Glucose Metabolism in Mouse Tumor and Liver With and Without Hyperthermia

We measured levels of glycolytic metabolites in mouse tumor and liver after administering a glucose load of 6 mg/g of body weight and after hyperthermia for one hour at 43°C. Metabolites included glucose, glucose-6-phosphate, fructose-1.6-diphosphate, dihydroxyacetone-phosphate, glycerol-3-phosphate, pyruvate, and lactate, as well as acetoacetate and β-hydroxybutyrate. The combined treatment led to an increase of the lactate level and apparently enhanced glucose degradation. The redoxequilibria states were shifted to the reduced metabolites. It is possible that hypoxia was induced or enhanced, which could have significance for tumor therapy. At later periods after hyperthermia, metabolic alterations occurred that have also been observed in severe diabetes. These alterations occurred in the liver as well. In both situations, such alterations must be considered in connection with potential damage to normal tissue from hyperthermia

Kaskadennutzung von Lignocellulose : LX-Verfahren trifft auf B. coagulans

Investigating alternatives for petrobased substrates, lignocellulose is an interesting yet complex feedstock that offers various possibilities for the design of new and sustainable chemical routes. The novel energy-saving LX-pretreatment was combined with thermophilic Bacillus coagulans. By this, corn straw was used in an innovative cascade obtaining biogas, lignin as well as polymerisable L-(+)-lactic acid of over 99 percents optical purity. © 2020, Die Autoren

Radiation dosimetry and biodistribution of 11C-ABP688 measured in healthy volunteers

Introduction: In this study, we assessed the whole-body biodistribution and radiation dosimetry of the new glutamatergic ligand 11C-ABP688. This ligand binds specifically to the metabotropic glutamatergic receptor of subtype 5 (mGluR5). Materials and methods: The study included five healthy male volunteers aged 20-29years. After intravenous injection of 240-260MBq, a series of four to ten whole-body positron emission tomography/computed tomography scans were initiated, yielding 60-80min of data. Residence times were then calculated in the relevant organs, and the software packages Mirdose and Olinda were used to calculate the absorbed radiation dose and the effective dose equivalent. Results: Of the excreted 11C activity at 1hour, approximately 80% were eliminated via the hepato-biliary pathway and 20% through the urinary tract. The absorbed dose (mGy/MBq) was highest in the liver (1.64 E -2 ± 5.08 E -3), gallbladder (8.13 E -3 ± 5.6 E -3), and kidneys (7.27 E -3 ± 2.79 E -3). The effective dose equivalent was 3.68 ± 0.84microSv/MBq. Brain uptake in the areas with high mGluR5 density was 2-3 (SUV). The agreement between the values obtained from Mirdose and the Olinda was excellent. Conclusion: 11C-ABP688 is a very promising ligand for the investigation of mGluR5 receptors in humans. Brain uptake is high and the effective dose equivalent so low that serial examinations in the same subject seem feasibl

Enhanced brain activity may precede the diagnosis of Alzheimer's disease by 30 years

Presenilin 1 (PSEN1) mutations cause autosomal dominant familial Alzheimer's disease (FAD). PSEN1 mutation carriers undergo the course of cognitive deterioration, which is typical for sporadic Alzheimer's disease but disease onset is earlier and disease progression is faster. Here, we sought to detect signs of FAD in presymptomatic carriers of the PSEN1 mutation (C410Y) by use of a neuropsychological examination, functional MRI during learning and memory tasks and MRI volumetry. We examined five non-demented members of a FAD family and 21 non-related controls. Two of the five family members were carrying the mutation; one was 20 years old and the other 45 years old. The age of clinical manifestation of FAD in the family studied here is ∼48 years. Neuropsychological assessments suggested subtle problems with episodic memory in the 20-year-old mutation carrier. The middle-aged mutation carrier fulfilled criteria for amnestic mild cognitive impairment. The 20-year-old mutation carrier exhibited increased, while the middle-aged mutation carrier exhibited decreased brain activity compared to controls within memory-related neural networks during episodic learning and retrieval, but not during a working-memory task. The increased memory-related brain activity in the young mutation carrier might reflect a compensatory effort to overcome preclinical neural dysfunction caused by first pathological changes. The activity reductions in the middle-aged mutation carrier might reflect gross neural dysfunction in a more advanced stage of neuropathology. These data suggest that functional neuroimaging along with tasks that challenge specifically those brain areas which are initial targets of Alzheimer's disease pathology may reveal activity alterations on a single-subject level decades before the clinical manifestation of Alzheimer's diseas

Test-retest reliability and longitudinal analysis of automated hippocampal subregion volumes in healthy ageing and Alzheimer's disease populations

The hippocampal formation is a complex brain structure that is important in cognitive processes such as memory, mood, reward processing and other executive functions. Histological and neuroimaging studies have implicated the hippocampal region in neuropsychiatric disorders as well as in neurodegenerative diseases. This highly plastic limbic region is made up of several subregions that are believed to have different functional roles. Therefore, there is a growing interest in imaging the subregions of the hippocampal formation rather than modelling the hippocampus as a homogenous structure, driving the development of new automated analysis tools. Consequently, there is a pressing need to understand the stability of the measures derived from these new techniques. In this study, an automated hippocampal subregion segmentation pipeline, released as a developmental version of Freesurfer (v6.0), was applied to T1-weighted magnetic resonance imaging (MRI) scans of 22 healthy older participants, scanned on 3 separate occasions and a separate longitudinal dataset of 40 Alzheimer's disease (AD) patients. Test-retest reliability of hippocampal subregion volumes was assessed using the intra-class correlation coefficient (ICC), percentage volume difference and percentage volume overlap (Dice). Sensitivity of the regional estimates to longitudinal change was estimated using linear mixed effects (LME) modelling. The results show that out of the 24 hippocampal subregions, 20 had ICC scores of 0.9 or higher in both samples; these regions include the molecular layer, granule cell layer of the dentate gyrus, CA1, CA3 and the subiculum (ICC > 0.9), whilst the hippocampal fissure and fimbria had lower ICC scores (0.73-0.88). Furthermore, LME analysis of the independent AD dataset demonstrated sensitivity to group and individual differences in the rate of volume change over time in several hippocampal subregions (CA1, molecular layer, CA3, hippocampal tail, fissure and presubiculum). These results indicate that this automated segmentation method provides a robust method with which to measure hippocampal subregions, and may be useful in tracking disease progression and measuring the effects of pharmacological intervention