Effects of anti-malarial drugs on the electrocardiographic QT interval modelled in the isolated perfused guinea pig heart system

<p>Abstract</p> <p>Background</p> <p>Concern over the potential cardiotoxicity of anti-malarial drugs inducing a prolonged electrocardiographic QT interval has resulted in the almost complete withdrawal from the market of one anti-malarial drug - halofantrine. The effects on the QT interval of four anti-malarial drugs were examined, using the guinea pig heart.</p> <p>Methods</p> <p>The guinea pig heart was isolated, mounted on a Langendorff apparatus, and was then perfused with pyruvate-added Klebs-Henseleit solutions containing graded concentrations of the four agents such as quinidine (0.15 - 1.2 μM), quinine (0.3 - 2.4 μM), halofantrine (0.1 - 2.0 μM) and mefloquine (0.1 - 2.0 μM). The heart rate-corrected QaTc intervals were measured to evaluate drug-induced QT prolongation effects.</p> <p>Results</p> <p>Quinidine, quinine, and halofantrine prolonged the QaTc interval in a dose-dependent manner, whereas no such effect was found with mefloquine. The EC₅₀values for the QaTc prolongation effects, the concentration that gives a half-maximum effect, were quinidine < quinine ≈ halofantrine.</p> <p>Conclusions</p> <p>In this study, an isolated, perfused guinea pig heart system was constructed to assess the cardiotoxic potential of anti-malarial drugs. This isolated perfused guinea pig heart system could be used to test newly developed anti-malarial drugs for their inherent QT lengthening potential. More information is required on the potential variation in unbound drug concentrations in humans, and their role in cardiotoxicity.</p

The effect of fluoride and iron content on the clinkering of Alite-ye’elimite-ferrite (AYF) cement systems

Abstract Alite–ye’elimite–ferrite (AYF) cement is a more sustainable alternative to Portland cement (PC) that may offer improved mechanical, rheological, and chemical performance. Using traditional raw materials and conventional clinker processing conditions, alite (C₃S) and ye’elimite (C₄A₃), the major phases in PC and calcium sulfoaluminate (CSA) cements, respectively, cannot be coproduced. The typical formation temperature in the kiln for alite is >1350°C, but ye’elimite normally breaks down above 1300°C. However, with careful composition control and in the presence of fluoride, alite can be mineralized and formed at lower temperatures, thus enabling the production of AYF clinkers in a single stage. In this study, the production of AYF cement clinkers with different chemical compositions is attempted at 1250°C. The sensitivity of the fluoride content is initially assessed with a fixed target clinker composition to determine the optimal requirements. The effect of altering the target ferrite (C₄AF) and alite (C₃S) contents is also assessed followed by the effect of altering the target C₄AF and C₄A₃ contents. It is shown that AYF clinkers can be produced in a single stage through the careful control of the fluoride content in the mix; however, the formation/persistence of belite and mayenite could not be avoided under the conditions tested. It is also shown that ∼10 wt% ferrite in the target composition provides sufficient AYF clinker burnability and the amount of fluoride needs to be controlled to avoid stabilization of mayenite

Production and properties of ferrite-rich CSAB cement from metallurgical industry residues

Abstract Blast furnace slag from the steel industry is commercially utilized as a cement replacement material without major processing requirements; however, there are many unutilized steel production slags which differ considerably from the blast furnace slag in chemical and physical properties. In this study, calcium sulfoaluminate belite (CSAB) cement clinkers were produced using generally unutilized metallurgical industry residues: AOD (Argon Oxygen Decarburisation) slag from stainless steel production, Fe slag from zinc production, and fayalitic slag from nickel production. CSAB clinker with a target composition of ye’elimite-belite-ferrite was produced by firing raw materials at 1300 °C. The phase composition of the produced clinkers was identified using quantitative XRD analyses, and the chemical composition of the clinker phases produced was established using FESEM-EDS and mechanical properties were tested through compressive strength test. It is demonstrated that these metallurgical residues can be used successfully as alternative raw materials for the production of CSAB cement that can be used for special applications. In addition, it is shown that the available quantities of these side-streams are enough for significant replacement of virgin raw materials used in cement production

Ferritic calcium sulfoaluminate belite cement from metallurgical industry residues and phosphogypsum:clinker production, scale-up, and microstructural characterisation

Abstract The production of ferrite-rich calcium sulfoaluminate belite (CSABF) cement clinker, also containing MgO, from ladle slag, Fe-slag, and phosphogypsum was translated from a lab-scale to a pilot demonstration in a 7-metre kiln at 1260 °C. An account of the pilot trials/manufacturing is presented, and the process was robust. Laboratory tests prior to scale-up showed that gehlenite formation can be inhibited in the CSABF clinker by adding excess CaO in the raw meal; however, this reduces the amount of iron (Fe) that can be incorporated into ye’elimite and leads to higher ferrite (C₆AF₂) content. Detailed microstructural analyses were performed on the clinker to reveal the clinker composition as well as the partition of the minor elements. Different ferrite phases with varying amounts of titanium and iron are distinguished. Eighty-five percent of the clinker raw meal was comprised of side-stream materials and the clinker produced in the kiln had chemical raw-material CO₂ emissions 90% lower than that of Portland cement made from virgin raw materials. These results can have a significant impact in regions with a prospering metallurgical industry, enabling industrial decarbonisation and resource efficiency

Study of Strangeness Photo-production in the Threshold Region at LNS-Tohoku(I. Nuclear Physics)

We have successfully measured neutral kaons, bombarding a liquid deuterium target with a photon beam in the threshold region from 0.8 to 1.1GeV. It was the first data for K^0 photoproduction on the deuteron in this energy region. The momentum spectra of K^0 production were compared with theoretical spectra calculated assuming isobar models for the elementary process and a realistic deuteron wave function for the target The present experiment has demonstrated a usefulness of the neutral kaon measurement for the investigation of photo strangeness production reactions