Evaluation of Age and Sex-Related Metabolic Changes in Healthy Subjects: An Italian Brain 18F-FDG PET Study

Background: 18F-fluorodeoxyglucose (18F-FDG) positron-emission-tomography (PET) allows detection of cerebral metabolic alterations in neurological diseases vs. normal aging. We assess age- and sex-related brain metabolic changes in healthy subjects, exploring impact of activity normalization methods. Methods: brain scans of Italian Association of Nuclear Medicine normative database (151 subjects, 67 Males, 84 Females, aged 20–84) were selected. Global mean, white matter, and pons activity were explored as normalization reference. We performed voxel-based and ROI analyses using SPM12 and IBM-SPSS software. Results: SPM proved a negative correlation between age and brain glucose metabolism involving frontal lobes, anterior-cingulate and insular cortices bilaterally. Narrower clusters were detected in lateral parietal lobes, precuneus, temporal pole and medial areas bilaterally. Normalizing on pons activity, we found a more significant negative correlation and no positive one. ROIs analysis confirmed SPM results. Moreover, a significant age × sex interaction effect was revealed, with worse metabolic reduction in posterior-cingulate cortices in females than males, especially in post-menopausal age. Conclusions: this study demonstrated an age-related metabolic reduction in frontal lobes and in some parieto-temporal areas more evident in females. Results suggested pons as the most appropriate normalization reference. Knowledge of age- and sex-related cerebral metabolic changes is critical to correctly interpreting brain 18F-FDG PET imaging.

Outside testing of wearable robots for gait assistance shows a higher metabolic benefit than testing on treadmills

Most wearable robots that assist the gait of workers, soldiers, athletes, and hobbyists are developed towards a vision of outdoor, overground walking. However, so far, these devices have predominantly been tested indoors on laboratory treadmills. It is unclear whether treadmill-based laboratory tests are an accurate representation of overground ambulation outdoors with respect to essential outcomes such as the metabolic benefits of robotic assistance. In this study, we investigated the metabolic benefits of the Myosuit, a wearable robot that assists hip and knee extension during the stance phase of gait, for eight unimpaired participants during uphill walking trials in three settings: outside, on a self-paced treadmill with a virtual reality display, and on a standard treadmill at a fixed gait speed. The relative metabolic reduction with Myosuit assistance was most pronounced in the outside setting at − 10.6% and significantly larger than in the two treadmill settings (− 6.9%, p = 0.015 and − 6.2%, p = 0.008). This indicates that treadmill tests likely result in systematically low estimate for the true metabolic benefits of wearable robots during outside, overground walking. Hence, wearable robots should preferably be tested in an outdoor environment to obtain more representative—and ultimately more favorable—results with respect to the metabolic benefit of robotic gait assistance.

Vine-Shoots as Enological Additives. A Study of Acute Toxicity and Cytotoxicity

Toasted vine-shoots have been recently proposed as enological additives that can be used to improve the sensorial profile of wines. However, the possible toxicity of this new winery practice has not been studied so far. The aim of this study was to evaluate the toxicity of Tempranillo, Cencibel, and Cabernet Sauvignon toasted vine-shoots when used in winemaking. First, vine-shoots were characterized in terms of minerals and phenolic and furan compounds, and then their acute toxicity and cytotoxicity were studied using Microtox® and the metabolic reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. High EC50 values were obtained when the Microtox® assay was applied to vine-shoot aqueous extracts, similar to the case of herbal infusions. When the MTT assay was used, a cell viability above 70% was observed in all the wines made with those vine-shoots, and an even greater viability was observed in the case of Cabernet Sauvignon. Therefore, it was concluded that those vine-shoots have no cytotoxic potential.

Therapeutic Potential of Selenium as a Component of Preservation Solutions for Kidney Transplantation

Selenium has strong antioxidant properties and diverse effects on the immune system. The aim of the study was to analyse the protective effect of selenium as a component of a kidney preservation solution on the prevention of ischemia-reperfusion injury of nephrons. The solution was modified by the addition of Se (1 µg/L), prolactin (0.1 µg/L) and Se with prolactin (1 µg/L Se + 0.1 µg/L PRL). The study used a model for storing isolated porcine kidneys in Biolasol® (modified Biolasol®), which minimizes ischemia-reperfusion injury of grafts. The introduction of Se4+ ions at a dose of 1 µg/L into the Biolasol® preservation solution in the form of Na2SeO3 caused an increase in the activity/concentration of the analysed biochemical parameters: aspartate transaminase, alanine transaminase, urea and protein. This suggests an adverse effect of Se4+ on nephron function during ischemia-reperfusion. The best graft protection was obtained by using Biolasol® modified with the addition of selenium (IV) at a dose of 1 µg/L and prolactin at a concentration of 0.1 µg/L. We proposed the mechanism of prolactin action in the metabolic reduction of selenite (SO32−) during ischemia/reperfusion.

Doxorubicin metabolism moderately attributes to putative toxicity in prodigiosin/doxorubicin synergism in vitro cells

Doxorubicin (Dox) is a widely neoplasm chemotherapeutic drug with high incidences of cardiotoxicity. Prodigiosin (PG), a red bacterial pigment from Serratia marcescens, has been demonstrated to potentiate Dox’s cytotoxicity against oral squamous cell carcinoma cells through elevating Dox influx and identified as a Dox enhancer via PG-induced autophagy; however, toxicity of normal cell remains unclear. This study is conducted to evaluate putative cytotoxicity features of PG/Dox synergism in the liver, kidney, and heart cells and further elucidate whether PG augmented Dox’s effect via modulating Dox metabolism in normal cells. Murine hepatocytes FL83B, cardio-myoblast h9c2, and human kidney epithelial cells HK-2 were sequentially treated with PG and Dox by measuring cell viability, cell death characteristics, oxidative stress, Dox flux, and Dox metabolism. PG could slightly significant increase Dox cytotoxicity in all tested normal cells whose toxic alteration was less than that of oral squamous carcinoma cells. The augmentation of Dox cytotoxicity might be attributed to the increase of Dox-mediated ROS accumulation that might cause slight reduction of Dox influx and reduction of Dox metabolism. It was noteworthy to notice that sustained cytotoxicity appeared in normal cells after PG and Dox were removed. Taken together, moderately metabolic reduction of Dox might be ascribed to the mechanism of increase Dox cytotoxicity in PG-induced normal cells; nevertheless, the determination of PG/Dox dose with sustained cytotoxicity in normal cells needs to be comprehensively considered.

Conspecific chemical cues drive density-dependent metabolic suppression independently of resource intake

ABSTRACTWithin species, individuals of the same size can vary substantially in their metabolic rate. One source of variation in metabolism is conspecific density – individuals in denser populations may have lower metabolism than those in sparser populations. However, the mechanisms through which conspecifics drive metabolic suppression remain unclear. Although food competition is a potential driver, other density-mediated factors could act independently or in combination to drive metabolic suppression, but these drivers have rarely been investigated. We used sessile marine invertebrates to test how food availability interacts with oxygen availability, water flow and chemical cues to affect metabolism. We show that conspecific chemical cues induce metabolic suppression independently of food and this metabolic reduction is associated with the downregulation of physiological processes rather than feeding activity. Conspecific cues should be considered when predicting metabolic variation and competitive outcomes as they are an important, but underexplored, source of variation in metabolic traits.

M139. DIFFERENTIAL PATTERNS OF BRAIN METABOLISM IN STABILIZED, ACTIVELY SYMPTOMATIC TREATMENT RESISTANT VS. TREATMENT RESPONDER SCHIZOPHRENIA PATIENTS: A STUDY BY 18F-FDG-POSITRON EMISSION TOMOGRAPHY AND STRUCTURAL 3T MRI

Background Schizophrenia is a disabling psychiatric disease with a lifetime prevalence of 1%, which usually starts in late adolescence or initial adulthood and has a rare possibility of recovery. According to the extent of antipsychotic response, schizophrenia individuals can be divided into treatment resistant schizophrenia (TRS) and Treatment responders (non-TRS). Currently, it is unclear whether these categories belong to different biological and prognostic groups. Therefore, in order to deepen the knowledge of these conditions, we analyzed the cerebral metabolism of a sample of stabilized but still actively symptomatic TRS and non-TRS patients with substantial cognitive deficits. Methods We recruited 35 schizophrenia patients (18 TRS and 17 non-TRS) among approximately 80 consecutive non-affective psychotic patients, that were referred to our academic outpatient unit for supposed resistance to antipsychotics. The diagnosis of TRS was made by a structured diagnostic flowchart, according to published guidelines. Patients underwent a wide set of clinical and cognitive evaluations by trained raters. All patients who exhibited substantial cognitive deficits (at least two BACS/MATRICS items < than 1 - adjusted scores) and met inclusion/not met exclusion criteria were included in the neuroimaging study by 18F-fluorodeoxyglucose PET scans and structural 3T Magnetic Resonance Imaging. There were no statistically significant differences in age, chlorpromazine equivalents, and duration of illness between the TRS/non-TRS groups. Patients groups were matched with a control group. PET images were normalized on SPM template and then examined in visual and voxel-based analyses. Results Globally, the visual analysis of the images showed a diffuse relative metabolic reduction in the cerebral cortex with prevalent frontal involvement in the majority of the patients of the TRS group and to a lesser extent in the non-TRS group. The voxel-per-voxel analysis revealed an extensive cluster of significant relative metabolic reduction in TRS patients compared to controls and to non-TRS patients (13653 voxels) localized bilaterally in the frontal cortex with a mild left prevalence. In particular, the metabolic reduction peaks involved the upper right and left medial frontal girder (BA6 and BA8, respectively), left opercular frontal (BA44), middle frontal girth (BA10) bilaterally, left lower frontal girth (BA47). Notably, at least three patients from the TRS group were excluded from the initial pool due to the observation of previously unrecognized structural brain anomalies. Discussion In this study, we observed that TRS patients had a relative hypometabolic state in dorsal and medial prefrontal cortex, including frontobasal areas, compared to controls and to non-TRS patients, while the striatum and the occipital cortex appeared relatively preserved. In non-TRS patients, brain distribution of 18F-FDG was more homogeneous and only slightly reduced in the cerebral cortex, as compared to controls. These patterns of brain metabolism cannot be associated with more severe cognitive dysfunctions in TRS patients since all patients included in the study had substantial cognitive impairments, irrespective of being TRS or non-TRS. Although it cannot be excluded that these differential patterns may stem from the lack of response to antipsychotics, our findings suggest distinct neurobiological alterations in TRS vs. non-TRS patients, which may include more relevant brain disconnections in non-responder ones.

Candida albicans Biofilm Heterogeneity and Tolerance of Clinical Isolates: Implications for Secondary Endodontic Infections

Aim: Endodontic infections are caused by the invasion of various microorganisms into the root canal system. Candida albicans is a biofilm forming yeast and the most prevalent eukaryotic microorganism in endodontic infections. In this study we investigated the ability of C. albicans to tolerate treatment with standard endodontic irrigants NaOCl (sodium hypochlorite), ethylenediaminetetraacetic acid (EDTA) and a combination thereof. We hypothesized that biofilm formed from a panel of clinical isolates differentially tolerate disinfectant regimens, and this may have implications for secondary endodontic infections. Methodology: Mature C. albicans biofilms were formed from 30 laboratory and oral clinical isolates and treated with either 3% NaOCl, 17% EDTA or a sequential treatment of 3% NaOCl followed by 17% EDTA for 5 min. Biofilms were then washed, media replenished and cells reincubated for an additional 24, 48 and 72 h at 37 °C. Regrowth was quantified using metabolic reduction, electrical impedance, biofilm biomass and microscopy at 0, 24, 48 and 72 h. Results: Microscopic analysis and viability readings revealed a significant initial killing effect by NaOCl, followed by a time dependent significant regrowth of C. albicans, but with inter-strain variability. In contrast to NaOCl, there was a continuous reduction in viability after EDTA treatment. Moreover, EDTA significantly inhibited regrowth after NaOCl treatment, though viable cells were still observed. Conclusions: Our results indicate that different C. albicans biofilm phenotypes grown in a non-complex surface topography have the potential to differentially tolerate standard endodontic irrigation protocols. This is the first study to report a strain dependent impact on efficacy of endodontic irrigants. Its suggested that within the complex topography of the root canal, a more difficult antimicrobial challenge, that existing endodontic irrigant regimens permit cells to regrow and drive secondary infections.