Vitamin E (α-tocopherol) supplementation in diabetic rats: effects on the proximal colon

Background  

Neuropathy is one of the complications caused by diabetes mellitus which is directly related to the gastrointestinal manifestations of the disease. Antioxidant substances, such as vitamin E, may play an important role in the reduction of the neurological damage caused by diabetes mellitus. The aim of the present study was to determine whether vitamin E (α-tocopherol) at different concentrations induces any effects on the morphology of the intestinal wall and intrinsic innervation in the proximal colon of diabetic rats.     

Uncertainties analysis for the plutonium dosimetry model, doses-2005, using Mayak bioassay data

The Doses-2005 model is a combination of the International Commission on Radiological Protection (ICRP) models modified using data from the Mayak Production Association cohort. Surrogate doses from inhaled plutonium can be assigned to approximately 29% of the Mayak workers using their urine bioassay measurements and other history records. The purpose of this study was to quantify and qualify the uncertainties in the estimates for radiation doses calculated with the Doses-2005 model by using Monte Carlo methods and perturbation theory. The average uncertainty in the yearly dose estimates for most organs was approximately 100% regardless of the transportability classification. The relative source of the uncertainties comes from three main sources: 45% from the urine bioassay measurements, 29% from the Doses-2005 model parameters, and 26% from the reference masses for the organs. The most significant reduction in the overall dose uncertainties would result from improved methods in bioassay measurement with additional improvements generated through further model refinement. Additional uncertainties were determined for dose estimates resulting from changes in the transportability classification and the smoking toggle. A comparison was performed to determine the effect of using the model with data from either urine bioassay or autopsy data; no direct correlation could be established. Analysis of the model using autopsy data and incorporation of results from other research efforts that have utilized plutonium ICRP models could improve the Doses-2005 model and reduce the overall uncertainty in the dose estimates.     

Cardiac disease in pregnancy

Cardiac disease in pregnancy remains the leading cause of maternal mortality. In this review article we discuss our approach to caring for pregnant women with cardiac disease, and how the physiological changes of pregnancy can impact pre-existing conditions. This is illustrated by case discussions and practice points. Multi-disciplinary, individualised care is paramount to optimising outcomes for pregnant women with cardiac disease and their babies.     

Cloning and characterization of Aplysia neutral endopeptidase, a metallo-endopeptidase involved in the extracellular metabolism of neuropeptides in Aplysia californica

Cell surface metallo-endopeptidases play important roles in cell communication by controlling the levels of bioactive peptides around peptide receptors. To understand the relative relevance of these enzymes in the CNS, we characterized a metallo-endopeptidase in the CNS of Aplysia californica, whose peptidergic pathways are well described at the molecular, cellular, and physiological levels. The membrane-bound activity cleaved Leu-enkephalin at the Gly3-Phe4 bond with an inhibitor profile similar to that of the mammalian neutral endopeptidase (NEP). This functional homology was supported by the molecular cloning of cDNAs from the CNS, which demonstrated that the Aplysia and mammalian NEPs share all the same amino acids that are essential for the enzymatic activity. The protein is recognized both by specific anti-Aplysia NEP (apNEP) antibodies and by the [125I]-labeled NEP-specific inhibitor RB104, demonstrating that the apNEP gene codes for the RB104-binding protein. In situ hybridization experiments on sections of the ganglia of the CNS revealed that apNEP is expressed in neurons and that the mRNA is present both in the cell bodies and in neurites that travel along the neuropil and peripheral nerves. When incubated in the presence of a specific NEP inhibitor, many neurons of the buccal ganglion showed a greatly prolonged physiological response to stimulation, suggesting that NEP-like metallo-endopeptidases may play a critical role in the regulation of the feeding behavior in Aplysia. One of the putative targets of apNEP in this behavior is the small cardioactive peptide, as suggested by RP-HPLC experiments. More generally, the presence of apNEP in the CNS and periphery may indicate that it could play a major role in the modulation of synaptic transmission in Aplysia and in the metabolism of neuropeptides close to their point of release.     

Metabolism and dosimetry of actinide elements in occupationally-exposed personnel of Russia and the United States: a summary progress report

The United States Transuranium and Uranium Registries (USTUR) and the Dosimetry Registry of the Mayak Industrial Association (DRMIA) have been independently collecting tissues at autopsy of plutonium workers in their respective countries for nearly 30 y. The tissues are analyzed radiochemically and the analytical data are used to develop, modify, or refine biokinetic models that describe the depositions and translocations of plutonium and transplutonium elements in the human body. The purpose of this collaborative research project is to combine the unique information on humans, gathered by the two Registries, into a joint database and perform analyses of the data. A series of project tasks are directly concerned with dosimetry in Mayak workers and involve biokinetic modeling for actinide elements. Transportability coefficients derived from in-vitro solubility measurements of actinide-containing aerosols (as measured by the DRMIA) were related to specific workplaces within Mayak facilities. The transportability coefficients of inhaled aerosols significantly affected the translocation rates of plutonium from the respiratory tract to the systemic circulation. Parameters for a simplified lung model, used by Branch No. 1, Federal Research Center Institute of Biophysics (FIB-1) and the Mayak Production Association for dose assessment at long times after inhalation of plutonium-containing aerosols, were developed on the basis of joint USTUR and DRMIA data. This model has separate sets of deposition and transfer parameters for three aerosol transportability groups, allowing work histories of the workers to be considered in the dose-assessment process. FIB-1 biokinetic models were extended to include the distributions of actinide elements in systemic organs of workers, and a relationship between the health of individual workers and plutonium distribution in tissues was determined. Workers who suffered from liver diseases generally had a smaller fraction of systemic plutonium in the liver at death and a larger fraction in the skeleton than did relatively healthy workers. Also, the fraction of total systemic plutonium excreted per day was significantly greater for workers with liver diseases than for relatively healthy workers. These observations could have a considerable effect on organ dosimetry in health-impaired workers whose dose assessments were based solely on urinary excretion rates. A comparison of this model to other biokinetic models, such as those published by the International Commission for Radiological Protection, is currently underway as is the documentation of uncertainty estimates associated with the model.     

238Pu: accumulation, tissue distribution, and excretion in Mayak workers after exposure to plutonium aerosols

The alpha spectrometry measurements of specific activity of 238Pu and 239Pu in urine from bioassay examinations of 1,013 workers employed at the radiochemical and plutonium production facilities of the Mayak Production Association and in autopsy specimens of lung, liver, and skeleton from 85 former nuclear workers who died between 1974-2009, are summarized.The accumulation fraction of 238Pu in the body and excreta has not changed with time in workers involved in production of weapons-grade plutonium production (e.g., the plutonium production facility and the former radiochemical facility). The accumulation fraction of 238Pu in individuals exposed to plutonium isotopes at the newer Spent Nuclear Fuel Reprocessing Plant ranged from 0.13% up to 27.5% based on the autopsy data. No statistically significant differences between 238Pu and 239Pu in distribution by the main organs of plutonium deposition were found in the Mayak workers. Based on the bioassay data,the fraction of 238Pu activity in urine is on average 38-69% of the total activity of 238Pu and 239Pu, which correlates with the isotopic composition in workplace air sampled at the Spent Nuclear Fuel Reprocessing Plant. In view of the higher specific activity of 238Pu, the contribution of 238Pu to the total internal dose, particularly in the skeleton and liver, might be expected to continue to increase, and continued surveillance is recommended.     

Methods underpinning national clinical guidelines for hypertension: describing the evidence shortfall

Background  

To be useful, clinical practice guidelines need to be evidence based; otherwise they will not achieve the validity, reliability and credibility required for implementation.     

Extrapulmonary organ distribution of plutonium in healthy workers exposed by chronic inhalation at the Mayak production association

The systemic distribution of plutonium was determined for "healthy" workers who chronically inhaled plutonium at the radiochemical plants of the Mayak Production Association. The data were obtained by radiochemical analysis of soft tissues and bones samples collected upon autopsy of 120 workers who died from acute coronary diseases and accidents. The soft tissue samples were wet-ashed using nitric acid and hydrogen peroxide. Bone samples were ashed in a muffle furnace at 500 degrees C. Plutonium was extracted on anionite and coprecipitated with bismuth phosphate. The precipitation was blended with ZnS powder, and the alpha-activity was measured by ZnS solid scintillation counting in a low-background alpha radiometer. Twenty-five years after the beginning of inhalation exposures, the average percentage of plutonium in the skeleton and liver was 50% and 42% of systemic burden, respectively. A multivariate regression was used to quantify the effects of exposure time, "transportability" of the various compounds, plutonium body content, and age on systemic plutonium distribution. The early retention of plutonium in the liver is assumed to be greater than that in the skeleton. The initial distribution of plutonium between the liver and the skeleton, immediately after entering the circulatory system, was 50:38%, respectively. With time, the fraction of plutonium found in the liver decreased, while the fraction in the skeleton increased at a rate of 0.5% y(-1) of systemic deposition. Exposure time had a greater effect on the relative retention of plutonium in the main organs when compared to age. The statistical estimates that characterized the relative plutonium distribution were less stable for the liver than for the skeleton, likely due to the slower turnover of skeletal tissues and the retention of plutonium in bone.