Quinine, an old anti-malarial drug in a modern world: role in the treatment of malaria

Quinine remains an important anti-malarial drug almost 400 years after its effectiveness was first documented. However, its continued use is challenged by its poor tolerability, poor compliance with complex dosing regimens, and the availability of more efficacious anti-malarial drugs. This article reviews the historical role of quinine, considers its current usage and provides insight into its appropriate future use in the treatment of malaria. In light of recent research findings intravenous artesunate should be the first-line drug for severe malaria, with quinine as an alternative. The role of rectal quinine as pre-referral treatment for severe malaria has not been fully explored, but it remains a promising intervention. In pregnancy, quinine continues to play a critical role in the management of malaria, especially in the first trimester, and it will remain a mainstay of treatment until safer alternatives become available. For uncomplicated malaria, artemisinin-based combination therapy (ACT) offers a better option than quinine though the difficulty of maintaining a steady supply of ACT in resource-limited settings renders the rapid withdrawal of quinine for uncomplicated malaria cases risky. The best approach would be to identify solutions to ACT stock-outs, maintain quinine in case of ACT stock-outs, and evaluate strategies for improving quinine treatment outcomes by combining it with antibiotics. In HIV and TB infected populations, concerns about potential interactions between quinine and antiretroviral and anti-tuberculosis drugs exist, and these will need further research and pharmacovigilance

Feasibility of a recombinant human apolipoprotein E reference material.

The aim of this work was to prepare a recombinant apo E material and to determine its suitability as a reference material. We produced human apo E3 using recombinant DNA technology. The cDNA of human apo E3 was cloned in the pARHS bacterial expression vector and used to transfect E. Coli BL21 (DE3) cells. The recombinant protein was then purified in one step by affinity chromatography on a Ni-chelated agarose column under denaturing conditions. The purity of the protein estimated by SDS PAGE was greater than 96%. The physicochemical properties and biological and immunological reactivity of the purified recombinant apo E3 were shown to be close to those of the protein purified from human plasma VLDL. A limited batch of lyophilized apo E material was then prepared. The stability of the lyophilized apo E material examined by temperature accelerated degradation was acceptable. No degradation of the measured apo E was observed after storage of the lyophilized material at +4°C and -20°C for 11 months. The reconstituted lyophilized material, in comparison with human fresh serum samples and with apo E purified from human VLDL, showed no major alteration of its immunological reactivity when assayed by immunoturbidimetry or ELISA. © Springer-Verlag 1998

Antioxidant network expression abrogates oxidative posttranslational modifications in mice

Antioxidant enzymatic pathways form a critical network that detoxifies ROS in response to myocardial stress or injury. Genetic alteration of the expression levels of individual enzymes has yielded mixed results with regard to attenuating in vivo myocardial ischemia-reperfusion injury, an extreme oxidative stress. We hypothesized that overexpression of an antioxidant network (AON) composed of SOD1, SOD3, and glutathione peroxidase (GSHPx)-1 would reduce myocardial ischemia-reperfusion injury by limiting ROS-mediated lipid peroxidation and oxidative posttranslational modification (OPTM) of proteins. Both ex vivo and in vivo myocardial ischemia models were used to evaluate the effect of AON expression. After ischemia-reperfusion injury, infarct size was significantly reduced both ex vivo and in vivo, ROS formation, measured by dihydroethidium staining, was markedly decreased, ROS-mediated lipid peroxidation, measured by malondialdehyde production, was significantly limited, and OPTM of total myocardial proteins, including fatty acid-binding protein and sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)2a, was markedly reduced in AON mice, which overexpress SOD1, SOD3, and GSHPx-1, compared with wild-type mice. These data demonstrate that concomitant SOD1, SOD3, and GSHPX-1 expression confers marked protection against myocardial ischemia-reperfusion injury, reducing ROS, ROS-mediated lipid peroxidation, and OPTM of critical cardiac proteins, including cardiac fatty acid-binding protein and SERCA2a