Increasing evidence suggests that glutamate activates the generation of lactate from glucose in astrocytes; this lactate is shuttled to neurons that use it as a preferential energy source. We explore this multicellular "lactate shuttle" with a novel dual-cell, dual-gene therapy approach and determine the neuroprotective potential of enhancing this shuttle. Viral vector-driven overexpression of a glucose transporter in glia enhanced glucose uptake, lactate efflux, and the glial capacity to protect neurons from excitotoxicity. In parallel, overexpression of a lactate transporter in neurons enhanced lactate uptake and neuronal resistance to excitotoxicity. Finally, overexpression of both transgenes in the respective cell types provided more protection than either therapy alone, demonstrating that a dual-cell, dual-gene therapy approach gives greater neuroprotection than the conventional single-cell, single-gene strategy.
Anaemia is a common problem in patients with renal failure. For the past 10 years, recombinant human erythropoietin (r-HuEPO) has been the mainstay of treatment for anaemic patients on dialysis.Many factors, including infection, inflammation, hyperparathyroidism, aluminium toxicity, vitamin B,J folate and iron deficiency, can reduce the response to r-HuEPO. The use of other iron formulations, androgen, carnitine, insulin-like growth factor (1GF)-1 and zinc may have a role in augmenting the response to r-HuEPO.The pharmacology, pharmacokinetics, side-effects, costs and availability of nandrolone decanoate, l-camitine, iron sucrose, IGF-1 and zinc will be discussed
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