22 results on '"Jessica Karlsson"'
Search Results
2. Author response for 'Time Trends in Trajectories of Forearm Mineral Content and Bone Size During Childhood—Results from Cross‐Sectional Measurements with the Same Apparatus Four Decades Apart'
- Author
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null Björn E. Rosengren, null Jessica Karlsson, null Erika Bergman, null Henrik Ahlborg, null Lars Jehpsson, and null Magnus K. Karlsson
- Published
- 2022
3. Downturn in Childhood Bone Mass: A Cross-Sectional Study Over Four Decades
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Jessica Karlsson, Erika Bergman, Lars Jehpsson, Henrik G. Ahlborg, Magnus Karlsson, and Björn E. Rosengren
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Orthopedic surgery ,FRACTURE RISK ASSESSMENT ,business.industry ,Cross-sectional study ,Endocrinology, Diabetes and Metabolism ,Dentistry ,Diseases of the musculoskeletal system ,Original Articles ,FRACTURE PREVENTION ,RC925-935 ,BMD ,Medicine ,Orthopedics and Sports Medicine ,Fracture prevention ,Original Article ,business ,RD701-811 ,SINGLE‐PHOTON ABSORBTIOMETRY ,Bone mass - Abstract
Screen time and physical inactivity have increased among children. As physical activity is a determinant of bone mass, there is a concern that children today have lower bone mass than earlier. If this is true, fractures may become more common in the future. In 2017–2018, we used single‐photon absorptiometry (SPA) to measure distal forearm bone mineral density (BMD; mg/cm2) in a normative cohort of 238 boys and 204 girls aged 7 to 15 years. We compared these results to BMD in a normative cohort collected in 1979–1981 (55 boys and 61 girls aged 7 to 15 years) measured by the same scanner. To investigate difference between the two cohorts, we used multiple linear regression with age, sex, and cohort as predictors. Predicted bone density at age 16 years was estimated through the slope values. The bone density‐age slope was flatter in the cohort measured in 2017–2018 than in the cohort measured 1979–1981 (−5.6 mg/cm2/yr [95% confidence interval −9.6 to −1.5]). Predicted bone density was at age 16 years in 2017–2018 in boys was 10% lower (−0.9 SD) and in girls 11% lower (−1.1 SD) than in their counterparts measured in 1979–1981. We found indications that children nowadays develop lower bone mass than four decades ago, giving concern that they may have a higher risk of osteoporosis and fragility fractures as they grow old. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
- Published
- 2021
4. Low mRNA expression and activity of monoacylglycerol lipase in human SH-SY5Y neuroblastoma cells
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Janis Szeremeta, Mireille Alhouayek, Jessica Karlsson, Christopher J. Fowler, and UCL - SSS/LDRI - Louvain Drug Research Institute
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Glycerol ,0301 basic medicine ,Physiology ,Mrna expression ,030204 cardiovascular system & hematology ,Decitabine ,Hydroxamic Acids ,Biochemistry ,Epigenesis, Genetic ,Neuroblastoma cell ,Neuroblastoma ,03 medical and health sciences ,0302 clinical medicine ,Cell Line, Tumor ,medicine ,Humans ,RNA, Messenger ,Gene ,Pharmacology ,chemistry.chemical_classification ,Sh sy5y neuroblastoma ,Hydrolysis ,Cell Biology ,medicine.disease ,Endocannabinoid system ,Monoacylglycerol Lipases ,Cell biology ,Gene Expression Regulation, Neoplastic ,Monoacylglycerol lipase ,030104 developmental biology ,Enzyme ,chemistry ,lipids (amino acids, peptides, and proteins) ,Endocannabinoids - Abstract
Relatively little is known about the endocannabinoid system in human neuroblastoma cell lines. In the present study, we have investigated the expression of the genes coding for the enzymes involved in the synthesis and catabolism of endocannabinoids in the SH-SY5Y cell line. The expression of MGLL, the gene coding for the 2-arachidonoylglycerol hydrolytic enzyme monoacylglycerol lipase (MAGL), was found to be 85 and 340 fold lower than the expression levels for the genes coding for alpha/beta-hydrolase domain containing 6 and 12 (ABHD6, ABHD12), which are alternative hydrolytic enzymes for this endocannabinoid. In comparison, mRNA levels of MGLL were 1.5 fold higher than ABHD6 and 2 fold lower than the levels of ABHD12 in DU-145 human prostate cells. In functional assays, the hydrolysis of the 2-arachidonoylglycerol homologue 2-oleoylglycerol by intact SH-SY5Y cells was partially inhibited by the ABHD6 inhibitor WWL70, but not by the MAGL inhibitor JZL184, whereas the reverse was true in DU-145 cells. The combination of JZL184 + WWL70 did, however produce a significantly greater inhibition of 2-OG hydrolysis than seen with WWL70 alone in the SH-SY5Y cells. The low MGLL expression in the SH-SY5Y cells was not due to epigenetic silencing, since levels were not affected by treatment with the methylation inhibitor 5-aza-2'-deoxycytidine and/or the histone acetylase inhibitor trichostatin A. The low MGLL expression in SH-SY5Y cells should be taken into account when using these cells in experiments investigating the involvement of the endocannabinoid system in models of physiological and pathological processes.
- Published
- 2019
5. Design, synthesis and
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Alessandro, Deplano, Jessica, Karlsson, Federica, Moraca, Mona, Svensson, Claudia, Cristiano, Carmine Marco, Morgillo, Christopher J, Fowler, Roberto, Russo, Bruno, Catalanotti, and Valentina, Onnis
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Male ,Models, Molecular ,Static Electricity ,Mice, Inbred Strains ,Flurbiprofen amides ,Amidohydrolases ,Rats, Sprague-Dawley ,Mice ,Structure-Activity Relationship ,fatty acid amide hydrolase ,Animals ,non-steroidal anti-inflammatory drugs ,Enzyme Inhibitors ,Rats, Wistar ,hyperalgesia ,allodynia ,Analgesics ,Dose-Response Relationship, Drug ,Molecular Structure ,endocannabinoid ,Amides ,Rats ,FAAH inhibition ,cyclooxygenase ,Flurbiprofen ,Cyclooxygenase 2 ,Drug Design ,Quantum Theory ,lipids (amino acids, peptides, and proteins) ,Research Article ,Research Paper - Abstract
Compounds combining dual inhibitory action against FAAH and cyclooxygenase (COX) may be potentially useful analgesics. Here, we describe a novel flurbiprofen analogue, N-(3-bromopyridin-2-yl)-2-(2-fluoro-(1,1'-biphenyl)-4-yl)propanamide (Flu-AM4). The compound is a competitive, reversible inhibitor of FAAH with a Ki value of 13 nM and which inhibits COX activity in a substrate-selective manner. Molecular modelling suggested that Flu-AM4 optimally fits a hydrophobic pocket in the ACB region of FAAH, and binds to COX-2 similarly to flurbiprofen. In vivo studies indicated that at a dose of 10 mg/kg, Flu-AM4 was active in models of prolonged (formalin) and neuropathic (chronic constriction injury) pain and reduced the spinal expression of iNOS, COX-2, and NFκB in the neuropathic model. Thus, the present study identifies Flu-AM4 as a dual-action FAAH/substrate-selective COX inhibitor with anti-inflammatory and analgesic activity in animal pain models. These findings underscore the potential usefulness of such dual-action compounds., Graphical Abstract
- Published
- 2021
6. Design, synthesis and in vitro and in vivo biological evaluation of flurbiprofen amides as new fatty acid amide hydrolase/cyclooxygenase-2 dual inhibitory potential analgesic agents
- Author
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Jessica Karlsson, Federica Moraca, Valentina Onnis, Alessandro Deplano, Mona Svensson, Bruno Catalanotti, Roberto Russo, Claudia Cristiano, Christopher J. Fowler, Carmine Marco Morgillo, Deplano, A., Karlsson, J., Moraca, F., Svensson, M., Cristiano, C., Morgillo, C. M., Fowler, C. J., Russo, R., Catalanotti, B., and Onnis, V.
- Subjects
Amide ,Male ,Models, Molecular ,Flurbiprofen ,Pharmacology ,01 natural sciences ,Mice, Inbred Strain ,Rats, Sprague-Dawley ,Mice ,Fatty acid amide hydrolase ,Drug Discovery ,fatty acid amide hydrolase ,non-steroidal anti-inflammatory drugs ,Enzyme Inhibitor ,Amidohydrolase ,biology ,Molecular Structure ,Chemistry ,Läkemedelskemi ,General Medicine ,Farmakologi och toxikologi ,Endocannabinoid system ,cyclooxygenase ,Hyperalgesia ,flurbiprofen amides ,lipids (amino acids, peptides, and proteins) ,medicine.symptom ,medicine.drug ,Static Electricity ,RM1-950 ,Flurbiprofen amides ,Pharmacology and Toxicology ,Inhibitory postsynaptic potential ,Flurbiprofen amide ,Structure-Activity Relationship ,non-steroidal anti-inflammatory drug ,In vivo ,medicine ,Rats, Wistar ,allodynia ,hyperalgesia ,Dose-Response Relationship, Drug ,010405 organic chemistry ,Animal ,endocannabinoid ,In vitro ,0104 chemical sciences ,FAAH inhibition ,010404 medicinal & biomolecular chemistry ,Cyclooxygenase 2 ,Drug Design ,biology.protein ,Quantum Theory ,Rat ,Analgesic ,Cyclooxygenase ,Therapeutics. Pharmacology ,Medicinal Chemistry - Abstract
Compounds combining dual inhibitory action against FAAH and cyclooxygenase (COX) may be potentially useful analgesics. Here, we describe a novel flurbiprofen analogue, N-(3-bromopyridin-2-yl)-2-(2-fluoro-(1,1'-biphenyl)-4-yl)propanamide (Flu-AM4). The compound is a competitive, reversible inhibitor of FAAH with a Ki value of 13 nM and which inhibits COX activity in a substrate-selective manner. Molecular modelling suggested that Flu-AM4 optimally fits a hydrophobic pocket in the ACB region of FAAH, and binds to COX-2 similarly to flurbiprofen. In vivo studies indicated that at a dose of 10 mg/kg, Flu-AM4 was active in models of prolonged (formalin) and neuropathic (chronic constriction injury) pain and reduced the spinal expression of iNOS, COX-2, and NFκB in the neuropathic model. Thus, the present study identifies Flu-AM4 as a dual-action FAAH/substrate-selective COX inhibitor with anti-inflammatory and analgesic activity in animal pain models. These findings underscore the potential usefulness of such dual-action compounds.
- Published
- 2021
7. The fatty acid amide hydrolase and cyclooxygenase-inhibitory properties of novel amide derivatives of carprofen
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Alessandro Deplano, Jessica Karlsson, Christopher J. Fowler, and Valentina Onnis
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Carbazoles ,Pharmacology ,Biochemistry ,Amidohydrolases ,chemistry.chemical_compound ,Mice ,Fatty acid amide hydrolase ,Amide ,Drug Discovery ,medicine ,Animals ,Humans ,Cyclooxygenase Inhibitors ,Carprofen ,Molecular Biology ,chemistry.chemical_classification ,Fenoprofen ,biology ,Organic Chemistry ,Anti-Inflammatory Agents, Non-Steroidal ,Anandamide ,Enzyme ,chemistry ,biology.protein ,Arachidonic acid ,Cyclooxygenase ,medicine.drug - Abstract
In experimental animals, inhibition of fatty acid amide hydrolase (FAAH) reduces the gastrointestinal damage produced by non-steroidal anti-inflammatory agents that act by inhibition of cyclooxygenase (COX). This suggests that compounds able to inhibit both enzymes may be potentially useful therapeutic agents. In the present study, we have investigated eight novel amide analogues of carprofen, ketoprofen and fenoprofen as potential FAAH/COX dual action inhibitors. Carpro-AM1 (2-(6-Chloro-9H-carbazol-2-yl)-N-(3-methylpyridin-2-yl)propenamide) and Carpro-AM6 (2-(6-Chloro-9H-carbazol-2-yl)-N-(3-chloropyridin-2-yl)propenamide) were found to be fully reversible inhibitors of the hydrolysis of 0.5 µM [3H]anandamide in rat brain homogenates with IC50 values of 94 and 23 nM, respectively, i.e. 2–3 orders of magnitude more potent than carprofen in this respect. Both compounds inhibited the cyclooxygenation of arachidonic acid by ovine COX-1, and were more potent inhibitors of human recombinant COX-2 when 2-arachidonoylglycerol was used as substrate than when arachidonic acid was used. It is concluded that Carpro-AM1 and Carpro-AM6 are dual-acting FAAH/substrate-selective COX inhibitors.
- Published
- 2020
8. Exploring the fatty acid amide hydrolase and cyclooxygenase inhibitory properties of novel amide derivatives of ibuprofen
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Mona Svensson, Jessica Karlsson, Valentina Onnis, Christopher J. Fowler, Bruno Catalanotti, Federica Moraca, Alessandro Deplano, Deplano, A, Karlsson, J, Svensson, M, Moraca, F, Catalanotti, B, Fowler, Cj, and Onnis, V
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Ibuprofen ,01 natural sciences ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Fatty acid amide hydrolase ,Amide ,Drug Discovery ,fatty acid amide hydrolase ,Enzyme Inhibitors ,biology ,Molecular Structure ,Chemistry ,Ibuprofen amides ,Läkemedelskemi ,General Medicine ,Farmakologi och toxikologi ,Endocannabinoid system ,Molecular Docking Simulation ,cyclooxygenase ,Biochemistry ,lipids (amino acids, peptides, and proteins) ,medicine.drug ,Research Paper ,RM1-950 ,Pharmacology and Toxicology ,Inhibitory postsynaptic potential ,Amidohydrolases ,Structure-Activity Relationship ,medicine ,Animals ,Humans ,Rats, Wistar ,Pharmacology ,Sulindac ,Dose-Response Relationship, Drug ,010405 organic chemistry ,endocannabinoid ,Amides ,digestive system diseases ,0104 chemical sciences ,Rats ,FAAH inhibition ,010404 medicinal & biomolecular chemistry ,Cyclooxygenase 2 ,Ibuprofen amides, FAAH inhibition, fatty acid amide hydrolase, endocannabinoid, cyclooxygenase ,biology.protein ,Cyclooxygenase 1 ,Therapeutics. Pharmacology ,Cyclooxygenase ,Medicinal Chemistry - Abstract
Inhibition of fatty acid amide hydrolase (FAAH) reduces the gastrointestinal damage produced by non-steroidal anti-inflammatory agents such as sulindac and indomethacin in experimental animals, suggesting that a dual-action FAAH-cyclooxygenase (COX) inhibitor could have useful therapeutic properties. Here, we have investigated 12 novel amide analogues of ibuprofen as potential dual-action FAAH/COX inhibitors. N-(3-Bromopyridin-2-yl)−2-(4-isobutylphenyl)propanamide (Ibu-AM68) was found to inhibit the hydrolysis of [3H]anandamide by rat brain homogenates by a reversible, mixed-type mechanism of inhibition with a Ki value of 0.26 µM and an α value of 4.9. At a concentration of 10 µM, the compound did not inhibit the cyclooxygenation of arachidonic acid by either ovine COX-1 or human recombinant COX-2. However, this concentration of Ibu-AM68 greatly reduced the ability of the COX-2 to catalyse the cyclooxygenation of the endocannabinoid 2-arachidonoylglycerol. It is concluded that Ibu-AM68 is a dual-acting FAAH/substrate-selective COX inhibitor.
- Published
- 2020
9. Effects of orthotopic implantation of rat prostate tumour cells upon components of the N-acylethanolamine and monoacylglycerol signalling systems : an mRNA study
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Christopher J. Fowler, Mireille Alhouayek, Jessica Karlsson, Sofia Halin Bergström, and Linda Stafberg
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Male ,Cancer microenvironment ,Polyunsaturated Alkamides ,medicine.medical_treatment ,lcsh:Medicine ,Arachidonic Acids ,Article ,Amidohydrolases ,chemistry.chemical_compound ,Fatty acid amide hydrolase ,N-Acylethanolamine ,Cell Line, Tumor ,medicine ,Phospholipase D ,Animals ,Humans ,RNA, Messenger ,lcsh:Science ,Cancer models ,chemistry.chemical_classification ,Messenger RNA ,Cancer och onkologi ,Multidisciplinary ,Prostate cancer ,Catabolism ,lcsh:R ,Prostatic Neoplasms ,Anandamide ,Lipids ,Rats ,Monoacylglycerol lipase ,Gene Expression Regulation, Neoplastic ,Disease Models, Animal ,Cytokine ,Enzyme ,chemistry ,Ethanolamines ,Cancer and Oncology ,Cancer research ,Monoglycerides ,lcsh:Q ,Metabolic Networks and Pathways ,Endocannabinoids ,Signal Transduction - Abstract
There is good evidence that the N-acylethanolamine (NAE)/monoacylglycerol (MAG) signalling systems are involved in the pathogenesis of cancer. However, it is not known how prostate tumours affect these systems in the surrounding non-malignant tissue and vice versa. In the present study we have investigated at the mRNA level 11 components of these systems (three coding for anabolic enzymes, two for NAE/MAG targets and six coding for catabolic enzymes) in rat prostate tissue following orthotopic injection of low metastatic AT1 cells and high metastatic MLL cells. The MLL tumours expressed higher levels of Napepld, coding for a key enzyme in NAE synthesis, and lower levels of Naaa, coding for the NAE hydrolytic enzyme N-acylethanolamine acid amide hydrolase than the AT1 tumours. mRNA levels of the components of the NAE/MAG signalling systems studied in the tissue surrounding the tumours were not overtly affected by the tumours. AT1 cells in culture expressed Faah, coding for the NAE hydrolytic enzyme fatty acid amide hydrolase, at much lower levels than Naaa. However, the ability of the intact cells to hydrolyse the NAE arachidonoylethanolamide (anandamide) was inhibited by an inhibitor of FAAH, but not of NAAA. Treatment of the AT1 cells with interleukin-6, a cytokine known to be involved in the pathogenesis of prostate cancer, did not affect the expression of the components of the NAE/MAG system studied. It is thus concluded that in the model system studied, the tumours show different expressions of mRNA coding for key the components of the NAE/MAG system compared to the host tissue, but that these changes are not accompanied by alterations in the non-malignant tissue.
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- 2020
10. Effects of culturing prostate cancer cells in acidic conditions upon the endocannabinoid signalling system
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Jessica Karlsson, Linda Stafberg, and Christopher J. Fowler
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Prostate cancer ,Chemistry ,Applied Mathematics ,General Mathematics ,Signalling system ,Cancer research ,medicine ,medicine.disease ,Endocannabinoid system - Published
- 2018
11. Metabolism of N ‐Acylethanolamines: To Phase <scp>II</scp> and Back Again
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Jessica Karlsson and Christopher J. Fowler
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Dual target ,chemistry.chemical_compound ,Biochemistry ,Chemistry ,Fatty acid amide hydrolase ,N-Acylethanolamine ,Signalling molecules ,media_common.quotation_subject ,TRPV1 ,Appetite ,Endogeny ,Metabolism ,media_common - Abstract
N-acylethanolamines (NAEs) are a family of endogenous signalling molecules involved in various effects of the body including pain, inflam- mation, appetite and sleep. NAEs are mainly degraded by fa ...
- Published
- 2017
12. Patient-reported recovery in upper abdominal cancer surgery care: A prospective study
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Jessica Karlsson, Bergthor Björnsson, Anna Johansson, Jenny Drott, Anna Lindhoff Larsson, Victoria Fomichov, and Per Sandström
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medicine.medical_specialty ,Surgery ,patient-reported measurements ,recovery ,supportive cancer care ,upper abdominal cancer ,Multidisciplinary ,Quantitative design ,business.industry ,General surgery ,General Practice ,Patient Discharge ,Allmänmedicin ,03 medical and health sciences ,0302 clinical medicine ,Neoplasms ,030220 oncology & carcinogenesis ,medicine ,Humans ,In patient ,Patient Reported Outcome Measures ,Postoperative Period ,Prospective Studies ,030212 general & internal medicine ,business ,Prospective cohort study ,Cancer surgery - Abstract
Background To describe and analyse patient-reported recovery in patients after upper abdominal cancer surgery.Methods This study had a quantitative and prospective design. Patients eligible for upper abdominal cancer surgery were consecutively included in a university hospital in southern Sweden. Twenty-four patients answered the Postoperative Recovery Profile (PRP) questionnaire at 3 measurement points. The PRP includes 5 dimensions of recovery: physical symptoms, physical function, psychological function, social function, and activity.Results The results were based on 72 answered questionnaires. All 5 dimensions were affected. Symptoms were rated preoperatively, and >60% of patients were not fully recovered upon discharge according to the PRP. In the physical symptoms dimension, the majority of patients reported a lack of energy upon discharge. High levels of anxiety were reported. Over 50% of patients reported some degree of depressed mood at all three measurement points. In the social dimension, the majority of patients reported some degree of inconvenience with respect to being dependent on help from others and restrictions in everyday life at four weeks after discharge.Conclusion Patients undergoing surgery for upper abdominal cancer are affected by psychological, physiological, social, and habitual factors, and according to the PRP, most estimates of these symptoms increase significantly after the surgery. Few patients are fully recovered at four weeks after discharge, and the majority of patients experience symptoms preoperatively. Individual patient-reported recovery estimates based on preoperative status and follow-up data may be valuable in identifying and planning interventions tailored to each patient's needs throughout the care process.
- Published
- 2021
13. Corrigendum to 'The fatty acid amide hydrolase and cyclooxygenase-inhibitory properties of novel amide derivatives of carprofen' [Bioorg. Chem. 101 (2020) 104034]
- Author
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Alessandro Deplano, Jessica Karlsson, Christopher J. Fowler, and Valentina Onnis
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biology ,Stereochemistry ,Organic Chemistry ,Inhibitory postsynaptic potential ,Biochemistry ,chemistry.chemical_compound ,chemistry ,Fatty acid amide hydrolase ,Amide ,Drug Discovery ,medicine ,biology.protein ,Carprofen ,Cyclooxygenase ,Molecular Biology ,medicine.drug - Published
- 2020
14. Portrayals of gender in preschool environment : A qualitative text- and picture analysis of gender portrayals in picture books
- Author
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Jessica, Karlsson
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Annan humaniora ,picture books ,Genus ,förskola ,bilderböcker som utspelar sig i förskolemiljö ,litteraturanalys ,Gender ,Social Sciences ,Samhällsvetenskap ,preschool ,picture books that take place in the preschool environment ,bilderböcker ,jämställdhet ,förskolepedagoger ,Other Humanities ,equality ,literature analysis ,preschool pedagogues - Abstract
The study is a qualitative literature analysis with the purpose of examining how children and preschool pedagogues were portrayed in picture books that take place in the preschool environment, based on gender perspectives. To define the material, books that take place in the preschool environment had been selected. The purpose of the study was also to examine how relationships between children and preschool pedagogues were portrayed, from a gender perspective. And whether there was a difference between the gender portrayals depending on the year when the book was published. The picture book analysis has created an understanding of how preschool pedagogues can work gender pedagogically with literature as a tool, together with the children. The analysis and the results have shown that there are variations in how gender and gender roles were portrayed in the picture books. It also showed that there are picture books that are gender conscious and that some maintain and enhance gender roles.
- Published
- 2018
15. Comparison of neurons derived from mouse P19, rat PC12 and human SH-SY5Y cells in the assessment of chemical- and toxin-induced neurotoxicity
- Author
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Jessica Karlsson, Dina Popova, and Stig O. P. Jacobsson
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0301 basic medicine ,Okadaic acid ,SH-SY5Y ,Cell ,Retinoic acid-treated SH ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Pharmacology (medical) ,Membrane Potential, Mitochondrial ,Neurons ,Acrylamide ,In vitro cytotoxicity ,Methylmercury ,Cell Differentiation ,Methylmercury Compounds ,Farmakologi och toxikologi ,Glutathione ,P19 cell ,medicine.anatomical_structure ,Nerve growth factor-treated PC12 cells ,Neurotoxicity Syndromes ,Research Article ,Neurite ,Retinoic acid-treated P19 cells ,Cell Survival ,Pharmacology and Toxicology ,Biology ,Models, Biological ,Retinoic acid-treated SH-SY5Y cells ,03 medical and health sciences ,lcsh:RA1190-1270 ,Cell Line, Tumor ,medicine ,Neurotoxicity ,Animals ,Humans ,Buthionine sulfoximine ,Viability assay ,Buthionine Sulfoximine ,lcsh:Toxicology. Poisons ,Pharmacology ,Neuronal cell cultures ,lcsh:RM1-950 ,medicine.disease ,Molecular biology ,Rats ,lcsh:Therapeutics. Pharmacology ,030104 developmental biology ,chemistry ,030217 neurology & neurosurgery - Abstract
Background: Exposure to chemicals might be toxic to the developing brain. There is a need for simple and robust in vitro cellular models for evaluation of chemical-induced neurotoxicity as a complement to traditional studies on animals. In this study, neuronally differentiated mouse embryonal carcinoma P19 cells (P19 neurons) were compared with human neuroblastoma SH-SY5Y cells and rat adrenal pheochromocytoma PC12 cells for their ability to detect toxicity of methylmercury (MeHg), okadaic acid and acrylamide. Methods: Retinoic acid-treated P19 and SH-SY5Y cells and nerve growth factor-stimulated PC12 cells, allowed to differentiate for 6 days, were exposed to MeHg, okadaic acid and acrylamide for 48 h. Cell survival and neurite outgrowth were assessed with the calcein-AM assay and fluorescence detection of antibodies against the cytoskeletal neuron-specific protein beta III-tubulin, respectively. The effects of glutathione (GSH) and the potent inhibitor of GSH synthesis buthionine sulfoximine (BSO) on the MeHg induced-toxicity were assessed using the PrestoBlue (TM) cell viability assay and the TMRE mitochondrial membrane potential assay. Results: Differentiated P19 cells developed the most extensive neuronal network among the three cell models and were the most sensitive neuronal model to detect neurotoxic effects of the test compounds. MeHg produced a concentration-dependent toxicity in differentiated P19 cells and SH-SY5Y cells, with statistically significant effects at concentrations from 0.1 mu M in the P19 neurons and 1 mu M in the SH-SY5Y cells. MeHg induced a decrease in the cellular metabolic activity and mitochondrial membrane potential (Delta Psi m) in the differentiated P19 cells and SH-SY5Y cells, that were attenuated by GSH. Okadaic acid and acrylamide also showed statistically significant toxicity in the P19 neurons, but not in the SH-SY5Y cells or the P12 cells. Conclusions: P19 neurons are more sensitive to detect cytotoxicity of MeHg, okadaic acid and acrylamide than retinoic acid-differentiated SH-SY5Y cells and nerve growth factor-treated PC12 cells. P19 neurons are at least as sensitive as differentiated SH-SY5Y cells to detect the loss of mitochondrial membrane potential produced by MeHg and the protective effects of extracellular GSH on MeHg toxicity. P19 neurons may be a useful model to study neurotoxic effects of chemicals.
- Published
- 2017
16. Anatomy of the inferior extensor retinaculum and its role in lateral ankle ligament reconstruction: a pictorial essay
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Jessica Karlsson, Yutaka Yasui, Gino M. M. J. Kerkhoffs, John G. Kennedy, James D. F. Calder, Miki Dalmau-Pastor, Other Research, Orthopedic Surgery and Sports Medicine, and Universitat de Barcelona
- Subjects
medicine.medical_specialty ,Lateral ankle ,Lligaments ,Tendons ,03 medical and health sciences ,0302 clinical medicine ,Articulacions ,medicine ,Humans ,Orthopedics and Sports Medicine ,Anatomia humana ,Fascia ,Turmell ,Orthopedic surgery ,030222 orthopedics ,Brostrom gould ,Ankle stability ,Ligaments ,Inferior extensor retinaculum ,business.industry ,Foot ,Cirurgia ortopèdica ,030229 sport sciences ,Anatomy ,musculoskeletal system ,Lateral ankle ligaments ,body regions ,medicine.anatomical_structure ,Peu ,Ligaments, Articular ,Human anatomy ,Ligament ,Surgery ,Joints ,Ankle ,Lateral Ligament, Ankle ,business ,Ankle Joint - Abstract
The inferior extensor retinaculum (IER) is an aponeurotic structure, which is in continuation with the anterior part of the sural fascia. The IER has often been used to augment the reconstruction of the lateral ankle ligaments, for instance in the Broström-Gould procedure, with good outcomes reported. However, its anatomy has not been described in detail and only a few studies are available on this structure. The presence of a non-constant oblique supero-lateral band appears to be important. This structure defines whether the augmentation of the lateral ankle ligaments reconstruction is performed using true IER or only the anterior part of the sural fascia. It is concluded that the use of this structure will have an impact on the resulting ankle stability.
- Published
- 2016
17. Characterisation of (R)-2-(2-Fluorobiphenyl-4-yl)-N-(3-Methylpyridin-2-yl)Propanamide as a Dual Fatty Acid Amide Hydrolase: Cyclooxygenase Inhibitor
- Author
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Alessandro Deplano, Valentina Onnis, Mona Svensson, Christopher J. Fowler, Cenzo Congiu, Jessica Karlsson, Marcus Fredriksson Sundbom, Sandra Gouveia-Figueira, and Sanaz Hashemian
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Lipopolysaccharides ,Male ,lcsh:Medicine ,chemistry.chemical_compound ,Mice ,Fatty acid amide hydrolase ,lcsh:Science ,Multidisciplinary ,Arachidonic Acid ,biology ,Hydrolysis ,Ionomycin ,Brain ,Stereoisomerism ,Farmakologi och toxikologi ,Endocannabinoid system ,Isoenzymes ,Biochemistry ,Benzamides ,Arachidonic acid ,lipids (amino acids, peptides, and proteins) ,psychological phenomena and processes ,Research Article ,Stereochemistry ,Polyunsaturated Alkamides ,Prostaglandin ,Pharmacology and Toxicology ,Arachidonic Acids ,Amidohydrolases ,Interferon-gamma ,Animals ,Humans ,Cyclooxygenase Inhibitors ,lcsh:R ,Substrate (chemistry) ,Lipid Metabolism ,Propanamide ,Amides ,RAW 264.7 Cells ,nervous system ,chemistry ,Flurbiprofen ,Cyclooxygenase 2 ,biology.protein ,Cyclooxygenase 1 ,Prostaglandins ,lcsh:Q ,Cyclooxygenase ,Carbamates ,Endocannabinoids - Abstract
Background Increased endocannabinoid tonus by dual-action fatty acid amide hydrolase (FAAH) and substrate selective cyclooxygenase (COX-2) inhibitors is a promising approach for pain-relief. One such compound with this profile is 2-(2-fluorobiphenyl-4-yl)-N-(3-methylpyridin-2-yl)propanamide (Flu-AM1). These activities are shown by Flu-AM1 racemate, but it is not known whether its two single enantiomers behave differently, as is the case towards COX-2 for the parent flurbiprofen enantiomers. Further, the effects of the compound upon COX-2-derived lipids in intact cells are not known. Methodology/Principal Findings COX inhibition was determined using an oxygraphic method with arachidonic acid and 2-arachidonoylglycerol (2-AG) as substrates. FAAH was assayed in mouse brain homogenates using anandamide (AEA) as substrate. Lipidomic analysis was conducted in unstimulated and lipopolysaccharide + interferon gamma-stimulated RAW 264.7 macrophage cells. Both enantiomers inhibited COX-2 in a substrate-selective and time-dependent manner, with IC50 values in the absence of a preincubation phase of: (R)-Flu-AM1, COX-1 (arachidonic acid) 6 mu M; COX-2 (arachidonic acid) 20 mu M; COX-2 (2-AG) 1 mu M; (S)-Flu-AM1, COX-1 (arachidonic acid) 3 mu M; COX-2 (arachidonic acid) 10 mu M; COX-2 (2-AG) 0.7 mu M. The compounds showed no enantiomeric selectivity in their FAAH inhibitory properties. (R)-Flu-AM1 (10 mu M) greatly inhibited the production of prostaglandin D2 and E2 in both unstimulated and lipopolysaccharide + interferon.-stimulated RAW 264.7 macrophage cells. Levels of 2-AG were not affected either by (R)-Flu-AM1 or by 10 mu M flurbiprofen, either alone or in combination with the FAAH inhibitor URB597 (1 mu M). Conclusions/Significance Both enantiomers of Flu-AM1 are more potent inhibitors of 2-AG compared to arachidonic acid oxygenation by COX-2. Inhibition of COX in lipopolysaccharide + interferon.-stimulated RAW 264.7 cells is insufficient to affect 2-AG levels despite the large induction of COX-2 produced by this treatment.
- Published
- 2015
18. Older adults' experiences of participating in a study circle about aging and drugs
- Author
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Karin Josefsson, Jessica Karlsson, and Johanna Gmeiner
- Subjects
Gerontology ,business.industry ,Older adults ,aging ,Health Sciences ,Study circle ,Medicine ,Primary care ,Hälsovetenskaper ,business ,drugs ,Compliance (psychology) ,study circle - Abstract
Background: Primary care physicians have a responsibility to inform older adults about the drugs and drug treatments they are prescribed so as to increase patients’ compliance. However, this need is not always met. Use of a ‘study circle’ exercise may help older adults to obtain and increase their knowledge in a community setting, having the opportunity to share experiences with others in similar situations. The aim of this study was to describe older adults’ experiences of taking part in a study circle about aging and drugs. Methods: The study was designed to be descriptive with an inductive approach. Eleven older adults took part in focus group interviews in 2014, and the content of these interviews was analysed. Results: Participants felt the design of the study circle exercise was good; having a syllabus to follow but at the same time allowing individuals’ problems to be discussed. They described the leader of the study circle to be competent, with characteristics they appreciated. Participants found the study circle material informative, and it could be used as a reference for reflection. Participants’ knowledge of natural and pathological aging was increased, as was their knowledge of drugs and their formulations. Participants felt more confident; they dared to ask questions, challenged new drugs, and proactively took action by seeking care when needed. The study circle format was recommended to other older adults. Participants suggested that in future the study circle could be extended and repeated, and that they could be provided with supplementary educational materials or exercises. Conclusions: Use of a study circle about aging and drugs increased older adults’ knowledge, and empowered them to ask questions and take an active part in their drug treatment. We believe that older adults have a desire to want to know more about the drugs they are prescribed, and want to be involved with their treatment, not simply passive recipients.
- Published
- 2015
19. A novel RHCE*02 allele, containing the single‐nucleotide change c.460A>G, encodes weakened expression of C and e antigens
- Author
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Emma Pesjak, Åsa Hellberg, Jessica Karlsson, and Jill R. Storry
- Subjects
medicine.medical_specialty ,Erythrocytes ,Genotype ,Immunology ,Blood Donors ,030204 cardiovascular system & hematology ,Biology ,03 medical and health sciences ,0302 clinical medicine ,Antigen ,Internal medicine ,medicine ,Humans ,Immunology and Allergy ,Nucleotide ,Hepatitis B e Antigens ,Allele ,Alleles ,chemistry.chemical_classification ,Genetics ,Rh-Hr Blood-Group System ,Hematology ,Antibodies, Monoclonal ,Hepatitis B Core Antigens ,Molecular biology ,Phenotype ,Haplotypes ,chemistry ,Monoclonal ,biology.protein ,sense organs ,Antibody ,030215 immunology - Abstract
We report a novel RHCE*02 allele in a Swedish blood donor that is characterized by the change c.460A>G (Arg154Gly). The blood donor's red blood cells showed variable reactivity with different monoclonal anti-C and anti-e and antigen strength was markedly weakened. We believe that these changes represent both a quantitative and qualitative alteration of the antigens encoded by this allele.
- Published
- 2016
20. Effects of tumour necrosis factor α upon the metabolism of the endocannabinoid anandamide in prostate cancer cells
- Author
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Christopher J. Fowler, Jessica Karlsson, Sandra Gouveia-Figueira, and Mireille Alhouayek
- Subjects
Lipopolysaccharides ,Male ,0301 basic medicine ,Enzyme Metabolism ,lcsh:Medicine ,Phospholipase ,Biochemistry ,Mice ,chemistry.chemical_compound ,0302 clinical medicine ,Tandem Mass Spectrometry ,Fatty acid amide hydrolase ,Medicine and Health Sciences ,Enzyme Chemistry ,lcsh:Science ,Chromatography, High Pressure Liquid ,DU145 cells ,Multidisciplinary ,Prostate Cancer ,Hydrolysis ,Prostate Diseases ,Chemical Reactions ,Neurochemistry ,Anandamide ,Plants ,Legumes ,Farmakologi och toxikologi ,Lipids ,Endocannabinoid system ,Gene Expression Regulation, Neoplastic ,Chemistry ,Oncology ,030220 oncology & carcinogenesis ,Physical Sciences ,Cell lines ,lipids (amino acids, peptides, and proteins) ,Tumor necrosis factor alpha ,Neurochemicals ,Biological cultures ,Research Article ,medicine.medical_specialty ,Polyunsaturated Alkamides ,Urology ,Arachidonic Acids ,Pharmacology and Toxicology ,Biology ,Amidohydrolases ,Enzyme Regulation ,03 medical and health sciences ,DU145 ,Cell Line, Tumor ,Internal medicine ,medicine ,Animals ,Humans ,Tumor Necrosis Factor-alpha ,lcsh:R ,Organisms ,Peas ,Cancers and Neoplasms ,Biology and Life Sciences ,Prostatic Neoplasms ,Research and analysis methods ,Genitourinary Tract Tumors ,RAW 264.7 Cells ,030104 developmental biology ,Endocrinology ,chemistry ,Cyclooxygenase 2 ,Cell culture ,Cancer cell ,Enzymology ,Prostaglandins ,lcsh:Q ,Endocannabinoids ,Neuroscience - Abstract
Tumour necrosis factor a (TNF alpha) is involved in the pathogenesis of prostate cancer, a disease where disturbances in the endocannabinoid system are seen. In the present study we have investigated whether treatment of DU145 human prostate cancer cells affects anandamide (AEA) catabolic pathways. Additionally, we have investigated whether cyclooxygenase- 2 (COX-2) can regulate the uptake of AEA into cells. Levels of AEA synthetic and catabolic enzymes were determined by qPCR. AEA uptake and hydrolysis in DU145 and RAW264.7 macrophage cells were assayed using AEA labeled in the arachidonic and ethanolamine portions of the molecule, respectively. Levels of AEA, related N-acylethanolamines (NAEs), prostaglandins (PG) and PG-ethanolamines (PG-EA) in DU145 cells and medium were quantitated by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis. TNF alpha treatment of DU145 cells increased mRNA levels of PTSG2 (gene of COX-2) and decreased the mRNA of the AEA synthetic enzyme N-acylphosphatidylethanolamine selective phospholipase D. mRNA levels of the AEA hydrolytic enzymes fatty acid amide hydrolase (FAAH) and N-acylethanolamine-hydrolyzing acid amidase were not changed. AEA uptake in both DU145 and RAW264.7 cells was inhibited by FAAH inhibition, but not by COX-2 inhibition, even in RAW264.7 cells where the expression of this enzyme had greatly been induced by lipopolysaccharide + interferon. treatment. AEA and related NAEs were detected in DU145 cells, but PGs and PGE(2)-EA were only detected when the cells had been preincubated with 100 nM AEA. The data demonstrate that in DU145 cells, TNFa treatment changes the relative expression of the enzymes involved in the hydrolytic and oxygenation catabolic pathways for AEA. In RAW264.7 cells, COX-2, in contrast to FAAH, does not regulate the cellular accumulation of AEA. Further studies are necessary to determine the extent to which inflammatory mediators are involved in the abnormal endocannabinoid signalling system in prostate cancer.
- Published
- 2017
21. Inhibition of Endocannabinoid Metabolism by the Metabolites of Ibuprofen and Flurbiprofen
- Author
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Jessica Karlsson and Christopher J. Fowler
- Subjects
Science ,Flurbiprofen ,Ibuprofen ,Pharmacology and Toxicology ,Pharmacology ,Biochemistry ,Rats, Sprague-Dawley ,medicine ,Medicine and Health Sciences ,Animals ,Cyclooxygenase Inhibitors ,Rats, Wistar ,Multidisciplinary ,Chemistry ,Oxygen metabolism ,organic chemicals ,Prostaglandin synthesis ,Biology and Life Sciences ,Brain ,Neurochemistry ,Metabolism ,musculoskeletal system ,Farmakologi och toxikologi ,Endocannabinoid system ,Lipids ,Rats ,Sprague dawley ,Medicine ,lipids (amino acids, peptides, and proteins) ,Drug metabolism ,medicine.drug ,Research Article ,Endocannabinoids - Abstract
BackgroundIn addition to their effects upon prostaglandin synthesis, the non-steroidal anti-inflammatory drugs ibuprofen and flurbiprofen inhibit the metabolism of the endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide (AEA) by cyclooxygenase-2 (COX-2) and fatty acid amide hydrolase (FAAH), respectively. Here, we investigated whether these effects upon endocannabinoid metabolism are shared by the main metabolites of ibuprofen and flurbiprofen.Methodology/principal findingsCOX activities were measured via changes in oxygen consumption due to oxygenation of arachidonic acid (for COX-1) and arachidonic acid and 2-AG (for COX-2). FAAH activity was quantified by measuring hydrolysis of tritium labelled AEA in rat brain homogenates. The ability of ibuprofen and flurbiprofen to inhibit COX-2-catalysed oxygenation of 2-AG at lower concentrations than the oxygenation of arachidonic acid was seen with 4'-hydroxyflurbiprofen and possibly also 3'-hydroxyibuprofen, albeit at lower potencies than the parent compounds. All ibuprofen and flurbiprofen metabolites retained the ability to inhibit FAAH in a pH-dependent manner, although the potency was lower than seen with the parent compounds.Conclusions/significanceIt is concluded that the primary metabolites of ibuprofen and flurbiprofen retain some of the properties of the parent compound with respect to inhibition of endocannabinoid metabolism. However, these effects are unlikely to contribute to the actions of the parent compounds in vivo.
- Published
- 2014
22. Biologically active ADAMTS13 is expressed in renal tubular epithelial cells
- Author
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Diana Karpman, Jessica Karlsson, Zivile Békássy, Ramesh Tati, and Minola Manea
- Subjects
Nephrology ,Male ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Renal cortex ,ADAMTS13 Protein ,Gene Expression ,Biology ,Immunofluorescence ,urologic and male genital diseases ,Pediatrics ,Kidney Tubules, Proximal ,Tubulopathy ,Internal medicine ,Cell Line, Tumor ,hemic and lymphatic diseases ,medicine ,Humans ,RNA, Messenger ,Child ,Carcinoma, Renal Cell ,Kidney ,Protease ,medicine.diagnostic_test ,Epithelial Cells ,medicine.disease ,Molecular biology ,Immunohistochemistry ,Kidney Neoplasms ,ADAM Proteins ,medicine.anatomical_structure ,Cell culture ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Female ,Kidney Diseases - Abstract
ADAMTS13 mRNA, which encodes the von Willebrand factor-cleaving protease, has been detected in a variety of tissues, including the kidney. The aim of our study was to characterize tubular expression and bioactivity of ADAMTS13. ADAMTS13 mRNA was detected in cultured primary human renal tubular epithelial cells (HRTEC) and in A498 cells, a human renal carcinoma cell line, by real-time PCR. Protein was detected using immunofluorescence and immunoblotting. Immunoblots demonstrated that the protein was secreted. The protease was proteolytically active in both cell lysates and cleaved the FRETS–VWF73 substrate. ADAMTS13 was demonstrated in situ in the renal cortex by immunohistochemistry. Protease was detected in both the proximal and distal renal tubules in normal renal tissue (n = 3) as well as in patients with tubular disorders (n = 3). Immunoblotting revealed that ADAMTS13 was present in the urine of patients with tubulopathy (n = 5) but not in normal urine. ADAMTS13 in urine had a molecular size similar to that in plasma, which indicates that the protease originates in the tubuli because such large proteins do not normally pass the glomerular filter. In conclusion, human renal tubular epithelial cells synthesize biologically active ADAMTS13 which may, after release from tubuli, regulate hemostasis in the local microenvironment.
- Published
- 2010
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