Biomedical subjects

B Gallez

Publications and source records attributed to B Gallez.

At least 19 recordsLinked to original sources

PubMed2006

Characterization of self-assembling copolymers in aqueous solutions using Electron Paramagnetic Resonance and Fluorescence spectroscopy.

Electron Paramagnetic Resonance and fluorescence spectroscopy have been used to determine the micropolarity and microviscosity of self-assembling systems based on mmePEG-p(CL-co-TMC) having different PEG chain lengths and different CL/TMC ratios and PEG/MOG/SA (45/5/50) polymers with different PEG chain lengths. Four reporter probes have been used: two spin probes, 16-doxyl stearic acid and 5-doxylstearic acid, and two fluorescent probes, pyrene and 1,3-bis(1-pyrenyl) propane (P3P). We found that the micelles based on mmePEG-p(CL-co-TMC) polymers are of a biphasic nature. The micelles are made of a hydrophilic corona with low viscosity while the core of the micelle is more hydrophobic and more viscous. The outer shell is made up of PEG chains, the hydrophobic part of the chains making the core. The partial hydration of the shell seems to lead to a looser chain network than that associated with deeper domains in the micelles. By contrast, in micelles composed of PEG/MOG/SA, there is no clear domain separation. This is consistent with a spatial configuration of random polymeric chains forming a loose network. In these micelles, the microviscosity is low and the hydrophobicity is high.

Caproates↗

PubMed2005

Development and evaluation of biocompatible films of polytetrafluoroethylene polymers holding lithium phthalocyanine crystals for their use in EPR oximetry.

Electron paramagnetic resonance (EPR) oximetry is a powerful technology that allows the monitoring of oxygenation in tissues. The measurement of tissue oxygenation can be achieved using lithium phthalocyanine (LiPc) crystals as oxygen reporters. In order to have biocompatibility for the sensing system and to assure long-term stability in the responsiveness of the system, we developed films of Teflon AF 2400 with embedded LiPc crystals. These systems can be used as retrievable inserts or parts of an implantable resonator or catheter. Atomic force microscopy studies revealed that the surface of the films was regular and planar. The response to oxygen of the sensor (EPR linewidth as a function of pO(2)) remained unchanged after implantation in mice, and was not affected by sterilization or irradiation. The use of resonators, holding LiPc embedded in Teflon AF 2400, implanted in the gastrocnemius muscle of rabbits allowed the monitoring of oxygen during several weeks. Several assays also demonstrated the biocompatibility of the system: (1) no hemolytic effect was noted; (2) no toxicity was found using the systemic injection test of extracts; (3) histological analysis in rabbit muscle in which the films were implanted for 1 week or 3 months was similar to standard polyethylene biocompatible devices. These advanced oxygen sensors are promising tools for future pre-clinical and clinical developments of EPR oximetry. These developments can be applied for other applications of biosensors where there is a need for oxygen permeable membranes.

Absorption↗

PubMed2005

Multi-frequency electron paramagnetic resonance study of irradiated human finger phalanxes.

Electron paramagnetic resonance (EPR) is often used in dosimetry using biological samples such as teeth and bones. It is generally assumed that the radicals, formed after irradiation, are similar in both tissues as the mineral part of bone and tooth is carbonated hydroxyapatite. However, there is a lack of experimental evidence to support this assumption. The aim of the present study was to contribute to that field by studying powder and block samples of human finger phalanxes that were irradiated and analyzed by multi-frequency EPR. The results obtained from bones are different from the ones obtained in enamel by several respects: the ordering of the apatite crystallites is much smaller in bone, complicating the assignment of the observed CO2- radicals to a specific location, and one type of CO3(3-) radical was only found in enamel. Moreover, a major difference was found in the non-CO2- and non-CO3(3-) signals. The elucidation of the nature of these native signals (in bone and tooth enamel) still represents a big challenge.

Bone and Bones↗

PubMed2004

Non-invasive determination of the irradiation dose in fingers using low-frequency EPR.

Several reports in the literature have described the effects of radiation in workers who exposed their fingers to intense radioactive sources. The radiation injuries occurring after local exposure to a high dose (20 to 100 Gy) could lead to the need for amputation. Follow-up of victims needs to be more rational with a precise knowledge of the irradiated area that risks tissue degradation and necrosis. It has been described previously that X-band electron paramagnetic resonance (EPR) spectroscopy could be used to assess the dose in irradiated amputated fingers. Here, we propose the use of low-frequency EPR spectroscopy to evaluate non-invasively the absorbed dose. Low-frequency microwaves are indeed less absorbed by water and penetrate more deeply into living material (approximately 10 mm in tissues using 1 GHz spectrometers). This work presents preliminary results obtained with baboon and human fingers compared with human dry phalanxes placed inside a surface-coil resonator. The EPR signal increased linearly with the dose. The ratio of the slopes of the dry bone to whole finger linear regression lines was around 5. The detection limit achievable with the present spectrometer and resonator is around 60 Gy, which is well within the range of accidentally exposed fingers. It is likely that the detection limit could be improved in the future, thanks to further technical spectrometer and resonator developments as well as to appropriate spectrum deconvolution into native and dosimetric signals.

Animals↗

PubMed2003

Retrospective dosimetry after criticality accidents using low-frequency EPR: a study of whole human teeth irradiated in a mixed neutron and gamma-radiation field.

In the context of accidental or intentional radiation exposures (nuclear terrorism), it is essential to separate rapidly those individuals with substantial exposures from those with exposures that do not constitute an immediate threat to health. Low-frequency electron paramagnetic resonance (EPR) spectroscopy provides the potential advantage of making accurate and sensitive measurements of absorbed radiation dose in teeth without removing the teeth from the potential victims. Up to now, most studies focused on the dose-response curves obtained for gamma radiation. In radiation accidents, however, the contribution of neutrons to the total radiation dose should not be neglected. To determine how neutrons contribute to the apparent dose estimated by EPR dosimetry, extracted whole human teeth were irradiated at the SILENE reactor in a mixed neutron and gamma-radiation field simulating criticality accidents. The teeth were irradiated in free air as well as in a paraffin head phantom. Lead screens were also used to eliminate to a large extent the contribution of the gamma radiation to the dose received by the teeth. The EPR signals, obtained with a low-frequency (1.2 GHz) spectrometer, were compared to dosimetry measurements at the same location. The contribution of neutrons to the EPR dosimetric signal was negligible in the range of 0 to 10 Gy and was rather small (neutron/gamma-ray sensitivity in the range 0-0.2) at higher doses. This indicates that the method essentially provides information on the dose received from the gamma-ray component of the radiation.

Adolescent↗

PubMed2002

Removal of local field gradient artefacts in BOLD contrast imaging of head and neck tumours.

Monitoring of oxygenation in tumours is an important issue in predicting the success of anti-cancer treatments such as radiotherapy. Gradient echo (GE) imaging sequences can be used for monitoring changes in tumour blood flow and oxygenation. However, the application of this method in head and neck tumours is hampered by significant artefacts and losses of the MR signal near air-tissue interfaces. We investigated the usefulness of a gradient-echo slice excitation profile (GESEPI) sequence that should keep the oxygen contrast while recovering the signal loss caused by susceptibility artefacts. A tumour model was implanted in the neck and in the leg of mice. MR imaging was performed at 4.7 T. GE and GESEPI sequences were used for monitoring the blood oxygen level dependent (BOLD) contrast after carbogen breathing. The pO2 was also monitored in tumours using an OxyLite probe (Oxford Optronics). Using the tumours implanted in the leg, we found that the variations of signal intensity after carbogen breathing were similarin both sequences. In the tumour implanted in the neck, it was possible, using GESEPI sequences, to recover the signal loss caused by susceptibility artefacts and to monitor the effect of carbogen-induced changes in the tumour.

Animals↗

PubMed2002

An in vitro L-band electron paramagnetic resonance study of highly irradiated whole teeth.

Regarding in vivo L-band dosimetry with human teeth, a number of preliminary experiments were carried out that were linked to the resonators response and the relative contribution of enamel to the EPR signal intensity of irradiated whole teeth. The sensitivity of the extended loop resonator varies in the antenna plane, but this variation tends to vanish when the sample is moved away from this plane. When the loop antenna is placed just above the highly irradiated molar, around 88% of the dosimetric signal is due to the crown enamel. The sensitivity inside a birdcage cavity is approximately equal over the volume of a molar; only 30% of the molar's total dosimetric signal results from enamel. Some decrease in the intensity of the dosimetric signal from enamel is observed after irradiation. At room temperature, the signal is reduced by about 20% within 90 days and approaches a plateau with a time constant of about 35 days.

Bicuspid↗

PubMed2001

Assessment of [18F]fluoroethylflumazenil metabolites using high-performance liquid chromatography and tandem mass spectrometry.

A simple procedure using HPLC and tandem mass spectrometry has been developed for the determination of fluoroethylflumazenil metabolites. Samples were precipitated with acetonitrile, evaporated to dryness followed by reconstitution with methanol. As mobile phase, 50 mM ammonium formate-methanol (58:42, v/v) was used. The method is valid both for cold and radiolabelled metabolites. Various cold metabolites (hydroxylated and/or dealkylated) were identified in rat and human microsome preparations. Radiolabelled metabolites arise from two or more transformations including hydroxylation. The methodology developed can be applied for further characterisation of metabolites, and for the determination of non metabolised [18F]fluoroethylflumazenil in routine clinical analysis.

Animals↗

PubMed2001

Development of biocompatible oxygen-permeable films holding paramagnetic carbon particles: evaluation of their performance and stability in EPR oximetry.

EPR oximetry using paramagnetic particles relies on the measurement of the EPR linewidth, which is directly related to the pO2. It was previously found that some of the paramagnetic materials with optimal EPR spectroscopic properties in vitro may lose their responsiveness to oxygen in tissues (change of the calibration curve of the EPR linewidth as a function of the pO2). We hypothesized that coating paramagnetic particle materials could improve the stability of response, as well as the biocompatibility. In this study, very thin films holding paramagnetic materials were prepared with different biopolymers (cellulose acetate, cellulose triacetate, cellulose nitrate, silicone, and polyurethane) that already are accepted for clinical applications. Their performance was evaluated in EPR oximetry by measuring the stability of the calibration curves (EPR linewidth as a function of pO2) after a prolonged period in an aqueous environment (1 week in saline) or in vivo (implantation for 3 weeks under the skin of mice). We found that one type of silicone film was able to stabilize the responsiveness of an intrinsically unstable carbon material (a wood char).

Animals↗

PubMed2001

Non invasive quantification of manganese deposits in the rat brain by local measurement of NMR proton T1 relaxation times.

Up to now, there is no reliable non invasive biomarker for the concentration of manganese (Mn) in the brain after intoxication to this metal. The aim of the present experimental study was to determine the predictive value of the localized measurement of the proton NMR relaxation time T1 as a quantitative estimation of the concentration of Mn in brain. The relationship of the proton relaxation rates (1/T1) was established in rat brain homogenates as a function of the Mn, iron, and copper concentration. Subsequently, an experimental model of Mn neurotoxicity was used: rats were stereotactically injected with increasing amounts of Mn2+ (as MnCl2) in the ventricles. After 3 weeks, local measurements of T1 were carried out in live rats. They were then sacrificed in order to sample the striatum, the cortex, and the cerebellum from the brain and to perform a quantitative determination of the concentration of Mn in these tissues by atomic absorption spectrometry (AAS). The results indicate excellent correlation coefficients between relaxation rates and tissue Mn concentrations (r= 0.84, 0.77 and 0.92 for the striatum, the cortex and the cerebellum, respectively). This methodology offers a unique toolfor monitoring the degree of Mn concentration in different areas of the brain in animal models of Mn intoxication. It will be useful for evaluating the efficacy of treatments aimed at decreasing the metal in the brain. The method could be potentially useful for being transposed in the clinical situation for monitoring Mn-exposed workers.

Animals↗

PubMed2001

Biodistribution, binding specificity and metabolism of [18F]fluoroethylflumazenil in rodents.

Pre-clinical studies were carried out in order to characterize in rodents the biodistribution, the binding specificity and the metabolism of [18F]Fluoroethylflumazenil ([18F]FEF), a potential candidate for in vivo imaging of the benzodiazepine receptors. In vivo competition with flumazenil indicates that [18F]FEF binds specifically to the benzodiazepine receptor in the brain. The accumulation of [18F]FEF was significantly lower than using [3H]Flumazenil. The rather low accumulation in the brain is due to a rapid metabolism of [18F]FEF in hydrophylic metabolites which cannot cross the blood brain barrier, and are rapidly eliminated in the urine. Inhibition of the metabolism by acetaminophen (chemically induced hepatitis) led to a significant increase of the radioactivity found in the circulating blood and in the brain, while these results were not observed using classical inhibitors of the cytochrome CYP450, cimetidine and ketoconazole.

Animals↗

PubMed2000

Changes in tumor oxygenation/perfusion induced by the no donor, isosorbide dinitrate, in comparison with carbogen: monitoring by EPR and MRI.

PURPOSE: In an effort to improve radiotherapy treatments, methods aimed at increasing the quantity of oxygen delivered to tumors were investigated. The aim of this study was to evaluate the effect of one nitric oxide (NO) donor (isosorbide dinitrate) on pO(2) and blood flow in a murine tumor model. The effect was compared to carbogen, used as a reference treatment. METHODS AND MATERIALS: Thirty-six liver tumors implanted in mouse thighs were imaged using magnetic resonance imaging (MRI) at 4.7 Tesla with dynamic Gd-DTPA and blood oxygen level-dependent (BOLD) contrast-enhanced imaging after administration of isosorbide dinitrate or carbogen. The effect on the pO(2) was also tested by EPR oximetry (1.1 GHz) on 52 mice. RESULTS: A significant increase in MRI intensity was observed for both treatments in comparison with the control group. EPR oximetry showed a dose-dependant increase in tumor pO(2) for isosorbide dinitrate (by 5.9 mmHg at 0.2 mg/kg) and a substantially greater change for carbogen breathing (by 23 mmHg). CONCLUSION: Both tumor blood flow and pO(2) were increased by isosorbide dinitrate and carbogen. Carbogen is more efficient than isosorbide dinitrate in increasing the BOLD image intensity, as well as the tumor pO(2), but as efficient as isosorbide dinitrate in the Gd-DTPA contrast-enhanced imaging. We conclude that the effects of carbogen on improving tumor pO(2) involve both improved blood flow and improved hemoglobin oxygenation, whereas the effects of isosorbide dinitrate are predominantly mediated by improved blood flow alone.

Animals↗

PubMed2000

Accurate and sensitive measurements of pO(2) in vivo using low frequency EPR spectroscopy: how to confer biocompatibility to the oxygen sensors.

Within the last few years, there has been a significant amount of progress using EPR oximetry, which has resulted in the availability of instrumentation and paramagnetic materials capable of measuring pO(2) in tissues with an accuracy and sensitivity comparable to or greater than that available by any other method. While the results obtained with EPR so far indicate that criteria for the measurements of pO(2)-such as accuracy, sensitivity, repeatability, and noninvasiveness-can be met, some of the paramagnetic materials with optimum spectroscopic properties (i.e., strong simple signals which are appropriately responsive to changes in pO(2)) may have some undesirable interactions with tissues, causing reactions with and/or losing responsiveness to oxygen. In this paper, several approaches are discussed, such as encapsulation procedures, which can result in the availability of oxygen-sensitive materials in a suitable configuration for long-term studies (absence of toxicity and preservation of the responsiveness to oxygen).

Animals↗

PubMed2000

Free radicals in licorice-flavored sweets can Be detected noninvasively using low frequency electron paramagnetic resonance after oral administration to mice.

The observation of the fate of free radicals coming from food after oral administration could be important in evaluating their reactivity in vivo. The aim of this study was to demonstrate that it is feasible to detect directly in vivo free radicals coming from food with the use of low frequency electron paramagnetic resonance (EPR) spectroscopy. Because polyphenols are easily oxidized into stable radicals, we assumed that these radicals could be detected in food. We chose licorice, which contains several types of polyphenols. The presence of free radicals was demonstrated in licorice-flavored sweets. Using low frequency EPR spectroscopy, we detected these free radicals directly and noninvasively after oral administration to mice. These radicals were rather stable in the guts of the mice. This study is the first report demonstrating noninvasively the presence of free radicals in vivo coming from food.

Administration, Oral↗

PubMed1999

Microencapsulation of paramagnetic particles by pyrroxylin to preserve their responsiveness to oxygen when used as sensors for in vivo EPR oximetry.

Using the broadening of the electron paramagentic resonance (EPR) linewidth of paramagnetic particles by oxygen, it is possible to make measurements of the partial pressure of oxygen in vivo. While the results obtained so far with EPR oximetry are very encouraging, several paramagnetic materials may lose their responsiveness to oxygen in tissues. This aim of this study was to provide evidence that an appropriate coating can preserve the oxygen sensitivity of paramagnetic materials in vivo. Two charcoals that have the oxygen-sensing properties required for EPR oximetry (combined with a tendency to lose responsiveness to oxygen when placed in tissues) were coated using pyroxylin. Sensitivity to variations in pO2 was checked by inducing hypoxia in the muscles of mice injected with charcoal. While the uncoated material lost responsiveness to oxygen within few days, the particles coated with 20-30% of pyroxylin did not lose their responsiveness for more than 2 months.

Animals↗

PubMed1999

Pharmacological modifications of the partial pressure of oxygen in murine tumors: evaluation using in vivo EPR oximetry.

EPR oximetry using an implantable paramagnetic probe was used to quantify the partial pressure of oxygen (pO(2)) in tissues in a transplantable mouse tumor model (TLT) after administration of 34 different vasodilators belonging to one of the following classes: angiotensin-converting enzyme inhibitors, calcium antagonists, alpha antagonists, potassium channel openers, beta-blockers, NO donors, and peripheral vasoactive agents. Twenty-four compounds were efficient in significantly increasing the local pO(2) in a majority of tumors. The increase of local pO(2) using pharmacological treatments was lower than that achieved by using oxygen or carbogen breathing. This technique offers an unprecedented tool for rapidly and accurately measuring treatment-induced modifications of pO(2) in tumors. Magn Reson Med 42:627-630, 1999.

Animals↗

PubMed1999

Evidence for a neuroprotective effect of pyrid-3-yl-sulphonyl-urea in photochemically induced focal ischaemia in rats: magnetic resonance imaging evaluation.

A neuroprotective effect can be obtained with N-[(4-cycloheptylaminopyrid-3-yl)sulphonyl]N'-cycloheptyl urea (BM27), a pyrid-3-yl-sulphonylurea structurally related to torasemide, a loop diuretic. We have investigated the neuroprotective effect of BM27 by magnetic resonance imaging and use of the photothrombotic model of cerebral infarction in the rat. This method enables non-invasive quantification of the extent of the cerebral oedema from T2-weighted spin-echo images. This article reports the evolution of the extent of oedema with time (0.5, 1, 2, 4, 6, 24 and 48 h, 7 and 15 days and 1 month after induction of the lesion) in rats pretreated with 5 mg kg(-1) BM27 or an appropriate control. At all times, the rats treated with BM27 had, on average, smaller lesions than control rats (30% decrease between 2 h and 6 h). These results strongly suggest a significant (P < 0.01) but modest neuroprotective effect of BM27 in ischaemic cerebral stroke. Further investigations should be performed to determine if BM27 or its analogues are of clinical interest.

Animals↗

PubMed1998

Checking the integrity of albumin after pasteurisation: a fluorescent assay for quantitating monomeric albumin using anthroyloxy-fatty acids analogs.

This study presents a new assay based on the binding of anthroyloxy-stearates to albumin and the change in the fluorescence intensity when these fluorescent probes are bound to the protein. This assay permits the quantification of the albumin monomers present in a mixture of monomers and polymers, and allows to check the integrity of albumin after pasteurisation.

Animals↗