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University for Health Sciences, Medical Informatics and Technology (UMIT TIROL), Tirol, Austria
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Institute for Medical Biometry, Informatics and Epidemiology (IMBIE), Faculty of Medicine, University of Bonn, Bonn, Germany
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Department of Neurology, Faculty of Medicine, University of Bonn, Bonn, Germany
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Introduction Maintaining muscle function throughout life is critical for healthy ageing ( 1 ). Progressive loss of muscle mass and function with age is a feature of primary sarcopenia and negatively affects mobility, functional independence
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Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands
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. Osteoporosis International 1999 9 351 – 35 7 . ( https://doi.org/10.1007/s001980050158 ) 16 Roof BS Piel CF Hansen J Fudenberg HH Serum parathyroid hormone levels and serum calcium levels from birth to senescence . Mechanisms of Ageing and
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life and motivation to exercise in ageing men . Age 2015 37 25 . ( doi:10.1007/s11357-015-9763-3 ) 10.1007/s11357-015-9763-3 8 Klein C Cunningham DA Paterson DH Taylor AW. Fatigue and recovery contractile properties of young
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following exercise training in ageing men . Aging Male 2015 18 67 – 70 . ( doi:10.3109/13685538.2015.1018158 ) 17 Knowles AM Herbert P Easton C Sculthorpe N Grace FM. Impact of low-volume, high-intensity interval training on
Department of Urology, Foundation IRCCS Ca’ Granda – Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
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University Vita-Salute San Raffaele, Milan, Italy
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University Vita-Salute San Raffaele, Milan, Italy
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University Vita-Salute San Raffaele, Milan, Italy
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University Vita-Salute San Raffaele, Milan, Italy
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University Vita-Salute San Raffaele, Milan, Italy
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University Vita-Salute San Raffaele, Milan, Italy
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University Vita-Salute San Raffaele, Milan, Italy
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University Vita-Salute San Raffaele, Milan, Italy
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University Vita-Salute San Raffaele, Milan, Italy
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, Ring et al . investigated the clinical utility of testing SHBG/cFT values in infertile men ( 7 ). Several factors are known to influence serum SHBG levels such as ageing, obesity, diabetes mellitus (DM), thyroid diseases and cirrhosis ( 8 , 9 , 10
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ageing and the development of age-related diseases. In addition, insulin resistance (IR) is considered to be a predictor of atherosclerosis and CVD independently of other risk factors, such as blood lipid levels, and hyperglycaemia results in ageing
Endocrine Unit, Royal Victoria Infirmary, Newcastle upon Tyne, UK
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Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
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Endocrine Unit, Royal Victoria Infirmary, Newcastle upon Tyne, UK
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Background
The highly plastic nature of adrenal cortex suggests the presence of adrenocortical stem cells (ACSC), but the exact in vivo identity of ACSC remains elusive. A few studies have demonstrated the differentiation of adipose or bone marrow-derived mesenchymal stem cells (MSC) into steroid-producing cells. We therefore investigated the isolation of multipotent MSC from human adrenal cortex.
Methods
Human adrenals were obtained as discarded surgical material. Single-cell suspensions from human adrenal cortex (n = 3) were cultured onto either complete growth medium (CM) or MSC growth promotion medium (MGPM) in hypoxic condition. Following ex vivo expansion, their multilineage differentiation capacity was evaluated. Phenotype markers were analysed by immunocytochemistry and flow cytometry for cell-surface antigens associated with bone marrow MSCs and adrenocortical-specific phenotype. Expression of mRNAs for pluripotency markers was assessed by q-PCR.
Results
The formation of colony-forming unit fibroblasts comprising adherent cells with fibroblast-like morphology were observed from the monolayer cell culture, in both CM and MGPM. Cells derived from MGPM revealed differentiation towards osteogenic and adipogenic cell lineages. These cells expressed cell-surface MSC markers (CD44, CD90, CD105 and CD166) but did not express the haematopoietic, lymphocytic or HLA-DR markers. Flow cytometry demonstrated significantly higher expression of GLI1 in cell population harvested from MGPM, which were highly proliferative. They also exhibited increased expression of the pluripotency markers.
Conclusion
Our study demonstrates that human adrenal cortex harbours a mesenchymal stem cell-like population. Understanding the cell biology of adrenal cortex- derived MSCs will inform regenerative medicine approaches in autoimmune Addison’s disease.
Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
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Department of General Surgery, St. Elisabeth’s Hospital, Graz, Austria
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The prevalence of vitamin D deficiency in intensive care units ranges typically between 40 and 70%. There are many reasons for being or becoming deficient in the ICU. Hepatic, parathyroid and renal dysfunction additionally increases the risk for developing vitamin D deficiency. Moreover, therapeutic interventions like fluid resuscitation, dialysis, surgery, extracorporeal membrane oxygenation, cardiopulmonary bypass and plasma exchange may significantly reduce vitamin D levels. Many observational studies have consistently shown an association between low vitamin D levels and poor clinical outcomes in critically ill adults and children, including excess mortality and morbidity such as acute kidney injury, acute respiratory failure, duration of mechanical ventilation and sepsis. It is biologically plausible that vitamin D deficiency is an important and modifiable contributor to poor prognosis during and after critical illness. Although vitamin D supplementation is inexpensive, simple and has an excellent safety profile, testing for and treating vitamin D deficiency is currently not routinely performed. Overall, less than 800 patients have been included in RCTs worldwide, but the available data suggest that high-dose vitamin D supplementation could be beneficial. Two large RCTs in Europe and the United States, together aiming to recruit >5000 patients, have started in 2017, and will greatly improve our knowledge in this field. This review aims to summarize current knowledge in this interdisciplinary topic and give an outlook on its highly dynamic future.
Department of Clinical Physiology and Nuclear Medicine, Bispebjerg and Frederiksberg Hospital, University Hospital of Copenhagen, Copenhagen, Denmark
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Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark
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Department of Geriatrics, Bispebjerg and Frederiksberg Hospital, University Hospital of Copenhagen, Copenhagen, Denmark
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Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
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Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
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Glucose-dependent insulinotropic polypeptide (GIP) in combination with hyperinsulinemia increase blood flow and triglyceride clearance in subcutaneous abdominal adipose tissue in lean humans. The present experiments were performed to determine whether the increase involves capillary recruitment. Eight lean healthy volunteers were studied before and after 1 h infusion of GIP or saline during a hyperglycemic–hyperinsulinemic clamp, raising plasma glucose and insulin to postprandial levels. Subcutaneous abdominal adipose tissue blood flow (ATBF) was measured by the 133Xenon clearance technique, and microvascular blood volume was determined by contrast-enhanced ultrasound imaging. During infusion of saline and the clamp, both ATBF (2.7 ± 0.5 mL/min 100 g/tissue) and microvascular blood volume remained unchanged throughout the experiments. During GIP infusion and the clamp, ATBF increased ~fourfold to 11.4 ± 1.9 mL/min 100 g/tissue, P < 0.001. Likewise, the contrast-enhanced ultrasound signal intensity, a measure of the microvascular blood volume, increased significantly 1 h after infusion of GIP and the clamp (P = 0.003), but not in the control experiments. In conclusion, the increase in ATBF during GIP infusion involves recruitment of capillaries in healthy lean subjects, which probably increases the interaction of circulating lipoproteins with lipoprotein lipase, thus promoting adipose tissue lipid uptake.
School of Nursing, Institute of Clinical Sciences, University of Birmingham, Edgbaston, Birmingham, UK
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Vitamin D has well-documented effects on calcium homeostasis and bone metabolism but recent studies suggest a much broader role for this secosteroid in human health. Key components of the vitamin D system, notably the vitamin D receptor (VDR) and the vitamin D-activating enzyme (1α-hydroxylase), are present in a wide array of tissues, notably macrophages, dendritic cells and T lymphocytes (T cells) from the immune system. Thus, serum 25-hydroxyvitamin D (25D) can be converted to hormonal 1,25-dihydroxyvitamin D (1,25D) within immune cells, and then interact with VDR and promote transcriptional and epigenomic responses in the same or neighbouring cells. These intracrine and paracrine effects of 1,25D have been shown to drive antibacterial or antiviral innate responses, as well as to attenuate inflammatory T cell adaptive immunity. Beyond these mechanistic observations, association studies have reported the correlation between low serum 25D levels and the risk and severity of human immune disorders including autoimmune diseases such as inflammatory bowel disease, multiple sclerosis, type 1 diabetes and rheumatoid arthritis. The proposed explanation for this is that decreased availability of 25D compromises immune cell synthesis of 1,25D leading to impaired innate immunity and over-exuberant inflammatory adaptive immunity. The aim of the current review is to explore the mechanistic basis for immunomodulatory effects of 25D and 1,25D in greater detail with specific emphasis on how vitamin D-deficiency (low serum levels of 25D) may lead to dysregulation of macrophage, dendritic cell and T cell function and increase the risk of inflammatory autoimmune disease.
