Ergolinalkaloidvorkommen bei Convolvulaceen : Biochemische und ökologische Interaktionen einer Pflanze-Pilz-Symbiose

Ergolinalkaloide kommen sowohl in Pilzen aus der Familie der Clavicipitaceen als auch in Pflanzen aus der Familie der Convolvulaceen vor. Es stellte sich die Frage, ob die Pflanzen selber oder symbiontische Mikroorganismen die Alkaloide biosynthetisieren. Als Vorbild diente die langjährige Forschung über Symbiosen von Poaceen und Ergolinalkaloid-bildenden Pilzen. Im Rahmen der vorliegenden Arbeit wurden auf den Blattoberflächen der Convolvulaceen Ipomoea asarifolia und Turbina corymbosa epibiontische Pilze entdeckt. Mittels ökologischer und biochemischer Experimente sowie mittels mikroskopischer und analytischer Methoden wurde versucht, die Pflanze-Pilz-Interaktionen von Turbina corymbosa und Ipomoea asarifolia aufzuklären. Fungizidversuchsreihen zeigten, dass das Vorkommen der Ergolinalkaloide in den Pflanzen unmittelbar mit dem Vorkommen der Pilze korreliert. Die daraus abgeleitete Vermutung, die Pilze könnten die Alkaloidproduzenten sein, wurde durch die Untersuchungen der Pflanze-Pilz-Interaktionen gestützt. Alle Beobachtungen lassen darauf schließen, dass es sich um ein sehr ausgewogenes Kosten-Nutzen-Verhältnis handelt, mit der Kapazität beider Partner, Leistungen zu erbringen die dem Anderen nützen. Die Möglichkeit der Alkaloidbiosynthese eröffnet den Pilzen offensichtlich eine einzigartige ökologische Nische. In diesem Kontext kann die Alkaloidbiosynthese durch die Convolvulaceen weitgehend ausgeschlossen werden

Diagnostic performance of the specific uptake size index for semi-quantitative analysis of I-123-FP-CIT SPECT: harmonized multi-center research setting versus typical clinical single-camera setting

Introduction: The specific uptake size index (SUSI) of striatal FP-CIT uptake is independent of spatial resolution in the SPECT image, in contrast to the specific binding ratio (SBR). This suggests that the SUSI is particularly appropriate for multi-site/multi-camera settings in which camera-specific effects increase inter-subject variability of spatial resolution. However, the SUSI is sensitive to inter-subject variability of striatum size. Furthermore, it might be more sensitive to errors of the estimate of non-displaceable FP-CIT binding. This study compared SUSI and SBR in the multi-site/multi-camera (MULTI) setting of a prospective multi-center study and in a mono-site/mono-camera (MONO) setting representative of clinical routine. Methods: The MULTI setting included patients with Parkinson’s disease (PD, n = 438) and healthy controls (n = 207) from the Parkinson Progression Marker Initiative. The MONO setting included 122 patients from routine clinical patient care in whom FP-CIT SPECT had been performed with the same double-head SPECT system according to the same acquisition and reconstruction protocol. Patients were categorized as “neurodegenerative” (n = 84) or “non-neurodegenerative” (n = 38) based on follow-up data. FP-CIT SPECTs were stereotactically normalized to MNI space. SUSI and SBR were computed for caudate, putamen, and whole striatum using unilateral ROIs predefined in MNI space. SUSI analysis was repeated in native patient space in the MONO setting. The area (AUC) under the ROC curve for identification of PD/“neurodegenerative” cases was used as performance measure. Results: In both settings, the highest AUC was achieved by the putamen (minimum over both hemispheres), independent of the semi-quantitative method (SUSI or SBR). The putaminal SUSI provided slightly better performance with ROI analysis in MNI space compared to patient space (AUC = 0.969 vs. 0.961, p = 0.129). The SUSI (computed in MNI space) performed slightly better than the SBR in the MULTI setting (AUC = 0.993 vs. 0.991, p = 0. 207) and slightly worse in the MONO setting (AUC = 0.969 vs. AUC = 0.976, p = 0.259). There was a trend toward larger AUC difference between SUSI and SBR in the MULTI setting compared to the MONO setting (p = 0.073). Variability of voxel intensity in the reference region was larger in misclassified cases compared to correctly classified cases for both SUSI and SBR (MULTI setting: p = 0.007 and p = 0.012, respectively). Conclusions: The SUSI is particularly useful in MULTI settings. SPECT images should be stereotactically normalized prior to SUSI analysis. The putaminal SUSI provides better diagnostic performance than the SUSI of the whole striatum. Errors of the estimate of non-displaceable count density in the reference region can cause misclassification by both SUSI and SBR, particularly in borderline cases. These cases might be identified by visual checking FP-CIT uptake in the reference region for particularly high variability

Cerebellar volume is linked to cognitive function in temporal lobe epilepsy: A quantitative MRI study

AbstractIntroductionChronic intractable temporal lobe epilepsy (TLE) is associated with certain comorbidities including cognitive impairment. A less common condition among patients with TLE is intermittent explosive disorder (IED), a specific form of aggressive behavior that has been linked to low intelligence and structural pathology in the amygdala. We aimed to identify other neuroanatomical substrates of both cognitive dysfunction and IED in patients with TLE, with special focus on the cerebellum, a brain region known to participate in functional networks involved in neuropsychological and affective processes.MethodsMagnetic resonance imaging-based volumetric data from 60 patients with temporal lobe epilepsy (36 with and 24 without IED) were evaluated. Cerebellar, hippocampal, and total brain volumes were processed separately. In a total of 50 patients, the relationship between volumetric measurements and clinical and neuropsychological data (full-scale, verbal, and performance intelligence quotients) was analyzed.ResultsIntermittent explosive disorder in patients with TLE was not significantly linked to any of the regional volumes analyzed. However, cognitive performance showed a significant association both with total brain volume and cerebellar volume measurements, whereby the left cerebellar volume showed the strongest association. A deviation from normal cerebellar volumes was related to lower intelligence. Of note, left cerebellar volume was influenced by age and duration of epilepsy. Hippocampal volumes had a minor influence on cognitive parameters.ConclusionOur findings suggest that cerebellar volume is not linked to IED in patients with TLE but is significantly associated with cognitive dysfunction. Our findings support recent hypotheses proposing that the cerebellum has a relevant functional topography

Combining Biocompatible and Biodegradable Scaffolds and Cold Atmospheric Plasma for Chronic Wound Regeneration

Skin regeneration is a quite complex process. Epidermal differentiation alone takes about 30 days and is highly regulated. Wounds, especially chronic wounds, affect 2% to 3% of the elderly population and comprise a heterogeneous group of diseases. The prevailing reasons to develop skin wounds include venous and/or arterial circulatory disorders, diabetes, or constant pressure to the skin (decubitus). The hallmarks of modern wound treatment include debridement of dead tissue, disinfection, wound dressings that keep the wound moist but still allow air exchange, and compression bandages. Despite all these efforts there is still a huge treatment resistance and wounds will not heal. This calls for new and more efficient treatment options in combination with novel biocompatible skin scaffolds. Cold atmospheric pressure plasma (CAP) is such an innovative addition to the treatment armamentarium. In one CAP application, antimicrobial effects, wound acidification, enhanced microcirculations and cell stimulation can be achieved. It is evident that CAP treatment, in combination with novel bioengineered, biocompatible and biodegradable electrospun scaffolds, has the potential of fostering wound healing by promoting remodeling and epithelialization along such temporarily applied skin replacement scaffolds

Basic concepts of mixture toxicity and relevance for risk evaluation and regulation

Exposure to multiple substances is a challenge for risk evaluation. Currently, there is an ongoing debate if generic “mixture assessment/allocation factors” (MAF) should be introduced to increase public health protection. Here, we explore concepts of mixture toxicity and the potential influence of mixture regulation concepts for human health protection. Based on this analysis, we provide recommendations for research and risk assessment. One of the concepts of mixture toxicity is additivity. Substances may act additively by affecting the same molecular mechanism within a common target cell, for example, dioxin-like substances. In a second concept, an “enhancer substance” may act by increasing the target site concentration and aggravating the adverse effect of a “driver substance”. For both concepts, adequate risk management of individual substances can reliably prevent adverse effects to humans. Furthermore, we discuss the hypothesis that the large number of substances to which humans are exposed at very low and individually safe doses may interact to cause adverse effects. This commentary identifies knowledge gaps, such as the lack of a comprehensive overview of substances regulated under different silos, including food, environmentally and occupationally relevant substances, the absence of reliable human exposure data and the missing accessibility of ratios of current human exposure to threshold values, which are considered safe for individual substances. Moreover, a comprehensive overview of the molecular mechanisms and most susceptible target cells is required. We conclude that, currently, there is no scientific evidence supporting the need for a generic MAF. Rather, we recommend taking more specific measures, which focus on compounds with relatively small ratios between human exposure and doses, at which adverse effects can be expected

Forebrain microglia from wild-type but not adult 5xFAD mice prevent amyloid-beta plaque formation in organotypic hippocampal slice cultures

The role of microglia in amyloid-beta (A beta) deposition is controversial. In the present study, an organotypic hippocampal slice culture (OHSC) system with an in vivo-like microglial-neuronal environment was used to investigate the potential contribution of microglia to A beta plaque formation. We found that microglia ingested A beta, thereby preventing plaque formation in OHSCs. Conversely, A beta deposits formed rapidly in microglia-free wild-type slices. The capacity to prevent A beta plaque formation was absent in forebrain microglia from young adult but not juvenile 5xFamilial Alzheimer's disease (FAD) mice. Since no loss of A beta clearance capacity was observed in both wild-type and cerebellar microglia from 5xFAD animals, the high A beta(1-42) burden in the forebrain of 5xFAD animals likely underlies the exhaustion of microglial A beta clearance capacity. These data may therefore explain why A beta plaque formation has never been described in wild-type mice, and point to a beneficial role of microglia in AD pathology. We also describe a new method to study A beta plaque formation in a cell culture setting

Functional Selectivity of Coumarin Derivates Acting via GPR55 in Neuroinflammation

Anti-neuroinflammatory treatment has gained importance in the search for pharmacological treatments of different neurological and psychiatric diseases, such as depression, schizophrenia, Parkinson’s disease, and Alzheimer’s disease. Clinical studies demonstrate a reduction of the mentioned diseases’ symptoms after the administration of anti-inflammatory drugs. Novel coumarin derivates have been shown to elicit anti-neuroinflammatory effects via G-protein coupled receptor GPR55, with possibly reduced side-effects compared to the known anti-inflammatory drugs. In this study, we, therefore, evaluated the anti-inflammatory capacities of the two novel coumarin-based compounds, KIT C and KIT H, in human neuroblastoma cells and primary murine microglia. Both compounds reduced PGE$_{2}$-concentrations likely via the inhibition of COX-2 synthesis in SK-N-SH cells but only KIT C decreased PGE$_{2}$-levels in primary microglia. The examination of other pro- and anti-inflammatory parameters showed varying effects of both compounds. Therefore, the differences in the effects of KIT C and KIT H might be explained by functional selectivity as well as tissue- or cell-dependent expression and signal pathways coupled to GPR55. Understanding the role of chemical residues in functional selectivity and specific cell- and tissue-targeting might open new therapeutic options in pharmacological drug development and might improve the treatment of the mentioned diseases by intervening in an early step of their pathogenesis

18F-FDG PET/CT-derived total lesion glycolysis predicts abscess formation in patients with surgically confirmed infective endocarditis: Results of a retrospective study at a tertiary center

Background Abnormal activity of 18F-FDG PET/CT is a major Duke criterion in the diagnostic work-up of infective prosthetic valve endocarditis (IE). We hypothesized that quantitative lesion assessment by 18F-FDG PET/CT-derived standard maximum uptake ratio (SURmax), metabolic volume (MV), and total lesion glycolysis (TLG) might be useful in distinct subgroups of IE patients (e.g. IE-related abscess formation). Methods All patients (n = 27) hospitalized in our tertiary IE referral medical center from January 2014 to October 2018 with preoperatively performed 18F-FDG PET/CT and surgically confirmed IE were included into this retrospective analysis. Results Patients with surgically confirmed abscess formation (n = 10) had significantly increased MV (by ~ fivefold) and TLG (by ~ sevenfold) as compared to patients without abscess (n = 17). Receiver operation characteristics (ROC) analyses demonstrated that TLG (calculated as MV × SURmean, i.e. TLG (SUR)) had the most favorable area under the ROC curve (0.841 [CI 0.659 to 1.000]) in predicting IE-related abscess formation. This resulted in a sensitivity of 80% and a specificity of 88% at a cut-off value of 14.14 mL for TLG (SUR). Conclusion We suggest that 18F-FDG PET/CT-derived quantitative assessment of TLG (SUR) may provide a novel diagnostic tool in predicting endocarditis-associated abscess formation