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The aggregation of gel-filtered human platelets induced by A23187 is very sensitive to inhibition by ethanol. Similarly when platelets preloaded with [3H]5-hydroxytryptamine ([3H]5HT) are studied in a superfusion system under conditions where aggregation is likely (high platelet density, presence of Ca2+) the rate of release of [3H]5HT induced by A23187 is reduced by the presence of ethanol. However when platelet aggregation is less likely (low platelet density, absence of Ca2+) ethanol does not reduce the rate of [3H]5HT efflux induced by A23187 in superfused platelets. In addition, in contrast to the effects of ethanol on platelet aggregation, the transformation of human red cells to echinocytes induced by A23187 is accelerated by the presence of ethanol. Similarly the increased efflux of 3H from superfused rat striatal slices preloaded with [3H]dopamine which is produced by A23187 is potentiated by ethanol. It is concluded that the inhibitory effect of ethanol on the action of A23187 may be confined to platelet aggregation. This may be because the mechanisms of action of either A23187 or ethanol on platelet aggregation differ from those on other cell functions.

Inositol monophosphatase can be modified at two sites by pyrene maleimide. These sites have been identified as Cys141 and Cys218. Stoichiometric addition of pyrene maleimide allows the sole modification of Cys218. The fluorescence of the pyrene moiety on the modified protein can be excited directly or by resonance energy transfer. The fluorescence properties of the pyrene group on Cys218 allows the interaction of ligands with the enzyme to be monitored. This feature has allowed dissociation constants for various metal ions to be determined and allowed the formation of various enzyme/ligand complexes to be observed. These studies have demonstrated that Mg2+ is required to support Pi binding and that Li+ interacts with a post‐catalytic complex which is only formed in the forward reaction.

The storage and transport of gases in coal is of tremendous importance in the utilisation of coalbeds, and in particular the recovery of methane. There is also increasing interest in the use of coal mines as sites for carbon dioxide sequestration to alleviate the potentially harmful effects of global warming. This paper demonstrates the use of magnetic resonance imaging to investigate the spatiotemporal dynamics of gas transport in coal. The presence of significant structural heterogeneities in the coal was observed. Dynamical effects displayed a broad range of time constants ranging from minutes to days.

While the harmful effects of alcohol abuse are well documented, experimental and clinical data support a potential benefit of light to moderate alcohol consumption. Cross-sectional studies have suggested an association between alcohol consumption and multiple sclerosis (MS) disability. In the absence of prospective, longitudinal studies, the causal nature of this relationship cannot be established. It remains possible that patients with increased disability progression reduce their alcohol intake. Even though there is substantial evidence for anti-inflammatory effects of low-to-moderate doses of alcohol, the associations need to be interpreted very cautiously. This study discusses the current state of knowledge about MS and alcohol consumption, and the limitations in conducting research with retrospective data in patients with MS.

Phospholipase C (PLC) activity was measured by the incorporation of [3H]-inositol into lipids and by the breakdown of [3H]-inositol-labelled phosphatidylinositols (PI) and polyphosphatidylinositols (PPI) to [3H]-inositol phosphates; phospholipase A2 (PLA2) activity by the breakdown of [3H]oleic acid-labelled phosphatidylcholine [( 3H]PC) to [3H]oleic acid and the enzymes of phospholipid base exchange (PLBE) by the incorporation of [14C]serine into membrane lipids. The activities of these enzymes in rat brain preparations were all increased by procedures which increase intracellular Ca2+, and were all inhibited to a varying extent by the presence of ethanol, 50 mM, in vitro. In contrast, the activities of PLA2 and PLBE enzymes were markedly increased in preparations from animals which had received ethanol chronically in vivo. Similarly, although the basal activity of PLC was only slightly increased in such preparations, depolarization induced the breakdown of a significantly greater fraction of radiolabelled PI than that which was obtained in control preparations. The results suggest compensatory alterations in the activity of Ca2+-activated enzymes of phospholipid metabolism in brain tissue during the continued presence of ethanol in vivo.

The dynamics of granular materials, particularly radial and axial segregation in horizontal rotating cylinders containing large and small particles, is studied by Magnetic Resonance Imaging (MRI). Stationary three-dimensional (3D) images and real-time two-dimensional (2D) structural images showing radial segregation, band formation, and band merging are reported. Quantitative local particle concentrations are measured in a noninvasive manner from the different magnetic resonance responses of the seeds throughout segregation. Data are acquired with sufficiently high temporal (300 ms for 2D images) and spatial resolutions (0.94 mm cubic voxels), to give insights into the underlying mechanisms of both radial and axial segregation. In particular, the increasing rate of the local particle concentration during radial segregation is quantified. Particle migration is observed in the bulk material of the 75% and 82% full cylinders during both radial and axial segregation, showing that this region beneath the avalanche layer does not behave as a solid body. We also provide direct experimental evidence to support recent numerical simulations of band merging.

Systemic delivery of therapeutic agents remains ineffective against diffuse intrinsic pontine glioma (DIPG), possibly due to an intact blood-brain-barrier (BBB) and to dose-limiting toxicity of systemic chemotherapeutic agents. Convection-enhanced delivery (CED) into the brainstem may provide an effective local delivery alternative for DIPG patients.The aim of this study is to develop a method to perform CED into the murine brainstem and to test this method using the chemotherapeutic agent carmustine (BiCNU). To this end, a newly designed murine CED catheter was tested in vitro and in vivo. After determination of safety and distribution, mice bearing VUMC-DIPG-3 and E98FM-DIPG brainstem tumors were treated with carmustine dissolved in DW 5% or carmustine dissolved in 10% ethanol.Our results show that CED into the murine brainstem is feasible and well tolerated by mice with and without brainstem tumors. CED of carmustine dissolved in 5% DW increased median survival of mice with VUMC-DIPG-3 and E98FM-DIPG tumors with 35% and 25% respectively. Dissolving carmustine in 10% ethanol further improved survival to 45% in mice with E98FM-DIPG tumors.Since genetically engineered and primary DIPG models are currently only available in mice, murine CED studies have clear advantages over CED studies in other animals.CED in the murine brainstem can be performed safely, is well tolerated and can be used to study efficacy of chemotherapeutic agents orthotopically. These results set the foundation for more CED studies in murine DIPG models.

Abstract— Chronic ethanol ingestion in rats leads to a slow rise in brain alcohol dehydrogenase activity which levels off after 2 weeks at approximately twice the initial activity. The half‐time of the rise is approximately 8 days. Abrupt withdrawal of the ethanol is followed by a rapid decline of the brain alcohol dehydrogenase activity to the normal level with a half‐time of approximately 15 h. The difference in time constants between the rise in enzyme activity during ethanol‐feeding and its decline following withdrawal suggests that the increased enzyme activity is at least in part the result of a reduced rate constant of enzyme degradation in the presence of ethanol. The effect of ethanol on brain alcohol dehydrogenase activity is not altered by supplementation of the diet with carbohydrate or vitamins. The effect is seen only in the cerebral hemispheres and not in the brain‐stem. Acquisition of tolerance to ethanol during chronic ethanol ingestion and its extinction following withdrawal follow almost the same time courses as the changes in brain alcohol dehydrogenase activity.