and there was an increase up to birth. Only SSTR1 protein co-localized to a higher extent with the islet hormones studied. SSTR2 was present in all islet endocrine cells except for beta-cells. In contrast, the immunostaining for SSTR3-4 was co-localized with insulin and PP, and, finally, SSTR5 with glucagon and pancreatic polypeptide. In mRNA isolated from whole rat embryos SSTR1-2 and SSTR4 expression showed a peak at day 14, while SSTR3 mRNA was not present until day 15. Conclusion. The present data suggest a role for SSTRs during the development of the rat embryo. Subsequent functional studies may elucidate regulatory roles of specific SSTRs for the growth and differentiation of the pancreas as well as other organs.

  • 45.
    Ludvigsen, Eva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Janson, Eva T.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Sandler, Stellan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Altered Expression of Somatostatin Receptors in Pancreatic Islets from NOD Mice Cultured at Different Glucose Concentrations In Vitro and in Islets Transplanted to Diabetic NOD Mice In Vivo2011In: Experimental Diabetes Research, ISSN 1687-5214, E-ISSN 1687-5303, Vol. 2011, p. 623472-Article in journal (Refereed)
    Abstract [en]

    Somatostatin acts via five receptors (sst1-5). We investigated if the changes in pancreatic islet sst expression in diabetic NOD mice compared to normoglycemic mice are a consequence of hyperglycemia or the ongoing immune reaction in the pancreas. Pancreatic islets were isolated from NOD mice precultured for 5 days and further cultured for 3 days at high or low glucose before examined. Islets were also isolated from NOD mice and transplanted to normal or diabetic mice in a number not sufficient to cure hyperglycemia. After three days, the transplants were removed and stained for sst1-5 and islet hormones. Overall, changes in sst islet cell expression were more common in islets cultured in high glucose concentration in vitro as compared to the islet transplantation in vivo to diabetic mice. The beta and PP cells exhibited more frequent changes in sst expression, while the alpha and delta cells were relatively unaffected by the high glucose condition. Our findings suggest that the glucose level may alter sst expressed in islets cells; however, immune mechanisms may counteract such changes in islet sst expression.

  • 46. Mattsson, Niklas
    et al.
    Portelius, Erik
    Rolstad, Sindre
    Gustavsson, Mikael
    Andreasson, Ulf
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Wallin, Anders
    Blennow, Kaj
    Zetterberg, Henrik
    Longitudinal Cerebrospinal Fluid Biomarkers over Four Years in Mild Cognitive Impairment2012In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 30, no 4, p. 767-778Article in journal (Refereed)
    Abstract [en]

    Cerebrospinal fluid (CSF) measurements of amyloid-β42 (Aβ42), total-tau (T-tau), and phosphorylated tau (P-tau) may be used to predict future Alzheimer's disease (AD) dementia in patients with mild cognitive impairment (MCI). The precise temporal development of these biomarkers in relation to clinical progression is unclear. Earlier studies have been hampered by short follow-up. In an MCI cohort, we selected 15 patients who developed AD (MCI-AD) and 15 who remained cognitively stable during 4 years of follow-up. CSF was sampled at three serial occasions from each patient and analyzed for Aβ peptides, the soluble amyloid-β protein precursor protein fragments sAβPPα and sAβPPβ, T-tau, P-tau, and chromogranin B, which is a protein linked to regulated neuronal secretion. We also measured, for the first time in MCI patients, an extended panel of Aβ peptides by matrix-assisted-laser-desorption/ionization time-of-flight mass spectrometry (MS). Most biomarkers were surprisingly stable over the four years with coefficients of variation below or close to 10%. However, MCI-AD patients decreased in CSF AβX-40 and chromogranin B concentrations, which may indicate a reduced number of functional neurons or synapses with disease progression. The MS Aβ peptide panel was more useful than any single Aβ peptide to identify MCI-AD patients already at baseline. Knowledge on these biomarkers and their trajectories may facilitate early diagnosis of AD and be useful in future clinical trials to track effects of disease modifying drugs.

  • 47.
    Myhre, P.
    et al.
    Akershus Univ Hosp, Div Med, Akershus, Norway..
    Ottesen, A. H.
    Akershus Univ Hosp, Div Med, Akershus, Norway..
    Okkonen, M.
    Univ Helsinki, Cent Hosp, Div Intes Care Med, Dept Anesthesiol Intens Care & Pain Med, Helsinki, Finland..
    Linko, R.
    Univ Helsinki, Cent Hosp, Div Intes Care Med, Dept Anesthesiol Intens Care & Pain Med, Helsinki, Finland..
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology. Uppsala Univ, Dept Med Sci, Uppsala, Sweden..
    Nygard, S.
    Univ Oslo, Oslo, Norway..
    Christensen, G.
    Univ Oslo, Oslo, Norway..
    Pettila, V.
    Univ Helsinki, Cent Hosp, Div Intes Care Med, Dept Anesthesiol Intens Care & Pain Med, Helsinki, Finland..
    Omland, T.
    Akershus Univ Hosp, Div Med, Akershus, Norway..
    Rosjo, H.
    Akershus Univ Hosp, Div Med, Akershus, Norway..
    The novel cardiovascular biomarker secretoneurin provides valuable prognostic information in patients with acute respiratory failure2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, no Suppl. 1, p. 39-40Article in journal (Other academic)
  • 48.
    Myhre, Peder L.
    et al.
    Akershus Univ Hosp, Div Med, Sykehusveien 25, N-1478 Lorenskog, Norway.;Univ Oslo, Ctr Heart Failure Res, Oslo, Norway..
    Ottesen, Anett H.
    Akershus Univ Hosp, Div Med, Sykehusveien 25, N-1478 Lorenskog, Norway.;Univ Oslo, Ctr Heart Failure Res, Oslo, Norway..
    Okkonen, Marjatta
    Oslo Univ Hosp Ulleval, Ctr Clin Heart Res, Oslo, Norway.;Univ Helsinki, Intens Care & Pain Med, Dept Anesthesiol, Div Intens Care Med, Helsinki, Finland.;Helsinki Univ Hosp, Helsinki, Finland..
    Linko, Rita
    Oslo Univ Hosp Ulleval, Ctr Clin Heart Res, Oslo, Norway.;Univ Helsinki, Intens Care & Pain Med, Dept Anesthesiol, Div Intens Care Med, Helsinki, Finland.;Helsinki Univ Hosp, Helsinki, Finland..
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Nygård, Ståle
    Oslo Univ Hosp, Bioinformat Core Facil, Oslo, Norway.;Univ Oslo, Oslo, Norway..
    Christensen, Geir
    Univ Oslo, Ctr Heart Failure Res, Oslo, Norway.;Oslo Univ Hosp, Expt Med Res Inst, Oslo, Norway..
    Pettilä, Ville
    Oslo Univ Hosp Ulleval, Ctr Clin Heart Res, Oslo, Norway.;Univ Helsinki, Intens Care & Pain Med, Dept Anesthesiol, Div Intens Care Med, Helsinki, Finland.;Helsinki Univ Hosp, Helsinki, Finland.;Univ Bern, Univ Hosp Bern, Dept Intens Care Med, Bern, Switzerland..
    Omland, Torbjörn
    Akershus Univ Hosp, Div Med, Sykehusveien 25, N-1478 Lorenskog, Norway.;Univ Oslo, Ctr Heart Failure Res, Oslo, Norway..
    Rösjö, Helge
    Akershus Univ Hosp, Div Med, Sykehusveien 25, N-1478 Lorenskog, Norway.;Univ Oslo, Ctr Heart Failure Res, Oslo, Norway..
    Prognostic Value of Secretoneurin in Patients with Acute Respiratory Failure: Data from the FINNALI Study2016In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 62, no 10, p. 1380-1389Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We examined whether secretoneurin (SN), a biomarker associated with cardiomyocyte Ca2+ handling, provides prognostic information in patients with acute respiratory failure (ARF).

    METHODS: We included 490 patients with ARF, defined as ventilatory support >6 h, with blood samples available on admission to the intensive care unit (ICU). SN concentrations were measured by RIA.

    RESULTS: A total of 209 patients (43%) were hospitalized with cardiovascular (CV)-related ARF, and 90-day mortality rates were comparable between CV- and non CV-related ARF (n = 281): 31% vs 24%, P = 0.11. Admission SN concentrations were higher in nonsurvivors than in survivors in both CV -related (median 148 [quartile 1-3, 117-203] vs 108 [87-143] pmol/L, P < 0.001) and non CV-related ARF (139 [115-184] vs 113 [91-139] pmol/L, P < 0.001). In patients with CV -related ARF, SN concentrations on ICU admission were associated with 90-day mortality [odds ratio (OR) 1.97 (95% CI, 1.04-3.73, P = 0.04)] after adjusting for established risk indices, including N-terminal-pro-B-type natriuretic peptide (NT-proBNP) concentrations. SN also improved patient classification in CV -related ARF as assessed by the net reclassification index: 0.32 (95% CI, 0.04-0.59), P = 0.03. The area under the curve (AUC) of SN to predict mortality in patients with CV -related ARF was 0.72 (95% CI, 0.65-0.79), and the AUC of NT-proBNP was 0.64 (0.56-0.73). In contrast, SN concentrations on ICU admission did not provide incremental prognostic value to established risk indices in patients with non CV-related ARF, and the AUC was 0.67 (0.60-0.75).

    CONCLUSIONS: SN concentrations measured on ICU admission provided incremental prognostic information to established risk indices in patients with CV -related ARF, but not in patients with non CV-related ARF.

  • 49. Myhre, Peder Langeland
    et al.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Linko, Rita
    Okkonen, Marjatta
    Nygård, Ståle
    Christensen, Geir
    Pettilä, Ville
    Omland, Torbjørn
    Røsjø, Helge
    Circulating chromogranin B levels in patients with acute respiratory failure: data from the FINNALI Study2017In: Biomarkers, ISSN 1354-750X, E-ISSN 1366-5804, Vol. 22, no 8, p. 775-781Article in journal (Refereed)
    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.

  • 50.
    Myrelid, Åsa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Frisk, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Annerén, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Normal growth hormone secretion in overweight young adults with Down syndrome2010In: Growth Hormone & IGF Research, ISSN 1096-6374, E-ISSN 1532-2238, Vol. 20, no 2, p. 174-178Article in journal (Refereed)
    Abstract [en]

    Down syndrome (DS) is associated with short stature and obesity. Adults with DS have several features in common with growth hormone (GH) deficient adult subjects. The aim of this study was to investigate GH secretion in young adults with DS and its relation to body composition as well as glucose and lipid metabolism. Ten young adults with DS (aged 24-32 years; 5 F) and ten controls matched for age and sex were examined regarding spontaneous nocturnal GH secretion and body composition. Stable isotope tracers were used to study glucose and lipid metabolism in the DS subjects. There was no difference in secretion of GH between the DS subjects and controls. The DS subjects had a higher BMI, fat mass proportion and HOMA (homeostasis model assessment) index compared with the controls. The rates of production of glucose and glycerol (reflecting lipolysis) in the DS subjects were increased (15.5+/-5.07 and 3.5+/-1.68 micromol/kg/min, respectively). The DS subjects showed normal GH secretion despite increased BMI and fat mass. The increased HOMA index and high rate of glucose production indicate peripheral and hepatic insulin resistance in adult DS subjects.

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