| 1. |
- Sotak, Matus, et al.
(författare)
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Intestinal sodium/glucose cotransporter 3 expression is epithelial and downregulated in obesity.
- 2021
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Ingår i: Life sciences. - : Elsevier BV. - 1879-0631 .- 0024-3205. ; 267
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Tidskriftsartikel (refereegranskat)abstract
- We aimed to determine whether the sodium/glucose cotransporter family member SGLT3, a proposed glucose sensor, is expressed in the intestine and/or kidney, and if its expression is altered in mouse models of obesity and in humans before and after weight-loss surgery.We used in-situ hybridization and quantitative PCR to determine whether the Sglt3 isoforms 3a and 3b were expressed in the intestine and kidney of C57, leptin-deficient ob/ob, and diabetic BTBR ob/ob mice. Western blotting and immunohistochemistry were also used to assess SGLT3 protein levels in jejunal biopsies from obese patients before and after weight-loss Roux-en-Y gastric bypass surgery (RYGB), and in lean healthy controls.Sglt3a/3b mRNA was detected in the small intestine (duodenum, jejunum and ileum), but not in the large intestine or kidneys of mice. Both isoforms were detected in epithelial cells (confirmed using intestinal organoids). Expression of Sglt3a/3b mRNA in duodenum and jejunum was significantly lower in ob/ob and BTBR ob/ob mice than in normal-weight littermates. Jejunal SGLT3 protein levels in aged obese patients before Roux-en-Y gastric bypass (RYGB) were lower than in lean individuals, but substantially upregulated 6months post-RYGB.Our study shows that Sglt3a/3b is expressed primarily in epithelial cells of the small intestine in mice. Furthermore, we observed an association between intestinal mRNA Sglt3a/3b expression and obesity in mice, and between jejunal SGLT3 protein levels and obesity in humans. Further studies are required to determine the possible role of SGLT3 in obesity.
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| 2. |
- Sigurdsson, Gudmundur Vignir, 1985, et al.
(författare)
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Altered body composition profiles in young adults with childhood-onset inflammatory bowel disease
- 2020
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 55:2, s. 169-177
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patients with inflammatory bowel disease (IBD) often develop alterations in body composition in terms of their proportions of lean mass and fat mass, as well as reduced bone mineral density (BMD). However, there are limited data on the skeletal muscle index (SMI) and percentage fat (fat %) for young adults with childhood-onset IBD. Our aim was to investigate the body compositions of these patients, with the focus on SMI and fat %. Methods: Body composition was estimated by dual x-ray absorptiometry for 94 young adults with childhood-onset IBD aged 18–27 years, 65 of whom had ulcerative colitis. The Z-scores for SMI, fat %, and BMD were calculated using the normative data from 1,289 individuals with corresponding age. Based on the SMI and fat % Z-scores, each patient was classified as having a body composition profile that was: (i) normal; (ii) obese (fat % Z-score >1); (iii) myopenic (SMI Z-score < −1); or (iv) myopenic-obese. Results: A higher proportion of young adults with childhood-onset IBD had a body composition profile classified as myopenic (24%) or myopenic-obese (9%), as compared to the controls (myopenic [16%, p =.016]; myopenic-obese [2%, p =.002]). Patients with the myopenic or myopenic-obese profile had significantly lower total body BMD Z-scores (−1.3 ± 0.7 and −1.4 ± 0.9, respectively) than patients with the normal profile (−0.2 ± 1.1; p <.001 and p =.004, respectively). Diagnosis of IBD in childhood represented an additional risk for low BMD, regardless of SMI Z-score. Conclusion: Young adults with childhood-onset IBD have a high risk for having altered body composition traits.Summary Young adults with childhood-onset IBD carry a high risk for altered body composition traits. The myopenic and myopenic-obese body composition profiles were more frequently observed in patients with IBD than controls, and these profiles were strongly associated with low BMD.
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| 3. |
- Sigurdsson, Gudmundur Vignir, 1985, et al.
(författare)
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Physical exercise is associated with beneficial bone mineral density and body composition in young adults with childhood-onset inflammatory bowel disease
- 2021
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 56:6, s. 699-707
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Tidskriftsartikel (refereegranskat)abstract
- Background Patients with inflammatory bowel disease (IBD) have an increased risk of compromised bone mineral density (BMD) and body composition. There are limited data on the physical exercise (PE) habits of patients with childhood-onset IBD and on the associations between PE and BMD and body composition. Patients and methods In total, 72 young adults with childhood-onset IBD and 1341 normative young adult controls answered questionnaires regarding PE [hours/week (h/w)] in the last 12 months. BMD and body composition were measured with dual x-ray absorptiometry (DXA) and presented as age- and gender-adjusted Z-scores for BMD, skeletal muscle index (SMI, the weight of lean mass in arms and legs/m(2)), and percentage body fat (Fat %). Results A total of 41 (57%) patients with IBD engaged in PE during the previous 12 months, as compared to 913 (68%) of the controls (p = .053). Sedentary patients had significantly lower median BMD, SMI, and Fat % Z-scores than the controls with corresponding PE habits (all p < .05). In contrast, highly active (>4 h/week) patients had total body BMD, SMI, and Fat % in the same range as the controls with corresponding PE levels (p = .151, p = .992, and p = .189, respectively), albeit with lower BMDs in the spine (p = .007) and femoral neck (p = .015). Using multiple regression analyses, a diagnosis of childhood-onset IBD was independently associated with inferior BMD and body composition, regardless of the amount of PE. Conclusion Physical exercise is associated with beneficial bone mineral density and body composition in patients with IBD despite the negative effects of the disease.
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| 4. |
- Welen, Karin, et al.
(författare)
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COVIDENZA - A prospective, multicenter, randomized PHASE II clinical trial of enzalutamide treatment to decrease the morbidity in patients with Corona virus disease 2019 (COVID-19): a structured summary of a study protocol for a randomised controlled trial.
- 2021
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- The main goal of the COVIDENZA trial is to evaluate if inhibition of testosterone signalling by enzalutamide can improve the outcome of patients hospitalised for COVID-19. The hypothesis is based on the observation that the majority of patients in need of intensive care are male, and the connection between androgen receptor signalling and expression of TMPRSS2, an enzyme important for SARS-CoV-2 host cell internalization.Hospitalised COVID-19 patients will be randomised (2:1) to enzalutamide plus standard of care vs. standard of care designed to identify superiority.Included participants, men or women above 50 years of age, must be hospitalised for PCR confirmed COVID-19 symptoms and not in need of immediate mechanical ventilation. Major exclusion criteria are breast-feeding or pregnant women, hormonal treatment for prostate or breast cancer, treatment with immunosuppressive drugs, current symptomatic unstable cardiovascular disease (see Additional file 1 for further details). The trial is registered at Umeå University Hospital, Region Västerbotten, Sweden and 8 hospitals are approved for inclusion in Sweden.Patients randomised to the treatment arm will be treated orally with 160 mg (4x40 mg) enzalutamide (Xtandi®) daily, for five consecutive days. The study is not placebo controlled. The comparator is standard of care treatment for patients hospitalised with COVID-19.The primary endpoints of the study are (time to) need of mechanical ventilation or discharge from hospital as assessed by a clinical 7-point ordinal scale (up to 30 days after inclusion).Randomisation was stratified by center and sex. Each strata was randomized separately with block size six with a 2:1 allocation ratio (enzalutamide + "standard of care": "standard of care"). The randomisation list, with consecutive subject numbers, was generated by an independent statistician using the PROC PLAN procedure of SAS version 9.4 software (SAS Institute, Inc, Cary, North Carolina) BLINDING (MASKING): This is an open-label trial.The trial is designed to have three phases. The first, an exploration phase of 45 participants (30 treatment and 15 control) will focus on safety and includes a more extensive laboratory assessment as well as more frequent safety evaluation. The second prolongation phase, includes the first 100 participants followed by an interim analysis to define the power of the study. The third phase is the continuation of the study up to maximum 600 participants included in total.The current protocol version is COVIDENZA v2.0 as of September 10, 2020. Recruitment started July 29, 2020 and is presently in safety pause after the first exploration phase. Recruitment is anticipated to be complete by 31 December 2021.Eudract number 2020-002027-10 ClinicalTrials.gov Identifier: NCT04475601 , registered June 8, 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
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