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3. Wall Shear Stress Alteration: a Local Risk Factor of Atherosclerosis

Author

Malik, J, Novakova, L, Valerianova, A, Chytilova, E, Lejsek, V, Buryskova Salajova, K, Lambert, L, Grus, T, Porizka, M, and Michalek, P

Subjects
Risk Factors, Hemodynamics, Humans, Stress, Mechanical, Atherosclerosis, Cardiology and Cardiovascular Medicine
Abstract

Wall shear stress describes the mechanical influence of blood flow on the arterial wall. In this review, we discuss the role of the wall shear stress in the development of atherosclerosis and its complications.Areas with chronically low, oscillating wall shear stress are most prone to plaque development and include outer bifurcation walls and inner walls of arches. In some diseases, patients have lower wall shear stress even in straight arterial segments; also, these findings were associated with atherosclerosis. High wall shear stress develops in the distal part (shoulder) of a stenosis and contributes to plaque destabilization. Wall shear stress changes are involved in the development of atherosclerosis. They are not fully understood yet and act in concert with tangential wall stress.

Published
2022

4. Isolation and biological activity of alkaloids from Vinca minor L. related to Alzheimerʼs disease

Author

Vrabec, R, primary, Kroustkova, J, additional, Locarek, M, additional, Hulcova, D, additional, Korabecny, J, additional, Hostalkova, A, additional, Kunes, J, additional, Chlebek, J, additional, Kucera, T, additional, Hrabinova, M, additional, Jun, D, additional, Soukup, O, additional, Andrisano, V, additional, Jenco, J, additional, Havelek, R, additional, Safratova, M, additional, Novakova, L, additional, Opletal, L, additional, and Cahlikova, L, additional

Published
2022
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9. Inflammation-related plasma and CSF biomarkers for multiple sclerosis

Author

Huang, J, Khademi, M, Fugger, L, Lindhe, Ö, Novakova, L, Axelsson, M, Malmeström, C, Constantinescu, C, Lycke, J, Piehl, F, Olsson, T, and Kockum, I

Subjects
Inflammation/blood, EXPRESSION, Adult, Chemokine CCL11, Male, Proteomics, Proximity extension assay, BLOOD, Multiple Sclerosis, multiple sclerosis, PLACEBO-CONTROLLED TRIAL, Severity of Illness Index, cerebrospinal fluid, Cohort Studies, Young Adult, Immunology and Inflammation, CEREBROSPINAL-FLUID, extension assay, Humans, Chemokine CCL11/analysis, NATALIZUMAB, Inflammation, Chemokine CCL20, Multiple Sclerosis/blood, DISABILITY, proximity, Reproducibility of Results, biomarkers, NEUROFILAMENT, Chemokine CCL20/blood, MULTIPLE-SCLEROSIS, Middle Aged, Biological Sciences, Prognosis, CHEMOKINES, Case-Control Studies, T-CELLS, proximity extension assay, Female, Biomarkers/blood
Abstract

Significance Molecular biomarkers for multiple sclerosis have so far mainly been limited to measures in cerebrospinal fluid (CSF). Here, we identified additional biomarkers for multiple sclerosis, 2 in plasma as well as 10 in CSF. Furthermore, we identified 2 biomarkers: eotaxin-1 (CCL11), associated with disease duration and progression in both CSF and plasma, and plasma CCL20 which showed association with disease severity. However, these findings will require further validation. The capability of measuring biomarkers for multiple sclerosis may assist in the monitoring of patients during routine clinical care such as assessing treatment response but may also allow researchers to more accurately characterize pathological processes of inflammation and neurodegeneration in both the CNS and periphery of patients with multiple sclerosis., Effective biomarkers for multiple sclerosis diagnosis, assessment of prognosis, and treatment responses, in particular those measurable in blood, are largely lacking. We have investigated a broad set of protein biomarkers in cerebrospinal fluid (CSF) and plasma using a highly sensitive proteomic immunoassay. Cases from two independent cohorts were compared with healthy controls and patients with other neurological diseases. We identified and replicated 10 cerebrospinal fluid proteins including IL-12B, CD5, MIP-1a, and CXCL9 which had a combined diagnostic efficacy similar to immunoglobulin G (IgG) index and neurofilament light chain (area under the curve [AUC] = 0.95). Two plasma proteins, OSM and HGF, were also associated with multiple sclerosis in comparison to healthy controls. Sensitivity and specificity of combined CSF and plasma markers for multiple sclerosis were 85.7% and 73.5%, respectively. In the discovery cohort, eotaxin-1 (CCL11) was associated with disease duration particularly in patients who had secondary progressive disease (PCSF < 4 × 10−5, Pplasma < 4 × 10−5), and plasma CCL20 was associated with disease severity (P = 4 × 10−5), although both require further validation. Treatment with natalizumab and fingolimod showed different compartmental changes in protein levels of CSF and peripheral blood, respectively, including many disease-associated markers (e.g., IL12B, CD5) showing potential application for both diagnosing disease and monitoring treatment efficacy. We report a number of multiple sclerosis biomarkers in CSF and plasma for early disease detection and potential indicators for disease activity. Of particular importance is the set of markers discovered in blood, where validated biomarkers are lacking.

Published
2020

15. Natalizumab, rituximab and fingolimod as escalation therapy in multiple sclerosis

Author

Boremalm, Malin, Juto, A., Axelsson, M., Novakova, L., Frisell, T., Svenningsson, A., Lycke, J., Piehl, F., Salzer, Jonatan, Boremalm, Malin, Juto, A., Axelsson, M., Novakova, L., Frisell, T., Svenningsson, A., Lycke, J., Piehl, F., and Salzer, Jonatan

Abstract

Background and purpose: Breakthrough disease on first-line injectables in relapsing-remitting multiple sclerosis (RRMS) is a common clinical situation where comparative studies between different escalation therapies are lacking. The aim of this study was to compare the efficacy, safety and medication persistence of natalizumab (NTZ), rituximab (RTX) and fingolimod (FGL) as escalation therapy in RRMS. Methods: Patients switching from interferon or glatiramer acetate to NTZ, RTX or FGL due to breakthrough disease were identified through the Swedish multiple sclerosis (MS) registry at four large MS centers in this retrospective observational study. Data were collected from the MS registry and medical charts. Hazard ratios (HRs) for relapses, adverse events and drug discontinuation with 95% confidence interval (CI) were calculated using multivariable confounder-adjusted Cox proportional hazard models. Results: A total of 241 patients were included. The annualized relapse rates were 0.02 for NTZ, 0.03 for RTX and 0.07 for FGL. Compared with NTZ, the adjusted HR for relapse was 1.0 (95% CI, 0.2-5.6) for RTX and 3.4 (95% CI, 1.3-9.2) for FGL. The annualized drug discontinuation rates were 0.15, 0.01 and 0.15 for NTZ, RTX and FGL, respectively. The adjusted HR for drug discontinuation was 0.05 (95% CI, 0.01-0.38) for RTX and 1.0 (95% CI, 0.6-1.7) for FGL vs. NTZ. Conclusions: In patients with RRMS on interferon/glatiramer acetate with breakthrough disease, switching to NTZ or RTX was associated with less disease activity compared with FGL. RTX displayed superior medication persistence compared with both NTZ and FGL.

Published
2019
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26. Use of ultra high performance liquid chromatography-tandem mass spectrometry to demonstrate decreased serum statin levels after extracorporeal LDL-cholesterol elimination

Author

Blaha, M., VlCkova, H., Novakova, L., Solichova, D., Solich, P., Lanska, M., Maly, J., and Blaha, V.

Subjects
Care and treatment, Usage, Physiological aspects, Research, Health aspects, Low density lipoproteins -- Physiological aspects -- Research, Simvastatin -- Health aspects -- Research, Liquid chromatography -- Usage, Hypercholesterolemia -- Care and treatment -- Research
Abstract

1. Introduction Familial hypercholesterolemia (FH) is a severe metabolic disorder that leads to accelerated atheromatosis [1]. A complete change in lifestyle, a strict diet, and intensive combined pharmacotherapy are necessary [...], Background. Using our statin analysis method, it was possible to uncover a significant drop in statin levels (atorvastatin, simvastatin, and metabolites) after extracorporeal LDL-cholesterol elimination (EE) in severe familial hypercholesterolemia (FH). The purpose of this work was to identify the mechanism underlying this drop and its clinical significance as well as to propose measures to optimize a pharmacotherapeutical regimen that can prevent the loss of statins. Methods. Ultra High Performance Liquid Chromatography (UHPLC) connected to the triple quadrupole MS/MS system was used. Patients. A group of long-term treated patients (3-12 years of treatment) with severe FH (12 patients) and treated regularly by LDL-apheresis (immunoadsorption) or haemorheopheresis (cascade filtration) were included in this study. Results. After EE, the level of statins and their metabolites decreased (atorvastatin before/after LDL-apheresis: 8.83/3.46 nmol/l; before/after haemorheopheresis: 37.02/18.94 nmol/l). A specific loss was found (concentration of atorvastatin for LDL-apheresis/haemorheopheresis: 0.28/3.04 nmol/l in washing fluids; 11.07 nmol/l in filters). To prevent substantial loss of statin concentrations, a pharmacotherapeutic regimen with a longer time interval between the dose of statins and EE is recommended (15 hours). Conclusions. A specific loss of statins was found in adsorbent columns and filters. The decrease can be prevented by the suggested dosage scheme.

Published
2011
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27. Neurofilament light in serum for monitoring multiple sclerosis : A new quantitative tool for measuring disease activity and therapeutic response

Author

Novakova, L., Zetterberg, H., Axelsson, M., Sundström, Peter, Khademi, M., Gunnarsson, M., Malmestrom, C., Svenningsson, A., Olsson, T., Piehl, F., Blennow, K., Lycke, J., Novakova, L., Zetterberg, H., Axelsson, M., Sundström, Peter, Khademi, M., Gunnarsson, M., Malmestrom, C., Svenningsson, A., Olsson, T., Piehl, F., Blennow, K., and Lycke, J.

Published
2017
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32. Superior efficacy and tolerability of rituximab as compared to fingolimod for MS patients switching from natalizumab due to positive JC virus serology

Author

Alping, P., Islam-Jakobsson, Protik, Novakova, L., Salzer, Jonatan, Björck, A., Axelsson, M., Malmeström, C., Fink, K., Frisell, T., Lycke, J., Svenningsson, Anders, Piehl, F., Alping, P., Islam-Jakobsson, Protik, Novakova, L., Salzer, Jonatan, Björck, A., Axelsson, M., Malmeström, C., Fink, K., Frisell, T., Lycke, J., Svenningsson, Anders, and Piehl, F.

Abstract

Supplement

Published
2015

36. Dasatinib in imatinib-resistant or -intolerant CML patients: data from the clinical practice of 6 hematological centers in the Czech Republic

Author

Klamova H, Faber E, Zackova D, Markova M, Voglova J, Cmunt E, Novakova L, Kateřina Machová Poláková, Moravcova J, Dvorakova D, Michalova K, Brezinova J, Oltova A, Jarosova M, Cetkovsky P, Indrak K, and Mayer J

Subjects
Adult, Male, Salvage Therapy, Dasatinib, Fusion Proteins, bcr-abl, Antineoplastic Agents, Middle Aged, Protein-Tyrosine Kinases, Piperazines, Survival Rate, Thiazoles, Young Adult, Pyrimidines, Treatment Outcome, Drug Resistance, Neoplasm, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Benzamides, Mutation, Imatinib Mesylate, Humans, Female, Protein Kinase Inhibitors, Aged
Abstract

Dasatinib is effective second line treatment for patients with chronic myeloid leukemia (CML) resistant or intolerant to imatinib. We report here the first experiences with dasatinib therapy in 71 CML patients resistant or intolerant to imatinib from the real clinical practice of 6 hematological centers in the Czech Republic. Dose 100 mg daily and 70 mg twice daily was administered to patients with chronic phase (CP) and advanced phases (AP) CML. In chronic phase (n=46), complete hematological reponse (CHR) was achieved in 97%, major cytogenetic reponse (MCgR) in 77% and complete cytogenetic response (CCgR) in 67%. Major molecular reponse (MMR) was achieved in 19/31 patients in median of 10 months. In advanced phase (n=25), CHR was attained in 77%, MCgR in 39%, CCgR in 33% and MMR in 2/18 patients. Eleven different baseline mutations were followed up in 15 patients. Dasatinib eliminated mutations in most of the patients, but 3 patients acquired a new one. Novel mutations were detected under dasatinib therapy in 2 patients. Dasatinib was well tolerated, cytopenias were common and was managed by dose modification. The estimated progression free survival (PFS) at 12 months was 97+/-3% in CP and 62+/-21% in AP. The median time to treatment failure was 605 days in AP while it was not reached in CP patients. Our clinical experiences, described here, confirmed that dasatinib is associated with high response rates especially in imatinib resistant or intolerant CML patients in chronic phase.

Published
2010

37. What asset structure generates the highest possible profit for a manufacturing enterprise?

Author

Krulický Tomáš and Nováková Lucie

Subjects
asset structure, financial analysis, activity ratio, profitability ratio, liquidity ratio, comparison with the sector, Social Sciences
Abstract

The objective of the paper is to determine the most suitable operational redundant assets and asset structure for a manufacturing enterprise. They are determined by the financial analysis of ratios, vertical and horizontal analysis, and the calculation of Altman Z-score. The recommended sizes of activity ratios are: the turnover of total assets should be equal to the value of 1, the time of inventory turnover should be as short as possible, the turnover of inventories should be as large as possible, the time of debt collection should be the shortest possible, the due date of fulfilling obligations should be equal to 2 or higher. The ratios are compared with the sector and the position of enterprise is assessed. The limit of the research is the incapability to determine the best asset structure, but only the best possible one, on the basis of comparing with the sector that sets the bar in a specific field. Every enterprise aspiring to be competitive should meet the sector standards, at least.

Published
2023
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41. 175 Czech MDS Group experience with azacitidine in treatment of high risk MDS and AML patients

Author

Jonasova, A., primary, Cermak, J., additional, Cervinek, L., additional, Novakova, L., additional, Vondrakova, J., additional, Belohlavkova, P., additional, Sykora, M., additional, Seifertova, N., additional, Walterova, L., additional, Libiger, J., additional, Michalova, K., additional, Zemanova, Z., additional, Brezinova, J., additional, Kacmarova, K., additional, and Klapka, R., additional

Published
2011
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42. 124 Are we warranted to include patients with del 5q and trisomy 8 into the 5q minus syndrome?

Author

Neuwirtova, R., primary, Vozobulova, V., additional, Jonasova, A., additional, Voglova, J., additional, Vondrakova, J., additional, Cermak, J., additional, Sponerova, D., additional, Novakova, L., additional, Stejskal, L., additional, Zmolikova, J., additional, Maskova, Z., additional, Klimova, O., additional, Kessler, P., additional, Cervinek, L., additional, Seifertova, N., additional, and Zemanova, Z., additional

Published
2011
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44. 250 Are Fli1, EKLF, PU.1, HDM2 and TP53 factors implicated in refractory anemia and megakaryopoiesis in 5q- syndrome?

Author

Neuwirtova, R., primary, Fuchs, O., additional, Jonasova, A., additional, Holicka, M., additional, Vostry, M., additional, Kostecka, A., additional, Hajkova, H., additional, Cermak, J., additional, Vondrakova, J., additional, Hochova, I., additional, Siskova, M., additional, Libiger, J., additional, Sponerova, D., additional, Kadlckova, E., additional, Novakova, L., additional, Cerna, O., additional, Cmejla, R., additional, Pospisilova, D., additional, Brezinova, J., additional, Zemanova, Z., additional, Michalova, K., additional, and Seifertova, N., additional

Published
2011
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45. Incidence of second malignancies during treatment of chronic myeloid leukemia with tyrosine kinase inhibitors in the Czech Republic and Slovakia

Author

VOGLOVA, J., primary, MUZIK, J., additional, FABER, E., additional, ZACKOVA, D., additional, KLAMOVA, H., additional, STEINEROVA, K., additional, MICHALOVICOVA, Z., additional, DEMITROVICOVA, L., additional, CMUNT, E., additional, NOVAKOVA, L., additional, TOTHOVA, E., additional, BELOHLAVKOVA, P., additional, MAYER, J., additional, and INDRAK, K., additional

Published
2011
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