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Årstrand, Kerstin
Publications (10 of 12) Show all publications
Nezirevic Dernroth, D., Årstrand, K., Greco, G., Panzella, L., Napolitano, A. & Kågedal, B. (2010). Pheomelanin-related benzothiazole isomers in the urine of patients with diffuse melanosis of melanoma. Clinica Chimica Acta, 411(17-18), 1195-1203
Open this publication in new window or tab >>Pheomelanin-related benzothiazole isomers in the urine of patients with diffuse melanosis of melanoma
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2010 (English)In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 411, no 17-18, p. 1195-1203Article in journal (Refereed) Published
Abstract [en]

Currently used as structural markers for pheomelanin identification and quantitation, benzothiazole compounds derived from isomeric cysteinyldopas have been indicated by recent in vitro studies as new potential pheomelanogenesis intermediates. Prompted by previous reports on the occurrence of large amounts of 5-S-cysteinyldopa (5-S-CD) and trichochromes in urine of patient with diffuse melanosis of melanoma we investigated the presence of benzothiazole compounds in the urine of these patients.

Hydrophilic interaction liquid chromatography on zwitterionic stationary phase (ZIC-HILIC) and photo-diode array (PDA) detection was used for analysis of 6-(2-amino-2-carboxyethyl)-4-hydroxybenzothiazole-2-carboxylic acid (BTCA-5), and 7-(2-amino-2-carboxyethyl)-4-hydroxybenzothiazole-2-carboxylic acid (BTCA-2), derived from 5-S-CD and 2-S-cysteinyldopa (2-S-CD) isomers, respectively. Isocratic mobile phase with minimal sample preparation allowed efficient separation of the compounds, which were safely identified by their typical absorption features.

Among 21 melanoma patients examined three showed diffuse melanosis. The levels of urinary BTCAs were found to be highly associated with melanosis but more loosely to excreted 5-S-CD. Analysis of the pigmented fraction of urine following alkaline hydrogen peroxide degradation and quantitation of BTCAs provided evidence for the presence of pheomelanins at higher levels in patients with melanosis.

Place, publisher, year, edition, pages
lsevier Science B.V., Amsterdam, 2010
Keywords
Benzothiazole, benzothiazole-2-carboxylic acids, diffuse melanosis, melanoma, HILIC, pheomelanin, BTCA
National Category
Other Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-21817 (URN)10.1016/j.cca.2010.04.019 (DOI)000280033400005 ()
Available from: 2009-10-05 Created: 2009-10-05 Last updated: 2017-12-13Bibliographically approved
Nord, M., Zsigmond, P., Kullman, A., Årstrand, K. & Dizdar (Dizdar Segrell), N. (2010). The Effect of Peripheral Enzyme Inhibitors on Levodopa Concentrations in Blood and CSF. Movement Disorders, 25(3), 363-367
Open this publication in new window or tab >>The Effect of Peripheral Enzyme Inhibitors on Levodopa Concentrations in Blood and CSF
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2010 (English)In: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 25, no 3, p. 363-367Article in journal (Refereed) Published
Abstract [en]

Levodopa combined with a dopa-decarboxylase inhibitor, such as carbidopa. shifts the metabolism to the COMT pathway. Adding the peripheral acting COMT inhibitor entacapone provides improvement for patients with PD suffering from motor fluctuations. We studied the effects of the enzyme inhibitors entacapone and carbidopa on the levodopa concentrations in CSF and in blood. Five PD patients with wearing-off underwent lumbar drainage and intravenous microdialysis. Samples were taken 12 h daily for 3 days. Day I; intravenous levodopa was given, day 2; additional oral entacapone 200 mg tid, day 3; additional oral entacapone 200 mg bid and carbidopa 25 mg bid. Levodopa in CSF and in dialysates was analysed. The AUC for levodopa increased both in blood and CSF when additional entacapone was given alone and in combination with carbidopa. The C-max of levodopa in both CSF and blood increased significantly. Additional entacapone to levodopa therapy gives an increase of C-max in CSF and in blood. The increase is more evident when entacapone is combined with carbidopa.

Place, publisher, year, edition, pages
John Wiley & Sons, 2010
Keywords
Parkinsons Disease, levodopa, continuous infusion, COMT
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-54855 (URN)10.1002/mds.22613 (DOI)000276136900016 ()
Available from: 2010-04-16 Created: 2010-04-16 Last updated: 2018-01-12
Nezirevic Dernroth, D., Årstrand, K. & Kågedal, B. (2007). Hydrophilic interaction liquid chromatographic analysis of aminohydroxyphenylalanines from melanin pigments. Journal of Chromatography A, 1163(1-2), 70-79
Open this publication in new window or tab >>Hydrophilic interaction liquid chromatographic analysis of aminohydroxyphenylalanines from melanin pigments
2007 (English)In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1163, no 1-2, p. 70-79Article in journal (Refereed) Published
Abstract [en]

Malignant melanomas are more often seen in subjects with light colored skin who tan poorly than in persons who tan more rapidly. This has been attributed to the structure of their pigment, pheomelanin, which differs markedly from the eumelanin of persons with darker skin. To study the hydrolysis products of pheomelanin pigments a new method was developed for analysis of 4-amino-3-hydroxyphenylalanine (4-AHP) and 3-amino-4-hydroxyphenylalanine (3-AHP). Pheomelanin samples were hydrolyzed and extracted with solid-phase extraction columns using strong cation-exchange (SCX) cartridges. Separation of 4-AHP and 3-AHP was achieved on a ZIC-HILIC column (150 mm × 2.1 mm I.D.) with a mobile phase consisting of acetonitrile:0.1 M ammonium acetate buffer, pH 4.5 (82:18, v/v). Detection was performed with an electrochemical detector at +400 mV. Run time was 30 min. The limits of detection were 73 pg and 51 pg for 4-AHP and 3-AHP respectively, using 2 μl injections. Good linearity was found within the range 0.05-5.0 μg/ml. Absolute recovery was 70% and relative recovery was 100%. The AHPs were stable for 1 year in the hydrolyzed samples, for 4 days in the eluates from solid-phase sorbents stored in the refrigerator, and for 2 days diluted with mobile phase and stored in the autosampler at 10 °C. The within-day imprecision was <5% and the between-day imprecision was <7% for the two analytes. The method, applied to the analysis of pheomelanin in urine from human melanoma patients, allows the analysis of 30 samples in one set and is suitable for routine work with human hair and melanoma cells. By using the ZIC-HILIC stationary phase, ion-pairing reagents could be avoided, which makes the method suitable to further analysis of degradation products from pheomelanins using mass spectrometric detection. © 2007 Elsevier B.V. All rights reserved.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-39471 (URN)10.1016/j.chroma.2007.06.007 (DOI)48765 (Local ID)48765 (Archive number)48765 (OAI)
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13Bibliographically approved
Årstrand, K., Kullman, A., Andersson, R., Rasmuson, T. & Kågedal, B. (2004). Improved method for analysis of cysteinyldopa in human serum. Scandinavian Journal of Clinical and Laboratory Investigation, 64(6), 559-564
Open this publication in new window or tab >>Improved method for analysis of cysteinyldopa in human serum
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2004 (English)In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 64, no 6, p. 559-564Article in journal (Refereed) Published
Abstract [en]

5-S-L-Cysteinyl-L-dopa is a well-known pigment intermediate and analysis of its serum concentration is well suited for evaluation of treatment and follow-up of stage III and IV malignant melanoma. A simplified analytical method is described using organic extraction followed by clean-up on a boronate gel to capture the compound containing vicinal hydroxyls. Weak acid solution elutes the 5-S-cysteinyldopa suitable for high-performance liquid chromatography (HPLC). The absolute recoveries of cysteinyldopa and its diastereomer 5-S-D-cysteinyl-L-dopa (used as an internal standard) were 81.5±2.8% and 81.3±2.7%, respectively, and use of the internal standard for the whole procedure gave an analytical recovery of 101±0.8%. The limit of quantitation was 1.5 nmol/L and the imprecision of the method was < 5.0% over the analytical range 1.5-500 nmol/L. The method is cheap and easy to perform and compares well with other described techniques. The use of the method is illustrated by results obtained during treatment of a patient with metastatic malignant melanoma.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-23708 (URN)10.1080/00365510410007026 (DOI)3211 (Local ID)3211 (Archive number)3211 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13
Takasaki, A., Nezirevic Dernroth, D., Årstrand, K., Wakamatsu, K., Ito, S. & Kågedal, B. (2003). HPLC analysis of pheomelanin degradation products in human urine. Pigment Cell Research, 16(5), 480-486
Open this publication in new window or tab >>HPLC analysis of pheomelanin degradation products in human urine
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2003 (English)In: Pigment Cell Research, ISSN 1755-1471, E-ISSN 1755-148X, Vol. 16, no 5, p. 480-486Article in journal (Refereed) Published
Abstract [en]

A sensitive and specific high performance liquid chromatography (HPLC) method was developed to quantify 4-amino-3-hydroxyphenylalanine (4-AHP) and 3-amino-4-hydroxyphenylalanine (3-AHP) in urine. In degradation studies of melanin pigment, 4-AHP and 3-AHP are derived from benzothiazine units of pheomelanin and pheomelanin-related metabolites such as trichochromes. 5-S-Cysteinyldopa-derived benzothiazine products give 4-AHP while 2-S-cysteinyldopa-derived benzothiazine products give 3-AHP. 3-AHP is also derived from nitrotyrosine formed by nitration of tyrosine with reactive nitrogen species. For this reason, the influence of this biological process on the amount of 3-AHP found in biological material have been investigated. The method is based on hydriodic acid hydrolysis of the melanin polymer and reversed-phase HPLC with electrochemical detection of the degradation products 4-AHP and 3-AHP. The mobile phase consists of 25 mM ammonium acetate and sodium octanesulfonate as an ion-pairing reagent. The 4-AHP and 3-AHP peaks were well separated and the detector response was linear within the range 0-2 ng injected for both compounds. With the developed chromatographic system, 4-AHP and 3-AHP showed good separation in the biological samples. There was a strong correlation between 4-AHP and 3-AHP in the urine of 50 malignant melanoma patients and two healthy subjects (R0.977). The two compounds were also strongly correlated with 5-S-cysteinyldopa in urine, the correlation coefficients being 0.862 and 0.907, respectively. The method described is sensitive enough for analysis of pheomelanin in urine and in several other biological samples. The results indicate that 3-AHP in urine is not influenced by excreted 3-nitrotyrosine and the data indicate that pheomelanins are excreted in the urine of melanoma patients.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-21494 (URN)10.1034/j.1600-0749.2003.00086.x (DOI)12950724 (PubMedID)
Available from: 2009-10-02 Created: 2009-10-02 Last updated: 2017-12-13Bibliographically approved
Dizdar (Dizdar Segrell), N., Årstrand, K. & Kågedal, B. (2002). Analysis of L-dopa in human serum. BioTechniques, 33(5), 1000-1002
Open this publication in new window or tab >>Analysis of L-dopa in human serum
2002 (English)In: BioTechniques, ISSN 0736-6205, E-ISSN 1940-9818, Vol. 33, no 5, p. 1000-1002Article in journal (Refereed) Published
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-24989 (URN)9408 (Local ID)9408 (Archive number)9408 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2018-01-12
Johansson, M., Takasaki, A., Lenner, L., Årstrand, K. & Kågedal, B. (2002). Quantitative relationships between pigment-related mRNA and biochemical melanoma markers in melanoma cell lines. Melanoma research, 12(3), 193-200
Open this publication in new window or tab >>Quantitative relationships between pigment-related mRNA and biochemical melanoma markers in melanoma cell lines
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2002 (English)In: Melanoma research, ISSN 0960-8931, E-ISSN 1473-5636, Vol. 12, no 3, p. 193-200Article in journal (Refereed) Published
Abstract [en]

The use of reverse transcription polymerase chain reaction (RT-PCR) analysis of melanoma-specific transcripts for the identification of circulating melanoma cells has shown very variable results in different studies on melanoma patients. We have therefore developed quantitative methods to study both analytical and biological variations as possible causes of this phenomenon. Pigment-related and S-100β transcripts were quantified in 12 different melanoma cell lines and related to the amounts of 5-S-cysteinyldopa, pigment and S-100B protein. A real-time PCR method was used and the results were expressed as absolute number of transcripts per cell. Tyrosinase, tyrosinase-related protein (TRP)-1, TRP-2 and MART-1/Melan-A mRNA varied from undetectable (< 10-4 transcripts/cell) to 103 transcripts/cell, i.e. by a factor > 107 in the different cell lines. S-100β mRNA varied from 2.8 to 165 transcripts/cell, i.e. by a factor of 60. Tyrosinase, TRP-1 and TRP-2 mRNA correlated significantly with the amount of 5-S-cysteinyldopa, an intermediate pigment metabolite (P < 0.001, P < 0.001 and P < 0.01, respectively). The amount of S-100β mRNA correlated significantly with the amount of S-100B protein (P < 0.001). No cross-correlations were seen between the pigment-related and S-100-related analytes. We conclude that one reason behind the negative results of RT-PCR measurement of pigment-related mRNA may be that these transcripts are not always expressed in the particular cells present in the patient's blood. Furthermore, variation in the expression of the order of 107 must have great impact on the diagnostic sensitivity. Measurement of S-100β mRNA would be more sensitive, but the use of this transcript is hampered by its presence in the blood cells. © 2002 Lippincott Williams & Wilkins.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25118 (URN)10.1097/00008390-200206000-00002 (DOI)12140375 (PubMedID)9551 (Local ID)9551 (Archive number)9551 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13
Johansson, M., Årstrand, K., Håkansson, A., Lindholm, C. & Kågedal, B. (2000). Quantitative analysis of tyrosinase and tyrosinase-related protein-2 mRNA from melanoma cells in blood by real-time polymerase chain reaction. Melanoma research, 10(3), 213-222
Open this publication in new window or tab >>Quantitative analysis of tyrosinase and tyrosinase-related protein-2 mRNA from melanoma cells in blood by real-time polymerase chain reaction
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2000 (English)In: Melanoma research, ISSN 0960-8931, E-ISSN 1473-5636, Vol. 10, no 3, p. 213-222Article in journal (Refereed) Published
Abstract [en]

Several studies have evaluated the use of polymerase chain reaction (PCR) amplification of tyrosinase mRNA to detect melanoma cells in blood. However, contradictory results have been obtained from different groups. We therefore have developed and validated a quantitative PCR method for tyrosinase and tyrosinase-related protein-2 (TRP-2) mRNA. An important methodological finding was that high concentrations of reverse transcriptase or RNA sample inhibited the following PCR. This could be abolished by dilution of the cDNA sample before the PCR. Standard curves with a linear range over at least five logs were obtained with dilutions of melanoma cell cDNA. Controls (RNA and cDNA) consisting of melanoma cells (1000/ml) added to blood were analysed repeatedly over 3 months, resulting in means between 880 and 1074 AU/ml. The RNA controls were stable, whereas the cDNA controls, as well as the calibrators, showed a tendency to change over time. The variation in the RNA controls was 25% for tyrosinase and 22% for TRP-2. Seven stage III-IV melanoma patients were tested for tyrosinase and TRP-2 transcripts in blood drawn from a peripheral vein and from a Port-a-cath. Tyrosinase mRNA was found in three patients (0.8-12.4 AU/ml). For TRP-2, the same amount was found in the patients as in healthy donors. No differences were seen between blood from a peripheral vein and from the Port-a-cath. We here present fast and sensitive methods for the quantification of tyrosinase and TRP-2 mRNA in blood.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25089 (URN)10890374 (PubMedID)9520 (Local ID)9520 (Archive number)9520 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13
Johansson, M., Pisa, E., Törmänen, V., Årstrand, K. & Kågedal, B. (2000). Quantitative analysis of tyrosinase transcripts in blood. Clinical Chemistry, 46(7), 921-927
Open this publication in new window or tab >>Quantitative analysis of tyrosinase transcripts in blood
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2000 (English)In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 46, no 7, p. 921-927Article in journal (Refereed) Published
Abstract [en]

Background: Tyrosinase is an enzyme unique to pigment-forming cells. Methods using this transcript for detection of melanoma cells in blood have given divergent results. Quantitative analytical procedures are therefore needed to study the analytical performance of the methods.

Methods: Mononucleated cells were isolated by Percoll centrifugation. RNA was isolated by each of three methods: UltraspecTM-II RNA isolation system, FastRNATM GREEN Kit, and QIAamp RNA Blood Mini Kit. cDNA was synthesized using random hexamer primers. A tyrosinase-specific product of 207 bp was amplified by PCR. As an internal standard (and competitor) we used a 207-bp cDNA with a base sequence identical to the tyrosinase target except for a 20-bp probe-binding region. The PCR products were identified by 2,4-dinitrophenol (DNP)-labeled probes specific for tyrosinase (5′DNP-GGGGAGCCTTGGGGTTCTGG-3′) and internal standard (5′DNP-CGGAGCCCCGAAACCACATC-3′) and quantified by ELISA.

Results: The calibration curves were linear and had a broad dynamic measuring range. A detection limit (2 SD above zero) of 48 transcripts/mL of blood was obtained from a low control. The analytical imprecision was 50% and 48% at concentrations of 1775 and 17 929 transcripts/mL (n = 12 and 14, respectively). With the cell line SK-Mel 28 added to blood and RNA extracted with the Ultraspec, Fast RNA, and QIAamp RNA methods, we found (mean ± SD) 1716 ± 1341, 2670 ± 3174, and 24 320 ± 5332 transcripts/mL of blood. Corresponding values were 527 ± 497, 2497 ± 1033, 14 930 ± 1927 transcripts/mL of blood when the cell line JKM86-4 was added. One high-risk patient was followed by repeated analysis of tyrosinase transcripts in blood. The melanoma marker 5-S-cysteinyldopa in serum and urine was within reference values, but tyrosinase mRNA was slightly increased (120–168 transcripts/mL of blood). The tyrosinase mRNA increased to 1860 transcripts/mL concomitant with the increase in 5-S-cysteinyldopa; later a spleen metastasis was found.

Conclusions: The results obtained with different RNA extraction methods illustrate the importance of quantitative methods for validation of methods. The use of QIAamp RNA improved the extraction efficiency considerably. Data from a case study suggest the assay is suitable in the follow-up of patients with high risk of developing metastases.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25119 (URN)9552 (Local ID)9552 (Archive number)9552 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13
Kärnell, R., Kågedal, B., Lindholm, C., Nilsson, B., Årstrand, K. & Ringborg, U. (2000). The value of cysteinyldopa in the follow-up of disseminated malignant melanoma. Melanoma research, 10(4), 363-369
Open this publication in new window or tab >>The value of cysteinyldopa in the follow-up of disseminated malignant melanoma
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2000 (English)In: Melanoma research, ISSN 0960-8931, E-ISSN 1473-5636, Vol. 10, no 4, p. 363-369Article in journal (Refereed) Published
Abstract [en]

In a series of 92 patients with malignant melanoma, clinical stage III or IV, both 5-S-cysteinyldopa (5SCD) and 6-hydroxy-5-methoxyindole-2-carboxylic acid (6H5MI2C) were measured in urine during chemotherapy. A total of 434 urine specimens were analysed. The sensitivity of 5SCD for the detection of stage III-IV melanoma was 83%, while the corresponding sensitivity of 6H5MI2C was 52%. Fifty per cent of patients with one metastatic site had increased 5SCD excretion, while all patients with four or more metastatic sites had increased excretion. A significant correlation was found between 5SCD decrease and clinical regression (P < 0.001) and between 5SCD increase and clinical progression (P < 0.001). Corresponding correlations were not found for 6H5MI2C. Increments in 5SCD excretion (median 269 ╡mol/mol creatinine) were seen for 83% of the occasions when clinical progression was recorded, and decrements in 5SCD excretion (median 145 ╡mol/mol creatinine) were seen for 85% of the occasions when clinical regression was seen. During clinical 'stable disease' increases in 5SCD excretion were seen in 59% and decreases in 41%. The median value of 5SCD changes for stable disease was 7.0 ╡mol/mol creatinine, indicating a chemical marker stability in many cases. We recommend the use of 5SCD in urine as a valuable, reliable and simple biochemical marker to use in the clinical follow-up of melanoma patients with advanced disease.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25195 (URN)10.1097/00008390-200008000-00008 (DOI)9634 (Local ID)9634 (Archive number)9634 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13
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