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Biomedical subjects

A Maes

Publications and source records attributed to A Maes.

At least 19 recordsLinked to original sources

Determination of amiodarone and desethylamiodarone in horse plasma and urine by high-performance liquid chromatography combined with UV detection and electrospray ionization mass spectrometry.

A rapid method for the quantification of amiodarone and desethylamiodarone in animal plasma using high-performance liquid chromatography combined with UV detection (HPLC-UV) is presented. The sample preparation includes a simple deproteinisation step with acetonitrile. In addition, a sensitive method for the quantification of amiodarone and desethylamiodarone in horse plasma and urine using high-performance liquid chromatography combined with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) is described. The sample preparation includes a solid-phase extraction (SPE) with a SCX column. Tamoxifen is used as an internal standard for both chromatographic methods. Chromatographic separation is achieved on an ODS Hypersil column using isocratic elution with 0.01% diethylamine and acetonitrile as mobile phase for the HPLC-UV method and with 0.1% formic acid and acetonitrile as mobile phase for the LC-MS/MS method. For the HPLC-UV method, good linearity was observed in the range 0-5 microg ml(-1), and in the range 0-1 microg ml(-1) for the LC-MS/MS method. The limit of quantification (LOQ) was set at 50 and 5 ng ml(-1) for the HPLC-UV method and the LC-MS/MS method, respectively. For the UV method, the limit of detection (LOD) was 15 and 10 ng ml(-1) for amiodarone and desethylamiodarone, respectively. The LODs of the LC-MS/MS method in plasma were much lower, i.e. 0.10 and 0.04 ng ml(-1) for amiodarone and desethylamiodarone, respectively. The LODs obtained for the urine samples were 0.16 and 0.09 ng ml(-1) for amiodarone and desethylamiodarone, respectively. The methods were shown to be of use in horses. The rapid HPLC-UV method was used for therapeutic drug monitoring after amiodarone treatment, while the LC-MS/MS method showed its applicability for single dose pharmacokinetic studies.

Amiodarone↗

Evaluation of the mutagenic and antimutagenic effects of South African plants.

Dichloromethane and 90% methanol extracts of 42 South African plants were screened for mutagenicity and antimutagenicity using the Salmonella/microsome mutagenicity assay (Ames) against Salmonella typhimurium TA98 and TA100 bacterial strains in the presence and absence of metabolic activator S9. The methanol extracts from whole plants of Helichrysum simillimum, Helichrysum herbaceum and Helichrysum rugulosum indicated mutagenicity. These are the first reported tests on the mutagenicity of Helichrysum species. Six species indicated antimutagenic properties, all in the presence of S9: methanol leaf extract of Bauhinia galpinii, and dichloromethane leaf extracts of Bauhinia galpinii, Clerodendrum myricoides, Datura stramonium, Buddleja saligna, Millettia sutherlandii and Sutherlandia frutescens.

Antimutagenic Agents↗

Investigation of co-genotoxic effects of radiofrequency electromagnetic fields in vivo.

We investigated the possible combined genotoxic effects of radiofrequency (RF) electromagnetic fields (900 MHz, amplitude modulated at 217 Hz, mobile phone signal) with the drinking water mutagen and carcinogen 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX). Female rats were exposed to RF fields for a period of 2 years for 2 h per day, 5 days per week at average whole-body specific absorption rates of 0.3 or 0.9 W/kg. MX was given in the drinking water at a concentration of 19 microg/ml. Blood samples were taken at 3, 6 and 24 months of exposure and brain and liver samples were taken at the end of the study (24 months). DNA damage was assessed in all samples using the alkaline comet assay, and micronuclei were determined in erythrocytes. We did not find significant genotoxic activity of MX in blood and liver cells. However, MX induced DNA damage in rat brain. Co-exposures to MX and RF radiation did not significantly increase the response of blood, liver and brain cells compared to MX exposure only. In conclusion, this 2-year animal study involving long-term exposures to RF radiation and MX did not provide any evidence for enhanced genotoxicity in rats exposed to RF radiation.

Animals↗

Column precipitation chromatography: an approach to quantitative analysis of eigencolloids.

A new column precipitation chromatography (CPC) technique, capable of quantitatively measuring technetium eigencolloids in aqueous solutions, is presented. The CPC technique is based on the destabilization and precipitation of eigencolloids by polycations in a confined matrix. Tc(IV) colloids can be quantitatively determined from their precipitation onto the CPC column (separation step) and their subsequent elution upon oxidation to pertechnetate by peroxide (elution step). A clean-bed particle removal model was used to explain the experimental results.

Chromatography↗

[Sudden death at young age and the importance of molecular-pathologic investigation].

The autopsy of a 16-year-old boy who had died suddenly revealed hypertrophic cardiomyopathy (HCM). Molecular genetic investigation revealed mutations in the MYBPC3 gene. His surviving family members could then be examined and reassured that they did not carry the mutation. An 18-year-old boy who died suddenly turned out to have known HCM. No further investigations were done and no tissue was saved. Genetic investigation of his immediate family was impossible due to the lack of a known mutation in the family. Periodic examination in clinically unaffected family members was therefore advised. Sudden cardiac death at young age is not infrequently the first symptom of an inherited cardiac disease. Because these diseases usually inherit as an autosomal dominant trait, first-degree family members have a 50% chance of carrying the same genetic defect. Besides clinical cardiologic examination of the remaining family members, post-mortem molecular genetic investigation can be of value in reaching a diagnosis and in determining the subsequent therapeutic options for immediate relatives.

Adolescent↗

Single-dose pharmacokinetics and tolerability of alendronate 35- and 70-milligram tablets in children and adolescents with osteogenesis imperfecta type I.

CONTEXT: Alendronate (ALN) is a bisphosphonate compound that can be administered orally and has potential use in pediatric osteoporotic conditions. OBJECTIVE: The objective was to evaluate the pharmacokinetics and single-dose tolerability of ALN in children with osteogenesis imperfecta. DESIGN: ALN was administered iv and orally in a two-period, randomized crossover study, with doses separated by a 2-wk washout and follow-up carried out within 2 wk after the last ALN dose. SETTING: The study was conducted at the pediatric metabolic bone research unit at the Shriners Hospital for Children, Montréal, Canada. PATIENTS: Twenty-four children (aged 4-16 yr; eight girls) with osteogenesis imperfecta type I participated. INTERVENTIONS: All patients received iv ALN at a dose of 125 mug. In addition, patients weighing less than 40 kg received an oral dose of ALN 35 mg, whereas those weighing 40 kg or more received ALN 70 mg orally. MAIN OUTCOME MEASURES: Total urinary excretion and oral bioavailability of ALN, blood and urine safety parameters, and adverse events were the main outcome measures. RESULTS: The total urinary excretion of ALN after the iv dose was similar for both weight groups. The mean oral bioavailability (95% confidence interval) was 0.43% (0.28, 0.64%) for patients weighing less than 40 kg and 0.56% (0.36, 0.87%) for patients weighing 40 kg or more. Eighteen patients reported a total of 44 clinical adverse experiences, none of which were serious. The most common adverse experiences were mild to moderate headache (n = 7), nausea (n = 7), fever (n = 5), and abdominal pain (n = 6). Eighty percent of the adverse experiences (35 of 44) occurred within 48 h of medication administration, 91% (40 of 44) lasted less than 24 h, and 84% (37 of 44) were reported after oral dosing. Laboratory safety monitoring revealed a marginal decrease in absolute lymphocyte count and serum alkaline phosphatase after the study compared with baseline for both weight categories. CONCLUSIONS: The mean oral bioavailability of 35- and 70-mg ALN tablets was less than 0.6%, comparable to adult studies. Adverse experiences from single-dose ALN were minor, and the drug was generally well-tolerated.

Adolescent↗

Selenite reduction in Boom clay: Effect of FeS(2), clay minerals and dissolved organic matter.

Several experiments were set up to study Se speciation and solubility in the reducing Boom clay environment, starting from oxidized Se species which were added in oversaturation with respect to the thermodynamic solubility of reduced Se solid phases. Upon introduction of SeO3(2-) to FeS(2)-containing samples, adsorption of SeO3(2-) occurred at the FeS2 surface, and led to a reduction and precipitation of a Se0 solid phase with a solubility of 3x10(-9) M (after 60 days). In the presence of humic substances, an association of Se with these humic substances was observed and the 3x10(-9) M solubility limit was not reached in the same time delay. Upon introduction of SeO3(2-) to Boom clay suspensions (equilibration up to 9 months), the initial adsorption of SeO3(2-) on the solid phase was increased with respect to systems containing only FeS2, due to the presence of (illite) clay minerals. This competing adsorption process, and the presence of humic substances, again decreased the kinetics of reduction with respect to FeS2 samples. Also, an association of Se with Boom clay humic substances was observed, and amounted up to approximately 10(-7) M in some samples after 9 months equilibration.

Aluminum Silicates↗

Cost-effectiveness of 18F-fluorodeoxyglucose positron emission tomography in the assessment of early dementia from a Belgian and European perspective.

(18)F-fluoro-deoxyglucose positron emission tomography (FDG PET) can aid to predict AD in an early stage. The aim of this study was to estimate the economic effects of incorporating FDG PET in the diagnostic work-up of AD in a Belgian and European setting. A decision tree analysis was followed comparing a conventional algorithm using diagnostic clinical criteria and one that also incorporates PET. Major outcome terms were overall cost per patient in either strategy; diagnostic accuracy and cost per accurate diagnosis. A sensitivity analysis was performed for four critical variables: cost of PET, sensitivity and specificity of PET and delay in cognitive decline because of appropriate medication. Cost-savings per accurate diagnosis ranged from 623-6110 Euro in favour of the proposed algorithm with PET. For the same cost, more accurate diagnoses were made, resulting in benefit for patients and society. The positive results were maintained over a wide range of values for the critical variables and were expandable to other European countries with a similar health system. Therefore, incorporation of FDG PET into the clinical diagnostic work up of patients with early symptoms of cognitive decline can be advocated.

Algorithms↗

[Unnatural and unexplained death in a paediatric intensive-care unit, 1993-2002].

OBJECTIVE: To analyse the causes of unnatural death in a general paediatric intensive-care unit. DESIGN: Retrospective and descriptive. METHODS: The cause of death was reviewed for all deceased children who were admitted to the paediatric intensive-care unit of the Emma Children's Hospital/Academic Medical Centre in Amsterdam, the Netherlands from 1993 through 2002. Three investigators independently categorised the cause of death as 'natural' or 'unnatural'. Unnatural death was defined as death by external cause, such as drowning, suffocation or violence, whether intentional or not. For all patients who died an unnatural death the cause of death and (if available) results of autopsy were analysed. RESULTS: During the study period, 5523 patients were admitted to the ICU, of whom 360 (6.5%) died during the period of admission. In 45 (12.5%) of these this was an unnatural death. In 7 (16%) patients there was a suspicion of death by deliberately caused injury. In 4 of these patients forensic autopsy was performed. The results of autopsy confirmed the suspicion of child battery in 3 patients, whereas in 1 case the diagnosis was refuted. CONCLUSION: In 16% of the children who died of unnatural causes there was a suspicion of child battery. A forensic autopsy was useful in all cases to confirm or refute the suspicion of child battery, but was not carried out in all cases.

Autopsy↗

Evidence for the interaction of technetium colloids with humic substances by X-ray absorption spectroscopy.

Spectroscopic extended X-ray absorption fine structure (EXAFS) evidence was obtained on the chemical environment of 99Tc(IV) atoms formed upon introduction of TcO4- into four types of laboratory-scale synthetic and natural systems which mimic in situ natural reducing conditions in humic-rich geochemical environments: (a) magnetite/pyrite in synthetic groundwater in the absence of humic substances (HSs), (b) magnetite/pyrite in natural Gorleben groundwater in the presence of HSs, (c) Boom clay sediment mixed with synthetic groundwater, and (d) Gorleben sand mixed with natural Gorleben groundwater. The investigated systems obey to pH 8-9 conditions, and all measured samples show similar EXAFS spectra for Tc, which could be fitted by a hydrated TcO2 x xH2O phase. The results are interpreted as follows: upon introduction of high concentrations (millimolar to micromolar) of TcO4-to chemically reducing environments, small Tc(IV) oxidic polymers are formed, which either may aggregate into larger units (colloids) and finally precipitate or may interact in their polymeric form with (dissolved and immobile) humic substances. This latter type of interaction--Tc(IV) colloid sorption onto HSs--differs significantly from the generally accepted metal--humate complexation and therefore offers new views on the possible reaction pathways of metals and radionuclides in humic-rich environments.

Aluminum Silicates↗

Investigation of the antimutagenic effects of selected South African medicinal plant extracts.

Dichloromethane extracts from different parts of Rhamnus prinoides, Ornithogalum longibracteatum, Gardenia volkensii, Spirostachys africana, Diospyros whyteana, Syzigium cordatum and Prunus africana were investigated for mutagenic and antimutagenic effects in Salmonella/microsome and micronucleus tests. None of the extracts tested in the Ames test were found to induce mutations or to modify the effect of the mutagen 4-nitroquinoline-oxide (4NQO). In the micronucleus test, extracts from twigs/bark of R. prinoides, twigs of D. whyteana, P. africana and S. cordatum significantly lowered the effect of the mutagen mitomycin C (MMC). Extracts from twigs/bark of G. volkensii and S. africana were genotoxic in the micronucleus test, while extracts of O. longibracteatum leaves potentiated the genotoxicity of MMC. This preliminary investigation shows that plant extracts used in traditional medicine may have particular effects with regard to mutagenicity and antimutagenicity indicating careful use in some instances and the need to isolate their active principles for further research.

4-Nitroquinoline-1-oxide↗

Limitation of point source pesticide pollution: results of bioremediation system.

Groundwater and surface water is at risk of contamination from the use of some agricultural pesticides. In many circumstances pesticide contamination of water resources is more likely to result from point sources than from diffuse sources following approved application to crops in the field. Such point sources include areas on farms where pesticides are handled, filled into sprayers or where sprayers are washed down. To overcome this way of contamination different kind of bio-remediation systems are nowadays in development. In Flanders, Belgium two pilot plants of bioremediation systems for the in situ retention and/or degradation of pesticides were installed. Both systems were based on the Phytobac concept, a watertight excavation filled with straw, peat, compost and soil. The channel was made in the bottom from plastic foil. All kinds of spray rests were captured by the phytobacs. This study focuses on what level pesticides leach, bio-degrade or are retained by the filling of the phytobac. The soil-properties of the filling were investigated. Pesticide tracers were added for monitoring to both phytobacs. Soil and water samples were taken during one year. Pesticides are retained at least for one month by the filling of the phytobac. Almost no pesticide leached out. In winter hardly any pesticide degradation was observed in the filling of the phytobac. In summer no detectable pesticides were still left in the phytobacs.

Air Pollution↗

RP-HPLC separation of the diastereomers of technetium-99m labelled tropanes and identity confirmation using radio-LC-MS.

99mTc-TRODAT-1 (technetium(V)-oxo-2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3.2.1]oct-2-yl]methyl](2-mercaptoethyl)amino]ethyl]]amino]-ethanethiolato(3-)) and 99mTc-TRODAT-M, the 4-methylphenyl derivative of 99mTc-TRODAT-1, are at this moment being evaluated in clinical trials as imaging agents for the central nervous dopamine transporter system. Both compounds are formed as a mixture of two major diastereomers. As the tracer concentration in preparations for clinical investigations is very low (30-150 pmol/ml), identification of these 99mTc-complexes was, up to now, carried out indirectly using X-ray diffraction analysis of the corresponding rhenium complexes which can be synthesized in gram amounts. In this study, we developed a convenient and practical reversed phase HPLC-method for purification and isolation of the respective diastereomers of 99mTc-TRODAT-1 and three of its derivatives using mixtures of solvents which are compatible with biological studies, i.e. aqueous buffers and ethanol. Furthermore, direct identity confirmation of the 99mTc-complexes using radio-LC-MS was successfully elaborated.

Chromatography, High Pressure Liquid↗

Metal partitioning in a sulfidic canal sediment: metal solubility as a function of pH combined with EDTA extraction in anoxic conditions.

The chemical forms of low concentrations of metals (Zn, Pb, Cu, Cd, Co and Mn) and main components (Fe and Ca) were determined under the original reducing conditions of a sulfide-rich sediment from the Gent-Terneuzen Canal (Belgium). Therefore, dissolution experiments as a function of pH were made in a salt solution mimicking the canal water. The centrifugates remaining after the dissolution vs. pH experiments were subsequently further extracted with 0.1 M EDTA/0.5 M NaAc (pH 4.65) to determine eventually readsorbed and/or reprecipitated metal ions. The experimental dissolution vs. pH edge of calcium, iron, manganese and cobalt had a lower slope than theoretically expected on the basis of the solubility of, respectively, calcium carbonate, iron sulfide/iron carbonate, manganese sulfide/manganese carbonate and cobalt sulfide and was explained by the combination of (a) the solubilities of the various minerals and (b) metal readsorption onto clay minerals and organic matter. Higher metal recoveries were measured in the 0.1 M EDTA/0.5 M NaAc mixture and proved that in addition coprecipitate formation with iron sulfide/iron carbonate minerals may occur. The solubility of zinc, lead, cadmium and copper was very low in the mimicking salt solution even at very low pH values (up to pH 1) in agreement with the theoretical solubility of their discrete metal sulfides. However, by using an additional 0.1 M EDTA/0.5 M NaAc extraction on the centrifugates remaining after the dissolution vs. pH experiments, it was qualitatively shown that zinc and lead were partly associated with iron sulfide/iron carbonate phases in the real sediment (in addition to their presence in discrete metal sulfides). Cadmium was present solely in discrete cadmium sulfide phases. It was not possible to verify whether copper was present in discrete copper sulfide phases and/or in mixed coprecipitates with iron sulfide/iron carbonate minerals.

Journal Article↗

Quantification of the interaction of Tc with dissolved boom clay humic substances.

Technetium-99 (Tc), a fission product of uranium-238, is an important radionuclide because of its long half-life and its high yield in radioactive waste. To elucidate the Tc geochemical behavior in reducing environments relevant to geological disposal and in the presence of humic substances (HS), experiments were set up that resulted forthe first time in the determination of an interaction constant for Tc with dissolved humic substances. A number of lab-scale Boom Clay (a possible geological underground High-Level Radioactive Waste storage site in Mol, Belgium) batch experiments were set up, combining both different initial Tc(VII) concentrations and different solid/liquid ratios. On these batches several sequential extraction steps with HS-free synthetic Boom Clay water were performed. Equilibration times were fixed at 1 week for each extraction step. Tc(VII) was found to be readily reduced to Tc(IV) by the solid Boom Clay phase. This solid phase was able to sorb Tc(IV) to a very large extent (log Kd approximately 2.5-4.0), and two sorption sinks (one of which is humic substances) were detected. In solution, Tc(IV) was mainly associated with HS. Concentrations in solution were found up to the order of 2 x 10(-6) M. The results were quantitatively described as a competition for Tc(IV) between the solid phase and the dissolved HS (Schubert-like approach). It was concluded that a hydrophobic sorption of uncharged Tc(IV) species in solution would act as the dominating interaction mechanism with HS, with an interaction constant log K(HS) = 5.3 +/- 0.3.

Adsorption↗

Assessment of myocardial viability in a porcine model of chronic coronary artery stenosis with dual dose dobutamine magnetic resonance imaging.

In a non-surgical porcine coronary stenosis model resulting in chronic left ventricle dysfunction, we aimed in this study to evaluate the potential of magnetic resonance imaging (MRI) to distinguish dysfunctional but viable from necrotic myocardium by using multiple levels of dobutamine inotropic stimulation during a cine MRI protocol (F.P. van Rugge et al. Circulation 1994; 90: 127-138). We compared our results with histopathology. We were able to demonstrate a biphasic effect at increasing doses of dobutamine in a subgroup of animals with a high-grade coronary stenosis, while in another subgroup the coronary stenosis produced a chronic myocardial infarction, in which no functional recovery could be obtained. In this experimental protocol, dual dose dobutamine MRI proved to be an accurate and reproducible technique to perform viability studies in chronic obstructive coronary artery disease. It permits distinguishing chronic ischemic, but viable myocardium from infarcted tissue. The detection of chronically underperfused but potentially salvageable myocardium is of significant clinical importance since it may aid in determining which patients are eligible for revascularization.

Animals↗