| 1. |
- Dalin, Frida, 1984-, et al.
(författare)
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Clinical and immunological characteristics of Autoimmune Addison's disease : a nationwide Swedish multicenter study
- 2017
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 102:2, s. 379-389
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Studies on clinical and immunological features of Autoimmune Addison's disease (AAD) are needed to understand the disease burden and increased mortality.OBJECTIVE: To provide upgraded data on autoimmune comorbidities, replacement therapy, autoantibody profiles and cardiovascular risk factors.DESIGN, SETTING AND PARTICIPANTS: Cross sectional, population-based study. 660 AAD patients were included utilizing the Swedish Addison Registry (SAR) 2008-2014. When analyzing cardiovascular risk factors, 3,594 individuals from the population-based survey in Northern Sweden, MONICA (MONItoring of Trends and Determinants of CArdiovascular Disease), served as controls.MAIN OUTCOME MEASURE: Prevalence of autoimmune comorbidities and cardiovascular risk factors. Autoantibodies against 13 autoantigens were determined.RESULTS: Sixty percent of the SAR cohort consisted of females. Mean age at diagnosis was significantly higher for females than for males (36.8 vs. 31.1 years). The proportion of 21-hydroxylase autoantibody positive patients was 83% and 62% of patients had one or more associated autoimmune diseases, more frequently coexisting in females (p<0.0001). AAD patients had lower BMI (p<0.0001) and prevalence of hypertension (p=0.027) compared with controls. Conventional hydrocortisone tablets were used by 89% of patients; with the mean dose 28.1±8.5 mg/day. The mean hydrocortisone equivalent dose normalized to body surface was 14.8±4.4 mg/m(2)/day. Higher hydrocortisone equivalent dose was associated with higher incidence of hypertension (p=0.046).CONCLUSIONS: Careful monitoring of AAD patients is warranted to detect associated autoimmune diseases. Contemporary Swedish AAD patients do not have increased prevalence of overweight, hypertension, T2DM or hyperlipidemia. However, high glucocorticoid replacement doses may be a risk factor for hypertension.
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| 2. |
- Bjursell, Magnus K., et al.
(författare)
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Adenosine Kinase Deficiency Disrupts the Methionine Cycle and Causes Hypermethioninemia, Encephalopathy, and Abnormal Liver Function
- 2011
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 89:4, s. 507-515
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Tidskriftsartikel (refereegranskat)abstract
- Four inborn errors of metabolism (IEMs) are known to cause hypermethioninemia by directly interfering with the methionine cycle. Hypermethioninemia is occasionally discovered incidentally, but it is often disregarded as an unspecific finding, particularly if liver disease is involved. In many individuals the hypermethioninemia resolves without further deterioration, but it can also represent an early sign of a severe, progressive neurodevelopmental disorder. Further investigation of unclear hypermethioninemia is therefore important. We studied two siblings affected by severe developmental delay and liver dysfunction. Biochemical analysis revealed increased plasma levels of methionine, S-adenosylmethionine (Ado Met), and S-adenosylhomocysteine (AdoHcy) but normal or mildly elevated homocysteine (Hcy) levels, indicating a block in the methionine cycle. We excluded S-adenosylhomocysteine hydrolase (SAHH) deficiency, which causes a similar biochemical phenotype, by using genetic and biochemical techniques and hypothesized that there was a functional block in the SAHH enzyme as a result of a recessive mutation in a different gene. Using exome sequencing, we identified a homozygous c.902C>A (p.Ala301Glu) missense mutation in the adenosine kinase gene (ADK), the function of which fits perfectly with this hypothesis. Increased urinary adenosine excretion confirmed ADK deficiency in the siblings. Four additional individuals from two unrelated families with a similar presentation were identified and shown to have a homozygous c.653A>C (p.Asp218Ala) and c.38G>A (p.Gly13Glu) mutation, respectively, in the same gene. All three missense mutations were deleterious, as shown by activity measurements on recombinant enzymes. ADK deficiency is a previously undescribed, severe IEM shedding light on a functional link between the methionine cycle and adenosine metabolism.
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| 3. |
- Alarcon, Sonia, et al.
(författare)
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Endocrine, metabolic and apical effects of in utero and lactational exposure to non-dioxin-like 2,2 ',3,4,4 ',5,5 '-heptachlorobiphenyl (PCB 180) : A postnatal follow-up study in rats
- 2021
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Ingår i: Reproductive Toxicology. - : Elsevier. - 0890-6238 .- 1873-1708. ; 102, s. 109-127
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Tidskriftsartikel (refereegranskat)abstract
- PCB 180 is a persistent and abundant non-dioxin-like PCB (NDL-PCB). We determined the developmental toxicity profile of ultrapure PCB 180 in developing offspring following in utero and lactational exposure with the focus on endocrine, metabolic and retinoid system alterations. Pregnant rats were given total doses of 0, 10, 30, 100, 300 or 1000 mg PCB 180/kg bw on gestational days 7-10 by oral gavage, and the offspring were sampled on postnatal days (PND) 7, 35 and 84. Decreased serum testosterone and triiodothyronine concentrations on PND 84, altered liver retinoid levels, increased liver weights and induced 7-pentoxyresorufin O-dealkylase (PROD) activity were the sensitive effects used for margin of exposure (MoE) calculations. Liver weights were increased together with induction of the metabolizing enzymes cytochrome P450 (CYP) 2B1, CYP3A1, and CYP1A1. Less sensitive effects included decreased serum estradiol and increased luteinizing hormone levels in females, decreased prostate and seminal vesicle weight and increased pituitary weight in males, increased cortical bone area and thickness of tibial diaphysis in females and decreased cortical bone mineral density in males. Developmental toxicity profiles were partly different in male and female offspring, males being more sensitive to increased liver weight, PROD induction and decreased thyroxine concentrations. MoE assessment indicated that the 95th percentile of current maternal PCB 180 concentrations do not exceed the estimated tolerable human lipid-based PCB 180 concentration. Although PCB 180 is much less potent than dioxin-like compounds, it shares several toxicological targets suggesting a potential for interactions.
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| 4. |
- Askelöf, M, et al.
(författare)
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Eating behaviour and body image in overweight adolescent girls with or without hyperandrogenicity
- 2007
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Ingår i: Eating and Weight Disorders. - 1124-4909 .- 1590-1262. ; 12:1, s. 41-47
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Tidskriftsartikel (refereegranskat)abstract
- We addressed the question of whether a combination of obesity and hyperandrogenicity has a more severe influence on psychosocial behaviours, as reflected by eating behaviour and body image, compared to obesity alone. AIM: To study eating behaviour and body image in age-, pubertal- and BMI-matched overweight adolescent girls with and without hyperandrogenicity, and to compare the data with those from a control group of normal weight girls. METHODS: Overweight adolescent girls in late puberty with (n=10) and without hyperandrogenicity (n=8) and a control group of normal weight girls (n=9) were studied. The Eating Disorder Inventory for children (EDI-C) questionnaire was used to obtain information on eating behaviours and psychological characteristics, and silhouettes were used to evaluate body image. RESULTS: The girls with overweight but without hyperandrogenicity showed more disturbed eating behaviour and more psychological problems than did the girls with both overweight and hyperandrogenicity as compared to the healthy controls. The overweight group also had more feelings of ineffectiveness than the hyperandrogenic group. Both the overweight and the hyperandrogenic girls estimated themselves as being significantly larger and their ideal shape as being significantly smaller than their Current shape. However, all overweight girls considered their Current shape to be significantly smaller than it was objectively. CONCLUSIONS: The girl With overweight alone seemed to have more disturbed eating behaviour and more psychological problems than girls with combined overweight and hyperandrogenicity. This could indicate that different therapeutic interventions might be needed in attempts to reduce weight in the two groups.
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| 5. |
- Bagger, Alexander, et al.
(författare)
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Ab Initio Cyclic Voltammetry on Cu(111), Cu(100) and Cu(110) in Acidic, Neutral and Alkaline Solutions
- 2019
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Ingår i: ChemPhysChem. - : Wiley. - 1439-4235 .- 1439-7641. ; 20
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Tidskriftsartikel (refereegranskat)abstract
- Electrochemical reactions depend on the electrochemical interface between the electrode surfaces and the electrolytes. To control and advance electrochemical reactions there is a need to develop realistic simulation models of the electrochemical interface to understand the interface from an atomistic point-of-view. Here we present a method for obtaining thermodynamic realistic interface structures, a procedure we use to derive specific coverages and to obtain ab initio simulated cyclic voltammograms. As a case study, the method and procedure is applied in a matrix study of three Cu facets in three different electrolytes. The results have been validated by direct comparison to experimental cyclic voltammograms. The alkaline (NaOH) cyclic voltammograms are described by H* and OH*, while in neutral medium (KHCO3) the CO3* species are dominating and in acidic (KCl) the Cl* species prevail. An almost one-to-one mapping is observed from simulation to experiments giving an atomistic understanding of the interface structure of the Cu facets. Atomistic understanding of the interface at relevant eletrolyte conditions will further allow realistic modelling of electrochemical reactions of importance for future eletrocatalytic studies.
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| 6. |
- Bogdanska, Jasna, et al.
(författare)
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Tissue distribution of (35)S-labelled perfluorooctane sulfonate in adult mice after oral exposure to a low environmentally relevant dose or a high experimental dose
- 2011
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Ingår i: Toxicology. - : Elsevier BV. - 0300-483X .- 1879-3185. ; 284:1-3, s. 54-62
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Tidskriftsartikel (refereegranskat)abstract
- The widespread environmental pollutant perfluorooctane sulfonate (PFOS), detected in most animal species including the general human population, exerts several effects on experimental animals, e.g., hepatotoxicity, immunotoxicity and developmental toxicity. However, detailed information on the tissue distribution of PFOS in mammals is scarce and, in particular, the lack of available information regarding environmentally relevant exposure levels limits our understanding of how mammals (including humans) may be affected. Accordingly, we characterized the tissue distribution of this compound in mice, an important experimental animal for studying PFOS toxicity. Following dietary exposure of adult male C57/BL6 mice for 1-5 days to an environmentally relevant (0.031 mg/kg/day) or a 750-fold higher experimentally relevant dose (23 mg/kg/day) of (35)S-PFOS, most of the radioactivity administered was recovered in liver, bone (bone marrow), blood, skin and muscle, with the highest levels detected in liver, lung, blood, kidney and bone (bone marrow). Following high daily dose exposure, PFOS exhibited a different distribution profile than with low daily dose exposure, which indicated a shift in distribution from the blood to the tissues with increasing dose. Both scintillation counting (with correction for the blood present in the tissues) and whole-body autoradiography revealed the presence of PFOS in all 19 tissues examined, with identification of thymus as a novel site for localization for PFOS and bone (bone marrow), skin and muscle as significant body compartments for PFOS. These findings demonstrate that PFOS leaves the bloodstream and enters most tissues in a dose-dependent manner.
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| 7. |
- Bondesson, Maria, et al.
(författare)
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A CASCADE of effects of bisphenol A.
- 2009
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Ingår i: Reproductive Toxicology. - : Elsevier BV. - 0890-6238 .- 1873-1708. ; 28:4, s. 563-7
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Tidskriftsartikel (refereegranskat)
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| 8. |
- Borg, Daniel, et al.
(författare)
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Perinatal tissue distribution of perfluorooctane sulphonate (PFOS) in mice.
- 2009
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Ingår i: Abstracts of the 46th Congress of the European Societies of Toxicology. - : Elsevier BV. ; 189:SI, s. S147-S147
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Konferensbidrag (refereegranskat)abstract
- Perfluorooctane sulfonate (PFOS) is an industrial chemical that has been used as a surfactant and surface protector for more than fifty years. It has during the last decade emerged as an environmental contaminant due to its widespread presence in humans and wildlife and its persistant, bioaccumulative and toxic properties. PFOS is developmentally toxic and late in utero exposure in rodents affects neonatal survival and growth. Observed symptoms suggest impaired pulmonary function, but the cause of the mortality has not been clarified. The purpose of this study was to determine the perinatal tissue distribution of S35-labelled PFOS in mice using whole-body autoradiography (WBA) combined with liquid scintillation counting (LSC). Pregnant C57Bl/6 mice were dosed orally on gestation day (GD) 16 and sampled on GD18, GD20 and postnatal day (PND) 1 (dams + pups). The results from the WBA and the LSC were unequivocal. In dams, PFOS accumulated primarily in the liver, but also the lungs contained levels higher than the blood. PFOS was readily transferred to the fetus. At GD18 general PFOS levels were higher in the fetus than in the blood of the corresponding dam with accumulation in the liver. At GD20, general PFOS levels remained higher in the fetus than in the dam, with substantial accumulation also in the lung. The accumulation in the lung persisted at PND1. Our results show that the fetus is exposed to higher levels of PFOS than the dam and point towards the lung being the main perinatal target organ of PFOS.
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| 9. |
- Borg, D., et al.
(författare)
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Tissue distribution of S-35-labelled perfluorooctane sulfonate (PFOS) in C57Bl/6 mice following late gestational exposure
- 2010
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Ingår i: Reproductive Toxicology. - : Elsevier BV. - 0890-6238 .- 1873-1708. ; 30:4, s. 558-565
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Tidskriftsartikel (refereegranskat)abstract
- Exposure of rodents in utero to perfluorooctane sulfonate (PFOS) impairs perinatal development and survival Following intravenous or gavage exposure of C57Bl/6 mouse dams on gestational day (GD) 16 to S-35-PFOS (12 5 mg/kg) we determined the distribution in dams fetuses (GD18 and GD20) and pups (postnatal day 1 PND1) employing whole-body autoradiography and liquid scintillation counting In dams levels were highest in liver and lungs After placental transfer S-35-PFOS was present on GD18 at 2-3 times higher levels in lungs liver and kidneys than in maternal blood In PND1 pups levels in lungs were significantly higher than in GD18 fetuses A heterogeneous distribution of S-35-PFOS was observed in brains of fetuses and pups with levels higher than in maternal brain This first demonstration of substantial localization of PFOS to both perinatal and adult lungs is consistent with evidence describing the lung as a target for the toxicity of PFOS at these ages.
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| 10. |
- Bozzola, Mauro, et al.
(författare)
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Treatment adherence with the easypod (TM) growth hormone electronic auto-injector and patient acceptance : survey results from 824 children and their parents
- 2011
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Ingår i: BMC Endocrine Disorders. - : Springer Science and Business Media LLC. - 1472-6823. ; 11, s. 4-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Accurately monitoring adherence to treatment with recombinant human growth hormone (r-hGH) enables appropriate intervention in cases of poor adherence. The electronic r-hGH auto-injector, easypod(TM), automatically records the patient's adherence to treatment. This study evaluated adherence to treatment of children who started using the auto-injector and assessed opinions about the device. Methods: A multicentre, multinational, observational 3-month survey in which children received r-hGH as part of their normal care. Physicians reviewed the recorded dose history and children (with or without parental assistance) completed a questionnaire-based survey. Children missing <= 2 injections per month (92% of injections given) were considered adherent to treatment. Adherence was compared between GH treatment-naive and treatment-experienced children. Results: Of 834 recruited participants, 824 were evaluated. The median (range) age was 11 (1-18) years. From the recorded dose history, 87.5% of children were adherent to treatment over the 3-month period. Recorded adherence was higher in treatment-naive (89.7%, n = 445/496) than in treatment-experienced children (81.7%, n = 152/186) [Fisher's exact test FI(X) = 7.577; p = 0.0062]. According to self-reported data, 90.2% (607/673) of children were adherent over 3 months; 51.5% (421/817) missed >= 1 injection over this period (mainly due to forgetfulness). Concordance between reported and recorded adherence was 84.3%, with a trend towards self-reported adherence being higher than recorded adherence. Most children liked the auto-injector: over 80% gave the top two responses from five options for ease of use (720/779), speed (684/805) and comfort (716/804). Although 38.5% (300/780) of children reported pain on injection, over half of children (210/363) considered the pain to be less or much less than expected. Given the choice, 91.8% (732/797) of children/parents would continue using the device. Conclusions: easypod(TM) provides an accurate method of monitoring adherence to treatment with r-hGH. In children who received treatment with r-hGH using easypod(TM), short-term adherence is good, and significantly higher in treatment-naive children compared with experienced children. Children/parents rate the device highly. The high level of acceptability of the device is reflected by a desire to continue using it by over 90% of the children in the survey.
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