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Biomedical subjects

M Marek

Publications and source records attributed to M Marek.

At least 19 recordsLinked to original sources

Polyomavirus EGFP-pseudocapsids: analysis of model particles for introduction of proteins and peptides into mammalian cells.

A vector for preparation of mouse polyomavirus capsid-like particles for transfer of foreign peptides or proteins into cells was constructed. Model pseudocapsids carrying EGFP fused with the C-terminal part of the VP3 minor protein (EGFP-VLPs) have been prepared and analysed for their ability to be internalised and processed by mouse cells and to activate mouse and human dendritic cells (DC) in vitro. EGFP-VLPs entered mouse epithelial cells, fibroblasts and human and mouse DC efficiently and were processed by both, lysosomes and proteasomes. Surprisingly, they did not induce upregulation of DC co-stimulation molecules or maturation markers in vitro; however, they did induce interleukin 12 secretion.

Animals↗

The mechanism of corrosion of palladium-silver binary alloys in artificial saliva.

Palladium dental casting alloys are alternatives to gold alloys. The aim of this study was to determine the electrochemical behaviour and the corrosion mechanism of binary silver-palladium alloys. Seven binary silver-palladium alloys and pure palladium and silver were tested in a model saliva solution. Electrochemical tests included corrosion potential, polarization resistance, and potentiodynamic polarization measurements. The corrosion products, which may be theoretically formed, were determined by thermodynamic calculation. The behaviour of silver and silver-rich alloys was dominated by the preferential formation of a thiocyanate surface layer, which controlled the free corrosion potential. Palladium dissolved in the form of a thiocyanate complex, but the surface became passivated by either palladium oxide or solid palladium thiocyanate layer, the thermodynamic calculations indicating preference for the oxide. Palladium-rich alloys showed evidence of silver depletion of the surface, resulting in behaviour similar to palladium. Examination of binary silver-palladium alloys has made possible determination of the role of the components of the alloys and model saliva in the corrosion behaviour. The findings are applicable to the more complex commercial dental alloys containing silver and palladium as major components.

Biocompatible Materials↗

An international dosimetry exchange for boron neutron capture therapy. Part I: Absorbed dose measurements.

An international collaboration was organized to undertake a dosimetry exchange to enable the future combination of clinical data from different centers conducting neutron capture therapy trials. As a first step (Part I) the dosimetry group from the Americas, represented by MIT, visited the clinical centers at Studsvik (Sweden), VTT Espoo (Finland), and the Nuclear Research Institute (NRI) at Rez (Czech Republic). A combined VTT/NRI group reciprocated with a visit to MIT. Each participant performed a series of dosimetry measurements under equivalent irradiation conditions using methods appropriate to their clinical protocols. This entailed in-air measurements and dose versus depth measurements in a large water phantom. Thermal neutron flux as well as fast neutron and photon absorbed dose rates were measured. Satisfactory agreement in determining absorbed dose within the experimental uncertainties was obtained between the different groups although the measurement uncertainties are large, ranging between 3% and 30% depending upon the dose component and the depth of measurement. To improve the precision in the specification of absorbed dose amongst the participants, the individually measured dose components were normalized to the results from a single method. Assuming a boron concentration of 15 microg g(-1) that is typical of concentrations realized clinically with the boron delivery compound boronophenylalanine-fructose, systematic discrepancies in the specification of the total biologically weighted dose of up to 10% were apparent between the different groups. The results from these measurements will be used in future to normalize treatment plan calculations between the different clinical dosimetry protocols as Part II of this study.

Biophysical Phenomena↗

Progress with the NCT international dosimetry exchange.

The international collaboration that was organized to undertake a dosimetry exchange for purposes of combining clinical data from different facilities conducting neutron capture therapy has continued since its founding at the 9th ISNCT symposium in October 2000. The thrust towards accumulating physical dosimetry data for comparison between different participants has broadened to include facilities in Japan and the determination of spectral descriptions of different beams. Retrospective analysis of patient data from the Brookhaven Medical Research Reactor is also being considered for incorporation into this study to increase the pool of available data. Meanwhile the next essential phase of comparing measurements of visiting dosimetry groups with treatment plan calculations from the host institutes has commenced. Host centers from Petten, Finland and the Czech Republic in Europe and MIT in the USA have applied the regular calculations and clinical calibrations from their current clinical studies, to generate treatment plans in the large standard phantom used for measurements by visiting participants. These data have been exchanged between the participants and scaling factors to relate the separate dose components between the different institutes are being determined. Preliminary normalization of measured and calculated dosimetry for patients is nearing completion to enable the physical radiation doses that comprise a treatment prescription at a host institute to be directly related to the corresponding measured doses of a visiting group. This should serve as an impetus for the direct comparison of patient data although the clinical requirements for achieving this need to be clearly defined. This may necessitate more extensive comparisons of treatment planning calculations through the solution of test problems and clarification regarding the question of dose specification from treatment calculations in general.

Boron Neutron Capture Therapy↗

Spatial characterization of BNCT beams.

The space distribution of the epithermal neutron flux was determined for the epithermal neutron beams of several NCT facilities in USA (FCB at MIT), Europe (HFR at JRC, Petten; FiR at VTT, Espoo; LVR-15 at NRI, Rez) and Japan (JRR-4 at JAERI, Tokai). Using p-n diodes with (6)Li radiator and the set of Bonner sphere spectrometer (BSS) the beams were quantified in-air. Axial beam profiles along the beam axes and the radial distributions at two distances from the beam aperture were measured. Except for the well-collimated HFR beam, the spatial characteristics of the other studied beams were found generally similar, which results from their similar designs.

Boron Neutron Capture Therapy↗

Development of equipments for determination of BNCT source spectral parameters.

The knowledge of neutron and gamma ray energy spectra can strongly influence the BNCT information about delivered dose to target volume as well as to the surface healthy tissue region. This region is very often decisive to stay within the recommended healthy tissue limit. Modification of neutron Bonner spectrometer to one block i.e. Bonner spectrometer monoblock (BSM) and gamma ray Si semiconductor spectrometer are being developed and verified in real conditions of LVR-15 reactor beam. Test measurements were also carried out in conditions of known standard spectra. The accepted procedure and the first results documenting the sensitivity BSM to different spectra are presented.

Boron Neutron Capture Therapy↗

[Neutron capture therapy in the treatment of glioblastoma multiforme. Initial experience in the Czech Republic].

BACKGROUND: Glioblastoma multiforme is the most frequent primary brain tumor in adults. Despite advances in surgery, radiotherapy and chemotherapy, its treatment remains unsatisfactory with very limited overall survival. In the year 2001, in cooperation with Department of Neurosurgery, Nemocnice Na Homolce and Nuclear Research Institute in Rez, we have started to treat glioblastoma patients with boron neutron capture therapy (BNCT). METHODS AND RESULTS: Cells of malignant brain tumors, especially that of glioblastomas, are able to accumulate boron compounds. If BNCT should be successful, it is necessary to reach selective accumulation of sufficient amount of 10B in the tumor and low accumulation in the normal brain tissue. After BSH administration, radiation with low energy thermal neutrons is delivered. It results in nuclear capture and fission reactions with subsequent selective damage of tumor cells. At the time of analysis 9 patients have been enrolled. Therapy was completed in 5 patients. Treatment has been very well tolerated. We observed minimal acute toxicity associated with radiation and no laboratory abnormalities after administrations of BSH. Unfortunately treatment results were quite unsatisfactory. The median time to progression and overall survival were shorter then expected with conventional treatment. CONCLUSIONS: BNCT is very well tolerated with only a modest toxicity. In contrast to standard radiation, BNCT patients receive only one dose of radiation. Nevertheless, in this small pilot study first results were inferior when compared either to outcomes of conventional therapy or to results reported from other BNCT groups. It might be explained that lower dose of radiation had been used. Further study will show whether the higher dose radiation can improve treatment results.

Adult↗

Influence of an external electric field on cAMP wave patterns in aggregating Dictyostelium discoideum.

Effects of an external electric field on the propagation of excitable cyclic adenosin monophosphate (cAMP) pulses in aggregating cells of Dictyostelium discoideum have been studied by means of numerical simulations. The mathematical model includes a three-variable version of the Martiel-Goldbeter kinetic model of cAMP production by cells, and diffusion and electromigration of cAMP through intercellular space. Electric field effects on the planar pulses propagating in a spatially one-dimensional system and on circular and spiral pulses propagating in a spatially two-dimensional system include changes in the propagation velocities of pulses initiated in the field-free system, the annihilation of pulses propagating towards the cathode by electric fields of high intensities, and the formation of region(s) of spontaneous excitation permanently generating trains of cAMP pulses. The spiral patterns were found to drift in the electric fields of low intensities, fields of high intensities were found to decompose the spiral arms on the side facing the negative electrode.

Animals↗

Nonlinear behaviour of simple ionic systems in hydrogel in an electric field.

The stationary behavior of ionic reaction-transport systems contained in hydrogel located between two reservoirs of electrolytes is investigated. The effects of the applied voltage, the composition of the electrolytes in the reservoirs and the distribution of fixed charge in the hydrogel on the spatial patterns of charge, electric potential, temperature and concentrations of the individual components are studied systematically by mathematical modelling. Such systems, containing only several ions (for example, Cl-, K+, OH- and H+) can function as electrolyte diodes and transistors and can exhibit oscillations and hysteresis. The mathematical description of the studied systems is based on balances of species, enthalpy and charge, on Poisson's equation and on the finite rate description of the water dissociation/recombination reaction, without assuming local electroneutrality. The modeling results are compared with experiments, including the system with hydrogel connecting reservoirs of strong base and acid studied by Noszticzius and co-workers. [L.H. Hegedus, N. Kirschner, M. Wittmann and Z. Noszticzius, J. Phys. Chem. A, 1998, 102, 6491 (ref. 1); L. H. Hegedus, N. Kirschner, M. Wittmann, P. Simon and Z. Noszticzius, Chaos, 1999, 9, 283 (ref. 2).]

Journal Article↗

Properties of polyethylene films with incorporated benzoic anhydride and/or ethyl and propyl esters of 4-hydroxybenzoic acid and their suitability for food packaging.

Benzoic anhydride and ethyl and propyl esters of 4-hydroxybenzoic acid (ETP and PRP, respectively, also termed parabens) incorporated into low density polyethylene (LDPE) film were studied with regard to migration into food and food simulants at 6 degrees C and 25 degrees C, and changes in selected properties of the film were investigated. Antimicrobials were incorporated into polymer film in concentrations of 5 g/kg and 10 g/kg. The addition of parabens into the polymer was more difficult than benzoic anhydride due to their volatility. For benzoic anhydride, 30-40% and 10-20% of the added amount was found to leach from the film into aqueous and olive oil food simulants, respectively. The migration into both water and olive oil followed a very similar course in the case of parabens. Migration levels over 90% and in the range of 70% to 80%, relative to the amount of agent in the film, were determined for ETP and PRP respectively. The incorporation of antimicrobials into the film significantly changed the functional characteristics of the packaging material, i.e. permeability of oxygen, carbon dioxide and water vapour, tensile strength, coefficient of friction, sealing strength and transparency. Shelf life tests with packaged cheese and toasted bread demonstrated the efficiency of the film containing 10 g/kg of BA against mould growth on the food surface during storage at 6 degrees C.

Anhydrides↗

[Pedicled osteocutaneous groin flap in the compound reconstruction procedures of the fingers].

The paper presents the authors own experiences with pedicled oseocutaneous groin flaps based on superficial circumflex iliac vessels with a vascularized bone graft (size ranging from 2.5 cm to 5 cm) from the ilium. Eight patients, 7 males and 1 female, (aged 9-46 years, mean age 24 years) were treated using this method because a bone defect of the first metacarpal bone or the middle phalanx of the III finger. The flap pedicle was cut off after 17-36 days. Treatment was successful in all patients, although complications of the healing process were noted in 7 flaps. In 5 cases an inflammatory reaction around the sutures or superficial necrosis of the skin was observed. In two cases extensive infection of the flap's tissues was noted which in one case lead to partial necrosis of the soft tissues.

Adolescent↗

Ability of Ni-containing biomedical alloys to activate monocytes and endothelial cells in vitro.

Nickel-containing alloys commonly are used in medical and dental applications that place them into long-term contact with soft tissues. The release of Ni ions from these alloys is disturbing because of the toxic, immunologic, and carcinogenic effects that have been documented for some Ni compounds. In particular, Ni ions in solution recently have been shown to cause expression of inflammatory mediators, such as interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and intercellular adhesion molecules (ICAMs) from keratinocytes, monocytes, and endothelial cells. However, the ability of the solid alloys themselves to induce these inflammatory effects has not been demonstrated. An in vitro system was used to determine if Ni-containing biomedical alloys could cause secretion of either IL-1beta or TNF-alpha from monocytes or expression of ICAMs on endothelial cells. Pure nickel, titanium, and three biomedical alloys-18-8 stainless steel, NiTi, and Rexillium III-were evaluated. First, it was determined whether or not the alloys or pure metals could cause cytotoxicity to THP-1 human monocytes or human microvascular endothelial cells (HMVECs) by measuring the succinic dehydrogenase (SDH) activity of the cells. Then, using identical conditions of exposure, the secretion of IL-1beta or TNF-alpha from monocytes or ICAM-1 expression on the HMVECs was determined. Only pure nickel suppressed (by 48% compared to Teflon controls) the SDH activity of the HMVECs or THP-1 monocytes. No alloy or metal caused the HMVECs to express ICAM-1, but the NiTi alloy caused a significant (ANOVA/Tukey) secretion of IL-1beta from the THP-1 monocytes. Secretion of TNF-alpha induced by NiTi was detectable but not statistically significant. The levels of IL-1beta secretion from monocytes were sufficient to induce ICAM-1 expression on HMVECs. The release of Ni from the NiTi was a logical suspect in causing the IL-1beta secretion by monocytes, but its role was not confirmed since other alloys, such as Rexillium III, released the same quantities of Ni yet did not activate the THP-1 monocytes. Within the limitations of in vitro conditions, our results indicate that NiTi alloys pose a risk of promoting an inflammatory response in soft tissues by activating monocytes. Further study is needed to substantiate this finding in vivo.

Alloys↗

Galvanic interaction between titanium and gallium alloy or dental amalgam.

OBJECTIVES: The objective was to examine in vitro the galvanic interaction between titanium and a high-copper dental amalgam or a gallium-based direct filling alloy at different area ratios, and to relate the observed interactions to the electrochemical characteristics of the alloys. METHODS: The tested materials were cast titanium, a single-composition, spherical high-copper amalgam, and a gallium-based direct filling alloy. Polarization curves were recorded. The galvanic couples were prepared at Ti/filling alloy ratios of 1:1, 2:1, 4:1 and 6:1. The couples were exposed to synthetic saliva at 37 degrees C and the galvanic currents and potentials were measured as a function of time. The results were analyzed by ANOVA and Tukey tests (p < or = 0.05). RESULTS: Freshly abraded titanium initially was anodic to both the amalgam and the gallium alloy, but the polarity reversed after a period of exposure. The galvanic potential and current density increased with the increasing Ti/alloy area ratio. The potential increase was smaller and the current increase larger for the Ga alloy than for the amalgam. The difference was consistent with the polarization characteristics. The galvanic current density was of the order of 10(-8) A/cm2 for the Ti/amalgam couple, and 10(-7) to 10(-6) A/cm2 for the Ti/gallium alloy couple. SIGNIFICANCE: The results show that the galvanic interaction between titanium and direct filling alloys is small. High copper dental amalgams should suffer little galvanic corrosion when in contact with Ti. For gallium direct filling alloys, the galvanic interaction may be more detrimental because of the inherently lower corrosion resistance.

Analysis of Variance↗

Evaluation of key parameters in a potentiostatic corrosion test for dental amalgam.

OBJECTIVES: Participation in a Round Robin study of potentiostatic corrosion test guidelines for dental amalgam was undertaken for the purpose of developing an accurate set of draft guidelines. METHODS: Dispersalloy, sybraloy, aristalloy, phasealloy, and tytin were used as the amalgam specimens. They were prepared following the guidelines, then coupled to a copper wire, cemented into glass tubes, and polished to a 600-grit finish. A corrosion cell was prepared using a carbon counter-electrode, a standard calomel electrode (SCE) as the reference electrode, and amalgam as the working electrode. A 37 degrees C solution of 10 g/l NaCl with a minimum volume of 300 ml was used. Within 5 min of polishing, the open circuit potential (OCP) was recorded for 10 min. Next, the specimen was polarized to 0 mV versus SCE, and the currents were recorded for a 24-h time period. Corrosion results were analyzed statistically with one-way ANOVA (p < 0.05) and the multiple comparisons Student-Newman-Keuls post-hoc test. RESULTS: Problems that occurred with evaporation, beaker size, carbon electrode length, SCE cap removal, glass tube fracture, polishing technique, and fresh electrolyte are easily avoidable with further explanation or reminder notes. Observations made concerning starting time, initial OCP recording, millivoltage, and solution temperature were determined to be necessary for the accuracy of test results. Analysis of results should include clarification of units, and graph interpretations. Finally, the number of specimens per amalgam should be increased from one to three so that statistical analysis can be performed. Using three specimens per amalgam, the method revealed corrosion susceptibility as measured by the improved test: aristalloy > sybraloy > (dispersalloy, phasealloy, tytin). SIGNIFICANCE: Having run the initially proposed guidelines, a number of clarifying changes were made so that the corrosion susceptibilities of five dental amalgams could be clearly differentiated.

American Dental Association↗

Accurate titration of avidin and streptavidin with biotin-fluorophore conjugates in complex, colored biofluids.

A new fluorimetric assay is presented for the specific and reliable quantitation of >/=2 nM avidin and streptavidin. The assay is based on pronounced changes in the fluorescence properties of commercial fluorescein-biotin, or of a newly synthesized biotin-poly(ethylene glycol)-pyrene conjugate, which occur upon binding to avidin and streptavidin. Accurate measurement of (strept)avidin in complex, colored biofluids, such as crude egg white or serum relies on a simple titration protocol. Only occasional recalibration of the reagent solution is required. Due to these merits the proposed assay is particularly suited for rapid measurement of few samples on short notice, for functional control of (strept)avidin-containing reagents after storage, and for the monitoring of (strept)avidin concentrations in large scale processes.

Animals↗

Dissolution of mercury vapor in simulated oral environments.

OBJECTIVE: The aim of this investigation was to determine the effects of variables on the dissolution of atomic mercury in simulated oral fluids. This study was based on a hypothesis that the rate of mercury vapor dissolution in synthetic saliva is affected by the oxidation power and stirring of the solution. METHOD: The reference solution was synthetic saliva, and the oxidation power was increased by hydrogen peroxide or decreased by ascorbic acid. Test solutions were exposed to mercury vapor in a sealed container, and the dissolved mercury concentration was determined after exposures ranging from 2 to 48 h. The results were analyzed by ANOVA and Tukey's multiple comparison test (p < 0.05). The effect of stirring was examined for a 24 h exposure. Student t-tests were used to compare this data (p < 0.05). The analysis for mercury was performed by cold-vapor atomic absorption spectrophotometry. RESULTS: Mercury dissolved much faster in the highly oxidizing solution with hydrogen peroxide than in the other two solutions, which dissolved mercury at the same rate. In the less oxidizing solutions, the dissolved mercury concentration reached a nearly constant value. Stirring the solution increased the rate of mercury dissolution for the highly oxidizing solution but had no effect on the less oxidizing solutions. SIGNIFICANCE: The results show the importance of the transformation of mercury from the atomic to the ionic state. When dissolving atomic mercury is not oxidized, it may evaporate and be inhaled, but the dissolution rate becomes low. Under more oxidizing conditions, mercury dissolves faster, but does not generate mercury vapor. Diffusion in the liquid affects the mercury dissolution rate only under highly oxidizing conditions.

Analysis of Variance↗

The effect of tin in the Ag-Hg phase of dental amalgam on dissolution of mercury.

OBJECTIVES: The aim of this study was to determine the relationship between the tin content in the gamma 1 phase of dental amalgam and the kinetics of mercury dissolution. METHODS: The tested materials were the same eleven commercial amalgams used by Mahler et al. (1994) to study mercury evaporation, which contained from 0.13% to 2.49% Sn in the gamma 1. In one set of tests, specimens were stabilized in air before exposure to synthetic saliva for three 24 h sampling periods. In another set of tests, they were exposed for 2 h immediately after wet-grinding. Solutions were analyzed for mercury by atomic absorption spectrophotometry. The results were analyzed by ANOVA and Turkey tests (p < 0.05). RESULTS: For air-stabilized specimens, the 24 h Hg loss was independent of the tin content in gamma 1 for 0.92 to 2.49% Sn. The loss was higher for amalgams containing 0.13% and 0.32% Sn. For abraded specimens, the 2 h Hg loss decreased with increasing tin content in gamma 1. It is proposed that tin oxide growth is initially controlled by diffusion of tin to the gamma 1/tin oxide interface, the rate of which increases with increasing Sn content in gamma 1. Later the growth becomes controlled by the electric field across the oxide. Mercury release rate, controlled by diffusion through the oxide, is inversely proportional to the oxide thickness and initially lower for high Sn content in gamma 1. For a steady state oxide thickness, tin diffusion and tin content in gamma 1 no longer affect mercury dissolution. When tin oxide film dissolves, a minimum tin content is required to maintain a barrier against mercury dissolution. SIGNIFICANCE: The results show the importance of rapid formation of a surface oxide to minimize mercury dissolution. The theoretical analysis provides a quantitative model for explanation of the effects of tin content and time.

Analysis of Variance↗

Dissolution of mercury from dental amalgam at different pH values.

Dissolution of mercury from dental amalgam has been shown to be diminished by the formation of a tin oxide film on the surface of the mercury-rich gamma 1 phase (Marek, 1990b). Since tin oxides dissolve at low pH values (Deltombe et al., 1974), acidic conditions in the oral cavity may cause an increase in the mercury release. The purpose of this study was to determine the effect of acidity in the range of pH 1 to pH 8 on the rate of mercury dissolution in synthetic saliva from tin-free and tin-containing gamma 1 phase and two commercial dental amalgams. The tested hypothesis was that pH affects mercury dissolution only when a protective oxide film dissolves in an acidic environment. After exposures of the specimens for 2 hr or 24 hr in sealed glass bottles, the solutions were analyzed by flameless atomic absorption spectrophotometry for mercury and silver. The results have shown pH-independent mercury dissolution in the range of pH 3 to 8, and a much faster dissolution at pH 1. At all pH values, more mercury dissolved from the tin-free phase than from the tin-containing phase, and the rate of dissolution was lowest for the dental amalgams. The results were affected by the length of the test exposure. The pH independence in a wide range of pH values has been attributed to the atomic mechanism of mercury dissolution. The low rate of mercury dissolution from specimens containing tin has been explained by the formation of a barrier tin oxide film, which dissolved only at the lowest pH. Dissolution of silver at low pH values is believed to have accelerated dissolution of mercury from the tin-free gamma 1 phase. Variation of the dissolution rate with concentration of the dissolved species and kinetics of oxide film dissolution caused the effect of the exposure period.

Analysis of Variance↗