Oral choline supplementation for postoperative pain.

BACKGROUND: Activation of nicotinic receptors with nicotine has been shown to reduce post-surgical pain in clinical and preclinical studies. Choline is a selective agonist at α7-type nicotinic receptors that does not have addictive or sympathetic activating properties. It is anti-nociceptive in animal studies. We conducted a double-blind randomized trial of oral choline supplementation with lecithin to aid in the treatment of pain after gynaecological surgery. METHODS: Sixty women having open gynaecological surgery were randomly assigned to receive 20 g of lecithin before surgery or placebo. Plasma choline concentration and tumour necrosis factor (TNF) were measured. Pain report was the primary outcome measure. RESULTS: We achieved a small but statistically significant increase in choline after surgery with oral supplementation. Plasma TNF was not decreased and pain report was not different between groups at rest or with movement. There were no adverse effects of treatment. CONCLUSIONS: Oral supplementation with lecithin during the perioperative period resulted in very slow absorption and thus only a small increase in plasma choline was achieved. This concentration was inadequate to reduce TNF as has been shown in other studies. The absence of an anti-inflammatory effect was likely related to our failure to demonstrate efficacy in pain reduction.

Improved performance of nanowire-quantum-dot-polymer solar cells by chemical treatment of the quantum dot with ligand and solvent materials.

We report a nanowire-quantum-dot-polymer solar cell consisting of a chemically treated CdSe quantum dot film deposited on n-type ZnO nanowires. The electron and hole collecting contacts are a fluorine-doped tin-oxide/zinc oxide layer and a P3HT/Au layer. This device architecture allows for enhanced light absorption and an efficient collection of photogenerated carriers. A detailed analysis of the chemical treatment of the quantum dots, their deposition, and the necessary annealing processes are discussed. We find that the surface treatment of CdSe quantum dots with pyridine, and the use of 1,2-ethanedithiol (EDT) ligands, critically improves the device performance. Annealing at 380 °C for 2 h is found to cause a structural conversion of the CdSe from its initial isolated quantum dot arrangement into a polycrystalline film with excellent surface conformality, thereby resulting in a further enhancement of device performance. Moreover, long-term annealing of 24 h leads to additional increases in device efficiency. Our best conversion efficiency reached for this type of cell is 3.4% under 85 mW cm(-2) illumination.

Laser annealing of photoluminescent ZnO nanorods grown at low temperature.

We report on pulsed laser annealing as an efficient method for improving the structural and optical properties of ZnO nanorods grown at low temperature. We find that the excitonic luminescence at 390 nm can be improved by as much as a factor of 8. We also show that laser annealing can be carried out in typical device structures, in particular by illumination through glass/indium-tin-oxide substrates and through polymer/indium-tin-oxide substrates.

Efficacy and tolerability of celecoxib compared with diclofenac slow release in the treatment of acute ankle sprain in an Asian population.

INTRODUCTION: Cyclooxygenase (COX)-2 selective inhibitors are attractive candidates for treatment of ankle sprain because of their efficacy as anti-inflammatory and analgesic agents and their overall safety, including lack of effect on platelet aggregation. The objective of this study was to assess the efficacy and tolerability of celecoxib compared with diclofenac slow release (SR) in the treatment of acute ankle sprain in an Asian population. METHODS: In this seven-day, multicentre, double-blind, randomised, parallel-group trial, 370 patients with first- or second-degree ankle sprain occurring at or less than 48 hours prior to the first dose of study medication were randomised to receive celecoxib 200 mg bid (189 patients) after a 400 mg loading dose or diclofenac SR 75 mg bid (181 patients). Patients were required to demonstrate moderate to severe ankle pain on weight bearing (45 mm or greater on a 100 mm visual analogue scale [VAS]) at baseline. The primary efficacy end point was the patient's assessment of ankle pain (VAS on full weight bearing) on day 4. RESULTS: Celecoxib was as effective as diclofenac SR in improving the signs and symptoms of ankle sprain. At day 4, mean VAS scores for celecoxib and diclofenac SR had decreased to 28 mm and 30 mm, respectively. Treatment differences were not statistically significant. Incidence of upper gastrointestinal adverse events was low in both treatment groups (0.5 percent versus 2.2 percent for celecoxib and diclofenac SR, respectively). CONCLUSION: Celecoxib, a COX-2 selective inhibitor, is as effective as diclofenac SR in treating ankle sprains. With its platelet-sparing properties, celecoxib may offer an advantage over diclofenac SR in managing musculoskeletal injuries.

Growth of (101) faces of tetragonal lysozyme crystals: measured growth-rate trends.

Previous extensive measurements of the growth rates of the (110) face of tetragonal lysozyme crystals have shown unexpected dependencies on the supersaturation. In this study, similar growth-rate measurements were performed for the (101) faces of the crystals. The data show a similar dependence on the supersaturation, becoming appreciable only at high supersaturations, reaching a maximum value and then decreasing. The (101) growth rates are larger at low supersaturations than the (110) growth rates under the same conditions and are smaller at high supersaturations. These trends suggest that the growth mechanism of the (101) face is similar to that of the (110) face: both processes involve the addition of multimeric growth units formed in solution, but the average size of the units for the (101) face is likely to be smaller than for the (110) face.

Growth of (101) faces of tetragonal lysozyme crystals: determination of the growth mechanism.

Measurements of the macroscopic growth rates of the (101) face of tetragonal lysozyme crystals indicate an unusual dependence on the supersaturation [Forsythe et al. (1999), Acta Cryst. D55, 1005-1011] similar to that observed for the (110) face. As performed previously for the (110) face, the surface packing arrangement for the (101) face was constructed in this study based on earlier microscopic observations and theoretical analysis of the internal molecular packing. This allowed the minimum growth unit for this face to be identified as a tetramer corresponding to a single turn of helices centered about the 43 axes and the minimum growth step to be identified as of unimolecular height. A macroscopic mathematical model for the growth of the (101) face was developed based on the reversible formation of multimeric growth units in solution and the addition of a unit to the crystal face by dislocation and two-dimensional nucleation mechanisms. The calculations showed that the best fits were obtained for tetramer or octamer growth units in this model. This and other evidence suggests that while growth may proceed by a variety of growth units, the average size of these units is between that of a tetramer and an octamer.

Determining the molecular-packing arrangements on protein crystal faces by atomic force microscopy.

Previous atomic force microscopy (AFM) studies and periodic bond-chain (PBC) analyses of tetragonal lysozyme crystals have suggested that the (110) face consists of chains of molecules related to one another by 43 axes parallel to the crystal face. In this study, high-resolution AFM images of the (110) face were obtained and analyzed in order to verify this prediction. A computer program was employed which constructs the theoretical AFM image corresponding to a specific crystallographic molecular-packing arrangement and AFM tip shape. The packing arrangement and tip shape were varied in order to obtain the maximum possible correlation between experimental and theoretical images. The prediction from PBC analysis of an arrangement involving 43 helices was confirmed in this manner, while the alternate arrangement, consisting of molecules related to one another by 21 axes, was not observed. However, the surface structure was found to differ significantly even from this crystallographic arrangement. The molecules were found to pack slightly closer about what will become the 43 axes within the interior of the crystal, suggesting the occurrence of surface reconstruction or rearrangement on the tetragonal lysozyme (110) face. This study represents a new approach for more precise determination of the molecular-packing arrangements on protein crystal faces employing AFM.

Determining the molecular-growth mechanisms of protein crystal faces by atomic force microscopy.

A high-resolution atomic force microscopy (AFM) study has shown that the molecular packing on the tetragonal lysozyme (110) face corresponds to only one of two possible packing arrangements, suggesting that growth layers on this face are of bimolecular height [Li et al. (1999). Acta Cryst. D55, 1023-1035]. Theoretical analyses of the packing also indicated that growth of this face should proceed by the addition of growth units of at least tetramer size, corresponding to the 43 helices in the crystal. In this study, an AFM linescan technique was used to measure the dimensions of individual growth units on protein crystal faces as they were being incorporated into the lattice. Images of individual growth events on the (110) face of tetragonal lysozyme crystals were observed, shown by jump discontinuities in the growth step in the linescan images. The growth-unit dimension in the scanned direction was obtained from these images. A large number of scans in two directions on the (110) face were performed and the distribution of lysozyme growth-unit sizes were obtained. A variety of unit sizes corresponding to 43 helices were shown to participate in the growth process, with the 43 tetramer being the minimum observed size. This technique represents a new application for AFM, allowing time-resolved studies of molecular processes to be carried out.

Locations of bromide ions in tetragonal lysozyme crystals.

Anions have been shown to play a dominant role in the crystallization of chicken egg-white lysozyme from salt solutions. Previous studies employing X-ray crystallography have found one chloride ion binding site in the tetragonal crystal form of the protein and four nitrate ion binding sites in the monoclinic form. In this study the anion positions in the tetragonal form were determined from the difference Fourier map obtained from lysozyme crystals grown in bromide and chloride solutions. Five possible anion-binding sites were found in this manner. Some of these sites were in pockets containing basic residues while others were near neutral, but polar, residues. The sole chloride ion binding site found in previous studies was confirmed, while four further sites were found which corresponded to the four binding sites found for nitrate ions in monoclinic crystals. The study suggests that most of the anion-binding sites in lysozyme remain unchanged even when different anions and different crystal forms of lysozyme are employed.

Growth mechanism of the (110) face of tetragonal lysozyme crystals.

The measured macroscopic growth rates of the (110) face of tetragonal lysozyme show an unexpectedly complex dependence on the supersaturation. In earlier studies it has been shown that an aggregate growth unit could account for experimental growth-rate trends. In particular molecular packing and interactions in the growth of the crystal were favored by completion of the helices along the 4(3) axes. In this study the molecular orientations of the possible growth units and the molecular growth mechanism were identified. This indicated that growth was a two-step process: aggregate growth units corresponding to the 4(3) helix are first formed in the bulk solution by stronger intermolecular bonds and then attached to the crystal face by weaker bonds. A more comprehensive analysis of the measured (110) growth rates was also undertaken. They were compared with the predicted growth rates from several dislocation and two-dimensional nucleation growth models, employing tetramer and octamer growth units in polydisperse solutions and monomer units in monodisperse solutions. The calculations consistently showed that the measured growth rates followed the expected model relations with octamer growth units, in agreement with the predictions from the molecular level analyses.

CCD video observation of microgravity crystallization of lysozyme and correlation with accelerometer data.

Lysozyme has been crystallized using the ESA Advanced Protein Crystallization Facility onboard the NASA Space Shuttle Orbiter during the IML-2 mission. CCD video monitoring was used to follow the crystallization process and evaluate the growth rate. During the mission some tetragonal crystals were observed moving over distances of up to 200 micrometers. This was correlated with microgravity disturbances caused by firings of vernier jets on the Orbiter. Growth-rate measurement of a stationary crystal (which had nucleated on the growth reactor wall) showed spurts and lulls correlated with an onboard activity: astronaut exercise. The stepped growth rates may be responsible for the residual mosaic block structure seen in crystal mosaicity and topography measurements.

Growth mechanism and morphology of tetragonal lysozyme crystals.

The tetragonal form of hen egg-white lysozyme is the most investigated protein crystal for growth studies, but the relationship between its surface morphology and internal structure is still not well understood. One method of determining this relationship for inorganic crystals is by employing the periodic bond chain (PBC) theory of Hartman & Perdok [Hartman & Perdok (1955). Acta Cryst. 8, 49-52, 521-524, 525-529]. However, complexities resulting from the packing arrangements and the number of intermolecular bonds in protein crystals have resulted in the use of only simplified versions of this theory so far. In this study a more complete PBC analysis of tetragonal lysozyme crystals was carried out, coupled with an approach incorporating the molecular orientations of the crystal structure. The analysis revealed the existence of a helical tetramer building block of the entire crystal structure, centered around the 4(3) crystallographic axes, resulting in double-layered slices and PBC's throughout. The analysis also indicated that the crystallizing units for the faces are at least as large as this tetramer, with the experimental evidence suggesting that it is a tetramer unit for the {101} faces and an octamer unit for the {110} faces. The {110} faces were shown to be molecularly smooth F faces, while the {101} to be essentially rough S faces. The predicted morphology and growth mechanisms were found to explain numerous experimental observations from electron and atomic force microscopy, etching studies, lysozyme aggregation studies and measurements of growth kinetics.