Investigation of the presynaptic effects of quinine and quinidine on the release and uptake of monoamines in rat brain tissue

Quinine and quinidine are reported to potentiate the behavioural effects of serotonergic agents and monoamine uptake inhibitors. We have therefore investigated the presynaptic actions of quinine and quinidine on monoamine uptake and release in rat brain tissue in vitro. Quinidine evoked the release of [3H]5-HT, [3H]noradrenaline and [3H]dopamine from pre-loaded rat brain slices in a concentration dependent manner with EC50 values of 175, 486 and 150 microM, respectively. Quinine induced [3H]monoamine release with similar potencies. Both quinine and quinidine also inhibited the active uptake of [3H]5-HT, [3H]noradrenaline and [3H]dopamine into rat brain synaptosomes with IC50 values in the range 0.13-12.4 microM. The potency of each drug to inhibit [3H]5-HT uptake was significantly higher than that for [3H]noradrenaline or [3H]dopamine. The relative potency of quinidine compared to quinine was more marked in the case of [3H]5-HT (58-fold) than for [3H]noradrenaline (3-fold) or [3H]dopamine (4-fold). The inhibition of [3H]5-HT uptake by quinine and quinidine was competitive in nature and corresponded with the potencies of these drugs to inhibit [3H]paroxetine binding. No correlation was observed between the potencies of quinine and quinidine to induce the release of [3H]monoamines and to inhibit their uptake, suggesting that these effects are mediated by two distinct mechanisms. We conclude that the presynaptic actions of quinine and quinidine on monoamine uptake and release may be implicated in their potentiation of the effects of serotonergic agents and uptake blockers.     

Comparative evaluation of FUNGITEST and broth microdilution methods for antifungal drug susceptibility testing of Candida species and Cryptococcus neoformans

The FUNGITEST method (Sanofi Diagnostics Pasteur, Paris, France) is a microplate-based procedure for the breakpoint testing of six antifungal agents (amphotericin B, flucytosine, fluconazole, itraconazole, ketoconazole, and miconazole). We compared the FUNGITEST method with a broth microdilution test, performed according to National Committee for Clinical Laboratory Standards document M27-A guidelines, for determining the in vitro susceptibilities of 180 isolates of Candida spp. (50 C. albicans, 50 C. glabrata, 10 C. kefyr, 20 C. krusei, 10 C. lusitaniae, 20 C. parapsilosis, and 20 C. tropicalis isolates) and 20 isolates of Cryptococcus neoformans. Overall, there was 100% agreement between the methods for amphotericin B, 95% agreement for flucytosine, 84% agreement for miconazole, 83% agreement for itraconazole, 77% agreement for ketoconazole, and 76% agreement for fluconazole. The overall agreement between the methods exceeded 80% for all species tested with the exception of C. glabrata (71% agreement). The poorest agreement between the results for individual agents was seen with C. glabrata (38% for fluconazole, 44% for ketoconazole, and 56% for itraconazole) and C. tropicalis (50% for miconazole). The FUNGITEST method misclassified as susceptible 2 of 12 (16.6%) fluconazole-resistant isolates, 2 of 10 (20%) itraconazole-resistant isolates, and 4 of 8 (50%) ketoconazole-resistant isolates of several Candida spp. Further development of the FUNGITEST procedure will be required before it can be recommended as an alternative method for the susceptibility testing of Candida spp. or C. neoformans.     

Just a matter of time

As Midwestern foodservice directors & dietitians recently discovered when an earthquake alert was sounded in their area, it's never too early to review & update emergency plans. Herein is a compendium of tips that can be used by any foodservice professional working in an area at risk of disaster, whether it be earthquake, tornado, hurricane, blackout or flood.     

Effect of precipitate type and morphology on high-temperature creep and internal stress in Al-Li based alloys

The tensile creep of a series of aluminium-lithium-based alloys, two binary alloys containing precipitate, and the 2090 alloy containing and T₁ precipitate, has been studied over a range of stresses at 150°C. In some cases the internal stress developed during creep has been determined using the strain transient dip test. The results have been compared with similar data previously obtained for the 8090 alloy containing and S precipitates. The solid solution alloy and the binary alloy containing shearable particles exhibited normal Class II behaviour, with the development of sub-grains and a stress dependence of the creep rate given by a single stress exponent,n, between 4 and 5 at all applied stresses. The alloys containing particles not easily sheared by dislocations, coarse , S and T₁, exhibited similar stress dependencies of the creep rate at low stresses but exhibited large values ofn, between 18 and 35 at high stresses. The internal stress, _i, in these alloys was found to be approximately constant at high stresses possibly due to partial shearing of the coarse , T₁, and the S on sub-boundaries. The stress dependence of the minimum creep rate, , could be represented at all applied stresses, _a, by , where (_a–_i) is the effective stress driving dislocations during creep, andn is a single stress exponent of between 5 and 6 for all applied stresses. The internal stress, which increases with applied stress, at least at a low applied stress, arises from inhomogeneity of plastic deformation, due to hard sub-boundaries or hard particles which are Orowan looped. These two types of contribution to the internal stress are of similar magnitude in the alloys containing coarse and T₁ but the majority of the internal stress in the 8090 alloy may arise as a result of the hardening of sub-boundaries by the S precipitate.     

Fabrication and microstructure-mechanical property relationships in Ce-TZPs

Ceria-stabilized tetragonal zirconia polycrystals(Ce-TZPs) have been fabricated via conventional sintering of commercially available electrofused and electrorefined CeO₂-doped ZrO₂ powder at 1550°C for various periods from 0.5–30 h. The resultant grain sizes of the sintered materials were in the range 2–15 m. The sintering of such electrorefined powder appears to occur by a liquid state sintering process, evinced in terms of the grain-size dependence on sintering time at 1550°C and by direct TEM observation. The mechanical properties of the sintered materials have been characterized, including single-edge notch bend fracture toughness and three-point bend fracture strength. The grain-size dependence of these properties in the CeO₂-stabilized tetragonal polycrystals is very much different from that in Y₂O₃ stabilized tetragonal zirconia polycrystals (Y-TZPs). The transformation plasticity, which is represented by the yield stress behaviour and the total strain to fracture, plays an important role in the microstructure-property interrelationship in the Ce-TZPs.     

Hafnia and hafnia-toughened ceramics

Hafnia (HfO₂) and hafnium-based materials are traditionally regarded as technologically important materials in the nuclear industry, a consequence of their exceptionally high neutron absorption coefficient. Following the discovery of transformation toughening in the mid 1970s, a considerable research effort has been devoted to zirconia (ZrO₂)-toughened ceramics (ZTCs). They are considered to be potentially useful materials for structural applications at low and intermediate temperatures (T<1000 °C). Their unsuitability for high-temperature structural applications (T>1000 °C) is related to the low temperature of the tetragonal to monoclinic transformation in ZrO₂. On the basis that HfO₂ exhibits a similar crystal structure and in particular that its tetragonal to monoclinic transformation temperature (1700 °C) is approximately 700 °C higher than that for ZrO₂, it has been suggested that high-temperature transformation toughening could be possible in HfO₂-toughened ceramics (HTCs). Although the concepts behind this suggestion are universally appreciated, only a limited success has been made of the fabrication and the microstructural and mechanical property evaluation of these materials. The fracture toughness values obtained so far in HfO₂ toughened ceramics are, in fact, considerably lower than those obtained in their ZrO₂ counterparts. A great deal of further research work is therefore required in order to understand fully and to exploit toughened ceramics in the HfO₂-based and HfO₂-containing systems. This review covers the science and technology of HfO₂ and HfO₂-toughened ceramics in terms of processing, phase transformation, microstructure, and mechanical properties.     

Polyphenol Supplementation Reverses Age-Related Changes in Microglial Signaling Cascades

Microglial activity in the aging neuroimmune system is a central player in aging-related dysfunction. Aging alters microglial function via shifts in protein signaling cascades. These shifts can propagate neurodegenerative pathology. Therapeutics require a multifaceted approach to understand and address the stochastic nature of this process. Polyphenols offer one such means of rectifying age-related decline. Our group used mass spectrometry (MS) analysis to explicate the complex nature of these aging microglial pathways. In our first experiment, we compared primary microglia isolated from young and aged rats and identified 197 significantly differentially expressed proteins between these groups. Then, we performed bioinformatic analysis to explore differences in canonical signaling cascades related to microglial homeostasis and function with age. In a second experiment, we investigated changes to these pathways in aged animals after 30-day dietary supplementation with NT-020, which is a blend of polyphenols. We identified 144 differentially expressed proteins between the NT-020 group and the control diet group via MS analysis. Bioinformatic analysis predicted an NT-020 driven reversal in the upregulation of age-related canonical pathways that control inflammation, cellular metabolism, and proteostasis. Our results highlight salient aspects of microglial aging at the level of protein interactions and demonstrate a potential role of polyphenols as therapeutics for age-associated dysfunction.     

The multivariable model-based control of the non-alumina electrolyte variables in aluminum smelting cells

This paper investigates the application of multivariable model-based control to improve the regulatory control of electrolyte temperature, aluminum fluoride concentration, liquidus temperature, superheat, and electrolyte height. Also examined are therappropriateness of different control structures and the possible inclusion of recently developed sensors for alumina concentration and individual cell duct flowrate, temperature, and heat loss. For the smelter in this study, the maximum improvement possible with a multivariable model-based controller is predicted to be 30–40% reduction in standard deviation in electrolyte temperature, aluminum fluoride concentration, liquidus temperature, and superheat, and around half this for electrolyte height. Three control structures were found to be appropriate; all are different than the existing control structure, which was found to be suboptimal. Linear Quadratic Gaussian controllers were designed for each control structure and their predicted performance compared. Comalco Research.     

Allelopathic polyacetylenes fromCentaurea repens (Russian knapweed)

The allelopathic weed Russian knapweed (Centaurea repens) was found to contain polyacetylenes VIII–XIV in the roots. Dose vs. response of the root length elongation against lettuce, alfalfa, barnyard grass, and red millet showed IX to be active. Closely related isomers were not active. Examination of the soil surrounding the Russian knapweed roots revealed the presence of IX in sufficient concentration to have an appreciable effect on the surrounding plant community.