Evaluation of the effects of hypergravity exposure and caging restraint on bone mineralization in the Beagle by in vivo photon absorptiometry

Photon absorptiometry was used to evaluate bone mineral kinetics associated with normal development and the possible perturbations to bone development resulting from hypergravity exposure over a period of six months in developing Beagles. A series of seven measurements were performed at specific times with the first measurement prior to treatment and subsequent measurements at 2, 5, 9, 14, 20 and 26 weeks from the onset of the experiment. Four groups of six male Beagle pups, ranging in age from 85 to 92 days were studied. Two groups were chronically exposed to hypergravity treatments by centrifugation of 2.0 G (18.0 RPM, 11.7 ft radius) and 2.6 G (18.0 RPM, 19.8 ft radius) for the 26 week period. A third group of six dogs served as a caged control to evaluate possible changes due to confinement in small plexiglass cages similar to those of the centrifuge. Thus this control group was subjected to limited exercise due to caging restraint. The fourth group of animals was housed in open runs to allow exercise without the spatial confinement of the smaller plexiglass cages. Results show highly significant differences in body weight, bone length, increase in bone density of control group relative to other groups, and a decrease in bone mineral content in the two gravity treated groups

Acute stress increases monocyte levels and modulates receptor expression in healthy females

There has been a growing recognition of the involvement of the immune system in stress-related disorders. Acute stress leads to the activation of neuroendocrine systems, which in turn orchestrate a large-scale redistribution of innate immune cells, such as monocytes. Even though acute stress/monocyte interactions have been wellcharacterized in mice, this is not the case for humans. As such, this study aimed to investigate whether acute stress modulates blood monocyte levels in a subtype-dependent manner and whether the receptor expression of stress-related receptors is affected in humans. Blood was collected from healthy female volunteers at baseline and 1 h after the socially evaluated cold pressor test, after which blood monocyte levels and receptor expression were assessed by flow cytometry. Our results reveal a stress-induced increase in blood monocyte levels, which was independent of monocyte subtypes. Furthermore, colony stimulating factor 1 receptor (CSF-1R) and CD29 receptor expression was increased, while CD62L showed a trend towards increased expression. These results provide novel insights into how acute stress affects the innate immune system

Human 13N-ammonia PET studies: the importance of measuring 13N-ammonia metabolites in blood

Dynamic 13N-ammonia PET is used to assess ammonia metabolism in brain, liver and muscle based on kinetic modeling of metabolic pathways, using arterial blood 13N-ammonia as input function. Rosenspire et al. (1990) introduced a solid phase extraction procedure for fractionation of 13N-content in blood into 13N-ammonia, 13N-urea, 13N-glutamine and 13N-glutamate. Due to a radioactive half-life for 13N of 10 min, the procedure is not suitable for blood samples taken beyond 5–7 min after tracer injection. By modifying Rosenspire’s method, we established a method enabling analysis of up to 10 blood samples in the course of 30 min. The modified procedure was validated by HPLC and by 30-min reproducibility studies in humans examined by duplicate 13N-ammonia injections with a 60-min interval. Blood data from a 13N-ammonia brain PET study (from Keiding et al. 2006) showed: (1) time courses of 13N-ammonia fractions could be described adequately by double exponential functions; (2) metabolic conversion of 13N-ammonia to 13N-metabolites were in the order: healthy subjects > cirrhotic patients without HE > cirrhotic patients with HE; (3) kinetics of initial tracer distribution in tissue can be assessed by using total 13N-concentration in blood as input function, whereas assessment of metabolic processes requires 13N-ammonia measurements

Recipe for a Healthy Gut: Intake of Unpasteurised Milk Is Associated with Increased Lactobacillus Abundance in the Human Gut Microbiome

peer-reviewedIntroduction: The gut microbiota plays a role in gut–brain communication and can influence psychological functioning. Diet is one of the major determinants of gut microbiota composition. The impact of unpasteurised dairy products on the microbiota is unknown. In this observational study, we investigated the effect of a dietary change involving intake of unpasteurised dairy on gut microbiome composition and psychological status in participants undertaking a residential 12-week cookery course on an organic farm. Methods: Twenty-four participants completed the study. The majority of food consumed during their stay originated from the organic farm itself and included unpasteurised milk and dairy products. At the beginning and end of the course, participants provided faecal samples and completed self-report questionnaires on a variety of parameters including mood, anxiety and sleep. Nutrient intake was monitored with a food frequency questionnaire. Gut microbiota analysis was performed with 16S rRNA gene sequencing. Additionally, faecal short chain fatty acids (SCFAs) were measured. Results: Relative abundance of the genus Lactobacillus increased significantly between pre- and post-course time points. This increase was associated with participants intake of unpasteurised milk and dairy products. An increase in the faecal SCFA, valerate, was observed along with an increase in the functional richness of the microbiome profile, as determined by measuring the predictive neuroactive potential using a gut–brain module approach. Conclusions: While concerns in relation to safety need to be considered, intake of unpasteurised milk and dairy products appear to be associated with the growth of the probiotic bacterial genus, Lactobacillus, in the human gut. More research is needed on the effect of dietary changes on gut microbiome composition, in particular in relation to the promotion of bacterial genera, such as Lactobacillus, which are recognised as being beneficial for a range of physical and mental health outcomes

Deep Brain Stimulation of Nucleus Accumbens Region in Alcoholism Affects Reward Processing

The influence of bilateral deep brain stimulation (DBS) of the nucleus nucleus (NAcc) on the processing of reward in a gambling paradigm was investigated using H2[15O]-PET (positron emission tomography) in a 38-year-old man treated for severe alcohol addiction. Behavioral data analysis revealed a less risky, more careful choice behavior under active DBS compared to DBS switched off. PET showed win- and loss-related activations in the paracingulate cortex, temporal poles, precuneus and hippocampus under active DBS, brain areas that have been implicated in action monitoring and behavioral control. Except for the temporal pole these activations were not seen when DBS was deactivated. These findings suggest that DBS of the NAcc may act partially by improving behavioral control

Altered stress responses in adults born by Caesarean section

peer-reviewedBirth by Caesarean-section (C-section), which increases the risk for metabolic and immune disorders, disrupts the normal initial microbial colonisation of the gut, in addition to preventing early priming of the stress and immune-systems.. Animal studies have shown there are enduring psychological processes in C-section born mice. However, the long-term impact of microbiota-gut-brain axis disruptions due to birth by C-section on psychological processes in humans is unknown. Forty age matched healthy young male university students born vaginally and 36 C-section delivered male students were recruited. Participants underwent an acute stressor, the Trier social stress test (TSST), during a term-time study visit. A subset of participants also completed a study visit during the university exam period, representing a naturalistic stressor. Participants completed a battery of cognitive tests and self-report measures assessing mood, anxiety, and perceived stress. Saliva, blood, and stool samples were collected for analysis of cortisol, peripheral immune profile, and the gut microbiota. Young adults born by C-section exhibit increased psychological vulnerability to acute stress and a prolonged period of exam-related stress. They did not exhibit an altered salivary cortisol awakening response to the TSST, but their measures of positive affect were significantly lower than controls throughout the procedure. Both C-section and vaginally-delivered participants performed equally well on cognitive assessments. Most of the initial effects of delivery mode on the gut microbiome did not persist into adulthood as the gut microbiota profile showed modest changes in composition in adult vaginally-delivered and C-sectioned delivered subjects. From an immune perspective, concentrations of IL-1β and 1L-10 were higher in C-section participants. These data confirm that there is a potential enduring effect of delivery mode on the psychological responses to acute stress during early adulthood. The mental health implications of these observations require further study regarding policies on C-section use

Nonuniform Cardiac Denervation Observed by 11C-meta-Hydroxyephedrine PET in 6-OHDA-Treated Monkeys

Parkinson's disease presents nonmotor complications such as autonomic dysfunction that do not respond to traditional anti-parkinsonian therapies. The lack of established preclinical monkey models of Parkinson's disease with cardiac dysfunction hampers development and testing of new treatments to alleviate or prevent this feature. This study aimed to assess the feasibility of developing a model of cardiac dysautonomia in nonhuman primates and preclinical evaluations tools. Five rhesus monkeys received intravenous injections of 6-hydroxydopamine (total dose: 50 mg/kg). The animals were evaluated before and after with a battery of tests, including positron emission tomography with the norepinephrine analog 11C-meta-hydroxyephedrine. Imaging 1 week after neurotoxin treatment revealed nearly complete loss of specific radioligand uptake. Partial progressive recovery of cardiac uptake found between 1 and 10 weeks remained stable between 10 and 14 weeks. In all five animals, examination of the pattern of uptake (using Logan plot analysis to create distribution volume maps) revealed a persistent region-specific significant loss in the inferior wall of the left ventricle at 10 (P<0.001) and 14 weeks (P<0.01) relative to the anterior wall. Blood levels of dopamine, norepinephrine (P<0.05), epinephrine, and 3,4-dihydroxyphenylacetic acid (P<0.01) were notably decreased after 6-hydroxydopamine at all time points. These results demonstrate that systemic injection of 6-hydroxydopamine in nonhuman primates creates a nonuniform but reproducible pattern of cardiac denervation as well as a persistent loss of circulating catecholamines, supporting the use of this method to further develop a monkey model of cardiac dysautonomia

Attentional Set-Shifting Deficit in Parkinson’s Disease Is Associated with Prefrontal Dysfunction: An FDG-PET Study

The attentional set-shifting deficit that has been observed in Parkinson’s disease (PD) has long been considered neuropsychological evidence of the involvement of meso-prefrontal and prefrontal-striatal circuits in cognitive flexibility. However, recent studies have suggested that non-dopaminergic, posterior cortical pathologies may also contribute to this deficit. Although several neuroimaging studies have addressed this issue, the results of these studies were confounded by the use of tasks that required other cognitive processes in addition to set-shifting, such as rule learning and working memory. In this study, we attempted to identify the neural correlates of the attentional set-shifting deficit in PD using a compound letter task and 18F-fluoro-deoxy-glucose (FDG) positron emission tomography during rest. Shift cost, which is a measure of attentional set-shifting ability, was significantly correlated with hypometabolism in the right dorsolateral prefrontal cortex, including the putative human frontal eye field. Our results provide direct evidence that dysfunction in the dorsolateral prefrontal cortex makes a primary contribution to the attentional set-shifting deficit that has been observed in PD patients

R-Allyl Nickel(II) Complexes with Chelating N-Heterocyclic Carbenes: Synthesis, Structural Characterization, and Catalytic Activity

The N-heterocyclic carbene (NHC) nickel complexes [(L)Ni(NHC)][BArF4] (ArF = 3,5-bis(trifluoromethyl)- phenyl; L = allyl (1), methylallyl (2); NHC = 1-(2-picolyl)-3-methylimidazol-2-ylidene (a), 1-(2-picolyl)-3-isopropylimidazol-2-ylidene (b), 1-(2-picolyl)-3-n-butylimidazol-2-ylidene (c), 1-(2-picolyl)-3-phenylimidazol-2-ylidene (d), 1-(2-picolyl)-3- methylbenzoimidazol-2-ylidene (e), 1-(2-picolyl)-4,5-dichloro-3-methylimidazol-2-ylidene (f)) have been obtained in high yields and characterized by NMR spectroscopy. Furthermore, 1d was unambiguously characterized by single-crystal X-ray crystallography. Complexes 1a−f/2a−f have shown catalytic activity toward dimerization and hydrosilylation of styrenes. In particular, 1a proved to be the most efficient catalyst in the dimerization of styrene derivatives in the absence of cocatalyst. Also, complexes 1a,d showed high selectivity and moderate to good yields in hydrosilylation reactions