The impact of iron overload and its treatment on quality of life: results from a literature review

BACKGROUND: To assess the literature for the impact of iron overload and infusion Iron Chelation Therapy (ICT) on patients' quality of life (QoL), and the availability of QoL instruments for patients undergoing infusion ICT. Also, to obtain patients' experiences of having iron overload and receiving infusion ICT, and experts' clinical opinions about the impact of treatment on patients' lives. METHODS: A search of studies published between 1966 and 2004 was conducted using Medline and the Health Economic Evaluation Database (HEED). Qualitative results from patient and expert interviews were analysed. Hand searching of relevant conference abstracts completed the search. RESULTS: Few studies measuring the impact of ICT with deferoxamine (DFO) on patients QoL were located (n = 15). QoL domains affected included: depression; fatigue; dyspnoea; physical functioning; psychological distress; decrease in QoL during hospitalization. One theme in all articles was that oral ICT should improve QoL. No iron overload or ICT-specific QoL instruments were located in the articles. Interviews revealed that the impact of ICT on patients with thalassemia, sickle cell disease, and myelodysplastic syndromes is high. CONCLUSION: A limited number of studies assessed the impact of ICT or iron overload on QoL. All literature suggested a need for easily administered, efficacious and well tolerated oral iron overload treatments, given the impact of current ICT on adherence. Poor adherence to ICT was documented to negatively impact survival. Further research is warranted to continue the qualitative and quantitative study of QoL using validated instruments in patients receiving ICT to further understanding the issues and improve patients QoL

Ratiometric high-resolution imaging of JC-1 fluorescence reveals the subcellular heterogeneity of astrocytic mitochondria

Using the mitochondrial potential (ΔΨm) marker JC-1 (5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolylcarbocyanine iodide) and high-resolution imaging, we functionally analyzed mitochondria in cultured rat hippocampal astrocytes. Ratiometric detection of JC-1 fluorescence identified mitochondria with high and low ΔΨm. Mitochondrial density was highest in the perinuclear region, whereas ΔΨm tended to be higher in peripheral mitochondria. Spontaneous ΔΨm fluctuations, representing episodes of increased energization, appeared in individual mitochondria or synchronized in mitochondrial clusters. They continued upon withdrawal of extracellular Ca2+, but were antagonized by dantrolene or 2-aminoethoxydiphenylborate (2-APB). Fluo-3 imaging revealed local cytosolic Ca2+ transients with similar kinetics that also were depressed by dantrolene and 2-APB. Massive cellular Ca2+ load or metabolic impairment abolished ΔΨm fluctuations, occasionally evoking heterogeneous mitochondrial depolarizations. The detected diversity and ΔΨm heterogeneity of mitochondria confirms that even in less structurally polarized cells, such as astrocytes, specialized mitochondrial subpopulations coexist. We conclude that ΔΨm fluctuations are an indication of mitochondrial viability and are triggered by local Ca2+ release from the endoplasmic reticulum. This spatially confined organelle crosstalk contributes to the functional heterogeneity of mitochondria and may serve to adapt the metabolism of glial cells to the activity and metabolic demand of complex neuronal networks. The established ratiometric JC-1 imaging—especially combined with two-photon microscopy—enables quantitative functional analyses of individual mitochondria as well as the comparison of mitochondrial heterogeneity in different preparations and/or treatment conditions

Haemocyte apoptosis as a general cellular immune response of Lymnaea stagnalis, to a toxicant.

International audienceThe effects of a xenobiotic on the circulating haemocytes of Lymnaea stagnalis were investigated after short-term (24 h, 96 h) and long-term (504 h) exposure of snails to environmental concentrations. Fomesafen, a prooxidant generator led to the activation of the haemocyte apoptotic program by promoting reactive oxygen species (ROS). Cells entering apoptosis underwent a series of events, both on the plasma membrane and in the mitochondria; these events were quantified by flow cytofluorometry. The data showed a loss of mitochondrial transmembrane potential (Δψm), which was dose-dependent and timedependent and related to an increased release of superoxide anions. The phosphatidylserine that was exposed at the outer plasma membrane was not related to the disruption of either ROS or Δψm but was strongly correlated with the haemocyte concentration (total haemocyte count). This cascade of apoptotic processes occurred in a dose-independent manner and was not strengthened over time. The increase of circulating haemocytes depended upon the life span of the cells and might have reflected either facilitated cell turn-over or the accompanying presence of haemocytes phagocytosing apoptotic cells