Potentially toxic elements in different tissues of great cormorant (Phalacrocorax carbo) at a wetland area.

Concentrations of 4 potentially toxic elements (As, Cd, Hg, Pb) were investigated in the feather, liver, kidney, and bone of great cormorants (Phalacrocorax carbo). The tissue samples were taken at the Central Tisza - Jászság Nature Conservation Area in Hungary. They were analysed by inductively coupled plasma optical emission spectroscopy (ICP-OES). The goal of the investigation was to analyse the metal burden of the above-mentioned elements in the various tissues of these wild birds and to provide important information for monitoring the environmental pollution.Amongst the examined potentially toxic elements no statistical gender difference was observed, so the data were not separated based on them during the statistical analysis. The concentration of mercury was the highest in the feather, followed by the liver, kidney, and bone. The lead was detected in the feather with the highest level followed by the kidney, liver, and bone. The cadmium was determined in all investigated tissues with the next descending order: kidney > bone > liver > feather. Highest arsenic concentration was measured in the feather, followed by liver, kidney, and bone with the same concentration.The detected concentrations of the investigated potentially toxic elements in different tissues of great cormorants (feathers, liver, kidney, bone) means that the living area of this birds is not highly contaminated to induce health problems or toxic signs, or even other undesirable effect in the animals.

Synthesis and Anticancer Activity of Phosphinoylated and Phosphonoylated N-Heterocycles Obtained by the Microwave-Assisted Palladium Acetate-Catalyzed Hirao Reaction.

A literature survey showed that different derivatives with the 9-phenyl-9H-carbazole or the dihydroindoline scaffold may be of biological activity including cytotoxic effect. Driven by this experience, P-functionalized derivatives of these N-heterocycles were synthesized. Three N-heterocycles, 9-(4-bromophenyl)-9H-carbazole, 3-bromo-9-phenyl-9H-carbazole and 1-(5-bromoindolin-1-yl)ethan-1-one, were coupled with dialkyl phosphites and diarylphosphine oxides using Pd(OAc)2 (10 %) as the catalyst precursor and triethylamine as the base in ethanol under microwave irradiation. The excess of the Y2 P(O)H reagent (Y=alkoxy, aryl) (30 %) served as the P-ligand in its trivalent tautomeric form (Y2 POH), hence there was no need for the usual P-ligands meaning cost and environmental burden. Hence, the presented method is a "green" approach that proved to be more efficient than the preparation by the traditional method. The products, dialkyl phosphonates and tertiary phosphine oxides obtained in 58-84 % yields were characterized, one of them also by single crystal X-ray analysis, and were subjected to in vitro biological activity evaluation. A (carbazol)yl-phenylphosphonate, an N-phenyl-(carbazol)yl-phosphonate, a (carbazol)yl-phenylphosphine oxide and an N-phenyl-(carbazol)ylphosphine oxide revealed a significant cytotoxic activity on A549 human non-small-cell lung carcinoma and MonoMac-6 acute monocytic leukemia cancer cells. The cytotoxic effect was significant as compared to that of the reference compounds.

A Study of the Bisphosphonic Derivatives from the Pudovik Reaction of Dialkyl α-Oxophosphonates and >P(O)H Reagents: X-ray Structure and Bioactivity.

New hydroxy-methylenebisphosphonic derivatives were prepared with different P-functions. The outcome of the reaction of α-oxophosphonates (YC(O)P(O)(OR)2) and dialkyl phosphites or diarylphosphine oxides depended on the Y substituent of the oxo-compound, the nature of the P-reagent and the amount of the diethylamine catalyst. Starting from dimethyl α-oxoethylphosphonate, in the presence of 5% of diethylamine, the corresponding Pudovik adduct was the single product. While using 40% of the catalyst, the rearranged species with the >P(O)-O-CH-P(O)< skeleton was the exclusive component. A similar reaction of α-oxobenzylphosphonate followed the rearrangement protocol. X-ray crystallography revealed not only the spatial structures of the three products, but also an intricate pattern evolving from the interplay of slight chemical differences, solvent inclusion and disorder as well as H-bridge patterns, which invite further investigation. In vitro activity of the compounds was assessed on different tumor cell cultures using end-point-type cell tetrazolium-based measurements. These structure-activity studies revealed a cytostatic effect for four rearranged derivatives containing aromatic units. One of them had a pronounced effect on MDA-MB 231 and Ebc-1 cells, showing IC50 = 37.8 and 25.9 µM, respectively.

Metal Load of Potentially Toxic Elements in Tuna (Thunnus albacares)-Food Safety Aspects.

The consumption of marine fishes has a positive effect on a consumer's health; however, it poses a potential risk due to their level of heavy metals in their body. Heavy metals can be naturally found in the environment, but their concentration can be increased with anthropogenic activities. Samples of tuna (Thunnus albacares) were collected at a fishery market. The potentially toxic elements (arsenic, cadmium, lead, and mercury) were determined with a validated method in the flesh of fish using inductively plasma optical emission spectrometry after microwave digestion. Generally, the average concentration of them was below the official limit values regulated by the European Union, except for lead. Based on the concentrations of arsenic (inorganic derivates: 0.05 ± 0.02 mg/kg) and cadmium (0.03 ± 0.01 mg/kg) in the tuna fish samples, and their calculated EDI values (As: 0.03-0.09 µg/kg/day; Cd: 0.05-0.07 µg/kg/day), the investigated food could be declared safe for human consumption. Generally, mercury content was below the official regulated limit, and the calculated EDI value was below the dietary reference value (0.3 µg/kg/day) in most of the samples (90%), exceeding it only in two samples (0.69 and 0.82 µg/kg/day); thus, they may not be harmful to the consumer. The concentration of lead above the official maximum limit (0.30 mg/kg) in 40% of tuna samples (0.30-1.59 mg/kg), as well as the exceeding of the dietary reference value for lead (adult: 0.16 µg/kg/day; children: 0.26 µg/kg/day) based on the calculated EDI values (0.28-1.49 µg/kg/day), draw attention to the importance of environmental pollution and the protection of consumers' health.

Cytotoxic Activity of α-Aminophosphonic Derivatives Coming from the Tandem Kabachnik-Fields Reaction and Acylation.

Encouraged by the significant cytotoxic activity of simple α-aminophosphonates, a molecular library comprising phosphonoylmethyl- and phosphinoylmethyl-α-aminophosphonates, a tris derivative, and N-acylated species was established. The promising aminophosphonate derivatives were subjected to a comparative structure-activity analysis. We evaluated 12 new aminophosphonate derivatives on tumor cell cultures of different tissue origins (skin, lung, breast, and prostate). Several derivatives showed pronounced, even selective cytostatic effects. According to IC50 values, phosphinoylmethyl-aminophosphonate derivative 2e elicited a significant cytostatic effect on breast adenocarcinoma cells, but it was even more effective against prostatic carcinoma cells. Based on our data, these new compounds exhibited promising antitumor activity on different tumor types, and they might represent a new group of alternative chemotherapeutic agents.

Influence of the Drug Position on Bioactivity in Angiopep-2-Daunomycin Conjugates.

The blood-brain barrier (BBB) is a semipermeable system, and, therefore, most of the active substances are poorly transported through this barrier, resulting in decreased therapeutic effects. Angiopep-2 (TFFYGGSRGKRNNFKTEEY) is a peptide ligand of low-density lipoprotein receptor-related protein-1 (LRP1), which can cross the BBB via receptor-mediated transcytosis and simultaneously target glioblastomas. Angiopep-2 contains three amino groups that have previously been used to produce drug-peptide conjugates, although the role and importance of each position have not yet been investigated. Thus, we studied the number and position of drug molecules in Angiopep-2 based conjugates. Conjugates containing one, two, and three daunomycin molecules conjugated via oxime linkage in all possible variations were prepared. The in vitro cytostatic effect and cellular uptake of the conjugates were investigated on U87 human glioblastoma cells. Degradation studies in the presence of rat liver lysosomal homogenates were also performed in order for us to better understand the structure-activity relationship and to determine the smallest metabolites. Conjugates with the best cytostatic effects had a drug molecule at the N-terminus. We demonstrated that the increasing number of drug molecules does not necessarily increase the efficacy of the conjugates, and proved that modification of the different conjugation sites results in differing biological effectiveness.

Targeting the Gastrin-Releasing Peptide Receptor (GRP-R) in Cancer Therapy: Development of Bombesin-Based Peptide-Drug Conjugates.

Targeted tumour therapy has proved to be an efficient alternative to overcome the limitations of conventional chemotherapy. Among several receptors upregulated in cancer cells, the gastrin-releasing peptide receptor (GRP-R) has recently emerged as a promising target for cancer imaging, diagnosing and treatment due to its overexpression on cancerous tissues such as breast, prostate, pancreatic and small-cell lung cancer. Herein, we report on the in vitro and in vivo selective delivery of the cytotoxic drug daunorubicin to prostate and breast cancer, by targeting GRP-R. Exploiting many bombesin analogues as homing peptides, including a newly developed peptide, we produced eleven daunorubicin-containing peptide-drug conjugates (PDCs), acting as drug delivery systems to safely reach the tumour environment. Two of our bioconjugates revealed remarkable anti-proliferative activity, an efficient uptake by all three tested human breast and prostate cancer cell lines, high stability in plasma and a prompt release of the drug-containing metabolite by lysosomal enzymes. Moreover, they revealed a safe profile and a consistent reduction of the tumour volume in vivo. In conclusion, we highlight the importance of GRP-R binding PDCs in targeted cancer therapy, with the possibility of further tailoring and optimisation.

Synthesis and SAR Analysis of Novel 4-Hydroxytamoxifen Analogues Based on Their Cytotoxic Activity and Electron-Donor Character.

Utilizing McMurry reactions of 4,4'-dihydroxybenzophenone with appropriate carbonyl compounds, a series of 4-Hydroxytamoxifen analogues were synthesized. Their cytotoxic activity was evaluated in vitro on four human malignant cell lines (MCF-7, MDA-MB 231, A2058, HT-29). It was found that some of these novel Tamoxifen analogues show marked cytotoxicity in a dose-dependent manner. The relative ROS-generating capability of the synthetized analogues was evaluated by cyclic voltammetry (CV) and DFT modeling studies. The results of cell-viability assays, CV measurements and DFT calculations suggest that the cytotoxicity of the majority of the novel compounds is mainly elicited by their interactions with cellular targets including estrogen receptors rather than triggered by redox processes. However, three novel compounds could be involved in ROS-production and subsequent formation of quinone-methide preventing proliferation and disrupting the redox balance of the treated cells. Among the cell lines studied, HT-29 proved to be the most susceptible to the treatment with compounds having ROS-generating potency.

Calibration of micro-channel plate detector in a Thomson spectrometer for protons and carbon ions with energies below 1 MeV.

The calibration of an ion detection system was carried out for protons and carbon ions from a few tens of keV up to about 1 MeV energies. A Thomson spectrometer deflecting the particle beam accelerated from a laser plasma creates the ion spectra on a phosphor screen behind a micro-channel plate (MCP), which are recorded by a camera. During calibration, the ion spectra simultaneously hit the slotted CR-39 track detector installed in front of the MCP and, passing through the adjacent CR-39 stripes, the MCP. The calibration provides the ratio of the interpolated values between two consecutive stripes of the camera signal and the total number of particles recorded on the corresponding stripe of CR-39. The efficiency of proton detection by CR-39 was also measured in a conventional accelerator beam and found to drop by 20% below 100 keV.

Efficient Synthesis of Acylated, Dialkyl α-Hydroxy-Benzylphosphonates and Their Anticancer Activity.

An efficient method applying acyl chlorides as reagents was developed for the acylation of the hindered hydroxy group of dialkyl α-hydroxy-benzylphosphonates. The procedure did not require any catalyst. A few acylations were also performed with the SC-enantiomer of dimethyl α-hydroxy-benzylphosphonate, and the optical purity was retained. A part of the acyloxyphosphonates was tested against eight tumor cell lines of different tissue origin at c = 50 µM concentration. The compounds elicited moderate cytostatic effect against breast, skin, prostate, colon, and lung carcinomas; a melanoma cell line; and against Kaposi's sarcoma cell lines. Then, dose-dependent cytotoxicity was assayed, and benzoylation of the α-hydroxy group was identified as a moiety that increases anticancer cytotoxicity across all cell lines. Surprisingly, a few analogues were more toxic to multidrug resistant cancer cell lines, thus evading P-glycoprotein mediated drug extrusion.

Comparison of metal burden in different muscle tissues of Great cormorant (Phalacrocorax carbo).

Concentrations of 12 metals (As, Ba, Cd, Co, Cr, Cu, Hg, Mn, Mo, Ni, Pb and Zn) were examined in the pectoral and thigh muscle of great cormorants (Phalacrocorax carbo). The samples were collected from Central Tisza-Jászság Nature Conservation Area in Hungary. The tissue samples were analysed by inductively coupled plasma optical emission spectroscopy (ICP-OES). The aim of the study was to examine the impacts of heavy metal pollution on the water birds, determine the concentrations of the abovementioned metals in the different muscle tissues of these wetland birds, and provide the basic materials for monitoring the environmental pollution. Among the investigated elements/metals, the detected concentrations of As, Ba, Cd, Co, Cr, Mo and Ni were below the detection limit. Higher concentration of Cu, Hg, Mn and Pb was measured in the pectoral muscle compared to the thigh muscle, but only in the case of Cu and Mn were found significant differences between the tissues. In the case of the Zn concentration, the higher value was detected in the thigh muscle. There were no statistical differences between males and females in either metal concentrations.

Reproductive toxicological changes in avian embryos due to a pesticide and an environmental contaminant.

Single and simultaneous toxic effects of glyphosate (Amega Up, 360 g L-1, 4%) and copper sulphate (0.01%) were studied in avian embryos treated either with injection directly into the air chamber or by immersion application for 30 min on day 0 of incubation. Alterations of the chicken embryos were evaluated during necropsy performed on day 19 of incubation, together with mortality, body weight and the type of developmental abnormalities. Based on the results, the injection application appeared to be more toxic than the immersion method, as it induced increased mortality and reduced the average body weight, and resulted in a higher incidence of congenital anomalies. Supposedly, a toxicodynamic interaction occurs between copper sulphate and glyphosate, which may reduce the vitality of embryos and thus decrease the number of offspring in wild birds.

Synthesis, structure and in vitro antiproliferative effects of alkyne-linked 1,2,4-thiadiazole hybrids including erlotinib- and ferrocene-containing derivatives.

Chemotherapy is an indispensable tool to treat cancer, therefore, the development of new drugs that can treat cancer with minimal side effects and lead to more favorable prognoses is of crucial importance. A series of eleven novel 1,2,4-thiadiazoles bearing erlotinib (a known anticancer agent), phenylethynyl, ferrocenyl, and/or ferrocenethynyl moieties were synthesized in this work and characterized by NMR, IR and mass spectroscopies. The solid-phase structures were determined by single-crystal X-ray diffraction. Partial isomerisation of bis(erlotinib)-1,2,4-thiadiazole into its 1,3,4-thiadiazole isomer, leading to the isolation of a 3 : 2 isomer mixture, was observed and a plausible mechanism for isomerisation is suggested. The in vitro cytostatic effect and the long-term cytotoxicity of these thiadiazole-hybrids, as well as that of erlotinib, 3,5-dichloro-1,2,4-thiadiazole and 3,5-diiodo-1,2,4-thiadiazole were investigated against A2058 human melanoma, HepG2 human hepatocellular carcinoma, U87 human glioma, A431 human epidermoid carcinoma, and PC-3 human prostatic adenocarcinoma cell lines. Interestingly, erlotinib did not exhibit a significant cytostatic effect against these cancer cell lines. 1,2,4-Thiadiazole hybrids bearing one erlotinib moiety or both an iodine and a ferrocenethynyl group, as well as 3,5-diiodo-1,2,4-thiadiazole demonstrated good to moderate cytostatic effects. Among the synthesized 1,2,4-thiadiazole hybrids, the isomer mixture of bis-erlotinib substituted 1,2,4- and 1,3,4-thiadiazoles showed the most potent activity. This isomer mixture was proven to be the most effective in long-term cytotoxicity, too. 3,5-Diiodo-1,2,4-thiadiazole and its hybrid with one erlotinib fragment were also highly active against A431 and PC-3 proliferation. These novel compounds may serve as new leads for further study of their antiproliferative properties.

Novel Polycondensed Partly Saturated ß-Carbolines Including Ferrocene Derivatives: Synthesis, DFT-Supported Structural Analysis, Mechanism of Some Diastereoselective Transformations and a Preliminary Study of Their in vitro Antiproliferative Effects.

Use of a Pictet-Spengler reaction of tryptamine and l-tryptophan methyl ester and subsequent reduction of the nitro group followed by further cyclocondensation with aryl aldehydes and formyl-substituted carboxylic acids, including ferrocene-based components, furnished a series of diastereomeric 6-aryl-substituted 5,6,8,9,14,14b-hexahydroindolo[2',3':3,4]pyrido[1-c]-quinazolines and 5,5b,17,18-tetrahydroindolo[2',3':3,4]pyrido[1,2-c]isoindolo[2,1-a]quinazolin-11-(15bH)-ones with the elements of central-, planar and conformational chirality. The relative configuration and the conformations of the novel polycyclic indole derivatives were determined by 1H- and 13C-NMR methods supplemented by comparative DFT analysis of the possible diastereomers. The structure of one of the pentacyclic methyl esters with defined absolute configuration "S" was also confirmed by single crystal X-ray diffraction measurement. Accounting for the characteristic substituent-dependent diastereoselective formation of the products multistep mechanisms were proposed on the basis of the results of DFT modeling. Preliminary in vitro cytotoxic assays of the products revealed moderate-to-significant antiproliferative effects against PANC-1-, COLO-205-, A-2058 and EBC-1 cell lines that proved to be highly dependent on the stereostructure and on the substitution pattern of the pending aryl substituent.

[Optimization of peptide-drug conjugates for targeted tumor therapy]. / Célzott tumorterápiára alkalmas peptidhatóanyag konjugátumok szerkezetének optimalizálása.

In case of cancers with high mortality rate and lacking efficient medication there is a huge need of new, innovative treatments. Targeted tumor therapy, a real breakthrough in this field, is based on the concept that the antitumor agent is linked to a targeting molecule (e.g. peptide) specifically recognizing receptors or antigens that are tumor specific or overexpressed by tumor cells. The efficiency of this conjugate can be influenced by several factors. Among these, the structure of the targeting device, the type and number of the antitumor drug, its position in the conjugate and the chemical bonding of the drug to the targeting molecule are all important features that can determine receptor affinity and cellular uptake, and also the release and the cellular localization of the free drug or its active metabolite. Our goal in the framework of the grant NVKP_16-1-2016-0036 was to generate conjugates against cancers with high mortality rate. Through the below described studies, we introduce the course of the research process through which conjugates are optimized in order to develop more efficient drug candidates.

Biomonitoring of toxic metals in feathers of predatory birds from eastern regions of Hungary.

The aim of our study was to investigate the concentrations of toxic metals in the feathers of predatory birds in the Hortobágyi Madárpark (Bird Hospital Foundation). Samples were collected from different predatory birds originated from the eastern and north-eastern region of Hungary. Inductively coupled plasma optical emission spectrometry was used to determine the concentration of toxic metals. The mean values varied between bird species groups, their concentrations were between 0.29 ± 0.24 and 0.40 ± 0.30 mg/kg for arsenic (As), 0.09 ± 0.03 and 0.20 ± 0.18 mg/kg for cadmium (Cd), 1.15 ± 1.40 to 2.30 ± 1.52 mg/kg for lead (Pb) and 0.58 ± 0.31 to 2.19 ± 1.25 mg/kg for mercury (Hg), respectively. The measured values are not over the considered threshold values for these toxic metals and in accordance with similar concentrations of them recorded in similar species within Europe. No significant differences were found in their concentration between genders or age in the species. According to the detected concentrations of these metals, their levels accumulated in the feather of the investigated birds do not indicate the possibility of poisoning.

Sequence modification of heptapeptide selected by phage display as homing device for HT-29 colon cancer cells to improve the anti-tumour activity of drug delivery systems.

Development of peptide-based conjugates for targeted tumour therapy is a current research topic providing new possibilities in cancer treatment. In this study, VHLGYAT heptapeptide selected by phage display technique for HT-29 human colon cancer was investigated as homing peptide for drug delivery. Daunomycin was conjugated to the N-terminus of the peptide directly or through Cathepsin B cleavable spacers. Conjugates showed moderate in vitro cytostatic effect. Therefore, sequence modifications were performed by Ala-scan and positional scanning resulting in conjugates with much higher bioactivity. Conjugates in which Gly was replaced by amino acids with bulky apolaric side chains provided the best efficacy. The influence of the cellular uptake, stability and drug release on the anti-tumour activity was investigated. It was found that mainly the difference in the cellular uptake of the conjugates generated the distinct effect on cell viability. One of the most efficient conjugate Dau = Aoa-LRRY-VHLFYAT-NH2 showed tumour growth inhibition on orthotopically developed HT-29 colon cancer in mice with negligible toxic side effect compared to the free drug. We also indicate that this sequence is not specific to HT-29 cells, but it has a remarkable effect on many other cancer cells. Nevertheless, the Phe-containing conjugate was more active in all cases compared to the conjugate with the parent sequence. The literature data suggested that this sequence is highly overlapped with peptides that recognize Hsp70 membrane bound protein overexpressed in many types of tumours.

An optimized small animal tumour model for experimentation with low energy protons.

BACKGROUND: The long-term aim of developing laser based particle acceleration towards clinical application requires not only substantial technological progress, but also the radiobiological characterization of the resulting ultra-short and ultra-intensive particle beam pulses. After comprehensive cell studies a mouse ear tumour model was established allowing for the penetration of low energy protons (~20 MeV) currently available at laser driven accelerators. The model was successfully applied for a first tumour growth delay study with laser driven electrons, whereby the need of improvements crop out. METHODS: To optimise the mouse ear tumour model with respect to a stable, high take rate and a lower number of secondary tumours, Matrigel was introduced for tumour cell injection. Different concentrations of two human tumour cell lines (FaDu, LN229) and Matrigel were evaluated for stable tumour growth and fulfilling the allocation criteria for irradiation experiments. The originally applied cell injection with PBS was performed for comparison and to assess the long-term stability of the model. Finally, the optimum suspension of cells and Matrigel was applied to determine applicable dose ranges for tumour growth delay studies by 200 kV X-ray irradiation. RESULTS: Both human tumour models showed a high take rate and exponential tumour growth starting at a volume of ~10 mm3. As disclosed by immunofluorescence analysis these small tumours already interact with the surrounding tissue and activate endothelial cells to form vessels. The formation of delimited, solid tumours at irradiation size was shown by standard H&E staining and a realistic dose range for inducing tumour growth delay without permanent tumour control was obtained for both tumour entities. CONCLUSION: The already established mouse ear tumour model was successfully upgraded now providing stable tumour growth with high take rate for two tumour entities (HNSCC, glioblastoma) that are of interest for future irradiation experiments at experimental accelerators.

Cellular Uptake Mechanism of Cationic Branched Polypeptides with Poly[l-Lys] Backbone.

Cationic macromolecular carriers can be effective carriers for small molecular compounds, drugs, epitopes, or nucleic acids. Polylysine-based polymeric branched polypeptides have been systematically studied on the level of cells and organisms as well. In the present study, we report our findings on the cellular uptake characteristics of nine structurally related polylysine-based polypeptides with cationic side chains composed of (i) single amino acid (poly[Lys(Xi)], XiK) or (ii) oligo[dl-alanine] (poly[Lys(dl-Alam)], AK) or (iii) oligo[dl-alanine] with an additional amino acid (X) at the terminal position (poly[Lys(Xi-dl-Alam)] (XAK)) or (iv) at the position next to the polylysine backbone (poly[Lys(dl-Alam-Xi)] (AXK)). In vitro cytotoxicity and cellular uptake were characterized on HT-29 human colon carcinoma and HepG2 human hepatocarcinoma cell lines. Data indicate that the polycationic polypeptides studied are essentially nontoxic in the concentration range studied, and their uptake is very much dependent on the side chain structure (length, identity of amino acid X, and distance between the terminal positive charges) and also on the cell lines. Our findings in uptake inhibition studies suggest that predominantly macropinocytosis and caveole/lipid raft mediated endocytosis are involved. The efficacy of their internalization is markedly influenced by the hydrophobicity and charge properties of the amino acid X. Interestingly, the uptake properties of the these polypeptides show certain similarities to the entry pathways of several cell penetrating peptides.

[Prevalence and predisposing factors of methicillin-resistant Staphylococcus aureus in long-term care facilities. An international view]. / A methicillin-rezisztens Staphylococcus aureus gyakorisága és kockázati tényezoi a bentlakásos szociális intézményekben. Nemzetközi kitekintés.

INTRODUCTION: Methicillin-resistant Staphylococcus aureus is one of the most important pathogens of healthcare and long-term care-associated infections over the world, resulting high morbidity, mortality and extra costs in these settings. AIM: The authors analyze the prevalence and predisposing factors of methicillin-resistant Staphylococcus aureus in long-term care facilities. METHOD: Systematic review using PubMed, ScienceDirect and Cochrane Library CENTRAL databases between January 1, 2006 and December 31, 2015 was performed. RESULTS: In the past ten years methicillin-resistant Staphylococcus aureus prevalence in European long-term care facilities (12.6%) was lower than in North America (33.9%). The most frequent predisposing factor was previous antimicrobial therapy, hospital admission and infection/colonisation, chronic wounds, and high care need. CONCLUSIONS: Based on the results, the prevention and control of methicillin-resistant Staphylococcus aureus is an important public health priority in the European and Hungarian long-term care facilities.