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- Bodén, Ida, 1977-
(author)
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Near infrared and skin impedance spectroscopic in vivo measurements on human skin : development of a diagnostic tool for skin cancer
- 2011
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Doctoral thesis (other academic/artistic)abstract
- Every year approximately 2800 Swedes are diagnosed with malignant melanoma, the form of cancer that is most rapidly increasing in incidence in the Western world. The earlier we can identify and diagnose a malignant melanoma, the better is the prognosis. In Sweden, 155 000 benign naevi, harmless skin tumours or moles, are surgically excised each year, many of them because melanoma cannot be dismissed by non-invasive methods. The excisions result in substantial medical costs and cause unrest and suffering of the individual patient. For untrained physicians, it is often difficult to make an accurate diagnosis of melanoma, thus a tool that could help to strengthen the diagnosis of suspected melanomas would be highly valuable. This thesis describes the development and assessment of a non-invasive method for early skin cancer detection. Using near infrared (NIR) and skin impedance spectroscopy, healthy and diseased skin of various subjects was examined to develop a new instrument for detecting malignant melanoma. Due to the complex nature of skin and the numerous variables involved, the spectroscopic data were analysed multivariately using Principal Component Analysis (PCA) and partial leas square discriminant analysis (PLS-DA). The reproducibility of the measurements was determined by calculating Scatter Values (SVs), and the significance of separations between overlapping groups in score plots was determined by calculating intra-model distances. The studies indicate that combining skin impedance and NIR spectroscopy measurements adds value, therefore a new probe-head for simultaneous NIR and skin impedance measurements was introduced. Using both spectroscopic techniques it was possible to separate healthy skin at one body location from healthy skin at another location due to the differences in skin characteristics at various body locations. In addition, statistically significant differences between overlapping groups of both age and gender in score plots were detected. However, the differences in skin characteristics at different body locations had stronger effects on the measurements than both age and gender. Intake of coffee and alcohol prior to measurement did not significantly influence the outcome data. Measurements on dysplastic naevi were significantly separated in a score plot and the influence of diseased skin was stronger than that of body location. This was confirmed in a study where measurements were performed on 12 malignant melanomas, 19 dysplastic naevi and 19 benign naevi. The malignant melanomas were significantly separated from both dysplastic naevi and benign naevi. Overall, the presented findings show that the instrument we have developed provides fast, reproducible measurements, capable of distinguishing malignant melanoma from dysplastic naevi and benign naevi non-invasively with 83% sensitivity and 95% specificity. Thus, the results are highly promising and the instrument appears to have high potential diagnostic utility.
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- Delaine, Tamara, 1981, et al.
(author)
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A structure activity relationship study of geranial derivatives
- 2012
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In: Contact Dermatitis 11th congress of the European society of contact dermatitis (ESCD) 13-16 june 2012, Malmö, Sweden. - : Wiley. ; 66:Suppl. 2
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Conference paper (peer-reviewed)abstract
- Background: Fragrances are common causes of contact allergy. Skin exposure to geranial is frequent since citral (mixture of geranial and neral) is commonly used in fragrances and flavors and is considered as a moderate allergen. Previous studies according to the local lymphnodeassay (LLNA)in micehaverevealed large variations in the sensitizing capacity of different geranial derivatives. Objectives: For a better understanding of these variations, a structure-activity relationship (SAR) study on a series of derivatives of geranial was carried out. Methods: The chemical reactivity of the compounds towards a model peptide was investigated using LC-MS. The adduct formation and the non-reacted peptide depletion were monitored. Adducts formed with model amino acids were investigated and structural determination was performed. Additional derivatives were synthesized and their sensitization potencies were evaluated in relation to their physicochemical and reactivity properties. Results: Most of the derivatives were shown to bind covalently to the cysteine residue of the model peptide. The percentage of depletion of the non-reacted peptide ranged from 0% to 100% after 24 hr, constant rate of depletion revealed a large difference between the fastest and lowest reacting derivatives. These resultswere congruent with the skin sensitization potencies obtained with the LLNA. Conclusions: A good correlation between the reactivity and the sensitizing potency was observed. Small changes in the chemical structure of geranial result in significant differences in sensitizing capacity and chemical reactivity. Conflicts of interest: The authors have declared no conflicts.
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- Delaine, Tamara, 1981, et al.
(author)
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Epoxyalcohols: bioactivation and conjugation required for skin sensitization.
- 2014
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In: Chemical research in toxicology. - : American Chemical Society (ACS). - 1520-5010 .- 0893-228X. ; 27:10, s. 1860-70
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Journal article (peer-reviewed)abstract
- Allylic alcohols, such as geraniol 1, are easily oxidized by varying mechanisms, including the formation of both 2,3-epoxides and/or aldehydes. These epoxides, aldehydes, and epoxy-aldehydes can be interconverted to each other, and the reactivity of them all must be considered when considering the sensitization potential of the parent allylic alcohol. An in-depth study of the possible metabolites and autoxidation products of allylic alcohols is described, covering the formation, interconversion, reactivity, and sensitizing potential thereof, using a combination of in vivo, in vitro, in chemico, and in silico methods. This multimodal study, using the integration of diverse techniques to investigate the sensitization potential of a molecule, allows the identification of potential candidate(s) for the true culprit(s) in allergic responses to allylic alcohols. Overall, the sensitization potential of the investigated epoxyalcohols and unsaturated alcohols was found to derive from metabolic oxidation to the more potent aldehyde where possible. Where this is less likely, the compound remains weakly or nonsensitizing. Metabolic activation of a double bond to form a nonconjugated, nonterminal epoxide moiety is not enough to turn a nonsensitizing alcohol into a sensitizer, as such epoxides have low reactivity and low sensitizing potency. In addition, even an allylic 2,3-epoxide moiety is not necessarily a potent sensitizer, as shown for 2, where formation of the epoxide weakens the sensitization potential.
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- Delaine, Tamara, 1981, et al.
(author)
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Structure-Activity Relationship between the in Vivo Skin Sensitizing Potency of Analogues of Phenyl Glycidyl Ether and the Induction of Nrf2-Dependent Luciferase Activity in the KeratinoSens in Vitro Assay.
- 2011
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In: Chemical research in toxicology. - : American Chemical Society (ACS). - 1520-5010 .- 0893-228X. ; 24:8, s. 1312-8
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Journal article (peer-reviewed)abstract
- Because of regulatory constraints and ethical considerations, research on alternatives to animal testing to predict the skin sensitization potential of novel chemicals has become a high priority. Ideally, these alternatives should not only predict the hazard of novel chemicals but also rate the potency of skin sensitizers. Currently, no alternative method gives reliable potency estimations for a wide range of chemicals in differing structural classes. Performing potency estimations within specific structural classes has thus been proposed. Detailed structure-activity studies for the in vivo sensitization capacity of a series of analogues of phenyl glycidyl ether (PGE) were recently published. These studies are part of an investigation regarding the allergenic activity of epoxy-resin monomers. Here we report data on the same chemicals in the KeratinoSens in vitro assay, which is based on a stable transgenic keratinocyte cell line with a luciferase gene under the control of an antioxidant response element. A strong correlation between the EC3 values in the local lymph node assay (LLNA) and both the luciferase-inducing concentrations and the cytotoxicity in the cell-based assay was established for six analogues of PGE. This correlation allowed the potency in the LLNA of two novel structurally closely related derivatives to be predicted by read-across with errors of 1.4- and 2.6-fold. However, the LLNA EC3 values of two structurally different bifunctional monomers were overpredicted on the basis of this data set, indicating that accurate potency estimation by read-across based on in vitro data might be restricted to a relatively narrow applicability domain.
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- Ericsson, Olle, et al.
(author)
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Clinical validation of a novel automated cell-free DNA screening assay for trisomies 21, 13, and 18 in maternal plasma.
- 2019
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In: Prenatal diagnosis. - : Wiley. - 1097-0223 .- 0197-3851. ; 39:11, s. 1011-1015
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Journal article (peer-reviewed)abstract
- To evaluate clinical performance of a new automated cell-free (cf)DNA assay in maternal plasma screening for trisomies 21, 18, and 13, and to determine fetal sex.Maternal plasma samples from 1200 singleton pregnancies were analyzed with a new non-sequencing cfDNA method, which is based on imaging and counting specific chromosome targets. Reference outcomes were determined by either cytogenetic testing, of amniotic fluid or chorionic villi, or clinical examination of neonates.The samples examined included 158 fetal aneuploidies. Sensitivity was 100% (112/112) for trisomy 21, 89% (32/36) for trisomy 18, and 100% (10/10) for trisomy 13. The respective specificities were 100%, 99.5%, and 99.9%. There were five first pass failures (0.4%), all in unaffected pregnancies. Sex classification was performed on 979 of the samples and 99.6% (975/979) provided a concordant result.The new automated cfDNA assay has high sensitivity and specificity for trisomies 21, 18, and 13 and accurate classification of fetal sex, while maintaining a low failure rate. The study demonstrated that cfDNA testing can be simplified and automated to reduce cost and thereby enabling wider population-based screening.
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| 7. |
- Hagvall, Lina, 1978, et al.
(author)
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Assessment of cross-reactivity of new less sensitizing epoxy resin monomers in epoxy resin-allergic individuals
- 2016
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In: Contact Dermatitis. - : Wiley. - 0105-1873. ; 75:3, s. 144-150
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Journal article (peer-reviewed)abstract
- BackgroundMeasures to prevent occupational exposure to epoxy resins, including education, medical examination, and voluntary agreements between employers and workers, have not been effective enough to protect against skin sensitization. Therefore, alternatives to the major epoxy resin haptens that have been found to be less sensitizing in the local lymph node assay have been developed. ObjectivesTo study the cross-reactivity of two newly designed epoxy resin monomers, with decreased skin-sensitizing potency and good technical properties as compared with diglycidyl ether of bisphenol A (DGEBA), in subjects with known contact allergy to epoxy resin of DGEBA type. Patients and MethodsEleven individuals with previous positive patch test reactions to epoxy resin of DGEBA participated in the study. The two alternative epoxy resin monomers were synthesized and patch tested in dilution series in parallel with epoxy resin of DGEBA from the baseline series (containing 92% DGEBA). ResultsAll participants reacted to epoxy resin of DGEBA on retesting. Three participants reacted to monomer 1. No reactions were seen to monomer 2. ConclusionsThe alternative monomers studied showed little or no cross-reactivity with epoxy resin of DGEBA. Decreasing the risk of sensitization by using less sensitizing compounds is important, as contact allergy to epoxy resins is common in spite of thorough preventive measures.
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| 8. |
- Hagvall, Lina, 1978, et al.
(author)
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Can the epoxides of cinnamyl alcohol and cinnamal show new cases of contact allergy?
- 2018
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In: Contact dermatitis. - : Wiley. - 1600-0536 .- 0105-1873. ; 78:6, s. 399-405
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Journal article (peer-reviewed)abstract
- Cinnamyl alcohol is considered to be a prohapten and prehapten with cinnamal as the main metabolite. However, many individuals who are allergic to cinnamyl alcohol do not react to cinnamal. Sensitizing epoxides of cinnamyl alcohol and cinnamal have been identified as metabolites and autoxidation products of cinnamyl alcohol.To investigate the clinical relevance of contact allergy to epoxycinnamyl alcohol and epoxycinnamal.Irritative effects of the epoxides were investigated in 12 dermatitis patients. Epoxycinnamyl alcohol and epoxycinnamal were patch tested in 393 and 390 consecutive patients, respectively. In parallel, cinnamyl alcohol and cinnamal were patch tested in 607 and 616 patients, respectively.Both epoxides were irritants, but no more positive reactions were detected than when testing was performed with cinnamyl alcohol and cinnamal. Late allergic reactions to epoxycinnamyl alcohol were observed. In general, patients with late reactions showed doubtful or positive reactions to cinnamal and fragrance mix I at regular patch testing.The investigated epoxides are not important haptens in contact allergy to cinnamon fragrance. The high frequency of fragrance allergy among patients included in the irritancy study showed the difficulty of suspecting fragrance allergy on the basis of history; patch testing broadly with fragrance compounds is therefore important.
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| 9. |
- Karlsson, Isabella, et al.
(author)
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Nature-Derived Epoxy Resin Monomers with Reduced Sensitizing Capacity-Isosorbide-Based Bis-Epoxides
- 2023
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In: Chemical Research in Toxicology. - : American Chemical Society (ACS). - 0893-228X .- 1520-5010. ; 36:2, s. 281-290
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Journal article (peer-reviewed)abstract
- Epoxy resin systems (ERSs) are a class of thermosetting resins that become thermostable and insoluble polymers upon curing. They are widely used as components of protective surfaces, adhesives, and paints and in the manufacturing of composites in the plastics industry. The diglycidyl ether of bisphenol A (DGEBA) is used in 75-90% of ERSs and is thus by far the most used epoxy resin monomer (ERM). Unfortunately, DGEBA is a strong skin sensitizer and it is one of the most common causes of occupational contact dermatitis. Furthermore, DGEBA is synthesized from bisphenol A (BPA), which is a petroleum-derived chemical with endocrine-disruptive properties. In this work, we have used isosorbide, a renewable and nontoxic sugar-based material, as an alternative to BPA in the design of ERMs. Three different bisepoxide isosorbide derivatives were synthesized: the diglycidyl ether of isosorbide (1) and two novel isosorbide-based bis-epoxides containing either a benzoic ester (2) or a benzyl ether linkage (3). Assessment of the in vivo sensitizing potency of the isosorbide bis-epoxides in the murine local lymph node assay (LLNA) showed that all three compounds were significantly less sensitizing than DGEBA, especially 2 which was nonsensitizing up to 25% w/v. The peptide reactivity showed the same order of reactivity as the LLNA, i.e., 2 being the least reactive, followed by 3 and then 1, which displayed similar peptide reactivity as DGEBA. Skin permeation of 2 and 3 was compared to DGEBA using ex vivo pig skin and static Franz cells. The preliminary investigations of the technical properties of the polymers formed from 1-3 were promising. Although further investigations of the technical properties are needed, all isosorbide bis-epoxides have the potential to be less sensitizing renewable replacements of DGEBA, especially 2 that had the lowest sensitizing potency in vivo as well as the lowest peptide reactivity.
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