Degradation of structurally different non-digestible oligosaccharides by intestinal bacteria: glycosylhydrolases of Bifidobacterium adolescentis = Afbraak van in structuur verschillende niet-verteerbare oligosacchariden door darmbacteriën : glycosylhydrolasen van Bifidobacterium adolescentis

Non-digestible oligosaccharides (NDOs) are oligosaccharides, which resist digestion in the upper gastrointestinal tract, and which are fermented in the colon by intestinal bacteria. Some NDOs are considered bifidogenic, meaning that they selectively stimulate the growth of bifidobacteria in the colon microbiota. The degradative fermentation of structurally different oligosaccharides by intestinal bacteria was studied in this thesis, in order to establish the potentially bifidogenic effects of various types of NDOs. Structurally different oligosaccharides were produced using different routes. Arabino-, (arabino-)galacto-, (arabino-)xylo-, galacturono-, and rhamnogalacturono- oligosaccharides were derived by enzymatic hydrolysis of plant polysaccharides. Through transglycosylation reactions using glycosidases, transgalactooligosaccharides of theα- andβ-glycosyl linkage type were obtained.The chemical structure of the oligosaccharides clearly influenced their fermentation behaviour. It was concluded that species belonging to different groups, so not only bifidobacteria, have the capability of hydrolysing these oligosaccharides. Bi. adolescentis, being a major bifidobacterial species of the adult intestinal microflora, was able to utilise a wide range of oligosaccharides showing its wide range of glycosidases. Two novel arabinoxylan degrading enzymes were purified from Bi. adolescentis and these enzymes in combination with aβ-xylosidase are involved in the complete degradation of arabinoxylooligosaccharides. For the utilisation ofα-galactooligosaccharides Bi. adolescentis produced anα-galactosidase. Thisα-galactosidase was characterised as a retaining glycosidase and was used for the production of new types ofα-galactooligosaccharides. Theseα-1→6 linked-galactooligosaccharides could be utilised by various strains belonging to bifidobacteria and lactobacilli. Upon growth of Bi. adolescentis on transgalactooligosaccharides (TOS) a novelβ-galactosidase was produced, involved in the degradation of TOS. It was speculated that this enzyme was membrane or cell wall associated. After growth of Bi. adolescentis on TOS or on hydrolysed arabinogalactan theβ-galactosidase production of Bi. adolescentis increased compared to growth on galactose and this increasedβ-galactosidase activity could be linked to increased activity towards both polymeric and oligomeric galactan. In vivo dietary intervention with TOS also resulted in increased levels of v-galactosidase activity in feces. Although the nature and specificity of theβ-galactosidase is not yet known it can be concluded that glycosidase activity of the intestinal bacteria might be a useful biomarker of the colonic metabolic activity.</p

NEMA NU 2-2007 performance characteristics of GE Signa integrated PET/MR for different PET isotopes

BackgroundFully integrated PET/MR systems are being used frequently in clinical research and routine. National Electrical Manufacturers Association (NEMA) characterization of these systems is generally done with F-18 which is clinically the most relevant PET isotope. However, other PET isotopes, such as Ga-68 and Y-90, are gaining clinical importance as they are of specific interest for oncological applications and for follow-up of Y-90-based radionuclide therapy. These isotopes have a complex decay scheme with a variety of prompt gammas in coincidence. Ga-68 and Y-90 have higher positron energy and, because of the larger positron range, there may be interference with the magnetic field of the MR compared to F-18. Therefore, it is relevant to determine the performance of PET/MR for these clinically relevant and commercially available isotopes.MethodsNEMA NU 2-2007 performance measurements were performed for characterizing the spatial resolution, sensitivity, image quality, and the accuracy of attenuation and scatter corrections for F-18, Ga-68, and Y-90. Scatter fraction and noise equivalent count rate (NECR) tests were performed using F-18 and Ga-68. All phantom data were acquired on the GE Signa integrated PET/MR system, installed in UZ Leuven, Belgium.Results(18)F, Ga-68, and Y-90 NEMA performance tests resulted in substantially different system characteristics. In comparison with F-18, the spatial resolution is about 1mm larger in the axial direction for Ga-68 and no significative effect was found for Y-90. The impact of this lower resolution is also visible in the recovery coefficients of the smallest spheres of Ga-68 in image quality measurements, where clearly lower values are obtained. For Y-90, the low number of counts leads to a large variability in the image quality measurements. The primary factor for the sensitivity change is the scale factor related to the positron emission fraction. There is also an impact on the peak NECR, which is lower for Ga-68 than for F-18 and appears at higher activities.ConclusionsThe system performance of GE Signa integrated PET/MR was substantially different, in terms of NEMA spatial resolution, image quality, and NECR for Ga-68 and Y-90 compared to F-18. But these differences are compensated by the PET/MR scanner technologies and reconstructions methods

Highlights lecture EANM 2014: “Gimme gimme gimme those nuclear Super Troupers”

The EANM Congress 2014 took place in Gothenburg, Sweden, from 18 to 22 October under the presidency of Prof. Wim Oyen, chair of the EANM Scientific Committee. Prof. Peter Gjertsson chaired the Local Organizing Committee, according to the standardized EANM congress structure. The meeting was a highlight for the multidisciplinary community that forms the heart and soul of nuclear medicine; attendance was exceptionally high. In total almost 5,300 participants came to Gothenburg, and 1,397 colleagues participated via the EANM LIVE sessions (http://eanmlive.eanm.org/index.php). Participants from all continents were presented with an excellent programme consisting of symposia, scientific and featured sessions, CME sessions, and plenary lectures. These lectures were devoted to nuclear medicine therapy, hybrid imaging and molecular life sciences. Two tracks were included in the main programme, clustering multi-committee involvement: the 5th International Symposium on Targeted Radionuclide-therapy and Dosimetry (ISTARD) and the first Molecules to Man (M2M) track, an initiative of the EANM Committees for Translational Molecular Imaging, Radiopharmacy and Drug Development. The industry made a substantial contribution to the success of the congress demonstrating the latest technology and innovations in the field. During the closing Highlights Lecture, a selection of the best-rated abstracts was presented including diverse areas of nuclear medicine: physics and instrumentation, radiopharmacy, preclinical imaging, oncology (with a focus on the clinical application of newly developed tracers) and radionuclide therapy, cardiology and neurosciences. This Highlights Lecture could only be a brief summary of the large amount of data presented and discussed during the meeting, which can be found in much greater detail in the congress proceedings book, published as Volume 41, Supplement 2 of the European Journal of Nuclear Medicine and Molecular Imaging in October 2014

No difference in striatal dopamine transporter availability between active smokers, ex-smokers and non-smokers using [123I]FP-CIT (DaTSCAN) and SPECT

Background: Mesolimbic and nigrostriatal dopaminergic pathways play important roles in both the rewarding and conditioning effects of drugs. The dopamine transporter (DAT) is of central importance in regulating dopaminergic neurotransmission and in particular in activating the striatal D2-like receptors. Molecular imaging studies of the relationship between DAT availability/dopamine synthesis capacity and active cigarette smoking have shown conflicting results. Through the collaboration between 13 SPECT centres located in 10 different European countries, a database of FP-CIT-binding in healthy controls was established. We used the database to test the hypothesis that striatal DAT availability is changed in active smokers compared to non-smokers and ex-smokers. Methods: A total of 129 healthy volunteers were included. Subjects were divided into three categories according to past and present tobacco smoking: (1) non-smokers (n = 64), (2) ex-smokers (n = 39) and (3) active smokers (n = 26). For imaging of the DAT availability, we used [123I]FP-CIT (DaTSCAN) and single photon emission computed tomography (SPECT). Data were collected in collaboration between 13 SPECT centres located in 10 different European countries. The striatal measure of DAT availability was analyzed in a multiple regression model with age, SPECT centre and smoking as predictor. Results: There was no statistically significant difference in DAT availability between the groups of active smokers, ex-smokers and non-smokers (p = 0.34). Further, we could not demonstrate a significant association between striatal DAT and the number of cigarettes per day or total lifetime cigarette packages in smokers and ex-smokers. Conclusion: Our results do not support the hypothesis that large differences in striatal DAT availability are present in smokers compared to ex-smokers and healthy volunteers with no history of smoking

Changes in regional cerebral perfusion over time in idiopathic REM sleep behavior disorder

Background Idiopathic rapid eye movement sleep behavior disorder is associated with increased risk of neurodegeneration, but the temporal evolution of regional perfusion, a marker of cerebral activity, has not been characterized. The objective of the current study was to study longitudinal regional perfusion in patients with idiopathic rapid eye movement sleep behavior disorder. Methods Thirty‐seven patients and 23 controls underwent high‐resolution single‐photon emission computed tomography. After 17 months on average, scans were repeated for idiopathic rapid eye movement sleep behavior disorder patients. We compared regional cerebral blood flow between groups and over time. Results At baseline, patients showed lower relative regional perfusion in the anterior frontal and lateral parietotemporal cortex compared with controls. However, over time, patients showed an increase in relative regional perfusion in the anterior frontal, lateral parietal, and occipitotemporal cortex, reverting toward normal control levels. Conclusions Patients with idiopathic rapid eye movement sleep behavior disorder showed significant areas of relative regional hypoperfusion, which disappeared over time to finally return to average levels, suggesting possible developing compensation in areas affected by neurodegeneration

Reduction in camera-specific variability in [123I]FP-CIT SPECT outcome measures by image reconstruction optimized for multisite settings: impact on age-dependence of the specific binding ratio in the ENC-DAT database of healthy controls

Purpose Quantitative estimates of dopamine transporter availability, determined with [123I]FP-CIT SPECT, depend on the SPECT equipment, including both hardware and (reconstruction) software, which limits their use in multicentre research and clinical routine. This study tested a dedicated reconstruction algorithm for its ability to reduce camera-specific intersubject variability in [123I]FP-CIT SPECT. The secondary aim was to evaluate binding in whole brain (excluding striatum) as a reference for quantitative analysis. Methods Of 73 healthy subjects from the European Normal Control Database of [123I]FP-CIT recruited at six centres, 70 aged between 20 and 82 years were included. SPECT images were reconstructed using the QSPECT software package which provides fully automated detection of the outer contour of the head, camera-specific correction for scatter and septal penetration by transmission-dependent convolution subtraction, iterative OSEMreconstruction including attenuation correction, and camera-specific Bto kBq/ml^ calibration. LINK and HERMES reconstruction were used for head-to-head comparison. The specific striatal [123I]FP-CIT binding ratio (SBR) was computed using the Southampton method with binding in the whole brain, occipital cortex or cerebellum as the reference. The correlation between SBR and age was used as the primary quality measure. Results The fraction of SBR variability explained by age was highest (1) with QSPECT, independently of the reference region, and (2) with whole brain as the reference, independently of the reconstruction algorithm. Conclusion QSPECT reconstruction appears to be useful for reduction of camera-specific intersubject variability of [123I]FP-CIT SPECT in multisite and single-site multicamera settings. Whole brain excluding striatal binding as the reference provides more stable quantitative estimates than occipital or cerebellar binding