Pancreatic perfusion and its response to glucose as measured by simultaneous PET/MRI.

AIMS: Perfusion of the pancreas and the islets of Langerhans is sensitive to physiological stimuli and is dysregulated in metabolic disease. Pancreatic perfusion can be assessed by both positron emission tomography (PET) and magnetic resonance imaging (MRI), but the methods have not been directly compared or benchmarked against the gold-standard microsphere technique. METHODS: Pigs (n = 4) were examined by [15O]H2O PET and intravoxel incoherent motion (IVIM) MRI technique simultaneously using a hybrid PET/MRI scanner. The pancreatic perfusion was measured both at basal conditions and after intravenous (IV) administration of up to 0.5 g/kg glucose. RESULTS: Pancreatic perfusion increased by 35%, 157%, and 29% after IV 0.5 g/kg glucose compared to during basal conditions, as assessed by [15O]H2O PET, IVIM MRI, and microspheres, respectively. There was a correlation between pancreatic perfusion as assessed by [15O]H2O PET and IVIM MRI (r = 0.81, R2 = 0.65, p < 0.01). The absolute quantification of pancreatic perfusion (ml/min/g) by [15O]H2O PET was within a 15% error of margin of the microsphere technique. CONCLUSION: Pancreatic perfusion by [15O]H2O PET was in agreement with the microsphere technique assessment. The IVIM MRI method has the potential to replace [15O]H2O PET if the pancreatic perfusion is sufficiently large, but not when absolute quantitation is required.

Energy expenditure of rugby players during a 14-day in-season period, measured using doubly labelled water.

Criterion data for total energy expenditure (TEE) in elite rugby are lacking, which prediction equations may not reflect accurately. This study quantified TEE of 27 elite male rugby league (RL) and rugby union (RU) players (U16, U20, U24 age groups) during a 14-day in-season period using doubly labelled water (DLW). Measured TEE was also compared to estimated, using prediction equations. Resting metabolic rate (RMR) was measured using indirect calorimetry, and physical activity level (PAL) estimated (TEE:RMR). Differences in measured TEE were unclear by code and age (RL 4369 ± 979; RU 4365 ± 1122; U16, 4010 ± 744; U20, 4414 ± 688; U24, 4761 ± 1523 Kcal day- 1). Differences in PAL (overall mean 2.0 ± 0.4) were unclear. Very likely differences were observed in RMR by code (RL 2366 ± 296; RU 2123 ± 269 Kcal day- 1). Differences in relative RMR between U20 and U24 were very likely (U16, 27 ± 4; U20, 23 ± 3; U24, 26 ± 5 Kcal kg- 1 day- 1). Differences were observed between measured and estimated TEE, using Schofield, Cunningham and Harris-Benedict equations for U16 (187 ± 614, unclear; - 489 ± 564, likely and - 90 ± 579, unclear Kcal day- 1), U20 (- 449 ± 698, likely; - 785 ± 650, very likely and - 452 ± 684, likely Kcal day- 1) and U24 players (- 428 ± 1292; - 605 ± 1493 and - 461 ± 1314 Kcal day- 1, all unclear). Rugby players have high TEE, which should be acknowledged. Large inter-player variability in TEE was observed demonstrating heterogeneity within groups, thus published equations may not appropriately estimate TEE.

Loss of inhibition in sensorimotor networks in focal hand dystonia.

OBJECTIVE: To investigate GABA-ergic receptor density and associated brain functional and grey matter changes in focal hand dystonia (FHD). METHODS: 18 patients with FHD of the right hand and 18 age and gender matched healthy volunteers (HV) participated in this study. We measured the density of GABA-A receptors using [11C] Flumazenil and perfusion using [15O] H2O. Anatomical images were also used to measure grey matter volume with voxel-based morphometry (VBM). RESULTS: In FHD patients compared to HV, the vermis VI of the right cerebellum and the left sensorimotor cortex had a decrease of Flumazenil binding potential (FMZ-BP), whereas the striatum and the lateral cerebellum did not show significant change. Bilateral inferior prefrontal cortex had increased FMZ-BP and an increase of perfusion, which correlated negatively with disease duration. Only the left sensorimotor cortex showed a decrease of grey matter volume. INTERPRETATION: Impairments of GABAergic neurotransmission in the cerebellum and the sensorimotor cortical areas could explain different aspects of loss of inhibitory control in FHD, the former being involved in maladaptive plasticity, the latter in surround inhibition. Reorganization of the inferior prefrontal cortices, part of the associative network, might be compensatory for the loss of inhibitory control in sensorimotor circuits. These findings suggest that cerebellar and cerebral GABAergic abnormalities could play a role in the functional imbalance of striato-cerebello-cortical loops in dystonia.

Indirect Proton MR Imaging and Kinetic Analysis of 17O-Labeled Water Tracer in the Brain.

PURPOSE: The feasibility of steady-state sequences for 17O imaging was evaluated based on a kinetic analysis of the brain parenchyma and cerebrospinal fluid (CSF). MATERIALS AND METHODS: The institutional review board approved this prospective study with written informed consent. Dynamic 2D or 3D steady-state sequences were performed in five and nine participants, respectively, with different parameters using a 3T scanner. During two consecutive dynamic scans, saline was intravenously administered for control purposes in the first scan, and 20% 17O-labeled water (1 mL/Kg) was administered in the second scan. Signal changes relative to the baseline were calculated, and kinetic analyses of the curves were conducted for all voxels. Region of interest analysis was performed in the brain parenchyma, choroid plexus, and CSF spaces. RESULTS: Average signal drops were significantly larger in the 17O group than in the controls for most of the imaging parameters. Different kinetic parameters were observed between the brain parenchyma and CSF spaces. Average and maximum signal drops were significantly larger in the CSF spaces and choroid plexus than in the brain parenchyma. Bolus arrival, time to peak, and the first moment of dynamic curves of 17O in the CSF space were delayed compared to that in the brain parenchyma. Significant differences between the ventricle and subarachnoid space were also noted. CONCLUSION: Steady-state sequences are feasible for indirect 17O imaging with reasonable temporal resolution; this result is potentially important for the analysis of water kinetics and aquaporin function for several disorders.

Doubly labelled water assessment of energy expenditure: principle, practice, and promise.

The doubly labelled water method for the assessment of energy expenditure was first published in 1955, application in humans started in 1982, and it has become the gold standard for human energy requirement under daily living conditions. The method involves enriching the body water of a subject with heavy hydrogen (2H) and heavy oxygen (18O), and then determining the difference in washout kinetics between both isotopes, being a function of carbon dioxide production. In practice, subjects get a measured amount of doubly labelled water (2H 218 O) to increase background enrichment of body water for 18O of 2000 ppm with at least 180 ppm and background enrichment of body water for 2H of 150 ppm with 120 ppm. Subsequently, the difference between the apparent turnover rates of the hydrogen and oxygen of body water is assessed from blood-, saliva-, or urine samples, collected at the start and end of the observation interval of 1-3 weeks. Samples are analyzed for 18O and 2H with isotope ratio mass spectrometry. The doubly labelled water method is the indicated method to measure energy expenditure in any environment, especially with regard to activity energy expenditure, without interference with the behavior of the subjects. Applications include the assessment of energy requirement from total energy expenditure, validation of dietary assessment methods and validation of physical activity assessment methods with doubly labelled water measured energy expenditure as reference, and studies on body mass regulation with energy expenditure as a determinant of energy balance.

Ligand-based molecular MRI: O-17 JJVCPE amyloid imaging in transgenic mice.

BACKGROUND: Development of molecular MR imaging (MRI) similar to PET imaging using contrast agents such as gadolinium as probe have been inherently hampered by incompatibility between potential probe (charged molecules) and membrane permeability. Nevertheless, considering the inherent spatial resolution limit for PET of 700µ, the superior microscopic resolution of MRI of 4 µ presents a strong incentive for research into ligand-based molecular MRI. METHODS: (17) O exhibits JJ vicinal coupling with a covalently bound proton in a hydroxyl group. This (17) O coupled proton can be ionized in water solution and interexchange with other water protons. This property can be utilized as "probe" in T2-weighted imaging and developed into ligand-based molecular MRI. We examined ß-amyloid distribution in human APP overexpressed transgenic mice in vivo following injection of (17) O labeled Pittsburg compound B ((17) O-PiB). RESULTS: JJVCPE imaging successfully imaged (17) O-PiB, unequivocally establishing that (17) O JJVCPE imaging can be developed into PET-like molecular MRI in clinical medicine. CONCLUSIONS: The study represents the first successful ligand-based molecular MRI in vivo. This is also the first in vivo amyloid imaging using MRI. High-resolution molecular MRI with high specificity under clinical settings, such as in vivo microscopic imaging of senile plaque, is a foreseeable aim.

Direct (17)O MRI with partial volume correction: first experiences in a glioblastoma patient.

OBJECT: In tumor cells the energy production is shifted from aerobic to anaerobic metabolization of glucose, which makes the cerebral metabolic rate of oxygen consumption (CMRO2) a diagnostic parameter for tissue viability. Direct oxygen-17 ((17)O) MRI during inhalation of (17)O gas allows for a non-invasive determination of the CMRO2. However, the low spatial resolution and the fast transverse relaxation of (17)O lead to partial volume effects that severely bias the quantification of signal intensities. The aim of this work was to determine the CMRO2 in a tumor patient by (17)O MRI in combination with a partial volume correction (PVC) scheme. MATERIALS AND METHODS: Direct (17)O MRI was performed in a glioblastoma patient (F, 51 years) prior to surgery at 7 T. The 'geometric transfer matrix' algorithm for volume of interest based PVC was adapted to (17)O MRI to recover the true signal intensities. We determined the CMRO2 values of gray matter (GM), white matter (WM), cerebrospinal fluid (CSF) and the tumor areas of the contrast enhancing rim (CE), the necrotic center (NE), and the perifocal edema (PE) using a three-phase metabolic model. RESULTS: Large differences in the signal increase during (17)O2 inhalation were obtained ranging from less than 2% in the tumor center up to more than 20% in GM areas. After PVC of the signal time curves, we determined CMRO2 values of 0.67 ± 0.08 µmol/g/min (WM), 3.57 ± 0.67 µmol/g/min (GM), 0.35 ± 0.09 µmol/g/min (CE), and 0.42 ± 0.05 µmol/g/min (PE). In CSF and NE no oxygen uptake (i.e. CMRO2 = 0) was determined from the corrected signals, well in accordance with the underlying physiology in these regions. CONCLUSION: The results show that PVC has a strong effect on the resulting CMRO2 values obtained by (17)O MRI. We found substantial differences-especially in GM tissue-between corrected and non-corrected CMRO2 values. Additionally, we demonstrated the feasibility of CMRO2 assessment in a glioblastoma patient by (17)O MRI.

Intracellular and extracellular carbonic anhydrases cooperate non-enzymatically to enhance activity of monocarboxylate transporters.

Proton-coupled monocarboxylate transporters (MCTs) are carriers of high-energy metabolites such as lactate, pyruvate, and ketone bodies and are expressed in most tissues. It has previously been shown that transport activity of MCT1 and MCT4 is enhanced by the cytosolic carbonic anhydrase II (CAII) independent of its catalytic activity. We have now studied the influence of the extracellular, membrane-bound CAIV on transport activity of MCT1/4, heterologously expressed in Xenopus oocytes. Coexpression of CAIV with MCT1 and MCT4 resulted in a significant increase in MCT transport activity, even in the nominal absence of CO2/HCO3(-). CAIV-mediated augmentation of MCT activity was independent of the CAIV catalytic function, since application of the CA-inhibitor ethoxyzolamide or coexpression of the catalytically inactive mutant CAIV-V165Y did not suppress CAIV-mediated augmentation of MCT transport activity. The interaction required CAIV at the extracellular surface, since injection of CAIV protein into the oocyte cytosol did not augment MCT transport function. The effects of cytosolic CAII (injected as protein) and extracellular CAIV (expressed) on MCT transport activity, were additive. Our results suggest that intra- and extracellular carbonic anhydrases can work in concert to ensure rapid shuttling of metabolites across the cell membrane.

Quantitative cerebral blood flow with bolus tracking perfusion MRI: measurements in porcine model and comparison with H(2)(15)O PET.

PURPOSE: We recently presented a method for the quantitative measurement of the arterial input function which allows for determination of absolute cerebral blood flow (CBF) values without adjustable parameters. The aim of the present work is to estimate absolute CBF values by using this new technique and to compare it with the gold standard for cerebral perfusion, H(2)(15)O positron emission tomography. METHODS: Pigs (13) were comparatively investigated by each method performing multiple measurement runs. The reproducibility of both methods was assessed by a voxel-wise correlation of repeated measurements. An intersubject evaluation was performed on median whole-brain CBF estimates. RESULTS: The mean CBF (MRI) was 20±4mL/100g/min for gray matter, the mean CBF (positron emission tomography) was 24±6mL/100g/min for gray and white matter. The reproducibility for MRI correlated with r = 0.85 and P<0.0001, for positron emission tomography with r = 0.76 and P<0.0001. The correlation for the median whole-brain CBF in MRI and positron emission tomography was r = 0.60 and P = 0.04. CONCLUSIONS: The proposed method allows for determination of quantitative CBF without normalization factors. The relatively low estimates of absolute CBF most likely results from the higher age of the pigs as compared to other studies. The intermediate correlation between both methods is caused by physiological intraindividual fluctuations of the CBF and by a limited reproducibility of both methods.

Quantitative 17O imaging towards oxygen consumption study in tumor bearing mice at 7 T.

(17)O magnetic resonance imaging (MRI) using a conventional pulse sequence was explored as a method of quantitative imaging towards regional oxygen consumption rate measurement for tumor evaluation in mice. At 7 T, fast imaging with steady state (FISP) was the best among gradient echo, fast spin echo and FISP for the purpose. The distribution of natural abundance H2(17)O in mice was visualized under spatial resolution of 2.5 × 2.5mm(2) by FISP in 10 min. The signal intensity by FISP showed a linear relationship with (17)O quantity both in phantom and mice. Following the injection of 5% (17)O enriched saline, (17)O re-distribution was monitored in temporal resolution down to 5 sec with an image quality sufficient to distinguish each organ. The image of labeled water produced from inhaled (17)O2 gas was also obtained. The present method provides quantitative (17)O images under sufficient temporal and spatial resolution for the evaluation of oxygen consumption rate in each organ. Experiments using various model compounds of R-OH type clarified that the signal contribution of body constituents other than water in the present in vivo(17)O FISP image was negligible.

In vivo measurement of CBF using ¹7O NMR signal of metabolically produced H2¹7O as a perfusion tracer.

The cerebral metabolic rate of oxygen of small animals can be reliably imaged using the in vivo (17) O magnetic resonance approach at high field. However, a separate measurement is required for imaging the cerebral blood flow in the same animal. In this study, we demonstrate that the (17) O NMR signal of metabolically produced H2 (17) O in the rat brain following an (17) O2 inhalation can serve as a perfusion tracer and its decay rate can be used to determine the absolute values of cerebral blood flow across a wide range of animal conditions. This finding suggests that the in vivo (17) O magnetic resonance approach is capable of imaging both cerebral metabolic rate of oxygen and cerebral blood flow simultaneously and noninvasively; and it provides new utilities for studying the cerebral oxygen metabolism and perfusion commonly associated with brain function and diseases.

Simultaneous and noninvasive imaging of cerebral oxygen metabolic rate, blood flow and oxygen extraction fraction in stroke mice.

Many brain diseases have been linked to abnormal oxygen metabolism and blood perfusion; nevertheless, there is still a lack of robust diagnostic tools for directly imaging cerebral metabolic rate of oxygen (CMRO(2)) and cerebral blood flow (CBF), as well as the oxygen extraction fraction (OEF) that reflects the balance between CMRO(2) and CBF. This study employed the recently developed in vivo (17)O MR spectroscopic imaging to simultaneously assess CMRO(2), CBF and OEF in the brain using a preclinical middle cerebral arterial occlusion mouse model with a brief inhalation of (17)O-labeled oxygen gas. The results demonstrated high sensitivity and reliability of the noninvasive (17)O-MR approach for rapidly imaging CMRO(2), CBF and OEF abnormalities in the ischemic cortex of the MCAO mouse brain. It was found that in the ischemic brain regions both CMRO(2) and CBF were substantially lower than that of intact brain regions, even for the mildly damaged brain regions that were unable to be clearly identified by the conventional MRI. In contrast, OEF was higher in the MCAO affected brain regions. This study demonstrates a promising (17)O MRI technique for imaging abnormal oxygen metabolism and perfusion in the diseased brain regions. This (17)O MRI technique is advantageous because of its robustness, simplicity, noninvasiveness and reliability: features that are essential to potentially translate it to human patients for early diagnosis and monitoring of treatment efficacy.

In vitro and in vivo studies of 17O NMR sensitivity at 9.4 and 16.4 T.

In vivo 17O magnetic resonance spectroscopy has been successfully applied for imaging the cerebral metabolic rate of oxygen consumption through the detection of metabolically produced H2(17)O from the inhaled 17O-labeled oxygen in animals at high field. In this study, we compared the 17O sensitivity for detecting natural abundance H2(17)O signals from a phantom solution and rat brains at 9.4 and 16.4 T. The 17O signal-to-noise ratio measured at 16.4 T was 2.9- and 2.7-2.8-fold higher than that at 9.4 T for the phantom and rat brain studies, respectively. Similarly, three-dimensional 17O magnetic resonance spectroscopy imaging data showed a more than 2.7-fold higher signal-to-noise ratio in the central rat brain region at 16.4 T than that at 9.4 T. The substantial 17O signal-to-noise ratio gain at ultrahigh field significantly improved the reliability for imaging the cerebral metabolic rate of oxygen consumption and will provide an opportunity for in vivo assessment of altered oxidative metabolism associated with brain functions and neurological diseases.

Global application of stable hydrogen and oxygen isotopes to wildlife forensics.

Stable isotopes are being increasingly used in wildlife forensics as means of determining the origin and movement of animals. The heavy isotope content of precipitated water and snow (deltaD(p), delta(18)O(p)) varies widely and systematically across the globe, providing a label that is incorporated through diet into animal tissue. As a result, these isotopes are potentially ideal tracers of geographic origin. The hydrogen and oxygen isotope tracer method has excellent potential where (1) spatial variation of precipitation isotopes exist, and (2) strong, mechanistic relationships link precipitation and isotope ratios in biological tissue. Here, we present a method for interpolation of precipitation isotope values and use it to create global basemaps of growing-season (GS) and mean annual (MA) deltaD(p) and delta(18)O(p). The use of these maps for forensic application is demonstrated using previously published isotope data for bird feathers (deltaD(f)) in North America and Europe. The precipitation maps show that the greatest potential for applying hydrogen and oxygen isotope forensics exists in mid- to high-latitude continental regions, where strong spatial isotope gradients exist. We demonstrate that deltaD(f)/deltaD(p) relationships have significant predictive power both in North America and Europe, and show how zones of confidence for the assignment of origin can be described using these predictive relationships. Our analysis focuses on wildlife forensics, but the maps and approaches presented here will be equally applicable to criminal forensic studies involving biological materials. These maps are available in GIS format at http://www.waterisotopes.org.

Oxygen and nitrogen isotopic fractionations during human respiration.

Both oxygen and nitrogen isotope compositions (delta18O and delta15N) of exhaled air from 10 individuals were measured. Results show linear relations between isotope variation and the fraction of O2 used during the respiration process. The isotopic influence of physiological parameters such as smoking habits, age, haemoglobin count, oxygen fixation rate or physical exercise was assessed. Among them, only smoking habits do not have any effect on delta18O. Delta15N differences between inhaled and exhaled air may indicate an active (but minor) role for nitrogen during the human respiration process. Nevertheless, nitrogen fractionation is homogenous among all the individuals, which is coherent with the fact that nitrogen metabolism is controlled by the intestinal bacterial activity.

Centile reference charts for total energy expenditure in infants from 1 to 12 months.

BACKGROUND: A knowledge of energy expenditure in infancy is required for the estimation of recommended daily amounts of food energy, for designing artificial infant feeds, and as a reference standard for studies of energy metabolism in disease states. OBJECTIVES: The objectives of this study were to construct centile reference charts for total energy expenditure (TEE) in infants across the first year of life. METHODS: Repeated measures of TEE using the doubly labeled water technique were made in 162 infants at 1.5, 3, 6, 9 and 12 months. In total, 322 TEE measurements were obtained. The LMS method with maximum penalized likelihood was used to construct the centile reference charts. Centiles were constructed for TEE expressed as MJ/day and also expressed relative to body weight (BW) and fat-free mass (FFM). RESULTS: TEE increased with age and was 1.40,1.86, 2.64, 3.07 and 3.65 MJ/day at 1.5, 3, 6, 9 and 12 months, respectively. The standard deviations were 0.43, 0.47, 0.52,0.66 and 0.88, respectively. TEE in MJ/kg increased from 0.29 to 0.36 and in MJ/day/kg FFM from 0.36 to 0.48. CONCLUSIONS: We have presented centile reference charts for TEE expressed as MJ/day and expressed relative to BW and FFM in infants across the first year of life. There was a wide variation or biological scatter in TEE values seen at all ages. We suggest that these centile charts may be used to assess and possibly quantify abnormal energy metabolism in disease states in infants.

Cerebellar representation of the eyeblink response as revealed by PET.

Blink reflex-related areas in the human cerebellum were studied using [15O]H2O PET in eight healthy subjects. Eyeblinks were evoked by airpuff stimulation and recorded via surface electrodes. PET analysis revealed a cerebellar increase of regional cerebral blood flow in vermal lobule VI and a small ipsilateral paravermal extension in the eyeblink condition compared to rest. This activation partly overlapped with areas found in recent fMRI and animal studies investigating the cerebellar involvement in control of the unconditioned and acquisition of the conditioned eyeblink response. In conclusion, vermal lobule VI extending to ipsilateral paravermal areas appears to be involved in control of the unconditioned eyeblink response.

Comparison of microsphere-equivalent blood flow (15O-water PET) and relative perfusion (99mTc-tetrofosmin SPECT) in myocardium showing metabolism-perfusion mismatch.

UNLABELLED: Myocardial perfusion imaging with (99m)Tc-tetrofosmin is based on the assumption of a linear correlation between myocardial blood flow (MBF) and tracer uptake. However, it is known that (99m)Tc-tetrofosmin uptake is directly related to energy-dependent transport processes, such as Na(+)/H(+) ion channel activity, as well as cellular and mitochondrial membrane potentials. Therefore, cellular alterations that affect these energy-dependent transport processes ought to influence (99m)Tc-tetrofosmin uptake independently of blood flow. Because metabolism ((18)F-FDG)-perfusion ((99m)Tc-tetrofosmin) mismatch myocardium (MPMM) reflects impaired but viable myocardium showing cellular alterations, MPMM was chosen to quantify the blood flow-independent effect of cellular alterations on (99m)Tc-tetrofosmin uptake. Therefore, we compared microsphere-equivalent MBF (MBF_micr; (15)O-water PET) and (99m)Tc-tetrofosmin uptake in MPMM and in "normal" myocardium. METHODS: Forty-two patients with severe coronary artery disease, referred for myocardial viability diagnostics, were examined using (18)F-FDG PET and (99m)Tc-tetrofosmin perfusion SPECT. Relative (18)F-FDG and (99m)Tc-tetrofosmin uptake values were calculated using 18 segments per patient. Normal myocardium and MPMM myocardium were classified using a previously validated (99m)Tc-tetrofosmin SPECT/(18)F-FDG PET score. In addition, (15)O-water PET was performed to assess kinetic-modeled MBF (MBF_kin), the water-perfusable tissue fraction (PTF), and the resulting MBF_micr (MBF_kin x PTF), which is comparable to tracer uptake values. (99m)Tc-tetrofosmin uptake and MBF_micr values were calculated for all normal and MPMM segments and averaged within their respective classifications. RESULTS: Mean relative (99m)Tc-tetrofosmin uptake was 86% +/- 1% in normal myocardium and 56% +/- 1% in MPMM, showing a significant difference (P < 0.001), as was expected from the classification. Contrary to these findings, mean MBF_micr in MPMM myocardium was 0.60 +/- 0.03 mL x min(-1) x mL(-1), which did not significantly differ from normal myocardium (0.64 +/- 0.01 mL x min(-1) x mL(-1)). All values are given as mean +/- SEM. CONCLUSION: Differences between reduced (99m)Tc-tetrofosmin uptake and the unchanged MBF_micr in MPMM myocardium suggest that the pathophysiologic basis of MPMM is not a blood flow reduction but cellular alterations that affect uptake and retention of (99m)Tc-tetrofosmin independently of blood flow. Therefore, it seems that perfusion deficits in MPMM myocardium are greatly overestimated by (99m)Tc-tetrofosmin and that it tends to give false-positive findings.

Box-modeling of bone and tooth phosphate oxygen isotope compositions as a function of environmental and physiological parameters.

A time-dependent box model is developed to calculate oxygen isotope compositions of bone phosphate as a function of environmental and physiological parameters. Input and output oxygen fluxes related to body water and bone reservoirs are scaled to the body mass. The oxygen fluxes are evaluated by stoichiometric scaling to the calcium accretion and resorption rates, assuming a pure hydroxylapatite composition for the bone and tooth mineral. The model shows how the diet composition, body mass, ambient relative humidity and temperature may control the oxygen isotope composition of bone phosphate. The model also computes how bones and teeth record short-term variations in relative humidity, air temperature and delta18O of drinking water, depending on body mass. The documented diversity of oxygen isotope fractionation equations for vertebrates is accounted for by our model when for each specimen the physiological and diet parameters are adjusted in the living range of environmental conditions.

18O incorporation in the oxidation of N-methylcarbazole by lignin peroxidase and a model compound: a mechanistic insight into the oxidative N-demethylation of aromatic tertiary amines.

Using 18O labelled reactants and/or solvent, the origin of the oxygen in the products of the oxidation of N-methylcarbazole by H2O2 catalysed by lignin peroxidase and a model compound has been determined, so getting important information about the mechanism of the oxidative N-demethylation of aromatic tertiary amines.