Wound fluids collected postoperatively from patients with breast cancer induce epithelial to mesenchymal transition but intraoperative radiotherapy impairs this effect by activating the radiation-induced bystander effect.

Wound fluids (WF) are believed to play a role in the local recurrences by inducing an inflammatory process in scar tissue area. Given that most local relapse in primary breast cancer patients occur within the scar tissue area, researchers have investigated whether localized radiotherapy, such as intraoperative radiotherapy (IORT), could be more effective than postoperative RT in inhibiting local tumor recurrence. The epithelial-mesenchymal transition (EMT) program plays a critical role in promoting metastasis in epithelium-derived carcinoma. Given this background the main aim of the present study was to determine the mechanisms by which IORT decreases the tumorigenic potential of WF. We assumed that postoperative fluids from patients would activate the radiation-induced bystander effect (RIBE) in treated cells, thus altering the tumor microenvironment. To confirm this hypothesis, WF collected from patients after breast conserving surgery (BCS) alone, after BCS followed by IORT treatment or WF from BCS patients together with RIBE medium were incubated with MCF7 and MDA-MB-468 cells. Changes in the CSC phenotype, in EMT program and potential to migrate were performed to determine the possible role of WF on the migration of breast cancer cells. Our findings show that wound fluids stimulate the CSC phenotype and EMT program in breast cancer cell lines. This effect was partially abrogated when the cells were incubated in wound fluids collected from patients after breast-conserving surgery followed by IORT. Additionally, we confirmed the role of radiation-induced bystander effect in altering the properties of the WF to induce the CSC phenotype and EMT program.

Dose to 'water-like' media or dose to tissue in MV photons radiotherapy treatment planning: still a matter of debate.

The difference between Monte Carlo Treatment Planning (MCTP) based on the assumption of 'water-like' tissues with densities obtained from CT procedures, or on tissue compositions derived from CT-determined densities, have been investigated. Stopping powers and electron fluences have been calculated for a range of media and body tissues for 6 MV photon beams, including changes in their physical data (density and stopping powers). These quantities have been used to determine absorbed doses using cavity theory. It is emphasized that tissue compositions given in ICRU or ICRP reports should not be given the standing of physical constants as they correspond to average values obtained for a limited number of human-body samples. It has been shown that mass stopping-power ratios to water are more dependent on patient-to-patient composition differences, and therefore on their mean excitation energies (I-values), than on mass density. Electron fluence in different media are also more dependent on media composition (and their I-values) than on density. However, as a consequence of the balance between fluence and stopping powers, doses calculated from their product are more constant than what the independent stopping powers and fluence variations suggest. Additionally, cancelations in dose ratios minimize the differences between the 'water-like' and 'tissue' approaches, yielding practically identical results except for bone, and to a lesser extent for adipose tissue. A priori, changing from one approach to another does not seem to be justified considering the large number of approximations and uncertainties involved throughout the treatment planning tissue segmentation and dose calculation procedures. The key issue continues to be the composition of tissues and their I-values, and as these cannot be obtained for individual patients, whatever approach is selected does not lead to significant differences from a water reference dose, the maximum of these being of the order of 5% for bone tissues. Considering, however, current developments in advanced dose calculation methods, planning in terms of dose-to-tissue should be the preferred choice, under the expectancy that progress in the field will gradually improve some of the crude approximations included in MCTP and numerical transport methods. The small differences obtained also show that a retrospective conversion from dose-to-tissue to dose-to-water, based on a widely used approach, would mostly increase the final uncertainty of the treatment planning process. It is demonstrated that, due to the difference between electron fluence distributions in water and in body tissues, the conversion requires an additional fluence correction that has so far been neglected. An improved expression for the conversion and data for the fluence correction factor are provided. These will be necessary even in a dose-to-tissue environment, for the normalization of the treatment plan to the reference dosimetry of the treatment unit, always calibrated in terms of absorbed dose to water.

Protein-polymer functionalized aqueous ferrofluids showing high T2 relaxivity.

Controlled size, shape and dispersibility of superparamagnetic iron oxide nanoparticles (SPIONs), has been achieved in a protein-polymer colloidal dispersion. Stable ferrofluid (FF) is synthesized in an aqueous medium of collagen, bovine serum albumin and poly(vinyl) alcohol that equilibrates with time, at ambient conditions, into an organized matrix with iron oxide particles sterically caged at defined sites. It mimics a biomineralization system; hence the process is termed biomimetics. Though the exact mechanism is not understood at this stage, we have established, with serial dilution of the protein-polymer solution that the SPIONs are formed inside the self-contained clusters of the two proteins and the polymer, which show a tendency to self assemble. More than the interparticle dipolar attractions of magnetic particles, electrostatic interactions play a role in cluster formation and collagen is responsible for the overall stability, supported by systematic dynamic light scattering data. The basic aim of this study was to increase magnetization of a previously synthesized ferrofluid without hampering stability, by reducing the total macromolecular concentration. Thrice the magnetization was achieved and in addition, the synthesized FFs exhibited very high transverse relaxivity and showed good contrast in mice liver, in the in vivo studies.

Proteomics in radiation research: present status and future perspectives.

Rapidly developing postgenome research has made proteins an attractive target for biological analysis. The well-established term of proteome is defined as the complete set of proteins expressed in a given cell, tissue or organism. Unlike the genome, a proteome is rapidly changing as it tends to adapt to microenvironmental signals. The systematic analysis of the proteome at a given time and state is referred to as proteomics. This technique provides information on the molecular and cellular mechanisms that regulate physiology and pathophysiology of the cell. Applications of proteome profiling in radiation research are increasing. However, the large-scale proteomics data sets generated need to be integrated into other fields of radiation biology to facilitate the interpretation of radiation-induced cellular and tissue effects. The aim of this review is to introduce the most recent developments in the field of radiation proteomics.

Monopolar radiofrequency use in deep gluteal space endoscopy: sciatic nerve safety and fluid temperature.

PURPOSE: The purpose of this study was to evaluate the temperature at the sciatic nerve when using a monopolar radiofrequency (RF) probe to control bleeding in deep gluteal space endoscopy, as well as assess the fluid temperature profile. METHODS: Ten hips in 5 fresh-frozen human cadaveric specimens from the abdomen to the toes were used for this experiment. Temperatures were measured at the sciatic nerve after 2, 5, and 10 seconds of continuous RF probe activation over an adjacent vessel, a branch of the inferior gluteal artery. Fluid temperatures were then measured at different distances from the probe (3, 5, and 10 mm) after 2, 5, and 10 seconds of continuous probe activation. All tests were performed with irrigation fluid flow at 60 mm Hg allowing outflow. RESULTS: After 2, 5, or 10 seconds of activation over the crossing branch of the inferior gluteal artery, the mean temperature increased by less than 1°C on the surface and in the perineurium of the sciatic nerve. Considering the fluid temperature profile in the deep gluteal space, the distance and duration of activation influenced temperature (P < .05). Continuous delivery of RF energy for 10 seconds caused fluid temperature increases of 1.2°C, 2°C, and 3.1°C on average at 10 mm, 5 mm, and 3 mm of distance, respectively. CONCLUSIONS: This study found the tested monopolar RF device to be safe during use in vessels around the sciatic nerve after 2, 5, and 10 seconds of continuous activation. The maximum fluid temperature (28°C) after 10 seconds of activation at 3 mm of distance is lower than the minimal reported temperature necessary to cause nerve changes (40°C to 45°C). CLINICAL RELEVANCE: Monopolar RF seems to be safe to the neural structures when used at more than 3 mm of distance and with less than 10 seconds of continuous activation in deep gluteal space endoscopy with fluid inflow and outflow.

Optodynamic energy-conversion efficiency during an Er:YAG-laser-pulse delivery into a liquid through different fiber-tip geometries.

When an erbium-laser pulse is directed into water through a small-diameter fiber tip (FT), the absorption of the laser energy superheats the water and its boiling induces a vapor bubble. We present the influence of different FT geometries and pulse parameters on the vapor-bubble dynamics. In our investigation, we use a free-running erbium: yttrium aluminum garnet (Er:YAG) (λ=2.94 µm) laser that was designed for laser dentistry. Its pulse is directed into the water through FTs with a flat and conical geometry. Our results show that in the case of the conical FT, a spherical bubble is induced, while a channel-like bubble develops for the flat FT. The ratio between the mechanical energy of the liquid medium and the pulse energy, which we call the optodynamic energy-conversion efficiency, is examined using shadow photography. The results indicate that this efficiency is significantly larger when a conical FT is used and it increases with increasing pulse energy and decreasing pulse duration. The spherical bubbles are compared with the Rayleigh model in order to present the influence of the pulse duration on the dynamics of the bubble's expansion.

Bond strength determination of hydroxyapatite coatings on Ti-6Al-4V substrates using the LAser Shock Adhesion Test (LASAT).

An adhesion test procedure applied to plasma-sprayed hydroxyapatite (HA) coatings to measure the "LASAT threshold" (LAser Shock Adhesion test) is described. The good repeatability and minimal discrepancy of the laser-driven adhesion test data were ascertained for conventional plasma sprayed HA coatings. As a further demonstration, the procedure was applied to HA coatings with diverse characteristics on the ceramic/metal interface. Different preheating and grit blasting conditions and the presence of a thick plasma-sprayed Ti sublayer or a thin TiO(2) layer prepared by oxidation were investigated through LASAT. It was assessed that a rough surface can significantly improve the coating's bond strength. However, it was also demonstrated that a thin TiO(2) layer on a smooth Ti-6Al-4V substrate can have a major influence on adhesion as well. Preheating up to 270°C just prior to the first HA spraying pass had no effect on the adhesion strength. Further development of the procedure was done to achieve an in situ LASAT with in vitro conditions applied on HA coatings. To that end, different crystalline HA contents were soaked in simulated body fluid (SBF). Beyond the demonstration of the capability of this laser-driven adhesion test devoted to HA coatings in dry or liquid environment, the present study provided empirical information on pertinent processing characteristics that could strengthen or weaken the HA/Ti-6Al-4V bond.

The effect of radiation processing and filler morphology on the biomechanical stability of a thermoset polyester composite.

The effect of radiation processing and filler morphology on the biodegradation and biomechanical stability of a poly(propylene fumarate)/hydroxyapatite composite was investigated. Radiation processing influenced both cross-linking and biodegradation of the composites. Irradiation with a dose of 3 Mrad resulted in enhanced cross-linking, mechanical properties and a higher storage modulus which are favourable for dimensional stability of the implant. The particle morphology of the added hydroxyapatite in the highly cross-linked state significantly influenced the biomechanical and interfacial stability of the composites. Reorganization of agglomerated hydroxyapatite occurred in the cross-linked polymeric matrix under dynamic mechanical loading under simulated physiological conditions. Such a reorganization may increase the damping characteristics of the composite.

Reliability and validity of a bioimpedance measurement device in the assessment of UVR damage to the skin.

Ultraviolet radiation (UVR) is the primary cause of skin cancers. However, it is difficult to evaluate the amount of UVR absorbed into the skin retrospectively. Therefore, objective and non-invasive quantitative method would be valuable for epidemiological UVR exposure assessment. Photodamage reduces the amount of bound water in the skin, and thus, measuring the skin's dielectric constant can provide an opportunity for assessing the cumulative UVR exposure. The purpose of the study was to assess the reliability and validity of the bioimpedance device, Moisture Meter-D. The measurements were performed on 100 subjects at three separate measurement times. A questionnaire was used to obtain information on the host factors and on the past UVR exposure. The biological samples, to determine the elastin proportion of the dermis, were collected. Some long-term as well as seasonal variations in the dielectric constants were detected. Also, a weak relationship between the dielectric constant and the UVR exposure indicators and host factors was observed. The MoistureMeter-D appears not to measure structural alterations in the skin caused by photodamage, and thus it is not a valid instrument for the assessment of photodamage, i.e., past UVR exposure.

Magnetic separation of micro-spheres from viscous biological fluids.

A magnetically based detoxification system is being developed as a therapeutic tool for selective and rapid removal of biohazards, i.e. chemicals and radioactive substances, from human blood. One of the key components of this system is a portable magnetic separator capable of separating polymer-based magnetic nano/micro-spheres from arterial blood flow in an ex vivo unit. The magnetic separator consists of an array of alternating and parallel capillary tubing and magnetizable wires, which is exposed to an applied magnetic field created by two parallel permanent magnets such that the magnetic field is perpendicular to both the wires and the fluid flow. In this paper, the performance of this separator was evaluated via preliminary in vitro flow experiments using a separator unit consisting of single capillary glass tubing and two metal wires. Pure water, ethylene glycol-water solution (v:v=39:61 and v:v=49:51) and human whole blood were used as the fluids. The results showed that when the viscosity increased from 1.0 cp to 3.0 cp, the capture efficiency (CE) decreased from 90% to 56%. However, it is still feasible to obtain >90% CE in blood flow if the separator design is optimized to create higher magnetic gradients and magnetic fields in the separation area.

[Use of laser correlation spectroscopy for evaluation of metabolic changes in workers engaged in radiation-dangerous industry].

The pattern of metabolic changes was studied in nuclear fuel plant workers by laser correlation spectroscopy (LCS) of biological fluids (blood serum and plasma, urine, oropharyngeal lavages (OPL). Plasma samples were divided into 3 groups: 1) control (unirradiated) samples; 2) those irradiated by below 100 mZv; 2) those irradiated by more than 100 mZv. With larger dose irradiation, the contribution of small particles (6-8 nm) to the dispersion of increased and the proportion of large components (300-400 nm) decreased. There was a correlation between the total accumulated dose, the dose in the past 9 months and the changes in the contribution of the above groups of particles to light diffusion. The found regulations in the changes of the subfraction composition of blood agree with earlier data on changes in the serum of nuclear fuel workers. Analysis of urine samples revealed an increase in the contribution of catabolic processes. That of OPL showed the preponderance of anabolic changes over catabolic ones in the presence of a considerable contribution of normologically similar LC spectra. Differences were found in the pattern of metabolic changes in relation to technological stages. Although the nature of the observed spectral transformations remains unknown, the simplicity and rapidity of the LCS technique may be considered as a suitable tool for detecting the effects caused by small dose irradiation and other factors.

The three-photon yield from e+ annihilation in various fluids.

Positronium in the triplet state decays by the emission of three photons and it has been proposed that their simultaneous detection can be used for medical imaging. The three-photon yield has been observed to be enhanced in low O(2) levels in some fluids but has never been measured in biologically relevant liquids. In this study, the delayed three-photon decay yield, at both high and low O(2) levels, has been extracted by fitting the time dependence of the two-photon yield to a set of coupled differential equations. The differential equations, in a simple yet seemingly satisfactory fashion, account for the e(+) capture to form positronium, its decay and the interconversion of the two spin configurations. Our results indicate that the delayed three-photon fraction is 0.25% in water (or blood-like) samples and exhibits no (or exceedingly small) dependence on the dissolved oxygen content. If one assumes that the direct component contributes a fraction expected by annihilation on free electrons (1/372), then the total three-photon fraction is 0.52% in the samples of biological relevance.

Development of methods for the quantification of essential and toxic elements in human biomonitoring.

Analytical methods using sector field ICP-MS and ICP-AES were developed for the determination of Al, Ba, Be, Bi, Ca, Cd, Co, Cr, Cu, Fe, Hg, Li, Mg, Mn, Mo, Ni, Pb, Sb, Si, Sn, Sr, Tl, V, W, Zn and Zr in cerebrospinal fluid, urine, serum and blood. Sample treatment procedures merging high sample throughput, simplicity and low contamination risk were set up. Method performances were evaluated in terms of detection limits, accuracy and precision. The limits were below 0.05 ng ml(-1) for all the elements, except for Al (all matrices), Hg (blood), Pb (blood) and Sn (serum and blood). The accuracy varied from 86% to 110% and the precision was always below 6%.

Studies on depth-dose-distribution controls by deuteration and void formation in boron neutron capture therapy.

Physical studies on (i) replacement of heavy water for body water (deuteration), and (ii) formation of a void in human body (void formation) were performed as control techniques for dose distribution in a human head under neutron capture therapy. Simulation calculations were performed for a human-head-size cylindrical phantom using a two-dimensional transport calculation code for mono-energetic incidences of higher-energy epi-thermal neutrons (1.2-10 keV), lower-energy epi-thermal neutrons (3.1-23 eV) and thermal neutrons (1 meV to 0.5 eV). The deuteration was confirmed to be effective both in thermal neutron incidence and in epi-thermal neutron incidence from the viewpoints of improvement of the thermal neutron flux distribution and elimination of the secondary gamma rays. For the void formation, a void was assumed to be 4 cm in diameter and 3 cm in depth at the surface part in this study. It was confirmed that the treatable depth was improved almost 2 cm for any incident neutron energy in the case of the 10 cm irradiation field diameter. It was made clear that the improvement effect was larger in isotropic incidence than in parallel incidence, in the case that an irradiation field size was delimited fitting into a void diameter.

Interfacial effect of extremely low frequency electromagnetic fields (EM-ELF) on the vaporization step of carbon dioxide from aqueous solutions of body simulated fluid (SBF).

Spontaneous processes in an aqueous solution of body simulated fluid (SBF) were monitored in closed vessel for a period of 1 month at 310 K, at atm pressure, and initial pH of 7.2, both with and without exposure to a square pulsed extremely low frequency electromagnetic fields (EM-ELF) of 250 microT, repeated at 75 Hz. The most important findings are that the SBF surface tension (gamma), evaluated under the EM-ELF field, is lower than the corresponding value measured without EM-ELF at any time. Furthermore, the pH of the exposed SBF is always more basic than that of the unexposed solution. As a consequence, when the EM-ELF is applied, calcium phosphate salts do not precipitate from the SBF solution for a period as long as 30 days. Behind all these experimental evidences there is only one mechanism: the vaporisation from the SBF-air interface of the CO(2)(aq) dissolved into the aqueous electrolyte solution. Thermodynamic analysis of these results establish that, at any given time, the difference, Delta, between the measured surface tensions with and without EM-ELF applied, gives the work of the electromagnetic forces to change the extent at which the CO(2)(aq) adsorbs at the liquid-air interface. It has been demonstrated that the work supply per second and per unit of area by the electromagnetic forces, 3.73 x 10(-10) mJ/s cm(2), is very near to the experimental slope in the plot Delta vs. t 1.7 x 10(-10) mJ/s cm(2). This leads to the conclusion that the EM-ELF fields have an interfacial effect on the concentration value of the CO(2) (aq) at the SBF-air interface. Because of that, the EM-ELF field is enhancing the CO(2) vaporisation rate; thus any other steps, which are a consequence of this mechanism, are changing. These results allow explanation of previous experiments concerning the precipitation of calcium carbonate from flowing hydrogen carbonate aqueous solution in the temperature range 353-373 K at a pressure of 0.1 MPa under the effect of static magnetic fields.

The biological reductive capacity of tissues is decreased following exposure to oxidative stress: a cyclic voltammetry study of irradiated rats.

The reductive capacity of rat tissue homogenates and body fluids was determined by cyclic voltammetric measurements. The reductive capacity of rat lung, liver and kidney homogenates was significantly reduced four days after total body gamma-ray irradiation with 5.5 Gy as compared to controls. In parallel, reduced ability of the irradiated organ homogenates to scavenge hydroxyl radicals and to destroy hydrogen peroxide was recorded. However, no difference in their superoxide dismutase activity was found. The possible use of cyclic voltammetry as a method for qualitative evaluation of the ability of biological tissues to cope with oxidative stress is discussed.

[Formation of liquid crystal structures in the tissue fluid in wound healing during periodic irradiation with helium-neon laser]. / Formirovanie zhidkokristallicheskikh struktur v tkanevoi zhidkosti v protsesse zazhivleniia rany v isloviiakh periodicheskogo oblucheniia gelii-neonovym lazerom.

Rabbit tissue fluid at different stages of wound healing was studied. Interaction between the formation of liquid crystalline fractions and the course of healing was revealed both under natural conditions and under periodic laser irradiation of the wound.

[The transformation of liquid crystal complexes in biological body fluids during local laser stimulation of the healing process in an experimental suppurative wound]. / Transformatsiia zhidkokristallicheskikh kompleksov v biologicheskikh zhidkostiakh organizma pri lokal'nom lazernom stimulirovanii protsessa zazhivleniia gnoinoi rany v éksperimente.

It was established that localized exposure of an inflammatory focus to laser radiation causes, besides the well-known effect on biochemical activity, structural photophysical reorganization of the liquid crystalline complexes not only in the irradiated tissues but also in parts of the organism situated at a distance from the exposed area.

Immediate effect of ultraviolet-B radiation on epidermal lysosomal hydrolases.

The immediate effect of ultraviolet-B radiation on epidermal lysosomal enzymes in vivo was studied by irradiating the roof of suction blisters. The activities of ten lysosomal hydrolases were determined in the blister fluid and in the epidermal homogenates. The enzyme values were decreased in the irradiated epidermis compared with the non-irradiated epidermis of control suction blisters, but the values found in the fluid of irradiated blisters were not decreased compared with control fluid.