Copper and iron homeostasis in Arabidopsis: responses to metal deficiencies, interactions and biotechnological applications

Plants have developed sophisticated mechanisms to tightly control the acquisition and distribution of copper and iron in response to environmental fluctuations. Recent studies with Arabidopsis thaliana are allowing the characterization of the diverse families and components involved in metal uptake, such as metal-chelate reductases and plasma membrane transporters. In parallel, emerging data on both intra- and intercellular metal distribution, as well as on long-distance transport, are contributing to the understanding of metal homeostatic networks in plants. Furthermore, gene expression analyses are deciphering coordinated mechanisms of regulation and response to copper and iron limitation. Prioritizing the use of metals in essential versus dispensable processes, and substituting specific metalloproteins by other metal counterparts, are examples of plant strategies to optimize copper and iron utilization. The metabolic links between copper and iron homeostasis are well documented in yeast, algae and mammals. In contrast, interactions between both metals in vascular plants remain controversial, mainly owing to the absence of copper-dependent iron acquisition. This review describes putative interactions between both metals at different levels in plants. The characterization of plant copper and iron homeostasis should lead to biotechnological applications aimed at the alleviation of iron deficiency and copper contamination and, thus, have a beneficial impact on agricultural and human health problems.     

CAM Use in Pediatric Neurology: An Exploration of Concurrent Use with Conventional Medicine

Background

Previous studies have found that up to 60% of children with neurologic conditions have tried complementary and alternative medicine (CAM).

Objective

To assess the use of CAM among patients presenting to neurology clinics at two academic centers in Canada.

Methods

A survey instrument was developed to inquire about use of CAM products and therapies, including reasons for use, perceived helpfulness, and concurrent use with conventional medicine, and administered to patients or their parents/guardians at the Stollery Children''s Hospital in Edmonton and the Children''s Hospital of Eastern Ontario (CHEO) in Ottawa.

Results

Overall CAM use at the Stollery was 78%, compared to 48% at CHEO. The most common CAM products used were multi-vitamins (84%), vitamin C (37%), homeopathic remedies (24%), and fish oil/omega 3 s (22%). The most common CAM practices used were massage (47%), chiropractic (37%), faith healing (18%), aromatherapy (16%), homeopathy (16%), and relaxation (16%). Many patients used CAM products at the same time as conventional medicine but just over half (57%) discussed this concurrent use with their physician.

Conclusion

CAM use is common in pediatric neurology patients and most respondents felt that it was helpful, with few or no harms associated. However, this use is often undisclosed, increasing possibility of interactions with conventional drugs. We urge clinicians to inquire about CAM use during routine history taking at every patient visit. Parents would clearly like more information about CAM from their specialty clinics; such information would be easier to share if more primary data were available about the safety and effectiveness of commonly used therapies.     

Immunotherapy of murine leukemia following non-myeloablative conditioning with naïve or G-CSF mobilized blood or bone marrow stem cells

Allogeneic stem cell transplantation (SCT) is the treatment of choice for a large number of hematologic malignancies. Its major advantage over conventional chemotherapy lies in the graft-versus-leukemia (GVL) effects mediated by allo- or tumor-reactive donor lymphocytes given in the course of SCT or post transplantation as donor lymphocyte infusions (DLI). The benefits of cell-mediated immunotherapy over myeloablative radiochemotherapy have also made it possible to reduce the intensity of conditioning regimens. Mobilized peripheral blood has proved preferable to bone marrow (BM) as a source of stem cells for transplantation, since it provides a larger number of stem cells on the one hand and immunologically competent lymphocytes on the other. The use of granulocyte colony stimulating factor (G-CSF), which is necessary to mobilize and increase the number of stem cells, may down-regulate the GVL effect by suppression of donor effector T lymphocytes by inducing Th₁Th₂ cytokine switch. It has previously been shown that GVL effects may be amplified by both in vivo and in vitro activation of donor lymphocytes with human recombinant interleukin-2 (rIL-2). Our studies using a leukemic murine model prepared for transplantation with low intensity conditioning prior to infusion of G-CSF-mobilized peripheral blood stem cells (PBSC) have demonstrated that mobilization of blood cells with G-CSF and in vivo treatment with rIL-2 following low-intensity conditioning enhances the GVL effects and prolongs survival of recipients inoculated with BCL1. Activation of donor lymphocytes with rIL-2 may thus be useful for amplifying GVL effects following mobilization with G-CSF.     

Priming of mesenchymal stem cells with a hydrosoluble form of curcumin allows keeping their mesenchymal properties for cell-based therapy development

Mesenchymal stem cells are increasingly studied for their use as drug-carrier in addition to their intrinsic potential for regenerative medicine. They could be used to transport molecules with a poor bioavailability such as curcumin in order to improve their clinical usage. This natural polyphenol, well-known for its antioxidant and anti-inflammatory properties, has a poor solubility that limits its clinical potential. For this purpose, the use of NDS27, a curcumin salt complexed with hydroxypropyl-beta-cyclodextrin (HPβCD), displaying an increased solubility in aqueous solution, is preferred. This study aims to evaluate the uptake of NDS27 into skeletal muscle-derived mesenchymal stem cells (mdMSCs) and the effects of such uptake onto their mesenchymal properties. It appeared that the uptake of NDS27 into mdMSCs is concentration-dependent and not time-dependent. The use of a concentration of 7 µmol/L which does not affect the viability and proliferation also allows preservation of their adhesion, invasion and T cell immunomodulatory abilities.