Insulin sensitivity and metabolic flexibility decrease in response to bed rest, but the temporal and causal adaptations in human skeletal muscle metabolism are not fully defined. Here, we use an integrative approach to assess human skeletal muscle metabolism during bed rest and provide a multi-system analysis of how skeletal muscle and the circulatory system adapt to short- and long-term bed rest (German Clinical Trials: DRKS00015677). We uncover that intracellular glycogen accumulation after short-term bed rest accompanies a rapid reduction in systemic insulin sensitivity and less GLUT4 localization at the muscle cell membrane, preventing further intracellular glycogen deposition after long-term bed rest. We provide evidence of a temporal link between the accumulation of intracellular triglycerides, lipotoxic ceramides, and sphingomyelins and an altered skeletal muscle mitochondrial structure and function after long-term bed rest. An intracellular nutrient overload therefore represents a crucial determinant for rapid skeletal muscle insulin insensitivity and mitochondrial alterations after prolonged bed rest.
tIn this study we aimed to identify genes that are responsive to pertussis toxin (PTx) and might eventu-ally be used as biological markers in a testing strategy to detect residual PTx in vaccines. By microarrayanalysis we screened six human cell types (bronchial epithelial cell line BEAS-2B, fetal lung fibroblastcell line MRC-5, primary cardiac microvascular endothelial cells, primary pulmonary artery smooth mus-cle cells, hybrid cell line EA.Hy926 of umbilical vein endothelial cells and epithelial cell line A549 andimmature monocyte-derived dendritic cells) for differential gene expression induced by PTx. Imma-ture monocyte-derived dendritic cells (iMoDCs) were the only cells in which PTx induced significantdifferential expression of genes. Results were confirmed using different donors and further extendedby showing specificity for PTx in comparison to Escherichia coli lipopolysaccharide (LPS) and Bordetellapertussis lipo-oligosaccharide (LOS). Statistical analysis indicated 6 genes, namely IFNG, IL2, XCL1, CD69,CSF2 and CXCL10, as significantly upregulated by PTx which was also demonstrated at the protein levelfor genes encoding secreted proteins. IL-2 and IFN- gave the strongest response. The minimal PTx con-centrations that induced production of IL-2 and IFN- in iMoDCs were 12.5 and 25 IU/ml, respectively.High concentrations of LPS slightly induced IFN- but not IL-2, while LOS and detoxified pertussis toxindid not induce production of either cytokine. In conclusion, using microarray analysis we evaluated sixhuman cell lines/types for their responsiveness to PTx and found 6 PTx-responsive genes in iMoDCs ofwhich IL2 is the most promising candidate to be used as a biomarker for the detection of residual PTx.
Acne vulgaris is considered one of the most common medical skin conditions globally, affecting approximately 85% of individuals worldwide. While acne is most prevalent among adolescents between 15 to 24 years old, it is not uncommon in adults either. Acne addresses a number of different challenges, causing a multidimensional disease burden. These challenges include clinical sequelae, such as post inflammatory hyperpigmentation (PIH) and the chance of developing lifelong disfiguring scars, psychological aspects such as deficits in health related quality of life, chronicity of acne, economic factors, and treatment-related issues, such as antimicrobial resistance. The multidimensionality of the disease burden stipulates the importance of an effective and timely treatment in a well organised care system. Within the Netherlands, acne care provision is managed by several types of professional care givers, each approaching acne care from different angles: (I) general practitioners (GPs) who serve as ‘gatekeepers’ of healthcare within primary care; (II) dermatologists providing specialist medical care within secondary care; (III) dermal therapists, a non-physician medical professional with a bachelor’s degree, exclusively operating within the Australian and Dutch primary and secondary health care; and (IV) beauticians, mainly working within the cosmetology or wellness domain. However, despite the large variety in acne care services, many patients experience a delay between the onset of acne and receiving an effective treatment, or a prolonged use of care, which raises the question whether acne related care resources are being used in the most effective and (cost)efficient way. It is therefore necessary to gain insights into the organization and quality of Dutch acne health care beyond conventional guidelines and protocols. Exploring areas of care that may need improvement allow Dutch acne healthcare services to develop and improve the quality of acne care services in harmony with patient needs.
