Lorazepam-valproate interaction: studies in normal subjects and isolated perfused rat liver

Valproate (VPA) has been shown to interact with all the major antiepileptic drugs (AEDs) through two mechanisms of action: displacement from albumin binding sites and inhibition of drug metabolism. More recently, evidence showed that VPA inhibits the elimination of drugs metabolized by glucuronide conjugation. Lorazepam (LZP), which is primarily eliminated by conjugation with glucuronic acid, is administered concurrently with VPA both in treatment of epilepsy and in patients treated with VPA for psychiatric disorders. Therefore, a significant drug interaction is likely. We investigated such interaction both in in vitro isolated perfused rat liver (IPRL) and in normal subjects. LZP [2 mg, intravenous (i.v.) bolus] was administered to 8 normal volunteers before and after chronic dosing with VPA. In 6 of 8 subjects, VPA significantly decreased LZP plasma clearance by an average of 40% (p < 0.05) and increased LZP concentrations by decreasing formation clearance of the LZP glucuronide. In the IPRL studies, VPA also significantly decreased formation of LZP glucuronide (from 0.72 +/- 0.14 to 0.22 +/- 0.15 ml/h/kg, p < 0.05), indicating that IPRL is a useful tool for evaluation of the effect of VPA on drugs eliminated by glucuronide conjugation.     

K-winner networks.

A special class of mutually inhibitory networks is analyzed, and parameters for reliable K-winner performance are presented. The network dynamics are modeled using interactive activation, and results are compared with the sigmoid model. For equal external inputs, network parameters that select the units with the larger initial activations (the network converges to the nearest stable state) are derived. Conversely, for equal initial activations, networks that select the units with larger external inputs (the network converges to the lowest energy stable state) are derived. When initial activations are mixed with external inputs, anomalous behavior results. These discrepancies are analyzed with several examples. Restrictions on initial states are derived which ensure accurate K-winner performance when unequal external inputs are used.     

The role of occlusion in the perception of depth, lightness, and opacity.

A theory is presented that explains how the visual system infers the lightness, opacity, and depth of surfaces from stereoscopic images. It is shown that the polarity and magnitude of image contrast play distinct roles in surface perception, which can be captured by 2 principles of perceptual inference. First, a contrast depth asymmetry principle articulates how the visual system computes the ordinal depth and lightness relationships from the polarity of local, binocularly matched image contrast. Second, a global transmittance anchoring principle expresses how variations in contrast magnitudes are used to infer the presence of transparent surfaces. It is argued that these principles provide a unified explanation of how the visual system computes the 3-D surface structure of opaque and transparent surfaces. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A new adaptation of mapping method to study mixing of multiphase flows in mixers with complex geometries

The main objective of the present work is to modify the traditional mapping method for the simulation of distributive mixing of multiphase flows in geometries involving moving parts such as, internal mixers or twin-screw extruders without a limitation on their geometrical periodicity. The periodicity condition, limits the results of traditional mapping method to tracking mapping mesh between specific discrete time intervals or distances for that geometry is repeated, hence, result is only for fixed orientation of rotors. Imaginary domain method is introduced to track mapping mesh from one state to the next free of geometrical periodicity limitations. In this work the method is introduced and its applicability and accuracy is discussed in details. A two-dimensional (2D) simulation of mixing of two Newtonian fluids with different viscosities in an intermeshing internal mixer is used as a test case study. In this example the key issues of ability to predict mixing state in details for all orientations of rotors is presented. To reduce diffusion errors of mapping method in the boundaries of the rotors, mapping mesh refinement technique that relies upon one single reference mesh is also presented.     

Alpha 2 mRNA of Na+K+ ATPase is increased in astroctyes of rat hippocampus after treatment with kainic acid

The Na+K+ ATPase (Na+ pump) plays a central role in regulating cation homeostasis and is thought to have an important role in cell proliferation. The multitude of subunit isoforms comprising the functional Na+K+ ATPase has raised the possibility that specific subunit isoform combinations may be involved in different cellular processes. We have investigated the involvement of the specific isoforms in neurons and glia at the site of a CNS lesion. Intracerebroventricular injection of kainic acid was used to induce neuronal cell loss and reactive gliosis in rat hippocampus and levels of Na+K+ ATPase subunit isoform mRNA levels were determined in cells of rat hippocampus using in situ hybridization. alpha 2 mRNA levels increased 35-40% in CA1 and CA3 astrocytes between 1-3 weeks after KA injection with no significant change in other subunit isoform mRNA levels. In addition alpha 3 mRNA levels in CA1 pyramidal neurons were decreased by approx. 35%. Small neurons in the CA1 and CA3 region showed no changes in mRNA levels for any of the Na+K+ ATPase subunit isoforms. These results may indicate a possible role for alpha 2 subunit isoform in the conversion of glial cells from a normal phenotype to the reactive phenotype characteristic in this model of CNS injury.     

The domain composition method applied to Poisson's equation in two dimensions

Domain composition, a recently described method for formulating continuum field problems, removes certain restrictions on the construction of finite element models such that it is possible to solve a finite element problem without using a global compatible mesh. The domain composition method couples or otherwise constrains meshes in local regions to obtain a solution equivalent to that produced by conventional finite element methods. In particular, the domain composition method enables finite element models to be formulated with overlapping elements. Several advantages come from this, including an ability to automatically generate a finite element model from a solid geometric model, an ability to use a variety of element types in a single finite element model and an ability to exactly match element boundaries to the local geometry. This paper shows in detail a finite element formulation of Poisson's equation using domain composition and presents certain key algorithms that incorporate the domain composition method into well-established finite element procedures.     

Behavioral and pharmacologic approaches to smoking cessation

Cigarette smoking continues to be the single, most preventable cause of death and disability in the United States. For individuals who have cancer, continuing to smoke negatively impacts their treatment, survival, and risk for second primary tumors. This review of behavioral and pharmacological approaches to smoking cessation focuses on the recent comprehensive review of cessation interventions by the Agency for Health Care Policy and Research (AHCPR), as well as on new developments in the field. An intervention model is outlined that provides oncologists with a brief and easily implemented method of systematically treating patients who smoke. By assessing patient smoking status, advising smoking patients to quit, and proactively assisting their patients in quitting, oncologists can significantly influence patient health and fulfill their professional and ethical responsibility to address this life-threatening behavior.     

Solidification Behavior of Undercooled Liquid Aluminum Oxide

Solidification of aluminum oxide from undercooled melts was investigated in containerless experiments. Specimens were levitated in a gas jet, stabilized with an acoustic positioning device, and melted with cw CO₂ laser beams. Cooling curves were obtained by optical pyrometry when the laser intensity was reduced. The materials examined were high-purity Verneuil sapphire, 99.5% polycrystalline alumina, and oxide materials recovered from the effluent of an aluminum-fueled rocket motor. The degree of undercooling, the apparent temperature behavior during the thermal arrest on solidification, and the structure of the materials formed were different in argon and oxygen atmospheres. Undercooling of the sapphire and alumina materials was 360 ± 10 K in an oxygen atmosphere and approximately 450 K in argon. Melting and solidification of high-purity sapphire resulted in a dendritic and porous polycrystalline material in oxygen. Dense, larger crystals were obtained in argon. Products formed from 99.5% alumina were discolored and the cores were white, indicating impurity segregation effects. More reproducible behavior was observed for the sapphire and 99.5% alumina than for the tungstencontaminated rocket motor effluent materials.