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Marta Karaniewicz-ada Dagmara Krzyaska Dorota Danielak Janusz Rzeniczak Franciszek Gwka Marek Somczyski Pawe Burchardt 《European journal of clinical pharmacology》2020,76(3):419-430
Impaired antiplatelet effect of clopidogrel (CLP) can result from drug-drug interactions and genetic polymorphisms of drug-metabolizing enzymes. The aim of the study was to evaluate the effect of genetic polymorphisms of ABCB1 and the selected cytochrome P450 isoenzymes on the pharmacodynamics and pharmacokinetics of CLP and its metabolites in patients co-treated with atorvastatin or rosuvastatin. The study involved 50 patients after coronary angiography/angioplasty treated with CLP and atorvastatin (n = 25) or rosuvastatin (n = 25) for at least 6 months. Plasma concentrations of CLP, diastereoisomers of thiol metabolite (inactive H3 and active H4), and inactive CLP carboxylic acid metabolite were measured by UPLC-MS/MS method. Identification of the CYP2C19*2, CYP2C19*17, CYP3A4*1G, CYP1A2*1F, and ABCB1 C3435T genetic polymorphisms was performed by PCR-RFLP, while platelet reactivity units (PRU) were tested using the VerifyNow P2Y12 assay. There were significant differences in the pharmacokinetic parameters of the H4 active metabolite of CLP in the atorvastatin and rosuvastatin group divided according to their CYP2C19 genotype. There were no significant associations between CYP3A4, CYP1A2, and ABCB1 genotypes and pharmacokinetic parameters in either statin groups. In the multivariate analysis, CYP2C19*2 genotype and non-genetic factors including BMI, age, and diabetes significantly affected platelet reactivity in the studied groups of patients (P < 0.01). In the atorvastatin group, CYP2C19*2, CYP3A4*1G, and ABCB1 C3435T TT genotypes were independent determinants of PRU values (P < 0.01). The CYP2C19*2 allele is the primary determinant of the exposition to the H4 active metabolite of clopidogrel and platelet reactivity in patients co-treated with atorvastatin or rosuvastatin. 相似文献
84.
Pionke-Ubych Renata Frydecka Dorota Cechnicki Andrzej Krężołek Martyna Nelson Barnaby Gawęda Łukasz 《European archives of psychiatry and clinical neuroscience》2022,272(6):1073-1085
European Archives of Psychiatry and Clinical Neuroscience - The hypothesis of the psychosis continuum enables to study the mechanisms of psychosis risk not only in clinical samples but in... 相似文献
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Pieles G Geyer SH Szumska D Schneider J Neubauer S Clarke K Dorfmeister K Franklyn A Brown SD Bhattacharya S Weninger WJ 《Journal of anatomy》2007,211(1):132-137
Rapid and precise phenotyping analysis of large numbers of wild-type and mutant mouse embryos is essential for characterizing the genetic and epigenetic factors regulating embryogenesis. We present a novel methodology that permits precise high-throughput screening of the phenotype of embryos with both targeted and randomly generated mutations. To demonstrate the potential of this methodology we show embryo phenotyping results produced in a large-scale ENU-mutagenesis study. In essence this represents an analysis pipeline, which starts with simultaneous micro-magentic resonance imaging (microMRI) screening (voxel size: 25.4 x 25.4 x 24.4 microm) of 32 embryos in one run. Embryos with an indistinct phenotype are then cut into parts and suspect organs and structures are analysed with HREM (high-resolution episcopic microscopy). HREM is an imaging technique that employs 'positive' eosin staining and episcopic imaging for generating three-dimensional (3D) high-resolution (voxel size: 1.07 x 1.07 x 2 microm) digital data of near histological contrast and quality. The results show that our method guarantees the rapid availability of comprehensive phenotype information for high numbers of embryos in, if necessary, histological quality and detail. The combination of high-throughput microMRI with HREM provides an alternative screening pipeline with advantages over existing 3D phenotype screening methods as well as traditional histology. Thus, the microMRI-HREM phenotype analysis pipeline recommends itself as a routine tool for analysing the phenotype of transgenic and mutant embryos. 相似文献
87.
Majewska MD 《Acta neurobiologiae experimentalis》2007,67(3):219-233
Ion channels are vital components of plasma membranes. This article presents an evolutionary view of the biochemical mechanism of controlling activity of ion channels by rigid lipids, such as steroids or biophysically similar molecules, which were instrumental in formation and control of ion channels in cell membranes at the very origin of life. Such regulatory mechanisms exist in all cellular forms of life from ancient bacteria to humans and participate in a diversity of biological functions, from the most basic, such as maintenance of cell shape, homeostasis, feeding, cell fusion, and reproduction to the most intricate, such as the mind. Learning about the regulation of membrane ion channels by steroids and like molecules is important for understanding the evolution of life and various aspects of cell and organism physiology, for unraveling the mysteries of mind, and for practical purposes such as developing new pharmacotherapies. 相似文献
88.
Joanna Zielińska Jacek Stadnik Anna Bierczyńska-Krzysik Dorota Stadnik 《Pharmaceutical research》2018,35(7):143
Purpose
Isolation and identification of unknown impurities of recombinant insulin lispro (produced at IBA) formed during accelerated stability testing of pharmaceutical solutions. For comparative purposes also commercially available formulations of recombinant human insulin (Humulin S®; Lilly), recombinant insulin lispro (Humalog®; Lilly), recombinant insulin aspart (NovoRapid® Penfill®; Novo Nordisk), recombinant insulin detemir (Levemir®; Novo Nordisk) and recombinant insulin glargine (Lantus®; Sanofi-Aventis) were analyzed.Methods
The impurities of insulin analogs were isolated by RP-HPLC and identified with peptide mass fingerprinting using MALDI-TOF/TOF mass spectrometry.Results
The identified derivatives were N-terminally truncated insulin analog impurities of decreased molecular mass of 119, 147 and 377 Da related to the original protein. The modifications resulting in a mass decrease were detected at the N-terminus of B chains of insulin lispro, insulin aspart, human insulin, insulin glargine, insulin detemir in all tested formulations. To our knowledge it is the first time that these impurities are reported.Conclusions
The following derivatives formed by truncation of the B chain in insulin analogs were identified in pharmaceutical formulations: desPheB1-N-formyl-ValB2 derivative, desPheB1 derivative, pyroGluB4 derivative.89.
Sara Garcia-Ptacek Beatriz Contreras Escamez Eva Zupanic Dorota Religa Lena von Koch Kristina Johnell Mia von Euler Ingemar Kåreholt Maria Eriksdotter 《Journal of the American Medical Directors Association》2018,19(2):154-161
Objectives
To explore the association between prestroke mobility dependency and dementia on functioning and mortality outcomes after stroke in patients>65 years of age.Design
Longitudinal cohort study based on SveDem, the Swedish Dementia Registry and Riksstroke, the Swedish Stroke Registry.Participants
A total of 1689 patients with dementia >65 years of age registered in SveDem and suffering a first stroke between 2007 and 2014 were matched with 7973 controls without dementia with stroke.Measurements
Odds ratios (ORs) and 95% confidence intervals (CIs) for intrahospital mortality, and functioning and mortality outcomes at 3 months were calculated. Functioning included level of residential assistance (living at home without help, at home with help, or nursing home) and mobility dependency (independent, needing help to move outdoors, or needing help indoors and outdoors).Results
Prestroke dependency in activities of daily living and mobility were worse in patients with dementia than controls without dementia. In unadjusted analyses, patients with dementia were more often discharged to nursing homes (51% vs 20%; P < .001). Mortality at 3 months was higher in patients with dementia (31% vs 23% P < .001) and fewer were living at home without help (21% vs 55%; P < .001). In adjusted analyses, prestroke dementia was associated with higher risk of 3-month mortality (OR 1.34; 95% CI 1.18–1.52), requiring a higher level of residential assistance (OR 4.07; 3.49–.75) and suffering from more dependency in relation to mobility (OR 2.57; 2.20–3.02). Patients with dementia who were independent for mobility prestroke were more likely to be discharged to a nursing home compared with patients without dementia with the same prestroke mobility (37% vs 16%; P < .001), but there were no differences in discharge to geriatric rehabilitation (19% for both; P = .976). Patients, who moved independently before stroke, were more often discharged home (60% vs 28%) and had lower mortality. In adjusted analyses, prestroke mobility limitations were associated with higher odds for poorer mobility, needing more residential assistance, and death.Conclusions
Patients with mobility impairments and/or dementia present a high burden of disability after a stroke. There is a need for research on stroke interventions among these populations. 相似文献90.