Direct inhibition of the pancreatic beta-cell ATP-regulated potassium channel by alpha-ketoisocaproate

The ATP-regulated potassium (KATP) channel plays an essential role in the control of insulin release from the pancreatic beta-cell. In the present study we have used the patch-clamp technique to study the direct effects of alpha-ketoisocaproate on the KATP channel in isolated patches and intact pancreatic beta-cells. In excised inside-out patches, the activity of the KATP channel was dose-dependently inhibited by alpha-ketoisocaproate, half-maximal concentration being approximately 8 mM. The blocking effect of alpha-ketoisocaproate was fully reversible. Stimulation of channel activity by the addition of ATP/ADP (ratio 1) did not counteract the inhibitory effect of alpha-ketoisocaproate. In the presence of the metabolic inhibitor sodium azide, alpha-ketoisocaproate was still able to inhibit single channel activity in excised patches and to block whole cell KATP currents in intact cells. No effect of alpha-ketoisocaproate could be obtained on either the large or the small conductance Ca2+-regulated K+ channel. Enzymatic treatment of the patches with trypsin prevented the inhibitory effect of alpha-ketoisocaproate. Based on these observations, it is unlikely that the blocking effect of alpha-ketoisocaproate is due to an unspecific effect on K+ channel pores. Leucine, the precursor of alpha-ketoisocaproate, did not affect KATP channel activity in excised patches. Our findings are compatible with the view that alpha-ketoisocaproate not only affects the beta-cell stimulus secretion coupling by generation of ATP but also by direct inhibition of the KATP channel.     

The electrochemical properties of imidazol-linked iron phthalocyanine—carbon electrodes

Electrodes for the electrochemical reduction of oxygen have been studied galvanostatically. The electrodes were of the activated carbon-polymeric iron phthalocyanine (FePc) type, made hydrophobic with a Teflon treatment. A link between the FePc and the carbon was achieved by covalently binding imidazol to the carbon surface and then letting the FePc co-ordinate to the free nitrogen of the imidazol molecule. In this way an initial improvement of the stability of the electrode potential and the polarization data was achieved. It has furthermore been established that the potential responds more rapidly to changes, i.e. it is more reversible, than an analogous electrode based on carbon that has not been treated with imidazol.     

Studies of teratogenic effects of the dithiocarbamates maneb, mancozeb, and propineb

Oral administration of high dosages of the dithiocarbamate pesticides maneb and mancozeb was teratogenic in rats but not in mice. The malformations, severe limb and craniofacial defects, were pronounced after maneb treatment but less so after mancozeb and propineb, zinc-containing compounds. The teratogenic effect of maneb was progressively reduced by simultaneously administering increasing amounts of zinc acetate. The mechanism of the teratogenic effect may involve the compounds being chelating agents, trapping zinc required for many important enzyme systems.     

Spatial analysis of annual air pollution exposure and mortality

The aim of this study was to relate ambient air pollution levels to mortality in Auckland, New Zealand. We used urban airshed modelling and GIS-based techniques to quantify long-term exposure to ambient air pollution levels and associated mortality. After adjusting for age, sex, ethnicity, socio-economic status, and urban/rural domicile there was a 1.3% (95%CI: 1-1.5%) increase in non-external cause mortality, and 1.8% (95%CI: 1.5-2.1%) increase in circulatory and respiratory causes per 1 microg/m(3) increase in annual average NO(2). Based on these exposure-response relationships and applying an annual average threshold of 13 microg/m(3), the average annual (for 1996-1999) number of people estimated to die from non-external causes and circulatory and respiratory causes attributable to air pollution in Auckland is 268 (95% range: 227-310) (3.9% of total all cause deaths) and 203 (95% range: 169-237) (5.9% of total circulatory and respiratory deaths) per year, respectively. The number of attributable deaths found in this study are consistent with a previous New Zealand risk assessment using a different methodology, and is approximately twice the number of people dying from motor vehicle accidents in the region, which is on average (1996-1999) 103 per year. The GIS-based exposure maps identify high exposure areas for policy developers and planners in a simple and realistic manner. Taken together with overseas studies the study provides additional evidence that long-term exposure to poor air quality, even at levels below current standards, is a hazard to the public health.     

Synthesis of branched 'nanotrees' by controlled seeding of multiple branching events

The formation of nanostructures with controlled size and morphology has been the focus of intensive research in recent years. Such nanostructures are important in the development of nanoscale devices and in the exploitation of the properties of nanomaterials. Here we show how tree-like nanostructures ('nanotrees') can be formed in a highly controlled way. The process involves the self-assembled growth of semiconductor nanowires via the vapour-liquid-solid growth mode. This bottom-up method uses initial seeding by catalytic nanoparticles to form the trunk, followed by the sequential seeding of branching structures. Each level of branching is controlled in terms of branch length, diameter and number, as well as chemical composition. We show, by high-resolution transmission electron microscopy, that the branching mechanism gives continuous crystalline (monolithic) structures throughout the extended and complex tree-like structures. The controlled seeding method that we report here has potential as a generic means of forming complex branching structures, and may also offer opportunities for applications, such as the mimicking of photosynthesis in nanotrees.     

Atmospheric transport of polybrominated diphenyl ethers and polychlorinated biphenyls to the Baltic Sea

The atmospheric transport of polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) was compared by measuring concentrations in air and deposition on an island located in the central basin of the Baltic Sea. Median sigmaPBDE and sigmaPCB concentrations (gaseous + particle) were 8.6 and 7.4 pg m(-3), respectively. Airborne PCBs were mainly found in the gaseous phase, while most of the PBDEs were detected on particles, which agrees with predicted particle/gas distributions. SigmaPBDE levels were dominated by the decabrominated BDE209 followed bythe tetrabrominated BDE47 and pentabrominated BDE99. BDE209 is a marker for the environmental distribution of the commercial deca-BDE formulation (>99.5% BDE209), whereas BDE47 and BDE99 are markers for the commercial penta-BDE mixture. General correlations between PBDEs and PCBs suggested similarities in sources and transport mechanism, while more detailed examination of the data identified notable behaviors and exceptions. Differences in regression slopes among tetra-, penta-, and decabrominated PBDEs may reflect different transport processes and the change in usage pattern. Tetra- and pentabrominated PBDEs may originate from secondary sources such as air surface exchange in a manner similar to that of the PCBs, while the deca-BDE209 formulation still has primary sources. The tribrominated BDE17 was also detected and is proposed to be a breakdown product due to atmospheric debromination processes. PBDEs had higher washout ratios than PCBs, explaining their higher concentrations compared to PCBs in precipitation (median of 6.0 and 0.5 ng L(-1) for sigmaBDE and sigmaPCB concentrations ("dissolved" + particle), respectively) than in air. The calculated yearly deposition of PBDEs and PCBs indicated that the atmospheric input of PBDEs to the Baltic Proper is currently exceeding that of the PCBs by a factor of 40, while that of the PCBs is decreasing.     

Ligand distributions in agarose particles as determined by confocal Raman spectroscopy and confocal scanning laser microscopy

Confocal Raman spectroscopy and confocal scanning laser microscopy have been used to analyze ligand distributions within individual chromatographic adsorbent particles. Three different types of particles have been investigated. The first type was synthesized to have a uniform distribution of allyl groups, whereas the two others were designed to have a surface layer of sulphopropyl groups and cores containing allyl groups and dextran, respectively. With confocal Raman spectroscopy it was possible to follow the distribution of both the surface layer and the interior. The distribution of sulphopropyl groups was evaluated with both confocal scanning laser microscopy and confocal Raman spectroscopy, whereas the distributions of allyl groups and dextran were evaluated only with the latter method. The results from the confocal measurements showed the expected result with a uniform distribution of allyl groups in the first type of particle and surface layers of sulphopropyl groups and cores with dextran or allyl groups for the two others.     

Efficiency of methods for Karl Fischer determination of water in oils based on oven evaporation and azeotropic distillation

The efficiency of azeotropic distillation and oven evaporation techniques for trace determination of water in oils has recently been questioned by the National Institute of Standards and Technology (NIST), on the basis of measurements of the residual water found after the extraction step. The results were obtained by volumetric Karl Fischer (KF) titration in a medium containing a large excess of chloroform (> or = 65%), a proposed prerequisite to ensure complete release of water from the oil matrix. In this work, the extent of this residual water was studied by means of a direct zero-current potentiometric technique using a KF medium containing more than 80% chloroform, which is well above the concentration recommended by NIST. A procedure is described that makes it possible to correct the results for dilution errors as well as for chemical interference effects caused by the oil matrix. The corrected values were found to be in the range of 0.6-1.5 ppm, which should be compared with the 12-34 ppm (uncorrected values) reported by NIST for the same oils. From this, it is concluded that the volumetric KF method used by NIST gives results that are much too high.