In thrombin stimulated human platelets Citalopram, Promethazine, Risperidone, and Ziprasidone, but not Diazepam, may exert their pharmacological effects also through intercalation in membrane phospholipids in a receptor-independent manner

Intercalation of drugs in the platelet membrane affects phospholipid-requiring enzymatic processes according to the drugs’ intercalation capability. We investigated effects of Promethazine, Citalopram, Ziprasidone, Risperidone, and Diazepam on phospholipase A2 (PLA2) and polyphosphoinositide (PPI) metabolism in thrombin-stimulated human platelets. We also examined effects of the drugs on monolayers of glycerophospholipids using the Langmuir technique. Diazepam did not influence PLA2 activity, had no effects on PPI cycle, and caused no change in mean molecular area of phospholipid monolayers. The remaining psychotropic drugs affected these parameters in different ways and levels of potency suggesting that they act by being intercalated between the molecules of adjacent membrane phospholipids, thus causing changes in substrate availability for phospholipid-hydrolyzing enzymes (PLA2 and Phospholipase C). We show that several psychotropic drugs can also have other cellular effects than receptor antagonism. These effects may be implicated in the psychotropic effects of the drugs and/or their side effects

Calcium/calmodulin-dependent protein kinase activity in primary astrocyte cultures

Calcium, calmodulin-dependent protein kinase (Ca/CaM kinase) is an important component of calcium signalling mechanisms in the brain, but little is known about the properties of this protein phosphorylation system in astrocytes. Addition of calcium and calmodulin to supernatant or membrane fractions obtained from rat astrocytes in primary culture increased phosphate incorporation into an exogenously added substrate, casein, and into endogenous protein substrates; this increase was greater than that observed with either calcium alone or calmodulin alone. The calcium, calmodulin-stimulated increase was inhibited by trifluoperazine, and this inhibition could be overcome by the addition of excess calmodulin. The major substrates for Ca/CaM kinase activity were proteins with molecular weights of 59 and 53 kDa, which were similar, but not identical, to the subunits of Ca/CaM kinase type II from brain. The specific activity of Ca/CaM kinase and the phosphorylation of 59 kDa were increased in astrocyte cultures treated and maintained in dibutyryl cyclic adenosine monophosphate (dBcAMP). These results indicate that astrocytes contain Ca/CaM kinase activity and suggest an interaction between the cAMP and calcium/calmodulin messenger systems in these cells

Improvements in patient treatment planning systems

The Boron Neutron Capture Therapy, Radiation treatment planning environment (BNCT-Rtpe) software system is used to develop treatment planning information. In typical use BNCT-Rtpe consists of three main components: (1) Semi-automated geometric modeling of objects (brain, target, eyes, sinus) derived from MRI, CT, and other medical imaging modalities, (2) Dose computations for these geometric models with rtt-MC, the INEL Monte Carlo radiation transport computer code, and (3) Dose contouring overlaid on medical images as well as generation of other dose displays. We continue to develop a planning system based on three-dimensional image-based reconstructions using Bspline surfaces. Even though this software is in an experimental state, it has been applied for large animal research and for an isolated case of treatment for a human glioma. Radiation transport is based on Monte Carlo, however there will be implementations of faster methods (e.g. diffusion theory) in the future. The important thing for treatment planning is the output which must convey, to the radiologist, the deposition of dose to healthy and target tissue. Many edits are available such that one can obtain contours registered to medical image, dose/volume histograms and most information required for treatment planning and response assessment. Recent work has been to make the process more automatic and easier to use. The interface, now implemented for contouring and reconstruction, utilizes the Xwindowing system and the MOTIF graphical users interface for effective interaction with the planner. Much work still remains before the tool can be applied in a routine clinical setting

Innovation and Reduction in Contemporary Qualitative Methods: The Case of Conceptual Coupling, Activity-Type Pairs and Auto-Ethnography

During the course of this paper we mobilise an ideal typical framework that identifies three waves of reduction within contemporary qualitative inquiry as they relate to key aspects of the sociological tradition. The paper begins with a consideration of one of sociology's key questions; namely how is social organisation possible? The paper aims to demonstrate how this question moves from view as increased specialisation and differentiation in qualitative methodology within sociology and related disciplines results in a fragmentation and decontextualisation of social practices from social orders. Indeed, the extent to which qualitative methods have been detached from sociological principles is considered in relation to the emergence of a reductionist tendency. The paper argues that the first wave is typified by conceptual couplings such as 'discourse and the subject', 'narrative and experience', 'space and place' and the second by 'activity type couplings' such as 'walking and talking' and 'making and telling' and then, finally, the third wave exemplified through auto-ethnography and digital lifelogging. We argue each of these three waves represent a series of steps in qualitative reduction that, whilst representing innovation, need to reconnect with questions of action, order and social organisation as a complex whole as opposed to disparate parts