| 1. |
- Alfvén, Tobias, et al.
(author)
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Low-level cadmium exposure and osteoporosis.
- 2000
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In: Journal of Bone and Mineral Research. - 0884-0431 .- 1523-4681. ; 15, s. 1579-1586
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Journal article (peer-reviewed)abstract
- Osteoporosis is a major cause of morbidity worldwide. A number of risk factors, such as age and gender, are well established. High cadmium exposure causes renal damage and in severe cases also causes osteoporosis and osteomalacia, We have examined whether long-term Pow-level cadmium exposure increases the risk of osteoporosis. Bone mineral density (BMD) in the forearm was measured in 520 men and 544 women, aged 16-81 years, environmentally or occupationally exposed to cadmium, using dual-energy X-ray absorptiometry (DXA) technique. Cadmium in urine was used as the dose estimate and protein HC was used: as a marker of renal tubular damage. There was a clear dose-response relation between cadmium dose and the prevalence of tubular proteinuria. Inverse relations were found between cadmium dose, tubular proteinuria, and BMD, particularly apparent in persons over 60 years of age, There was a dose-response relation between cadmium dose and osteoporosis. The odds ratios (ORs) for men were 2.2 (95% CI, 1.0-4.8) in the dose group 0.5-3 nmol Cd/mmol creatinine and 5.3 (2.0-14) in the highest dose category (greater than or equal to 3 nmol/mmol creatinine) compared with the lowest dose group (<0.5 nmol Cd/mmol creatinine). For women, the OR was 1.8 (0.65-5.3) in the dose group 0.53 nmol Cd/mmol creatinine. We conclude that exposure to low levels of cadmium is associated with an increased risk of osteoporosis.
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| 2. |
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| 3. |
- Carlsson, Björn, et al.
(author)
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Enantioselective Analysis of Citalopram and Metabolites in Adolescents
- 2001
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In: Therapeutic drug monitoring. - : Ovid Technologies (Wolters Kluwer Health). - 0163-4356. ; 23, s. 658-
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Journal article (peer-reviewed)abstract
- Studies of the antidepressant effect and pharmacokinetics of citalopram have been performed in adults, but the effects on children and adolescents have only been studied to a minor extent despite its increasing use in these age groups. The aim of this study was to investigate a group of adolescents treated for depression, with respect to the steady-state plasma concentrations of the enantiomers of citalopram and its demethylated metabolites desmethylcitalopram and didesmethylcitalopram. Moreover, the authors studied the genotypes for the polymorphic cytochrome P450 enzymes CYP2D6 and CYP2C19 in relation to the different enantiomers. The S/R ratios of citalopram and desmethylcitalopram found in this study of 19 adolescents were similar to studies involving older patients. The concentrations of the R-(-)- and S-(+)-enantiomers of citalopram and desmethylcitalopram were also in agreement with values from earlier studies, the R-(-)-enantiomer (distomer) being the major enantiomer. The results indicate that the use of oral contraceptives may have some influence on the metabolism of citalopram. This might be because of an interaction of the contraceptive hormones with the CYP2C19 enzyme.
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| 4. |
- Carlsson, Josefine, et al.
(author)
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Disperse azo dyes, arylamines and halogenated dinitrobenzene compounds in synthetic garments on the Swedish market
- 2022
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In: Contact Dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 87:4, s. 315-324
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Journal article (peer-reviewed)abstract
- Background: Azobenzene disperse dyes (azo DDs) are well-known as textile allergens, but the knowledge of their occurrence in garments is low. The numerous azo DDs and dye components found in textiles constitute a potential health risk, but only seven azo DDs are included in the European baseline patch test series (EBS).Objectives: To investigate non-regulated azo DDs and dye components in synthetic garments on the Swedish market.Methods: High-performance liquid chromatography/mass spectrometry, gas chromatography/mass spectrometry and computerized data mining.Results: Sixty-two azo DDs were detected, with Disperse Red 167:1 occurring in 67%, and 14 other DDs each found in >20% of the garments. Notably, the EBS dyes were less common, three even not detected, while arylamines were frequently detected and exceeded 1 mg/g in several garments. Also, halogenated dinitrobenzenes were identified in 25% of the textiles.Conclusion: Azo DDs and dye components, in complex compositions and with large variations, occurred frequently in the synthetic garments. The arylamines were shown to occur at much higher levels compared to the azo DDs, suggesting the former constitute a potentially higher health risk. The role of arylamines and halogenated dinitrobenzenes in textile allergy has to be further investigated.
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| 5. |
- Carlsson, Josefine, 1989-
(author)
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Is your wardrobe making you sick? : Textile Chemicals with Focus on Skin Sensitizers – Analytical Methods, Occurrence and Dermal Exposure
- 2024
-
Doctoral thesis (other academic/artistic)abstract
- Textile production includes the use of a large diversity of chemicals, often in high amounts, and their presence in the finished textiles has become a topic of increasing concern. One of the health concerns associated with several of these compounds is skin sensitization, which may lead to the development of textile allergy. This thesis has a special focus on skin allergens and presents analytical methods and workflows to gain a deeper understanding of these chemicals in clothing.In Paper I, a suspect screening of disperse azo dyes in synthetic clothing was conducted using liquid chromatography/high-resolution mass spectrometry (LC/HRMS). In addition, gas chromatography/mass spectrometry (GC/MS) was applied to screen for volatile/semi-volatile dye components. Various disperse azo dyes and arylamines were identified. Notably, most of the dyes used today to diagnose textile allergy were rarely identified. Further, the well-known skin sensitizer 2,4-dinitrochlorobenzene was shown to occur in garments for the first time. Paper II presents a screening method for textiles with automated thermal desorption (ATD) coupled to GC/MS. This method was used for accurate quantification of more than 30 volatile/semi-volatile compounds in textiles, but is also suitable for a wider range of semi-volatiles. Most analytes had method detection limits below 1 µg/g (26 out of 31 analytes) with a relative standard deviation <15%. The ATD-GC/MS method would allow companies to simultaneously screen for multiple components with a minimum of sample preparation, significantly enhancing efficiency and the ability to comply with regulations. Since several compounds identified in Papers I and II are suspected to cause skin sensitization, this was further studied and is the focus of Paper III. A combination of in vitro methods was employed to study the first and third key events of contact allergy as well as mutagenicity. Two hitherto unreported skin sensitizers and two mutagenic compounds were discovered. Despite this, the risks for skin sensitization or other non-carcinogenic health effects from exposure to these compounds in textiles were estimated as acceptable, at least when considering individual compounds and the levels so far reported.In Paper IV, cellulose nanocrystals (CNCs) produced from upcycling post-consumer garments were screened for textile chemicals using a non-target/suspect screening approach with GC/MS and LC/HRMS. Generally, lower levels were detected in the cellulose nanocrystals. However, phthalates were found to remain mainly in the CNCs. Although the levels of phthalates in this case were below the EU regulation, this emphasizes the need for control of the garments.In conclusion, this thesis has developed analytical methods and approaches that can be used for the surveillance and screening of chemicals in textiles, facilitating future identification of substances that constitute potential health risks.
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| 6. |
- Carlsson, Josefine, et al.
(author)
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Solvent-free automated thermal desorption-gas chromatography/mass spectrometry for direct screening of hazardous compounds in consumer textiles
- 2023
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In: Analytical and Bioanalytical Chemistry. - 1618-2642 .- 1618-2650. ; 415:19, s. 4675-4687
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Journal article (peer-reviewed)abstract
- The global production of textiles utilizes numerous large-volume chemicals that may remain to some extent in the finished garments. Arylamines, quinolines, and halogenated nitrobenzene compounds are possible mutagens, carcinogens and/or skin sensitizers. For prevention, control of clothing and other textiles must be improved, especially those imported from countries without regulations of textile chemicals. An automated analytical methodology with on-line extraction, separation, and detection would largely simplify screening surveys of hazardous chemicals in textiles. Automated thermal desorption-gas chromatography/mass spectrometry (ATD-GC/MS) was developed and evaluated as a solvent-free, direct chemical analysis for screening of textiles. It requires a minimum of sample handling with a total run time of 38 min including sample desorption, chromatographic separation, and mass spectrometric detection. For most of the studied compounds, method quantification limit (MQL) was below 5 mu g/g for 5 mg of textile sample, which is sufficiently low for screening and control of quinoline and arylamines regulated by EU. Several chemicals were detected and quantified when the ATD-GC/MS method was applied in a limited pilot screening of synthetic fiber garments. A number of arylamines were detected, where some of the halogenated dinitroanilines were found in concentrations up to 300 mu g/g. This is ten times higher than the concentration limit for similar arylamines listed by the EU REACH regulation. Other chemicals detected in the investigated textiles were several quinolines, benzothiazole, naphthalene, and 3,5-dinitrobromobenzene. Based on the present results, we suggest ATD-GC/MS as a screening method for the control of harmful chemicals in clothing garments and other textiles.
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| 7. |
- Carlsson, Josefine, et al.
(author)
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Suspect and non-target screening of chemicals in clothing textiles by reversed-phase liquid chromatography/hybrid quadrupole-Orbitrap mass spectrometry
- 2021
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In: Analytical and Bioanalytical Chemistry. - : Springer Science and Business Media LLC. - 1618-2642 .- 1618-2650. ; 414:3, s. 1403-1413
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Journal article (peer-reviewed)abstract
- The global manufacturing of clothing is usually composed of multistep processes, which include a large number of chemicals. However, there is generally no information regarding the chemical content remaining in the finished clothes. Clothes in close and prolonged skin contact may thus be a significant source of daily human exposure to hazardous compounds depending on their ability to migrate from the textiles and be absorbed by the skin. In the present study, twenty-four imported garments on the Swedish market were investigated with respect to their content of organic compounds, using a screening workflow. Reversed-phase liquid chromatography coupled to electrospray ionization/high-resolution mass spectrometry was used for both suspect and non-target screening. The most frequently detected compound was benzothiazole followed by quinoline. Nitroanilines with suspected mutagenic and possible skin sensitization properties, and quinoline, a carcinogenic compound, were among the compounds occurring at the highest concentrations. In some garments, the level of quinoline was estimated to be close to or higher than 50,000 ng/g, the limit set by the REACH regulation. Other detected compounds were acridine, benzotriazoles, benzothiazoles, phthalates, nitrophenols, and organophosphates. Several of the identified compounds have logP and molecular weight values enabling skin uptake. This pilot study indicates which chemicals and compound classes should be prioritized for future quantitative surveys and control of the chemical content in clothing as well as research on skin transfer, skin absorption, and systemic exposure. The results also show that the current control and prevention from chemicals in imported garments on the Swedish market is insufficient.
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| 8. |
- Iadaresta, Francesco, 1985-, et al.
(author)
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Strategies Towards Suspect and Non-target Screening of Chemicals in Clothing Textiles by Reverse Phase Liquid Chromatography–hybrid Linear Ion Trap Orbitrap Mass Spectrometry
-
Other publication (other academic/artistic)abstract
- Textile industry uses a large number of various chemicals in the multi-step production chain. Some of these chemicals are intentionally used to give specific features to textile materials (softness, color, improve fastness, flame resistant etc.). Some other are unintentionally added, such us transformation products (e.g. dye degradation production), impurities of other used compounds and/or biocides. Due to the large number of cloths manufacturing steps, starting from fabric production to clothes trade, information regarding the chemicals used are not always available. Clothes are in close and prolonged contact with the skin, making possible a human exposure to chemicals present in textile material. Furthermore, chemicals, if not removed from wastewater treatment plants, can be released in the environment through the laundry of textile materials. In the present study, reverse phase liquid chromatography coupled to high resolution mass spectrometry was used for screening of suspect and unknown compounds in twenty-four textile samples. Strategies towards suspect and non-target screening are discussed considering the experimental conditions and the subsequent data treatment. Suspect compounds belonging to benzotriazoles, benzothiazoles, nitroanilines, quinolines and phthalates were confirmed in the analyzed samples. The method was able also to successfully identify compounds not included in the suspect list, such as nitrophenols, acridine, and phosphates.
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| 9. |
- Jakobsen Falk, Ingrid, et al.
(author)
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Pharmacogenetic study of the impact of ABCB1 single-nucleotide polymorphisms on lenalidomide treatment outcomes in patients with multiple myeloma: results from a phase IV observational study and subsequent phase II clinical trial
- 2018
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In: Cancer Chemotherapy and Pharmacology. - : SPRINGER. - 0344-5704 .- 1432-0843. ; 81:1, s. 183-193
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Journal article (peer-reviewed)abstract
- Purpose Despite therapeutic advances, patients with multiple myeloma (MM) continue to experience disease relapse and treatment resistance. The gene ABCB1 encodes the drug transporter P-glycoprotein, which confers resistance through drug extrusion across the cell membrane. Lenalidomide (Len) is excreted mainly via the kidneys, and, given the expression of P-gp in the renal tubuli, single-nucleotide polymorphisms (SNPs) in the ABCB1 gene may influence Len plasma concentrations and, subsequently, the outcome of treatment. We, therefore, investigated the influence of ABCB1 genetic variants on Len treatment outcomes and adverse events (AEs). Methods Ninety patients with relapsed or refractory MM, who received the second-line Len plus dexamethasone in the Rev II trial, were genotyped for the ABCB1 SNPs 1199G amp;gt; A (Ser400Asn, rs2229109), 1236C amp;gt; T (silent, rs1128503), 2677G amp;gt; T/A (Ala893Ser, rs2032582), and 3435C amp;gt; T (silent, rs1045642) using pyrosequencing, and correlations to response parameters, outcomes, and AEs were investigated. Results No significant associations were found between genotype and either best response rates or hematological AEs, and 1236C amp;gt; T, 2677G amp;gt; T or 3435C amp;gt; T genotypes had no impact on survival. There was a trend towards increased time to progression (TTP) in patients carrying the 1199A variant, and a significant difference in TTP between genotypes in patients with standard-risk cytogenetics. Conclusions Our findings show a limited influence of ABCB1 genotype on lenalidomide treatment efficacy and safety. The results suggest that 1199G amp;gt; A may be a marker of TTP following Len treatment in standard-risk patients; however, larger studies are needed to validate and clarify the relationship.
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| 10. |
- Järup, Lars, et al.
(author)
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Low level exposure to cadmium and early kidney damage : The OSCAR study
- 2000
-
In: Occupational and Environmental Medicine. - : BMJ. - 1351-0711 .- 1470-7926. ; 57:10, s. 668-672
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Journal article (peer-reviewed)abstract
- Objectives - To study the dose-response relation between cadmium dose and renal tubular damage in a population of workers and people environmentally or occupationally exposed to low concentrations of cadmium. Methods - Early kidney damage in 1021 people, occuptionally or environmentally exposed to cadmium, was assessed from cadmium in urine to estimate dose, and protein HC (a1-microglobulin) in urine to assess tubular pvoteinuria. Results - There was an age and sex adjusted correlation between cadmium in urine and urinary protein HC. The prevalence of tubular proteinuria ranged from 5% among unexposed people to 50% in the most exposed group. The corresponding prevalence odds ratio was 6.0 (95% confidence interval (95% CI) 1.6 to 22) for the highest exposure group, adjusted for age and sex. Multiple logistic regression analysis showed an increasing prevalence of tubular proteinuria with urinary cadmium as well as with age. After adjusment to the mean age of the study population (53 years), the results show an increased prevalence of 10% tubular proteinuria (taking into account a background prevalence of 5%) at a urinary cadmium concentration of 1.0 nmol/mmol creatinine. Conclusion - Renal tubular damage due to exposure to cadmium develops at lower levels of cadmium body burden than previously anticipated.
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| 11. |
- Kesteris, Uldis, et al.
(author)
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Contamination of polyethylene cups with polymethyl methacrylate particles: an experimental study
- 2001
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In: Journal of Arthroplasty. - : Elsevier BV. - 0883-5403. ; 16:7, s. 905-908
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Journal article (peer-reviewed)abstract
- The articulating surfaces of 6 ultra-high molecular weight polyethylene cups were exposed to curing polymethyl methacrylate (PMMA) bone-cement and examined with scanning electron microscopy and laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS). Three of the cups were exposed to blood and bone-cement, and the rest were exposed to bone-cement only. After removal of the bone-cement bulk, PMMA particles were found and identified in all 6 cups. The particles were verified by identifying zirconium with energy-dispersive x-ray fluorescence spectroscopy in 5 cups and with LA-ICPMS in 1 cup. The degree of surface contamination was estimated with LA-ICPMS. The number of zirconium-containing particles detected was on average 10 to 20/mm2. PMMA bone-cement left in polyethylene cups during polymerization can contaminate the articulating surface with adherent PMMA particles.
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| 12. |
- Lund, Johan, et al.
(author)
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Lenalidomide versus lenalidomide plus dexamethasone prolonged treatment after second-line lenalidomide plus dexamethasone induction in multiple myeloma
- 2018
-
In: Cancer Medicine. - : WILEY. - 2045-7634. ; 7:6, s. 2256-2268
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Journal article (peer-reviewed)abstract
- Lenalidomide (Len) plus dexamethasone (Dex) is approved for the treatment of relapsed or refractory multiple myeloma (RRMM). It is possible that single-agent Len may be effective as prolonged treatment regimen in RRMM once patients demonstrate an initial response to Len+Dex induction. Patients with RRMM who responded to first-line Len+Dex in an observational study (NCT01430546) received up to 24 cycles of either Len (25mg/day) or Len+Dex (25mg/day and 40mg/week) as prolonged treatment in a subsequent phase 2 clinical trial (NCT01450215). In the observational study (N = 133), median time to response was 1.7 (range 0.6-9.6) months. A complete response to all treatments received in both studies was observed in 11% of patients; very good partial response and partial response rates were 31% and 38%, respectively. Corresponding response rates in the subgroup of patients who did not enter the phase 2 trial (n = 71) were 3%, 18%, and 39%, respectively. Rates of disease progression at 2years in the phase 2 trial were 47% versus 31% for Len versus Len+Dex (P = 0.14). After 36months median follow-up in surviving patients, median time to progression was not reached with Len+Dex and was 24.9months (95% confidence interval 12.5-not calculable, P amp;lt; 0.001) with Len. Three-year OS among the total observational study population was 61% (95% CI, 52-69%). The corresponding rate among patients who entered the phase 2 clinical trial was 73% (95% CI, 60-83%) and was significantly lower among those patients who achieved PR but did not proceed into the phase 2 trial (55%; P = 0.01). In the phase 2 trial, OS was 73% in both treatment arms (P = 0.70). Neutropenia and thrombocytopenia were more common with prolonged (phase 2 trial) versus short-term (observational study) Len administration but remained manageable. Prolonged treatment with Len with or without Dex provides sustained, clinically relevant responses and demonstrates an acceptable safety profile.
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| 13. |
- Persborn, Mats, et al.
(author)
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Effects of probiotics (Ecologic 825) on barrier function during maintenance treatment for severe pouchitis
-
Other publication (other academic/artistic)abstract
- Background : About 10-15% of patients with an ileoanal pouch develop a severe, form of pouchitis that necessitates long and/or frequent use of antibiotics and in rare cases even pouch excision. Probiotics have been shown to reduce the risk of recurrence after induction treatment with antibiotics. The mechanisms behind the positive effects of probiotics are not fully understood. The aim of our study was to examine the mucosal barrier function in relation to pouchitis, before and after treatment with probiotics. Methods: 16 patients with a history of severe pouchitis underwent endoscopy with biopsies of the pouch on three occasions: Once during active pouchitis, second after 4 weeks of treatment with antibiotics until clinical remission and third after eight weeks of probiotic treatment. 13 controls with an ileoanal pouch with no recent history of pouchitis were used. The biopsies were mounted in Ussing chambers and mucosal barrier function was assessed by electrophysiology, transmucosal uptake of E coli K12, permeability to Cr-EDTA and Horseradish peroxidase (HRP). Pouchitis Disease Activity Index (PDAI) was used in all subjects. Results: PDAI was significantly improved after treatment with antibiotics and probiotics. There was a significant difference in E. coli K12 passage before treatment compared to controls (3.7 units (3.4-8.5) vs 1.7 units (1.0-2.4) p< 0.01). E. coli K12 passage did not change after antibiotic treatment (5.0 units (3.3-7.1) p = ns vs controls). In contrast a significant reduction in bacterial uptake was seen after probiotics (2.2 units (1.8-3.3) p< 0.05). Likewise, a significant normalization of HRP flux was seen after probiotic treatment. Pouchitis did not affect paracellular permability or electrophysiology. Conclusion: Probiotic treatment restored the increased permeation to E. coli and HRP in patients with chronic pouchitis. This could be an important factor behind the positive effects of probiotics in patients with chronic pouchitis.
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| 14. |
- Persborn, Mats, et al.
(author)
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The effects of probiotics on barrier function and mucosal pouch microbiota during maintenance treatment for severe pouchitis in patients with ulcerative colitis
- 2013
-
In: Alimentary Pharmacology and Therapeutics. - : Wiley-Blackwell. - 0269-2813 .- 1365-2036. ; 38:7, s. 772-783
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Journal article (peer-reviewed)abstract
- Background less thanbrgreater than less thanbrgreater thanA total of 10-15% of patients with an ileoanal pouch develop severe pouchitis necessitating long-term use of antibiotics or pouch excision. Probiotics reduce the risk of recurrence of pouchitis, but mechanisms behind these effects are not fully understood. less thanbrgreater than less thanbrgreater thanAim less thanbrgreater than less thanbrgreater thanTo examine mucosal barrier function in pouchitis, before and after probiotic supplementation and to assess composition of mucosal pouch microbiota. less thanbrgreater than less thanbrgreater thanMethods less thanbrgreater than less thanbrgreater thanSixteen patients with severe pouchitis underwent endoscopy with biopsies of the pouch on three occasions: during active pouchitis; clinical remission by 4 weeks of antibiotics; after 8 weeks of subsequent probiotic supplementation (Ecologic 825, Winclove, Amsterdam, the Netherlands). Thirteen individuals with a healthy ileoanal pouch were sampled once as controls. Ussing chambers were used to assess transmucosal passage of Escherichia coli K12, permeability to horseradish peroxidase (HRP) and Cr-51-EDTA. Composition and diversity of the microbiota was analysed using Human Intestinal Tract Chip. less thanbrgreater than less thanbrgreater thanResults less thanbrgreater than less thanbrgreater thanPouchitis Disease Activity Index (PDAI) was significantly improved after antibiotic and probiotic supplementation. Escherichia coli K12 passage during active pouchitis [3.7 (3.4-8.5); median (IQR)] was significantly higher than in controls [1.7 (1.0-2.4); P andlt; 0.01], did not change after antibiotic treatment [5.0 (3.3-7.1); P = ns], but was significantly reduced after subsequent probiotic supplementation [2.2 (1.7-3.3); P andlt; 0.05]. No significant effects of antibiotics or probiotics were observed on composition of mucosal pouch microbiota; however, E. coli passage correlated with bacterial diversity (r = -0.40; P = 0.018). Microbial groups belonging to Bacteroidetes and Clostridium clusters IX, XI and XIVa were associated with healthy pouches. less thanbrgreater than less thanbrgreater thanConclusions less thanbrgreater than less thanbrgreater thanProbiotics restored the mucosal barrier to E. coli and HRP in patients with pouchitis, a feasible factor in prevention of recurrence during maintenance treatment. Restored barrier function did not translate into significant changes in mucosal microbiota composition, but bacterial diversity correlated with barrier function.
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