Long-term performance of a gas chromatography/tandem mass spectrometry assay for tebufelone in plasma

An automated gas chromatography/tandem mass spectrometry (GC/MS/MS) based method for the rapid determination of tebufelone (TE) in animal and human plasma has been routinely applied in our laboratory to more than 3000 samples over a 2-year period. The selectivity of MS/MS conducted on a triple quadrupole instrument, combined with the use of a stable-isotope-labeled internal standard, results in excellent analytical figures of merit, as well as minimal sample preparation, rapid analysis, and high assay reliability. The work described here goes beyond initial method development and validation studies by evaluating the long-term performance of quantitative GC/MS/MS. Electron ionization produces M.+ ions for TE and the [13C, 18O]TE internal standard, which are selected in Q1 and undergo collisionally activated dissociation in Q2. Quantitation is based on monitoring daughter ions at m/z 248 and 251, respectively, in Q3. A linear range of 1-3000 ng of TE/sample (20 pg to 60 ng injected) provides access to an effective concentration range of 0.5-30,000 ppb TE in plasma (0.1-2-g samples). The assay shows no bias and less than 10% relative standard deviation over this range. In the automated mode, less than 7 min elapse from injection to report printout and more than 70 plasma samples are routinely prepared and analyzed in a day. Such performance is consistently maintained throughout long-term application.     

A Model for the Diffusion of Moisture in Adhesive Joints. Part I: Equations Governing Diffusion

A methodology is proposed to relate the diffusion coefficient of small penetrant molecules in polymers to temperature, strain, and penetrant concentration. The approach used is based on well-known free volume theories. It is assumed that the transport kinetics is governed by the constant redistribution of the free volume, caused by the segmental motions of the polymeric chains. An expression for the diffusion coefficient is inferred from the temperature, strain, and penetrant concentration dependence of the free volume. The stress dependence of solubility is predicted from the Hildebrand theory. It is shown that the resulting constitutive equations exhibit many features desirable for joint durability studies. Finally, a non-Fickian driving force arising from differential swelling is included in the governing equations.     

Promoting Forgiveness Among Co-Workers Following a Workplace Transgression: The Effects of Social Motivation Training.

Forgiveness is one construct that is beginning to demonstrate promise as a health and relationship promoter within the workplace. The primary aim of this research was to examine the effects of one psychological intervention (social motivational training) that was developed to promote forgiveness among co-workers. In the first of two studies, workers were randomly assigned to one of two intervention conditions (i.e., job satisfaction training, social motivational training). Participants read a vignette in which they were to imagine themselves as victims of a co-worker transgression. Judgments of responsibility and co-worker forgiveness were then measured at two intervals: before and after training. In Study 2, workers recounted an actual critical incident involving a co-worker transgression, completed a pretraining questionnaire measuring judgments of responsibility, self-image, and forgiveness, received either a one-on-one job satisfaction training or social motivational training session, and completed a post-training questionnaire. Results from both studies indicated that social motivational training enhanced participants' forgiveness of a hypothetical and actual co-worker. In addition, Study 2 showed an increase in workers' self-image following social motivational training, suggesting affirmation of the self as a possible mechanism for the effects of social motivational training on forgiveness. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Contact angle hysteresis on smooth and homogenous surfaces in gravitational fields

In an experiment conducted on a space shuttle flight, contact angle hysteresis was observed for the water-glass system. Surface heterogeneities have usually been taken as the cause of the observed hysteresis. In order to examine if other factors such as adsorption could be the cause of the observed hysteresis, contact angles on homogenous, smooth surfaces of glass were examined in ground-based experiments. Ten glass cylinders with different inside diameters were constructed with a capillary tube in the centre of each cylinder. The cylinders were filled with prepared water and the meniscus heights inside the capillary tube and in the glass cylinder were measured. Using the values of these parameters, the pressure in the vapour and the contact angle at the three-phase line of each interface were calculated from the equilibrium conditions. In each of the cylinders, a difference in the contact angle at the three-phase line of the capillary and the three-phase line of the cylinder was observed. This contact angle hysteresis cannot be explained by surface heterogeneity or line tension effect. The observed contact angle hysteresis is predicted to be the result of the pressure profile in the system. This suggests adsorption and its extraordinary sensitivity to vapour-phase pressure as the source of the contact angle hysteresis.     

Remembrance of sounds past: Memory and psychophysical scaling.

What is the role of long-term memories of previous stimulus-response mappings, and of previous sensory and perceptual experiences generally, in psychophysical scaling judgments? In each of 4 experiments, subjects made judgments of the loudness of sounds on 3 successive days. Stimulus intensities were drawn randomly from the same set on Days 1 and 3 but from a different set on Day 2. Four different types of psychophysical scaling judgments were studied. The first two methods required completely relative judgment, the last two completely absolute judgment. Data from all methods reveal profound effects of stimulus-response mappings experienced on previous days and immediately previous stimuli and responses on responses to current stimuli. Responses were typically a compromise between absolute and relative judgment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of essential fatty acid depletion on tissue phospholipid fatty acids in spontaneously hypertensive and normotensive rats

Weanling male spontaneously hypertensive (SHR) and normotensive (WKY) rats were maintained on a fat-free semisynthetic diet and killed at various intervals. The effects of fat-depletion on the appearance of essential fatty acid (EFA) deficiency symptoms, the progressive changes of major fatty acids in plasma, liver, heart, and kidney phospholipids (PL), and in skin total lipids were compared between these two strains. After five weeks on the diet, the slower growth and the appearance of EFA deficiency symptoms became evident in SHR. In general, fat-depletion reduced the levels of n−6 fatty acids, whereas it increased those of 20∶3n−9. However, the fat-depletion induced reduction of 18∶2n−6 in heart PL and 20∶4n−6 in kidney, while the elevation of 20∶3n−9 in plasma, heart, and kidney PL were greater in WKY than in SHR. As a result, the elevation of biochemical EFA deficiency index—20∶3n−9/20∶4n−6 ratio—was greater in WKY than in SHR. In comparison with WKY, the concentrations of liver triacylglycerols and the weights of adipose tissues in SHR were reduced to a greater extent, indicating an active catabolism of triacylglycerols in SHR. This study suggests that the earlier appearance of morphological symptoms of EFA deficiency in SHR was not associated with the reducing n−6 EFA levels or with an elevation of triene/tetraene ratio, but possibly to a reduced supply of n−6 EFA for skin prostaglandin synthesis.     

Atopy and reaction to nail dust inhalation

Inhalation of nail dust is a chronic problem facing podiatric physicians. This problem is compounded in physicians who develop allergic reactions to nail dust. This article defines atopy, reviews the characteristics of nail dust, and suggests methods to reduce the potential hazard that nail dust presents to the podiatric physicians and their employees.     

Mutations in purine nucleoside phosphorylase deficiency

PURPOSE: The aim of this study was to investigate the incidence of unexpected malignant uveal melanoma in the age of ultrasound diagnostics and to highlight the reasons for misdiagnosis. PATIENTS AND METHODS: All eyes were surgically removed and histologic examination was performed between 1981 and 1995. The eyes were investigated for the incidence of uveal melanoma, and the history of the unexpected malignant melanoma of the uvea or ciliary body highlighted. RESULTS: 225 (18.7%) eyes with malignant melanoma out of 2583 enucleated eyes were found. Eight (3.6%) of 225 were clinically unexpected. The clinical misdiagnoses were secondary angle closure or open angle glaucoma (6), retinal detachment (5), iritis (1), scleritis (1), cataract (4) and an intraocular mass that was believed to be a metastasis of a colon carcinoma. Seven of eight eyes were blind, and one eye had light perception only. The longest follow up before enucleation was 13 years. On three eyes diagnostic ultrasound was reportedly performed without specific diagnosis of uveal melanoma. Surgery was performed on four eyes for reasons of uncontrollable intraocular pressure or retinal detachment up to five years before enucleation. Histologic diagnoses were 3 epitheloid-type, 2 spindel-type and 3 necrotic melanoma of the uvea. Four eyes showed scleral invasion by tumor cells and one eye an invasion into the episcleral space. CONCLUSIONS: Even today the rate of unexpected uveal melanoma, according to our study is 3.6%. Therefore, all blind eyes without visualisation of the posterior pole should be examined with ultrasound in order to diagnose an uveal melanoma prior to enucleation.     

Ligation of the T cell co-stimulatory receptor CD28 activates the serine-threonine protein kinase protein kinase B

The intracellular signaling pathways activated upon ligation of the co-stimulatory receptor CD28 remain relatively ill-defined, although CD28 ligation does result in the strong association with, and activation of, phosphatidylinositol (PI) 3-kinase. The downstream effector targets of the CD28-activated PI 3-kinase-dependent signaling pathway remain poorly defined, but recent evidence from other systems has shown that Akt/protein kinase B (PKB) is a major target of PI 3-kinase and have indicated that a major function of PKB is the regulation of cell survival events. Given the strong coupling of CD28 to PI 3-kinase and the known protective effects of both CD28 and PI 3-kinase against apoptosis in different cell models, we investigated the effects of CD28 on PKB activation. We demonstrate that ligation of CD28 by either anti-CD28 monoclonal antibodies or the natural ligand B7.1, results in the marked activation of PKB in both the leukemic T cell line Jurkat and freshly isolated human peripheral blood-derived normal T lymphocytes. Our data suggest therefore, that PKB may be an important intracellular signal involved in CD28 signal transduction and demonstrate CD28 coupling to downstream elements of a signaling cascade known to promote cell survival.