• MeSH
• Aspirin therapeutic use   MeSH
• Heparin, Low-Molecular-Weight administration & dosage   therapeutic use   MeSH
• Platelet Aggregation Inhibitors therapeutic use   MeSH
• Humans MeSH
• Multiple Myeloma * complications   MeSH
• Antineoplastic Agents adverse effects   therapeutic use   MeSH
• Thromboembolism * etiology   chemically induced   prevention & control   MeSH
• Warfarin therapeutic use   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Practice Guideline MeSH

Aging is an unavoidable process characterized by gradual failure of homeostasis that constitutes a critical risk factor for several age-related disorders. It has been unveiled that manipulation of various key pathways may decelerate the aging progression and the triggering of age-related diseases. As a consequence, the identification of compounds, preferably natural-occurring, administered through diet, with lifespan-extending, anti-aggregation and anti-oxidation properties that in parallel exhibit negligible side-effects is the main goal in the battle against aging. Here we analyze the role of 2,3-dehydrosilybin A/B (DHS A/B), a minor component of silymarin used in a plethora of dietary supplements. This flavonolignan is well-known for its anti-oxidative and neuroprotective properties, among others. We demonstrate that DHS A/B confers oxidative stress resistance not only in human primary cells but also in the context of a multi-cellular aging model, namely Caenorhabditis elegans (C. elegans) where it also promotes lifespan extension. We reveal that these DHS A/B outcomes are FGT-1 and DAF-16 dependent. We additionally demonstrate the anti-aggregation properties of DHS A/B in human cells of nervous origin but also in nematode models of Alzheimer's disease (AD), eventually leading to decelerated progression of AD phenotype. Our results identify DHS A/B as the active component of silymarin extract and propose DHS A/B as a candidate anti-aging and anti-aggregation compound.

• MeSH
• Cell Line MeSH
• Caenorhabditis elegans MeSH
• CHO Cells MeSH
• Cricetulus MeSH
• Longevity drug effects   MeSH
• Cricetinae MeSH
• Humans MeSH
• Protective Agents pharmacology   MeSH
• Oxidative Stress MeSH
• Protein Aggregation, Pathological prevention & control   MeSH
• Drug Evaluation, Preclinical MeSH
• Caenorhabditis elegans Proteins metabolism   MeSH
• Glucose Transport Proteins, Facilitative metabolism   MeSH
• Silymarin pharmacology   MeSH
• Cell Survival drug effects   MeSH
• Animals MeSH
• Check Tag
• Cricetinae MeSH
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH

• MeSH
• Clinical Medicine MeSH
• Statistics as Topic MeSH
• Publication type
• Abstracts MeSH
• Conference Proceedings MeSH
• Collected Work MeSH
• News MeSH

• Conspectus
• Patologie. Klinická medicína
• NML Fields
• statistika, zdravotnická statistika
• lékařství

• MeSH
• Nuclear Medicine MeSH
• Publication type
• Periodical MeSH
• Ephemera MeSH

• Conspectus
• Lékařské vědy. Lékařství
• NML Fields
• radiologie, nukleární medicína a zobrazovací metody

• MeSH
• Cell Aggregation MeSH
• Leukemia complications   pathology   MeSH
• Leukocytes physiology   pathology   MeSH
• Lymphadenitis MeSH
• Lung physiopathology   pathology   MeSH
• Vascular Patency MeSH
• Thrombosis MeSH
• Publication type
• Review MeSH

• MeSH
• Molecular Biology MeSH
• Spectrum Analysis MeSH
• Publication type
• Abstracts MeSH

• Conspectus
• Biochemie. Molekulární biologie. Biofyzika
• NML Fields
• biologie
• radiologie, nukleární medicína a zobrazovací metody

Cultures of three-dimensional aggregates of embryonic stem cells (ESCs) called embryoid bodies (EBs) provide a valuable system for analyzing molecular mechanisms that regulate differentiation of this unique cell type. Cyclin-dependent kinase inhibitor p27Kip1 (p27) becomes elevated during the differentiation of mouse ESCs (mESCs). In this study, various aspects of differentiation of EBs produced from normal and p27-deficient mESCs were analyzed to address the biological significance of this elevation. It was found that EBs lacking p27 grew significantly bigger, but this was not accompanied by detect-able abnormalities in the activities of cyclin-dependent kinases (CDKs). In most EB cells, downregulation of activating cyclins rather than upregulation of inhibiting p27 is probably responsible for lowering the activity of their CDKs. Abnormalities in the development of specific cell lineages were also observed in p27-deficient EBs. These included elimination of cells positive for cytokeratin endo-A (TROMA-I) and increased proliferation and formation of cavities originating from cells positive for Lewis-X. Our data also suggest that although two different pools of Lewis-X-expressing cells, cluster forming (ESC-like) and cavity forming (neural progenitors), normally exist in EBs, the absence of p27 leads to the enhancement of only the neural pool. No failure was found when the neurogenic capacity of p27-deficient mESCs was tested using various protein markers. Together, our data point to a dual role of p27 in mESCs, with one role being in the regulation of proliferation and the other role in establishing some other aspects of a differentiated phenotype.

• MeSH
• Lewis X Antigen metabolism   MeSH
• Cell Differentiation MeSH
• Cell Cycle MeSH
• Time Factors MeSH
• Down-Regulation MeSH
• Embryo, Mammalian physiology   MeSH
• Phenotype MeSH
• Financing, Organized MeSH
• Microscopy, Fluorescence MeSH
• Immunohistochemistry MeSH
• Immunoprecipitation MeSH
• Cyclin-Dependent Kinase Inhibitor p27 MeSH
• Stem Cells metabolism   MeSH
• Mice MeSH
• Tumor Suppressor Proteins physiology   genetics   MeSH
• Neurons metabolism   MeSH
• Cell Proliferation MeSH
• Cell Cycle Proteins physiology   genetics   MeSH
• Flow Cytometry MeSH
• Up-Regulation MeSH
• Cell Survival MeSH
• Blotting, Western MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH

The potential for gene exchange across ploidy levels has long been recognized, but only a few studies have explored the rate of gene flow among different cytotypes. In addition, most of the existing knowledge comes from contact zones between diploids and tetraploids. The purpose of this paper was to investigate relationships between diploid and hexaploid individuals within the Aster amellus aggregate. A. amellus is known to occur in diploid and hexaploid cytotypes in Europe, with a complex contact zone in central Europe. Patterns of genetic diversity were investigated using seven microsatellite loci at three different spatial scales: (1) in the single known mixed-ploidy population; (2) in populations at the contact zone and (3) in a wider range of populations across Europe. The results show clear separation of the cytotypes at all three spatial scales. In addition, analysis of molecular variance strongly supported a model predicting a single origin of the hexaploids, with no or very limited gene flow between the cytotypes. Some hexaploid individuals found in the mixed-ploidy population, however, fell into the diploid cluster. This could suggest recurrent polyploid formation or occasional cross-pollination between cytotypes; however, there are strong post-zygotic breeding barriers between the two cytotypes, making the latter less plausible. Overall, the results suggest that the cytotypes could represent two cryptic species. Nevertheless, their formal separation is difficult as they cannot be distinguished morphologically, occupy very similar habitat conditions and have largely overlapping distribution ranges. These results show that polyploid complexes must be treated with caution as they can hide biological diversity and can have different adaptation potentials, evolving independently.

• MeSH
• Principal Component Analysis MeSH
• Aster Plant genetics   MeSH
• Bayes Theorem MeSH
• Diploidy * MeSH
• Phylogeography MeSH
• Genetic Variation MeSH
• Microsatellite Repeats MeSH
• Models, Genetic MeSH
• Polyploidy * MeSH
• Genes, Plant MeSH
• Gene Flow * MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Europe MeSH

• MeSH
• Medicine MeSH
• Publication type
• Periodical MeSH

• Conspectus
• Lékařské vědy. Lékařství
• NML Fields
• lékařství

Drug repurposing is a versatile strategy to improve current therapies. Disulfiram has long been used in the treatment of alcohol dependency and multiple clinical trials to evaluate its clinical value in oncology are ongoing. We have recently reported that the disulfiram metabolite diethyldithiocarbamate, when combined with copper (CuET), targets the NPL4 adapter of the p97VCP segregase to suppress the growth of a spectrum of cancer cell lines and xenograft models in vivo. CuET induces proteotoxic stress and genotoxic effects, however important issues concerning the full range of the CuET-evoked tumor cell phenotypes, their temporal order, and mechanistic basis have remained largely unexplored. Here, we have addressed these outstanding questions and show that in diverse human cancer cell models, CuET causes a very early translational arrest through the integrated stress response (ISR), later followed by features of nucleolar stress. Furthermore, we report that CuET entraps p53 in NPL4-rich aggregates leading to elevated p53 protein and its functional inhibition, consistent with the possibility of CuET-triggered cell death being p53-independent. Our transcriptomics profiling revealed activation of pro-survival adaptive pathways of ribosomal biogenesis (RiBi) and autophagy upon prolonged exposure to CuET, indicating potential feedback responses to CuET treatment. The latter concept was validated here by simultaneous pharmacological inhibition of RiBi and/or autophagy that further enhanced CuET's tumor cytotoxicity, using both cell culture and zebrafish in vivo preclinical models. Overall, these findings expand the mechanistic repertoire of CuET's anti-cancer activity, inform about the temporal order of responses and identify an unorthodox new mechanism of targeting p53. Our results are discussed in light of cancer-associated endogenous stresses as exploitable tumor vulnerabilities and may inspire future clinical applications of CuET in oncology, including combinatorial treatments and focus on potential advantages of using certain validated drug metabolites, rather than old, approved drugs with their, often complex, metabolic profiles.

• MeSH
• Zebrafish metabolism   MeSH
• Disulfiram * metabolism   MeSH
• Humans MeSH
• Cell Line, Tumor MeSH
• Tumor Suppressor Protein p53 genetics   metabolism   MeSH
• Neoplasms * metabolism   MeSH
• Ribosomes metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

The 26S proteasome degrades the majority of cellular proteins and affects all aspects of cellular life. Therefore, the 26S proteasome abundance, proper assembly, and activity in different life contexts need to be precisely controlled. Impaired proteasome activity is considered a causative factor in several serious disorders. Recent advances in proteasome biology have revealed that the proteasome can be activated by different factors or small molecules. Thus, activated ubiquitin-dependent proteasome degradation has effects such as extending the lifespan in different models, preventing the accumulation of protein aggregates, and reducing their negative impact on cells. Increased 26S proteasome-mediated degradation reduces proteotoxic stress and can potentially improve the efficacy of engineered degraders, such as PROTACs, particularly in situations characterized by proteasome malfunction. Here, emerging ideas and recent insights into the pharmacological activation of the proteasome at the transcriptional and posttranslational levels are summarized.

• Publication type
• Journal Article MeSH
• Review MeSH

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic form of familial small vessel disease; no preventive or curative therapy is available. CADASIL is caused by mutations in the NOTCH3 gene, resulting in a mutated NOTCH3 receptor, with aggregation of the NOTCH3 extracellular domain (ECD) around vascular smooth muscle cells. In this study, we have developed a novel active immunization therapy specifically targeting CADASIL-like aggregated NOTCH3 ECD. Immunizing CADASIL TgN3R182C150 mice with aggregates composed of CADASIL-R133C mutated and wild-type EGF1-5 repeats for a total of 4 months resulted in a marked reduction (38-48%) in NOTCH3 deposition around brain capillaries, increased microglia activation and lowered serum levels of NOTCH3 ECD. Active immunization did not impact body weight, general behavior, the number and integrity of vascular smooth muscle cells in the retina, neuronal survival, or inflammation or the renal system, suggesting that the therapy is tolerable. This is the first therapeutic study reporting a successful reduction of NOTCH3 accumulation in a CADASIL mouse model supporting further development towards clinical application for the benefit of CADASIL patients.

• MeSH
• Immunotherapy, Active MeSH
• CADASIL * genetics   therapy   MeSH
• Capillaries metabolism   MeSH
• Disease Models, Animal MeSH
• Brain metabolism   MeSH
• Mutation MeSH
• Mice MeSH
• Receptor, Notch3 genetics   metabolism   MeSH
• Receptors, Notch metabolism   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Cadmium (Cd), an environmental and industrial pollutant, poses a potential threat and affects many systems in human and animals. Although several reports on Cd toxicity were presented, the acute effect of Cd on systemic and thrombotic events was not reported so far. Cd (2.284 mg/kg) or saline (control) was injected intraperitoneally (ip), and the systemic parameters were assessed in mice. Compared to control group, acute intraperitoneal injection of Cd, in mice showed significant quickening of platelet aggregation (P<0.001) leading to pial cerebral thrombosis. Likewise, Cd exposure caused a significant increase in white blood cell numbers (P<0.05) indicating the occurrence of systemic inflammation. Also, alanine aminotransferase (ALT) (P<0.05) and creatinine (P<0.01) levels were both significantly increased. Interestingly, the superoxide dismutase activity was significantly decreased in Cd treated group compared to control group (P<0.001), suggesting the occurrence of oxidative stress. We conclude that the Cd exposure in mice causes acute thromboembolic events, oxidative stress and alter liver and kidney functions.

• MeSH
• Alanine Transaminase metabolism   MeSH
• Mice, Inbred Strains MeSH
• Liver metabolism   drug effects   MeSH
• Cadmium toxicity   MeSH
• Creatinine metabolism   MeSH
• Kidney metabolism   drug effects   MeSH
• Mice MeSH
• Oxidative Stress drug effects   MeSH
• Thromboembolism chemically induced   metabolism   MeSH
• Inflammation chemically induced   metabolism   MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH

Hyperparatyreóza (HPT) patří k onemocněním, jejichž incidence stoupá. Převážnou většinu primárních hyperparatyreóz (asi 80 %) tvoří adenomy. Karcinom příštítných tělísek je velmi vzácný. K lokalizaci adenomů příštítných tělísek se standardně používá ultrasonografie, scintigrafie, nejčastěji 99mTc-MIBI a CT. Při stanovení diagnózy primární hyperparatyreózy je operační výkon standardním léčebným postupem. Nezastupitelné postavení má peroperační ultrasonografie. V průběhu tří let bylo na našem pracovišti operováno celkem 21 pacientů s diagnózou adenom příštítného tělíska, který byl histologicky potvrzen u 19 pacientů. Náš malý soubor operovaných pacientů vykazuje úspěšnost 90,5 %.

Hyperparathyreosis is one of the diseases whose incidence has been increasing. Vast majority of hyperparathyreosis (about 80 %) is made up by adenomas. Carcinoma of parathyroid glands is very rare. Ultrasonography, scintigraphy, most frequently 99mTc-MIBI and CT are standardly being used for localization of the adenomas of parathyorid glands. Operation is a standard medical method in the process of determinating the diagnosis of primary hyperparathyreosis. Peroperative ultrasonography has irreplaceable position. 21 patients with diagnosis of adenoma of parathyroid glands which was histologically confirmed in 19 patiens have been operated in our workplace during three years. Our small aggregate of operated patients shows success rate 90,5 %.

• MeSH
• Adenoma * diagnosis   etiology   surgery   classification   therapy   MeSH
• Humans MeSH
• Magnetic Resonance Imaging methods   MeSH
• Parathyroid Neoplasms * diagnosis   etiology   surgery   classification   therapy   MeSH
• Intraoperative Care methods   statistics & numerical data   trends   MeSH
• Statistics as Topic MeSH
• Tomography, Emission-Computed methods   MeSH
• Ultrasonography methods   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

• MeSH
• Cell Aggregation MeSH
• Brain cytology   MeSH
• Mice MeSH
• Check Tag
• Mice MeSH

Five platinum(II) complexes bearing a (1,3-dibenzyl)imidazol-2-ylidene ligand but different leaving groups trans to it were examined for cytotoxicity, DNA and cell cycle interference, vascular disrupting properties, and nephrotoxicity. The cytotoxicity of complexes 3a-c increased with the steric shielding of their leaving chloride ligand, and complex 3c, featuring two triphenylphosphanes, was the most efficacious, with submicromolar IC50 concentrations. Complexes 3a-c interacted with DNA in electrophoretic mobility shift and ethidium bromide binding assays. The cationic complex 3c did not bind coordinatively to DNA but led to its aggregation, damage that is not amenable to the usual repair mechanisms. Accordingly, it arrested the cell cycle of melanoma cells in G1 phase, whereas cis-dichlorido[(1,3-dibenzyl)imidazol-2-ylidene](dimethyl sulfoxide) platinum(II) 3a induced G2/M phase arrest. Complex 3c also disrupted the blood vessels in the chorioallantoic membrane of fertilized chicken eggs. Ex vivo studies using precision-cut tissue slices suggested the nephrotoxicities of 3a-c to be clinically manageable.

• MeSH
• DNA drug effects   MeSH
• Heterocyclic Compounds chemistry   pharmacology   MeSH
• Humans MeSH
• Methane analogs & derivatives   chemistry   MeSH
• Cell Line, Tumor MeSH
• Antineoplastic Agents chemistry   pharmacology   MeSH
• Platinum Compounds chemistry   pharmacology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

• Keywords
• Biologie molekulární, Cytogenetika,
• MeSH
• Cell Biology MeSH
• Cells MeSH
• Cytogenetics MeSH
• Hormones MeSH
• Molecular Biology MeSH
• Antineoplastic Agents MeSH
• Viruses MeSH
• Publication type
• Conference Proceedings MeSH
• Collected Work MeSH

• Conspectus
• Buněčná biologie. Cytologie
• NML Fields
• cytologie, klinická cytologie

• MeSH
• Alanine biosynthesis   genetics   adverse effects   MeSH
• Alzheimer Disease etiology   genetics   MeSH
• Autophagy genetics   MeSH
• Research Support as Topic MeSH
• Glutamine biosynthesis   genetics   adverse effects   MeSH
• Huntington Disease etiology   genetics   MeSH
• Protein Conformation MeSH
• Humans MeSH
• Neurodegenerative Diseases etiology   metabolism   MeSH
• Parkinson Disease etiology   genetics   MeSH
• Proteins genetics   metabolism   adverse effects   MeSH
• Check Tag
• Humans MeSH

• MeSH
• Endopeptidases MeSH
• Cell Adhesion Molecules MeSH
• Antibodies MeSH
• Cattle MeSH
• Semen physiology   chemistry   MeSH
• Spermatozoa physiology   chemistry   MeSH
• Animals MeSH
• Check Tag
• Cattle MeSH
• Animals MeSH

Papillon-Lefèvre syndrome (PLS) is characterized by nonfunctional neutrophil serine proteases (NSPs) and fulminant periodontal inflammation of unknown cause. Here we investigated neutrophil extracellular trap (NET)-associated aggregation and cytokine/chemokine-release/degradation by normal and NSP-deficient human and mouse granulocytes. Stimulated with solid or soluble NET inducers, normal neutrophils formed aggregates and both released and degraded cytokines/chemokines. With increasing cell density, proteolytic degradation outweighed release. Maximum output of cytokines/chemokines occurred mostly at densities between 2 × 107 and 4 × 107 neutrophils/cm3. Assessment of neutrophil density in vivo showed that these concentrations are surpassed during inflammation. Association with aggregated NETs conferred protection of neutrophil elastase against α1-antitrypsin. In contrast, eosinophils did not influence cytokine/chemokine concentrations. The proteolytic degradation of inflammatory mediators seen in NETs was abrogated in Papillon-Lefèvre syndrome (PLS) neutrophils. In summary, neutrophil-driven proteolysis of inflammatory mediators works as a built-in safeguard for inflammation. The absence of this negative feedback mechanism might be responsible for the nonresolving periodontitis seen in PLS.-Hahn, J., Schauer, C., Czegley, C., Kling, L., Petru, L., Schmid, B., Weidner, D., Reinwald, C., Biermann, M. H. C., Blunder, S., Ernst, J., Lesner, A., Bäuerle, T., Palmisano, R., Christiansen, S., Herrmann, M., Bozec, A., Gruber, R., Schett, G., Hoffmann, M. H. Aggregated neutrophil extracellular traps resolve inflammation by proteolysis of cytokines and chemokines and protection from antiproteases.

• MeSH
• Chemokines metabolism   MeSH
• Cytokines metabolism   MeSH
• Adult MeSH
• Extracellular Traps metabolism   MeSH
• Protease Inhibitors metabolism   MeSH
• Ionomycin pharmacology   MeSH
• Uric Acid pharmacology   MeSH
• Humans MeSH
• Inflammation Mediators metabolism   MeSH
• Adolescent MeSH
• Mice, Inbred BALB C MeSH
• Mice MeSH
• NADPH Oxidases genetics   MeSH
• Neutrophils drug effects   metabolism   MeSH
• Periodontitis metabolism   MeSH
• Proteolysis MeSH
• Tetradecanoylphorbol Acetate pharmacology   MeSH
• Inflammation prevention & control   MeSH
• Animals MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

• MeSH
• Platelet Endothelial Cell Adhesion Molecule-1 MeSH
• Blood Coagulation * MeSH
• Blood MeSH
• Humans MeSH
• Check Tag
• Humans MeSH

• Publication type
• Meeting Abstract MeSH

• MeSH
• Escherichia coli O157 classification   pathology   MeSH
• Chickens microbiology   MeSH
• Lactobacillus physiology   genetics   isolation & purification   MeSH
• Cell Adhesion Molecules genetics   MeSH
• Polymerase Chain Reaction veterinary   MeSH
• Food Microbiology MeSH
• Cattle microbiology   MeSH
• Animals MeSH
• Check Tag
• Cattle microbiology   MeSH
• Female MeSH
• Animals MeSH

• MeSH
• Erythrocyte Aggregation MeSH
• Cystic Fibrosis MeSH
• Blood Proteins MeSH
• Humans MeSH
• Membrane Proteins MeSH
• In Vitro Techniques MeSH
• Check Tag
• Humans MeSH

• MeSH
• Cell Aggregation MeSH
• Bifidobacterium chemistry   MeSH
• Child MeSH
• Escherichia coli O157 chemistry   MeSH
• Feces microbiology   MeSH
• Research Support as Topic MeSH
• Hydrophobic and Hydrophilic Interactions MeSH
• Lactobacillus chemistry   MeSH
• Humans MeSH
• Mucins chemistry   MeSH
• Animals MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Animals MeSH

• MeSH
• Cell Aggregation MeSH
• Neurons MeSH
• In Vitro Techniques MeSH

• MeSH
• Cell Adhesion genetics   MeSH
• Escherichia coli pathogenicity   MeSH
• Lactobacillus pathogenicity   MeSH
• Diarrhea microbiology   MeSH
• Veterinary Medicine MeSH
• Animals MeSH
• Check Tag
• Animals MeSH

• MeSH
• Receptor Aggregation MeSH
• Leukemia, Basophilic, Acute pathology   MeSH
• Antigens, CD metabolism   MeSH
• Rats MeSH
• Mast Cells metabolism   drug effects   MeSH
• Protein Processing, Post-Translational MeSH
• Receptors, Immunologic metabolism   MeSH
• Histamine Release drug effects   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Animals MeSH
• Publication type
• Comparative Study MeSH

Cells have elaborated a complex strategy to maintain protein homeostasis under physiological as well as stress conditions with the aim to ensure the smooth functioning of vital processes and producing healthy offspring. Impairment of one of the most important processes in living cells, translation, might have serious consequences including various brain disorders in humans. Here, we describe a variant of the translation initiation factor eIF3a, Rpg1-3, mutated in its PCI domain that displays an attenuated translation efficiency and formation of reversible assemblies at physiological growth conditions. Rpg1-3-GFP assemblies are not sequestered within mother cells only as usual for misfolded-protein aggregates and are freely transmitted from the mother cell into the bud although they are of non-amyloid nature. Their bud-directed transmission and the active movement within the cell area depend on the intact actin cytoskeleton and the related molecular motor Myo2. Mutations in the Rpg1-3 protein render not only eIF3a but, more importantly, also the eIF3 core complex prone to aggregation that is potentiated by the limited availability of Hsp70 and Hsp40 chaperones. Our results open the way to understand mechanisms yeast cells employ to cope with malfunction and aggregation of essential proteins and their complexes.

• MeSH
• Eukaryotic Initiation Factor-3 genetics   MeSH
• Humans MeSH
• Actin Cytoskeleton genetics   MeSH
• Mitochondria MeSH
• Mutation MeSH
• Myosin Type V genetics   MeSH
• Protein Aggregates genetics   MeSH
• HSP40 Heat-Shock Proteins genetics   MeSH
• HSP70 Heat-Shock Proteins genetics   MeSH
• Saccharomyces cerevisiae Proteins genetics   MeSH
• Saccharomyces cerevisiae genetics   growth & development   MeSH
• Myosin Heavy Chains genetics   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

• MeSH
• Cell Aggregation MeSH
• Clinical Laboratory Techniques MeSH
• Serum Albumin chemistry   MeSH

Práce poskytuje přehled principů agregace, dostupných metod jejího měření a úskalí interpretace naměřených výsledků. V seznamu osmi agregometrických metod jsou popsány metody měření krvácivosti, optická a impedanční agregometrie, trombelastografie a průtoková cytometrie, jakož i měření metabolitu tromboxanu v moči. Referujeme o podmíněnosti agregačních indukcí, které ovlivňují výsledek. Agregace absolutní je dosud sama o sobě neměřitelná. Efekt prevence aterosklerotických komplikací cestou antiagregační léčby se odvozuje většinou z výsledků studií, jež detekují dopad zredukované trombogeneze a emboligeneze na kliniku. Úprava dávkovacích schémat vychází z těchto sekundárních a odvozených poznatků. Samotná intenzita agregační pohotovosti se pro své obtížné měření prosazuje v těchto rozhodnutích pouze velmi pozvolna. Sumarizujeme též současné pohledy na rezistenci vůči kyselině acetylsalicylové, ve dvou variantách její povahy – rezistenci klinické a laboratorní. Uzavíráme pohledem na budoucí možnosti agregačního monitoringu.

This paper reviews the principles of thrombocytic aggregation, available methods of measuring it and pitfalls in the interpretation of results obtained. A list of eight aggregometric methods provides descriptions of the evaluation of bleeding times, of optic and impedance whole blood aggregometry, of thrombelastography and flow cytometry, as well as describing measurements of urine levels of the metabolite thromboxan. We report how results depend on the way in which the aggregation is induced. Absolute aggregation remains, as yet, immeasurable. The effectiveness of prevention of atherosclerotic complications using anti-aggregation therapy is usually determined on the basis of studies that observe the impact of reduced thrombogenesis and emboligenesis on clinical outcome. Modifications in drug dosage are usually stipulated by such secondary and derived data. The intensity of aggregation readiness itself – due to difficulties in assessing it – plays only a minor role in these decisions and is only slowly achieving credibility. We also summarize current views on resistance to acetylsalicylic acid, which appears in two variants: clinical resistance and laboratory resistance. We conclude with an overview of future possibilities for monitoring aggregation.

• Keywords
• agregace, metody měření, kyselina acetylsalicylová, rezistence, prevence iktů, ischemický iktus, trombogeneze,
• MeSH
• Platelet Aggregation physiology   drug effects   MeSH
• Aspirin therapeutic use   MeSH
• Stroke drug therapy   prevention & control   MeSH
• Financing, Organized MeSH
• Hematologic Tests methods   instrumentation   utilization   MeSH
• Platelet Aggregation Inhibitors administration & dosage   adverse effects   therapeutic use   MeSH
• Clinical Laboratory Techniques instrumentation   utilization   MeSH
• Drug Resistance genetics   immunology   drug effects   MeSH
• Humans MeSH
• Meta-Analysis as Topic MeSH
• Flow Cytometry methods   utilization   MeSH
• Thromboxanes isolation & purification   urine   MeSH
• Thrombelastography methods   utilization   MeSH
• Blood Coagulation Tests methods   utilization   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

• MeSH
• Cell Aggregation drug effects   MeSH
• Interleukin-15 physiology   MeSH
• Neutrophils MeSH
• Blood Platelets MeSH

Po chirurgické revaskularizaci myokardu bez použití mimotělního oběhu (MO) jsou popisovány častější uzávěry především žilních bypassů. Některé práce udávají jako možnou příčinu existenci "hyperkoagulačního" stavu po tomto typu operací. Cílem práce je porovnat časnou (pooperační) a pozdní aktivitu trombocytů u pacientů operovaných s a bez MO. Aktivita trombocytů bude měřena testem agregability a průtokovou cytometrií. Záměrem je prokázat zvýšenou aktivitu trombocytů po operacích bez MO. Průkaz vyšší aktivity destiček by se mohl stát základem nové léčebné strategie u pacientů operovaných bez MO.; More frequent venous graft closures have been reported to be associated with off-pump compared with on-pump myocardial revascularization procedures. Hypercoagulation is hypothesized to play a role in this phenomenon. The objective is to compare early andlate platelet activity in on-pump and off-pump patients. Platelet activity will be measured by the aggregability test and flow cytometry. Hypothesis of platelet higher activity after off-pump compared with on-pump procedures will be tested.

• MeSH
• Platelet Adhesiveness MeSH
• Platelet Aggregation MeSH
• Coronary Artery Bypass, Off-Pump MeSH
• Coronary Circulation MeSH
• Coronary Artery Disease surgery   MeSH
• Flow Cytometry MeSH
• Myocardial Revascularization MeSH
• Blood Platelets MeSH

• Conspectus
• Patologie. Klinická medicína
• NML Fields
• kardiologie
• angiologie
• NML Publication type
• závěrečné zprávy o řešení grantu IGA MZ ČR

Autoři prezentují případ nemocného, který prodělal akutní infarkt myokardu již ve svých 35 letech. Následná krvácivá komplikace při kombinované antiagregační a antikoagulační terapii u tohoto nemocného vedla k nálezu dlaždicobuněčného karcinomu v oblasti rekta, který byl úspěšně odstraněn. V případě akutního infarktu myokardu provázeného krvácivou komplikací je nezbytné komplexní vyšetření nemocného, včetně onkologického screeningu i u mladého jedince.

The authors present the case of a man developing an acute myocardial infarction when only 35 years old. A subsequent bleeding complication while receiving antiplatelet and anticoagulation therapy led to the finding of squamous cell carcinoma in the rectal region; the carcinoma was successfully removed. Patients developing acute myocardial infarction associated with a bleeding complication require comprehensive assessment including cancer screening tests even in young individuals.

• Keywords
• Antiagregační terapie, Dlaždicobuněčný karcinom,
• MeSH
• Angioplasty, Balloon, Coronary methods   utilization   MeSH
• Diagnostic Techniques, Cardiovascular utilization   MeSH
• Adult MeSH
• Financing, Organized MeSH
• Myocardial Infarction diagnosis   complications   therapy   MeSH
• Platelet Aggregation Inhibitors administration & dosage   adverse effects   therapeutic use   MeSH
• Hemorrhage complications   MeSH
• Humans MeSH
• Rectal Neoplasms diagnosis   surgery   complications   MeSH
• Tomography, X-Ray Computed methods   utilization   MeSH
• Carcinoma, Squamous Cell diagnosis   surgery   complications   MeSH
• Stents utilization   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Case Reports MeSH

Cancer incidence is rising and this global challenge is further exacerbated by tumour resistance to available medicines. A promising approach to meet the need for improved cancer treatment is drug repurposing. Here we highlight the potential for repurposing disulfiram (also known by the trade name Antabuse), an old alcohol-aversion drug that has been shown to be effective against diverse cancer types in preclinical studies. Our nationwide epidemiological study reveals that patients who continuously used disulfiram have a lower risk of death from cancer compared to those who stopped using the drug at their diagnosis. Moreover, we identify the ditiocarb-copper complex as the metabolite of disulfiram that is responsible for its anti-cancer effects, and provide methods to detect preferential accumulation of the complex in tumours and candidate biomarkers to analyse its effect on cells and tissues. Finally, our functional and biophysical analyses reveal the molecular target of disulfiram's tumour-suppressing effects as NPL4, an adaptor of p97 (also known as VCP) segregase, which is essential for the turnover of proteins involved in multiple regulatory and stress-response pathways in cells.

• MeSH
• Alcoholism drug therapy   epidemiology   MeSH
• Molecular Targeted Therapy MeSH
• Disulfiram chemistry   pharmacology   therapeutic use   MeSH
• Adult MeSH
• Nuclear Proteins chemistry   metabolism   MeSH
• Middle Aged MeSH
• Humans MeSH
• Copper chemistry   MeSH
• Mice MeSH
• Neoplasms drug therapy   metabolism   mortality   pathology   MeSH
• Alcohol Deterrents * pharmacology   therapeutic use   MeSH
• Drug Repositioning * MeSH
• Protein Aggregates MeSH
• Proteolysis drug effects   MeSH
• Antineoplastic Agents * pharmacology   therapeutic use   MeSH
• Heat-Shock Response drug effects   MeSH
• Protein Binding drug effects   MeSH
• Animals MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Denmark epidemiology   MeSH

Reticulate evolution is characterized by occasional hybridization between two species, creating a network of closely related taxa below and at the species level. In the present research, we aimed to verify the hypothesis of the allopolyploid origin of hexaploid C. album s. str., identify its putative parents and estimate the frequency of allopolyploidization events. We sampled 122 individuals of the C. album aggregate, covering most of its distribution range in Eurasia. Our samples included putative progenitors of C. album s. str. of both ploidy levels, i.e. diploids (C. ficifolium, C. suecicum) and tetraploids (C. striatiforme, C. strictum). To fulfil these objectives, we analysed sequence variation in the nrDNA ITS region and the rpl32-trnL intergenic spacer of cpDNA and performed genomic in-situ hybridization (GISH). Our study confirms the allohexaploid origin of C. album s. str. Analysis of cpDNA revealed tetraploids as the maternal species. In most accessions of hexaploid C. album s. str., ITS sequences were completely or nearly completely homogenized towards the tetraploid maternal ribotype; a tetraploid species therefore served as one genome donor. GISH revealed a strong hybridization signal on the same eighteen chromosomes of C. album s. str. with both diploid species C. ficifolium and C. suecicum. The second genome donor was therefore a diploid species. Moreover, some individuals with completely unhomogenized ITS sequences were found. Thus, hexaploid individuals of C. album s. str. with ITS sequences homogenized to different degrees may represent hybrids of different ages. This proves the existence of at least two different allopolyploid lineages, indicating a polyphyletic origin of C. album s. str.

• MeSH
• Chenopodium album genetics   MeSH
• Cytogenetic Analysis methods   MeSH
• DNA, Plant genetics   MeSH
• Phylogeny MeSH
• Genetic Variation genetics   MeSH
• Genomics MeSH
• Evolution, Molecular * MeSH
• Polyploidy * MeSH
• Publication type
• Journal Article MeSH

The interaction of α-synuclein with mitochondria in both typical and atypical Parkinson's disease is a critical component of degeneration. The mechanism of cell-to-cell propagation of pathological α-synuclein in synucleinopathies is unclear. Intercellular exchange of mitochondria along tunnelling nanotubes has been described in other diseases, such as cancer; however, its role in synucleinopathies is unknown. Pathological α-synuclein species have been demonstrated previously to move from cell to cell via tunnelling nanotubes. This process was further explored using co-culture and monoculture systems to determine if α-synuclein binds to migrating mitochondria within tunnelling nanotubes. Super-resolution analysis via stimulated emission depletion microscopy showed interaction between α-synuclein with the mitochondrial outer membrane and the presence of alpha-synuclein associated with mitochondria in tunnelling nanotubes between 1321N1, differentiated THP-1 and SH-SY5Y cell types. siRNA knockdown of Miro1, a critical protein-bridging mitochondria to the motor adaptor complex, had no effect on mitochondrial density or α-synuclein association with mitochondria in tunnelling nanotubes. The results show that α-synuclein aggregates associate with mitochondria in intercellular tunnelling nanotubes, suggesting that mitochondria-mediated α-synuclein transfer between cells may contribute to cell-to-cell spread of α-synuclein aggregates and disease propagation.

• MeSH
• alpha-Synuclein metabolism   MeSH
• Coculture Techniques MeSH
• Humans MeSH
• Mitochondria metabolism   pathology   MeSH
• Cell Line, Tumor MeSH
• Nanotubes * MeSH
• Protein Aggregation, Pathological metabolism   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

The effect of the yeast cell-death inducing agents, Bax and acetic acid, on mitochondrial structure of Schizosaccharomyces pombe was studied. Comparison of mitochondrial structures in cells grown on different substrates and visualized with different probes revealed variations in their morphology. Cells grown on respiratory C sources as well as in the presence of antimycin A exhibited punctuated mitochondria when visualized with mitochondrially targeted green fluorescent protein, while they still appeared as tubular structures when stained with DiOC6(3). Both expression of Bax and acetic acid treatment induced fragmentation and aggregation of mitochondrial network, which could be prevented by coexpression of Bcl-XL. Aberrant mitochondrial morphology generated by either Bax or acetic acid was not accompanied with the loss of mitochondrial genome (mtDNA), indicating that alterations of mitochondrial morphology following death stimuli follow different mechanisms than those involved in mitochondrial inheritance mutants.

• MeSH
• Acetates metabolism   MeSH
• Staining and Labeling methods   utilization   MeSH
• Cell Death genetics   drug effects   MeSH
• Cellular Structures MeSH
• Research Support as Topic MeSH
• Microscopy, Fluorescence methods   utilization   MeSH
• Mitochondria genetics   drug effects   MeSH
• Saccharomyces genetics   growth & development   MeSH
• Blotting, Southern methods   utilization   MeSH

The amyloid cascade hypothesis postulates that extracellular deposits of amyloid β (Aβ) are the primary and initial cause leading to the full development of Alzheimer's disease (AD) with intracellular neurofibrillary tangles; however, the details of this mechanism have not been fully described until now. Our preliminary data, coming from our day-to-day neuropathology practice, show that the primary location of the hyperphosphorylated tau protein is in the vicinity of the cell membrane of dystrophic neurites. This observation inspired us to formulate a hypothesis that presumes an interaction between low-density lipoprotein receptor-related protein 1 (LRP1) and fibrillar aggregates of, particularly, Aβ42 anchored at the periphery of neuritic plaques, making internalization of the LRP1-Aβ42 complex infeasible and, thus, causing membrane dysfunction, leading to the tauopathy characterized by intracellular accumulation and hyperphosphorylation of the tau protein. Understanding AD as a membrane dysfunction tauopathy may draw attention to new treatment approaches not only targeting Aβ42 production but also, perhaps paradoxically, preventing the formation of LRP1-Aβ42.

• MeSH
• Alzheimer Disease * metabolism   pathology   etiology   MeSH
• Amyloid beta-Peptides * metabolism   MeSH
• Cell Membrane metabolism   MeSH
• Phosphorylation MeSH
• Humans MeSH
• Peptide Fragments metabolism   MeSH
• Low Density Lipoprotein Receptor-Related Protein-1 * metabolism   MeSH
• tau Proteins * metabolism   MeSH
• Tauopathies * metabolism   pathology   etiology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Mounting evidence suggests that the neuronal cell membrane is the main site of oligomer-mediated neuronal toxicity of amyloid-β peptides in Alzheimer's disease. To gain a detailed understanding of the mutual interference of amyloid-β oligomers and the neuronal membrane, we carried out microseconds of all-atom molecular dynamics (MD) simulations on the dimerization of amyloid-β (Aβ)42 in the aqueous phase and in the presence of a lipid bilayer mimicking the in vivo composition of neuronal membranes. The dimerization in solution is characterized by a random coil to β-sheet transition that seems on pathway to amyloid aggregation, while the interactions with the neuronal membrane decrease the order of the Aβ42 dimer by attenuating its propensity to form a β-sheet structure. The main lipid interaction partners of Aβ42 are the surface-exposed sugar groups of the gangliosides GM1. As the neurotoxic activity of amyloid oligomers increases with oligomer order, these results suggest that GM1 is neuroprotective against Aβ-mediated toxicity.

• MeSH
• Amyloid chemistry   MeSH
• Amyloid beta-Peptides chemistry   metabolism   MeSH
• Cell Membrane metabolism   MeSH
• G(M1) Ganglioside metabolism   MeSH
• Protein Conformation MeSH
• Humans MeSH
• Lipid Bilayers metabolism   MeSH
• Protein Multimerization * MeSH
• Neurons metabolism   MeSH
• Molecular Dynamics Simulation MeSH
• Protein Binding MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Aβ, IAPP, α-synuclein, and prion proteins belong to the amyloidogenic intrinsically disordered proteins' family; indeed, they lack well defined secondary and tertiary structures. It is generally acknowledged that they are involved, respectively, in Alzheimer's, Type II Diabetes Mellitus, Parkinson's, and Creutzfeldt-Jakob's diseases. The molecular mechanism of toxicity is under intense debate, as many hypotheses concerning the involvement of the amyloid and the toxic oligomers have been proposed. However, the main role is represented by the interplay of protein and the cell membrane. Thus, the understanding of the interaction mechanism at the molecular level is crucial to shed light on the dynamics driving this phenomenon. There are plenty of factors influencing the interaction as mentioned above, however, the overall view is made trickier by the apparent irreproducibility and inconsistency of the data reported in the literature. Here, we contextualized this topic in a historical, and even more importantly, in a future perspective. We introduce two novel insights: the chemical equilibrium, always established in the aqueous phase between the free and the membrane phospholipids, as mediators of protein-transport into the core of the bilayer, and the symmetry-breaking of oligomeric aggregates forming an alternating array of partially ordered and disordered monomers.

• Publication type
• Journal Article MeSH
• Review MeSH

Amyotrophic lateral sclerosis (ALS) is a devastating, uniformly lethal progressive degenerative disorder of motor neurons that overlaps with frontotemporal lobar degeneration (FTLD) clinically, morphologically, and genetically. Although many distinct mutations in various genes are known to cause amyotrophic lateral sclerosis, it remains poorly understood how they selectively impact motor neuron biology and whether they converge on common pathways to cause neuronal degeneration. Many of the gene mutations are in proteins that share similar functions. They can be grouped into those associated with cell axon dynamics and those associated with cellular phagocytic machinery, namely protein aggregation and metabolism, apoptosis, and intracellular nucleic acid transport. Analysis of pathways implicated by mutant ALS genes has provided new insights into the pathogenesis of both familial forms of ALS (fALS) and sporadic forms (sALS), although, regrettably, this has not yet yielded definitive treatments. Many genes play an important role, with TARDBP, SQSTM1, VCP, FUS, TBK1, CHCHD10, and most importantly, C9orf72 being critical genetic players in these neurological disorders. In this mini-review, we will focus on the molecular mechanisms of these two diseases.

• Publication type
• Journal Article MeSH
• Review MeSH

Anafylaxe je akutní, potencionálně fatální multiorgánová alergická reakce. Mů že se vyskytnout i u nejmenších dětí. Reakce u dětí do 3 let věku má specifický průběh a př íznaky. V časná a správná diagnóza a léčba anafylaxe mnohdy zachrání život. Důležitá jsou následná vyšetření, která verifikují spouštěč reakce. Laboratorní diagnostika anafylaxe u dětí má svá úskalí. Úspěšná léčba zahrnuje komplex medikamentózních a nemedikamentózních opatření. Akutní intervence spočívá v podání adrenalinu a v dalších postupech, které jsou přiměřené vě ku dítěte. Léčbu úvodních projevů anafylaxe má ovládat zdravotník i laik. Dítě s prodělanou anafylaxí č i rizikový potravinový alergik musí být vybaven balíčkem první pomoci, jeho opatrovníci mají mít informace jak a kdy ho použít.

Anaphylaxis is an acute, potentionally fatal, multi-organ system, allergic reaction. It may happen even to the youngest childre n. The reaction has specific symptoms and course for children up to 3 years old. The early and proper diagnosis and treatment of anaphys is often l ife saving. The subsequent tests are important for identification of the reaction trigger. The laboratory diagnosis of anaphylaxis of children has certain obstacles. The successful treatment comprises of set of medical and non-medical measures. The acute management is based on intramuscular a dmission of adrenaline and other procedures depending on childs age. Both healthcare professionals and children caregivers should be famili ar with initial anaphylaxis management. The child dispensed after the anaphylaxis treatment or a patient with a food allergy and a risk of anap hylaxis must be equipped with an emergency package. The caregivers must be educated to know when and how to use it.

• MeSH
• Epinephrine * adverse effects   therapeutic use   MeSH
• Allergens immunology   isolation & purification   adverse effects   MeSH
• Anaphylaxis * diagnosis   etiology   therapy   MeSH
• Histamine Antagonists therapeutic use   MeSH
• Platelet Activating Factor isolation & purification   adverse effects   MeSH
• Glucagon therapeutic use   MeSH
• Glucocorticoids therapeutic use   MeSH
• Histamine immunology   isolation & purification   adverse effects   MeSH
• Immunoglobulins isolation & purification   therapeutic use   MeSH
• Clinical Laboratory Techniques methods   utilization   MeSH
• Infant * MeSH
• Humans MeSH
• Infant Food adverse effects   utilization   MeSH
• Child, Preschool MeSH
• First Aid * methods   nursing   utilization   MeSH
• Practice Guidelines as Topic MeSH
• Tryptases immunology   isolation & purification   adverse effects   MeSH
• Check Tag
• Infant * MeSH
• Humans MeSH
• Male MeSH
• Child, Preschool MeSH
• Publication type
• Case Reports MeSH

Předkládána jsou dvě pozorování angiotropního lymfomu, který se klinicky manifestoval nepříznačnou neurologickou symptomatologíí a byl diagnostikován u dvou nemocných žen až post mortem. V jednom případě zemřela pacientka po třech měsících neurčitého encefalitického syndromu, ve druhém přínadě došlo k úmrtí po nezvykle dlouhé tříleté periodě prohlubující se demence a postupných motorických dysfunkcí. Sekce u obou nemocných prokázala čistě intravaskulární maligní lymfoidní agregáty (LCA, CD 20, Bel 2 pozitivní) v mozku a ledvinách, u pacientky s delší anamnézou pak navíc diseminaci do plic. Nález byl pak definitivně uzavírán jako angio tropní lymfom z B buněk, resp. intravaskulámí lymfomatóza. Kůže, lymfatické uzliny, slezina a kostní dřeň nebyly postiženy ani v jednom případě. Klinická diferenciální diagnostika tuto vzácnou etiologii onemocnění CNS nezahrnula a ani provedená mozková biopsie u obou žen neumožnila lymfom spolehlivě rozpoznat.

Described are two cases of angiotropic lymphoma where eventually autopsy elucidated nonspecific neurologic symptoms. One patient suffering ambiguous encephalitic syndrome died three months later, the second one passed away after an unusually long three -year period of progressive dementia and cumulative motoric dysfunction. The autopsy disclosed pure intravascular malignant lymphoid aggregates (LCA, CD 20, Bel 2-positive) in the brain and kidney of both patients. In the patients with the longer disease period, a dissemination to lung was also found. Definitive diagnosis was issued as a B cell type of angiotropic lymphoma. Skin, lymph nodes, spleen, and bone marrow were not affected in any case. The clinical differential diagnosis algorithm did not involve this rare etiology in these particular uncommon neurologic cases and even brain biopsy performed in both women did not recognize the substantiality of the disease.

• MeSH
• Lymphoma, B-Cell diagnosis   pathology   MeSH
• Endothelium, Vascular pathology   MeSH
• Adult MeSH
• Immunohistochemistry methods   MeSH
• Humans MeSH
• Brain Neoplasms MeSH
• Neurologic Manifestations diagnosis   pathology   MeSH
• Signs and Symptoms pathology   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Case Reports MeSH

Antiagregancia patří mezi skupinu široce používaných léčiv v klinické praxi. V současné době zaznamenáváme velmi rychlý vývoj nových antiagregačních preparátů a jsme také svědky rozsáhlých diskusí o rezistenci na antiagregační léčbu. Cílem tohoto článku je popsat základy farmakologických vlastnosti již déle užívaných i nových antiagregačních léčiv, představit metody umožňující identifikovat pacienty rezistentní na antiagregační léčbu a ukázat na možný přínos těchto metod v běžné klinické praxi.

Antiaggregation treatment is widely used in daily clinical practice. New antiaggregation drugs have been presented and other are under rapid development. Physicians are facing large discussions regarding resistance and responsiveness to antiaggregation treatment. The goal of this review article is to describe pharmacological effect of previously used and new antiaggregant, present methods that can identify patients resistant to treatment and show possible impact of this testing in daily clinical practice.

• Keywords
• laboratorní metody,
• MeSH
• Adenosine Diphosphate antagonists & inhibitors   MeSH
• Platelet Aggregation drug effects   MeSH
• Aspirin pharmacokinetics   therapeutic use   MeSH
• Financing, Organized MeSH
• Drug Evaluation MeSH
• Platelet Aggregation Inhibitors pharmacokinetics   pharmacology   therapeutic use   MeSH
• Ischemia MeSH
• Cardiovascular Diseases drug therapy   prevention & control   MeSH
• Clinical Trials as Topic MeSH
• Drug Resistance MeSH
• Humans MeSH
• Flow Cytometry methods   utilization   MeSH
• Pyridines pharmacokinetics   classification   therapeutic use   MeSH
• Sensitivity and Specificity MeSH
• Platelet Function Tests methods   utilization   MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH