Copenhagen University Hospital
CURIS (Copenhagen University Research Information System)Not a member yet
395145 research outputs found
Sort by
A field observational study evaluating antemortem inspection as a predictive tool for postmortem lesion findings at a Portuguese pig abattoir
No full textRisk-based inspection of pigs at the abattoir depends on accurately identifying high-risk animals before slaughter. Food Chain Information (FCI) provides data on farm management, animal health, and treatments that can support this process; however, its limited completeness and reliability highlight the need for complementary approaches. Antemortem (AM) conditions may serve as practical predictors of postmortem (PM) lesions, supporting the development of risk-based inspection systems. This study investigated the potential of AM inspection in detecting PM lesions in finisher pigs, slaughtered at a commercial abattoir in Portugal. Data were collected from 62 batches (n = 9542 pigs) for a cross-sectional study, and 245 pigs for a case control study. Detection of coughing, skin lesions, and growth retardation was significantly higher when pigs were inspected from inside the pens, compared with unloading or outside the pens observations. At batch-level coughing at AM inspection was associated with a higher number of PM lesions, particularly pneumonia (OR = 1.08) and pleurisy (OR = 1.03). At animal-level, AM conditions showed consistent associations with PM lesions, including coughing with pneumonia (OR = 6.7), and lung lesion (OR = 6.2), lameness with arthritis (OR = 14.9) and growth retardation with several PM lesions. These findings are consistent with those reported in other countries and confirm that specific AM conditions can reliably predict certain PM lesions, contributing to the refinement of risk-based inspection approaches in Portugal
Co-administering clofazimine with infant formula enhances its oral bioavailability in rats and pigs
No full textMilk-based formulations have been proposed as enabling formulations for the delivery of poorly water-soluble drugs to children due to their safety, dose versatility and ability to improve drug solubilisation through the digestion process. In this study the feasibility of using commercially available infant formula as an enabling formulation to enhance the solubilisation and oral bioavailability of clofazimine, a poorly soluble lipophilic drug, following oral administration was investigated. The solubilisation of crystalline clofazimine in digesting infant formula was assessed in vitro using synchrotron small-angle X-ray scattering. An in vivo pharmacokinetic study was then conducted to determine the oral bioavailability of a suspension of clofazimine in infant formula compared to a lipid-free aqueous suspension in both a rat and piglet animal model. Clofazimine administered in infant formula produced significantly higher plasma concentrations than the aqueous vehicle and resulted in comparable enhancements in relative oral bioavailability in both the piglet (235%) and rat animal models (256%). Results from this study demonstrated that infant formula was an effective enabling formulation, with a positive correlation between improved drug solubilisation during in vitro digestion of infant formula and enhanced in vivo drug exposure following oral administration. Infant formula therefore offers an inexpensive and scalable formulation approach for improving the bioavailability of paediatric drugs, like clofazimine, and enabling the treatment of infections in children.</p
Ultrasound Treatment in Berry Puree Production: Effects on Sensory, Rheological, and Chemical Properties:Molecules
No full textBerries are a valuable source of health-promoting substances, including vitamins, microelements, and polyphenols. Optimising the extraction efficiency of these compounds during processing is crucial to minimise their loss into the waste stream. Ultrasound technology is recognised as a sustainable and promising tool for improving extraction; however, previous literature has not sufficiently addressed the optimal point of its application in fruit puree processing, and its impact on the sensory properties of the final product has only occasionally been explored. As one of the first reports, this study aimed to determine the optimal moment for ultrasound application within a puree production scheme. In the second stage of the experiment, four recipes based on strawberry and haskap berry were tested. The results demonstrated the potential for enhancing sensory quality of puree by using an ultrasound treatment. It was found that the ultrasound-treated purees showed significantly higher pectin levels and improved rheological properties, while the content of anthocyanins and L-ascorbic acid remained mainly unchanged. This indicates that the non-thermal nature of ultrasound treatment can induce positive changes from a sensory and rheological point of view without causing the degradation of health-promoting compounds, offering a viable strategy for improving berry puree quality
TFEB coordinates autophagosome biogenesis and ribophagy during starvation via SQSTM1
No full text(Macro)autophagy is a conserved cellular degradation pathway that delivers substrates to lysosomes via autophagosomes. Among various physiological stimuli, nutrient starvation is the most potent inducer of autophagy. In response to starvation, transcription factor EB (TFEB) is activated and up-regulates a broad set of autophagy-related genes. However, the mechanisms by which TFEB promotes autophagosome biogenesis remain incompletely understood. Here, we demonstrate that TFEB-mediated transcriptional induction of sequestosome 1 (SQSTM1; p62) triggers the formation of SQSTM1-positive bodies that recruit essential autophagy factors, thereby initiating autophagosome biogenesis. Genetic disruption of TFEB-dependent SQSTM1 regulation markedly impairs starvation-induced autophagy, underscoring the critical role of the TFEB-SQSTM1 axis in the autophagic response to nutrient stress. Furthermore, we show that these SQSTM1 bodies contain ubiquitinated ribosomal proteins and that TFEB promotes ribosomal protein ubiquitination by inducing the E3 ubiquitin ligase ZNF598. Collectively, our findings uncover a transcriptionally coordinated mechanism that regulates both autophagosome biogenesis and substrate ubiquitination, facilitating efficient cargo clearance during starvation-induced autophagy.</p
Blood-brain barrier integrity and prevalence of intrathecal T helper 17.1 cells in Huntingtons disease
No full textBackground Blood-brain barrier (BBB) involvement in the pathogenesis of Huntingtons disease (HD) is not well understood. We previously demonstrated increased prevalence of T Helper 17.1 (Th17.1) cells in the cerebrospinal fluid (CSF) of HD gene-expansion carriers (HDGECs), which might indicate a dysfunction in the BBB or the blood-CSF barrier (BCB) in HD.Objective The aim of this exploratory study is to investigate whether the CSF/plasma albumin quotient (Q-Alb) and CSF platelet-derived growth factor-beta (PDGFR-beta) can be used as biomarkers for BBB/BCB integrity in HD and if there is an association between Q-Alb and the prevalence of intrathecal Th17.1 cells in HDGECs.Methods A total of 145 HDGECs and controls were included in the Q-Alb analysis. Forty-four of these individuals underwent a second lumbar puncture after five years and were included in the analysis of changes in Q-Alb over time. CSF from 33 HDGECs and controls was analysed for Th17.1 cells and CSF from 100 HDGECs and controls was analysed for PDGFR-beta.Results No significant difference for Q-Alb was found between the pre-motor manifest HDGECs, motor manifest HDGECs, and controls (p = 0.49). We found a significant increase in Q-Alb in HDGECs over the 5-year period (p = 0.014), but when compared with controls, no significant difference was found (p = 0.32). No significant association was found between Q-Alb and the prevalence of Th17.1 cells (p = 0.97) nor Q-Alb and PDGFR-beta (p = 0.89) in HDGECs.Conclusion We found no evidence of increased BBB/BCB leakage of albumin in HDGECs compared to controls. Neither did we find signs of pericyte involvement as measured by PDGFR-beta in HDGECs. These results suggest that overt BBB/BCB disruption may be limited in HDGECs. Future longitudinal studies should employ more sensitive methods like dynamic contrast-enhanced magnetic resonance imaging to evaluate region specific microleaks
MistGo® Compared to Conventional Eye Drops:A Patient-Reported Evaluation of Comfort and User-Friendliness in Glaucoma Treatment
No full textBackground/Objectives: Poor adherence remains a key challenge in glaucoma management, often due to difficulties with accurate self-administration and discomfort associated with conventional eye drop bottles. MistGo (R) is a novel dispensing device that delivers precise micro-doses of medication as a fine mist, allowing dosing with a neutral head position. With its ergonomic design, eye rest, and dose release button, MistGo (R) aims to improve comfort and ease of use. This study compared the user-friendliness, comfort, and administration confidence of MistGo (R) versus conventional eye drop dispensers in patients using topical ocular hypotensive medications. Methods: Twenty-two patients with glaucoma or ocular hypertension who had used conventional eye drop dispensers for >= 3 months were enrolled. Participants used the MistGo (R) device for 14 days and subsequently rated comfort, user-friendliness, and administration confidence on 0-10 scales for both their conventional dispensers and the MistGo (R) device. Results: MistGo (R) was rated significantly higher than conventional eye drop dispensers in terms of comfort (p < 0.0001), caused less discomfort from excess fluid (p < 0.001), and was perceived as more user-friendly (p < 0.001). There was no significant difference in the perceived accuracy of administration (p = 0.5); however, participants reported a significantly lower likelihood of medication being applied outside the eye when using MistGo (R) (p < 0.001). Overall, 20 out of 22 patients preferred MistGo (R). Conclusions: Patients with glaucoma or ocular hypertension preferred MistGo (R) over conventional eye drop dispensers as they found it more comfortable and user-friendly. These findings suggest that MistGo (R) has the potential to reduce barriers to adherence in glaucoma care. Further studies are warranted to evaluate its long-term efficacy and broader applicability
Complement-Mediated Kidney Diseases:Role of Alternative Pathway in Glomerular Inflammation
No full textComplement-mediated kidney diseases (CMKDs) comprise a diverse group of rare disorders characterized by the activation of the complement system, leading to glomerular inflammation, kidney injury, and in some cases, kidney failure. Although the contribution of complement activation to disease pathogenesis varies across CMKDs, the alternative complement pathway appears to play a pivotal role in driving inflammation and tissue damage in the kidney by amplifying complement activation, regardless of the initiating complement pathway. A growing body of evidence links the alternative pathway with glomerular inflammation in CMKDs, including key mechanistic insights from preclinical in vivo models, the association of alternative pathway components with histologic kidney injury and disease severity, and the efficacy of alternative pathway inhibition in patients with these disorders. With an improved understanding of the mechanisms of alternative pathway overactivation in CMKDs, many novel complement inhibitors targeting the alternative pathway are in clinical development for the management of CMKDs, potentially offering a more precise, better-tolerated, and effective approach than conventional immunosuppressive agents or therapeutics that provide broader inhibition of the common terminal complement pathway. This review summarizes the role of the alternative pathway in the pathogenesis of CMKDs and provides evidence supporting its involvement in glomerular inflammation. In addition, we provide a future perspective on the principles guiding the treatment of glomerular inflammation with therapies that target the alternative pathway.Complement-mediated kidney diseases (CMKDs) comprise a diverse group of rare disorders characterized by the activation of the complement system, leading to glomerular inflammation, kidney injury, and in some cases, kidney failure. Although the contribution of complement activation to disease pathogenesis varies across CMKDs, the alternative complement pathway appears to play a pivotal role in driving inflammation and tissue damage in the kidney by amplifying complement activation, regardless of the initiating complement pathway. A growing body of evidence links the alternative pathway with glomerular inflammation in CMKDs, including key mechanistic insights from preclinical in vivo models, the association of alternative pathway components with histologic kidney injury and disease severity, and the efficacy of alternative pathway inhibition in patients with these disorders. With an improved understanding of the mechanisms of alternative pathway overactivation in CMKDs, many novel complement inhibitors targeting the alternative pathway are in clinical development for the management of CMKDs, potentially offering a more precise, better-tolerated, and effective approach than conventional immunosuppressive agents or therapeutics that provide broader inhibition of the common terminal complement pathway. This review summarizes the role of the alternative pathway in the pathogenesis of CMKDs and provides evidence supporting its involvement in glomerular inflammation. In addition, we provide a future perspective on the principles guiding the treatment of glomerular inflammation with therapies that target the alternative pathway.</p
