Prolonged effects of modified sham feeding on energy substrate mobilization

Background: Vagal stimulation in response to nutrients is reported to elicit an array of digestive and endocrine responses, including an alteration in postprandial lipid metabolism. Objective: The objective of this study was to assess whether neural stimulation could alter hormone and substrate metabolism during the late postprandial phase, with implications for body fat mobilization. Design: Vagal stimulation was achieved by using the modified sham feeding (MSF) technique, in which nutrients are chewed and tasted but not swallowed. Ten healthy subjects were studied on 3 separate occasions, 4 wk apart. Five hours after a high-fat breakfast (56 g fat), the subjects were given 1 of 3 test meals allocated in random order: water, a lunch containing a modest amount of fat (38 g), or MSF (38 g fat). Blood was collected for 3 h poststimulus for hormone and metabolite analyses. Results: Plasma insulin and pancreatic polypeptide concentrations peaked at 250% and 209% of baseline concentrations within 15 min of MSF. The plasma glucose concentration increased significantly (P = 0.038) in parallel with the changes observed in the plasma insulin concentration. The nonesterified fatty acid concentration was significantly suppressed (P = 0.006); maximum suppression occurred at a mean time of 114 min after MSF. This fall in nonesterified fatty acid was accompanied by a fall in the plasma glucagon concentration from 122 to 85 pmol/L (P = 0.018) at a mean time of 113 min after MSF. Conclusions: Effects on substrate metabolism after MSF in the postprandial state differ from those usually reported in the postabsorptive state. The effects of MSF were prolonged beyond the period of the cephalic response and these may be relevant for longer-term metabolic regulation.

Exposure to environmental oestrogenic chemicals and breast cancer.

The human population is now exposed on a daily basis to a multitude of environmental pollutant chemicals that would not have been present a century ago, and many of these chemicals have been detected in the human breast. The fatty nature of human breast tissue makes it a particular target for lipophilic as well as hydrophilic pollutant chemicals, which may enter the human body through oral, respiratory, or dermal routes. These chemicals possess a range of endocrine-disrupting properties and genotoxic activity, but from a breast cancer perspective the greatest concern has centered around their ability to mimic or interfere with the action of estrogen. The breast is an endocrine target organ and exposure to estrogen is a known risk factor for breast cancer.

Plastic films for polytunnels can prolong the effective residual life of cypermethrin to over 6 months

Synthetic pyrethroid insecticides are degraded almost entirely by ultraviolet (UV)-catalysed oxidation. A bioassay using the beetle Tribolium confusum duVal caged on bandages soaked in 0.04% a.i. cypermethrin showed large differences in residual insecticide-life under three plastic films available for cladding polytunnels. Cypermethrin exposed to a UV film that transmitted 70% of UVB and 80% of UVA killed all beetles for 8 weeks, compared to only 3 weeks for cypermethrin exposed in a clear plastic envelope. Cypermethrin under a UV-absorbing film that reduced the transmission of UVB and UVA to 14% and 50%, respectively, gave a complete kill for 17 weeks. Reducing the transmission of UVB to virtually zero, and that of UVA to only 3%, using a UV-opaque film prolonged the effective life of the cypermethrin residue to 26 weeks, and some beetles were still killed for a further 11 weeks. Even after this time, beetles exposed to cypermethrin from the UV-opaque treatment were still affected by the insecticide, and only showed near-normal mobility after 24 months of pesticide exposure to the UV-opaque film. These results have implications for the recommended intervals between cypermethrin treatment and crop harvest, and on the time of introduction of insect-based biological control agents, when UV-opaque films are used in commercial horticulture.

N-nitroso compound exposure-associated transcriptomic profiles are indicative of an increased risk for colorectal cancer

Endogenous formation of N-nitroso compounds (NOCs), which are known animal carcinogens, could contribute to human carcinogenesis but definitive evidence is still lacking. To investigate the relevance of NOCs in human colorectal cancer (CRC) development, we analyzed whole genome gene expression modifications in human colon biopsies in relation to fecal NOC exposure. We had a particular interest in patients suffering from intestinal inflammation as this may stimulate endogenous NOC formation, and consequently predispose to CRC risk. Inflammatory bowel disease (IBD) patients diagnosed with ulcerative colitis and irritable bowel syndrome patients without inflammation, serving as controls, were therefore recruited. Fecal NOC were demonstrated in the majority of subjects. By associating gene expression levels of all subjects to fecal NOC levels, we identified a NOC exposure-associated transcriptomic response that suggests that physiological NOC concentrations may potentially induce genotoxic responses and chromatin modifications in human colon tissue, both of which are linked to carcinogenicity. In a network analysis, chromatin modifications were linked to 11 significantly modulated histone genes, pointing towards a possible epigenetic mechanism that may be relevant in comprehending NOC-induced carcinogenesis. In addition, pro-inflammatory transcriptomic modifications were identified in visually non-inflamed regions of the IBD colon. However, fecal NOC levels were slightly but not significantly increased in IBD patients, suggesting that inflammation did not strongly stimulate NOC formation. We conclude that NOC exposure is associated with gene expression modifications in the human colon that may suggest a potential role of these compounds in CRC development.

Increasing food familiarity without the tears. A role for visual exposure?

Research has established the success of taste exposure paradigms as a means of increasing children’s acceptance, and liking, of previously unfamiliar or disliked foods. Yet, parents report that they tend to avoid the stress associated with repeatedly offering their children foods that are likely to be rejected. Given that successful taste exposure programmes often enhance children’s familiarity with a food’s appearance, as well as its taste, this article reviews the potential for exposure interventions that do not require repeated tastings to bring about positive attitude changes towards healthy foods. Recent evidence from studies that expose toddlers to picture books about fruit and vegetables suggest that familiarity with the origins and appearance of unfamiliar foods might increase children’s willingness to accept these into their diets.

Reducing contamination by exposure plus safety behaviour

Background and objectives: It has been proposed that the judicious use of safety behaviour can facilitate improvements in the acceptability of cognitive behaviour therapy (CBT). It was decided to explore the possibility of facilitating CBT by introducing a form of safety behaviour.We sought to assess the degree to which Exposure plus Safety Behaviour (E þ SB) is an effective intervention for contamination fears. Methods: A comparison was made between the effects of a control condition (Exposure and Response Prevention; ERP) and an experimental condition (Exposure plus Safety Behaviour; E þ SB) in which each exposure to a contaminant was followed by the use of a hygienic wipe in a sample of (n ¼ 80) undergraduate students. In session one, each participant touched a confirmed contaminant 20 times. After each exposure participants were asked to report their feelings of contamination, fear, disgust, and danger. In the second session, two weeks later, the same procedure was carried out for a further 16 trials. Results: The ERP and the E þ SB conditions both produced large, significant and stable reductions in contamination. Significant reductions in fear, danger and disgust were also reported in both conditions. Limitations: The treatment was provided to an analogue sample and over two sessions. Conclusions: The use of hygienic wipes, the safety behaviour used in this experiment, did not preclude significant reductions in contamination, disgust, fear and danger. If it is replicated and extended over a longer time-frame, this finding may enable practitioners to enhance the acceptability of cognitive behavioural treatments and boost their effectiveness.

Long-term acclimation of leaf production, development, longevity and quality following 3 yr exposure to free-air CO2 enrichment during canopy closure in Populus

The effects of elevated CO2 on leaf development in three genotypes of Populus were investigated during canopy closure, following exposure to elevated CO2 over 3 yr using free-air enrichment.• Leaf quality was altered such that nitrogen concentration per unit d. wt (Nmass) declined on average by 22 and 13% for sun and shade leaves, respectively, in elevated CO2. There was little evidence that this was the result of ‘dilution’ following accumulation of nonstructural carbohydrates. Most likely, this was the result of increased leaf thickness. Specific leaf area declined in elevated CO2 on average by 29 and 5% for sun and shade leaves, respectively.• Autumnal senescence was delayed in elevated CO2 with a 10% increase in the number of days at which 50% leaf loss occurred in elevated as compared with ambient CO2.• These data suggest that changes in leaf quality may be predicted following long-term acclimation of fast-growing forest trees to elevated CO2, and that canopy longevity may increase, with important implications for forest productivity.

Canonical Wnt signalling induces satellite-cell proliferation during adult skeletal muscle regeneration

Satellite cells represent the stem cell population of adult skeletal muscle. The molecular mechanisms that control the proliferation of satellite cells are not well understood. In this study, we show that in response to injury, myofibres activate Wnt ligand transcription and activate a reporter cell line that is sensitive to the canonical Wnt-signalling pathway. Activated satellite cells on isolated cultured myofibres show robust expression of activated-β-catenin (Act-β-Cat), a key downstream transcriptional coactivator of canonical Wnt signalling. We provide evidence that the Wnt family of secreted glycoproteins act on satellite cells in a ligand-specific manner. Overexpression of Wnt1, Wnt3a or Wnt5a protein causes a dramatic increase in satellite-cell proliferation. By contrast, exposure of satellite cells to Wnt4 or Wnt6 diminishes this process. Moreover, we show that the prolonged satellite-cell quiescence induced by inhibitory Wnt is reversible and exposing inhibited satellite cells to stimulatory Wnt signalling restores their proliferation rate. Stimulatory Wnt proteins induce premature satellite cell BrdU incorporation as well as nuclear translocation of Act-β-Cat. Finally, we provide evidence that the Act-β-Cat translocation observed in single fibres during in vitro culture also occurs in cases of acute and chronic skeletal muscle regeneration in rodents and humans. We propose that Wnt proteins may be key factors that regulate the rate of satellite-cell proliferation on adult muscle fibres during the wound-healing response.

Identification of potential mechanisms of toxicity after di-(2-ethylhexyl)-phthalate (DEHP) adult exposure in the liver using a systems biology approach

Phthalates are industrial additives widely used as plasticizers. In addition to deleterious effects on male genital development, population studies have documented correlations between phthalates exposure and impacts on reproductive tract development and on the metabolic syndrome in male adults. In this work we investigated potential mechanisms underlying the impact of DEHP on adult mouse liver in vivo. A parallel analysis of hepatic transcript and metabolic profiles from adult mice exposed to varying DEHP doses was performed. Hepatic genes modulated by DEHP are predominantly PPARalpha targets. However, the induction of prototypic cytochrome P450 genes strongly supports the activation of additional NR pathways, including Constitutive Androstane Receptor (CAR). Integration of transcriptomic and metabonomic profiles revealed a correlation between the impacts of DEHP on genes and metabolites related to heme synthesis and to the Rev-erbalpha pathway that senses endogenous heme level. We further confirmed the combined impact of DEHP on the hepatic expression of Alas1, a critical enzyme in heme synthesis and on the expression of Rev-erbalpha target genes involved in the cellular clock and in energy metabolism. This work shows that DEHP interferes with hepatic CAR and Rev-erbalpha pathways which are both involved in the control of metabolism. The identification of these new hepatic pathways targeted by DEHP could contribute to metabolic and endocrine disruption associated with phthalate exposure. Gene expression profiles performed on microdissected testis territories displayed a differential responsiveness to DEHP. Altogether, this suggests that impacts of DEHP on adult organs, including testis, could be documented and deserve further investigations.

Integrated cytokine and metabolic analysis of pathological responses to parasite exposure in rodents

Parasitic infections cause a myriad of responses in their mammalian hosts, on immune as well as on metabolic level. A multiplex panel of cytokines and metabolites derived from four parasite-rodent models, namely, Plasmodium berghei-mouse, Trypanosoma brucei brucei-mouse, Schistosoma mansoni-mouse, and Fasciola hepatica-rat were statistically coanalyzed. 1H NMR spectroscopy and multivariate statistical analysis were used to characterize the urine and plasma metabolite profiles in infected and noninfected animals. Each parasite generated a unique metabolic signature in the host. Plasma cytokine concentrations were obtained using the ‘Meso Scale Discovery’ multi cytokine assay platform. Multivariate data integration methods were subsequently used to elucidate the component of the metabolic signature which is associated with inflammation and to determine specific metabolic correlates with parasite-induced changes in plasma cytokine levels. For example, the relative levels of acetyl glycoproteins extracted from the plasma metabolite profile in the P. berghei-infected mice were statistically correlated with IFN-γ, whereas the same cytokine was anticorrelated with glucose levels. Both the metabolic and the cytokine data showed a similar spatial distribution in principal component analysis scores plots constructed for the combined murine data, with samples from all infected animals clustering according to the parasite species and whereby the protozoan infections (P. berghei and T. b. brucei) grouped separately from the helminth infection (S. mansoni). For S. mansoni, the main infection-responsive cytokines were IL-4 and IL-5, which covaried with lactate, choline, and D-3-hydroxybutyrate. This study demonstrates that the inherently differential immune response to single and multicellular parasites not only manifests in the cytokine expression, but also consequently imprints on the metabolic signature, and calls for in-depth analysis to further explore direct links between immune features and biochemical pathways.

Virtual reality Post Traumatic Stress Disorder (PTSD) exposure therapy results with active duty OIF/OEF service members

Posttraumatic stress disorder (PTSD) is reported to be caused by exposure to traumatic events including (but not limited to) military combat, violent personal assault, being kidnapped or taken hostage and terrorist attacks. Initial data suggest that at least 1 out of 6 Iraq War veterans are exhibiting symptoms of depression, anxiety and PTSD. Virtual reality (VR) delivered exposure therapy for PTSD has been used with reports of positive outcomes. The aim of the current paper, is to present the rationale and brief description of a Virtual Iraq/Afghanistan PTSD VR therapy application and present initial findings from its use with PTSD patients. Thus far, Virtual Iraq/Afghanistan consists of a series of customizable virtual scenarios designed to represent relevant Middle Eastern VR contexts for exposure therapy, including a city and desert road convoy environment. User-centered design feedback, needed to iteratively evolve the system, was gathered from returning Iraq War veterans in the USA and from a system deployed in Iraq and tested by an Army Combat Stress Control Team. Results from an open clinical trial at San Diego Naval Medical Center of the first 20 treatment completers indicate that 16 no longer met PTSD screening criteria at post-treatment, with only one not maintaining treatment gains at 3 month follow-up.

Resistance as a factor in environmental exposure of anticoagulant rodenticides: a modelling approach

Anticoagulant rodenticide (AR) resistance in Norway rat populations has been a problem for fifty years, however its impact on non-target species, particularly predatory and scavenging animals has received little attention. Field trials were conducted on farms in Germany and England where resistance to anticoagulant rodenticides had been confirmed. Resistance is conferred by different mutations of the VKORC1 gene in each of these regions: tyrosine139cysteine in Germany and leucine120glutamine in England. A modelling approach was used to study the transference of the anticoagulants into the environment during treatments for Norway rat control. Baiting with brodifacoum resulted in lower levels of AR entering the food chain via the rats and lower numbers of live rats carrying residues during and after the trials due to its lower application rate and efficacy against resistant rats. Bromadiolone and difenacoum resulted in markedly higher levels of AR uptake into the rat population and larger numbers of live rats carrying residues during the trials and for long periods after the baiting period. Neither bromadiolone nor difenacoum provided full control on any of the treated farms. In resistant areas where ineffective compounds are used there is the potential for higher levels of AR exposure to non-target animals, particularly predators of rats and scavengers of rat carcasses. Thus, resistance influences the total amount of AR available to non-targets and should be considered when dealing with rat infestations, as resistance-breakers may present a lower risk to wildlife.

Exposure of Escherichia coli and Salmonella enterica serovar Typhimurium to triclosan induces a species-specific response, including drug detoxification

Objectives: The use of triclosan within various environments has been linked to the development of multiple drug resistance (MDR) through the increased expression of efflux pumps such as AcrAB-ToIC. In this work, we investigate the effect of triclosan exposure in order to ascertain the response of two species to the presence of this widely used biocide. Methods: The transcriptomes of Salmonella enterica serovar Typhimurium SL1344 and Escherichia coli K-12 MG1655 after exposure to the MIC of triclosan (0.12 mg/L) were determined in microarray experiments. Phenotypic validation of the transcriptomic data included RT-PCR, ability to form a biofilm and motility assays. Results: Despite important differences in the triclosan-dependent transcriptomes of the two species, increased expression of efflux pump component genes was seen in both. Increased expression of soxS was observed in Salmonella Typhimurium, however, within E. coli, decreased expression was seen. Expression of fabBAGI in Salmonella Typhimurium was decreased, whereas in E. coli expression of fabABFH was increased. Increased expression of ompR and genes within this regulon (e.g. ompC, csgD and ssrA) was seen in the transcriptome of Salmonella Typhimurium. An unexpected response of E. coli was the differential expression of genes within operons involved in iron homeostasis; these included fhu, fep and ent. Conclusions: These data indicate that whilst a core response to triclosan exposure exists, the differential transcriptome of each species was different. This suggests that E. coli K-12 should not be considered the paradigm for the Enterobacteriaceae when exploring the effects of antimicrobial agents.