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| 6. |
- Van den Brink, P. J., et al.
(författare)
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Toward sustainable environmental quality: Priority research questions for Europe
- 2018
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Ingår i: Environmental Toxicology and Chemistry. - : Wiley. - 0730-7268 .- 1552-8618. ; 37:9, s. 2281-2295
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Tidskriftsartikel (refereegranskat)abstract
- The United Nations' Sustainable Development Goals have been established to end poverty, protect the planet, and ensure prosperity for all. Delivery of the Sustainable Development Goals will require a healthy and productive environment. An understanding of the impacts of chemicals which can negatively impact environmental health is therefore essential to the delivery of the Sustainable Development Goals. However, current research on and regulation of chemicals in the environment tend to take a simplistic view and do not account for the complexity of the real world, which inhibits the way we manage chemicals. There is therefore an urgent need for a step change in the way we study and communicate the impacts and control of chemicals in the natural environment. To do this requires the major research questions to be identified so that resources are focused on questions that really matter. We present the findings of a horizon-scanning exercise to identify research priorities of the European environmental science community around chemicals in the environment. Using the key questions approach, we identified 22 questions of priority. These questions covered overarching questions about which chemicals we should be most concerned about and where, impacts of global megatrends, protection goals, and sustainability of chemicals; the development and parameterization of assessment and management frameworks; and mechanisms to maximize the impact of the research. The research questions identified provide a first-step in the path forward for the research, regulatory, and business communities to better assess and manage chemicals in the natural environment. Environ Toxicol Chem 2018;37:2281-2295. (c) 2018 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.
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| 8. |
- Madler, C.F., et al.
(författare)
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Non-invasive diagnosis of coronary artery disease by quantitative stress echocardiography : Optimal diagnostic models using off-line tissue Doppler in the MYDISE study
- 2003
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Ingår i: European Heart Journal. - 0195-668X .- 1522-9645. ; 24:17, s. 1584-1594
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To develop optimal methods for the objective non-invasive diagnosis of coronary artery disease, using myocardial Doppler velocities during dobutamine stress echocardiography. Methods and results: We acquired tissue Doppler digital data during dobutamine stress in 289 subjects, and measured myocardial responses by off-line analysis of 11 left ventricular segments. Diagnostic criteria developed by comparing 92 normal subjects with 48 patients with coronary disease were refined in a prospective series of 149 patients referred with chest pain. Optimal diagnostic accuracy was achieved by logistic regression models, using systolic velocities at maximal stress in 7 myocardial segments, adjusting for independent correlations directly with heart rate and inversely with age and female gender (all p<0.001). Best cut-points from receiveroperator curves diagnosed left anterior descending, circumflex and right coronary disease with sensitivities and specificities of 80% and 80%, 91% and 80%, and 93% and 82%, respectively. All models performed better than velocity cut-offs alone (p<0.001). Conclusion: Non-invasive diagnosis of coronary artery disease by quantitative stress echocardiography is best performed using diagnostic models based on segmental velocities at peak stress and adjusting for heart rate, and gender or age. © 2003 Published by Elsevier Ltd on behalf of The European Society of Cardiology.
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| 9. |
- Venero, J. L., et al.
(författare)
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ARG1 expression in basal forebrain microglia modulates hippocampal innervation and cognition during postnatal development
- 2023
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Ingår i: Glia. - : John Wiley & Sons. - 0894-1491 .- 1098-1136. ; 71:Suppl. 1, s. E512-E512
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Diversity within microglia, the resident brain immune cells, is reported. Whether microglial subsets constitute different subtypes with intrinsic properties and unique functions has not been fully elucidated. Here, we describe a microglial subtype characterized by the expression of the enzyme Arginase-1, i.e.Arg1+microglia, which is found predominantly in the cholinergic neuron-rich forebrain region during early postnatal development. Arg1+microgliacontain cellular inclusions and exhibit a distinct molecular signature including upregulation of genes such as Apoe, Clec7a, Igf1, Lgals3and Mgl2. Arg1-knockout in microglia results in a deficient cholinergic innervation along with impaired dendritic spine maturation in the hippocampus where cholinergic neurons project, impaired long-term potentiation and cognitive behavioural deficiencies in female mice. Our results expand on microglia diversity and provide insights into distinctive spatiotemporal functions exerted by microglial subtypes.
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| 10. |
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| 11. |
- Madler, C. F., et al.
(författare)
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Non-invasive diagnosis of coronary artery disease by quantitative stress echocardiography : optimal diagnostic models using off-line tissue Doppler in the MYDISE study
- 2003
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 24:17, s. 1584-1594
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Tidskriftsartikel (refereegranskat)abstract
- Aims To develop optimal methods for the objective non-invasive diagnosis of coronary artery disease, using myocardial Doppler velocities during dobutamine stress echocardiography. Methods and results We acquired tissue Doppler digital data during dobutamine stress in 289 subjects, and measured myocardial responses by off-line analysis of 11 left ventricular segments. Diagnostic criteria developed by comparing 92 normal subjects with 48 patients with coronary disease were refined in a prospective series of 149 patients referred with chest pain. Optimal diagnostic accuracy was achieved by logistic regression models, using systolic velocities at maximal stress in 7 myocardial segments, adjusting for independent correlations directly with heart rate and inversely with age and female gender (all p<0.001). Best cut-points from receiver-operator curves diagnosed left anterior descending, circumflex and right coronary disease with sensitivities and specificities of 80% and 80%, 91% and 80%, and 93% and 82%, respectively. All models performed better than velocity cut-offs alone (p<0.001). Conclusion Non-invasive diagnosis of coronary artery disease by quantitative stress echocardiography is best performed using diagnostic models based on segmental velocities at peak stress and adjusting for heart rate, and gender or age.
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| 12. |
- Merid, Simon Kebede, et al.
(författare)
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Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age
- 2020
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Ingår i: Genome Medicine. - Stockholm : Karolinska Institutet, Dept of Clinical Science and Education, Södersjukhuset. - 1756-994X.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. Methods: We performed meta-analysis of Illumina's HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4-18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. Results: We identified 8899 CpGs in cord blood that were associated with gestational age (range 27-42 weeks), at Bonferroni significance, P < 1.06 × 10- 7, of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels. Conclusions: We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.
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| 13. |
- Castillo, N. A., et al.
(författare)
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Understanding pharmaceutical exposure and the potential for effects in marine biota : A survey of bonefish (Albula vulpes) across the Caribbean Basin
- 2024
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Ingår i: Chemosphere. - : Elsevier. - 0045-6535 .- 1879-1298. ; 349
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Tidskriftsartikel (refereegranskat)abstract
- Most research on pharmaceutical presence in the environment to date has focused on smaller scale assessments of freshwater and riverine systems, relying mainly on assays of water samples, while studies in marine ecosystems and of exposed biota are sparse. This study investigated the pharmaceutical burden in bonefish (Albula vulpes), an important recreational and artisanal fishery, to quantify pharmaceutical exposure throughout the Caribbean Basin. We sampled 74 bonefish from five regions, and analyzed them for 102 pharmaceuticals. We assessed the influence of sampling region on the number of pharmaceuticals, pharmaceutical assemblage, and risk of pharmacological effects. To evaluate the risk of pharmacological effects at the scale of the individual, we proposed a metric based on the human therapeutic plasma concentration (HTPC), comparing measured concentrations to a threshold of 1/3 the HTPC for each pharmaceutical. Every bonefish had at least one pharmaceutical, with an average of 4.9 and a maximum of 16 pharmaceuticals in one individual. At least one pharmaceutical was detected in exceedance of the 1/3 HTPC threshold in 39% of bonefish, with an average of 0.6 and a maximum of 11 pharmaceuticals exceeding in a Key West individual. The number of pharmaceuticals (49 detected in total) differed across regions, but the risk of pharmacological effects did not (23 pharmaceuticals exceeded the 1/3 HTPC threshold). The most common pharmaceuticals were venlafaxine (43 bonefish), atenolol (36), naloxone (27), codeine (27), and trimethoprim (24). Findings suggest that pharmaceutical detections and concentration may be independent, emphasizing the need to monitor risk to biota regardless of exposure diversity, and to focus on risk quantified at the individual level. This study supports the widespread presence of pharmaceuticals in marine systems and shows the utility of applying the HTPC to assess the potential for pharmacological effects, and thus quantify impact of exposure at large spatial scales.
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| 14. |
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| 15. |
- Girnita, L., et al.
(författare)
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Increased expression of insulin-like growth factor I receptor in malignant cells expressing aberrant p53 : Functional impact
- 2000
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 60:18, s. 5278-5283
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the functional impact of p53 on insulin-like growth factor I receptor (IGF-IR) expression in malignant cells. Using the BL-41tsp53-2 cell line, a transfectant carrying temperature-sensitive (ts) p53 and endogenous mutant p53 (codon 248), we demonstrated a drastic down-regulation of plasma membrane-bound IGF-IRs on induction of wild-type p53, However, a similar response was obtained by treatment of BL-41tsp53-2 cells expressing mutant ts p53 with a p53 antisense oligonucleotide. Thus, even if the negative effect of wild-type p53 predominates under a competitive condition, these data indicate that mutant p53 may be important for up-regulation of IGF-IR, To further elucidate this issue, three melanoma cell lines (BE, SK-MEL-5, and SK-MEL-28) that over expressed p53 were investigated. The BE cell line has a hot spot mutation (codon 248) and expresses only codon 248-mutant p53, SK-MEL-28 has a point mutation at codon 145. SK-MEL-5 cells did not exhibit any p53 mutations, but the absence of p21(Waf1) expression suggested functionally aberrant p53. Our data suggest that interaction with Mdm-2 may underlie p53 inactivation in these cells, Using p53 antisense oligonucleotides, we demonstrated a substantial down-regulation of cell surface expression of IGF-IR proteins in all melanoma cell lines after 24 h, This was paralleled by decreased tyrosine phosphorylation of IGF-IR and growth arrest, and, subsequently, massive cell death was observed (this was also seen in BL-41tsp53-2 cells with mutant conformation of ts p53). Taken together, our results suggest that up-regulation of IGF-IR as a result of expression of aberrant p53 may be important for the growth and survival of malignant cells.
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| 16. |
- Gohy, B, et al.
(författare)
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Monitoring independence in daily life activities after trauma in humanitarian settings: Item reduction and assessment of content validity of the Activity Independence Measure-Trauma (AIM-T)
- 2022
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Ingår i: PLOS global public health. - : Public Library of Science (PLoS). - 2767-3375. ; 2:12, s. e0001334-
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Tidskriftsartikel (refereegranskat)abstract
- A standardized set of measures to assess functioning after trauma in humanitarian settings has been called for. The Activity Independence Measure for Trauma (AIM-T) is a clinician-rated measure of independence in 20 daily activities among patients after trauma. Designed in Afghanistan, it has since been used in other contexts. Before recommending the AIM-T for wider use, its measurement properties required confirmation. This study aims at item reduction followed by content validity assessment of the AIM-T. Using a two-step revision process, first, routinely collected data from 635 patients at five facilities managing patients after trauma in Haiti, Burundi, Yemen, and Iraq were used for item reduction. This was performed by analyzing inter-item redundancy and distribution of the first version of the AIM-T (AIM-T1) item scores, resulting in a shortened version (AIM-T2). Second, content validity of the AIM-T2 was assessed by item content validity indices (I-CVI, 0–1) based on structured interviews with 23 health care professionals and 60 patients in Haiti, Burundi, and Iraq. Through the analyses, nine pairs of redundant items (r≥0.90) were identified in the AIM-T1, leading to the removal of nine items, and resulting in AIM-T2. All remaining items were judged highly relevant, appropriate, clear, feasible and representative by most of participants (I-CVI>0.5). Ten items with I-CVI 0.5–0.85 were revised to improve their cultural relevance or appropriateness and one item was added, resulting in the AIM-T3. In conclusion, the proposed 12-item AIM-T3 is overall relevant, clear, and representative of independence in daily activity after trauma and it includes items appropriate and feasible to be observed by clinicians across different humanitarian settings. While some additional measurement properties remain to be evaluated, the present version already has the potential to serve as a routine measure to assess patients after trauma in humanitarian settings.
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| 19. |
- Hetland, M. L., et al.
(författare)
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Active conventional treatment and three different biological treatments in early rheumatoid arthritis: phase IV investigator initiated, randomised, observer blinded clinical trial
- 2020
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Ingår i: Bmj-British Medical Journal. - : BMJ. - 1756-1833. ; 371
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To evaluate and compare benefits and harms of three biological treatments with different modes of action versus active conventional treatment in patients with early rheumatoid arthritis. DESIGN Investigator initiated, randomised, open label, blinded assessor, multiarm, phase IV study. SETTING Twenty nine rheumatology departments in Sweden, Denmark, Norway, Finland, the Netherlands, and Iceland between 2012 and 2018. PARTICIPANTS Patients aged 18 years and older with treatment naive rheumatoid arthritis, symptom duration less than 24 months, moderate to severe disease activity, and rheumatoid factor or anti-citrullinated protein antibody positivity, or increased C reactive protein. INTERVENTIONS Randomised 1:1:1:1, stratified by country, sex, and anti-citrullinated protein antibody status. All participants started methotrexate combined with (a) active conventional treatment (either prednisolone tapered to 5 mg/day, or sulfasalazine combined with hydroxychloroquine and intraarticular corticosteroids), (b) certolizumab pegol, (c) abatacept, or (d) tocilizumab. MAIN OUTCOME MEASURES The primary outcome was adjusted clinical disease activity index remission (CDAI <= 2.8) at 24 weeks with active conventional treatment as the reference. Key secondary outcomes and analyses included CDAI remission at 12 weeks and over time, other remission criteria, a non-inferiority analysis, and harms. RESULTS 812 patients underwent randomisation. The mean age was 54.3 years (standard deviation 14.7) and 68.8% were women. Baseline disease activity score of 28 joints was 5.0 (standard deviation 1.1). Adjusted 24 week CDAI remission rates were 42.7% (95% confidence interval 36.1% to 49.3%) for active conventional treatment, 46.5% (39.9% to 53.1%) for certolizumab pegol, 52.0% (45.5% to 58.6%) for abatacept, and 42.1% (35.3% to 48.8%) for tocilizumab. Corresponding absolute differences were 3.9% (95% confidence interval -5.5% to 13.2%) for certolizumab pegol, 9.4% (0.1% to 18.7%) for abatacept, and -0.6% (-10.1% to 8.9%) for tocilizumab. Key secondary outcomes showed no major differences among the four treatments. Differences in CDAI remission rates for active conventional treatment versus certolizumab pegol and tocilizumab, but not abatacept, remained within the prespecified non-inferiority margin of 15% (per protocol population). The total number of serious adverse events was 13 (percentage of patients who experienced at least one event 5.6%) for active conventional treatment, 20 (8.4%) for certolizumab pegol, 10 (4.9%) for abatacept, and 10 (4.9%) for tocilizumab. Eleven patients treated with abatacept stopped treatment early compared with 20-23 patients in the other arms. CONCLUSIONS All four treatments achieved high remission rates. Higher CDAI remission rate was observed for abatacept versus active conventional treatment, but not for certolizumab pegol or tocilizumab versus active conventional treatment. Other remission rates were similar across treatments. Non-inferiority analysis indicated that active conventional treatment was non-inferior to certolizumab pegol and tocilizumab, but not to abatacept. The results highlight the efficacy and safety of active conventional treatment based on methotrexate combined with corticosteroids, with nominally better results for abatacept, in treatment naive early rheumatoid arthritis.
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| 23. |
- Sigmund, G., et al.
(författare)
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Addressing chemical pollution in biodiversity research
- 2023
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Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 29:12, s. 3240-3255
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Tidskriftsartikel (refereegranskat)abstract
- Climate change, biodiversity loss, and chemical pollution are planetary-scale emergencies requiring urgent mitigation actions. As these "triple crises" are deeply interlinked, they need to be tackled in an integrative manner. However, while climate change and biodiversity are often studied together, chemical pollution as a global change factor contributing to worldwide biodiversity loss has received much less attention in biodiversity research so far. Here, we review evidence showing that the multifaceted effects of anthropogenic chemicals in the environment are posing a growing threat to biodiversity and ecosystems. Therefore, failure to account for pollution effects may significantly undermine the success of biodiversity protection efforts. We argue that progress in understanding and counteracting the negative impact of chemical pollution on biodiversity requires collective efforts of scientists from different disciplines, including but not limited to ecology, ecotoxicology, and environmental chemistry. Importantly, recent developments in these fields have now enabled comprehensive studies that could efficiently address the manifold interactions between chemicals and ecosystems. Based on their experience with intricate studies of biodiversity, ecologists are well equipped to embrace the additional challenge of chemical complexity through interdisciplinary collaborations. This offers a unique opportunity to jointly advance a seminal frontier in pollution ecology and facilitate the development of innovative solutions for environmental protection.
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| 24. |
- Sonkoly, E, et al.
(författare)
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MicroRNA-203 functions as a tumor suppressor in basal cell carcinoma.
- 2012
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Ingår i: Oncogenesis. - : Springer Science and Business Media LLC. - 2157-9024. ; 1
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Tidskriftsartikel (refereegranskat)abstract
- Basal cell carcinoma (BCC) of the skin represents the most common malignancy in humans. MicroRNAs (miRNAs), small regulatory RNAs with pleiotropic function, are commonly misregulated in cancer. Here we identify miR-203, a miRNA abundantly and preferentially expressed in skin, to be downregulated in BCCs. We show that activation of the Hedgehog (HH) pathway, critically involved in the pathogenesis of BCCs, as well as the EGFR/MEK/ERK/c-JUN signaling pathway suppresses miR-203. We identify c-JUN, a key effector of the HH pathway, as a novel direct target for miR-203 in vivo. Further supporting the role of miR-203 as a tumor suppressor, in vivo delivery of miR-203 mimics in a BCC mouse model results in the reduction of tumor growth. Our results identify a regulatory circuit involving miR-203 and c-JUN, which provides functional control over basal cell proliferation and differentiation. We propose that miR-203 functions as a 'bona fide' tumor suppressor in BCC, whose suppressed expression contributes to oncogenic transformation via derepression of multiple stemness- and proliferation-related genes, and its overexpression could be of therapeutic value.
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| 25. |
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| 26. |
- Yamamoto, T., et al.
(författare)
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Changes in circulating biomarkers during a single hemodialysis session
- 2013
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Ingår i: Hemodialysis International. - : Wiley. - 1492-7535 .- 1542-4758. ; 17:1, s. 59-66
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Tidskriftsartikel (refereegranskat)abstract
- The hemodialysis (HD) procedure induces an inflammatory response potentially contributing to cardiovascular disease. Here we investigated the acute impact of HD on circulating biomarkers. Circulating biomarkers (small solutes, middle molecular-sized peptides, and proteins) related to inflammation, oxidative stress, and vascular calcification (VC) were measured before and after a single session of HD in 45 clinically stable patients. Concentrations were corrected for ultrafiltration-induced hemoconcentration. Among vascular calcification-related biomarkers, osteoprotegerin and fetuin-A remained unchanged while fibroblast growth factor-23 (FGF23) decreased by -19%. Changes of FGF23 and changes of phosphate correlated (ρ=0.61, P<0.001). While C-reactive protein did not change, interleukin-6 (IL-6) increased by 14% and pentraxin 3 (PTX3) increased by 45%. IL-6 and PTX3 appear to be valid biomarkers of the intradialytic inflammatory response. VC-related markers were in general not affected by the single HD session; however, the observed correlation between acute changes of FGF-23 and phosphate during HD warrants further studies.
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| 29. |
- Andersson, L., et al.
(författare)
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Effect of CO2 pneumoperitoneum on ventilation-perfusion relationships during laparoscopic cholecystectomy
- 2002
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 46:5, s. 552-560
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previous studies have shown that pneumoperitoneum transiently reduces venous admixture as assessed by a calculation based on the shunt formula, and increases arterial oxygen tension (PaO2) in patients without heart or lung disease. The aim of the present study was to further explore the relationship between ventilation-perfusion ((V) over dot (A)/(Q) over dot) before and during pneumoperitoneum by using the multiple inert gas technique. Methods: Nine patients without heart or lung disease (ASA I), with a mean age of 42 years, scheduled for laparoscopic cholecystectomy were included. After premedication and induction of anaesthesia, radial artery and pulmonary artery catheters were introduced percutaneously. The (V) over dot (A)/(Q) over dot relationships were evaluated by the multiple inert gas elimination technique before and during pneurnoperitoneum to obtain a direct measure of the pulmonary shunt. Results: Induction of pneumoperitoneum decreased the pulmonary shunt from 5.8 (4.5) to 4.1 (3.2)% (P<0.05) and increased PaO2 from 21.7 (5.9) to 24.7 (4.8) kPa (P<0.01). During surgery, the shunt increased from 3.2 (2.8) to 5.2 (3.4)% to the same level as before pneumoperitoneum induction. No area with low (V) over dot (A)/(Q) over dot was seen. Dead space ventilation amounted to 20.0 (1.2)% in the supine position and did not change during the investigation. Conclusions: In patients without heart or lung disease, pneumoperitoneum at an intra-abdominal pressure level of 11-13 mmHg- causes a transient reduction of the pulmonary shunt. The mechanisms underlying the present finding remain to be elucidated.
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| 34. |
- Bertram, Michael G., et al.
(författare)
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Frontiers in quantifying wildlife behavioural responses to chemical pollution
- 2022
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Ingår i: Biological Reviews. - : John Wiley & Sons. - 1464-7931 .- 1469-185X. ; 97:4
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Tidskriftsartikel (refereegranskat)abstract
- Animal behaviour is remarkably sensitive to disruption by chemical pollution, with widespread implications for ecological and evolutionary processes in contaminated wildlife populations. However, conventional approaches applied to study the impacts of chemical pollutants on wildlife behaviour seldom address the complexity of natural environments in which contamination occurs. The aim of this review is to guide the rapidly developing field of behavioural ecotoxicology towards increased environmental realism, ecological complexity, and mechanistic understanding. We identify research areas in ecology that to date have been largely overlooked within behavioural ecotoxicology but which promise to yield valuable insights, including within- and among-individual variation, social networks and collective behaviour, and multi-stressor interactions. Further, we feature methodological and technological innovations that enable the collection of data on pollutant-induced behavioural changes at an unprecedented resolution and scale in the laboratory and the field. In an era of rapid environmental change, there is an urgent need to advance our understanding of the real-world impacts of chemical pollution on wildlife behaviour. This review therefore provides a roadmap of the major outstanding questions in behavioural ecotoxicology and highlights the need for increased cross-talk with other disciplines in order to find the answers.
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| 35. |
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| 36. |
- Breuer, O, et al.
(författare)
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Intravenous Infusion of High Dose Selenite in End-Stage Cancer Patients: Analysis of Systemic Exposure to Selenite and Seleno-Metabolites
- 2023
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Ingår i: Biomedicines. - : MDPI AG. - 2227-9059. ; 11:2
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is one of the main causes of human death globally and novel chemotherapeutics are desperately required. As a simple selenium oxide, selenite is a very promising chemotherapeutic because of pronounced its dose-dependent tumor-specific cytotoxicity. We previously published a first-in-man systematic phase I clinical trial in patients with cancer (from IV to end-stage) (the SECAR trial) showing that selenite is safe and tolerable with an unexpectable high maximum tolerated dose (MTD) and short half-life. In the present study, we analyzed the selenium species in plasma samples, from the patients participating in the SECAR trial and from various time points and dose cohorts using LC-ICP-MS. In conclusion, selenite, selenosugars, and 1–2 unidentified peaks that did not correspond to any standard, herein denoted ui-selenium, were detected in the plasma. However, trimethylated selenium (trimethylselenonoium) was not detected. The unidentified ui-selenium was eluting close to the selenium-containing amino acids (selenomethionine and selenocysteine) but was not part of a protein fraction. Our data demonstrate that the major metabolite detected was selenosugar. Furthermore, the identification of selenite even long after the administration is remarkable and unexpected. The kinetic analysis did not support that dosing per the body surface area would reduce interindividual variability of the systemic exposure in terms of trough concentrations.
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| 37. |
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| 38. |
- Brodin, N., et al.
(författare)
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Coaching patients with early rheumatoid arthritis to healthy physical activity : A multicenter, randomized, controlled study
- 2008
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Ingår i: Arthritis and Rheumatism. - Hoboken, NJ : Wiley. - 0004-3591 .- 1529-0131. ; 59:3, s. 325-331
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To investigate the effect of a 1-year coaching program for healthy physical activity on perceived health status, body function, and activity limitation in patients with early rheumatoid arthritis. Methods. A total of 228 patients (169 women, 59 men, mean age 55 years, mean time since diagnosis 21 months) were randomized to 2 groups after assessments with the EuroQol visual analog scale (VAS), Grippit, Timed-Stands Test, Escola Paulista de Medicina Range of Motion scale, walking in a figure-of-8, a visual analog scale for pain, the Health Assessment Questionnaire disability index, a self-reported physical activity questionnaire, and the Disease Activity Score in 28 joints. All patients were regularly seen by rheumatologists and underwent rehabilitation as prescribed. Those in the intervention group were further individually coached by a physical therapist to reach or maintain healthy physical activity (=30 minutes, moderately intensive activity, most days of the week). Results. The retention rates after 1 year were 82% in the intervention group and 85% in the control group. The percentages of individuals in the intervention and control groups fulfilling the requirements for healthy physical activity were similar before (47% versus 51%, P > 0.05) and after (54% versus 44%, P > 0.05) the intervention. Analyses of outcome variables indicated improvements in the intervention group over the control group in the EuroQol VAS (P = 0.025) and muscle strength (Timed-Stands Test, P = 0.000) (Grippit, P = 0.003), but not in any other variables assessed. Conclusion. A 1-year coaching program for healthy physical activity resulted in improved perceived health status and muscle strength, but the mechanisms remain unclear, as self-reported physical activity at healthy level did not change. © 2008, American College of Rheumatology.
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| 42. |
- Drosos, GC, et al.
(författare)
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EULAR recommendations for cardiovascular risk management in rheumatic and musculoskeletal diseases, including systemic lupus erythematosus and antiphospholipid syndrome
- 2022
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 81:6, s. 768-779
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Tidskriftsartikel (refereegranskat)abstract
- To develop recommendations for cardiovascular risk (CVR) management in gout, vasculitis, systemic sclerosis (SSc), myositis, mixed connective tissue disease (MCTD), Sjögren’s syndrome (SS), systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS).MethodsFollowing European League against Rheumatism (EULAR) standardised procedures, a multidisciplinary task force formulated recommendations for CVR prediction and management based on systematic literature reviews and expert opinion.ResultsFour overarching principles emphasising the need of regular screening and management of modifiable CVR factors and patient education were endorsed. Nineteen recommendations (eleven for gout, vasculitis, SSc, MCTD, myositis, SS; eight for SLE, APS) were developed covering three topics: (1) CVR prediction tools; (2) interventions on traditional CVR factors and (3) interventions on disease-related CVR factors. Several statements relied on expert opinion because high-quality evidence was lacking. Use of generic CVR prediction tools is recommended due to lack of validated rheumatic diseases-specific tools. Diuretics should be avoided in gout and beta-blockers in SSc, and a blood pressure target <130/80 mm Hg should be considered in SLE. Lipid management should follow general population guidelines, and antiplatelet use in SLE, APS and large-vessel vasculitis should follow prior EULAR recommendations. A serum uric acid level <0.36 mmol/L (<6 mg/dL) in gout, and disease activity control and glucocorticoid dose minimisation in SLE and vasculitis, are recommended. Hydroxychloroquine is recommended in SLE because it may also reduce CVR, while no particular immunosuppressive treatment in SLE or urate-lowering therapy in gout has been associated with CVR lowering.ConclusionThese recommendations can guide clinical practice and future research for improving CVR management in rheumatic and musculoskeletal diseases.
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- Gustafsson, A. C., et al.
(författare)
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HPV-related cancer susceptibility and p53 codon 72 polymorphism
- 2001
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Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 81, s. 125-
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Tidskriftsartikel (refereegranskat)abstract
- Conflicting results regarding the association of a polymorphism at codon 72 of the p53 tumour suppressor gene and susceptibility to develop human papilloma virus (HPV)-associated cervical cancer have been published over the last year, implicating differences in ethnic background, sample origin, sample size and/or detection assay, The material for this study was collected in the identical geographical region as for 2 previous reports with contradictory results regarding the association of codon 72 genotype with squamous cell cancer (SCC), We have used an alternative detection assay, based on pyrosequencing technology, that interrogates the variable position by the accuracy of DNA polymerase. In addition to cervical clinical specimens from SCC, HPV16- and HPV18-infected adenocarcinoma cases as well as cervical intraepithelial neoplasia (CM) were investigated. No significant association was found between p53 codon 72 genotype and the risk to develop adenocarcinoma, SCC or CIN in the Swedish population.
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- Hashemi, N., et al.
(författare)
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Feasibility of Myocardial Performance Index for Evaluation of Left Ventricular Function during Dobutamine Stress Echocardiography before and after Coronary Artery Bypass Grafting
- 2014
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Ingår i: Echocardiography. - : Wiley. - 0742-2822 .- 1540-8175. ; 31:8, s. 989-995
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Myocardial performance index (MPI) is a measure of combined systolic and diastolic myocardial function. In patients with coronary artery disease (CAD) an increase in MPI is consistent with myocardial dysfunction. The objectives of this study were to characterize the changes in MPI after coronary artery bypass graft (CABG) at rest and at peak dobutamine stress echocardiography (DSE). Methods and Results: Thirty-six patients diagnosed with CAD and accepted for CABG were studied by standard echocardiography and DSE 1 month prior and 3 month after CABG. The MPI was calculated using pulsed-wave tissue Doppler imaging (PW-TDI) of the left ventricular (LV) wall-motion velocity. At baseline, ejection fraction (EF; 42.7 ± 8%) and wall-motion score index (WMSI; 1.1 ± 0.2) were impaired at rest as well as at peak DSE (EF; 49.2 ± 9 and WMSI 1.4 ± 0.2). MPI was prolonged both at rest (0.61 ± 0.13) and at peak DSE (0.78 ± 0.16). After CABG, EF and WMSI did not improve at rest (43.7 ± 8% and 1.1 ± 0.2, respectively). On the other hand, MPI improved substantially both at rest (0.45 ± 0.08; P < 0.001) and at peak DSE (0.56 ± 0.1; P < 0.001). At peak DSE an improvement of EF (54.2 ± 9; P < 0.05) and WMSI (1.1 ± 0.16; P < 0.001) was seen as well. Conclusion: Myocardial performance index shows significant improvement after CABG in patients with CAD both at rest and peak DSE and appears to be a sensitive measure of myocardial function.
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- Järver, Peter, et al.
(författare)
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Single-Stranded Nucleic Acids Regulate TLR3/4/7 Activation through Interference with Clathrin-Mediated Endocytosis
- 2018
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Recognition of nucleic acids by endosomal Toll-like receptors (TLR) is essential to combat pathogens, but requires strict control to limit inflammatory responses. The mechanisms governing this tight regulation are unclear. We found that single-stranded oligonucleotides (ssON) inhibit endocytic pathways used by cargo destined for TLR3/4/7 signaling endosomes. Both ssDNA and ssRNA conferred the endocytic inhibition, it was concentration dependent, and required a certain ssON length. The ssON-mediated inhibition modulated signaling downstream ofTLRs that localized within the affected endosomal pathway. We further show that injection of ssON dampens dsRNA-mediated inflammatory responses in the skin of non-human primates. These studies reveal a regulatory role for extracellular ssON in the endocytic uptake of TLR ligands and provide a mechanistic explanation of their immunomodulation. The identified ssON-mediated interference of endocytosis (SOMIE) is a regulatory process that temporarily dampens TLR3/4/7 signaling, thereby averting excessive immune responses.
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