Publications by authors named "Tybring G"

Background: Longer pre-centrifugation times alter the quality of serum and plasma samples. Markers for such delays in sample processing and hence for the sample quality, have been identified.

Methods: Twenty cytokines in serum, EDTA plasma and citrate plasma samples were screened for changes in concentration induced by extended blood pre-centrifugation delays at room temperature.

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Background A number of factors regarding blood collection, handling and storage may affect sample quality. The purpose of this study was to assess the impact on plasma protein profiles by delayed centrifugation and plasma separation and multiple freeze-thaw cycles. Methods Blood samples drawn from 16 healthy individuals were collected into ethylenediaminetetraacetic acid tubes and kept either at 4 °C or 22 °C for 1-36 h prior to centrifugation.

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Motivation: Biobanks are important infrastructures for life science research. Optimal sample handling regarding e.g.

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Handling and processing of blood can significantly alter the molecular composition and consistency of biobank samples and can have a major impact on the identification of biomarkers. It is thus crucial to identify tools to determine the quality of samples to be used in biomarker discovery studies. In this study, a non-targeted gas chromatography/time-of-flight mass spectrometry (GC-TOFMS) metabolomic strategy was used with the aim of identifying quality markers for serum and plasma biobank collections lacking proper documentation of preanalytical handling.

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Biobanks produce and distribute biospecimens, ensuring their fitness for purpose and accurately qualifying them before distribution. In their efforts toward professionalization, biobanks can nowadays seek certification or accreditation. One of the requirements of these standards is regular participation in Proficiency Testing (PT) programs.

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The growing need for biobanks in health research presents an opportunity for building capacity in developing countries. In Zimbabwe, there is limited knowledge and awareness about biobanking. As such we report the proceedings of a biobanking course, which included research scientists, healthcare professionals, and regulatory authorities as a start to developing a framework for biobanking practice.

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This technical report presents quality control (QC) assays that can be performed in order to qualify clinical biospecimens that have been biobanked for use in research. Some QC assays are specific to a disease area. Some QC assays are specific to a particular downstream analytical platform.

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Purpose: We aimed to assess the influence of CYP2C19*17 on R-warfarin clearance as well as the effect of CYP2C19, CYP2C8, CYP2C9, and VKORC1 polymorphisms together with non-genetic factors on warfarin international normalized ratio (INR)/daily dose.

Methods: One hundred fifty Caucasian Italian outpatients with data on steady-state plasma concentrations of S- and R-warfarin were genotyped for CYP2C19 (*2, *3, *4, *17), CYP2C9 (*2, *3), CYP2C8*3, and VKORC1*2. The statistical analysis was performed on the effect of genotypes/haplotypes, age, sex, and body weight on the clearance of warfarin enantiomers and dose-normalized INR.

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Background: Citalopram and escitalopram, selective serotonin reuptake inhibitors, are primarily metabolized by cytochrome P450 (CYP) 2C19, which is a highly polymorphic enzyme known to cause inter-individual differences in pharmacokinetics. However, the impact of CYP2C19 polymorphisms on citalopram or escitalopram exposure has yet to be fully clarified, especially with regard to the quantitative impact of the CYP2C19*17 allele.

Objective: The objective of this study was to quantify the effect of functional CYP2C19 allele variants on citalopram/escitalopram exposure.

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With the increasing number of research biobanks and the importance of their role in supporting medical and biological research, the development and sharing of biobanking best practices and benchmarking standards has become paramount. To promote outstanding biobank services for research, the Research Biobank of the Year Competition (RBYC) has been inaugurated by the European, Middle-Eastern, and African Society for Biopreservation and Biobanking (ESBB) in October 2013. The procedures for the call and evaluation procedure, including the newly developed scoring system, are presented here.

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Unlabelled: Several biobanking initiatives have emerged to create extensive collections of specimen for biomedical studies and various analytical platforms. An affinity proteomic analysis with antibody suspension bead arrays was conducted to investigate the influence of the pre-analytical time and temperature conditions on blood derived samples. Serum and EDTA plasma prepared from 16 individuals was centrifuged and aliquots were kept either at 4°C or in ambient temperature for 1h and up to 36h prior to first storage.

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The first version of the Standard PREanalytical Code (SPREC) was developed in 2009 by the International Society for Biological and Environmental Repositories (ISBER) Biospecimen Science Working Group to facilitate documentation and communication of the most important preanalytical quality parameters of different types of biospecimens used for research. This same Working Group has now updated the SPREC to version 2.0, presented here, so that it contains more options to allow for recent technological developments.

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Studying gene-environment interactions requires that the amount and quality of the lifestyle data is comparable to what is available for the corresponding genomic data. Sweden has several crucial prerequisites for comprehensive longitudinal biomedical research, such as the personal identity number, the universally available national health care system, continuously updated population and health registries and a scientifically motivated population. LifeGene builds on these strengths to bridge the gap between basic research and clinical applications with particular attention to populations, through a unique design in a research-friendly setting.

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Background: There is little confidence in the consistency of estimation of DNA concentrations when samples move between laboratories. Evidence on this consistency is largely anecdotal. Therefore there is a need first to measure this consistency among different laboratories and then identify and implement remedies.

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The basis for interindividual variation in the CYP1A2 gene expression is not fully understood and the known genetic polymorphisms in the gene provide no explanation. We investigated whether the CYP1A2 gene expression is regulated by DNA methylation and displays allele-specific expression (ASE) using 65 human livers. Forty-eight percent of the livers displayed ASE not associated to the CYP1A2 mRNA levels.

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A requirement for performing robust genetic and statistical analyses on twins is correctly assigned zygosities. In order to increase the power to detect small risk factors of disease, zygosity testing should also be amenable for high throughput screening. In this study we validate and implement the use of a panel of 50 single nucleotide polymorphisms (SNPs) for reliable high throughput zygosity testing and compare it to a panel of 16 short tandem repeats (STRs).

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Self-collection of saliva has the potential to provide molecular epidemiologic studies with DNA in a user-friendly way. We evaluated the new Oragene saliva collection method and requested saliva samples by mail from 611 men (ages 53-87 years). We obtained a response rate of, on average, 80% [varying from 89% (ages 67-71 years) to 71% (ages 77-87 years)].

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This study aimed to investigate the effect of omeprazole on intragastric pH and gastrin release as well as the plasma concentration of omeprazole in relation to CYP2C19 genotypes after repeated doses in Korean patients. Twenty-six Korean patients with acid related disease were genotyped for CYP2C19 by allele specific PCR (wt/wt, CYP2C19*1/*1; wt/mut, CYP2C19*1/*2 or *1/*3; mut/mut, CYP2C19*2/*2, *2/*3 or *3/*3). Intragastric pH was monitored during 24 hr, and the plasma concentrations of omeprazole, hydroxyomeprazole, omeprazole sulfone and meal-stimulated gastrin were measured during 4 hr before and after 8 consecutive daily doses of 20 mg omeprazole.

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Objective: This in-vitro study aimed at an identification of cytochrome P(450) (CYP) enzymes catalysing the (S)- and (R)-hydroxylation of the widely used anticoagulant phenprocoumon (PPC) to its major, inactive metabolites.

Methods: Relevant catalysts were identified by kinetic, correlation and inhibition experiments using human liver microsomes and recombinant enzymes.

Results: Kinetics revealed (S)-7-hydroxylation as quantitatively most important.

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The aim of this study was to identify genes for hepatic fuel metabolism with a gender-differentiated expression and to determine which of these that might be regulated by the female-specific secretion of GH. Effects of gender and continuous infusion of GH to male rats were studied in the liver using cDNA microarrays representing 3200 genes. Sixty-nine transcripts displayed higher expression levels in females, and 177 displayed higher expression in males.

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Aims: The aim of this study was to assess the influence of concomitant caffeine intake on the pharmacokinetics of oral melatonin, a probe drug for CYP1A2 activity.

Methods: Twelve healthy subjects, six smokers and six nonsmokers, were given melatonin (6 mg) either alone or in combination with caffeine (3 x 200 mg). Blood samples for the analysis of melatonin or caffeine and paraxanthine were taken from 1 h before until 6 h after intake of melatonin.

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Aims: To investigate pharmacokinetics of the enantiomers of citalopram (CT) and its metabolites desmethylcitalopram (DCT) and didesmethylcitalopram (DDCT) in Swedish healthy volunteers in relation to CYP2C19 and CYP2D6 geno- and phenotypes.

Methods: Racemic CT was given for seven days to panels with different genotypes and the following mephenytoin (Me) and debrisoquine (De) hydroxylation phenotypes: EMDe/EMMe, PMDe/EMMe, EMDe/PMMe (n = 6 in all groups), and one PMDe/PMMe subject. Blood sampling was carried out during day 7, and all urine was collected for 12 h after the last dose of CT.

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