Pungent general anesthetics activate transient receptor potential-A1 to produce hyperalgesia and neurogenic bronchoconstriction

BACKGROUND: Volatile anesthetics such as isoflurane and halothane have been in clinical use for many years and represent the group of drugs most commonly used to maintain general anesthesia. However, despite their widespread use, the molecular mechanisms by which these drugs exert their effects are not completely understood. Recently, a seemingly paradoxical effect of general anesthetics has been identified: the activation of peripheral nociceptors by irritant anesthetics. This mechanism may explain the hyperalgesic actions of inhaled anesthetics and their adverse effects in the airways. METHODS: To test the hypothesis that irritant inhaled anesthetics activate the excitatory ion-channel transient receptor potential (TRP)-A1 and thereby contribute to hyperalgesia and irritant airway effects, we used the measurement of intracellular calcium concentration in isolated cells in culture. For our functional experiments, we used models of isolated guinea pig bronchi to measure bronchoconstriction and withdrawal threshold to mechanical stimulation with von Frey filaments in mice. RESULTS: Irritant inhaled anesthetics activate TRPA1 expressed in human embryonic kidney cells and in nociceptive neurons. Isoflurane induces mechanical hyperalgesia in mice by a TRPA1-dependent mechanism. Isoflurane also induces TRPA1-dependent constriction of isolated bronchi. Nonirritant anesthetics do not activate TRPA1 and fail to produce hyperalgesia and bronchial constriction. CONCLUSIONS: General anesthetics induce a reversible loss of consciousness and render the patient unresponsive to painful stimuli. However, they also produce excitatory effects such as airway irritation and they contribute to postoperative pain. Activation of TRPA1 may contribute to these adverse effects, a hypothesis that remains to be tested in the clinical setting.

Rational engineering of recombinant picornavirus capsids to produce safe, protective vaccine antigen

Foot-and-mouth disease remains a major plague of livestock and outbreaks are often economically catastrophic. Current inactivated virus vaccines require expensive high containment facilities for their production and maintenance of a cold-chain for their activity. We have addressed both of these major drawbacks. Firstly we have developed methods to efficiently express recombinant empty capsids. Expression constructs aimed at lowering the levels and activity of the viral protease required for the cleavage of the capsid protein precursor were used; this enabled the synthesis of empty A-serotype capsids in eukaryotic cells at levels potentially attractive to industry using both vaccinia virus and baculovirus driven expression. Secondly we have enhanced capsid stability by incorporating a rationally designed mutation, and shown by X-ray crystallography that stabilised and wild-type empty capsids have essentially the same structure as intact virus. Cattle vaccinated with recombinant capsids showed sustained virus neutralisation titres and protection from challenge 34 weeks after immunization. This approach to vaccine antigen production has several potential advantages over current technologies by reducing production costs, eliminating the risk of infectivity and enhancing the temperature stability of the product. Similar strategies that will optimize host cell viability during expression of a foreign toxic gene and/or improve capsid stability could allow the production of safe vaccines for other pathogenic picornaviruses of humans and animals.

Plenary Lecture 2: Milk and dairy produce and CVD: new perspectives on dairy and cardiovascular health

Cardiovascular diseases (CVD) are the leading cause of mortality and morbidity worldwide. One of the key dietary recommendations for CVD prevention is reduction of saturated fat intake. Yet despite milk and dairy foods contributing on average 27 % of saturated fat intake in the UK diet, evidence from prospective cohort studies does not support a detrimental effect of milk and dairy foods on risk of CVD. This paper provides a brief overview of the role of milk and dairy products in the diets of UK adults, and will summarise the evidence in relation to the effects of milk and dairy consumption on CVD risk factors and mortality. The majority of prospective studies and meta-analyses examining the relationship between milk and dairy product consumption and risk of CVD show that milk and dairy products, excluding butter, are not associated with detrimental effects on CVD mortality or risk biomarkers, that include serum LDL cholesterol. In addition, there is increasing evidence that milk and dairy products are associated with lower blood pressure and arterial stiffness. These apparent benefits of milk and dairy foods have been attributed to their unique nutritional composition, and suggest that the elimination of milk and dairy may not be the optimum strategy for CVD risk reduction.

Saturated Fatty Acids Produce an Inflammatory Response Predominantly through the Activation of TLR4 Signaling in Hypothalamus: Implications for the Pathogenesis of Obesity

In animal models of diet-induced obesity, the activation of an inflammatory response in the hypothalamus produces molecular and functional resistance to the anorexigenic hormones insulin and leptin. The primary events triggered by dietary fats that ultimately lead to hypothalamic cytokine expression and inflammatory signaling are unknown. Here, we test the hypothesis that dietary fats act through the activation of toll-like receptors 2/4 and endoplasmic reticulum stress to induce cytokine expression in the hypothalamus of rodents. According to our results, long-chain saturated fatty acids activate predominantly toll-like receptor 4 signaling, which determines not only the induction of local cytokine expression but also promotes endoplasmic reticulum stress. Rats fed on a monounsaturated fat-rich diet do not develop hypothalamic leptin resistance, whereas toll-like receptor 4 loss-of-function mutation and immunopharmacological inhibition of toll-like receptor 4 protects mice from diet-induced obesity. Thus, toll-like receptor 4 acts as a predominant molecular target for saturated fatty acids in the hypothalamus, triggering the intracellular signaling network that induces an inflammatory response, and determines the resistance to anorexigenic signals.

Screening of bacteria to produce polyhydroxyalkanoates from xylose

Although xylose is a major constituent of lignocellulosic feedstock and the second most abundant sugar in nature, only 22% of 3,152 screened bacterial isolates showed significant growth in xylose in 24 h. Of those 684, only 24% accumulated polyhydroxyalkanoates after 72 h. A mangrove isolate, identified as Bacillus sp. MA3.3, yielded the best results in literature thus far for Gram-positive strains in experiments with glucose and xylose as the sole carbon source. When glucose or xylose were supplied, poly-3-hydroxybutyrate (PHB) contents of cell dry weight were, respectively, 62 and 64%, PHB yield 0.25 and 0.24 g g(-1) and PHB productivity (P(PHB)) 0.10 and 0.06 g l(-1) h(-1). This 40% P(PHB) difference may be related to the theoretical ATP production per 3-hydroxybutyrate (3HB) monomer calculated as 3 mol mol(-1) for xylose, less than half of the ATP/3HB produced from glucose (7 mol mol(-1)). In PHB production using sugar mixtures, all parameters were strongly reduced due to carbon catabolite repression. PHB production using Gram-positive strains is particularly interesting for medical applications because these bacteria do not produce lipopolysaccharide endotoxins which can induce immunogenic reactions. Moreover, the combination of inexpensive substrates and products of more value may lead to the economical sustainability of industrial PHB production.

Study of a gold electrode modified by trans-[Ru(NH(3))(4)(Ist)SO(4)](+) to produce an electrochemical sensor for nitric oxide

The modification of a gold electrode surface by electropolymerization of trans-[Ru(NH(3))(4)(Ist)SO(4)](+) to produce an electrochemical sensor for nitric oxide was investigated. The influence of dopamine, serotonin and nitrite as interferents for NO detection was also examined using square-wave voltammetry (SWV). The characterization of the modified electrode was carried out by cyclic voltammetry, electrochemical quartz crystal microbalance (EQCM) and SERS techniques. The gold electrode was successfully modified by the trans-[Ru(NH(3))(4)(Ist)SO(4)](+) complex ion using cyclic voltammetry. The experiments show that a monolayer of the film is achieved after ten voltammetric cycles, that NO in solution can coordinate to the metal present in the layer, that dopamine, serotonin and nitrite are interferents for the detection of NO, and that the response for the nitrite is much less significant than the responses for dopamine and serotonin. The proposed modified electrode has the potential to be applied as a sensor for NO. (C) 2011 Elsevier Ltd. All rights reserved.

USING GIS NETWORK ANALYST TO IDENTIFY SUPPLIERS FOR A PRODUCE CO-OP IN WATERVILLE, ME

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Perceptions of power and dependence between retail buyers and fresh produce suppliers within the Australian fresh produce industry

The research aims to gain a deeper understanding of direct buyer-supplier relationships within the Australian fresh produce industry. Specifically, dependence and power within the buyer-supplier relationship are considered in terms of their antecedents and their relationships their-in. In-depth interviews with buyers and suppliers provided the means by which to expose perceptions with regard to the relative importance of dependence and power within the relationship. The research reveals that relationship antecedents (trading offer: price and quality) impact power and dependence and are, in tum, impacted by them.

Transesterification of fish oil to produce fatty acid ethyl esters using ultrasonic energy

This study evaluated the production of fatty acid ethyl esters from fish oil using ultrasonic energy and alkaline catalysts dissolved in ethanol. The feasibility of fatty acid ethyl ester production was determined using an ultrasonic bath and probe, and between 0.5 and 1% KOH (added to the fish oil). Furthermore, factors such as ultrasonic device (bath and probe), catalyst (KOH and C2H5ONa), temperature (20 and 60 °C), and duration of exposure (10–90 min) were assessed. Sodium ethoxide was found to be a more efficient catalyst than KOH when transesterifying fish oil. Ultrasonic energy applied for greater than 30 min at 60 °C using 0.8% of C2H5ONa as a catalyst transesterified over 98% fish oil triglycerides to fatty acid ethyl esters. It is reasonable to conclude that the yield of fatty acid ethyl esters produced by applying ultrasonic energy to fish oil is related to the sonication time. Due to increases in the surface area contact between the reactants and the catalyst, ultrasonic energy has the potential to reduce the production time required by a conventional large-scale commercial transesterification method that uses agitation as a way of mixing.

Reactive ball milling to produce nanocrystalline ZnO

Ball milling of zinc powders in oxygen atmosphere leads to nanocrystalline ZnO. The average grain size has a value of 9 nm. The zinc oxidation proceeds gradually. It is compared with the combustion oxidation reactions of metals (Zr, Ti, Fe and Sn) reported previously. We propose a new parameter ΔH/C_p(metal) instead of simplified adiabatic temperature to judge if the mechanochemical oxidation of a particular metal happens via gradual or combustion reaction.

Asexual reproduction does not produce clonal populations of the brooding coral Pocillopora damicornis on the Great Barrier Reef, Australia

We have investigated the relationship between genotypic diversity, the mode of production of brooded larvae and disturbance in a range of reef habitats, in order to resolve the disparity between the reproductive mode and population structure reported for the brooding coral Pocillopora damicornis. Within 14 sites across six habitats, the ratio of the observed (G o) to the expected (G e) genotypic diversity ranged from 69 to 100% of that expected for random mating. At three other sites in two habitats the G o /G e ranged from 35 to 53%. Two of these sites were recently bleached, suggesting that asexual recruitment may be favoured after disturbance. Nevertheless, our data suggest that brooded larvae, from each of five habitats surveyed, were asexually produced. While clonal recruitment may be important in disturbed habitats, the lack of clonality detected, both in this and earlier surveys of 40 other sites, implies that a disturbance is normally insufficient to explain this species’ continued investment in clonal reproduction.

Use of residual hydrogen to produce CP-Ti powder compacts for low temperature rolling

The present work investigates the optimal level of residual hydrogen in partially de-hydrogenated powder to produce CP-Ti plate compacts using ECAP with back pressure which are subsequently rolled at low temperature. A comparative study of the compaction of two TiH₂ powders and a CP-Ti powder, with particle sizes 150 um, 50um and 45 um respectively, has been carried out. The hydride powders have also been compacted in a partially de-hydrogenated state. The optimal level of residual hydrogen with respect to the density of the resulting compact and the associated mechanical properties has been defined. ECAP at 300°C produced compacts from these partially de-hydrogenated powders of 99.5% theoretical density, while CP-Ti was compacted to almost full theoretical density under the same ECAP conditions. Therefore, the compaction of powder by ECAP does not benefit from temporary hydrogen alloying.

These compacts then were rolled at temperatures ranging from room temperature to 500°C with an 80% reduction in a single pass. Heat treatment after the rolling can modify the microstructure to improve the resulting mechanical properties and in this regard the temporary alloying with hydrogen has been observed to offer some significant benefits. It is shown the ECAP followed by low temperature rolling is a promising route to the batch production of fully dense CP-Ti wrought product from powder feedstock that avoids the need to subject the material to temperatures greater than 500°C. This low temperature route is expected to be efficient from an energy point of view and it also avoids the danger of interstitial contamination that accompanies most high temperature powder processing.