Partial and total multiphoton detachment rates for H- in a perturbative B-spline-based approach

An ab initio approach has been applied to study multiphoton detachment rates for the negative hydrogen ion in the lowest nonvanishing order of perturbation theory. The approach is based on the use of B splines allowing an accurate treatment of the electronic repulsion. Total detachment rates have been determined for two- to six-photon processes as well as partial rates for detachment into the different final symmetries. It is shown that B-spline expansions can yield accurate continuum and bound-state wave functions in a very simple manner. The calculated total rates for two- and three-photon detachment are in good agreement with other perturbative calculations. For more than three-photon detachment little information has been available before now. While the total cross sections show little structure, a fair amount of structure is predicted in the partial cross sections. In the two-photon process, it is shown that the detached electrons mainly have s character. For four- and six-photon processes, the contribution from the d channel is the most important. For three- and five-photon processes p electrons dominate the electron emission spectrum. Detachment rates for s and p electrons show minima as a function of photon energy. © 1994 The American Physical Society.

The agonism and synergistic potentiation of weak partial agonists by triethylamine in alpha(1)-adrenergic receptor activation: Evidence for a salt bridge as the initiating process

alpha(1)-adrenergic receptor (AR) activation is thought to be initiated by disruption of a constraining interhelical salt bridge (Porter et al., 1996). Disruption of this salt bridge is achieved through a competition for the aspartic acid residue in transmembrane domain three by the protonated amine of the endogenous ligand norepinephrine and a lysine residue in transmembrane domain seven. To further test this hypothesis, we investigated the possibility that a simple amine could mimic an important functional group of the endogenous ligand and break this alpha(1)-AR ionic constraint leading to agonism. Triethylamine (TEA) was able to generate concentration-dependent increases of soluble inositol phosphates in COS-1 cells transiently transfected with the hamster alpha(1b)-AR and in Rat-1 fibroblasts stably transfected with the human alpha(1a)-AR subtype. TEA was also able to synergistically potentiate the second messenger production by weak partial alpha(1)-AR agonists and this effect was fully inhibited by the alpha(1)-AR antagonist prazosin. However, this synergistic potentiation was not observed for full alpha(1)-AR agonists. Instead, TEA caused a parallel rightward shift of the dose-response curve, consistent with the properties of competitive antagonism. TEA specifically bound to a single population of alpha(1)-ARs with a K-i of 28.7 +/- 4.7 mM. In addition, the site of binding by TEA to the alpha(1)-AR is at the conserved aspartic acid residue in transmembrane domain three, which is part of the constraining salt bridge. These results indicate a direct interaction of TEA in the receptor agonist binding pocket that leads to a disruption of the constraining salt bridge, thereby initiating alpha(1)-AR activation.

Hot-melt extrusion technology and pharmaceutical application

The use of hot-melt extrusion (HME) within the pharmaceutical industry is steadily increasing, due to its proven ability to efficiently manufacture novel products. The process has been utilized readily in the plastics industry for over a century and has been used to manufacture medical devices for several decades. The development of novel drugs with poor solubility and bioavailability brought the application of HME into the realm of drug-delivery systems. This has specifically been shown in the development of drug-delivery systems of both solid dosage forms and transdermal patches. HME involves the application of heat, pressure and agitation through an extrusion channel to mix materials together, and subsequently forcing them out through a die. Twin-screw extruders are most popular in solid dosage form development as it imparts both dispersive and distributive mixing. It blends materials while also imparting high shear to break-up particles and disperse them. HME extrusion has been shown to molecularly disperse poorly soluble drugs in a polymer carrier, increasing dissolution rates and bioavailability. The most common difficulty encountered in producing such dispersions is stabilization of amorphous drugs, which prevents them from recrystallization during storage. Pharmaceutical industrial suppliers, of both materials and equipment, have increased their development of equipment and chemicals for specific use with HME. Clearly, HME has been identified as an important and significant process to further enhance drug solubility and solid-dispersion production. © 2012 Future Science Ltd.

Determination of the drug solubility at the melt temperature in silicone intravaginal rings using dynamic mechanical analysis

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Primary Reflex Persistence in Children With Partial Hearing

Persistence of the asymmetrical tonic neck reflex (ATNR) was examined in children with partial hearing (aged 6–12 years). Core literacy skills were also assessed. Three groups of children were selected from three schools with special units for children with partial hearing. All children completed an upright ATNR test protocol and standardized tests of reading and spelling. Children with partial hearing had significant levels of ATNR persistence, and significant reading and spelling difficulties. The findings suggest that persistence of an early sub-cortical reflex system may be associated with some of the motor and cognitive difficulties experienced by children with partial hearing.

Analysing partial ranks by using smoothed paired comparison methods:An investigation of value orientation in Europe

This paper introduces the paired comparison model as a suitable approach for the analysis of partially ranked data. For example, the Inglehart index, collected in international social surveys to examine shifts in post-materialistic values, generates such data on a set of attitude items. However, current analysis methods have failed to account for the complex shifts in individual item values, or to incorporate subject covariates. The paired comparison model is thus developed to allow for covariate subject effects at the individual level, and a reparameterization allows the inclusion of smooth non-linear effects of continuous covariates. The Inglehart index collected in the 1993 International Social Science Programme survey is analysed, and complex non-linear changes of item values with age, level of education and religion are identified. The model proposed provides a powerful tool for social scientists.

Development of novel oral formulations prepared via hot melt extrusion for targeted delivery of photosensitizer to the colon

Colon-residing bacteria, such as vancomycin-resistant Enterococcus faecalis and Bacteroides fragilis, can cause a range of serious clinical infections. Photodynamic antimicrobial chemotherapy (PACT) may be a novel treatment option for these multidrug resistant organisms. The aim of this study was to formulate a Eudragit®-based drug delivery system, via hot melt extrusion (HME), for targeting colonic release of photosensitizer. The susceptibility of E. faecalis and B. fragilis to PACT mediated by methylene blue (MB), meso-tetra(N-methyl-4-pyridyl)porphine tetra-tosylate (TMP), or 5-aminolevulinic acid hexyl-ester (h-ALA) was determined, with tetrachlorodecaoxide (TCDO), an oxygen-releasing compound, added in some studies. Results show that, for MB, an average of 30% of the total drug load was released over a 6-h period. For TMP and h-ALA, these values were 50% and 16% respectively. No drug was released in the acidic media. Levels of E. faecalis and B. fragilis were reduced by up to 4.67 and 7.73 logs, respectively, on PACT exposure under anaerobic conditions, with increased kill associated with TCDO. With these formulations, photosensitizer release could potentially be targeted to the colon, and colon-residing pathogens killed by PACT. TCDO could be used in vivo to generate oxygen, which could significantly impact on the success of PACT in the clinic.

Partial purification of lymphokine activities by iso-electric focusing

A continuous cell-line has been shown to be adaptable to preparation of supernatants containing lymphokine activities. Separation and partial purification of migration inhibiting, colony stimulating and interferon activities from such preparations has been achieved by the use of density gradient iso-electric focusing.

Fasciola hepatica:localization and partial characterization of tubulin

The localisation and distribution of the cytoskeletal protein tubulin in the adult liver fluke Fasciola hepatica have been determined by an indirect immunofluorescence technique using a monoclonal antibody raised against beta-tubulin. Tubulin was demonstrated in the tegumental syncytium and in the tegumental cell bodies and their cytoplasmic connections with the surface syncytium. Immunostaining was also evident in the nerve fibres innervating sensory receptors in the tegument, in the nerve plexus innervating the sub-tegumental musculature and in the cytoplasmic extensions of the nurse cells within the vitelline follicle. Immunoblotting of whole fluke fractions produced a single band corresponding to a molecule of approximately 54 kDa in size. This figure corresponds with previous data obtained on tubulin from other helminth and eukaryotic sources.

Detection and partial characterization of human B cell colony stimulating activity in synovial fluids of patients with rheumatoid arthritis

The joint fluids of 37 patients with rheumatoid arthritis, eight patients with traumatic injuries to their joints, two patients with Reiter's syndrome and three patients with psoriatic arthritis were tested for the presence of B cell colony stimulating activity (B cell CSA). B cell CSA was found in all of the joint fluids from the patients with rheumatoid arthritis but in none of the joint fluids from patients with traumatic injuries to their joints or in the joint fluids from the patients with Reiter's syndrome. A trace of B cell CSA was found in the joint fluid of one of the three patients with psoriatic arthritis. There was a positive correlation (r = 0.796) between the amount of rheumatoid factor present in the joint fluids and the titre of B cell CSA. This correlation was highly significant (P less than 0.001). The B cell CSA was localized to component(s) with molecular weight ranges 115-129 kD and 64-72 kD and an isoelectric point of 6.8. Its activity was sensitive to reduction with 2-mercaptoethanol and to the oxidising action of potassium periodate.