Accuracy of a method based on atomic absorption spectrometry to determine inorganic arsenic in food : Outcome of the collaborative trial IMEP-41

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Leptin fails to blunt the lipopolysaccharide-induced activation of the hypothalamic-pituitary-adrenal axis in rats

Copyright @ 2013 The authors. This work is licensed under a Creative Commons Attribution 3.0 Unported License.Obesity is a risk factor for sepsis morbidity and mortality, whereas the hypothalamic-pituitary-adrenal (HPA) axis plays a protective role in the body's defence against sepsis. Sepsis induces a profound systemic immune response and cytokines serve as excellent markers for sepsis as they act as mediators of the immune response. Evidence suggests that the adipokine leptin may play a pathogenic role in sepsis. Mouse endotoxaemic models present with elevated leptin levels and exogenously added leptin increased mortality whereas human septic patients have elevated circulating levels of the soluble leptin receptor (Ob-Re). Evidence suggests that leptin can inhibit the regulation of the HPA axis. Thus, leptin may suppress the HPA axis, impairing its protective role in sepsis.We hypothesised that leptin would attenuate the HPA axis response to sepsis.We investigated the direct effects of an i.p. injection of 2 mg/kg leptin on the HPA axis response to intraperitoneally injected 25 μg/kg lipopolysaccharide (LPS) in the male Wistar rat. We found that LPS potently activated the HPA axis, as shown by significantly increased plasma stress hormones, ACTH and corticosterone, and increased plasma interleukin 1β (IL1β) levels, 2 h after administration. Pre-treatment with leptin, 2 h before LPS administration, did not influence the HPA axis response to LPS. In turn, LPS did not affect plasma leptin levels. Our findings suggest that leptin does not influence HPA function or IL1b secretion in a rat model of LPS-induced sepsis, and thus that leptin is unlikely to be involved in the acute-phase endocrine response to bacterial infection in rats.The section is funded by grants from the MRC, BBSRC, NIHR and an Integrative Mammalian Biology (IMB) Capacity Building Award, and by a FP7-HEALTH-2009-241592 EuroCHIP grant and is supported by the NIHR Imperial Biomedical Research Centre Funding Scheme. This work is supported by a BBSRC Doctoral Training-Strategic Skills Award grant (BB/F017340/1)

Postsynaptic density radiation signature following space irradiation

Introduction: The response of the brain to space radiation is an important concern for astronauts during space missions. Therefore, we assessed the response of the brain to 28Si ion irradiation (600 MeV/n), a heavy ion present in the space environment, on cognitive performance and whether the response is associated with altered DNA methylation in the hippocampus, a brain area important for cognitive performance.Methods: We determined the effects of 28Si ion irradiation on object recognition, 6-month-old mice irradiated with 28Si ions (600 MeV/n, 0.3, 0.6, and 0.9 Gy) and cognitively tested two weeks later. In addition, we determined if those effects were associated with alterations in hippocampal networks and/or hippocampal DNA methylation.Results: At 0.3 Gy, but not at 0.6 Gy or 0.9 Gy, 28Si ion irradiation impaired cognition that correlated with altered gene expression and 5 hmC profiles that mapped to specific gene ontology pathways. Comparing hippocampal DNA hydroxymethylation following proton, 56Fe ion, and 28Si ion irradiation revealed a general space radiation synaptic signature with 45 genes that are associated with profound phenotypes. The most significant categories were glutamatergic synapse and postsynaptic density.Discussion: The brain’s response to space irradiation involves novel excitatory synapse and postsynaptic remodeling

Most Probable Number Rapid Viability PCR Method to Detect Viable Spores of Bacillus anthracis in Swab Samples

This note presents a comparison of Most-Probable-Number Rapid Viability (MPN-RV) PCR and traditional culture methods for the quantification of Bacillus anthracis Sterne spores in macrofoam swabs generated by the Centers for Disease Control and Prevention (CDC) for a multi-center validation study aimed at testing environmental swab processing methods for recovery, detection, and quantification of viable B. anthracis spores from surfaces. Results show that spore numbers provided by the MPN RV-PCR method were in statistical agreement with the CDC conventional culture method for all three levels of spores tested (10{sup 4}, 10{sup 2}, and 10 spores) even in the presence of dirt. In addition to detecting low levels of spores in environmental conditions, the MPN RV-PCR method is specific, and compatible with automated high-throughput sample processing and analysis protocols

Selective APRIL Blockade Delays Systemic Lupus Erythematosus in Mouse

SLE pathogenesis is complex, but it is now widely accepted that autoantibodies play a key role in the process by forming excessive immune complexes; their deposits within tissues leading to inflammation and functional damages. A proliferation inducing ligand (APRIL) is a member of the tumor necrosis factor (TNF) superfamily mediating antibody-producing plasma cell (PC)-survival that may be involved in the duration of pathogenic autoantibodies in lupus. We found significant increases of APRIL at the mRNA and protein levels in bone marrow but not spleen cells from NZB/W lupus mice, as compared to control mice. Selective antibody-mediated APRIL blockade delays disease development in this model by preventing proteinuria, kidney lesions, and mortality. Notably, this was achieved by decreasing anti-DNA and anti-chromatin autoantibody levels, without any perturbation of B- and T- cell homeostasis. Thus, anti-APRIL treatment may constitute an alternative therapy in SLE highly specific to PCs compared to other B-cell targeting therapies tested in this disease, and likely to be associated with less adverse effects than any anti-inflammatory and immunosuppressant agents previously used

Developing Health-Based Pre-Planning Clearance Goals for Airport Remediation Following Chemical Terrorist Attack: Introduction and Key Assessment Considerations

In the event of a chemical terrorist attack on a transportation hub, post-event remediation and restoration activities necessary to attain unrestricted facility reuse and re-entry could require hours to multiple days. While restoration timeframes are dependent on numerous variables, a primary controlling factor is the level of pre-planning and decision-making completed prior to chemical terrorist release. What follows is the first of a two-part analysis identifying key considerations, critical information, and decision criteria to facilitate post-attack and post-decontamination consequence management activities. A conceptual site model and human health-based exposure guidelines are developed and reported as an aid to site-specific pre-planning in the current absence of U.S. state or Federal values designated as compound-specific remediation or re-entry concentrations, and to safely expedite facility recovery to full operational status. Chemicals of concern include chemical warfare nerve and vesicant agents and the toxic industrial compounds phosgene, hydrogen cyanide, and cyanogen chloride. This work has been performed as a national case study conducted in partnership with the Los Angeles International Airport and The Bradley International Terminal. All recommended guidelines have been selected for consistency with airport scenario release parameters of a one-time, short-duration, finite airborne release from a single source followed by compound-specific decontamination

Salivary and gut microbiomes play a significant role in in vitro oral bioaccessibility, biotransformation, and intestinal absorption of arsenic from food

The release of a toxicant from a food matrix during the gastrointestinal digestion is a crucial determinant of the toxicant's oral bioavailability. We present a modified setup of the human simulator of the gut microbial ecosystem (SHIME), with four sequential gastrointestinal reactors (oral, stomach, small intestine, and colon), including the salivary and colonic microbiomes. Naturally arsenic-containing rice, mussels, and nori seaweed were digested in the presence of microorganisms and in vitro oral bioaccessibility, bioavailability, and metabolism of arsenic species were evaluated following analysis by using HPLC/mass spectrometry. When food matrices were digested with salivary bacteria, the soluble arsenic in the gastric digestion stage increased for mussel and nori samples, but no coincidence impact was found in the small intestinal and colonic digestion stages. However, the simulated small intestinal absorption of arsenic was increased in all food matrices (1.2-2.7 fold higher) following digestion with salivary microorganisms. No significant transformation of the arsenic species occurred except for the arsenosugars present in mussels and nori. In those samples, conversions between the oxo arsenosugars were observed in the small intestinal digestion stage whereupon the thioxo analogs became major metabolites. These results expand our knowledge on the likely metabolism and oral bioavailabiltiy of arsenic during human digestion, and provide valuable information for future risk assessments of dietary arsenic

TCT-4 Efficacy and Safety of Concurrent Administration of Clopidogrel-loading (600mg) and Prasugrel-loading (60mg) in Patients with Acute ST-Segment Elevation Myocardial Infarction

Background: Current STEMI guideline recommendations limit the use of prasugrel to clopidogrel-naïve patients. However, in daily clinical practice a considerable proportion of STEMI patients undergoing primary PCI are preloaded with clopidogrel. Whether the use of prasugrel in clopidogrel pretreated STEMI patients is safe remains unknown. Similarly, the efficacy of a combined loading dose regimen has not been evaluated. Methods: Between 1 September 2009 and 15 October 2012, a total of 1,157 STEMI patients were included in the randomized COMFORTABLE AMI trial (NCT 00962416) and 891 STEMI patients in the SPUM ACS registry (NCT 01000701) at 12 centers. Patients were divided into three groups according to type of peri-procedural antiplatelet loading: (1) Clopidogrel and subsequent Prasugrel loading dose [CP], (2) Prasugrel loading dose alone [P] (3) Clopidogrel loading dose alone [C]; 23 patients were excluded because they were not exposed to Clopidogrel and Prasugrel. The primary safety endpoint was the rate of BARC type 3, 4 and 5 bleeding at 30 days. The primary efficacy endpoint was the composite of cardiac death, nonfatal MI and nonfatal stroke at 30 days. Outcomes were analyzed using Cox's Regressions (crude) and multinomial ITPW weighted Cox's Regressions. Results: A total of 2,025 patients were analysed of whom 428 (21.1%) had received CP, 447 (22.1%) patients P alone, and 1,150 (56.8%) patients C alone. The primary safety endpoint was observed among 1.2% of CP, 1.6% of P, and 1.5% of C patients (CP vs C ad. HR 0.99 (0.36-2.72), PC vs P ad. HR 0.73 (0.22-2.41). The primary safety endpoint occurred less frequently among CP (1.9%) compared with C patients (5.0%, adjusted HR 0.47 (0.22-1.00), but with similar frequency among P and C patients (2.9% vs 5.0%, ad. HR 0.68 (0.27-1.73). The net clinical benefit outcome parameter tended to be lower among CP (2.8%) compared with C patients (6.3%, ad. HR 0.56 (0.30-1.05), whereas no significant difference was observed between P and C patients (3.8% vs 6.3%, ad. HR 0.85 (0.39-1.86). Conclusions: Among STEMI patients preloaded with Clopidogrel, the concurrent administration of a Prasugrel loading dose appears safe and potentially more effective than Clopiogrel alone