Alcohol exposure during late gestation: Multiple developmental outcomes in sheep

Alcohol consumption during pregnancy remains common in many countries. Exposure to even low amounts of alcohol (i.e. ethanol) in pregnancy can lead to the heterogeneous fetal alcohol spectrum disorders (FASD), while heavy alcohol consumption can result in the fetal alcohol syndrome (FAS). FAS is characterized by cerebral dysfunction, growth restriction and craniofacial malformations. However, the effects of lower doses of alcohol during pregnancy, such as those that lead to FASD, are less well understood. In this article, we discuss the findings of recent studies performed in our laboratories on the effects of fetal alcohol exposure using sheep, in which we investigated the effects of late gestational alcohol exposure on the developing brain, arteries, kidneys, heart and lungs. Our studies indicate that alcohol exposure in late gestation can (1) affect cerebral white matter development and increase the risk of hemorrhage in the fetal brain, (2) cause left ventricular hypertrophy with evidence of altered cardiomyocyte maturation, (3) lead to a decrease in nephron number in the kidney, (4) cause altered arterial wall stiffness and endothelial and smooth muscle function and (5) result in altered surfactant protein mRNA expression, surfactant phospholipid composition and pro-inflammatory cytokine mRNA expression in the lung. These findings suggest that fetal alcohol exposure in late gestation can affect multiple organs, potentially increasing the risk of disease and organ dysfunction in later life

The site of embolization related to infarct size, oedema and clinical outcome in a rat stroke model - further translational stroke research

<p>Abstract</p> <p>Background and purpose</p> <p>Reliable models are essential for translational stroke research to study the pathophysiology of ischaemic stroke in an effort to find therapies that may ultimately reduce oedema, infarction and mortality in the clinic. The purpose of this study was to investigate the relation between the site of arterial embolization and the subsequent oedema, infarction and clinical outcome in a rat embolic stroke model.</p> <p>Methods</p> <p>Thirty-six male Sprague-Dawley rats were thromboembolized into the internal carotid artery. The site of occlusion was demonstrated by arteriography. Following histological preparation and evaluation, the size of the hemispheres and the infarcts were measured by quantitative histology and planimetry. Another parallel stroke model study was subsequently examined to investigate if the conclusions from the first study could be applied to the second study.</p> <p>Results</p> <p>The median size of the infarct was 40% of the ipsilateral hemisphere in both the 19 animals with occlusion localised to the intracranial part of the internal carotid artery and in the 11 animals where the main trunk of the middle cerebral artery was occluded. In 5 animals, occlusion of the extracranial part of the internal carotid artery resulted in significantly smaller infarcts compared to other groups (p < 0.01). Another independent study re-confirmed these results. Furthermore, significant correlations (R > 0.76, p < 0.0001) were found between 1) cortical, subcortical, and total infarct volumes, 2) oedema in percent of the left hemisphere, 3) clinical score before termination and 4) postoperative weight loss.</p> <p>Conclusions</p> <p>Distal occlusions of the intracranial part of the internal carotid or middle cerebral arteries resulted in comparable large sized infarctions and oedema. This indicates that investigators do not need a similar number of such occlusions in each experimental group. Contrary to observations in the clinic, distal internal carotid artery occlusions did not result in worse outcome than middle cerebral stem occlusions, but this finding may be explained by the controlled emboli size in this experimental stroke model.</p

The utility of system-level RAM analysis and standards for the US nuclear waste management system

The Department of Energy (DOE) Office of Civilian Radioactive Waste Management (OCRWM) is responsible for developing a system to manage spent nuclear fuel and high-level radioactive waste in accordance with the Nuclear Waste Policy Act of 1982 and its subsequent amendments. Pacific Northwest Laboratory (PNL) is assisting OCRWM in its investigation of whether system-level reliability, availability, and maintainability (RAM) requirements are appropriate for the waste management system and, if they are, what appropriate form should be for such requirements. Results and recommendations are presented

Evaluation of options for disposition of dispersible material in B-Cell

The radioactive contaminants in the dispersible material in B-cell of the 324 Building Radiochemical Energy (RE) hot-cell complex at the Hanford Site in southeastern Washington exceed the allowable level. In 1986, there was a spill of 1.3 million curies of concentrated cesium and strontium in B-cell. Cleanup is required, and candidate technologies for cleaning up or otherwise addressing problems associated with the dispersible material are being evaluated by Pacific Northwest Laboratory (PNL). The RE hot-cell complex in 324 Building was constructed in the late 1950s. From the early 1960s until today the complex has been the site of numerous research, development, and demonstration programs using radioactive and hazardous materials. In mid-FY 1988, a program to clean B-cell was initiated. At present, dispersible material has been collected from 45% of the cell floor area, and 64% of the equipment and support racks have been removed from the cell. The evaluation of decontamination procedures are described