Accurate evaluation of iron overload is necessary to establish the diagnosis of hemochromatosis and guide chelation treatment in transfusion-dependent anemia. The liver is the primary site for iron storage in patients...Accurate evaluation of iron overload is necessary to establish the diagnosis of hemochromatosis and guide chelation treatment in transfusion-dependent anemia. The liver is the primary site for iron storage in patients with hemochromatosis or transfusion-dependent anemia, therefore, liver iron concentration (LIC) accurately re? ects total body iron stores. In the past 20 years, magnetic resonance imaging (MRI) has emerged as a promising method for measuring LIC in a variety of diseases. We review the potential role of MRI in LIC determination in the most important disorders that are characterized by iron overload, that is, thalassemia major, other hemoglobinopathies, acquired anemia, and hemochromatosis. Most studies have been performed in thalassemia major and MRI is currently a widely accepted method for guiding chelation treatment in these patients. However, the lack of correlation between liver and cardiac iron stores suggests that both organs should be evaluated with MRI, since cardiac disease is the leading cause of death in this population. It is also unclear which MRI method is the most accurate since there are no large studies that have directly compared the different available techniques. The role of MRI in the era of genetic diagnosis of hemochromatosis is also debated, whereas data on the accuracy of the method in other hematological and liver diseases are rather limited. However, MRI is a fast, non-invasive and relatively accurate diagnostic tool for assessing LIC, and its use is expected to increase as the role of iron in the pathogenesis of liver disease becomes clearer.展开更多
The iron chelators can be utilized in target cells to improve 5-aminolaevulinic acid （ALA）-based photodynamic therapy （PDT）. The purpose of this study is to compare the effect of two kinds of iron chelators, desfe...The iron chelators can be utilized in target cells to improve 5-aminolaevulinic acid （ALA）-based photodynamic therapy （PDT）. The purpose of this study is to compare the effect of two kinds of iron chelators, desferrioxamine （DFO） and ethylenediaminetetraacetic acid （EDTA） on the enhancement of ALA-PDT. HaCat cells were cultured in medium containing 2.0 mmol/L of ALA and 0.5 mmol/L of DFO or EDTA. After 3-h incubation in the dark, the concentration of cellular pro-toporphyrin Ⅸ （PpⅨ） was detected by high performance liquid chromatography （HPLC）, and the fluorescence of PpⅨ was observed at 630 nm emission under confocal laser scanning microscope. For PDT, HaCat cells were irradiated using 632.8 nm laser, and the fractions of apoptotic and necrotic cells were flow cytometrically assayed. Related differences in morphology and ultrastructure of Ha-Cat cells were observed using optical microscope or transmission electron microscope. Compared to incubation with ALA alone, the addition of DFO or EDTA increased the concentration of cellular PpⅨ and the fluorescent density of PpⅨ, and also increased cell death ratio after PDT. PDT using ALA plus DFO produced the highest cellular PpⅨ level, greatest cell death ratio and most severe structural damage to the cells. It was concluded that both DFO and EDTA could enhance ALA-based PpⅨ production and PDT. Compared to the non-specific iron chelator of EDTA, the specific chelator, DFO, showed more potential for the enhancement.展开更多
Background: Anemia is a common complication of end-stage renal disease (ESRD) and is effectively managed by Erythropoietin Stimulating Agents (ESAs) and intravenous iron therapy. Management of anemia in ESRD patients ...Background: Anemia is a common complication of end-stage renal disease (ESRD) and is effectively managed by Erythropoietin Stimulating Agents (ESAs) and intravenous iron therapy. Management of anemia in ESRD patients with myelodysplastic syndrome (MDS) poses a unique challenge. ESAs even at extremely high doses do not result in a desired response, especially if the patients are iron-overloaded. Case: A 72-year-old man with history of ESRD and MDS on hemodialysis since September 2009 was severely anemic requiring massive doses of ESA in excess of 90,000 units/week. Iron saturation was consistently >60%;ferritin was >2500. Desferrioxamine (DFO) 125 mg IV/week was begun in November 2010. His PRBC transfusion and ESA requirements declined after the initiation of this therapy. He had 33 ER visits for PRBC transfusions (1 - 3 transfusions/visit) from September 2009 to November 2010 (average: 2.35/month), which decreased to 18 visits in 20 months (average: 0.9/month) after getting DFO. Conclusion: We report a case of MDS with ESRD on hemodialysis where anemia was managed with Desferrioxamine therapy along with ESA, after which it was noted that there was a significant reduction in the number of PRBC transfusions that the patient received along with a decrease in ESA requirements and a decrease in number of hospitalizations, which in the long term could be cost effective.展开更多
A significant challenge in bacterial detection is the identification of viable bacteria over debris, specifically post decontamination. Of increasing concern are antibiotic resistant strains that require accurate and ...A significant challenge in bacterial detection is the identification of viable bacteria over debris, specifically post decontamination. Of increasing concern are antibiotic resistant strains that require accurate and rapid post decontamination analysis. Current strategies are fraught with disadvantages and most of them are not selective for viable bacteria. However, bacteria are critically dependent upon iron sequestration, synthesizing and releasing siderophores (SDPs) to tightly bind iron, with the subsequent uptake of iron bound SDPs. This is a highly conserved process that occurs only in intact bacteria. Herein we report a facile method to use bacterial SDPs to selectively and rapidly identify only viable bacteria in complex matrices, and discriminate them from their dead counterparts. Desferrioxamine B (Desf B) tethered to a glass slide is used to specifically capture viable bacteria from a mixture of viable and dead Escherichia coli, as demonstrated by fluorescence microscopy. We re- port both direct conjugation of Desf B on thin-film-coated glass slides as well as biotin-streptavidin conjugation strategies, both of which are successful in the said goal. We have analyzed the density of images obtained upon fluorescence staining using edge detection with a Canny edge detector. This novel application of a software analysis tool originally developed for satellite imaging to biological staining allows for accurate quantitation of observed data.展开更多
文摘Accurate evaluation of iron overload is necessary to establish the diagnosis of hemochromatosis and guide chelation treatment in transfusion-dependent anemia. The liver is the primary site for iron storage in patients with hemochromatosis or transfusion-dependent anemia, therefore, liver iron concentration (LIC) accurately re? ects total body iron stores. In the past 20 years, magnetic resonance imaging (MRI) has emerged as a promising method for measuring LIC in a variety of diseases. We review the potential role of MRI in LIC determination in the most important disorders that are characterized by iron overload, that is, thalassemia major, other hemoglobinopathies, acquired anemia, and hemochromatosis. Most studies have been performed in thalassemia major and MRI is currently a widely accepted method for guiding chelation treatment in these patients. However, the lack of correlation between liver and cardiac iron stores suggests that both organs should be evaluated with MRI, since cardiac disease is the leading cause of death in this population. It is also unclear which MRI method is the most accurate since there are no large studies that have directly compared the different available techniques. The role of MRI in the era of genetic diagnosis of hemochromatosis is also debated, whereas data on the accuracy of the method in other hematological and liver diseases are rather limited. However, MRI is a fast, non-invasive and relatively accurate diagnostic tool for assessing LIC, and its use is expected to increase as the role of iron in the pathogenesis of liver disease becomes clearer.
基金supported by the National Basic Research Program of China (No. 2006CB504100)Major and General Programs of theNational Natural Science Foundation of China (No. 30393133, 30370536)Knowledge Innovation Program of the Chinese Academy ofSciences (No. KSCX2-YW-R-75)
文摘The iron chelators can be utilized in target cells to improve 5-aminolaevulinic acid （ALA）-based photodynamic therapy （PDT）. The purpose of this study is to compare the effect of two kinds of iron chelators, desferrioxamine （DFO） and ethylenediaminetetraacetic acid （EDTA） on the enhancement of ALA-PDT. HaCat cells were cultured in medium containing 2.0 mmol/L of ALA and 0.5 mmol/L of DFO or EDTA. After 3-h incubation in the dark, the concentration of cellular pro-toporphyrin Ⅸ （PpⅨ） was detected by high performance liquid chromatography （HPLC）, and the fluorescence of PpⅨ was observed at 630 nm emission under confocal laser scanning microscope. For PDT, HaCat cells were irradiated using 632.8 nm laser, and the fractions of apoptotic and necrotic cells were flow cytometrically assayed. Related differences in morphology and ultrastructure of Ha-Cat cells were observed using optical microscope or transmission electron microscope. Compared to incubation with ALA alone, the addition of DFO or EDTA increased the concentration of cellular PpⅨ and the fluorescent density of PpⅨ, and also increased cell death ratio after PDT. PDT using ALA plus DFO produced the highest cellular PpⅨ level, greatest cell death ratio and most severe structural damage to the cells. It was concluded that both DFO and EDTA could enhance ALA-based PpⅨ production and PDT. Compared to the non-specific iron chelator of EDTA, the specific chelator, DFO, showed more potential for the enhancement.
文摘Background: Anemia is a common complication of end-stage renal disease (ESRD) and is effectively managed by Erythropoietin Stimulating Agents (ESAs) and intravenous iron therapy. Management of anemia in ESRD patients with myelodysplastic syndrome (MDS) poses a unique challenge. ESAs even at extremely high doses do not result in a desired response, especially if the patients are iron-overloaded. Case: A 72-year-old man with history of ESRD and MDS on hemodialysis since September 2009 was severely anemic requiring massive doses of ESA in excess of 90,000 units/week. Iron saturation was consistently >60%;ferritin was >2500. Desferrioxamine (DFO) 125 mg IV/week was begun in November 2010. His PRBC transfusion and ESA requirements declined after the initiation of this therapy. He had 33 ER visits for PRBC transfusions (1 - 3 transfusions/visit) from September 2009 to November 2010 (average: 2.35/month), which decreased to 18 visits in 20 months (average: 0.9/month) after getting DFO. Conclusion: We report a case of MDS with ESRD on hemodialysis where anemia was managed with Desferrioxamine therapy along with ESA, after which it was noted that there was a significant reduction in the number of PRBC transfusions that the patient received along with a decrease in ESA requirements and a decrease in number of hospitalizations, which in the long term could be cost effective.
文摘A significant challenge in bacterial detection is the identification of viable bacteria over debris, specifically post decontamination. Of increasing concern are antibiotic resistant strains that require accurate and rapid post decontamination analysis. Current strategies are fraught with disadvantages and most of them are not selective for viable bacteria. However, bacteria are critically dependent upon iron sequestration, synthesizing and releasing siderophores (SDPs) to tightly bind iron, with the subsequent uptake of iron bound SDPs. This is a highly conserved process that occurs only in intact bacteria. Herein we report a facile method to use bacterial SDPs to selectively and rapidly identify only viable bacteria in complex matrices, and discriminate them from their dead counterparts. Desferrioxamine B (Desf B) tethered to a glass slide is used to specifically capture viable bacteria from a mixture of viable and dead Escherichia coli, as demonstrated by fluorescence microscopy. We re- port both direct conjugation of Desf B on thin-film-coated glass slides as well as biotin-streptavidin conjugation strategies, both of which are successful in the said goal. We have analyzed the density of images obtained upon fluorescence staining using edge detection with a Canny edge detector. This novel application of a software analysis tool originally developed for satellite imaging to biological staining allows for accurate quantitation of observed data.
