| 1. |
- Kia, Richard, et al.
(författare)
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MicroRNA-122 : a novel hepatocyte-enriched in vitro marker of drug-induced cellular toxicity
- 2015
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Ingår i: Toxicological Sciences. - : Oxford University Press. - 1096-6080 .- 1096-0929. ; 144:1, s. 173-185
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Tidskriftsartikel (refereegranskat)abstract
- Emerging hepatic models for the study of drug-induced toxicity include pluripotent stem cell-derived hepatocyte-like cells (HLCs) and complex hepatocyte-non-parenchymal cellular coculture to mimic the complex multicellular interactions that recapitulate the niche environment in the human liver. However, a specific marker of hepatocyte perturbation, required to discriminate hepatocyte damage from non-specific cellular toxicity contributed by non-hepatocyte cell types or immature differentiated cells is currently lacking, as the cytotoxicity assays routinely used in in vitro toxicology research depend on intracellular molecules which are ubiquitously present in all eukaryotic cell types. In this study, we demonstrate that microRNA-122 (miR-122) detection in cell culture media can be used as a hepatocyte-enriched in vitro marker of drug-induced toxicity in homogeneous cultures of hepatic cells, and a cell-specific marker of toxicity of hepatic cells in heterogeneous cultures such as HLCs generated from various differentiation protocols and pluripotent stem cell lines, where conventional cytotoxicity assays using generic cellular markers may not be appropriate. We show that the sensitivity of the miR-122 cytotoxicity assay is similar to conventional assays that measure lactate dehydrogenase activity and intracellular adenosine triphosphate when applied in hepatic models with high levels of intracellular miR-122, and can be multiplexed with other assays. MiR-122 as a biomarker also has the potential to bridge results in in vitro experiments to in vivo animal models and human samples using the same assay, and to link findings from clinical studies in determining the relevance of in vitro models being developed for the study of drug-induced liver injury.
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| 2. |
- Arnoldussen, Ilse A. C., et al.
(författare)
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Adiposity is related to cerebrovascular and brain volumetry outcomes in the RUN DMC study
- 2019
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Ingår i: Neurology. - : Wolters Kluwer. - 0028-3878 .- 1526-632X. ; 93:9, s. e864-e878
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Adiposity predictors, body mass index (BMI), waist circumference (WC), and blood leptin and total adiponectin levels were associated with components of cerebral small vessel disease (CSVD) and brain volumetry in 503 adults with CSVD who were ≥50 years of age and enrolled in the Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Imaging Cohort (RUN DMC).METHODS: RUN DMC participants were followed up for 9 years (2006-2015). BMI, WC, brain imaging, and dementia diagnoses were evaluated at baseline and follow-up. Adipokines were measured at baseline. Brain imaging outcomes included CSVD components, white matter hyperintensities, lacunes, microbleeds, gray and white matter, hippocampal, total brain, and intracranial volumes.RESULTS: Cross-sectionally among men at baseline, higher BMI, WC, and leptin were associated with lower gray matter and total brain volumes, and higher BMI and WC were associated with lower hippocampal volume. At follow-up 9 years later, higher BMI was cross-sectionally associated with lower gray matter volume, and an obese WC (>102 cm) was protective for ≥1 lacune or ≥1 microbleed in men. In women, increasing BMI and overweight or obesity (BMI ≥25 kg/m2 or WC >88 cm) were associated with ≥1 lacune. Longitudinally, over 9 years, a baseline obese WC was associated with decreasing hippocampal volume, particularly in men, and increasing white matter hyperintensity volume in women and men.CONCLUSIONS: Anthropometric and metabolic adiposity predictors were differentially associated with CSVD components and brain volumetry outcomes by sex. Higher adiposity is associated with a vascular-neurodegenerative spectrum among adults at risk for vascular forms of cognitive impairment and dementias.
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| 3. |
- Wickström, Hanna L, et al.
(författare)
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Comparing video consultation with inperson assessment for Swedish patients with hard-to-heal ulcers : registry-based studies of healing time and of waiting time
- 2018
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 8:2
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To investigate differences in ulcer healing time and waiting time between video consultation and inperson assessment for patients with hard-to-heal ulcers. Setting Patients treated at Blekinge Wound Healing Centre, a primary care centre covering the whole of Blekinge county (150 000 inhabitants), were compared with patients registered and treated according to the Registry of Ulcer Treatment, a Swedish national web-based quality registry. Participants In the study for analysing ulcer healing time, the study group consisted of 100 patients diagnosed through video consultation between October 2014 and September 2016. The control group for analysing healing time consisted of 1888 patients diagnosed through inperson assessment during the same period. In the study for analysing waiting time, the same study group (n=100) was compared with 100 patients diagnosed through inperson assessment. Primary and secondary outcome measures Differences in ulcer healing time were analysed using the log-rank test. Differences in waiting time were analysed using the Mann-Whitney U test. Results Median healing time was 59 days (95% CI 40 to 78) in the study group and 82 days (95% CI 75 to 89) in the control group (P<0.001). Median waiting time was 25 days (range: 1-83 days) in the study group and 32 days (range: 3-294 days) for patients diagnosed through inperson assessment (P=0.017). There were no significant differences between the study group and the control group regarding age, gender or ulcer size. Conclusions Healing time and waiting time were significantly shorter for patients diagnosed through video consultation compared with those diagnosed through inperson assessment.
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