Morphine has a dual concentration-dependent effect on K+-evoked substance P release from rat peripheral airways

Our previous investigations of possible lung mechanisms underlying the effectiveness of nebulized morphine for the relief of dyspnoea, have shown a high density of non-conventional opioid binding sites in rat airways with similar binding characteristics (opioid alkaloid-sensitive, opioid peptide-insensitive) to that of putative mu(3)-opioid receptors on immune cells. To investigate whether these lung opioid binding sites are functional receptors, this study was designed to determine (using superfusion) whether morphine modulates the K+-evoked release of the pro-inflammatory neuropeptide, substance P (SP), from rat peripheral airways. Importantly, K+-evoked SP release was Ca2+-dependent, consistent with vesicular release. Submicromolar concentrations of morphine (1 and 200 nM) inhibited K+-evoked SP release from rat peripheral airways in a naloxone (1 mu M) reversible manner. By contrast, 1 mu M morphine enhanced K+-evoked SP release and this effect was not reversed by 1 mu M naloxone. However, 100 mu M naloxone not only antagonized the facilitatory effect of 1 mu M morphine on K+-evoked SP release from rat peripheral airways but it inhibited release to a similar extent as 200 nM morphine. It is possible that these latter effects are mediated by non-conventional opioid receptors located on mast cells, activation of which causes naloxone-reversible histamine release that in turn augments the release of SP from sensory nerve terminals in the peripheral airways. Clearly, further studies are required to investigate this possibility. (C) 1997 Academic Press Limited.

The 1.1 angstrom resolution crystal structure of [Tyr(15)]EpI, a novel alpha-conotoxin from Conus episcopatus, solved by direct methods

Conotoxins are valuable probes of receptors and ion channels because of their small size and highly selective activity. alpha-Conotoxin EpI, a 16-residue peptide from the mollusk-hunting Conus episcopatus, has the amino acid sequence GCCSDPRCNMNNPDY(SO3H)C-NH2 and appears to be an extremely potent and selective inhibitor of the alpha 3 beta 2 and alpha 3 beta 4 neuronal subtypes of the nicotinic acetylcholine receptor (nAChR). The desulfated form of EpI ([Tyr(15)]EpI) has a potency and selectivity for the nAChR receptor similar to those of EpI. Here we describe the crystal structure of [Tyr(15)]EpI solved at a resolution of 1.1 Angstrom using SnB. The asymmetric unit has a total of 284 non-hydrogen atoms, making this one of the largest structures solved de novo try direct methods. The [Tyr(15)]EpI structure brings to six the number of alpha-conotoxin structures that have been determined to date. Four of these, [Tyr(15)]EpI, PnIA, PnIB, and MII, have an alpha 4/7 cysteine framework and are selective for the neuronal subtype of the nAChR. The structure of [Tyr(15)]EpI has the same backbone fold as the other alpha 4/7-conotoxin structures, supporting the notion that this conotoxin cysteine framework and spacing give rise to a conserved fold. The surface charge distribution of [Tyr(15)]EpI is similar to that of PnIA and PnIB but is likely to be different from that of MII, suggesting that [Tyr(15)]EpI and MII may have different binding modes for the same receptor subtype.

Corrosion behaviour of AZ21, AZ501 and AZ91 in sodium chloride

The corrosion behaviour of AZ21, AZ501 and AZ91 was studied in 1 N NaCl at pH 11 by measuring electrochemical polarization curves, electrochemical AC impedance spectroscopy (EIS) and simultaneously measuring the hydrogen evolution rate and the: magnesium dissolution rate. The corrosion rates increased in the following order: AZ501 < AZ21 < AZ91. The: corrosion behaviour was related to alloy microstructure as revealed by optical and electron microscopy. The beta phase was very stable in the test solution and was an effective cathode. The beta phase served two roles, as a barrier and as a galvanic cathode. If the beta phase is present in the alpha matrix as intergranular precipitates with a small volume fraction, then the beta phase mainly serves as a galvanic cathode, and accelerates the corrosion of the alpha matrix. If the beta Fraction is high, then the beta phase may mainly act as an anodic barrier to inhibit the overall corrosion of the alloy. The composition and compositional distribution in the alpha phase is also crucial to the overall corrosion performance of dual phase alloys. Increasing the aluminum concentration in the alpha phase increases the anodic dissolution rate and also increases the cathodic hydrogen evolution rate. Increasing the zinc concentration in the alpha phase may have the opposite effect. (C) 1998 Elsevier Science Ltd. All rights reserved.

Decoherence and fidelity in ion traps with fluctuating trap parameters

We consider two different kinds of fluctuations in an ion trap potential: external fluctuating electrical fields, which cause statistical movement (wobbling) of the ion relative to the center of the trap, and fluctuations of the spring constant, which an due to fluctuations of the ac component of the potential applied in the Paul trap for ions. We write down master equations for both cases and, averaging out the noise, obtain expressions for the heating of the ion. We compare our results to previous results for far-off resonance optical traps and heating in ion traps. The effect of fluctuating external electrical fields for a quantum gate operation (controlled-NOT) is determined and the fidelity for that operation derived. [S1050-2947(99)06005-9].

The crack tip strain field of AISI 4340 - Part III - Hydrogen influence

This paper studied the influence of hydrogen and water vapour environments on the plastic behaviour in the vicinity of the crack tip for AISI 4340. Hydrogen and water vapour (at a pressure of 15 Torr) significantly increased the crack tip opening displacement. The crack tip strain distribution in 15 Torr hydrogen was significantly different to that measured in vacuum. In the presence of sufficient hydrogen, the plastic zone was larger, was elongated in the direction of crack propagation and moreover there was significant creep. These observations support the hydrogen enhanced localised plasticity model for hydrogen embrittlement in this steel. The strain distribution in the presence of water vapour also suggests that SCC in AISI 4340 occurs via the hydrogen enhanced localised plasticity mechanism. (C) 1999 Kluwer Academic Publishers.

Quantifying the influence of intra-aggregate concentration gradients on solute transport

The physical nonequilibrium of solute concentration resulting from preferential now of soil water has often led to models where the soil is partitioned into two regions: preferential flow paths, where solute transport occurs mainly by advection, and the remaining region, where significant solute transport occurs through diffusive exchange with the flow paths. These two-region models commonly ignore concentration gradients within the regions. Our objective was to develop a simple model to assess the influence of concentration gradients on solute transport and to compare model results with experiments conducted on structured materials. The model calculates the distribution of solutes in a single spherical aggregate surrounded by preferential now paths and subjected to alternating boundary conditions representing either an exchange of solutes between the two regions (a wet period) or no exchange but redistribution of solutes within the aggregate (a dry period). The key parameter in the model is the aggregate radius, which defines the diffusive time scales. We conducted intermittent leaching experiments on a column of packed porous spheres and on a large (300 mm long by 216 mm diameter) undisturbed field soil core to test the validity of the model and its application to field soils. Alternating wet and dry periods enhanced leaching by up to 20% for this soil, which was consistent with the model's prediction, given a fitted equivalent aggregate radius of 1.8 cm, If similar results are obtained for other soils, use of alternating wet and dry periods could improve management of solutes, for example in salinity control and in soil remediation.

Electrochemistry of macrocyclic cobalt(III/II) hexaamines: Electrocatalytic hydrogen evolution in aqueous solution

The macrocyclic cobalt hexaamines [Co(trans-diammac)](3+) and [Co(cis-diammac)](3+) (diammac = 6,13-dimethyl-1,4,8,11-tetraazacyclotetradecane-6,13-diamine) are capable of reducing the overpotential for hydrogen evolution on a mercury cathode in aqueous solution. Protons are reduced in a catalytic process involving reoxidation of the Co-II species to its parent Co-III complex. The cycle is robust at neutral pH with no decomposition of catalyst. The stability of the [Co(trans-diammac)](2+) and [Co(cis-diammac)](2+) complexes depends on the pH of the solution and the coordinating properties of the supporting electrolyte. Electrochemical studies indicate that the adsorbed Co-II complex on the surface of mercury is the active catalyst for the reduction of protons to dihydrogen.

Conformations of cyclic octapeptides and the influence of heterocyclic ring constraints upon calcium binding

A comparison is made between the structures and calcium binding properties of four cyclic octapeptides that differ in the number of heterocyclic thiazole and oxazoline ring constraints. The conformations of the naturally occurring cyclic octapeptides ascidiacyclamide 1 and patellamide D 2, which each contain two oxazoline and two thiazole rings, are compared by H-1 NMR spectroscopy with the analogues cyclo(Thr-D-Val(Thz)-Ile)(2) 3 with just two thiazoles, and cyclo(Thr-D-Val-alpha Abu-Ile)(2) 4, with no 5-membered rings. The conformations observed in the solid state for ascidiacyclamide (saddle) and patellamide D (twisted figure of eight) were retained in solution, whilst peptide 3 was found to have a chair shape and peptide 4 displayed a range of conformations. The solid state structure of 4 revealed that the peptide takes a relatively planar conformation with a number of transannular hydrogen bonds, which are apparently retained in solution. Complexation studies utilising H-1 NMR and CD spectroscopy yielded 1∶1 calcium-peptide binding constants (log K) for the four peptides (2.9 (1), 2.8 (2), 4.0 (3) and 5.5 (4)) as well as a 1 : 2 metal-peptide binding constant for 3 (log K = 4.5). The affinity for Ca2+ thus decreases with increasing number of 5-membered ring constraints in the macrocycle (4 > 3 > 2 approximate to 1).

Quantum and classical chaos for a single trapped ion

In this paper we investigate the quantum and classical dynamics of a single trapped ion subject to nonlinear kicks derived from a periodic sequence of Gaussian laser pulses. We show that the classical system exhibits: diffusive growth in the energy, or heating,'' while quantum mechanics suppresses this heating. This system may be realized in current single trapped-ion experiments with the addition of near-field optics to introduce tightly focused laser pulses into the trap.

The influence of supra-optimal root-zone temperatures on growth and stomatal conductance in Capsicum annuum L.

Pepper (Capsicum annuum L.) plants were grown aeroponically in a Singapore greenhouse under natural diurnally fluctuating ambient shoot temperatures, but at two different root-zone temperatures (RZTs): a constant 20 +/- 2 degrees C RZT and a diurnally fluctuating ambient (A) (25-40 degrees C) RZT, Plants grown at 20-RZT had more leaves, greater leaf area and dry weight than A-RZT plants. Reciprocal transfer experiments were conducted between RZTs to investigate the effect on plant growth, stomatal conductance (g(s)) and water relations. Transfer of plants from A-RZT to 20-RZT increased plant dry weight, leaf area, number of leaves, shoot water potential (Psi(shoot)), and g(s); while transfer of plants from 20-RZT to A-RZT decreased these parameters. Root hydraulic conductivity was measured in the latter transfer and decreased by 80% after 23 d at A-RZT. Transfer of plants from 20-RZT to A-RZT had no effect on xylem ABA concentration or xylem nitrate concentration, but reduced xylem sap pH by 0.2 units. At both RZTs, g(s) measured in the youngest fully expanded leaves increased with plant development. In plants with the same number of leaves, A-RZT plants had a higher g(s) than 20-RZT plants, but only under high atmospheric vapour pressure deficit. The roles of chemical signals and hydraulic factors in controlling g(s) of aeroponically grown Capsicum plants at different RZTs are discussed.

Concentration-effect relationship of hydroxychloroquine in patients with rheumatoid arthritis - A prospective, dose ranging study

Objective. A 6 month prospective randomized double blind study was conducted to investigate hydroxychloroquine dose concentration-effect relationships in people with rheumatoid arthritis. Methods. Patients were randomized in 2 groups: one group received 200 mg hydroxychloroquine sulfate daily (A) and one group received 400 mg daily (B). Each month, 8 disease variables were assessed, adverse events recorded, and hydroxychloroquine blood concentrations determined. Results. Twenty-three patients were included: 10 in group A and 13 in group B. After 6 months of therapy, a significant improvement in disease activity was noted for 6 criteria with no statistical differences between groups: pain (assessed by a visual analog scale), joint scores (swelling and tenderness), impairment in daily Living activity (18 activities graded 0 to 8), patient assessment of disease state, and erythrocyte sedimentation rate. Hydroxychloroquine steady-state blood concentrations (Month 6) were significantly different between groups (mean +/- SD): 450.6 +/- 285.3 ng/ml (A) vs 870.3 +/- 329.3 ng/ml(B) (p = 0.0001). Steady-state concentrations were correlated with the daily dose (r = 0.63, p = 0.005), the improvement in activity of daily living (r = 0.49, p = 0.03), and the improvement in joint tenderness score (r = 0.47, p = 0.038). Conclusion. The data indicate that hydroxychloroquine is an effective therapy, but there were no further improvements observed in the group receiving 400 mg daily compared to those receiving 200 mg. There were some correlations between hydroxychloroquine steady-state blood concentrations and effects.

'Tetol': a stereo-rigid four-strand motif for alkali and alkaline earth metal ion coordination

The tetraalcohol 2,3,5,6-endo,endo,endo,endo-tetrakis(hydroxymethyl]bicyclo[2.2.1]heptane (tetol, 1) has been prepared and crystallises readily as the lithium(I) complex [Li(1)(2)]Cl, forming an oligomeric multi-chain structure in which pairs of alcohols from two crystallographically independent tetol molecules bind lithium ions tetrahedrally. However, formation of monomeric structures in solution is inferred from electrospray mass spectroscopy, which has also shown evidence of exchange of lithium ion in the complexed species by added alkaline earth ions. (C) 2000 Elsevier Science S.A. All rights reserved.

Entangled coherent-state qubits in an ion trap

We show how entangled qubits can be encoded as entangled coherent states of two-dimensional center-of-mass vibrational motion for two ions in an ion trap. The entangled qubit state is equivalent to the canonical Bell state, and we introduce a proposal for entanglement transfer from the two vibrational modes to the electronic states of the two ions in order for the Bell state to be detected by resonance fluorescence shelving methods.