Hydromorphone-3-glucuronide: Biochemical synthesis and preliminary pharmacological evaluation

Hydromorphone-3-glucuronide (H3G) was synthesized biochemically using rat liver microsomes, uridine-5'-diphosphoglucuronic acid (UDPGA) and the substrate, hydromorphone. Initially, the crude putative H3G product was purified by ethyl acetate precipitation and washing with acetonitrile, Final purification was achieved using semi-preparative high-performance-liquid-chromatography (HPLC) with ultraviolet (UV) detection. The purity of the final H3G product was shown by HPLC with electrochemical and ultraviolet detection to be > 99.9% and it was produced in a yield of approximate to 60% (on a molar basis). The chemical structure of the putative H3G was confirmed by enzymatic hydrolysis of the glucuronide moiety using P-glucuronidase, producing a hydrolysis product with the same HPLC retention time as the hydromorphone reference standard. Using HPLC with tandem mass spectrometry (HPLC-MS-MS) in the positive ionization mode, the molecular mass (M+1) was found to be 462 g/mol, in agreement with H3G's expected molecular weight of 461 g/mol. Importantly, proton-NMR indicated that the glucuronide moiety was attached at the 3-phenolic position of hydromorphone. A preliminary evaluation of H3G's intrinsic pharmacological effects revealed that following icy administration to adult male Sprague-Dawley rats in a dose of 5 mu g, H3G evoked a range of excitatory behavioural effects.including chewing, rearing, myoclonus, ataxia and tonic-clonic convulsions, in a manner similar to that reported previously for the glucuronide metabolites of morphine, morphine-3-glucuronide and normorphine-3-glucuronide.

Anatomy of the mouthparts and digestive tract during feeding in larvae of the parasitoid wasp Trichogramma australicum Girault (Hymenoptera : Trichogrammatidae)

To aid in the development of artificial diets for mass rearing parasitioids, we investigated the anatomical changes in the digestive tract during feeding behaviour of larval Trichogramma australicum (Hymenoptera: Trichogrammatidae). Larvae begin to feed immediately upon eclosion and feed continuously for 4 h until replete. Feeding is characterised by rhythmic muscle contractions (ca 1 per s) of the pharynx. Contractions of the pharyngeal dilator muscles lift the roof of the lobe-shaped pharynx away from the floor of the chamber, opening the mouth and pumping food into the pharyngeal cavity. Another muscle contraction occurs about 0.5 s later, forcing the bolus of food through the oesophagus and into the midgut. The junction of fore- and midgut is marked by a cardiac valve. The midgut occupies most of the body cavity and is lined with highly vacuolated, flattened cells and a dispersed layer of muscle cells. In the centre of the midgut, food has the appearance of host egg contents. Food near the midgut epithelial cells has a finer, more homogeneous appearance. This change in the physical properties of the gut contents is indicative of the digestion process. In the prepupa, where digestion is complete, the entire gut contents have this appearance. After eclosion, the vitelline membrane remains attached to the posterior end of the larva. We believe this attachment to be adaptive in two ways: (1) to anchor the larva against the movements of its anterior portion, thereby increasing the efficiency of foraging within the egg, and (2) to prevent a free-floating membrane from clogging the mouthparts during ingestion. 1998 Elsevier Science Ltd. All rights reserved.

Novel nano-organisms from Australian sandstones

We report the detection of living colonies of nano-organisms (nanobes) on Triassic and Jurassic sandstones and other substrates. Nanobes have cellular structures that are strikingly similar in morphology to Actinomycetes and fungi (spores, filaments, and fruiting bodies) with the exception that they are up to 10 times smaller in diameter (20 nm to 1.0 mu m). Nanobes are noncrystalline structures that are composed of C, O, and N. Ultra thin sections of nanobes show the existence of an outer layer or membrane that may represent a cell wall. This outer layer surrounds an electron dense region interpreted to be the cytoplasm and a less electron dense central region that may represent a nuclear area. Nanobes show a positive reaction to three DNA stains, [4',6-diamidino-2 phenylindole (DAPI), Acridine Orange, and Feulgen], which strongly suggests that nanobes contain DNA. Nanobes are communicable and grow in aerobic conditions at atmospheric pressure and ambient temperatures. While morphologically distinct, nanobes are in the same size range as the controversial fossil nannobacteria described by others in various rock types and in the Martian meteorite ALH84001.

Changes in quantum efficiency of Photosystem II of symbiotic dinoflagellates of corals after heat stress, and of bleached corals sampled after the 1998 Great Barrier Reef mass bleaching event Ross J. Jones , Selina Ward, Affendi Yang Amri and Ove Hoegh-Guldberg

Pulse-amplitude-modulation chlorophyll fluorometry was used to examine changes in dark-adapted F-v/F-m of endosymbiotic dinoflagellate microalgae within the tissues of the temperate coral Plesiastrea versipora exposed to elevated seawater temperature. The F-v/F-m was markedly reduced following exposure of corals to 28 degrees C for 48 h. When corals were returned to ambient (24 degrees C) conditions, F-v/F-m increased in an initial rapid and then secondary slower phase. Tissue discolouration (coral bleaching), caused by a significant decrease in the density of algae, was observed during the first 2-3 days of the recovery period. After 14 days, F-v/F-m was still significantly lower than in control corals. The recovery of F-v/F-m is discussed in terms of repair processes within the symbiotic algae, division of healthy algae and also the selective removal of photo-damaged dinoflagellates. Under field conditions, bleached corals sampled at Heron Island Reef during a bleaching event had significantly lower F-v/F-m than non-bleached colonies; four months after the bleaching event, there were no differences in F-v/F-m or algal density in corals marked as having bleached or having shown no signs of colour loss. The results of this laboratory and field study are consistent with the hypothesis that an impairment of photosynthesis occurs during heat-stress, and is the underlying cause of coral bleaching.

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.

Bonding effects and the crystal structures of (NH4)(2)[Cu(H2O)(6)](SO4)(2) and its (H2O)-O-18 substituted form at 9.5 K

The crystal structures of the Tutton salts (NH4)(2)[Cu(H2O)(6)](SO4)(2), diammonium hexaaquacopper disulfate, formed with normal water and isotopically substituted (H2O)-O-18, have been determined by X-ray diffraction at 9.5 K and are very similar, with Cu-O(7) the longest of the Cu-O bonds of the Jahn-Teller distorted octahedral [Cu(H2O)(6)](2+) complex. It is known that structural differences accompany deuteration of (NH4)(2)[Cu(H2O)(6)](SO4)(2), the most dramatic of which is a switch to Cu-O(8) as the longest such bond. The present result suggests that the structural differences are associated with hydrogen-bonding effects rather than with increased mass of the water ligands affecting the Jahn-Teller coupling. The Jahn-Teller distortions and hydrogen-bonding contacts in the compounds are compared with those reported for other Tutton salts at ambient and high pressure.

Cyclotron effective masses in layered metals

Many layered metals such as quasi-two-dimensional organic molecular crystals show properties consistent with a Fermi-liquid description at low temperatures. The effective masses extracted from the temperature dependence of the magnetic oscillations observed in these materials are in the range, m(c)*/m(e) similar to 1 - 7, suggesting that these systems are strongly correlated. However, the ratio m(c)*/m(e) contains both the renormalization due to the electron-electron interaction and the periodic potential of the lattice. We show that for any quasi-two-dimensional band structure, the cyclotron mass is proportional to the density-of-states at the Fermi energy. Due to Luttinger's theorem, this result is also valid in the presence of interactions. We then evaluate m(c) for several model band structures for the beta, kappa, and theta families of (BEDT-TTF)(2)X, where BEDT-TTF is bis-(ethylenedithia-tetrathiafulvalene) and X is an anion. We find that for kappa-(BEDT-TTF)(2)X, the cyclotron mass of the beta orbit, m(c)*(beta) is close to 2 m(c)*(alpha), where m(c)*(alpha) is the effective mass of the alpha orbit. This result is fairly insensitive to the band-structure details. For a wide range of materials we compare values of the cyclotron mass deduced from band-structure calculations to values deduced from measurements of magnetic oscillations and the specific-heat coefficient gamma.

Copper/MCM-41 as catalyst for the wet oxidation of phenol

A heterogeneous copper catalyst supported on mesoporous MCM-41 was developed. The parent MCM-41 has a large pore area of over 1400 m(2)/g. Copper was chosen as the active element of catalyst and loaded into MCM-41 by adsorption at ambient temperature. The prepared catalysts were evaluated in the catalytic wet oxidation of phenol solution with an initial concentration of 1,300 ppm at 150 and 200 degreesC. The catalyst was found to be of high catalytic activity. It is also shown that the catalyst with a higher copper loading exhibits higher ability of accelerating the catalytic reaction to certain extent but reaches its constant level afterwards. (C) 2001 Elsevier Science B.V. All rights reserved.

Estimating the cost of contact for non-resident parents: A budget standards approach

Most Western countries have, for some time, provided income support and/or taxation relief to parents with children in their care. The significant amount of research into the costs of children to couple and sole parent households has been important in assessing and developing family support policies. Changing societal expectations about the level of involvement of fathers in child rearing activities has highlighted the need to understand the costs facing usually male non-resident parents in having contact with their children. The budget standards methodology is used in this paper to estimate the costs for non-resident parents exercising regular contact with their children. Costs of contact are found to be high. For contact with one child for 20 per cent of the year, costs of contact represent about 40 per cent of the costs of that same child in an intact couple household with a medium income and more than half of the costs of that child in a household with low income. Household infrastructure and transportation is the reason for high costs. One implication of this finding is that the total cost of children substantially increases when parents separate. The article discusses some policy implications of these findings. This research is of relevance to social security, taxation, family law and child support policies and administration.

A transformation toughening white cast iron

An experimental white cast iron with the unprecedented fracture tough ness of 40 MPa m(1/2) is currently being studied to determine the mechanisms of toughening. This paper reports the investigation of the role of strain-induced martensitic (SIM) transformation. The dendritic microconstituent in the toughened alloy consists primarily of retained austenite, with precipitated M(7)C(3) carbides and some martensite. Refrigeration experiments and differential scanning calorimetry (DSC) were used to demonstrate, firstly, that this retained austenite has an ''effective'' sub-ambient M(S) temperature and, secondly, that SIM transformation can occur at ambient temperatures. Comparison between room temperature and elevated temperature K-Ic tests showed that the observed SIM produces a transformation toughening response in the alloy, contributing to, but not fully accounting for, its high tough ness. SIM as a mechanism for transformation toughening has not previously been reported for white cast irons. Microhardness traverses on crack paths and X-ray diffraction (XRD) on fracture surfaces confirmed the interpretation of the K-Ic experiments. Further DSC and quantitative XRD showed that, as heat-treatment temperature is varied, there is a correlation between fracture toughness and the volume fraction of unstable retained austenite.

Proton transport model in the ionosphere .1. Multistream approach of the transport equations

The suprathermal particles, electrons and protons, coming from the magnetosphere and precipitating into the high-latitude atmosphere are an energy source of the Earth's ionosphere. They interact with ambient thermal gas through inelastic and elastic collisions. The physical quantities perturbed by these precipitations, such as the heating rate, the electron production rate, or the emission intensities, can be provided in solving the kinetic stationary Boltzmann equation. This equation yields particle fluxes as a function of altitude, energy, and pitch angle. While this equation has been solved through different ways for the electron transport and fully tested, the proton transport is more complicated. Because of charge-changing reactions, the latter is a set of two-coupled transport equations that must be solved: one for protons and the other for H atoms. We present here a new approach that solves the multistream proton/hydrogen transport equations encompassing the collision angular redistributions and the magnetic mirroring effect. In order to validate our model we discuss the energy conservation and we compare with another model under the same inputs and with rocket observations. The influence of the angular redistributions is discussed in a forthcoming paper.

In vivo effects of chicken interferon-gamma during infection with Eimeria

Newly hatched chickens are highly susceptible to infection by opportunistic pathogens during the first 1 or 2 weeks of life, The use of cytokines as therapeutic agents has been studied in animal models as well as in immunosuppressed patients, This approach has become more feasible in livestock animals, in particular poultry, with the recent cloning of cytokine genes and the development of new technologies, such as live delivery vectors, We have recently cloned the gene for chicken interferon-gamma (Ch-IFN-gamma), Poly-HIS-tagged recombinant Ch-IFN-gamma was expressed in Escherichia coil, was purified by Ni chromatography, and was found to be stable at 4 degrees C and an ambient temperature for at least several months and Several weeks, respectively, Ch-IFN-gamma was capable of protecting chick fibroblasts from undergoing virus-mediated lysis, induced nitrite secretion from chicken macrophages in vitro, and enhanced MHC class II expression on macrophages, Administration of recombinant Ch-IFN-gamma to chickens resulted in enhanced weight gain over a 12-day period, Furthermore, the therapeutic potential of Ch-IFN-gamma was assessed using a coccidial challenge model, Birds were treated with Ch-IFN-gamma or a diluent control and then infected with Eimeria acervulina. Infected birds treated with Ch-IFN-gamma showed improved weight gain relative to noninfected birds, The ability of Ch-IFN-gamma to enhance weight gain in the face of coccidial infection makes it an excellent candidate as a therapeutic agent.

Photodegradation of irinotecan (CPT-11) in aqueous solutions: Identification of fluorescent products and influence of solution composition

The photodegradation of irinotecan (CPT-11), the semisynthetic derivative of the antitumor alkaloid 20(S)-camptothecin, has been investigated. The drug was exposed to laboratory light for up to 5 days in 0.9% saline solution (pH 8.5). Five significant photodegradation products were observed and a high-performance liquid chromatography (HPLC) assay was employed to isolate them from CPT-11 using gradient conditions. The structures were elucidated by nuclear magnetic resonance spectroscopy and tandem mass spectrometry and shown to be the result of extensive modifications of the lactone ring of CPT-11. Three of the compounds were found to belong to the mappicine group of alkaloids. In addition, the effect of light on the stability of CPT-11 in aqueous solutions and biological fluids was also assessed, Potassium phosphate buffers (0.05 M, pH 5.0-8.2) and saline, plasma, urine, and bile solutions containing 20 mu M CPT-11 were equilibrated in the dark for 24 h before being exposed to laboratory light for up to 171 h at ambient temperature. Four of the five identified photodegradation products were observed and quantitated by isocratic HPLC, using a different detection mode (fluorescence) than the one used for gradient elution, In general, CPT-11 was found to be unstable under neutral and alkaline conditions for all solutions investigated, with the exception of bile. We conclude that CPT-11 is photolabile and that care should be taken to protect samples, particularly those intended for the isolation and identification of novel metabolites of CPT-11.

Proximal arterial vasoconstriction precedes regression of the hyaloid vasculature

Purpose: To determine whether constriction of proximal arterial vessels precedes involution of the distal hyaloid vasculature in the mouse, under normal conditions, and whether this vasoconstriction is less pronounced when the distal hyaloid network persists, as it does in oxygen-induced retinopathy (OIR). Methods: Photomicrographs of the vasa hyaloidea propria were analysed from pre-term pups (1-2 days prior to birth), and on Days 1-11 post-birth. The OIR model involved exposing pups to similar to 90% O-2 from D1-5, followed by return to ambient air. At sampling times pups were anaesthetised and perfused with india ink. Retinal flatmounts were also incubated with FITC-lectin (BS-1, G. simplicifolia,); this labels all vessels, allowing identification of vessels not patent to the perfusate. Results: Mean diameter of proximal hyaloid vessels in preterm pups was 25.44 +/- 1.98 mum; +/-1 SEM). Within 3-12 hrs of birth, significant vasoconstriction was evident (diameter:12.45 +/- 0.88 mum), and normal hyaloid regression subsequently occurred. Similar vasoconstriction occurred in the O-2-treated group, but this was reversed upon return to room air, with significant dilation of proximal vessels by D7 (diameter: 31.75 +/- 11.99 mum) and distal hyaloid vessels subsequently became enlarged and tortuous. Conclusions: Under normal conditions, vasoconstriction of proximal hyaloid vessels occurs at birth, preceding attenuation of distal hyaloid vessels. Vasoconstriction also occurs in O-2-treated pups during treatment, but upon return to room air, the remaining hyaloid vessels dilate proximally, and the distal vessels become dilated and tortuous. These observations support the contention that regression of the hyaloid network is dependent, in the first instance, on proximal arterial vasoconstriction.

James Parkinson (1755-1824): A pioneer of child care

James Parkinson (1755-1824) of Parkinson's disease, is well recognized as a pioneer of clinical neurology; and is even more famous as a founder of modem palaeontology. We have reviewed from primary sources his extensive contributions to clinical child care and his pioneering advocacy for child welfare, protection and safety. His writings, outreach and advocacy for children's health characterizes him as one whose influence was an important springboard from which evolved the modern specialty of paediatrics. Parkinson was one of the first to write on child-rearing practices and in this context antedated Benjamin Spock by 150 years. Parkinson was a pioneer of child safety and the prevention of childhood trauma. He wrote of the resuscitation of near-drowned children and of first aid for injured children. This critical analysis reviews his pioneering description of child abuse and the development of post-abuse hydrocephalus. He wrote the datum description (in English) of the pathophysiology and pathology of appendicitis in children, of fatal rabies in children and highlighted the risk of death even when the biting dog was not clinically rabid. His advocacy for social reform for children's welfare was courageous and pioneering. James Parkinson, hitherto unacknowledged, was a significant founder of the evolving discipline of paediatrics and child health.