| 1. |
- Andersson, Henrik, et al.
(author)
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Assaying cardiac biomarkers for toxicity testing using biosensing and cardiomyocytes derived from human embryonic stem cells
- 2010
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In: JOURNAL OF BIOTECHNOLOGY. - : Elsevier Science B.V., Amsterdam.. - 0168-1656 .- 1873-4863. ; 150:1, s. 175-181
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Journal article (peer-reviewed)abstract
- Human embryonic stem cell (hESC) derived cardiomyocytes are in the present study being used for testing drug-induced cardiotoxicity in a biosensor set-up. The design of an in vitro testing alternative provides a novel opportunity to surpass previous methods based on rodent cells or cell lines due to its significantly higher toxicological relevance. In this report we demonstrate how hESC-derived cardiomyocytes release detectable levels of two clinically decisive cardiac biomarkers, cardiac troponin T and fatty acid binding protein 3, when the cardiac cells are exposed to the well-known cardioactive drug compound. doxorubicin. The release is monitored by the immuno-biosensor technique surface plasmon resonance, particularly appropriate due to its capacity for parallel and high-throughput analysis in complex media.
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| 2. |
- Andersson, Henrik, et al.
(author)
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Monitoring of troponin release from cardiomyocytes during exposure to toxic substances using surface plasmon resonance biosensing
- 2010
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In: ANALYTICAL AND BIOANALYTICAL CHEMISTRY. - : Springer Science Business Media. - 1618-2642 .- 1618-2650. ; 398:3, s. 1395-1402
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Journal article (peer-reviewed)abstract
- Troponin T (TnT) is a useful biomarker for studying drug-induced toxicity effects on cardiac cells. We describe how a surface plasmon resonance (SPR) biosensor was applied to monitor the release of TnT from active HL-1 cardiomyocytes in vitro when exposed to cardiotoxic substances. Two monoclonal human TnT antibodies were compared in the SPR immunosensor to analyse the TnT release. The detection limit of TnT was determined to be 30 ng/ml in a direct assay set-up and to be 10 ng/ml in a sandwich assay format. Exposure of the cardiomyocytes to doxorubicin, troglitazone, quinidine and cobalt chloride for periods of 6 and 24 h gave significant SPR responses, whereas substances with low toxicity showed insignificant effects (ascorbic acid, methotrexate). The SPR results were verified with a validated immunochemiluminescence method which showed a correlation of r(2)=0.790.
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| 3. |
- Bellanti, Francesco, et al.
(author)
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Do pharmacokinetic polymorphisms explain treatment failure in high-risk patients with neuroblastoma?
- 2011
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In: EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY. - : Springer Science Business Media. - 0031-6970 .- 1432-1041. ; 67, s. S87-S107
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Research review (peer-reviewed)abstract
- Purpose Neuroblastoma is the most common extracranial solid tumour in childhood. It accounts for 15% of all paediatric oncology deaths. In the last few decades, improvement in treatment outcome for high-risk patients has not occurred, with an overall survival rate andlt;30-40%. Many reasons may account for such a low survival rate. The aim of this review is to evaluate whether pharmacogenetic factors can explain treatment failure in neuroblastoma. Methods A literature search based on PubMeds database Medical Subject Headings (MeSH) was performed to retrieve all pertinent publications on current treatment options and new classes of drugs under investigation. One hundred and fifty-eight articles wer reviewed, and relevant data were extracted and summarised. Results and conclusions Few of the large number of polymorphisms identified thus far showed an effect on pharmacokinetics that could be considered clinically relevant. Despite their clinical relevance, none of the single nucleotide polymorphisms (SNPs) investigated can explain treatment failure. These findings seem to reflect the clinical context in which anti-tumour drugs are used, i.e. in combination with multi-modal therapy. In addition, many pharmacogenetic studies did not assess (differences in) drug exposure, which could contribute to explaining pharmacogenctic associations. Furthermore, it remains unclear whether the significant activity of new drugs on different neuroblastoma cell lines translates into clinical efficacy, irrespective of resistance or myelocytomatosis viral related oncogene, neuroblastoma derived (MYCN) amplification. Elucidation of the clinical role of pharmacogenetic factors in the treatment of neuroblastoma demands an integrated pharmacokinetic pharmacodynamic approach to the analysis of treatment response data.
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| 4. |
- Fyrberg, Anna, et al.
(author)
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Induction of fetal hemoglobin and ABCB1 gene expression in 9-β-D-arabinofuranosylguanine-resistant MOLT-4 cells
- 2011
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In: Cancer Chemotherapy and Pharmacology. - : Springer. - 0344-5704 .- 1432-0843. ; 68:3, s. 583-591
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Journal article (peer-reviewed)abstract
- PURPOSE: To characterize resistance mechanisms to the nucleoside analog 9-β-D-arabinofuranosylguanine (AraG) in the T-cell acute lymphoblastic leukemia cell line MOLT-4 and its AraG-resistant variant. METHODS: A gene expression microarray analysis was performed, as well as gene expression and enzyme activity measurements of key enzymes in the activation of AraG. Cytotoxicity of AraG and cross-resistance to other compounds were evaluated using a standard cytotoxicity assay. RESULTS: Gene expression microarray analysis revealed that fetal hemoglobin genes and the multidrug resistance ABCB1 gene, encoding the drug efflux pump P-gp, were the most highly upregulated genes in the resistant cells, while genes traditionally associated with nucleoside analog resistance were not. Fetal hemoglobin and ABCB1 induction can be due to global DNA hypomethylation. This phenomenon was studied using AraG during a period of 4 weeks in MOLT-4 cells and the lung adenocarcinoma cell line A549, leading to up-regulation of hemoglobin gamma and ABCB1 as well as DNA hypomethylation. Inhibiting P-gp in the AraG-resistant MOLT-4 cells led to decreased proliferation, reduced hemoglobin expression, and highly induced ABCB1 expression. CONCLUSIONS: We show that AraG can cause hypomethylation of DNA and induce the expression of the fetal hemoglobin gamma gene and the ABCB1 gene. We speculate that the induction of ABCB1/P-gp may occur in order to help with excretion of hemoglobin degradation products that would otherwise be toxic to the cells, and we present data supporting our theory that P-gp may be linked to the induction of hemoglobin.
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| 5. |
- Kågedal, Bertil
(author)
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Biologiska variabler i blod och urin - könsskillnader av stor betydelse för sjukdomsdiagnostik
- 2010. - 1
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In: Genus och kön inom medicin- och vårdutbildningar. - Lund : Studentlitteratur AB. - 9789144059501 ; , s. 497-516
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Book chapter (other academic/artistic)abstract
- Kvinnor och män är delvis lika, delvis olika. Det innebär att kvinnor och män både har behov av likadan behandling och av behandling som är anpassad till det egna könets förutsättningar. Denna antologi belyser kvinnors och mäns förutsättningar och behov inom en rad olika medicinska områden och tar upp både biologiska och sociala faktorer som påverkar hälsa och behandling. Den behandlar även den roll som kön spelar inom vårdens arbetsliv samt hur köns- och genusperspektiv kan integreras inom olika typer av medicin- och vårdutbildningar. Ett av bokens teman är våld, kränkningar och diskriminering, och inom ramen för detta behandlas några av de olika maktordningar som kommer till uttryck vid behandlingar inom hälso- och sjukvården. Antologin har en stor spännvidd när det gäller ämnen och författare. Förhoppningsvis ska den bredd som antologin uppvisar, leda fram till frågeställningar där läsaren utmanar sina förgivettaganden inom både genusvetenskap och mer traditionell medicin samt väcka nya frågor: Om könet snarare ses som en konstruktion än en fysisk realitet - kan då kvinnor lika gärna äta mediciner som är utprovade på män och opereras med metoder och verktyg anpassade till mäns fysiologi? Å andra sidan - hur objektiv är den naturvetenskapligt inriktade medicinska forskningen egentligen om man börjar granska den utifrån frågeställningar om perspektivval och genus? Antologin vänder sig till lärare på utbildningar inom medicin, hälsa och vård. Andra målgrupper är studenter på sådana utbildningar, vårdpersonal och en intresserad allmänhet.
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| 6. |
- Landberg, Eva, et al.
(author)
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Disialo–trisialo bridging of transferrin is due to increased branching and fucosylation of the carbohydrate moiety
- 2012
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In: Clinica Chimica Acta. - : Elsevier. - 0009-8981 .- 1873-3492. ; 414, s. 58-64
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Journal article (peer-reviewed)abstract
- BackgroundCarbohydrate deficient transferrin (CDT) is used for detection of alcohol abuse and follow-up. High performance liquid chromatography (HPLC) of transferrin glycoforms is highly specific for identification of alcohol abuse, but unresolved disialo- and trisialotransferrin glycoforms sometimes makes interpretation difficult. The cause of this phenomenon is unknown, cannot be explained by genetic variants of transferrin, but seems to be associated with liver disease.MethodsNineteen serum samples showing di–tri bridging when analyzed by HPLC were collected. Transferrin was purified by affinity chromatography, and N-linked oligosaccharides were released enzymatically. The N-glycans were further analyzed by high performance anion-exchange chromatography with pulsed amperometric detection and MALDI-TOF mass spectrometry.ResultsThe HPLC-analysis showed three different types of glycoform patterns. The N-glycans from fifteen samples showed patterns with increased number of triantennary structures containing one or two fucose residues. One sample contained an increased amount of triantennary glycans without fucose. Three samples showed a glycosylation pattern similar to normal transferrin.ConclusionsThe di–tri bridging phenomenon was associated with alterations in transferrin glycosylation in the majority of cases. Transferrin contained a higher extent of triantennary and often fucosylated N-linked oligosaccharides. These results may be important in future diagnostic approaches to liver diseases.
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| 7. |
- Nezirevic Dernroth, Dzeneta, 1969-, et al.
(author)
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Pheomelanin-related benzothiazole isomers in the urine of patients with diffuse melanosis of melanoma
- 2010
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In: Clinica Chimica Acta. - : lsevier Science B.V., Amsterdam. - 0009-8981 .- 1873-3492. ; 411:17-18, s. 1195-1203
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Journal article (peer-reviewed)abstract
- 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.
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| 8. |
- Zdolsek, Joachim, et al.
(author)
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Glomerular filtration rate is increased in burn patients
- 2010
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In: Burns. - : Elsevier Science B.V., Amsterdam.. - 0305-4179 .- 1879-1409. ; 36:8, s. 1271-1276
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Journal article (peer-reviewed)abstract
- Urinary output a key parameter guiding fluid resuscitation in burn trauma is an inadequate measure of renal function In this study the clearance of iohexol (CL) was used to follow the glomerular filtration rate during the first week after burn Nineteen adults with major burns received an intravenous bolus injection of iohexol every other day Plasma concentration of iohexol was measured over 4 h and CL was calculated by a one compartment kinetic model The results were compared to the CL as obtained by a two compartment model and also to the CL measured in 10 healthy controls The results show that CL values for burn patients were high The first day after burn median CL was 155 mL/min/1 73 m(2) (range 46-237) which exceeded that for the controls (mean 117 mL/min/1 73 m(2) P less than 0 01) However on day 7 the CL approached the expected baseline (mean 122 mL/min/1 73 m(2)) CL was 10% lower when calculated from two compartment kinetics and a correction factor of 0 9 was applied to all results obtained by the one compartment calculations to give results comparable to those from the two compartment kinetics In conclusion CL is increased early after burn The mechanism is unclear but it parallels the period of vascular dysfunction and increased cardiac output
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