| 1. |
- Kortenkamp, Andreas, et al.
(författare)
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Removing Critical Gaps in Chemical Test Methods by Developing New Assays for the Identification of Thyroid Hormone System-Disrupting Chemicals-The ATHENA Project
- 2020
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 21:9
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Tidskriftsartikel (refereegranskat)abstract
- The test methods that currently exist for the identification of thyroid hormone system-disrupting chemicals are woefully inadequate. There are currently no internationally validated in vitro assays, and test methods that can capture the consequences of diminished or enhanced thyroid hormone action on the developing brain are missing entirely. These gaps put the public at risk and risk assessors in a difficult position. Decisions about the status of chemicals as thyroid hormone system disruptors currently are based on inadequate toxicity data. The ATHENA project (Assays for the identification of Thyroid Hormone axis-disrupting chemicals: Elaborating Novel Assessment strategies) has been conceived to address these gaps. The project will develop new test methods for the disruption of thyroid hormone transport across biological barriers such as the blood-brain and blood-placenta barriers. It will also devise methods for the disruption of the downstream effects on the brain. ATHENA will deliver a testing strategy based on those elements of the thyroid hormone system that, when disrupted, could have the greatest impact on diminished or enhanced thyroid hormone action and therefore should be targeted through effective testing. To further enhance the impact of the ATHENA test method developments, the project will develop concepts for better international collaboration and development in the area of thyroid hormone system disruptor identification and regulation.
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| 2. |
- Sjöde, A., et al.
(författare)
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Enzyme-based control of oxalic acid in the pulp and paper industry
- 2008
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Ingår i: Enzyme and microbial technology. - : Elsevier BV. - 0141-0229 .- 1879-0909. ; 43:2, s. 78-83
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Tidskriftsartikel (refereegranskat)abstract
- Enzymatically catalyzed decomposition of oxalic acid in bleaching filtrates from the pulp and paper industry offers a possibility to enduringly prevent oxalate scaling problems by specific removal of the oxalic acid in the system rather than by attempting to avoid calcium oxalate precipitation by countermeasures aiming at improved solubility. To achieve a broad evaluation of various oxalate-degrading enzymes and to cover conditions encountered in various types of processes, 16 different bleaching filtrates were collected from pulp mills engaged in mechanical pulping of softwood, mechanical pulping of aspen, and kraft pulping of softwood. A novel oxalate-degrading enzyme provided by Novozymes was compared with commercially available oxalate oxidase from barley and oxalate decarboxylase from Aspergillus niger. The activity of the enzymes in the filtrates was investigated using kinetic analysis and multivariate data analysis. Kinetic analysis indicated that the degradation rates were governed more by inhibitors in the filtrates than by the concentration of oxalic acid. Multivariate data analysis suggested links between high concentrations of certain compounds in the filtrates and high or low enzyme activity, as exemplified by the link between high concentrations of chelators in filtrates from mechanical pulping and low activity of oxalate oxidase from barley. All three enzymes could degrade oxalic acid in all filtrates, despite the fact that very high concentrations of residual hydrogen peroxide were found in several of the filtrates.
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| 3. |
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| 4. |
- Abdel-Rehim, Mohamed
(författare)
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Microextraction by packed sorbent (MEPS) : A tutorial
- 2011
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Ingår i: Analytica Chimica Acta. - : Elsevier BV. - 0003-2670 .- 1873-4324. ; 701:2, s. 119-128
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Tidskriftsartikel (refereegranskat)abstract
- This tutorial provides an overview on a new technique for sample preparation, microextraction by packed sorbent (MEPS). Not only the automation process by MEPS is the advantage but also the much smaller volumes of the samples, solvents and dead volumes in the system. Other significant advantages such as the speed and the simplicity of the sample preparation process are provided. In this tutorial the main concepts of MEPS will be elucidated. Different practical aspects in MEPS are addressed. The factors affecting MEPS performance will be discussed. The application of MEPS in clinical and pre-clinical studies for quantification of drugs and metabolites in blood, plasma and urine will be provided. A comparison between MEPS and other extraction techniques such as SPE, LLE, SPME and SBSE will be discussed. (C) 2011 Elsevier B.V. All rights reserved.
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| 5. |
- Abdel-Rehim, Mohamed
(författare)
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On-Line Whole Blood Analysis Using Microextraction by Packed Sorbent and LC-MS-MS
- 2011
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Ingår i: LC GC North America. - 1527-5949 .- 1939-1889. ; 29:7, s. 612-618
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Tidskriftsartikel (refereegranskat)abstract
- Microextraction by packed sorbent (MEPS) is a new technique for sample preparation that can be connected on-line with liquid chromatography (LC) or gas chromatography (GC) systems without any modifications. This article describes the use of MEPS in clinical and preclinical studies to quantify different drugs in whole blood samples. MEPS was used to determine cyclophosphamide in mouse blood from preclinical g studies using 20 mu L of blood samples. The interday accuracies and 0 precisions ranged from 107-109% and from 2.0-7.0%, respectively. The determination of four immunosuppressive drugs in human blood by MEPS and liquid chromatography-mass spectrometry (LC-MS) is described. The method showed a good selectivity and sensitivity. The calibration curves for everolimus, sirolimus, and tacrolimus ranged from 0.5 to 50 ng/mL and for cyclosporine from 3.0 to 1500 ng/mL. Intraday precisions for the studied immunosuppressive drugs were 2.0-11.7% and interday precision ranged from 5.1 to 13.7% (CV).
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| 6. |
- Ashri, Nadia Y., et al.
(författare)
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Sample treatment based on extraction techniques in biological matrices
- 2011
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Ingår i: Bioanalysis. - 1757-6180 .- 1757-6199. ; 3:17, s. 2003-2018
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Forskningsöversikt (refereegranskat)abstract
- The importance of sample preparation methods as the first stage in bioanalysis is described. In this article, the sample preparation concept and strategies will be discussed, along with the requirements for good sample preparation. The most widely used sample preparation methods in the pharmaceutical industry are presented; for example, the need for same-day rotation of results from large numbers of biological samples in pharmaceutical industry makes high throughput bioanalysis more essential. In this article, high-throughput sample preparation techniques are presented; examples are given of the extraction and concentration of analytes from biological matrices, including protein precipitation, solid-phase extraction, liquid-liquid extraction and microextraction-related techniques. Finally, the potential role of selective extraction methods, including molecular imprinted phases, is considered.
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| 7. |
- Cavallini, Nicola, 1978, et al.
(författare)
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Neuropeptide release augments serum albumin loss and reduces ultrafiltration in peritoneal dialysis
- 2012
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Ingår i: Peritoneal Dialysis International. - : SAGE Publications. - 0896-8608 .- 1718-4304. ; 32:2, s. 168-176
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Tidskriftsartikel (refereegranskat)abstract
- Background: The triggers of the acute local inflammatory response to peritoneal dialysis (PD) fluid exposure remain unknown. In the present study, we investigated the effects of neurogenic inflammation and mast cell degranulation on water and solute transport in experimental PD. Methods: Single 2-hour dwells in rats with PD catheters were studied. Histamine and the neuropeptides substance P and calcitonin gene-related peptide (CGRP) were measured in PD fluid samples by ELISA. Radiolabeled albumin (I-125 and I-131 respectively) was used as an intraperitoneal (IP) and intravascular tracer. Glucose and urea concentrations were measured in plasma and PD fluid. The effects of varying the volume and osmolarity of a lactate-buffered PD fluid were compared and related to the effects of pharmacologic intervention. Results: Application of 20 mL 3.9% glucose PD fluid induced an IP histamine release during the first 30 minutes, blockable by the mast cell stabilizer doxantrazole and the substance P neurokinin-1 receptor (NK1R)-blocker spantide. Histamine release was also inhibited at a reduced PD volume (14 mL), but was not affected by normalizing the PD fluid osmolarity. Blockade of NK1R also reduced plasma albumin leakage to the peritoneal cavity. Inhibition of CGRP receptors by CGRP8-37 improved osmotic (transcapillary) and net ultrafiltration and reduced the dialysate urea concentration. Neuropeptide release was not clearly related to activation of the TrpV1 receptor, the classic trigger of neurogenic inflammation. Conclusions: Neuropeptide release exaggerated albumin loss and reduced ultrafiltration in this rat PD model. Intervention aimed at the neuropeptide action substantially improved PD efficiency.
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| 10. |
- Encarnacao, Joao Crispim, et al.
(författare)
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Impact of assay temperature on antibody binding characteristics in living cells : A case study
- 2017
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Ingår i: BIOMEDICAL REPORTS. - : Spandidos Publications. - 2049-9434 .- 2049-9442. ; 7:5, s. 400-406
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Tidskriftsartikel (refereegranskat)abstract
- Kinetic and thermodynamic studies of ligand-receptor interactions are essential for increasing the understanding of receptor activation mechanisms and drug behavior. The characterization of molecular interactions on living cells in real-time goes beyond most current binding assays, and provides valuable information about the dynamics and underlying mechanism of the molecules in a living system. The effect of temperature on interactions in cell-based assays is, however, rarely discussed. In the present study, the effect of temperature on binding of monoclonal antibodies, cetuximab and pertuzumab to specific receptors on living cancer cells was evaluated, and the affinity and kinetics of the interactions were estimated at selected key temperatures. Changes in the behavior of the interactions, particularly in the on- and off-rates were observed, leading to greatly extended time to reach the equilibrium at 21 degrees C compared with at 37 degrees C. However, the observed changes in kinetic characteristics were less than a factor of 10. It was concluded that it is possible to conduct real-time measurements with living cells at different temperatures, and demonstrated that influences of the ambient temperature on the interaction behavior are likely to be less than one order of magnitude.
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